Journal articles on the topic 'Lung and breast/ovarian cancer'
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1
Prat, Aleix, Barbara Adamo, Cheng Fan, Maria Vidal, Patricia Galvan, Enriqueta Felip, Jose Maria Del Campo, Josep Tabernero, and Javier Cortes. "Molecular identification of basal-like breast cancer through genomic analyses across five cancer types." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 1011. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.1011.
Abstract:
1011 Background: Common molecular alterations in different types of cancer are being identified and these might be successfully targeted regardless of the tumor´s tissue of origin. To better understand the genomic relationships among different types of cancer, we explored global gene expression patterns across breast, lung, ovarian, brain and colorectal cancers. Methods: A unified set of 1,707 samples of 5 human cancer types (breast [n=547], lung [squamous and adenocarcinomas, n=249], ovarian [serous carcinoma, n=489], brain [glioblastoma multiforme, n=202] and colorectal [n=220]) from The Cancer Genome Atlas (TCGA) project was evaluated. All microarrays were performed at the University of North Carolina under the same protocol and platform. All samples provided in each publication of TCGA were used, except for lung adenocarcinomas where we used TCGA public data. Consensus clustering was used to identify molecular entities, and breast cancer intrinsic subtyping was performed using the PAM50 predictor. Results: A total of 6 distinct and robust molecular entities were identified representing tumors from breast luminal/HER2-enriched, breast Basal-like, lung, ovarian, brain and colorectal cancers. Strikingly, 55%, 26%, 16% of Basal-like breast cancers were found to be more similar to squamous cell lung carcinomas, lung adenocarcinomas and ovarian cancers, respectively, compared to breast luminal/HER2-enriched tumors. Breast cancer intrinsic subtyping identified a Basal-like profile in 55% of squamous cell lung cancers, 53% of ovarian cancers and 8% of lung adenocarcinomas. Finally, single genes and gene signatures tracking cancer-related biological processes such as proliferation, angiogenesis and immune activation were found highly expressed in different proportions across the 6 molecular entities. Conclusions: These data suggest that breast tumors of the Basal-like subtype have a distinct cell of origin compared to luminal/HER2-enriched tumors. Clinical trials focusing on tumors with common profiles and/or biomarker expression rather than their tissue of origin are warranted with a special focus on Basal-like breast cancer, squamous cell lung carcinoma and serous ovarian cancer.
2
Achariyapota, Vuthinun, Tuenjai Chuangsuwanich, and Mongkol Benjapibal. "Inflammatory Breast Cancer from Metastatic Ovarian Cancer." Case Reports in Obstetrics and Gynecology 2016 (2016): 1–3. http://dx.doi.org/10.1155/2016/3476143.
Abstract:
Metastases to the breast from tumors other than breast carcinomas are extremely rare and represent only 0.2–1.3% of all diagnosed malignant breast tumors. Furthermore, while the most common sites for advanced ovarian cancer metastases are the liver, lung, and pleura, metastasis to the breast from a primary ovarian cancer is uncommon and has only been reported in 0.03–0.6% of all breast cancers. Here we describe a case report of a 50-year-old female patient with a rare case of breast metastases from an advanced ovarian cancer, presenting as inflammatory breast cancer. Our observations emphasize the clinical importance of distinguishing between primary and metastatic breast cancer during diagnosis for the purpose of appropriate prognosis and treatment.
3
R., Abhirup H., Priyanka Kenchetty, and Aishwarya K. Chidananda. "Breast ovarian cancer syndrome." International Surgery Journal 8, no. 8 (July 28, 2021): 2454. http://dx.doi.org/10.18203/2349-2902.isj20213144.
Abstract:
BRCA1 and BRCA2, known as breast and ovarian cancer predisposition genes, were discovered in the 1990s. As part of a normal genetic structure, these genes are intrinsic to all human beings, but they are mutated in some individuals increasing the risk for breast and ovarian cancers development. BRCA1 is not only expressed in endocrine tissues but is also detected in other cells such as the neuroepithelial cells in the early stage of cell development. Like BRCA1, BRCA2 is also expressed in a wide variety of tissues and is observed with higher rates in the breast and thymus and with lower rates in the lung, ovary and spleen. We presented to you a case of 40 year old female admitted in surgical ward with lump in the left breast since 2 months with ipsilateral discrete axillary lymphadenopathy. Bilateral sono-mammography showed BIRADS V lesion in left breasts with satellite nodules. Ultrasonography of abdomen and pelvis showed large left adnexal solid mass lesion and right sided ovarian cyst with retrocaval, preaortic lymphadenopathy. Patient underwent a diagnostic laparoscopy which was converted to a laparotomy. Total abdominal hysterectomy with bilateral salphingo-oophorectomy was done. For the breast lump, patient underwent left sided modified radical mastectomy. Gene testing for revealed BRCA1 positivity. Chemotherapy was given to cover both breast and ovarian carcinoma. Patient came back with abdominal distension after 9 months and was offered palliative care. Patient succumbed for disease after 1 year after diagnosis. We reviewed the literature for the same.
4
Abu-Tineh, Mohammad, Hind Elmalik, and Mohamed A. Yassin. "Metastatic Ovarian Cancer Presenting as Inflammatory Breast Cancer: A Case Report." Case Reports in Oncology 13, no. 2 (July 28, 2020): 867–74. http://dx.doi.org/10.1159/000508358.
Abstract:
Metastatic ovarian cancer to the breast is a rare presentation, with limited cases reported worldwide. Common sites for distant metastasis in ovarian cancer are to the liver, lung, and pleura [Dauplat et al. Cancer. 1987 Oct 1;60(7):1561–6]. Usually, such cases predict poor prognosis with troublesome management. We present one challenging case of a 54-year-old female patient with recurrent clear cell ovarian cancer, presenting with right breast mass of primary versus secondary origin, progressing into inflammatory breast cancer picture. Our report aims to shed light on the value of early suspicion and low threshold of detecting secondary breast masses of ovarian cancer origin.
5
Bacalbasa, Nicolae, Irina Balescu, Claudia Stoica, Cristina Martac, Valentin Varlas, Andrei Voichitoiu, Lucian Pop, Sorin Petrea, Mihaela Vilcu, and Iulian Brezean. "Breast metastases from ovarian cancer." Romanian Medical Journal 69, S4 (June 20, 2022): 14–16. http://dx.doi.org/10.37897/rmj.2022.s4.3.
Abstract:
Ovarian cancer represents one of the most aggressive malignancies which is characterized by a high capacity of spread via multiple pathways such as lymphatic, peritoneal and hematogenous route, the most commonly encountered sites for metastatic lesions being represented by lung, liver, peritoneum and lymph nodes. In extremely rare cases breast metastases with ovarian origin have been reported. In such cases different therapeutic strategies have been proposed; however the overall prognosis remains extremely poor, the presence of metastatic lesions at this level being usually the sign of disseminated disease.
6
Arora, Nimisha, Aline Talhouk, Jessica N. McAlpine, Michael R. Law, and Gillian E. Hanley. "Causes of death among women with epithelial ovarian cancer by length of survival post-diagnosis: a population-based study in British Columbia, Canada." International Journal of Gynecologic Cancer 29, no. 3 (December 21, 2018): 593–98. http://dx.doi.org/10.1136/ijgc-2018-000040.
Abstract:
ObjectivesLittle is known regarding the health of women who survive more than 5 years following their ovarian cancer diagnosis. To bridge an important gap in our knowledge about long term health of ovarian cancer survivors, we examined the causes of death among women diagnosed with epithelial ovarian cancer between 1990 and 2014 in British Columbia. These causes were stratified by years since diagnosis, and compared with age- standardized causes of death among women who have not been diagnosed with ovarian cancer.MethodsWe examined all women with epithelial ovarian cancer in British Columbia 1990–2014 using population- based administrative datasets. We stratified women into three groups: all epithelial ovarian cancer patients; women surviving 5 to 9 years post-diagnosis, and women surviving 10 or more years since diagnosis. All- cause and cause specific standardized mortality ratios (SMRs) were calculated.ResultsThere were 4246 deaths among 6427 women with epithelial ovarian cancer. About 55.9% of deaths were from ovarian cancer. When compared with the general population, the highest SMRs (SMR of 5 or higher) were for deaths from other cancers and external causes (44.4% from falls) among women surviving 5–9 years and 10 or more years post-diagnosis. Mortality from other cancers can largely be explained by deaths from breast cancer (15.8%), lung cancer (12.3%), and colorectal cancer (11%).ConclusionsWhile the majority of epithelial ovarian cancer patients continue to die from their ovarian cancer, our results suggest that long term ovarian cancer survivors are particularly vulnerable to deaths from other cancers and from falls in elderly survivors. These data could indicate closer surveillance for breast, lung, and colorectal cancer, and closer attention to bone health is warranted among women surviving for 5 or more years following their epithelial ovarian cancer diagnosis.
7
Haan, David, Anna Bergamaschi, Yuhong Ning, William Gibb, Michael Kesling, Adriana Pitea, Maryam Nabiyouni, et al. "Genome-wide 5hmC profiles to enable cancer detection and tissue of origin classification in breast, colorectal, lung, ovarian, and pancreatic cancers." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 3044. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.3044.
Abstract:
3044 Background: Epigenomics assays have recently become popular tools for identification of molecular biomarkers, both in tissue and in plasma. In particular 5-hydroxymethyl-cytosine (5hmC) method, has been shown to enable the epigenomic regulation of gene expression and subsequent gene activity, with different patterns, across several tumor and normal tissues types. In this study we show that 5hmC profiles enable discrete classification of tumor and normal tissue for breast, colorectal, lung ovary and pancreas. Such classification was also recapitulated in cfDNA from patient with breast, colorectal, lung, ovarian and pancreatic cancers. Methods: DNA was isolated from 176 fresh frozen tissues from breast, colorectal, lung, ovary and pancreas (44 per tumor per tissue type and up to 11 tumor tissues for each stage (I-IV)) and up to 10 normal tissues per tissue type. cfDNA was isolated from plasma from 783 non-cancer individuals and 569 cancer patients. Plasma-isolated cfDNA and tumor genomic DNA, were enriched for the 5hmC fraction using chemical labelling, sequenced, and aligned to a reference genome to construct features sets of 5hmC patterns. Results: 5hmC multinomial logistic regression analysis was employed across tumor and normal tissues and identified a set of specific and discrete tumor and normal tissue gene-based features. This indicates that we can classify samples regardless of source, with a high degree of accuracy, based on tissue of origin and also distinguish between normal and tumor status.Next, we employed a stacked ensemble machine learning algorithm combining multiple logistic regression models across diverse feature sets to the cfDNA dataset composed of 783 non cancers and 569 cancers comprising 67 breast, 118 colorectal, 210 Lung, 71 ovarian and 100 pancreatic cancers. We identified a genomic signature that enable the classification of non-cancer versus cancers with an outer fold cross validation sensitivity of 49% (CI 45%-53%) at 99% specificity. Further, individual cancer outer fold cross validation sensitivity at 99% specificity, was measured as follows: breast 30% (CI 119% -42%); colorectal 41% (CI 32%-50%); lung 49% (CI 42%-56%); ovarian 72% (CI 60-82%); pancreatic 56% (CI 46%-66%). Conclusions: This study demonstrates that 5hmC profiles can distinguish cancer and normal tissues based on their origin. Further, 5hmC changes in cfDNA enables detection of the several cancer types: breast, colorectal, lung, ovarian and pancreatic cancers. Our technology provides a non-invasive tool for cancer detection with low risk sample collection enabling improved compliance than current screening methods. Among other utilities, we believe our technology could be applied to asymptomatic high-risk individuals thus enabling enrichment for those subjects that most need a diagnostic imaging follow up.
8
Tkaczuk, Katherine R., Paula Rosenblatt, Ranee Mehra, Katherine A. Scilla, Nancy Tait, Katerra Caple, Binbin Yue, and Ginette Serrero. "Abstract CT240: On-going phase 1A clinical trial for AG01 an first-in-class anti-progranulin (GP88) monoclonal antibody in patients with advanced malignancies." Cancer Research 83, no. 8_Supplement (April 14, 2023): CT240. http://dx.doi.org/10.1158/1538-7445.am2023-ct240.
Abstract:
Abstract Progranulin (PGRN/GP88) is an 88 kDa glycoprotein characterized by seven and a half double cysteine rich repeats which is the largest member of the granulin-epithelin protein family. PGRN/GP88 has been demonstrated as a biological driver of tumorigenesis, survival, and drug resistance in several cancers including breast cancer (BC), lung prostate, ovarian and digestive cancers. PGRN/GP88 tissue expression is an independent prognostic factor of recurrence in breast, lung cancers while elevated serum PGRN/GP88 level in metastatic breast, lung, ovarian and prostate cancer patients. Elevated PGRN/GP88 levels are associated with poor outcomes such as progression and shortened survival. An anti-human PGRN/GP88 monoclonal antibody able to inhibit PGRN/GP88 action in vitro and in vivo has been developed, chimerized and expressed in CHO cells. All IND enabling activities including pharmacology, GMP manufacturing, formulation and GLP toxicology studies have been conducted. The IND application has been filed and cleared by the Food and Drug Administration. A first-in-human, first-in-class phase 1 safety and efficacy clinical study of AG01 in patients with solid tumors and advanced disease with special focus on patients with breast, lung and ovarian cancers has been initiated and is on-going at the University of Maryland Greenebaum Cancer Center. The trial is registered as NCT05627960 to clinicaltrials.gov site. Supported by grants R44CA162629 and R44CA224718 from the National Cancer Institute to GS. Citation Format: Katherine R. Tkaczuk, Paula Rosenblatt, Ranee Mehra, Katherine A. Scilla, Nancy Tait, Katerra Caple, Binbin Yue, Ginette Serrero. On-going phase 1A clinical trial for AG01 an first-in-class anti-progranulin (GP88) monoclonal antibody in patients with advanced malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT240.
9
Roland, Adjoby Cassou, Kouamé Arthur Didier, Koffi Achille, Kakou Charles, Konan Joachim, Andriamandimbison Zoly, Ahounkeng Patrick, and Nshimirimana Eric. "Metastatic ovarian tumor of a lung cancer at the hospital center of Chauny (France): a case report." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 6, no. 10 (September 23, 2017): 4682. http://dx.doi.org/10.18203/2320-1770.ijrcog20174464.
Abstract:
The ovary is an organ that can be the site of metastases for many cancers. In general, malignant ovarian tumors are primary; however, cases of extra gynecological metastatic tumors (breast, colon, stomach, and pancreas) have been reported. In most cases, the primary cancers of these ovarian tumors are gastrointestinal or gynecological, the lung being very rarely involved. We report a rare case of ovarian metastases of bronchial cancer discovered during an extensional assessment. The histological examination coupled with immunohistochemistry concludes that ovarian metastasis of small cell lung carcinoma. In addition to chemotherapy such as Taxol-Hycamtin, the management required cerebral radiotherapy for a cerebral metastasis detected.
10
Yurkovetsky, Zoya, Steven Skates, Aleksey Lomakin, Brian Nolen, Trenton Pulsipher, Francesmary Modugno, Jeffrey Marks, et al. "Development of a Multimarker Assay for Early Detection of Ovarian Cancer." Journal of Clinical Oncology 28, no. 13 (May 1, 2010): 2159–66. http://dx.doi.org/10.1200/jco.2008.19.2484.
Abstract:
PurposeEarly detection of ovarian cancer has great promise to improve clinical outcome.Patients and MethodsNinety-six serum biomarkers were analyzed in sera from healthy women and from patients with ovarian cancer, benign pelvic tumors, and breast, colorectal, and lung cancers, using multiplex xMAP bead-based immunoassays. A Metropolis algorithm with Monte Carlo simulation (MMC) was used for analysis of the data.ResultsA training set, including sera from 139 patients with early-stage ovarian cancer, 149 patients with late-stage ovarian cancer, and 1,102 healthy women, was analyzed with MMC algorithm and cross validation to identify an optimal biomarker panel discriminating early-stage cancer from healthy controls. The four-biomarker panel providing the highest diagnostic power of 86% sensitivity (SN) for early-stage and 93% SN for late-stage ovarian cancer at 98% specificity (SP) was comprised of CA-125, HE4, CEA, and VCAM-1. This model was applied to an independent blinded validation set consisting of sera from 44 patients with early-stage ovarian cancer, 124 patients with late-stage ovarian cancer, and 929 healthy women, providing unbiased estimates of 86% SN for stage I and II and 95% SN for stage III and IV disease at 98% SP. This panel was selective for ovarian cancer showing SN of 33% for benign pelvic disease, SN of 6% for breast cancer, SN of 0% for colorectal cancer, and SN of 36% for lung cancer.ConclusionA panel of CA-125, HE4, CEA, and VCAM-1, after additional validation, could serve as an initial stage in a screening strategy for epithelial ovarian cancer.
11
Tkaczuk, Katherine, Paula Rosenblatt, Ranee Mehra, Katherine Scilla, Nancy Tait, Binbin Yue, and Ginette Serrero. "Abstract PO5-18-06: On-going phase 1A clinical trial of A01, a chimerized monoclonal antibody to Progranulin/Glycoprotein 88 (GP88) in patients with advanced malignancy." Cancer Research 84, no. 9_Supplement (May 2, 2024): PO5–18–06—PO5–18–06. http://dx.doi.org/10.1158/1538-7445.sabcs23-po5-18-06.
Abstract:
Abstract Progranulin (PGRN/GP88) is an 88 kDa glycoprotein characterized by seven and a half double cysteine rich repeats which is the largest member of the granulin-epithelin protein family. PGRN/GP88 has been demonstrated as a biological driver of tumorigenesis, survival, and drug resistance in several cancers including breast cancer (BC), lung prostate, ovarian and digestive cancers. PGRN/GP88 tissue expression is an independent prognostic factor of recurrence in breast, lung cancers while elevated serum PGRN/GP88 level in metastatic breast, lung, ovarian and prostate cancer patients. Elevated PGRN/GP88 levels are associated with poor outcomes such as progression and shortened survival. An anti-human PGRN/GP88 monoclonal antibody able to inhibit the the in vitro and in vivo action of human PGRN/GP88 has been developed, chimerized and expressed in CHO cells. All IND enabling activities including pharmacology, GMP manufacturing, formulation and GLP toxicology studies have been conducted. The IND application has been filed and cleared by the Food and Drug Administration. A first-in-human, first-in-class phase 1 safety and efficacy clinical study of AG01 in patients with solid tumors and advanced disease with special focus on patients with breast, lung and ovarian cancers has been initiated and is on-going at the University of Maryland Greenebaum Cancer Center. The trial is registered as NCT05627960 to clinicaltrials.gov site. The presentation will provide an update on the number of patients enrolled in this on-going phase 1A trial. Supported by grants R44CA162629 and R44CA224718 from the National Cancer Institute to GS. Citation Format: Katherine Tkaczuk, Paula Rosenblatt, Ranee Mehra, Katherine Scilla, Nancy Tait, Binbin Yue, Ginette Serrero. On-going phase 1A clinical trial of A01, a chimerized monoclonal antibody to Progranulin/Glycoprotein 88 (GP88) in patients with advanced malignancy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-06.
12
Covic, Lidija, and Athan Kuliopulos. "Protease-Activated Receptor 1 as Therapeutic Target in Breast, Lung, and Ovarian Cancer: Pepducin Approach." International Journal of Molecular Sciences 19, no. 8 (July 31, 2018): 2237. http://dx.doi.org/10.3390/ijms19082237.
Abstract:
The G-protein coupled receptors (GPCRs) belong to a large family of diverse receptors that are well recognized as pharmacological targets. However, very few of these receptors have been pursued as oncology drug targets. The Protease-activated receptor 1 (PAR1), which is a G-protein coupled receptor, has been shown to act as an oncogene and is an emerging anti-cancer drug target. In this paper, we provide an overview of PAR1’s biased signaling role in metastatic cancers of the breast, lungs, and ovaries and describe the development of PAR1 inhibitors that are currently in clinical use to treat acute coronary syndromes. PAR1 inhibitor PZ-128 is in a Phase II clinical trial and is being developed to prevent ischemic and thrombotic complication of patients undergoing cardiac catheterization. PZ-128 belongs to a new class of cell-penetrating, membrane-tethered peptides named pepducins that are based on the intracellular loops of receptors targeting the receptor G-protein interface. Application of PZ-128 as an anti-metastatic and anti-angiogenic therapeutic agent in breast, lung, and ovarian cancer is being reviewed.
13
O'Shannessy, Daniel J., Darren W. Davis, Kenna Anderes, and Elizabeth B. Somers. "Isolation of Circulating Tumor Cells from Multiple Epithelial Cancers with ApoStream® for Detecting (or Monitoring) the Expression of Folate Receptor Alpha." Biomarker Insights 11 (January 2016): BMI.S35075. http://dx.doi.org/10.4137/bmi.s35075.
Abstract:
This study describes our efforts to further the field of noninvasive diagnostics, specifically in the area of liquid biopsies in oncology. We employed laser scanning cytometry using highly selective antibodies to interrogate circulating tumor cells (CTCs) that were isolated using ApoStream® technology to identify folate receptor alpha (FRα)–positive cells. We demonstrate that FRα+ CTCs can be isolated from patients with metastatic cancers, including NSCLC adenocarcinoma, breast cancer, and ovarian cancer, whereas squamous cell lung cancer and normal healthy controls were devoid of FRα+ CTCs. We believe that the developed methodology will have applications in both the diagnosis and the monitoring of FRα-expressing cancers. Folate receptor alpha (FRα) expression may have utility as a potential diagnostic and therapeutic target in solid tumors. As tissue samples are not always available for patient screening, this study evaluated a noninvasive assay in CTCs from blood samples to detect FRα expression. The presence of FRα+ CTCs enriched using ApoStream® and detected using laser capture cytometry was evaluated in blood samples from cancer patients [NSCLC adenocarcinoma ( n = 14), breast cancer ( n = 20), ovarian cancer ( n = 6), and squamous lung cancer patients ( n = 6)] and healthy subjects ( n = 20). The data demonstrated that FRα+ CTCs were detected in blood from NSCLC adenocarcinoma, breast, and ovarian cancer patients, whereas squamous cell lung cancer patients and normal healthy controls lacked FRα+ CTCs as previously known. We demonstrate that CTCs captured using ApoStream® can be used to detect FRα+ CTCs and may have clinical utility as a real-time liquid biopsy for assessing FRα levels in cancer patients.
14
Saad, Hebatallah M., Ghada F. Tourky, Hayder M. Al-kuraishy, Ali I. Al-Gareeb, Ahmed M. Khattab, Sohaila A. Elmasry, Abdulrahman A. Alsayegh, et al. "The Potential Role of MUC16 (CA125) Biomarker in Lung Cancer: A Magic Biomarker but with Adversity." Diagnostics 12, no. 12 (November 29, 2022): 2985. http://dx.doi.org/10.3390/diagnostics12122985.
Abstract:
Lung cancer is the second most commonly diagnosed cancer in the world. In terms of the diagnosis of lung cancer, combination carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125) detection had higher sensitivity, specificity, and diagnostic odds ratios than CEA detection alone. Most individuals with elevated serum CA125 levels had lung cancer that was either in stage 3 or stage 4. Serum CA125 levels were similarly elevated in lung cancer patients who also had pleural effusions or ascites. Furthermore, there is strong evidence that human lung cancer produces CA125 in vitro, which suggests that other clinical illnesses outside of ovarian cancer could also be responsible for the rise of CA125. MUC16 (CA125) is a natural killer cell inhibitor. As a screening test for lung and ovarian cancer diagnosis and prognosis in the early stages, CA125 has been widely used as a marker in three different clinical settings. MUC16 mRNA levels in lung cancer are increased regardless of gender. As well, increased expression of mutated MUC16 enhances lung cancer cells proliferation and growth. Additionally, the CA125 serum level is thought to be a key indicator for lung cancer metastasis to the liver. Further, CA125 could be a useful biomarker in other cancer types diagnoses like ovarian, breast, and pancreatic cancers. One of the important limitations of CA125 as a first step in such a screening technique is that up to 20% of ovarian tumors lack antigen expression. Each of the 10 possible serum markers was expressed in 29–100% of ovarian tumors with minimal or no CA125 expression. Therefore, there is a controversy regarding CA125 in the diagnosis and prognosis of lung cancer and other cancer types. In this state, preclinical and clinical studies are warranted to elucidate the clinical benefit of CA125 in the diagnosis and prognosis of lung cancer.
15
Bodogai, Monica, Purevdorj Olkhanud, Yrina Rochman, Enkhzol Malchinkhuu, Katarzyna Wejksza, Ronald Gress, Charles Hesdorffer, Warren Leonard, and Arya Biragyn. "Thymic stromal lymphopoietin mediates breast cancer progression and metastasis (48.9)." Journal of Immunology 186, no. 1_Supplement (April 1, 2011): 48.9. http://dx.doi.org/10.4049/jimmunol.186.supp.48.9.
Abstract:
Abstract Breast cancer escape and metastasis is an active process that requires inflammation and participation of immune cells. We have previously reported that this is a primary tumor-controlled process which activates lungs to produce CCL17 and CCL22 to facilitate lung metastasis together with the recruitment of CCR4+ regulatory T cells (Tregs). To understand the mechanism of this process, we performed expression array analysis in both metastatic and non-metastatic cancer cells and found that metastatic cells produced thymic stromal lymphopoietin (TSLP), an IL-7-like type 1 inflammatory cytokine that is often associated with the induction of Th2-type allergic responses in the lungs. Moreover, TSLP was also abundantly expressed in variety of human solid tumors, including breast, lung, colon and ovarian cancers. To gain further insights into the role of TSLP in cancer progression, we have blocked TSLP expression in cancer cells and found that TSLP is required for efficient breast cancer escape and metastasis. Moreover, utilizing adoptive transfer studies in TSLPR deficient mice, we demonstrated that by targeting CD4+ T cells to induce Th2-type inflammatory responses, cancer-produced TSLP promoted cancer escape. Taken together, our data indicate that TSLP is an important factor that needs to be controlled to effectively combat with cancer escape.
16
Karim, Md Adnan, Abdus Samad, Utpal Kumar Adhikari, Md Ashraful Kader, Md Masnoon Kabir, Md Aminul Islam, and Md Nazmul Hasan. "A Multi-Omics Analysis of Bone Morphogenetic Protein 5 (BMP5) mRNA Expression and Clinical Prognostic Outcomes in Different Cancers Using Bioinformatics Approaches." Biomedicines 8, no. 2 (January 21, 2020): 19. http://dx.doi.org/10.3390/biomedicines8020019.
Abstract:
Cumulative studies have provided controversial evidence for the prognostic values of bone morphogenetic protein 5 (BMP5) in different types of cancers such as colon, breast, lung, bladder, and ovarian cancer. To address the inconsistent correlation of BMP5 expression with patient survival and molecular function of BMP5 in relation to cancer progression, we performed a systematic study to determine whether BMP5 could be used as a prognostic marker in human cancers. BMP5 expression and prognostic values were assessed using different bioinformatics tools such as ONCOMINE, GENT, TCGA, GEPIA, UALCAN, PrognoScan, PROGgene V2 server, and Kaplan–Meier Plotter. In addition, we used cBioPortal database for the identification and analysis of BMP5 mutations, copy number alterations, altered expression, and protein–protein interaction (PPI). We found that BMP5 is frequently down-regulated in our queried cancer types. Use of prognostic analysis showed negative association of BMP5 down-regulation with four types of cancer except for ovarian cancer. The highest mutation was found in the R321*/Q amino acid of BMP5 corresponding to colorectal and breast cancer whereas the alteration frequency was higher in lung squamous carcinoma datasets (>4%). In PPI analysis, we found 31 protein partners of BMP5, among which 11 showed significant co-expression (p-value < 0.001, log odds ratio > 1). Pathway analysis of differentially co-expressed genes with BMP5 in breast, lung, colon, bladder and ovarian cancers revealed the BMP5-correlated pathways. Collectively, this data-driven study demonstrates the correlation of BMP5 expression with patient survival and identifies the involvement of BMP5 pathways that may serve as targets of a novel biomarker for various types of cancers in human.
17
Pinheiro, Céline, Rui M. Reis, Sara Ricardo, Adhemar Longatto-Filho, Fernando Schmitt, and Fátima Baltazar. "Expression of Monocarboxylate Transporters 1, 2, and 4 in Human Tumours and Their Association with CD147 and CD44." Journal of Biomedicine and Biotechnology 2010 (2010): 1–7. http://dx.doi.org/10.1155/2010/427694.
Abstract:
Monocarboxylate transporters (MCTs) are important cellular pH regulators in cancer cells; however, the value of MCT expression in cancer is still poorly understood. In the present study, we analysed MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44. MCT expression frequency was high and heterogeneous among the different tumours. Comparing with normal tissues, there was an increase in MCT1 and MCT4 expressions in breast carcinoma and a decrease in MCT4 plasma membrane expression in lung cancer. There were associations between CD147 and MCT1 expressions in ovarian cancer as well as between CD147 and MCT4 in both breast and lung cancers. CD44 was only associated with MCT1 plasma membrane expression in lung cancer. An important number of MCT1 positive cases are negative for both chaperones, suggesting that MCT plasma membrane expression in tumours may depend on a yet nonidentified regulatory protein.
18
Weiss, Jessica M., Muhammad Danyal Ahsan, Emily M. Webster, Sarah R. Levi, Murtaza Qazi, Benedict Harvey, Evelyn Cantillo, et al. "Hereditary breast and ovarian cancer syndrome: A misnomer?" Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): 10594. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.10594.
Abstract:
10594 Background: Germline pathogenic gene variants (PGV) in homologous recombination deficiency (HRD) genes are traditionally associated with breast, ovarian, pancreatic, prostate and melanoma skin cancer. Recent evidence suggests other cancers may also be associated with these genes. We analyzed the prevalence of somatic HRD mutations in common, traditionally non-hereditary breast and ovarian cancer (HBOC) associated incident cancers in the US. Methods: Data were collected from the American Association for Cancer Research’s (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database version 13.0 via cBioPortal (http://genie.cbioportal.org). This is a publicly available, multi-institutional database of next-generation sequencing (NGS) genomic profiles of tumor samples. The database was queried for all cancers with at least 20,000 incident cases in 2022, as reported by the American Cancer Society, excluding well established HBOC associated cancers – breast, ovarian, prostate, pancreatic, melanoma. Frequencies of somatic PGVs were reported for nine HRD genes currently included in National Comprehensive Cancer Network (NCCN) management guidelines for HBOC: ATM , BARD1, BRCA1, BRCA2, BRIP1, CHEK2, PALB2, RAD51C and RAD51D. Results: A total of 78,285 tumor samples across 12 cancer types were included. At least 1 somatic HRD was found in 6.8% of all included tumors. At least 1 HRD PGV was most common in: Uterine Cancer (694/5,760, 12.1%), Non-Melanoma Skin Cancer (127/1,209, 10.5%), Bladder Cancer (462/4,605, 10.0%), Colorectal Cancer (1306/14,625, 8.9%) Non-Hodgkin’s Lymphoma (5/58, 8.6%), Esophagogastric Cancer (356/4,649, 7.7%), Hepatobiliary Cancer (219/3,325, 6.6%), Lung Cancer (1,480/23,621, 6.3%), Kidney Cancer (113/2,564, 4.4%), Brain Cancer (420/10,206, 4.1%), Thyroid Cancer (89/2,246, 4.0%) and Leukemia (80/5,417, 1.5%). The most common PGVs across all cancer types were BRCA1/2 and ATM (Table). Conclusions: A pan-cancer analysis using NGS data demonstrates a substantial rate of somatic HRD PGVs in common, traditionally non-HBOC associated cancers in the US. These data raise the possibility that germline pathogenic variants in HRD genes could be associated with several more cancers than currently known, underscoring the need for studies evaluating risks of the aforementioned cancers in germline PGV carriers. Additionally, these findings present opportunities for trials evaluating the efficacy of HRD-targeting therapies in these cancers. [Table: see text]
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Arason, Agnarsson, Johannesdottir, Johannsson, Hilmarsdottir, Reynisdottir, and Barkardottir. "The BRCA1 c.4096+3A>G Variant Displays Classical Characteristics of Pathogenic BRCA1 Mutations in Hereditary Breast and Ovarian Cancers, But Still Allows Homozygous Viability." Genes 10, no. 11 (November 1, 2019): 882. http://dx.doi.org/10.3390/genes10110882.
Abstract:
Mutations in BRCA1 result in predisposal to breast and ovarian cancers, but many variants exist with unknown clinical significance (VUS). One is BRCA1 c.4096+3A>G, which affects production of the full-length BRCA1 transcript, while augmenting transcripts lacking most or all of exon 11. Nonetheless, homozygosity of this variant has been reported in a healthy woman. We saw this variant cosegregate with breast and ovarian cancer in several family branches of four Icelandic pedigrees, with instances of phenocopies and a homozygous woman with lung cancer. We found eight heterozygous carriers (0.44%) in 1820 unselected breast cancer cases, and three (0.15%) in 1968 controls (p = 0.13). Seeking conclusive evidence, we studied tumors from carriers in the pedigrees for wild-type-loss of heterozygosity (wtLOH) and BRCA1-characteristic prevalence of estrogen receptor (ER) negativity. Of 15 breast and six ovarian tumors, wtLOH occurred in nine breast and all six ovarian tumours, and six of the nine breast tumors with wtLOH were ER-negative. These data accord with a pathogenic BRCA1-mutation. Our findings add to the current knowledge of BRCA1, and the role of its exon 11 in cancer pathogenicity, and will be of use in clinical genetic counselling.
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Erickson-Miller, Connie L., Jennifer Kirchner, Kodandaram Pillarisetti, Lone Ottesen, Yasser Mostafa Kamel, Yuan Liu, Anne-Marie Martin, and Conrad Messam. "Eltrombopag Decreases Proliferation of Ovarian, Lung and Breast Tumor Cell Lines." Blood 114, no. 22 (November 20, 2009): 2409. http://dx.doi.org/10.1182/blood.v114.22.2409.2409.
Abstract:
Abstract Abstract 2409 Poster Board II-386 Background: Eltrombopag (Promacta®) is a novel, oral thrombopoietin receptor (TpoR) agonist that interacts with the TpoR on bone marrow progenitors to stimulate megakaryocyte production, thus increasing platelet counts in thrombocytopenic patients. The effects of eltrombopag on the proliferation of solid tumor cell lines and the expression of thrombopoietin receptor (MPL, TpoR) on patient tumors is of interest given that chemotherapy can cause thrombocytopenia. Materials and methods: Proliferation was measured by Cell Titer Glo assay on 3 ovarian (OVCAR3, OVCAR4, SKOV3), 4 lung (A549, NCI-H226, NCI-H510, NCI-H460) and 3 breast (BT-474, MCF7, HCC1937) cancer cell lines from the ATCC treated with 0.01 – 100 ug/mL eltrombopag. Quantitative RT-PCR (qRT-PCR) for MPL expression was performed on the tumor cell lines and on 40 tumor samples, each from subjects with ovarian, lung or breast cancer. Microarray analysis for MPL mRNA expression was examined from 118 subjects with breast cancer and 29 with non-small cell lung cancer (NSCLC). Microarray data was normalized using robust multiarray average (RMA) and relative mRNA expression was determined. To determine expression of TpoR protein, western blot analyses was performed on some of the tumor cell lines. Results: Eltrombopag induced an inhibition of proliferation on all of the ovarian, lung and breast solid tumor cell lines tested. The IC50 ranged from 3.7 to 49.7 ug/mL (see table below). The Cmax of ITP patients treated with 75 mg eltrombopag is 11.4 ug/mL, demonstrating that these concentrations are clinically achievable. There was no enhancement of proliferation at any concentration of eltrombopag, consistent with the very low or undetectable level of MPL expression on samples of tumors from patients with these diseases. MPL was expressed at very low or undetectable levels in these tumor cell lines with the exception of the lung cancer line, NCI-H510. However, western blot analyses showed no detectable TpoR protein expression regardless of the higher levels of MPL mRNA in NCI-H510 cells. Erythropoietin receptor (EPOR) mRNA was expressed at low-to-moderate levels, while ERBB2 and IGF1R were expressed at higher levels in these cell lines. Microarray analysis showed undetectable MPL mRNA levels in all 118 samples from patients with breast cancer and 52% of the NSCLC samples, the remaining NSCLC samples expressed low levels of MPL. In contrast, EPOR was expressed in 75–100% of the breast cancer, and NSCLC samples. ERBB2 was expressed in 97–100% of the samples and IGF1R was expressed in 54–100% of the samples. When 40 other tumor samples each from subjects with ovarian, lung and breast cancer were examined by qRT-PCR, MPL mRNA levels were also very low or undetectable. EPOR, ERBB2, and IGF1R expression levels varied according to tumor type, but were greater than MPL levels. Conclusions: In summary, similar to its effects on leukemia and lymphoma cell lines, all of the nine lung, ovarian, breast or prostate tumor cell lines demonstrated decreased proliferation in response to eltrombopag. The undetectable or very low levels of expression of MPL mRNA in tumors of patients with lung, ovarian, breast or prostate cancer supports the proliferation results. Disclosures: Erickson-Miller: GlaxoSmithKline: Employment, Equity Ownership, Patents & Royalties, Research Funding. Kirchner:GlaxoSmithKline: Employment. Pillarisetti:GSK: Employment, Equity Ownership, Patents & Royalties. Ottesen:GSK: Employment, Equity Ownership. Mostafa Kamel:GSK: Employment, Equity Ownership. Liu:GSK: Employment, Equity Ownership. Martin:GSK: Employment, Equity Ownership. Messam:GSK: Employment, Equity Ownership.
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Benti, Senyi, Purushottam B. Tiwari, Dustin W. Goodlett, Leily Daneshian, Grant B. Kern, Mark D. Smith, Aykut Uren, Maksymilian Chruszcz, Linda S. Shimizu, and Geeta Upadhyay. "Small Molecule Binds with Lymphocyte Antigen 6K to Induce Cancer Cell Death." Cancers 12, no. 2 (February 22, 2020): 509. http://dx.doi.org/10.3390/cancers12020509.
Abstract:
Elevated gene expression of Lymphocyte antigen 6K (LY6K) in cancer cells is associated with poor survival outcomes in multiple different cancer types including cervical, breast, ovarian, lung, and head and neck cancer. Since inhibition of LY6K expression inhibits cancer cell growth, we set out to explore whether pharmacological inhibition of LY6K could produce the same effect. We screened small molecule libraries for direct binding to recombinant LY6K protein in a surface plasmon resonance assay. We found that NSC243928 directly binds to the full-length and mature forms of LY6K and inhibits growth of HeLa cells that express LY6K. NSC243928 did not display binding with LY6D or LY6E. Our data demonstrate a first-time proof of principle study that pharmacological inhibition of LY6K using small molecules in cancer cells is a valid approach to developing targeted therapies against LY6K. This approach will be specifically relevant in hard-to-treat cancers where LY6K is highly expressed, such as cervical, pancreatic, ovarian, head and neck, lung, gastric, and triple-negative breast cancers.
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Calaf, Gloria M., Leodan A. Crispin, Juan P. Muñoz, Francisco Aguayo, and Tammy C. Bleak. "Muscarinic Receptors Associated with Cancer." Cancers 14, no. 9 (May 7, 2022): 2322. http://dx.doi.org/10.3390/cancers14092322.
Abstract:
Cancer has been considered the pathology of the century and factors such as the environment may play an important etiological role. The ability of muscarinic agonists to stimulate growth and muscarinic receptor antagonists to inhibit tumor growth has been demonstrated for breast, melanoma, lung, gastric, colon, pancreatic, ovarian, prostate, and brain cancer. This work aimed to study the correlation between epidermal growth factor receptors and cholinergic muscarinic receptors, the survival differences adjusted by the stage clinical factor, and the association between gene expression and immune infiltration level in breast, lung, stomach, colon, liver, prostate, and glioblastoma human cancers. Thus, targeting cholinergic muscarinic receptors appears to be an attractive therapeutic alternative due to the complex signaling pathways involved.
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Ferreira, Thamara, Thais Ferreira Bomfim-Palma, Isabelle Joyce de Lima Silva-Fernandes, Gabriela Espirito Santo Felix, Inacelli Queiroz De Souza Caires, Leandro Apolinário Silva, Luciana Garcia Landeiro, et al. "PALB2 mutations in Brazilian patients from North-Northeast regions." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e13670-e13670. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e13670.
Abstract:
e13670 Background: Loss-of-function mutations in PALB2 gene are associated with increased risk for breast cancer and possibly pancreatic, ovarian, male breast, prostate, colorectal as others cancers. In Brazil it has been estimated that up to 1,516 new cases of hereditary breast cancer for 2020 in the North and Northeast regions. Analysis of susceptibility gene mutations helps identify precisely the high-risk patient and their families, whom need specific and personalized clinical management as high-risk individuals. Methods: Twenty-six patients with pathogenic mutations in PALB2 gene identify by next-generation sequencing from states of Bahia (11), Ceará (9), Pernambuco (5) and Rondônia (1) in the North and Northeast regions were analyzed. Results: Most of the patients analyzed had only breast cancer (80%), including two cases of male breast cancer (9,5%); the others were isolated cases of endometrial cancer (4%), breast and pancreas cancers (4%), breast and lung cancers (4%), only ovarian cancer (4%) and ovarian and breast cancers (4%). Most cancers were stage II or III (65%). Family history of cancer was observed in 22/26 (84%); the most common tumors were breast, prostate, pancreas and thyroid. The founder mutations were more frequent in exons: 4 (58%) and 12 (15%). Eleven variants were found as follow: c.1240C > T (19%); c.3256delC (15%); c.1671_1674delTATT (11.5%); c.355delC (11.5%); NC_000016.9:g.(?_23632673)_(23652488_?)del (11,5%). The greatest variety of mutations was found in the state of Bahia, probably due to the greater number of patients included (42%). Conclusions: These data suggest that changes in clinical management of PALB2 patients are needed since the phenotype observed exhibited pattern of hereditary tumors, including male breast cancer. Besides that, PALB2 gene should be included in painel gene analysis in patients from the North and Northeast of Brazil because its high frequency of pathogenic variants.
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DUPONT, J., C. AGHAJANIAN, P. SABBATINI, and D. R. SPRIGGS. "New agents for the treatment of ovarian cancer: the next generation." International Journal of Gynecologic Cancer 15, Suppl 3 (November 2005): 252–57. http://dx.doi.org/10.1136/ijgc-00009577-200511001-00012.
Abstract:
Ovarian cancer shares many important characteristics with more common malignancies including breast, lung, and colon cancer. The relative chemosensitivity of ovarian cancer and other aspects of its unique biology provide opportunities for novel interventions. In this brief summary, some of the potential targets in ovarian cancer are discussed, including the HER kinases, heat shock protein, the 26S proteasome, and the angiogenesis pathway. The opportunities to change the treatment of ovarian cancer will require creative clinical trial design but the next decade promises to be filled the therapeutic advances for patients with ovarian cancer.
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Muggia, Franco M. "Significant developments in ovarian, breast and lung cancer therapy." Inpharma Weekly &NA;, no. 994 (July 1995): 3–5. http://dx.doi.org/10.2165/00128413-199509940-00002.
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Brown, Geoffrey. "Deregulation of All-Trans Retinoic Acid Signaling and Development in Cancer." International Journal of Molecular Sciences 24, no. 15 (July 28, 2023): 12089. http://dx.doi.org/10.3390/ijms241512089.
Abstract:
Cancer stem cells are the root cause of cancer, which, in essence, is a developmental disorder. All-trans retinoic acid (ATRA) signaling via ligand-activation of the retinoic acid receptors (RARs) plays a crucial role in tissue patterning and development during mammalian embryogenesis. In adults, active RARγ maintains the pool of hematopoietic stem cells, whereas active RARα drives myeloid cell differentiation. Various findings have revealed that ATRA signaling is deregulated in many cancers. The enzymes for ATRA synthesis are downregulated in colorectal, gastric, lung, and oropharyngeal cancers. ATRA levels within breast, ovarian, pancreatic, prostate, and renal cancer cells were lower than within their normal counterpart cells. The importance is that 0.24 nM ATRA activates RARγ (for stem cell stemness), whereas 100 times more is required to activate RARα (for differentiation). Moreover, RARγ is an oncogene regarding overexpression within colorectal, cholangiocarcinoma, hepatocellular, ovarian, pancreatic, and renal cancer cells. The microRNA (miR) 30a-5p downregulates expression of RARγ, and miR-30a/miR-30a-5p is a tumor suppressor for breast, colorectal, gastric, hepatocellular, lung, oropharyngeal, ovarian, pancreatic, prostate, and renal cancer. These complementary findings support the view that perturbations to ATRA signaling play a role in driving the abnormal behavior of cancer stem cells. Targeting ATRA synthesis and RARγ has provided promising approaches to eliminating cancer stem cells because such agents have been shown to drive cell death.
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Cole, Alexander P., Chang Lu, Marieke J. Krimphove, Julie Szymaniak, Maxine Sun, Sean A. Fletcher, Stuart R. Lipsitz, et al. "Comparing the Association Between Insurance and Mortality in Ovarian, Pancreatic, Lung, Colorectal, Prostate, and Breast Cancers." Journal of the National Comprehensive Cancer Network 17, no. 9 (September 2019): 1049–58. http://dx.doi.org/10.6004/jnccn.2019.7296.
Abstract:
Background: Insurance coverage is associated with better cancer outcomes; however, the relative importance of insurance coverage may differ between cancers. This study compared the association between insurance coverage at diagnosis and cancer-specific mortality (CSM; insurance sensitivity) in 6 cancers. Patients and Methods: Using the SEER cancer registry, data were abstracted for individuals diagnosed with ovarian, pancreatic, lung, colorectal, prostate, or breast cancer in 2007 through 2010. The association between insurance coverage at diagnosis and CSM was modeled using a Fine and Gray competing-risks regression adjusted for demographics. An interaction term combining insurance status and cancer type was used to test whether insurance sensitivity differed between cancers. Separate models were fit for each cancer. To control for lead-time bias and to assess whether insurance sensitivity may be mediated by earlier diagnosis and treatment, additional models were fit adjusting for disease stage and treatment. Results: Lack of insurance was associated with an increased hazard of CSM in all cancers (P<.01). The magnitude of the effect differed significantly between cancers (Pinteraction=.04), ranging from an adjusted hazard ratio of 1.13 (95% CI, 1.01–1.28) in ovarian and 1.19 (95% CI, 1.11–1.29) in pancreatic cancer to 2.19 (95% CI, 2.02–2.37) in breast and 2.98 (95% CI, 2.54–3.49) in prostate cancer. The benefit of insurance was attenuated after adjusting for stage and treatment (eg, screening/early treatment effect), with the largest reductions in prostate, breast, and colorectal cancers. Conclusions: Greater insurance sensitivity was seen in screening-detected malignancies with effective treatments for early-stage disease (eg, prostate, breast, and colorectal cancers). Given that this differential is significantly reduced after adjusting for stage and treatment, our results suggest that a significant portion (but not all) of the benefit of insurance coverage is due to detection and treatment of certain curable early-stage cancers.
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Solomon, Benjamin Maurice, Kari G. Rabe, Susan L. Slager, Jerry D. Brewer, James R. Cerhan, and Tait D. Shanafelt. "Overall and cancer-specific survival of breast, colon, and lung cancer in patients with and without chronic lymphocytic leukemia: A SEER population-based study of over 1 million patients." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 6571. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.6571.
Abstract:
6571 Background: Chronic lymphocytic leukemia (CLL) is associated with an increased risk of developing second cancers. However, it is unknown whether CLL alters the natural history of these cancers once they occur. Methods: All patients with breast (n=583,838), colon (n=412,932), prostate (n=632,922), lung (n=489,290), kidney (n=95,902), pancreas (n=82,121) and ovarian (n=61,958) cancer reported to the Surveillance, Epidemiology, and End Results (SEER) Program from 1990 to 2007 were identified. Overall survival (OS; death due to any cause) and cancer-specific survival (death due to cancer site of interest) were examined, comparing patients with or without pre-existing CLL. Age- and sex-adjusted hazard ratios (HRs) were calculated. Results: OS for patients with pre-existing CLL was inferior for patients with breast (HR=1.61; p<0.001), colon (HR=1.65; p<0.001), kidney (HR=1.41; p<0.001), prostate (HR=1.75; p<0.001), and lung (HR=1.22; p<0.001) cancer after adjusting for age and sex. After excluding CLL-related deaths, OS remained shorter among patients with breast (p<0.001), colon (p<0.001), kidney (p=0.03), prostate (p<0.001), and lung (p<0.001) cancer. Cancer-specific survival was inferior for patients with breast (HR=1.29; p=0.03), colon (HR=1.75; p<0.001), and lung cancer (HR=1.17; p<0.001) who had pre-existing CLL after adjusting for age and sex. Conclusions: Several common cancers, including breast, colon, and lung, have inferior overall and cancer-specific survival when there is coexistent CLL. [Table: see text]
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Lawler, Thomas, and Shaneda Warren Andersen. "Serum 25-Hydroxyvitamin D and Cancer Risk: A Systematic Review of Mendelian Randomization Studies." Nutrients 15, no. 2 (January 13, 2023): 422. http://dx.doi.org/10.3390/nu15020422.
Abstract:
Epidemiological studies suggest that higher serum 25-hydroxyvitamin D is associated with lower risk for several cancers, including breast, prostate, colorectal, and lung cancers. To mitigate confounding, genetic instrumental variables (IVs) have been used to estimate causal associations between 25-hydroxivtamin D and cancer risk via Mendelian randomization (MR). We provide a systematic review of 31 MR studies concerning 25-hydroxyvitamin D and cancer incidence and mortality identified from biomedical databases. MR analyses were conducted almost exclusively in European-ancestry populations and identified no statistically significant associations between higher genetically predicted 25-hydroxyvitamin D and lower risk for total cancer or colorectal, breast, prostate, lung, or pancreatic cancers. In recent studies including ≥80 genetic IVs for 25-hydroxyvitamin D, null associations were reported for total cancer (odds ratio [95% confidence interval] per 1-standard deviation increase: 0.98 [0.93–1.04]), breast (1.00 [0.98–1.02]), colorectal (0.97 [0.88–1.07]), prostate (0.99 [0.98–1.01]), and lung cancer (1.00 [0.93–1.03]). A protective association was observed for ovarian cancer in the Ovarian Cancer Association Consortium (0.78 [0.63–0.96] per 20 nmol/L increase, p-trend = 0.03), but not in the UK Biobank (1.10 [0.80–1.51]). Null associations were reported for other tumor sites (bladder, endometrium, uterus, esophagus, oral cavity and pharynx, kidney, liver, thyroid, or neural cells). An inconsistent protective association for cancer-specific mortality was also observed. Results from MR analyses do not support causal associations between 25-hydroxyvitamin D and risk for cancer incidence or mortality. Studies including non-White populations may be valuable to understand low 25-hydroxyvitamin D as a modifiable risk factor in populations with a higher risk of common cancers, including African ancestry individuals.
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Guo, Maoni, and San Ming Wang. "The BRCAness Landscape of Cancer." Cells 11, no. 23 (December 1, 2022): 3877. http://dx.doi.org/10.3390/cells11233877.
Abstract:
BRCAness refers to the damaged homologous recombination (HR) function due to the defects in HR-involved non-BRCA1/2 genes. BRCAness is the important marker for the use of synthetic lethal-based PARP inhibitor therapy in breast and ovarian cancer treatment. The success provides an opportunity of applying PARP inhibitor therapy to treat other cancer types with BRCAness features. However, systematic knowledge is lack for BRCAness in different cancer types beyond breast and ovarian cancer. We performed a comprehensive characterization for 40 BRCAness-related genes in 33 cancer types with over 10,000 cancer cases, including pathogenic variation, homozygotic deletion, promoter hypermethylation, gene expression, and clinical correlation of BRCAness in each cancer type. Using BRCA1/BRCA2 mutated breast and ovarian cancer as the control, we observed that BRCAness is widely present in multiple cancer types. Based on the sum of the BRCAneass features in each cancer type, we identified the following 21 cancer types as the potential targets for PARPi therapy: adrenocortical carcinoma, bladder urothelial carcinoma, brain lower grade glioma, colon adenocarcinoma, esophageal carcinoma, head and neck squamous carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, mesothelioma, rectum adenocarcinoma, pancreatic adenocarcinoma, prostate adenocarcinoma, sarcoma, skin cutaneous melanoma, stomach adenocarcinoma, uterine carcinosarcoma, and uterine corpus endometrial carcinoma.
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Cheng, En, Donghoon Lee, Rulla M. Tamimi, Susan Hankinson, Walter C. Willett, Edward L. Giovannucci, Heather Eliassen, et al. "Long-term cancer survival in cohorts of U.S. health professionals." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 12075. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.12075.
Abstract:
12075 Background: Few studies have investigated long-term survival and causes of death among men and women diagnosed with major cancers. Methods: We estimated overall and cause-specific mortality rates for men diagnosed with prostate, lung and bronchus, colon and rectum, bladder, and melanoma cancer in the Health Professionals Follow-up Study between 1986-2010+, and women with breast, lung and bronchus, colon and rectum, uterine corpus, thyroid, and ovarian cancer in the Nurses’ Health Study (NHS) between 1976-2010+ and NHS II between 1989-2010+. Kaplan-Meier curves were used to calculate cumulative mortality rates at 5, 10, 15, 20, and 30 years and competing risk methods were used to calculate cumulative cancer-specific mortality rates of major causes at 5, 10, 15, 20, and 30 years. Additionally, among women 40-year mortality rates were calculated. Results: Except for lung and ovarian, most major cancer patients are more likely to die from other causes than the index cancer. We observed two basic patterns for cumulative cancer-specific mortality rates. The first pattern is greatly diminished risk of index cancer-specific mortality 10 years or more following diagnosis - for colorectal cancer, cancer-specific mortality rate increased by less than 3% between 10 to 30- or 40-year following diagnosis (among men, from 35.1% to 36.7%; among women, from 34.8% to 37.7%), and this pattern also applied to bladder, melanoma, or uterine corpus cancer. The second one is sustained, but nevertheless low, excess risk - prostate cancer-specific mortality rate increased gradually and almost linearly from 5.3% to 15.1% after diagnosis from 5 to 30 years, and for breast cancer, it increased likewise from 7.2% to 18.9% after diagnosis from 5 to 40 years. Conclusions: Except for lung and ovarian cancers, patients diagnosed with major cancers were more likely to die from causes other than cancer. Colorectal, bladder, melanoma or uterine corpus cancer patients surviving more than 10 years after diagnosis are unlikely to ever die from that disease. [Table: see text]
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Tourassi, Georgia, Hong-Jun Yoon, Songhua Xu, and Xuesong Han. "The utility of web mining for epidemiological research: studying the association between parity and cancer risk." Journal of the American Medical Informatics Association 23, no. 3 (November 27, 2015): 588–95. http://dx.doi.org/10.1093/jamia/ocv141.
Abstract:
Background The World Wide Web has emerged as a powerful data source for epidemiological studies related to infectious disease surveillance. However, its potential for cancer-related epidemiological discoveries is largely unexplored. Methods Using advanced web crawling and tailored information extraction procedures, the authors automatically collected and analyzed the text content of 79 394 online obituary articles published between 1998 and 2014. The collected data included 51 911 cancer (27 330 breast; 9470 lung; 6496 pancreatic; 6342 ovarian; 2273 colon) and 27 483 non-cancer cases. With the derived information, the authors replicated a case-control study design to investigate the association between parity (i.e., childbearing) and cancer risk. Age-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each cancer type and compared to those reported in large-scale epidemiological studies. Results Parity was found to be associated with a significantly reduced risk of breast cancer (OR = 0.78, 95% CI, 0.75-0.82), pancreatic cancer (OR = 0.78, 95% CI, 0.72-0.83), colon cancer (OR = 0.67, 95% CI, 0.60-0.74), and ovarian cancer (OR = 0.58, 95% CI, 0.54-0.62). Marginal association was found for lung cancer risk (OR = 0.87, 95% CI, 0.81-0.92). The linear trend between increased parity and reduced cancer risk was dramatically more pronounced for breast and ovarian cancer than the other cancers included in the analysis. Conclusion This large web-mining study on parity and cancer risk produced findings very similar to those reported with traditional observational studies. It may be used as a promising strategy to generate study hypotheses for guiding and prioritizing future epidemiological studies.
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Luo, Huiyan, Pansong Li, Wei Wei, Yong-Bin Lin, Hong Yang, Han Yang, Kong-Jia Luo, et al. "High-sensitive multi-cancers early detection for 8 cancer types by cell-free DNA targeted methylation sequencing: A retrospective cohort study." Journal of Clinical Oncology 42, no. 16_suppl (June 1, 2024): 3043. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.3043.
Abstract:
3043 Background: Early screening effectively reduces mortality associated with cancer. Currently, most cancers lack effective screening paradigms. We developed blood-based multi-cancers early detection (MCED) and cancer signal origin (CSO) approaches in 8 types of cancers including esophageal, stomach, colorectal, pancreatic, liver, lung, breast and ovarian cancer. Methods: DNA methylation data generated based on GM-seq by public and internal whole genome methylation data. Based on these data, a panel of 155,362 CpG sites spanning the 2.0M genome was constructed and validated. We enrolled a case-control cohort of 746 participants (522 cancers, 224 non-cancers) for MCED model development. cell-free DNA (cfDNA) was isolated from 10 ml peripheral blood from each participant. A targeted methylation sequencing of cfDNA in plasma baseline was established using 224 non-cancers blood samples for 8 types of cancers. Finally, we developed a MCED model named AMBER for distinguishing cancer from non-cancer individuals. Results: DNA methylation data were from 8 types of cancers (cancer tissues: n=812, adjacent/normal tissues: n=416, cancer peripheral bloods: n=624, normal peripheral bloods: n=503) in internal and Infinium Human Methylation 450K array (cancer tissues: n=5000+, adjacent/normal tissues: n=1000+) from public data. 224 non-cancer individuals (healthy: n=196, cancer benign: n=28, male: female, 54.3%: 45.7%) were collected as control, while 522 cancer patients (male: female, 50.0%: 50.0%, stage I 26.9%, II 21.1%) from esophageal (n=56, stage I: n=10), stomach (n=47, stage I: n=11), colorectal (n=72, stage I: n=16), pancreatic (n=64, stage I: n=16), liver (n=69, stage I: n=22), lung (n=103, stage I: n=46), breast (n=41) and ovarian cancer (n=70, stage I: n=17). AMBER showed 99.1% specificity and total sensitivity 77.2% (95% confidence interval (CI): 73.4% to 80.7%). Of them, 56.8% (95% CI: 48.2% to 65.2%) of all stage I cases were detected, 70.6% (95% CI: 61.2% to 79.0%) for stage II, 84.5% (95% CI: 77.6% to 89.9%) for stage III, and 96.7% (95% CI: 91.8% to 99.1%) for stage IV. Strikingly, for stage I cancers, the sensitivity of esophageal, stomach, colorectal, pancreatic, liver, lung and ovarian cancer were 80.0%, 63.6%, 43.8%, 62.5%, 86.4%, 30.4% and 82.4% respectively. The sensitivity of esophageal, stomach, colorectal, pancreatic, liver, lung, breast and ovarian cancer reached 91.1%, 76.6%, 75.0%, 78.1%, 94.2%, 55.3%, 65.9% and 90.0%. For CSO model, the accuracy of TPO1 and TPO2 was 78.9% (95% CI: 74.6% to 82.8%) and 89.1% (95% CI: 85.6% to 92.0%). Conclusions: Our MCED tests demonstrated superior performance in detecting 8 types of cancers, especially early cancer screening, by utilizing cfDNA methylation information. It suggests the model can complement lack of multi-cancers early detection.
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Olea-Flores, Monserrat, Juan C. Juárez-Cruz, Miriam D. Zuñiga-Eulogio, Erika Acosta, Eduardo García-Rodríguez, Ana E. Zacapala-Gomez, Miguel A. Mendoza-Catalán, Julio Ortiz-Ortiz, Carlos Ortuño-Pineda, and Napoleón Navarro-Tito. "New Actors Driving the Epithelial–Mesenchymal Transition in Cancer: The Role of Leptin." Biomolecules 10, no. 12 (December 15, 2020): 1676. http://dx.doi.org/10.3390/biom10121676.
Abstract:
Leptin is a hormone secreted mainly by adipocytes; physiologically, it participates in the control of appetite and energy expenditure. However, it has also been linked to tumor progression in different epithelial cancers. In this review, we describe the effect of leptin on epithelial–mesenchymal transition (EMT) markers in different study models, including in vitro, in vivo, and patient studies and in various types of cancer, including breast, prostate, lung, and ovarian cancer. The different studies report that leptin promotes the expression of mesenchymal markers and a decrease in epithelial markers, in addition to promoting EMT-related processes such as cell migration and invasion and poor prognosis in patients with cancer. Finally, we report that leptin has the greatest biological relevance in EMT and tumor progression in breast, lung, prostate, esophageal, and ovarian cancer. This relationship could be due to the key role played by the enriched tumor microenvironment in adipose tissue. Together, these findings demonstrate that leptin is a key biomolecule that drives EMT and metastasis in cancer.
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Bacalbasa, N., A. Traistaru, and I. Balescu. "OVARIAN METASTATIC TUMORS – A LITERATURE REVIEW." Romanian Medical Journal 62, no. 2 (June 30, 2015): 115–18. http://dx.doi.org/10.37897/rmj.2015.2.6.
Abstract:
Ovarian metastatic tumors represents up to 10% of all ovarian malignancies. The most encountered tumors which may give birth to ovarian cancer are those originating from the gastric tube; however, other malignancies such as breast, cervix, lung or even skin may be associated with ovarian metastatic tumors. This is a literature review of the most frequently seen ovarian metastatic tumors.
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Adeboyeje, Gboyega, Eleanor O. Caplan, Yihua Xu, Monica Chase, Sheetal Sheth, Brandon T. Suehs, and Nicole Myer. "Abstract 4111: Trends in the use of broad genomic sequencing-directed therapy among Medicare patients with newly diagnosed advanced cancer in the United States from 2018-2020: A retrospective analysis from the SEQUENCE study." Cancer Research 82, no. 12_Supplement (June 15, 2022): 4111. http://dx.doi.org/10.1158/1538-7445.am2022-4111.
Abstract:
Abstract Introduction/Purpose: Recent advances have led to approval of multiple new targeted drugs across a variety of indications based on genomic markers. In part due to the increasing number of therapeutically actionable genomic markers in many cancers, whether a strategy of upfront broad next-generation sequencing (NGS) could potentially improve selection of patients for targeted drugs compared to narrow/single gene panels remains uncertain. We examined recent trends in the proportions of patients receiving sequencing-directed therapy following the use of broad NGS panel testing among newly diagnosed patients with advanced cancer in the United States (US). Methods: Using a retrospective cohort study design to analyze administrative claims data on patients (65-89 years) enrolled in a national US payer Medicare Advantage plans from 2018 through 2020, we identified patients with select incident advanced/metastatic cancer diagnoses (lung, colorectal [CRC], breast, ovarian) based on previously validated algorithms. We defined 2 cohorts by the occurrence of broad NGS (51+ genes) versus narrow (≤50 genes) sequencing within 182 days of diagnosis using a previously validated algorithm based on laboratory tax identification numbers, current procedural terminology codes, and diagnosis codes. We described the rates of sequencing-directed therapy (defined as receipt of an FDA-approved genomically targeted drug) within 90 days of testing by broad NGS versus narrow panels across tumor types and subgroups defined by race (White versus Black) and annual income (<$50,000 versus ≥$50,000) data. Results: We identified 32,130 patients with incident advanced cancer during the study period. Overall (broad plus narrow panels) testing rates varied by cancer type (lung, 40.1%; CRC 28.6%; breast 53.9%; ovarian 41.7%). Compared to narrow gene panels, a higher proportion of patients with lung and ovarian cancer sequenced with broad NGS panels initiated an FDA-approved genomically targeted drug within 90 days of testing (lung: 8.6% versus 7.5%; ovarian: 9.2% versus 5.5%). For CRC and breast cancer, narrow gene panels matched a higher proportion of patients with targeted drug within 90 days of testing versus broad NGS panel testing (CRC: 5.1 versus 4.5%; breast: 41.7% versus 35.7%). Conclusions: A higher proportion of patients initiated a genomically-targeted drug after broad NGS panel testing compared with narrow gene panels in lung and ovarian cancer. As the number of actionable genomic markers in advanced cancers increase, it will be important to ensure that this technology is adopted to improve upon the existing standard of care and that aligns with values important to patients. Citation Format: Gboyega Adeboyeje, Eleanor O. Caplan, Yihua Xu, Monica Chase, Sheetal Sheth, Brandon T. Suehs, Nicole Myer. Trends in the use of broad genomic sequencing-directed therapy among Medicare patients with newly diagnosed advanced cancer in the United States from 2018-2020: A retrospective analysis from the SEQUENCE study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4111.
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Yap, Timothy A., Arya Ashok, Jessica Stoll, Anna Ewa Schwarzbach, Kimberly L. Blackwell, Tianhong Li, Hyunseok Kang, Judy Ellen Garber, and Funda Meric-Bernstam. "Rate of incidental germline findings detected by tumor-normal matched sequencing in cancer types lacking hereditary cancer testing guidelines." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 10582. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.10582.
Abstract:
10582 Background: Up to 10% of all cancers are associated with hereditary cancer syndromes; however, guidelines for germline testing are currently limited to patients and families with specific cancer types (ovarian, breast, prostate, pancreatic, etc.). Although germline alterations have been shown in genes associated with cancers such as bile-duct, head & neck, brain, bladder, esophageal, and lung cancers, genetic testing is not routinely offered (PMID: 28873162). In such cancers, a guidelines-based approach may fail to detect cancer risk variants found by tumor-normal (T/N) matched sequencing. Here, we report the prevalence of incidental germline findings in patients with the aforementioned 6 cancer types and highlight frequently mutated genes by cancer type. Methods: We retrospectively analyzed next-generation sequencing data from de-identified records of 19,630 patients tested using Tempus|xT T/N matched assay. Incidental germline findings (i.e., single nucleotide variants and small insertions/deletions) detected in 50 hereditary cancer genes were determined for: bile duct (n = 466), head & neck (n = 673), esophageal (n = 395), brain (n = 1,391), bladder (n = 810), and lung (n = 5,544), where n = total patients. For comparison, we also included 4 cancer types that frequently undergo germline testing: ovarian (n = 2,042), breast (n = 3,542), prostate (n = 2,146), and pancreatic (n = 2,621). Results: We detected incidental pathogenic/likely pathogenic germline variants (P/LPV) in 6.5% (601/9,279) of patients diagnosed with the 6 selected cancer types lacking hereditary cancer testing guidelines. The highest prevalence of P/LPV was identified in patients with bladder (8%), brain (6.9%), and lung (6.5%) cancers. Frequently mutated genes (Table) include ATM (n = 62), BRCA2 (n = 60), BRCA1 (n = 33), APC (n = 27), and CHEK2 (n = 21). Of note, the Ashkenazi Jewish variant (p.I1307K) was the most frequent mutation in APC. For cancer types where patients frequently undergo germline testing, the rates of incidental germline findings in descending order were ovarian (15%), breast (12%), prostate (9.4%), and pancreatic (8.5%) cancers. Conclusions: In addition to enhanced variant calling, T/N matched sequencing may identify germline variants missed by a guidelines-based approach to testing. The identification of such germline findings may have clinical implications for the patient, as well as at-risk family members, thereby resulting in the opportunity for genetic counseling and risk-stratified intervention.[Table: see text]
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Vlasenkova, Ramilia, Alsina Nurgalieva, Natalia Akberova, Mikhail Bogdanov, and Ramziya Kiyamova. "Characterization of SLC34A2 as a Potential Prognostic Marker of Oncological Diseases." Biomolecules 11, no. 12 (December 14, 2021): 1878. http://dx.doi.org/10.3390/biom11121878.
Abstract:
The main goal of this study is to consider SLC34A2 as a potential prognostic marker of oncological diseases using the mutational, expression, and survival data of cancer studies which are publicly available online. We collected data from four databases (cBioPortal, The Cancer Genome Atlas; cBioPortal, Genie; International Cancer Genome Consortium; ArrayExpress). In total, 111,283 samples were categorized according to 27 tumor locations. Ninety-nine functionally significant missense mutations and twelve functionally significant indel mutations in SLC34A2 were found. The most frequent mutations were SLC34A2-ROS1, p.T154A, p.P506S/R/L, p.G257A/E/R, p.S318W, p.A396T, p.P410L/S/H, p.S461C, p.A473T/V, and p.Y503H/C/F. The upregulation of SLC34A2 was found in samples of myeloid, bowel, ovarian, and uterine tumors; downregulation was found in tumor samples of breast, liver, lung, and skin cancer tumors. It was found that the life expectancy of breast and thymus cancer patients with an SLC34A2 mutation is lower, and it was revealed that SLC34A2 overexpression reduced the life span of patients with brain, ovarian, and pancreatic tumors. Thereby, for these types of oncological diseases, the mutational profile of SLC34A2 can be a potential prognostic marker for breast and thymus cancers, and the upregulation of SLC34A2 can be a potential prognostic marker for brain, ovarian, and pancreatic cancers.
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Atta, Ihab Shafek, and Fahd Nasser AlQahtani. "Thyroid, Renal, and Breast Carcinomas, Chondrosarcoma, Colon Adenomas, and Ganglioneuroma: A New Cancer Syndrome, FAP, or Just Coincidence." Case Reports in Medicine 2016 (2016): 1–5. http://dx.doi.org/10.1155/2016/2928084.
Abstract:
We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner’s, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A.
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Heeke, Arielle Lutterman, Tabari Baker, Filipa Lynce, Michael J. Pishvaian, and Claudine Isaacs. "Prevalence of homologous recombination deficiency among all tumor types." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 1502. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.1502.
Abstract:
1502 Background: Triple negative breast and ovarian cancer are known to have a high frequency of homologous recombination deficiencies (HRDef). The prevalence of HRDef among all tumors is unknown. Methods: Molecular profiles of 48,733 tumors obtained from pts with bladder, breast, ovarian, pancreas, prostate, thyroid, cervical, hepatobiliary, colorectal (CRC), endometrial, gastric/esophageal (GE), head/neck, renal, non-small cell lung (NSCLC), small cell lung (SCLC), GIST, glioma, melanoma, sarcoma and unknown 1° cancers were reviewed to identify somatic pathogenic mutations (mut) in HR genes ATM, ATRX, BARD1, BLM, BRCA1/2, BRIP1, FANCA/C/D2/E/F/G/L, MRE11A, NBN, PALB2, PTEN, RAD50, RAD51, RAD51B, or WRN. Molecular profiles were generated from tumors submitted to Caris Life Sciences using multiple technologies including next generation sequencing (average read depth 500X). Results: Overall frequency of HR mut among all tumors is 11.61% (5658/48733). Cancer lineages with highest frequency of HR mut are endometrial (38.08%, 1956/5137), glioma (15.90%, 265/1667), ovarian (12.99%, 1151/8862), prostate (11.21%, 77/687), cervix (10.06%, 79/785) & breast (9.66%, 562/5818). Least commonly mutated lineages include GIST (1.50%, 3/200), sarcoma (3.12%, 55/1763), head/neck (3.70%, 24/648), hepatobiliary (4.72%, 39/827) & pancreas (5.05%, 102/2022). Frequencies of HR gene mutations are depicted in Table 1. Conclusions: HR mutations were seen in 11.61% of tumors. While the percentage of HRDef in pancreatic cancer pts is lower than what has been seen in other datasets, the percentage in breast and ovarian cancer, as well as the percentage of other tumors with HRDef, provide a path to employ HRDef-directed therapies such as platinums, but especially PARP inhibitors and newer agents such as ATRX inhibitors. [Table: see text]
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Bel’skaya, Lyudmila V., Elena A. Sarf, Alexandra I. Loginova, Dmitry M. Vyushkov, and En Djun Choi. "Potential Diagnostic Value of Salivary Tumor Markers in Breast, Lung and Ovarian Cancer: A Preliminary Study." Current Issues in Molecular Biology 45, no. 6 (June 10, 2023): 5084–98. http://dx.doi.org/10.3390/cimb45060323.
Abstract:
The aim of the study was to determine the content of tumor markers for breast, lung and ovarian cancer in saliva, as well as for benign diseases of the corresponding organs and in the control group, and to evaluate their diagnostic significance. Strictly before the start of treatment, saliva samples were obtained and the concentrations of tumor markers (AFP, NSE, HE4, CA15-3, CA72-4, CA125 and CEA) were determined using an enzyme immunoassay (ELISA). CA125 and HE4 were simultaneously determined to be in the blood serum of patients with ovarian cancer. The concentrations of salivary CEA, NSE, CA15-3, CA72-4 and CA125 of the control group were significantly lower than in oncological diseases; however, these tumor markers also increased in saliva with benign diseases. The content of tumor markers depends on the stage of cancer, and the presence of lymph node metastasis; however, the identified patterns are statistically unreliable. The determination of HE4 and AFP in saliva was not informative. In general, the area of potential use of tumor markers in saliva is extremely narrow. Thus, CEA may be diagnostic for breast and lung cancer, but not for ovarian cancer. CA72-4 is most informative for ovarian mucinous carcinoma. None of the markers showed significant differences between malignant and non-malignant pathologies.
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Chen, Lifeng, Binbing Ling, Jane Alcorn, and Jian Yang. "Quantitative Analysis of the Expression of Human N-myristoyltransferase 1 (hNMT-1) in Cancers." Open Biomarkers Journal 2, no. 1 (March 13, 2009): 6–10. http://dx.doi.org/10.2174/1875318300902010006.
Abstract:
Human N-myristoyltransferase 1 (hNMT-1) catalyzes the covalent attachment of myristic acid to N-terminal glycine residues (myristoylation) of numerous protein substrates. Overexpression of hNMT-1 in colorectal and gallbladder cancers makes it a potential biomarker and drug design target for such cancers. In this study, we investigated hNMT-1 expression during the progression of eight different human cancers using quantitative RT-PCR. The study results showed that hNMT-1 was up-regulated in breast, colon, lung and ovarian cancers but not kidney, liver, prostate and thyroid cancers. This suggests a role for hNMT-1 as a biomarker for detection of breast, colon, lung and ovarian cancers. This study also suggests the available hNMT-1 inhibitors may be potential therapeutic agents against breast and lung cancers through all disease stages, although their use would likely be limited to early stage colon and ovarian cancers.
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Curiel, Tyler, Suzanne Thibodeaux, Shawna Wall, Sri Lakshmi Pandeswara, Benjamin Daniel, Justin Drerup, Kruthi Murthy, Ilona Kryczek, Weiping Zou, and Brian Barnett. "Denileukin diftitox depletes regulatory T cells without clinical benefit in advanced stage epithelial ovarian carcinoma (VAC3P.945)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 73.7. http://dx.doi.org/10.4049/jimmunol.192.supp.73.7.
Abstract:
Abstract Denileukin diftitox (DT) depletes regulatory T cells (Treg) that correlates with immune and clinical benefits in metastatic human melanoma and improved clinical outcomes in a renal cancer vaccine trial. We tested immune and clinical effects of Treg depletion using DT in a phase 0/I cancer trial and a phase II ovarian cancer trial. In our phase 0/I trial, we noted reductions in blood Treg prevalence and concentration (median ~18% and ~50%, respectively) 3-7 days after one intravenous DT infusion at 9 or 12 μg/kg, in 6 of 7 evaluable patients with breast, lung, and ovarian cancers, and melanoma, and increased blood IFN-γ+ and Ki-67+ T cells. Weekly DT significantly reduced metastatic tumors in one ovarian cancer patient prompting a small phase II trial in epithelial ovarian cancers. 28 patients received DT once every 3-4 weeks which significantly depleted functional Tregs from blood and the tumor microenvironment, but with variable immune outcomes and no significant clinical efficacy. Weekly DT eventually reduced effector T cells. In mouse ovarian cancer models we found that: i) DT efficacy depended on adaptive immunity, ii) its IL-2 moiety did not mediate clinical effects, and iii) its treatment mechanism appeared distinct from anti-CD25 antibody, which depleted Tregs in a human breast cancer trial. DT depletes Tregs in various carcinomas but requires more dosing and schedule studies. Treg-specific agents and combination treatments could also improve Treg depletion efficacy.
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Detopoulou, Paraskevi, George I. Panoutsopoulos, Marina Mantoglou, Periklis Michailidis, Ifigenia Pantazi, Spyros Papadopoulos, and Andrea Paola Rojas Gil. "Relation of Mean Platelet Volume (MPV) with Cancer: A Systematic Review with a Focus on Disease Outcome on Twelve Types of Cancer." Current Oncology 30, no. 3 (March 14, 2023): 3391–420. http://dx.doi.org/10.3390/curroncol30030258.
Abstract:
Inflammatory proteins activate platelets, which have been observed to be directly related to cancer progression and development. The aim of this systematic review is to investigate the possible association between Mean Platelet Volume (MPV) and cancer (diagnostic capacity of MPV, relation to survival, the severity of the disease, and metastasis). A literature review was performed in the online database PubMed and Google Scholar for the period of 2010–2022. In total, 83 studies including 21,034 participants with 12 different types of cancer (i.e., gastric cancer, colon cancer, esophageal squamous cell carcinoma, renal cancer, breast cancer, ovarian cancer, endometrial cancer, thyroid cancer, lung cancer, bladder cancer, gallbladder cancer, and multiple myeloma) were identified. The role of MPV has been extensively investigated in several types of cancer, such as gastric, colon, breast, and lung cancer, while few data exist for other types, such as renal, gallbladder cancer, and multiple myeloma. Most studies in gastric, breast, endometrium, thyroid, and lung cancer documented an elevated MPV in cancer patients. Data were less clear-cut for esophageal, ovarian, and colon cancer, while reduced MPV was observed in renal cell carcinoma and gallbladder cancer. Several studies on colon cancer (4 out of 6) and fewer on lung cancer (4 out of 10) indicated an unfavorable role of increased MPV regarding mortality. As far as other cancer types are concerned, fewer studies were conducted. MPV can be used as a potential biomarker in cancer diagnosis and could be a useful tool for the optimization of treatment strategies. Possible underlying mechanisms between cancer and MPV are discussed. However, further studies are needed to elucidate the exact role of MPV in cancer progression and metastasis.
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Choi, Eunji, Justin Lee, Julie T. Wu, Heather A. Wakelee, Lidia Schapira, Allison W. Kurian, and Summer S. Han. "Abstract P055: Risk factors for second primary lung cancer among breast cancer survivors." Cancer Prevention Research 16, no. 1_Supplement (January 1, 2023): P055. http://dx.doi.org/10.1158/1940-6215.precprev22-p055.
Abstract:
Abstract Introduction: Breast cancer is the most common cancer in women in the U.S. As survival in breast cancer has improved, one of the key clinical problems in breast cancer survivors is the increased risk of second cancers. Over half (55%) of breast cancer survivors die from second cancers, of which lung cancer (i.e., second primary lung cancer [SPLC]) is the most frequent type. While smoking and radiotherapy have been identified as the risk factors for SPLC among breast cancer survivors, other potential factors (e.g., comorbidity, and medication) have been underexamined. In addition, women in general have shown higher susceptibility to smoking-induced lung cancer than men, suggesting the potential involvement of hormonal factors; however, the effect of hormone replacement therapy (HRT) on lung cancer risk has been controversial and has never been examined among breast cancer survivors. We aimed to examine the factors associated with SPLC risk among breast cancer survivors, focusing on the effect of HRT and its interaction with smoking. We also explored the potential of tailored risk-based management of SPLC for breast cancer survivors. Methods: We identified 5,552 patients diagnosed with breast cancer in 1993-2014 from the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. SPLC was defined as a newly diagnosed lung cancer after 6 months from the time of breast cancer diagnosis. We applied multivariable cause-specific Cox regression to identify new factors associated with SPLC risk, adjusting for multiple testing using the Bonferroni method (P<0.01). We developed a prediction model to predict a 5-year risk of SPLC among breast cancer survivors that included both ever- and never-smokers and evaluated the predictive accuracy vs. a well-established lung cancer risk model, PLCOm2012, that was developed for a cancer-free population who ever smoked. Results: Of 5,552 patients, 89 (1.6%) developed SPLC over 102,545 person-years. Several factors measured at baseline in PLCO were significantly associated with SPLC risk among breast cancer survivors, including liver comorbidity (Hazard Ratio [HR] 3.28; P<.001), prior history of other cancer (HR 2.02; P=0.01), and regular use of ibuprofen (HR 0.52; P=0.01). In addition, ever-use of HRT was associated with a 51% reduction in SPLC risk (HR 0.49; P=0.001). The effect of active smoking on SPLC risk vs non-active smoking (HR 7.09; P<.001) was validated in PLCO. Notably, the effect of active smoking was intensified among ever-HRT users (HR=10.5; P<.001) vs. never-HRT users (HR 4.1; P<.001), thus showing a significant interaction (Pinteraction=0.003). The prediction model for SPLC risk was validated through bootstrap and demonstrated higher discrimination (AUC 0.83) vs. the PLCOm2012 model (AUC 0.79). Conclusions: In a large prospective cohort of breast cancer survivors, smoking and HRT use showed a significant interaction on SPLC risk. The prediction model for SPLC could identify high-risk survivors for SPLC for tailored surveillance to improve the management of breast cancer survivors. Citation Format: Eunji Choi, Justin Lee, Julie T. Wu, Heather A. Wakelee, Lidia Schapira, Allison W. Kurian, Summer S. Han. Risk factors for second primary lung cancer among breast cancer survivors. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P055.
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Sah, Sunil Kumar, Naval Kishor Yadav, Roshan Kurmi, Ramanuj Rauniyar, Krishan Das Manandhar, and Birendra Prasad Gupta. "Pattern of Cancer in Nepal from 2003 to 2011." Nepal Journal of Biotechnology 4, no. 1 (December 31, 2016): 54–60. http://dx.doi.org/10.3126/njb.v4i1.16348.
Abstract:
Correction: On 15th January 2017, the authors Sunil Kumar Sah and Naval Kishor Yadav were added to the author list.Cancer is global burden of disease in developed and developing countries. It is one of the main causes of death. The environmental factor and life styles are major causes of cancer.This hospital based retrospective study was carried out using data retrieved from the register maintained at seven cancer centers. The most common basis of diagnosis were microscopic (histopathological and cytopathological examination). The diagnosis was also based on clinical examination, radiological examination, endoscopy, biochemical and immunological tests.Most of the cancer cases were diagnosed at BPKMCH (23908) followed by BPKIHS (9668) and BH (5959) and few cases from KCH (518) in 2003 to 2011. The total number of cancer cases were increasing from 2003 to 2011 and it become double in 2011. Out of 75 district of Nepal, more number of cancer cases was found in Kathmandu, Sunsari, Morang, Chitwan, Lalitpur, Jhapa, Kaski, Nawalparasi, Rupendehi and Kavrepalchowk in 2010. Similarly, in 2011 more number of cancer cases was found in Kathmandu, Morang, Jhapa, Sunsari, Chitwan, Lalitpur, Rupendehi, Kaski, Saptari, Bhaktapur. Lung cancer was the common cancer and similarly, other prevalent cancers were cervical, breast, stomach, ovarian and colo-rectum cancer in 2003 to 2011. The common cancers were lung, cervical, breast, stomach, ovarian and colo-rectum. The number of patients is increasing, which may be due to change in life style and lack of education.
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Lindsay, Colin R., Emily C. Shaw, Fiona Blackhall, Kevin G. Blyth, James D. Brenton, Anshuman Chaturvedi, Noel Clarke, et al. "Somatic cancer genetics in the UK: real-world data from phase I of the Cancer Research UK Stratified Medicine Programme." ESMO Open 3, no. 6 (September 2018): e000408. http://dx.doi.org/10.1136/esmoopen-2018-000408.
Abstract:
IntroductionPhase I of the Cancer Research UK Stratified Medicine Programme (SMP1) was designed to roll out molecular pathology testing nationwide at the point of cancer diagnosis, as well as facilitate an infrastructure where surplus cancer tissue could be used for research. It offered a non-trial setting to examine common UK cancer genetics in a real-world context.MethodsA total of 26 sites in England, Wales and Scotland, recruited samples from 7814 patients for genetic examination between 2011 and 2013. Tumour types involved were breast, colorectal, lung, prostate, ovarian cancer and malignant melanoma. Centralised molecular testing of surplus material from resections or biopsies of primary/metastatic tissue was performed, with samples examined for 3–5 genetic alterations deemed to be of key interest in site-specific cancers by the National Cancer Research Institute Clinical Study groups.Results10 754 patients (98% of those approached) consented to participate, from which 7814 tumour samples were genetically analysed. In total, 53% had at least one genetic aberration detected. From 1885 patients with lung cancer, KRAS mutation was noted to be highly prevalent in adenocarcinoma (37%). In breast cancer (1873 patients), there was a striking contrast in TP53 mutation incidence between patients with ductal cancer (27.3%) and lobular cancer (3.4%). Vast inter-tumour heterogeneity of colorectal cancer (1550 patients) was observed, including myriad double and triple combinations of genetic aberrations. Significant losses of important clinical information included smoking status in lung cancer and loss of distinction between low-grade and high-grade serous ovarian cancers.ConclusionNationwide molecular pathology testing in a non-trial setting is feasible. The experience with SMP1 has been used to inform ongoing CRUK flagship programmes such as the CRUK National Lung MATRIX trial and TRACERx.
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Sun, Ming-Yang, Chia-Lun Chang, Chang-Yun Lu, Szu-Yuan Wu, and Jia-Qiang Zhang. "Sarcopenia as an Independent Risk Factor for Specific Cancers: A Propensity Score-Matched Asian Population-Based Cohort Study." Nutrients 14, no. 9 (May 2, 2022): 1910. http://dx.doi.org/10.3390/nu14091910.
Abstract:
Purpose: Whether preexisting sarcopenia is an independent risk factor for cancer incidence remains unclear. Therefore, we performed this propensity score (PS)-matched (PSM) population-based cohort study to compare the incidence rate ratios (IRRs) of specific cancers between patients with and without sarcopenia. Patients and Methods: The patients were categorized into two groups according to the presence or absence of sarcopenia, matched at a 4:1 ratio. Results: PS matching yielded a final cohort of 77,608 patients (15,527 in the sarcopenia and 62,081 nonsarcopenia groups) eligible for further analysis. In our multivariate Cox regression analysis, compared with the nonsarcopenia group, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) for cancer risk in the sarcopenia group was 1.277 (1.10 to 1.36; p < 0.001). Furthermore, the adjusted IRRs (95% CIs) for sarcopenia patients were pancreatic cancer 3.77 (1.79 to 4.01), esophageal cancer 3.38 (1.87 to 4.11), lung cancer 2.66 (1.15 to 2.90), gastric cancer 2.25 (1.54 to 3.23), head and neck cancer 2.15 (1.44 to 2.53), colorectal cancer 2.04 (1.77 to 2.30), hepatocellular carcinoma 1.84 (1.30 to 2.36), breast cancer 1.56 (1.12 to 1.95), and ovarian cancer 1.43 (1.10 to 2.29), respectively. Conclusions: Sarcopenia might be a significant cancer risk factor for lung, colorectal, breast, head and neck, pancreas, gastric, esophageal, and ovarian cancer, as well as hepatocellular carcinoma.
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Metzen, Marlon, Michael Bruns, Wolfgang Deppert, and Udo Schumacher. "Infiltration of Immune Competent Cells into Primary Tumors and Their Surrounding Connective Tissues in Xenograft and Syngeneic Mouse Models." International Journal of Molecular Sciences 22, no. 8 (April 19, 2021): 4213. http://dx.doi.org/10.3390/ijms22084213.
Abstract:
To fight cancer more efficiently with cell-based immunotherapy, more information about the cells of the immune system and their interaction with cancer cells in vivo is needed. Therefore paraffin wax embedded primary breast cancers from the syngeneic mouse WAP-T model and from xenografted tumors of breast, colon, melanoma, ovarian, neuroblastoma, pancreatic, prostate, and small cell lung cancer were investigated for the infiltration of immunocompetent cells by immunohistochemistry using antibodies against leukocyte markers. The following markers were used: CD45 as a pan-leukocyte marker, BSA-I as a dendritic cell marker, CD11b as an NK cell marker, and CD68 as a marker for macrophages. The labeled immune cells were attributed to the following locations: adjacent adipose tissue, tumor capsule, intra-tumoral septae, and cancer cells directly. In xenograft tumors, the highest score of CD45 and CD11b positive, NK, and dendritic cells were found in the adjacent adipose tissue, followed by lesser infiltration directly located at the cancer cells themselves. The detected numbers of CD45 positive cells differed between the tumor entities: few infiltrating cells in breast cancer, small cell lung cancer, neuroblastoma, a moderate infiltration in colon cancer, melanoma and ovarian cancer, strongest infiltration in prostate and pancreatic cancer. In the syngeneic tumors, the highest score of CD45 and CD11b positive, NK and dendritic cells were observed in the tumor capsule, followed by a lesser infiltration of the cancer tissue. Our findings argue for paying more attention to investigate how immune-competent cells can reach the tumor cells directly.
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Kawashiri, Takehiro, Daisuke Kobayashi, Mayako Uchida, Shiori Hiromoto, Masashi Inoue, Hajime Ikeda, Mizuki Inoue, and Takao Shimazoe. "Analysis of Secondary Leukemia and Myelodysplastic Syndrome After Chemotherapy for Solid Organ Tumors Using the Food and Drug Administration Adverse Event Reporting System (FAERS)." Journal of Pharmacy & Pharmaceutical Sciences 24 (October 11, 2021): 499–508. http://dx.doi.org/10.18433/jpps31862.
Abstract:
Purpose: As the prognosis of cancer patients deteriorates, secondary carcinogenesis after chemotherapy, especially secondary hematological malignancies, becomes a serious problem. However, information on the frequency and time of onset of secondary hematological malignancies and the risk of hematological malignancy with different drugs is scarce. This study aimed to evaluate the incidence of leukemia and myelodysplastic syndrome in patients with solid tumors, including breast, colon, gastric, pancreatic, small cell lung, non-small cell lung, esophageal, ovarian, cervical, and endometrial cancers. Methods: Using the United States Food and Drug Administration Adverse Event Reporting System, we analyzed the reporting rates, reporting odds ratios, and the reporting onset times of secondary leukemia and myelodysplastic syndrome for each drug used. Results: The leukemia reporting rates were higher in breast, small cell lung, ovarian, and endometrial cancers than in other cancers, and the myelodysplastic syndrome reporting rates were higher in ovarian and endometrial cancers than in other cancers. For each cancer type, the reporting odds ratios of cytocidal anticancer agents, such as taxanes, anthracyclines, alkylating agents, platinum, and topoisomerase inhibitors, were higher than those of other drugs. Alternatively, the reporting odds ratios of molecular targeted drugs and immune checkpoint inhibitors were not higher than those of other drugs. Approximately half of the cases of leukemia and myelodysplastic syndrome were reported within 1 to 4 years after chemotherapy. Conclusions: Our study clarified the risks of leukemia and myelodysplastic syndrome for several anticancer drugs in patients with solid tumors. Our data may aid in the assessment of the risks of secondary leukemia and myelodysplastic syndrome when medical oncologists, clinical pharmacists, and patients select chemotherapy regimens.