Relevant bibliographies by topics / NSCLCs

Academic literature on the topic 'NSCLCs'

Author: Grafiati
Published: 10 December 2022
Last updated: 28 January 2023

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Journal articles on the topic "NSCLCs"

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Awad, Mark M., Geoffrey R. Oxnard, David M. Jackman, Daniel O. Savukoski, Dimity Hall, Priyanka Shivdasani, Jennifer C. Heng, et al. "MET Exon 14 Mutations in Non–Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression." Journal of Clinical Oncology 34, no. 7 (March 1, 2016): 721–30. http://dx.doi.org/10.1200/jco.2015.63.4600.

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Purpose Non–small-cell lung cancers (NSCLCs) harboring mutations in MET exon 14 and its flanking introns may respond to c-Met inhibitors. We sought to describe the clinical, pathologic, and genomic characteristics of patients with cancer with MET exon 14 mutations. Patients and Methods We interrogated next-generation sequencing results from 6,376 cancers to identify those harboring MET exon 14 mutations. Clinical characteristics of MET exon 14 mutated NSCLCs were compared with those of NSCLCs with activating mutations in KRAS and EGFR. Co-occurring genomic mutations and copy number alterations were identified. c-Met immunohistochemistry and real-time polymerase chain reaction to detect exon 14 skipping were performed where sufficient tissue was available. Results MET exon 14 mutations were identified in 28 of 933 nonsquamous NSCLCs (3.0%) and were not seen in other cancer types in this study. Patients with MET exon 14–mutated NSCLC were significantly older (median age, 72.5 years) than patients with EGFR-mutant (median age, 61 years; P < .001) or KRAS-mutant NSCLC (median age, 65 years; P < .001). Among patients with MET exon 14 mutations, 68% were women, and 36% were never-smokers. Stage IV MET exon 14–mutated NSCLCs were significantly more likely to have concurrent MET genomic amplification (mean ratio of MET to chromosome 7, 4.3) and strong c-Met immunohistochemical expression (mean H score, 253) than stage IA to IIIB MET exon 14–mutated NSCLCs (mean ratio of MET to chromosome 7, 1.4; P = .007; mean H score, 155; P = .002) and stage IV MET exon 14–wild-type NSCLCs (mean ratio of MET to chromosome 7, 1.2; P < .001; mean H score, 142; P < .001). A patient whose lung cancer harbored a MET exon 14 mutation with concurrent genomic amplification of the mutated MET allele experienced a major partial response to the c-Met inhibitor crizotinib. Conclusion MET exon 14 mutations represent a clinically unique molecular subtype of NSCLC. Prospective clinical trials with c-Met inhibitors will be necessary to validate MET exon 14 mutations as an important therapeutic target in NSCLC.
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Maitra, Radhashree, Parth Malik, and Tapan Kumar Mukherjee. "Targeting Estrogens and Various Estrogen-Related Receptors against Non-Small Cell Lung Cancers: A Perspective." Cancers 14, no. 1 (December 24, 2021): 80. http://dx.doi.org/10.3390/cancers14010080.

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Non-small cell lung cancers (NSCLCs) account for ~85% of lung cancer cases worldwide. Mammalian lungs are exposed to both endogenous and exogenous estrogens. The expression of estrogen receptors (ERs) in lung cancer cells has evoked the necessity to evaluate the role of estrogens in the disease progression. Estrogens, specifically 17β-estradiol, promote maturation of several tissue types including lungs. Recent epidemiologic data indicate that women have a higher risk of lung adenocarcinoma, a type of NSCLC, when compared to men, independent of smoking status. Besides ERs, pulmonary tissues both in healthy physiology and in NSCLCs also express G-protein-coupled ERs (GPERs), epidermal growth factor receptor (EGFRs), estrogen-related receptors (ERRs) and orphan nuclear receptors. Premenopausal females between the ages of 15 and 50 years synthesize a large contingent of estrogens and are at a greater risk of developing NSCLCs. Estrogen—ER/GPER/EGFR/ERR—mediated activation of various cell signaling molecules regulates NSCLC cell proliferation, survival and apoptosis. This article sheds light on the most recent achievements in the elucidation of sequential biochemical events in estrogen-activated cell signaling pathways involved in NSCLC severity with insight into the mechanism of regulation by ERs/GPERs/EGFRs/ERRs. It further discusses the success of anti-estrogen therapies against NSCLCs.
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Farago, Anna F., Martin S. Taylor, Robert C. Doebele, Viola W. Zhu, Shivaani Kummar, Alexander I. Spira, Theresa A. Boyle, et al. "Clinicopathologic Features of Non–Small-Cell Lung Cancer Harboring an NTRK Gene Fusion." JCO Precision Oncology, no. 2 (November 2018): 1–12. http://dx.doi.org/10.1200/po.18.00037.

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Purpose Gene rearrangements that involve NTRK1/2/3 can generate fusion oncoproteins that contain the kinase domains of TRKA/B/C, respectively. These fusions are rare in non–small-cell lung cancer (NSCLC), with frequency previously estimated to be < 1%. Inhibition of TRK signaling has led to dramatic responses across tumor types with NTRK fusions. Despite the potential benefit of identifying these fusions, the clinicopathologic features of NTRK fusion-positive NSCLCs are not well characterized. Methods We compiled a database of patients with NSCLCs that harbor NTRK fusions. We characterized clinical, molecular, and histologic features with central review of histology. Results We identified 11 patients with NSCLCs that harbor NTRK gene fusions verified by next-generation sequencing and with available clinical and pathologic data. Fusions involved NTRK1 (n = 7) and NTRK3 (n = 4), with five and two distinct fusion partners, respectively. Fifty-five percent of cohort patients were male with a median age at diagnosis of 47.6 years (range, 25.3 to 86.0 years) and a median smoking history of 0 pack-years (range, 0 to 58 pack-years). Seventy-three percent of patients had metastatic disease at diagnosis. No concurrent alterations in KRAS, EGFR, ALK, ROS1, or other known oncogenic drivers were identified. Nine patients had adenocarcinoma, including two with invasive mucinous adenocarcinoma and one with adenocarcinoma with neuroendocrine features; one had squamous cell carcinoma; and one had neuroendocrine carcinoma. By collating data on 4,872 consecutively screened, unique patients with NSCLC, we estimate a frequency of NTRK fusions in NSCLC of 0.23% (95% CI, 0.11% to 0.40%). Conclusion NTRK fusions occur in NSCLCs across sexes, ages, smoking histories, and histologies. Given the potent clinical activity of TRK inhibitors, we advocate that all NSCLCs be screened for NTRK fusions by using a multiplexed next-generation sequencing–based fusion assay.
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Nowinska, Jablonska, Pawelczyk, Piotrowska, Partynska, Gomulkiewicz, Ciesielska, et al. "Expression of Irisin/FNDC5 in Cancer Cells and Stromal Fibroblasts of Non-small Cell Lung Cancer." Cancers 11, no. 10 (October 11, 2019): 1538. http://dx.doi.org/10.3390/cancers11101538.

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Background: Recent in vitro studies have indicated that irisin inhibits proliferation, migration and epithelial-mesenchymal transition. Irisin expression has not been studied in tumour tissues of non-small cell lung cancer (NSCLC) patients yet. The aim of the study was to determine the irisin expression in NSCLCs in comparison to the clinicopathological factors and expression of TTF-1, p63 and Ki-67. Material and methods: Tissue microarrays with 729 NSCLC and 140 non-malignant lung tissue (NMLT) were used to perform immunohistochemical reactions. Laser Capture Microdissection (LCM) was used to collect cancer and stromal cells from NSCLCs. FNDC5 expression was tested for LCM samples, 75 NSCLCs and 25 NMLTs with the RT-PCR technique. Western-blot, immunofluorescence reaction and RT-PCR assays were performed on lung cancer cell lines. Results: Irisin expression was observed in NSCLC cancer cells and stromal fibroblasts. In cancer cells, irisin expression was decreased in higher grades (G) of malignancy, tumour size (T) and according to lymph node metastasis. In stromal cells, irisin expression was increased in higher G and advanced T. A shorter overall survival was observed in patients with higher irisin expression in NSCLC stromal cells. Conclusions: Irisin expression in stromal fibroblasts may influence cancer cell proliferation and may be a prognostic factor for survival in NSCLC.
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Yan, Dan, H. Shelton Earp, Deborah DeRyckere, and Douglas K. Graham. "Targeting MERTK and AXL in EGFR Mutant Non-Small Cell Lung Cancer." Cancers 13, no. 22 (November 11, 2021): 5639. http://dx.doi.org/10.3390/cancers13225639.

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MERTK and AXL are members of the TAM family of receptor tyrosine kinases and are abnormally expressed in 69% and 93% of non-small cell lung cancers (NSCLCs), respectively. Expression of MERTK and/or AXL provides a survival advantage for NSCLC cells and correlates with lymph node metastasis, drug resistance, and disease progression in patients with NSCLC. The TAM receptors on host tumor infiltrating cells also play important roles in the immunosuppressive tumor microenvironment. Thus, MERTK and AXL are attractive biologic targets for NSCLC treatment. Here, we will review physiologic and oncologic roles for MERTK and AXL with an emphasis on the potential to target these kinases in NSCLCs with activating EGFR mutations.
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Landre, Thierry, Gregoire Justeau, Jean-baptiste Assié, Kader Chouahnia, Chérifa Taleb, Christos Chouaid, and Boris Duchemann. "Anti PD-(L)1 in KRAS mutant advanced nsclcs: A meta-analysis of randomized controlled trials." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 9025. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.9025.

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9025 Background: KRAS comprise the most frequently found oncogene driver mutation in non-small cell lung cancer (NSCLC), accounting for 20-25% of these patients. Single-agent Anti PD-(L)1 clinical efficacy against KRAS mutant NSCLC is a topic of debate. Methods: This meta-analysis examined randomized-trial data comparing first-or second line Anti PD-(L)1 +/- chemotherapy (CT) vs CT alone for KRAS mutant advanced NSCLCs. Outcome measures included overall survival (OS) and progression-free survival (PFS). Analyses were computed using the Cochrane method of collaboration for meta-analyses, with Review Manager software (RevMan version 5.3; Oxford, UK). Results: We analyzed 3 trials in first line (IMPOWER-150, KEYNOTE-189 and KEYNOTE-042), as well as 3 trials in second line (OAK, POPLAR and CHECKMATE-057) including 1313 NSCLCs (386 KRAS mutant and 927 KRAS wild-type tumor). Anti PD-(L)1 +/- CT was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS (0.59 [0.49-0.72]; p < 0.00001) and PFS (0.58 [0.43-0.78]; p = 0.0003) compared to CT alone in KRAS mutant NSCLCs. Survival benefits occured in both first and second line. Survival benefits observed in KRAS wild-type NSCLCs were (0.87 [0.76-0.99]; p = 0.03) and (0.79 [0.56-1.11]; p = 0.17) respectively. OS benefit in KRAS mutant was significantly superior compared to OS benefit in KRAS wild-type (p = 0,001). Conclusions: Anti PD-(L)1 (+/- CT) appears superior to CT alone both for mutant and wild-type KRAS in advanced NSCLCs for OS and PFS with higher magnitude of benefit in KRAS mutated group for OS.
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Liu, Jia-Chun, Suresh Narva, Kang Zhou, and Wen Zhang. "A Review on the Antitumor Activity of Various Nitrogenous-based Heterocyclic Compounds as NSCLC Inhibitors." Mini-Reviews in Medicinal Chemistry 19, no. 18 (November 29, 2019): 1517–30. http://dx.doi.org/10.2174/1389557519666190312152358.

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At present, cancers have been causing deadly fears to humans and previously unpredictable losses to health. Especially, lung cancer is one of the most common causes of cancer-related mortality accounting for approximately 15% of all cancer cases worldwide. While Non-Small Cell Lung Carcinomas (NSCLCs) makes up to 80% of lung cancer cases. The patient compliance has been weakening because of serious drug resistance and adverse drug effects. Therefore, there is an urgent need for the development of novel structural agents to inhibit NSCLCs. Nitrogen-containing heterocyclic compounds exhibit wide range of biological properties, especially antitumor activity. We reviewed some deadly defects of clinical medicines for the lung cancer therapy and importance of nitrogen based heterocyclic derivatives against NSCLCs. Nitrogen heterocycles exhibit significant antitumor activity against NSCLCs. Nitrogen heterocyclic hybrids could be developed as multi-target-directed NSCLC inhibitors and it is believed that the review is significant for rational designs and new ideas in the development of nitrogen heterocyclic-based drugs.
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Wang, Hsiang-Sheng, Chien-Ying Liu, Sheng-Chi Hsu, Shih-Chiang Huang, Tsai-Hsien Hung, Kwai-Fong Ng, and Tse-Ching Chen. "A Single-Institute Experience with C-ros Oncogene 1 Translocation in Non-Small Cell Lung Cancers in Taiwan." International Journal of Molecular Sciences 23, no. 10 (May 21, 2022): 5789. http://dx.doi.org/10.3390/ijms23105789.

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(1) Background: The C-ros oncogene 1 (ROS1) gene translocation is an important biomarker for selecting patients for crizotinib-targeted therapy. The aim of this study was to understand the incidence, diagnostic algorithm, clinical course and objective response to crizotinib in ROS1 translocated lung non-small cell lung cancers (NSCLCs) in Taiwan. (2) Methods: First, we retrospectively studied the ROS1 status in 100 NSCLC samples using break-apart fluorescent in situ hybridization (FISH) and immunohistochemical (IHC) staining to establish a diagnostic algorithm. Then, we performed routine ROS1 IHC tests in 479 NSCLCs, as crizotinib was available from 2018 in Taiwan. We analyzed the objective response rate and the survival impact of crizotinib. (3) Results: Four ROS1 translocations were clustered in epidermal growth factor receptor (EGFR) wild-type adenocarcinomas but not in cases with EGFR mutations. Strong ROS1 expression was positively correlated with ROS1 translocation (p < 0.001). NSCLCs with ROS1 translocation had a poor prognosis compared to those without ROS1 translocation (p = 0.004) in the pre-crizotinib stage. Twenty NSCLCs were detected with ROS1 translocation in 479 wild-type EGFR specimens from 2018. Therefore, the incidence of ROS1 translocation is approximately 4.18% in EGFR wild-type NSCLCs. In these 20 ROS1 translocation cases, 19 patients received crizotinib treatment, with an objective response rate (ORR) of 78.95% (confidence interval = 69.34% to 88.56%), including 1 complete response, 14 partial responses, 3 stable cases and 1 progressive case. Overall survival and progression-free survival were better in the 19 ROS1-translocated NSCLCs of the prospective group with crizotinib treatment than the four ROS1-translocated NSCLCs of the retrospective group without crizotinib treatment. (4) Conclusions: ROS1-translocated NSCLCs had a poor prognosis and could have a beneficial outcome with crizotinib.
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Gasparini, Pierluigi, Luciano Cascione, Lorenza Landi, Stefania Carasi, Francesca Lovat, Carmelo Tibaldi, Greta Alì, et al. "microRNA classifiers are powerful diagnostic/prognostic tools in ALK-, EGFR-, and KRAS-driven lung cancers." Proceedings of the National Academy of Sciences 112, no. 48 (November 16, 2015): 14924–29. http://dx.doi.org/10.1073/pnas.1520329112.

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microRNAs (miRNAs) can act as oncosuppressors or oncogenes, induce chemoresistance or chemosensitivity, and are major posttranscriptional gene regulators. Anaplastic lymphoma kinase (ALK), EGF receptor (EGFR), and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) are major drivers of non-small cell lung cancer (NSCLC). The aim of this study was to assess the miRNA profiles of NSCLCs driven by translocated ALK, mutant EGFR, or mutant KRAS to find driver-specific diagnostic and prognostic miRNA signatures. A total of 85 formalin-fixed, paraffin-embedded samples were considered: 67 primary NSCLCs and 18 matched normal lung tissues. Of the 67 primary NSCLCs, 17 were echinoderm microtubule-associated protein-like 4–ALK translocated (ALK+) lung cancers; the remaining 50 were not (ALK−). Of the 50 ALK− primary NSCLCs, 24 were EGFR and KRAS mutation-negative (i.e., WT; triple negative); 11 were mutant EGFR (EGFR+), and 15 were mutant KRAS (KRAS+). We developed a diagnostic classifier that shows how miR-1253, miR-504, and miR-26a-5p expression levels can classify NSCLCs as ALK-translocated, mutant EGFR, or mutant KRAS versus mutation-free. We also generated a prognostic classifier based on miR-769-5p and Let-7d-5p expression levels that can predict overall survival. This classifier showed better performance than the commonly used classifiers based on mutational status. Although it has several limitations, this study shows that miRNA signatures and classifiers have great potential as powerful, cost-effective next-generation tools to improve and complement current genetic tests. Further studies of these miRNAs can help define their roles in NSCLC biology and in identifying best-performing chemotherapy regimens.
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Serresi, Michela, Bjorn Siteur, Danielle Hulsman, Carlos Company, Matthias J. Schmitt, Cor Lieftink, Ben Morris, et al. "Ezh2 inhibition in Kras-driven lung cancer amplifies inflammation and associated vulnerabilities." Journal of Experimental Medicine 215, no. 12 (November 28, 2018): 3115–35. http://dx.doi.org/10.1084/jem.20180801.

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Kras-driven non–small-cell lung cancers (NSCLCs) are a leading cause of death with limited therapeutic options. Many NSCLCs exhibit high levels of Ezh2, the enzymatic subunit of polycomb repressive complex 2 (PRC2). We tested Ezh2 inhibitors as single agents or before chemotherapy in mice with orthotopic Kras-driven NSCLC grafts, which homogeneously express Ezh2. These tumors display sensitivity to EZH2 inhibition by GSK126 but also amplify an inflammatory program involving signaling through NF-κB and genes residing in PRC2-regulated chromatin. During this process, tumor cells overcome GSK126 antiproliferative effects. We identified oncogenes that may mediate progression through an in vivo RNAi screen aimed at targets of PRC2/NF-κB. An in vitro compound screening linked GSK126-driven inflammation and therapeutic vulnerability in human cells to regulation of RNA synthesis and proteostasis. Interestingly, GSK126-treated NSCLCs in vivo also showed an enhanced response to a combination of nimesulide and bortezomib. Thus, Ezh2 inhibition may restrict cell proliferation and promote defined adaptive responses. Targeting these responses potentially improves outcomes in Kras-driven NSCLCs.
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Dissertations / Theses on the topic "NSCLCs"

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Chater, Emily. "Novel therapeutic targets in NSCLC resistance to Erlotinib." Thesis, Imperial College London, 2017. http://hdl.handle.net/10044/1/50699.

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Approximately 10% of non-small cell lung cancers (NSCLCs) have an activating mutation within the kinase domain of epidermal growth factor receptor (EGFR). Competitive tyrosine kinase inhibitors (TKIs), such as Erlotinib and Gefitinib, have been developed to therapeutically exploit this. These compounds have shown excellent clinical responses in approximately 77% of patients with EGFR-mutant driven lung cancer. However, despite positive initial response, patients develop resistance, and this is often attributed (50% of cases) to the T790M secondary mutation in the ATP binding pocket of EGFR. This mutation increases the receptors affinity for ATP which competes out reversible first-generation inhibitors such as erlotinib and gefitinib. This thesis aims to better understand the underlying mechanisms involved in the resistance to this compound. Changes in metabolism have frequently been associated with tumour progression and drug resistance in many cancer types. Here, to identify novel resistance mechanisms, 1H-NMR metabolic profiling was performed on EGFR-driven NSCLC cells with and without, the additional T790M-EGFR resistance mutation. This study identified both glutathione (GSH) and phosphatidylcholine metabolism as two key pathways perturbed in erlotinib-resistant cells. Interestingly, 1H-NMR revealed lower levels of both oxidised and reduced forms of GSH in erlotinib-resistant cell lines and this was verified by colorimetric assays. This change correlated with reduced mRNA expression of GSH synthesizing enzymes in resistant cell lines. Increasing cellular GSH levels by siRNA-mediated targeting of GSH degrading enzymes sensitised erlotinib-resistant cells to erlotinib treatment. In addition, the use of GSH synthesizing enzyme inhibitors such as Buthionine Sulfoximine (BSO), which targets the gamma-glutamylcysteine synthetase (GCS, GSH synthesising enzyme) and degrading enzyme inhibitors such as Ethacrynic acid (EA) (inhibits glutathione S-transferase) increased and decreased resistance to erlotinib, respectively. EA also showed promising results in vivo as BALB/c nude mice, injected subcutaneously with PC9ER cells, showed increased sensitivity to erlotinib treatment when co-administered with EA. Furthermore, we demonstrated that mutant EGFR signalling can modulate the transcription of GSH enzymes likely via changes in the regulation of the transcription factor, Nuclear Factor (Erythroid-Derived 2)-Like 2 (NRF2). Targeting NRF2 using siRNAs decreased GSH abundance and increased erlotinib resistance. However, at present we do not understand how raised GSH levels might cause resistance to erlotinib in lung cancer cells expressing activated T790M-EGFR. To discover other differences between erlotinib-resistant and sensitive cells, we employed reverse phase protein array (RPPA) and, following DAVID bio-informatics analysis, 4 identified changes in both beta-oxidation and ataxia telangiectasia mutated kinase (ATM)/Ataxia Telangiectasia and Rad3-related kinase (ATR) cell cycle checkpoint proteins. Changes in these signalling molecules were confirmed by Western blotting. Yet, only targeting the ATR pathway affected the resistance to erlotinib in PC9ER cell lines. Indeed, inhibition of WEE1 with the compound MK1775 may hold promise as a treatment for patients with erlotinib-resistant NSCLC. In short, this work has identified GSH degrading enzymes and WEE1 as novel targets for reversing erlotinib resistance in EGFR-driven NSCLC. However, further investigation is needed to understand the mechanisms involved.
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Holgersson, Georg. "Prognostic Factors in Non-Small Cell Lung Cancer (NSCLC)." Doctoral thesis, Uppsala universitet, Experimentell och klinisk onkologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-327925.

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Background: Non-small cell lung cancer (NSCLC) is the cancer disease with the highest mortality globally. About 75% of NSCLC patients are diagnosed in an advanced stage where surgical treatment is not possible. For patients with locally advanced disease without distant metastases, the treatment of choice is curatively intended radiotherapy. However, this treatment has considerable side effects and many patients relapse. To individualize the treatment strategy for these patients, it is essential to have as much prognostic information as possible. The aim of this thesis was to investigate the prognostic significance of histology and pre-treatment hematopoietic blood parameters. Material and Methods: Data were collected retrospectively for NSCLC patients treated between 1990 and 2000 with curatively intended radiotherapy. The data were obtained by manually searching patient records from all radiation oncology departments in Sweden. The prognostic significance of histology, and pre-treatment levels of hemoglobin (Hgb), white blood cells (WBC) and platelets (Plt) were analyzed in relation to overall survival using univariate and multivariate statistical methods. These prognostic factors were further analyzed in a chemoradiation patient cohort and in a cohort of patients with recurrent NSCLC treated with palliative docetaxel, or the insulin-like growth factor 1 receptor (IGF-1R) modulator AXL1717. Results: In the cohort of NSCLC patients treated between 1990 and 2000, squamous cell carcinoma (SCC) histology and pre-treatment anemia (Hgb <110 g/L), leukocytosis (WBC > 9.0 x109/L), and thrombocytosis (Plt >350 x109/L) were independent prognostic factors for shorter overall survival. However, in the chemoradiation cohort only thrombocytosis retained independent prognostic significance in a multivariate analysis. In the cohort of patients with recurrent disease treated with palliative systemic therapy, only leukocytosis was significantly associated with worse survival. Conclusions: Routine pre-treatment hematopoietic blood parameters—together with other prognostic factors such as disease stage and performance status—can provide decision-making support when individualizing treatment of NSCLC. The prognostic role of histology is unclear and further research is warranted to determine its significance.
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Stamatkin, Christopher W. "PHOSPHATIDYLINOSITOL 3-KINASE (PI3K) AS A THERAPEUTIC TARGET IN NSCLC." UKnowledge, 2014. http://uknowledge.uky.edu/pharmacy_etds/58.

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Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using isoform-specific inhibitors in a lung cancer model system. Treatment of non-small cell lung cancer (NSCLC) cell lines with PIK3CA, PIK3CB, PIK3CD or PIK3CB/D inhibitors resulted in pharmacokinetic and pharmacodynamic responses that frequently tracked with a specific mutation status. Activation of PIK3CA dictated response to the PIK3CA-specific inhibitor while deletion of PTEN phosphatase indicated response to the PIK3CB inhibitor. The PIK3CD isoform-specific inhibitors lacked efficacy in all NSCLC cell lines tested, however treatment at increased concentrations likely provide concurrent inhibition of both PIK3CB/D isoforms improving activity of either agent alone but did not track with a single biomarker. The observed pharmacodynamic and proliferation responses to isoform-specific inhibitors suggested that PI3K isoforms may functionally compensate for loss of another in certain genetic backgrounds. These studies demonstrate unanticipated cellular responses to PI3K isoform inhibition in NSCLC, suggesting that patient populations with specific mutations can benefit from certain isoform-selective inhibitors, or combinations, allowing for rational and targeted clinical use of these agents.
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Chatterjee, Saradiya. "Role of TLR7 in non-small cell lung carcinona (NSCLC)." Paris 6, 2013. http://www.theses.fr/2013PA066063.

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Le cancer du poumon cause de plus d’un million de décès par an, et le progonstique est très somber, avec un taux de survie à 5 ans de l’ordre de 8 à 12%. La stimulation des TLRs par des ligands agonistes naturels comme les PAMPs et les DAMPs résulte en l’activation d’une cascade de signalisation conduisant à l’expression de molecules proinflammatoires. Nous avons montré que la stimulation de lignées cellulaires de tumeur pulmonaire par des agonistes de TLR7 induit une survie cellulaire et une résistance à la mort induite par chimiothérapie in vitro. Nous avons étudié in vivo les effets d’injections d’agonistes de TLR7 sur la croissance tumorale et la résistance à la chimiothérapie dans des souris NOD/SCID et C57BL/6. L’injection de loxoribine, ou de CL264 a un effet pro-tumoral sur la croissance des cellules A549 et CL264, respectivement, et induit une chimioresistance dans des souris NOD/SCID. Le blocage de TLR7 réverse l’effet pro-tumoral de l’agoniste. Par ailleurs, l’injection de faible dose de CL264 a un effet anti-tumoral sur les cellules LL/2, alors que l’injection d’une forte concentration de l’agonsite a un effet pro-tumoral. Nous avons également démontré qu’une forte expression de TLR7 par les cellules tumorales de patients NSCLC est de mauvais pronostique sur la survie globale des patients. Ces résultats démontrent le rôle pro- tumoral de TLR7 et son implication potentielle dans le phénomène de chimiorésistance. Ainsi l’utilisation d’agonistes de TLR7 comme adjuvant de vaccination antitumorale devrait prendre en compte le niveau d’expression de TLR7 sur les cellules tumorales des patients
Lung cancer accounts for over 1 million deaths per year with a 5-year survival of 8-12%. Stimulation of TLRs by the natural ligands like the PAMPs and DAMPs results in a proinflammatory signaling cascade. We have shown that stimulation of lung cancer cell lines with TLR7 agonist lead to tumor cell survival and chemoresistance in vitro. We studied the effect of TLR7 agonists on A549 and LL/2 cells injected in NOD/SCID and C57BL/6 mice either treated or not with cisplatin. Loxoribine has a pro-tumoral effect on A549 cells and induces chemoresistance in NOD/SCID mice. Blockade of TLR7 with IRS661 reversed the pro-tumoral effect of TLR7 agonist on A549 cells. CL264 was also found to have a pro-tumoral effect on LL/2 cells and induced chemoresistance in NOD/SCID mice. On the other hand CL264 at lower concentration induces an anti-tumoral effect on LL/2 cells while at a higher concentration demonstrated a pro-tumoral effect in C57BL/6 mice. We also demonstrated an overall bad prognostic value for higher expression of TLR7 by tumoral cells among NSCLC patients treated and not treated with neoadjuvant chemotherapy. These results suggest a pro- tumoral role and induction of chemoresistance by TLR7 in NSCLC patients. Use of TLR7 agonist as therapeutic option is recommended based on the TLR7 expression level for individual NSCLC patients. TLR7 antagonist holds promise for treatment of NSCLC in future
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Recondo, Gonzalo. "Resistance Mechanisms to ALK Tyrosine Kinase Inhibitors (TKIs) in NSCLC." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS248/document.

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Les analyses moléculaires et la classification des adénocarcinomes bronchiques ont conduit au développement de thérapies ciblées sélectives visant à améliorer le contrôle de la maladie et la survie des patients. ALK (anaplastic lymphoma kinase) est un récepteur tyrosine kinase de la famille des récepteurs de l'insuline. Des réarrangements chromosomiques impliquant le domaine kinase d’ALK sont présents dans environ 3 à 6% des patients atteints d'un adénocarcinome bronchique. La protéine de fusion provoque une activation du domaine kinase de manière constitutive et indépendante du ligand. Lorlatinib est un inhibiteur d’ALK de troisième génération avec une efficacité et une sélectivité optimale, ainsi qu’une pénétration élevée vers le système nerveux central. Lorlatinib peut vaincre la résistance induite par plus de 16 mutations secondaires dans le domaine kinase d’ALK acquises lors de la progression aux ALK TKI de première et deuxième générations. Le traitement par lorlatinib est donc efficace chez les patients préalablement traités par un ALK TKI de première ou deuxième génération, et est actuellement approuvé pour cette indication. Le spectre complet de mécanismes de résistance au lorlatinib chez les patients reste à élucider. Il a récemment été rapporté que l'acquisition séquentielle de deux mutations ou plus dans le domaine kinase, également appelées mutations composées, est responsable de la progression de la maladie chez environ 35% des patients traités par le lorlatinib, principalement en altérant sa liaison au domaine kinase d’ALK. Cependant, l’effet de ces mutations sur la sensibilité aux différents inhibiteurs d’ALK peut varier, et les autres mécanismes de résistance survenant chez la plupart des patients restent inconnus. Mon travail de thèse avait pour but d’explorer la résistance au lorlatinib chez des patients atteints d'un cancer du poumon ALK réarrangé par la mise en œuvre de biopsies spatiales et temporelles et le développement de modèles dérivés de patients. Dans le cadre de l’étude institutionnelle MATCH-R (NCT02517892), nous avons effectué un séquençage à haut débit de l’exome, de l’ARN et ciblé, ainsi qu’un séquençage des ctDNA afin d’identifier les mécanismes de résistance. Nous avons établi des lignées cellulaires dérivées de patients et caractérisé de nouveaux mécanismes de résistance et identifiés de nouvelles stratégies thérapeutiques in vitro et in vivo. Nous avons identifié trois mécanismes de résistance chez quatre patients avec des biopsies appariées. Nous avons étudié l'induction de la transition épithélio-mésenchymateuse (EMT) par l'activation de SRC dans une lignée cellulaire, dérivée d’un patient, exposée au lorlatinib. Les cellules mésenchymateuses étaient sensibles à l’inhibition combinée de SRC et d'ALK, montrant que même en présence d'un phénotype agressif, des stratégies de combinaison peuvent surmonter la résistance aux ALK TKI. Nous avons identifié deux nouvelles mutations composées du domaine kinase d’ALK, F1174L / G1202R, C1156Y / G1269A survenues chez deux patients traités par le lorlatinib. Nous avons développé des modèles de cellules Ba / F3 exprimant les mutations simples et composées pour étudier leur effet sur la résistance au lorlatinib. Enfin, nous avons caractérisé un nouveau mécanisme de résistance provoqué par la perte de fonction de NF2 au moment de la progression du lorlatinib par l’utilisation de PDX et de lignées cellulaires dérivées de patients, et par CRISPR / CAS9 knock-out de NF2. Nous avons constaté que l'activation de mTOR par la perte de fonction de NF2 provoquait la résistance au lorlatinib et qu'elle pouvait être surmontée par le traitement avec des inhibiteurs de mTOR.Cette étude montre que les mécanismes de résistance au lorlatinib sont plus divers et complexes que prévu. Nos résultats démontrent également comment les études longitudinales de la dynamique tumorale permettent de déchiffrer la résistance aux TKI et d'identifier des stratégies thérapeutiques
The molecular study and classification of lung adenocarcinomas has led to the development of selective targeted therapies aiming to improve disease control and survival in patients. The anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor from the insulin tyrosine kinase receptor family, with a physiologic role in neural development. Gene rearrangements involving the ALK kinase domain occur in ~3-6% of patients with lung adenocarcinoma. The fusion protein dimerizes leading to transactivation of the ALK kinase domain in a ligand-independent and constitutive manner. Lorlatinib is a third generation ALK inhibitor with high potency and selectivity for this kinase in vitro and in vivo, and elevated penetrance in the central nervous system. Lorlatinib can overcome resistance mediated by over 16 secondary kinase domain mutations occurring in 13 residues upon progression to first - and second - generation ALK TKI. In addition, treatment with lorlatinib is effective for patients who have been previously treated with a first and a second generation or a second generation ALK TKI upfront and is currently approved for this indication. The full spectrum of biological mechanisms driving lorlatinib resistance in patients remains to be elucidated. It has been recently reported that the sequential acquisition of two or more mutations in the kinase domain, also referred as compound mutations, is responsible for disease progression in about 35% of patients treated with lorlatinib, mainly by impairing its binding to the ALK kinase domain. However, the effect of these compound mutations on the sensitivity to the repertoire of ALK inhibitors can vary, and other resistance mechanisms occurring in most patients are unknown. My PhD thesis aimed at exploring resistance to lorlatinib in patients with ALK-rearranged lung cancer through spatial and temporal tumor biopsies and development of patient-derived models. Within the institutional MATCH-R study (NCT02517892), we performed high-throughput whole exome, RNA and targeted next-generation sequencing, together with plasma sequencing to identify putative genomic and bypass mechanisms of resistance. We developed patient-derived cell lines and characterized novel mechanisms of resistance and personalized treatment strategies in vitro and in vivo. We characterized three mechanisms of resistance in four patients with paired biopsies. We studied the induction of epithelial-mesenchymal transition (EMT) by SRC activation in a patient-derived cell line exposed to lorlatinib. Mesenchymal cells were sensitive to combined SRC and ALK co-inhibition, showing that even in the presence of an aggressive and challenging phenotype, combination strategies can overcome ALK resistance. We identified two novel ALK kinase domain compound mutations, F1174L/G1202R, C1156Y/G1269A, occurring in two patients treated with lorlatinib. We developed Ba/F3 cell models harboring single and compound mutations to study the differential effect of these mutations on lorlatinib resistance. Finally, we characterized a novel mechanism of resistance caused by NF2 loss of function at the time of lorlatinib progression through the development of patients derived PDX and cell lines, and in vitro validation of NF2 knock-out with CRISPR/CAS9 gene editing. Downstream activation of mTOR was found to drive lorlatinib resistance by NF2 loss of function and was overcome by providing treatment with mTOR inhibitors.This study shows that mechanisms of resistance to lorlatinib are more diverse and complex than anticipated. Our findings also emphasize how longitudinal studies of tumor dynamics allow deciphering TKI resistance and identifying reversing strategies
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Baghai, Tabassom. "ATF3 as a Key Regulator of Cisplatin Cytotoxicity: Combining ATF3 Inducing Agents Enhances Cisplatin Activity in NSCLC." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/37963.

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Lung cancer is the leading cause of cancer and cancer deaths worldwide, with non-small-cell lung carcinomas (NSCLC) representing 85% of all diagnosed lung cancers. Platinum-combination chemotherapy is the current standard treatment for NSCLC, however, associated toxicities and resistance limit its efficacy. Our laboratory previously identified activating transcription factor 3 (ATF3), a stress-inducible gene whose elevated and sustained expression can trigger apoptosis to a wide variety of stressors, as a key regulator of cisplatin cytotoxicity as well. Thus, enhanced and sustained induction of ATF3 by combining platins with other ATF3 inducers potentially represents an effective therapeutic strategy. A chemical library screen identified vorinostat and topotecan as ATF3 inducers that also enhance cisplatin cytotoxicity. ATF3 plays a significant role in cisplatin, vorinostat and topotecan and their combinations cytotoxicity. Importantly, vorinostat and topotecan induced synergistic cytotoxicity with cisplatin in NSCLC cell lines and their cisplatin resistance sub-lines with enhanced ATF3 expression observed. Our study suggests a potential novel therapeutic approach where ATF3 inducing agents in combination with platins represents a rational combination based therapeutic strategy.
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Souza, Cristiano de Pádua. "Perfil de expressão de microRNAs e seus alvos moleculares em carcinoma pulmonar." Botucatu, 2016. http://hdl.handle.net/11449/140150.

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Orientador: Patrícia Pintor dos Reis
Resumo: Introdução: O câncer de pulmão é a principal causa de morte por câncer no mundo. Apesar dos avanços nas estratégias de diagnóstico e o desenvolvimento de novas terapias com alvos moleculares, pouco progresso tem sido observado quanto ao aumento de sobrevida dos pacientes. Portanto, a identificação de novos biomarcadores ainda é necessária para o desenvolvimento de novas terapêuticas para carcinomas pulmonares. Nesse contexto, os microRNAs (miRNAs) são moléculas promissoras, pois constituem uma classe de RNAs não-codantes reguladores da expressão gênica os quais têm sido evidenciados como biomarcadores diagnósticos, prognósticos e preditivos no câncer. Materiais e Métodos: Amostras de tecido pulmonar tumoral e normal de 38 pacientes com carcinoma de pulmão de células não pequenas (da sigla em inglês NSCLC), dos subtipos histológicos adenocarcinoma e carcinoma de células escamosas, foram avaliadas para a expressão global de miRNAs utilizando a plataforma TaqMan® Array Human MicroRNA card A v3.0 (Life Technologies). Os miRNAs com alterações na expressão (FC≥2,0) e p<0,05 foram considerados estatisticamente significativos. Os dados de expressão foram associados com a sobrevida global. Análises de bioinformática permitiram identificar genes-alvo regulados pelos miRNAs desregulados. A relação entre sobrevida global e a identificação de uma assinatura de expressão de miRNAs foi avaliada com objetivo de integrar nossos achados utilizando bancos de dados públicos. Resultados: Os resul... (Resumo completo, clicar acesso eletrônico abaixo)
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8

Campbell, Thomas. "The role of voltage-gated sodium channels in non-small cell lung cancer." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-voltagegated-sodium-channels-in-nonsmall-cell-lung-cancer(a65f4c5e-b217-483b-91d3-bb669965eb03).html.

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Various ion channels are expressed in human cancers where they are intimately involved in proliferation, angiogenesis, migration and invasion. Expression of functional voltage-gated sodium (Nav) channels is implicated in the metastatic potential of breast, prostate, colon, cervical and lung cancer cells. However, the cellular mechanisms that regulate Nav channel expression in cancer remain largely unknown. Growth factors are attractive candidates; they not only play crucial roles in cancer progression but are also key regulators of ion channel expression and activity in non-cancerous cells. Here, the role of epidermal growth factor receptor (EGFR) signalling and Nav channels in non-small cell lung cancer (NSCLC) cell lines have been examined. It is shown that functional expression of Nav1.7 promotes invasion in strongly metastatic H460 NSCLC cells. However, in non-invasive A549 NSCLC cells, Nav1.7 is completely absent. Inhibition of Nav1.7 either pharmacologically by tetrodotoxin (TTX) or genetically by small interfering RNA (siRNA) reduces H460 cell invasion by up to 50%. Whilst EGFR signalling enhances proliferation, migration and invasion of H460 cells, EGFR-mediated upregulation of Nav1.7 specifically, is required to promote invasive behaviour in these cells. Examination of Nav1.7 expression at the mRNA, protein and functional levels further reveals that EGFR signalling via the ERK1/2 pathway controls transcriptional regulation of Nav1.7 expression to promote cellular invasion in NSCLC. The role of Nav channels in promoting cancer cell invasion is also unclear. Therefore, the effect of Nav channel activity on two likely downstream contributors to cellular invasion, intracellular calcium concentration, [Ca2+]i, and intracellular pH, pHi, have been examined. It is shown that functional expression of Nav1.7 likely drives H460 NSCLC cell invasion via H+ efflux from the cell in an uncharacterised mechanism potentially involving NHE1, resulting in extracellular acidification of the perimembrane space. However, much more work is needed to understand this Na+-dependent invasive mechanism. Immunohistochemistry (IHC) of patient biopsies confirms the clinical relevance of Nav1.7 expression in NSCLC. Thus, Nav1.7 has significant potential as a novel target for therapeutic intervention, possibly in conjunction with existing EGFR inhibitors, and/or as a diagnostic/prognostic marker in NSCLC.
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Ben, hamed Ibtissem. "Réponses cellulaires rapides de l’halophyte Cakile maritima au choc salin : analyse de leur implication dans la mort cellulaire programmée et l’adaptation." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS444.

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Les travaux présentés dans cette thèse ont porté sur la specificité des réponses cellulaires de l’halophyte obligatoire Cakile maritima au choc salin et la régulation des événements précoces impliqués dans la mort cellulaire programmée et la survie en condition de salinité. Dans une première étape, nous avons montré que cette plante est aussi tolérante aux chocs salins répétés qu’au stress salin progressif. Cependant, on a observé de zones de mort cellulaires sur les feuilles âgées soumises à un choc salin sévère (400 mM NaCl). Pour mieux cerner la cascade d’événements impliqués dans ce processus de mort cellulaire, nous avons poursuivi nos expériences sur des suspensions cellulaires de C. maritima, dont nous avons-nous même optimisé les conditions d’obtention, et des suspensions cellulaires d’Arabidopsis thaliana (glycophyte modèle). Chez les deux espèces, nous avons observé une mort cellulaire programmée qui dépend de la durée et l’intensité du traitement salin appliqué, et qui met en jeu les mêmes événements cellulaires notamment la dépolarisation de la membrane plasmique due à l’entrée de Na+ par les NSCCs, un dysfonctionnement mitochondrial, une production d’anions superoxydes et une activation de protéines de type caspase. La tolérance de C. maritima au stress salin serait potentiellement due à une forte accumulation d’ascorbate qui permettrait à cette halophyte de mieux réduire les dommages générés par le stress oxydatif. C. maritima s’est aussi distinguée par une meilleure capacité de contrôler l’accumulation cytoplasmique de Na+, conduisant à la survie de ses cellules en condition de salinité. Cette étude sur la mort cellulaire induite par le NaCl chez les cellules en culture de C. maritima nous a aussi permis de mettre en évidence deux types de comportement dans cette population de cellules en culture : l’un lié à une dépolarisation soutenue en réponse au NaCl conduisant probablement à la mort de ces cellules, l’autre lié à une dépolarisation transitoire indiquant que l’influx de Na+ au travers des NSCC était régulé permettant probablement aux cellules présentant ce comportement de survivre en évitant l'accumulation excessive de Na+ dans le cytosol. Dans la dernière partie de ce travail, nous avons mis en évidence la capacité de C. maritima d’exclure Na+ via le système SOS. Ce résultat suggère l’existence d’une deuxième voie de signalisation induite parallèlement à celle conduisant à la mort cellulaire. Cette voie, impliquant une production rapide d’oxygène singulet, pourrait permettre un influx de Ca2+ dans le cytoplasme activant la protéine SOS3 et en cascade SOS2 et SOS1 et les H+-ATPases de la membrane plasmique permettant un efflux du Na+ via SOS1 hors des cellules
AbstractThis work aimed at understanding the specificity of cellular responses of the obligate halophyte Cakile maritima to salt shock and regulation of early events involved in programmed cell death and survival under salinity conditions. In a first step, we have shown that this plant is tolerant upon both repetitive salt shocks and gradual salt application. However, we have observed a cell death zones on older leaves subjected to a severe shock saline (400 mM NaCl). To better understand the cascade of events involved in the cell death process, we continued our experiments on suspension culture of C. maritima, which we have optimized ourselves the conditions for establishment and suspension culture of Arabidopsis thaliana (glycophyte model). In both species, salinity induced programmed cell death that depends on the duration and the intensity of the applied salt treatment. Also, the same cellular events, including depolarization of the plasma membrane due to the Na+ influx by NSCCs, mitochondrial dysfunction, production of superoxide anions and activation of caspase-like proteins, occurs early in response to salt stress. C. maritima tolerance to salt stress is potentially due to a strong accumulation of ascorbate that would allow this halophyte to better reduce damage generated by oxidative stress. C. maritima is also distinguished by a better ability to control the cytoplasmic accumulation of Na+, leading to the survival of its cells under salinity conditions. This study on cell death induced by NaCl in cell culture of C. maritima also allowed us to identify two types of behavior in this population of cells in culture: one related to a sustained depolarization in response to NaCl probably leading to death of these cells, the other linked to a transient depolarization indicating that the Na+ influx through the NSCC was probably regulated allowing cells exhibiting this behavior to survive by avoiding excessive accumulation of Na+ in the cytosol. In the last part of this work, we have demonstrated the ability of C. maritima to exclude Na+ via the SOS system. This result suggests the existence of a second signaling pathway induced in parallel to that leading to cell death. This pathway, involving a rapid production of singlet oxygen, could allow a Ca2+ influx in the cytoplasm that acts as an elicitor for activation of SOS3 protein and SOS2-SOS1 cascade and H+- ATPases of the plasma membrane allowing Na+ efflux via SOS1 out of cells
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Schaal, Courtney. "Regulation of nAChRs and Stemness by Nicotine and E-cigarettes in NSCLC." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6582.

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Lung cancer is the leading cause of cancer-related death in both men and women, nationally and internationally and kills more people each year than breast, prostate, and colon cancers combined. Non-small cell lung carcinoma (NSCLC) is the most common histological subtype of lung cancer, and accounts for 85% of all cases. Cigarette smoking is the single greatest risk factor for lung cancer, and is correlated with 80-90% of all lung cancer deaths. Nicotine, the addictive component of tobacco smoke, is not a carcinogen and cannot initiate tumors itself; however, it is known to act as a tumor promoter, by enhancing the proliferation, migration, and invasion of cells in vitro, thus accelerating tumor growth and metastasis in vivo. Nicotine exerts is tumor promoting effects primarily by binding to, and activation of, nicotinic acetylcholine receptors (nAChRs), specifically the α7 subunit of nAChRs. While α7 nAChR is expressed in a wide array of cells, how its expression is regulated is not fully understood. Here we sought to elucidate the transcriptional regulation of α7 nAChR in NSCLC cells. We report that α7 nAChR expression is induced by nicotine in an autoregulatory feedforward loop, and that the α7 gene promoter is differentially regulated by E2F1 and STAT1 transcription factors at an overlapping binding site suggesting a competitive interplay. Depletion of E2F1 resulted in a reduced ability of nicotine to induce α7 nAChR, while depletion of STAT1 resulted in enhanced induction, suggesting that nicotine might use these two transcription factors to modulate the expression of α7 nAChR in a very precise fashion. More recently, nicotine has been implicated in promoting self-renewal of stem-like side-population cells from lung cancers. Cancer stem-like cells have been implicated in tumor initiation as well as the maintenance, drug resistance, dormancy, recurrence, and metastasis of various tumor types. We had previously shown that the embryonic stem cell transcription factor, Sox2, is indispensable for self-renewal of stem-like cells from lung adenocarcinoma cell lines; hence we sought to determine whether nicotine enhances stemness of lung cancer stem-like cells through Sox2. We find that nicotine can induce the expression of Sox2 at the transcriptional level and this occurs through a nAChR-Src-Yap1-E2F1 signaling axis. Over recent years, electronic cigarettes (e-cigarettes) have emerged as healthy alternatives to traditional cigarette smoking as they do not contain tobacco; however, they do still contain nicotine. Our studies show that e-cigarette components can enhance tumor promoting properties of NSCLC cells similar to that observed with nicotine alone, and find that they can induce expression of Sox2 and mesenchymal markers as well as enhance migration and stemness of NSCLC cells. Taken together, these studies reveal novel molecular mechanisms by which exposure to nicotine, via cigarette smoke or e-cigarettes, could alter the oncogenic potential of NSCLC cells.
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Books on the topic "NSCLCs"

1

Cappuzzo, Federico. Guide to Targeted Therapies: EGFR mutations in NSCLC. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-03059-3.

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National Strength & Conditioning Association (U.S.), ed. NSCA's essentials of personal training. 2nd ed. Champaign, IL: Human Kinetics, 2012.

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1961-, Hoffman Jay, ed. NSCA's guide to program design. Champaign, IL: Human Kinetics, 2012.

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1967-, Miller Todd, ed. NSCA's guide to tests and assessments. Champaign, IL: Human Kinetics, 2012.

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Campbell, Bill. NSCA's guide to sport and exercise nutrition. Edited by National Strength & Conditioning Association (U.S.). Champaign, IL: Human Kinetics, 2011.

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1975-, Campbell Bill, and Spano Marie 1972-, eds. NSCA's guide to sport and exercise nutrition. Champaign, IL: Human Kinetics, 2011.

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Kim, Ho-jung. array-CGH rŭl iyong han piso sepʻo pʻyeam ŭi chogi chaebal pʻyojija mit chindan mohyŏng kaebal =: Development of early-recurrence detection marker and diagnostic model using array-CGH in NSCLC. [Seoul]: Pogŏn Pokchibu, 2007.

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Haffen, Bernard. Secrets exposed: Discrimination still exist in the nscs, in the good ole boy racing series, the proof and the truth shall set you free! New York: iUniverse Inc, 2009.

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Southern African People's Solidarity Network, ed. The 2008 [i.e 2009] SADC Peoples' Summit report: Reclaiming SADC for peoples' solidarity development cooperation : taking ownership of our resources for people solidarity : converned by the Southern Africa Peoples' Solidarity Network (SAPSN) in Kinshasa, Democratic Republc of Congo : hosted by Forum of Congolese Organisations in South Africa (FOSA) and Nouvelle Societe Civile Congolaise (NSCC) : dates 5-6 September 2009. Harare, Zimbabwe: Southern African Peoples' Solidarity Network, 2009.

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Cappuzzo, Federico. Guide to Targeted Therapies : EGFR mutations in NSCLC: EGFR mutations in NSCLC. Adis, 2014.

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Book chapters on the topic "NSCLCs"

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Shih, Helen. "BRAF in NSCLC." In Targeted Therapies in Lung Cancer: Management Strategies for Nurses and Practitioners, 39–49. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-16550-5_5.

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Du, Lingling, Saiama N. Waqar, and Daniel Morgensztern. "Multimodality Therapy for NSCLC." In Cancer Treatment and Research, 151–63. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-40389-2_7.

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Cappuzzo, Federico. "Therapy options for advanced NSCLC." In Guide to Targeted Therapies: Treatment Resistance in Lung Cancer, 5–25. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-20741-4_2.

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Doubre, H., C. Le Pechoux, and T. Le Chevalier. "Adjuvant Treatments in Resectable NSCLC." In Malignant Tumors of the Lung, 215–25. Berlin, Heidelberg: Springer Berlin Heidelberg, 2004. http://dx.doi.org/10.1007/978-3-642-18698-1_19.

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Ramírez, J. L., M. F. Salazar, J. Gupta, J. M. Sánchez, M. Taron, M. Sänchez-Ronco, Vicente Alberola, and R. de las Peñas. "Methylation Patterns and Chemosensitivity in NSCLC." In New trends in cancer for the 21st century, 195–209. Dordrecht: Springer Netherlands, 2006. http://dx.doi.org/10.1007/978-1-4020-5133-3_17.

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Blackhall, Fiona H. "Strategies in ALK Rearranged NSCLC Patients." In New Therapeutic Strategies in Lung Cancers, 147–56. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-06062-0_10.

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Louie, Brian E., and Eric Vallières. "Minimally Invasive Surgery for Early NSCLC." In New Therapeutic Strategies in Lung Cancers, 27–32. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-06062-0_3.

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Pisters, Katherine. "Adjuvant and Neoadjuvant Therapy of NSCLC." In Lung Cancer, 139–59. Totowa, NJ: Humana Press, 2010. http://dx.doi.org/10.1007/978-1-60761-524-8_6.

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Tsao, Anne S., and Jack A. Roth. "Novel and Emerging Agents in NSCLC." In Lung Cancer, 464–78. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2014. http://dx.doi.org/10.1002/9781118468791.ch30.

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Das, Millie, and Heather Wakelee. "Anti-Angiogenic Agents in Metastatic NSCLC." In Lung Cancer, 527–40. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2014. http://dx.doi.org/10.1002/9781118468791.ch34.

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Conference papers on the topic "NSCLCs"

1

Altenberger, Corinna, Gerwin Heller, Bianca Schmid, Barbara Ziegler, Leonhard Müllauer, György Lang, Adelheid End-Pfützenreuter, et al. "Abstract 397: Transcriptional regulation of SPAG6 by DNA methylation in NSCLCs." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-397.

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Britt, Rebecca R., and John D. Minna. "Abstract 3780: Autophagy targeting therapies in NSCLC: Autophagy induction vs. inhibition in combination with erlotinib shows Torin1 can sensitize NSCLCs with KRAS mutations to Erlotinib." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-3780.

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Challa, Sridevi, Jian-Ping Guo, Cheng-xiong Xu, Yajuan Li, Donghwa Kim, Douglas Cress, Eric Haura, Domenico Coppola, and Jin Cheng. "Abstract 1890: IKBKE is a substrate of EGFR and a therapeutic target in NSCLCs with activating mutations of EGFR." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-1890.

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Tagal, Vural, Shuguang Wei, Wei Zhang, Rolf A. Brekken, Bruce A. Posner, Adi F. Gazdar, and Michael G. Roth. "Abstract LB-318: SMARCA4-inactivating mutations increase sensitivity to Aurora kinase A-targeted therapies in non-small cell lung cancers (NSCLCs)." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-lb-318.

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Du, Liqin, Maria C. Subauste, Michael Baker, Christopher DeSevo, Robert Borkowski, Shihua Zhong, Jeoffrey J. Schageman, et al. "Abstract 4709: miR-337-3p and its targets STAT3 and RAP1A modulate paclitaxel sensitivity in non-small cell lung cancers (NSCLCs)." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-4709.

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Tagal, Vural, Shuguang Wei, Wei Zhang, Bruce A. Posner, John D. Minna, Adi F. Gazdar, and Michael G. Roth. "Abstract 573: BRG1-inactivating mutations as potential predictive markers for Aurora kinase A-targeted therapies in non-small cell lung cancers (NSCLCs)." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-573.

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Yan, Dan, Xiaodong Wang, Stephen V. Frye, Shelton H. Earp, Deborah DeRyckere, and Douglas K. Graham. "Abstract 1082: MerTK promotes resistance to irreversible EGFR TKIs by activation of the PI3K-AKT pathway in NSCLCs expressing wild-type EGFR." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-1082.

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Rauthan, Amit, Poonam Patil, Rajashree Aswath, Nitin Yashas, and Gaurav Ningade. "Immunotherapy in Patients with Lung Cancer with Driver Mutations: A Single-Centre Experience." In Annual Conference of Indian Society of Medical and Paediatric Oncology (ISMPO). Thieme Medical and Scientific Publishers Pvt. Ltd., 2021. http://dx.doi.org/10.1055/s-0041-1735365.

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Abstract Introduction Immunotherapy has revolutionized treatment in metastatic nonsmall cell lung cancer (NSCLC) without driver mutations. Trial data shows that programmed death-1/PDL1 blockade in epidermal growth factor receptor (EGFR) and other driver mutation positive lung cancers is not beneficial; and instead maybe detrimental. Here, we evaluated the efficacy of immune check point inhibitors in a series of patients with EGFR and other driver mutation–positive advanced NSCLC. Objectives This study was aimed to evaluate the efficacy of immune check point inhibitors in a series of patients with EGFR and other driver mutation–positive advanced NSCLC. Materials and Methods We retrospectively analyzed 75 patients which received PD1/PDL1 inhibitors for advanced NSCL between January 2017 and January 2020. Ten patients were detected to have driver mutations on either tumor tissue or blood by next-generation sequencing (NGS). PDL1 status was assessed on SP263 ventana platform. Results Out of 10 patients, 7 were male and 3 were female. EGFR was detected in six patients (three on tumor and three in blood NGS), MET exon 14 skipping mutation in two patients, and RAS mutation in two patients on NGS in blood. Immunotherapy combined with chemotherapy was given in 5 (50%) patients, immunotherapy + bevacizumab + chemotherapy in two (20%) and immunotherapy alone in three patients (30%). Immunotherapy was started as first line in four patients as tumor tissue was negative for EGFR, ALK, and ROS1 by single gene testing. The remaining six patients received immunotherapy on progression in the second or subsequent lines. On NGS testing at progression, EGFR mutation was detected in one patient, MET exon 14 skip mutation was detected in two patients, and RAS mutation was detected in two patients. Immunotherapy alone was used in three patients in view of advanced age and multiple comorbidities. The median progression-free survival (PFS) was 5 months (range: 2–11 months). Two patients who received chemotherapy + bevacizumab + immunotherapy continue to do well without progression at 9 months. Conclusion PD1/PDL1 checkpoint inhibitors seem to have a limited impact in treatment in patients with driver mutations. Molecular testing by NGS is recommended either on tumor tissue or on blood by NGS if single gene testing for EGFR/ALK/ROS1 alterations is negative. We recommend not using single agent checkpoint inhibitors in molecular driven advanced NSCLC even with high PDL1 expression. We do see benefit in patients who received PD1/PDL1 inhibitors in combination with chemotherapy with bevacizumab. In conclusion, in patients with molecular-driven NSCLC who progress after standard therapy can be treated with PD1/PDL1 inhibitors, but this should always be given in combination with chemotherapy and bevacizumab.
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Yenerall, Paul M., Rahul Kollipara, Ryan Carstens, Kenneth Huffman, Luc Girard, Jaime Rodriguez, Ignacio Wistuba, David Mangelsdorf, John Minna, and Ralf Kittler. "Abstract 4779: RUVBL1 and RUBVL2 are chromatin remodelers that represent prognostic and novel therapeutic targets for a subset of non-small cell lung cancers (NSCLCs)." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-4779.

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Greer, Rachel M., Michael Peyton, Luc Girard, Yang Xie, Adi F. Gazdar, Patrick Harran, Lai Wang, Rolf A. Brekken, Xiaodong Wang, and John D. Minna. "Abstract 3479: SMAC mimetic (JP1201) sensitizes non small cell lung cancers (NSCLCs) to multiple chemotherapy agents and erlotinib in an IAP dependent but TNFα independent manner." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-3479.

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Reports on the topic "NSCLCs"

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Young, Jamey D., and Young M. Whang. Targeting Redox Homeostasis in LKB1-deficient NSCLC. Fort Belvoir, VA: Defense Technical Information Center, September 2014. http://dx.doi.org/10.21236/ada614534.

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Peng, Yinglong, Jinwei Chen, Ziyan Wang, Yihui Cao, and Jie Zhao. A Systematic Review and meta-analysis of the efficacy of immunotherapy in the treatment of non-small cell lung cancer. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, June 2022. http://dx.doi.org/10.37766/inplasy2022.6.0094.

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Review question / Objective: This study aimed to compare the effectiveness of different ICIs in the treatment of NSCLC, and to provide a theoretical basis for clinical selection of different regimens. Condition being studied: Immunotherapy is a relatively new treatment method for non-small cell lung cancer (NSCLC), and clinical studies confirmed that immune checkpoint inhibitors (ICIs) showed prominent efficacy in the treatment of NSCLC patients. This study aimed to compare the effectiveness of different ICIs in the treatment of NSCLC, and to provide a theoretical basis for clinical selection of different regimens.
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Winkles, Jeffrey A. GrB-TWEAK: A Potential Novel Biologic for NSCLC Therapy. Fort Belvoir, VA: Defense Technical Information Center, September 2015. http://dx.doi.org/10.21236/ada624531.

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Freire, Mariana, Diana Martins, Maria Filomena Botelho, and Fernando Mendes. Biomarkers of resistance mechanisms in innovative lung cancer treatments - A systematic Review. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, September 2022. http://dx.doi.org/10.37766/inplasy2022.9.0011.

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Review question / Objective: This systematic review aims to provide an overview of the immunotherapy resistance mechanisms and identify potential biomarkers associated with immunotherapy response in NSCLC, as well as examine new treatment options to overcome this hurdle. Condition being studied: Lung Cancer (LC) remains one of the leading cancers worldwide. In 2020, were globally estimated 2 206 771 new cases and 1 796 144 deaths, representing the uttermost frequent cause of cancer death. LC is classified histologically into small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC), being the last one the most common, representing 80 to 85% of all LC. The three predominantly subtypes of NSCLC are lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) and large cell carcinoma (LCLC). NSCLC is usually diagnosed in advanced-staged disease due to ambiguous and delayed severe symptoms.
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Ouyang, Zhiqiang, Qian Li, Guangrong Zheng, Tengfei Ke, Jun Yang, and Chengde Liao. Radiomics for predicting tumor microenvironment phenotypes in non-small cell lung cance: A systematic review and meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, September 2022. http://dx.doi.org/10.37766/inplasy2022.9.0060.

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Review question / Objective: Tumor microenvironment (TIME) phenotype is an important factor to affect the response and prognosis of immunotherapy in non-small cell lung cancer (NSCLC). Recently, accumulating studies have noninvasivly perdited the TIME phenotypes of NSCLC by using CT or PET/CT based radiomics. We will conduct this study by means of meta-analysis to eveluate the power and value of CT or PET/CT based radiomics for predicting TIME phenotypes in NSCLC patients. Condition being studied: At present, several recent prospective or retrospective cohort studies and randomized controlled studies have confirmed that CT or PET/CT-based radiomics were the potential tools to predict TIME phenotypes in NSCLC. However, this conclusion is controversial because of the difference of prediction profermance of different studies. The published and unpublished investigations will be included in this study. We will comprehensively evaluate the heterogeneity of these investigations, and the power and value of radiomics for predicting TIME phenotypes.
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Kudryashov, Dmitri, and Elena Kudryashova. Split and Splice" Approach for Highly Selective Targeting of Human NSCLC Tumors". Fort Belvoir, VA: Defense Technical Information Center, October 2014. http://dx.doi.org/10.21236/ada613862.

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Kang, Jing, Jun Zhang, Zongsheng Tian, Ye Xu, Jiangbi Li, and Mingxina Li. The efficacy and safety of immune-checkpoint inhibitor plus chemotherapy versus chemotherapy for non-small cell lung cancer: an updated systematic review and meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, May 2022. http://dx.doi.org/10.37766/inplasy2022.5.0156.

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Review question / Objective: Population: histologically confirmed advanced NSCLC patients; Intervention: received immune-checkpoint inhibitor plus chemotherapy; Comparison:received chemotherapy; Outcome: reported OS, PFS, ORR and TRAEs; Study design: RCT. Condition being studied: Lung cancer is the primary cause of cancer-related deaths, with an estimated 2.20 million new cases and 1.79 million deaths every year, and 85% of all primary lung cancers are non-small cell lung cancer. Eligibility criteria: Studies were considered eligible if they met the following criteria: (1) being an randomized controlled trial published in English, (2) histologically confirmed advanced NSCLC patients, (3) reported OS, PFS, ORR and TRAEs, (4) the intervention group received immune-checkpoint inhibitor plus chemotherapy, while the control group received chemotherapy, (5) When numerous papers reporting the same trial were found, the most current or most complete publications were chosen. The following were the exclusion criteria: (1) duplicate articles, (2) reviews, meta-analyses, case reports, editorials and letters, (3) molecular biology or animal research, (4) retrospective or prospective observational cohort studies.
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Yendamuri, Saikrishna. Laser Capture Microdissection Assisted Identification of Epithelial MicroRNA Expression Signatures for Prognosis of Stage I NSCLC. Fort Belvoir, VA: Defense Technical Information Center, October 2013. http://dx.doi.org/10.21236/ada598453.

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Yendamuri, Saikrishna. Laser Capture Microdissection Assisted Identification of Epithelial MicroRNA Expression Signatures for Prognosis of Stage I NSCLC. Fort Belvoir, VA: Defense Technical Information Center, October 2011. http://dx.doi.org/10.21236/ada555298.

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Yendamuri, Sai. Laser Capture Microdissection Assisted Identification of Epithelial MicroRNA Expression Signatures for Prognosis of Stage I NSCLC. Fort Belvoir, VA: Defense Technical Information Center, December 2014. http://dx.doi.org/10.21236/ada621332.

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