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1

Greco, Federico, Luigi Giuseppe Quarta, Aldo Carnevale, Melchiore Giganti, Rosario Francesco Grasso, Bruno Beomonte Zobel, and Carlo Augusto Mallio. "Subcutaneous Adipose Tissue Reduction in Patients with Clear Cell Renal Cell Carcinoma and Peritumoral Collateral Vessels: A Retrospective Observational Study." Applied Sciences 11, no. 13 (June 30, 2021): 6076. http://dx.doi.org/10.3390/app11136076.

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Background: peritumoral collateral vessels adjacent to renal cell carcinoma (RCC) can be encountered in clinical practice. Cancer cachexia is defined as a decrease of adipose and skeletal muscle tissues. In this study we evaluated, using a quantitative CT imaging-based approach, the distribution of abdominal adipose tissue in clear cell RCC (ccRCC) male patients with and without collateral vessels. Methods: between November 2019 and February 2020, in this retrospective study we enrolled 106 ccRCC male Caucasian patients divided into two groups: a ccRCCa group without collateral vessels (n = 48) and a ccRCCp group with collateral vessels (n = 58). The total adipose tissue (TAT), visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured in both groups. Moreover, the VAT/SAT ratio was calculated for each subject. Results: a statistically significant difference between the two groups was found in the SAT area (p < 0.05), while no significant differences were found in the TAT area, VAT area and VAT/SAT ratio. Conclusion: this study demonstrates a reduction of SAT in ccRCC patients with peritumoral collateral vessels.
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2

Greco, Federico, Luigi Giuseppe Quarta, Rosario Francesco Grasso, Bruno Beomonte Zobel, and Carlo Augusto Mallio. "Increased visceral adipose tissue in clear cell renal cell carcinoma with and without peritumoral collateral vessels." British Journal of Radiology 93, no. 1112 (August 2020): 20200334. http://dx.doi.org/10.1259/bjr.20200334.

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Objective: The excessive amount of adipose tissue, mainly visceral, determines adiposopathy. With respect to oncogenesis, visceral adipose tissue (VAT) releases secretes adipokines, proinflammatory citokines and growth factors, considered mediating molecules in the development of obesity-related tumors. In this study, we quantify VAT in male patients with clear cell renal cell carcinoma (ccRCC) subgrouped according to the presence or absence of peritumoral collateral vessels. Methods: in this retrospective study, we enrolled 141 male caucasian patients divided into 2 groups: the ccRCC group (n = 106) composed of patients with ccRCC and control group (n = 35). The ccRCC group was further divided into two subgroups: the ccRCCa subgroup which showed absence of collateral vessels (n = 48) and ccRCCp subgroup with collateral vessels (n = 58). Total adipose tissue (TAT) area, VAT area and subcutaneous adipose tissue (SAT) area were measured in the groups and subgroups. VAT/SAT ratio was calculated for each subject. Results: Statistically significant differences were obtained between ccRCC group and control group for TAT area (p < 0.005), VAT area (p < 0.005) and SAT area (p = 0.01). Between ccRCCa subgroup and control group for TAT area (p < 0.001), VAT area (p = 0.005) and SAT area (p = 0.001). Between ccRCCp subgroup and control group for TAT area (p = 0.01) and VAT area (p = 0.01). Conclusion: This study confirms the increase of abdominal, especially visceral, adipose tissue in ccRCC patients and demonstrates a significant VAT accumulation in both categories of patients with and without peritumoral collateral vessels. Advances in knowledge: Visceral adiposity is present in patients with ccRCC regardless the presence of peritumoral collateral vessels, with surprisingly stronger results in the ccRCCa subgroup.
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3

Carraro, Amedeo, Elisabetta Trevellin, Matteo Fassan, Andromachi Kotsafti, Francesca Lunardi, Andrea Porzionato, Luigi Dall'Olmo, et al. "Esophageal adenocarcinoma microenvironment: Peritumoral adipose tissue effects associated with chemoresistance." Cancer Science 108, no. 12 (November 4, 2017): 2393–404. http://dx.doi.org/10.1111/cas.13415.

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4

Lee, Jeong Won, Sung Yong Kim, Sun Wook Han, Jong Eun Lee, Sung Hoon Hong, Sang Mi Lee, and In Young Jo. "Clinical Significance of Peritumoral Adipose Tissue PET/CT Imaging Features for Predicting Axillary Lymph Node Metastasis in Patients with Breast Cancer." Journal of Personalized Medicine 11, no. 10 (October 15, 2021): 1029. http://dx.doi.org/10.3390/jpm11101029.

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We investigated whether textural parameters of peritumoral breast adipose tissue (AT) based on F-18 fluorodeoxyglucose (FDG) PET/CT could predict axillary lymph node metastasis in patients with breast cancer. A total of 326 breast cancer patients with preoperative FDG PET/CT were retrospectively enrolled. PET/CT images were visually assessed and the maximum FDG uptake of axillary lymph nodes (LN SUVmax) was measured. From peritumoral breast AT, 38 textural features of PET imaging were extracted. The diagnostic ability of PET based on visual analysis, LN SUVmax, and textural features of peritumoral breast AT for predicting axillary lymph node metastasis were assessed using the area under the receiver operating characteristic curve (AUC) values. Among the 38 peritumoral breast AT textural features, grey-level co-occurrence matrix (GLCM) entropy showed the highest AUC value (0.830) for predicting axillary lymph node metastasis. The value of GLCM entropy was higher than that of visual analysis (0.739; p < 0.05) and the AUC value was comparable to that of LN SUVmax (0.793; p > 0.05). In the subgroup analysis of patients with negative findings on visual analysis, GLCM entropy still showed a high diagnostic ability (AUC: 0.759) in predicting lymph node metastasis. The findings suggest a potential diagnostic role of PET/CT imaging features of peritumoral breast AT in predicting axillary lymph node metastasis in patients with breast cancer.
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5

Greco, Federico, Luigi Giuseppe Quarta, Caterina Bernetti, Rosario Francesco Grasso, Mark Ivo van Berge Henegouwen, Bruno Beomonte Zobel, and Carlo Augusto Mallio. "Composition of Perinephric Fat and Fuhrman Grade in Clear Cell Renal Cell Carcinoma: The Role of Peritumoral Collateral Vessels." Applied Sciences 11, no. 9 (April 27, 2021): 3941. http://dx.doi.org/10.3390/app11093941.

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Background: The aim of this study was to investigate whether the presence of peritumoral collateral vessels could be indicative of a high Fuhrman grade (e.g., III and IV) in clear cell renal cell carcinoma (ccRCC). Methods: Between November 2019 and February 2020, a total of 267 ccRCC patients with histology-proven diagnoses were retrospectively analyzed and screened. Imaging analysis was performed on computed tomography (CT) images to assess the presence of peritumoral collateral vessels and understand the potential association with high Fuhrman grades. These vessels are defined as dilated and macroscopically visible peritumoral renal capsular veins. Results: A total of 190 ccRCC patients were included in the study, considering the exclusion criteria. In patients with peritumoral collateral vessels, there was a statistically significant greater presence of ccRCC with a high Fuhrman grade both among the total cohort of patients regardless gender (n = 190) (p < 0.001) as well as among ccRCC male patients only (n = 127) (p < 0.005). Conclusion: Here, we show a novel association between peritumoral collateral vessels and ccRCC with high Fuhrman grades in male patients. The presence of peritumoral collateral vessels in perinephric adipose tissue can be indicative of more aggressive ccRCC.
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6

Lo Iacono, Melania, Chiara Modica, Gaetana Porcelli, Ornella Roberta Brancato, Giampaolo Muratore, Paola Bianca, Miriam Gaggianesi, et al. "Targeting of the Peritumoral Adipose Tissue Microenvironment as an Innovative Antitumor Therapeutic Strategy." Biomolecules 12, no. 5 (May 14, 2022): 702. http://dx.doi.org/10.3390/biom12050702.

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The tumor microenvironment (TME) plays a key role in promoting and sustaining cancer growth. Adipose tissue (AT), due to its anatomical distribution, is a prevalent component of TME, and contributes to cancer development and progression. Cancer-associated adipocytes (CAAs), reprogrammed by cancer stem cells (CSCs), drive cancer progression by releasing metabolites and inflammatory adipokines. In this review, we highlight the mechanisms underlying the bidirectional crosstalk among CAAs, CSCs, and stromal cells. Moreover, we focus on the recent advances in the therapeutic targeting of adipocyte-released factors as an innovative strategy to counteract cancer progression.
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7

Fabienne, De Toni, Nigri Jeremy, Tomasini Richard, Galitzky Jean, Bouloumié Anne, and Garmy-Susini Barbara. "Peritumoral adipose tissue lipolysis activates the lymphatic system to promote PDAC-associated cachexia." Pancreatology 17, no. 3 (July 2017): S48. http://dx.doi.org/10.1016/j.pan.2017.05.150.

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8

Notarnicola, Maria, Angelica Miccolis, Valeria Tutino, Dionigi Lorusso, and Maria Gabriella Caruso. "Low Levels of Lipogenic Enzymes in Peritumoral Adipose Tissue of Colorectal Cancer Patients." Lipids 47, no. 1 (November 17, 2011): 59–63. http://dx.doi.org/10.1007/s11745-011-3630-5.

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9

Zoico, Elena, Vanni Rizzatti, Elena Darra, Simona Luciana Budui, Guido Franceschetti, Fabrizio Vinante, Corrado Pedrazzani, et al. "Morphological and Functional Changes in the Peritumoral Adipose Tissue of Colorectal Cancer Patients." Obesity 25 (October 31, 2017): S87—S94. http://dx.doi.org/10.1002/oby.22008.

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10

Trevellin, Elisabetta, Marco Scarpa, Amedeo Carraro, Francesca Lunardi, Andromachi Kotsafti, Andrea Porzionato, Luca Saadeh, et al. "Esophageal adenocarcinoma and obesity: peritumoral adipose tissue plays a role in lymph node invasion." Oncotarget 6, no. 13 (March 14, 2015): 11203–15. http://dx.doi.org/10.18632/oncotarget.3587.

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11

Amor, S., M. C. Iglesias-de la Cruz, E. Ferrero, O. García-Villar, V. Barrios, N. Fernandez, L. Monge, A. L. García-Villalón, and M. Granado. "Peritumoral adipose tissue as a source of inflammatory and angiogenic factors in colorectal cancer." International Journal of Colorectal Disease 31, no. 2 (October 22, 2015): 365–75. http://dx.doi.org/10.1007/s00384-015-2420-6.

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12

Tabuso, Maria, Raghu Adya, Richard Stark, Kishore Gopalakrishnan, Yee Wah Tsang, Sean James, Andrew White, et al. "Fibrotic Phenotype of Peritumour Mesenteric Adipose Tissue in Human Colon Cancer: A Potential Hallmark of Metastatic Properties." International Journal of Molecular Sciences 22, no. 5 (February 28, 2021): 2430. http://dx.doi.org/10.3390/ijms22052430.

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The impact of tumour associated stroma on cancer metastasis is an emerging field. However, cancer associated genes in peritumoral adipose tissue (pAT) in human colon cancer have not been explored. The aim of this study was to identify differentially expressed genes (DEGs) associated with cancer pathways in mesenteric pAT compared with adjacent adipose tissue. In total, nine patients with colon cancer pathological stage T2/T4 were employed in this study. DEGs were identified in 6 patients employing Nanostring PanCancer Pathway Panel and pathway enrichment analyses were performed. Differential expression of the 5 most up-regulated and 2 down regulated genes was validated with qRT-PCR. Results showed collagen type I alpha 1 chain (COL1A1) p = 0.007; secreted frizzled related protein (SFRP2) p = 0.057; fibroblast growth factor 7 (FGF7) not significant (ns); phospholipase A2, group IIA (PLA2G2A) ns; nerve growth factor receptor (NGFR) ns; lymphoid enhancer binding factor 1 (LEF1) p = 0.03; cadherin 1, Type 1, E-cadherin (epithelial) (CDH1) 0.09. Results have highlighted down-regulation of the Wingless/Integrated (Wnt) pathway in mesenteric pAT compared to distal adipose tissue. Highly upregulated genes in mesenteric pAT were involved in extracellular matrix (ECM)-receptor interactions and focal adhesion. Highly down regulated genes were involved in the cell cycle. Immunohistochemistry revealed differential distribution of COL1A1 showing maximum levels in tumour tissue and gradually decreasing in distant adipose tissue. COL1A1 and down regulation of Wnt pathway may have a role in local invasion and distant metastasis. COL1A1 may represent a stromal prognostic biomarker and therapeutic target in colon cancer.
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13

Li, Ming, and Renge Bu. "Biological Support to Obesity Paradox in Renal Cell Carcinoma: A Review." Urologia Internationalis 104, no. 11-12 (2020): 837–48. http://dx.doi.org/10.1159/000510245.

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Obesity is a proven risk factor and a debated prognostic factor in renal cell carcinoma (RCC). Termed as an “obesity paradox,” the topic has churned controversies, with a few arguing of no true biological association. Suggesting otherwise, a few studies revealed adiposity-induced altered molecular and transcriptomic signatures, at both the systemic and local (tumor and peritumoral adipose tissue) levels, in RCC patients, favoring the paradox. Summarizing such studies suggests of a considerable biological support to adiposity as a promising prognostic factor in RCC patients, although much needs to be clarified before adopting it as a valuable addition to the existing prognostic model.
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14

Ahn, Hyein, Jeong Won Lee, Si-Hyong Jang, Hyun Ju Lee, Ji-Hye Lee, Mee-Hye Oh, and Sang Mi Lee. "Prognostic significance of imaging features of peritumoral adipose tissue in FDG PET/CT of patients with colorectal cancer." European Journal of Radiology 145 (December 2021): 110047. http://dx.doi.org/10.1016/j.ejrad.2021.110047.

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15

García-Barquín, Paula, María Páramo, Arlette Elizalde, Luis Pina, Jon Etxano, Alejandro Fernandez-Montero, and Meylin Caballeros. "The effect of the amount of peritumoral adipose tissue in the detection of additional tumors with digital breast tomosynthesis and ultrasound." Acta Radiologica 58, no. 6 (November 12, 2016): 645–51. http://dx.doi.org/10.1177/0284185116668211.

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16

Trevellin, Elisabetta, Amedeo Carraro, Matteo Fassan, Andromachi Kotsafti, Matteo Cagol, Luca Maria Saadeh, Melania Scarpa, et al. "Tu1294 – Esophageal Adenocarcinoma Microenvironment: Leptin Expression in Peritumoral Adipose Tissue is Associated with Tumor Grading and Staging, Higher Immune Infiltration Within the Tumor and Neoadjuvant Treatment." Gastroenterology 156, no. 6 (May 2019): S—1484. http://dx.doi.org/10.1016/s0016-5085(19)40786-5.

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17

Trevellin, Elisabetta, Amedeo Carraro, Matteo Fassan, Andromachi Kotsafti, Matteo Cagol, Luca Maria Saadeh, Melania Scarpa, et al. "221 – Esophageal Adenocarcinoma Microenvironment: Cd34 Expression in Peritumoral Adipose Tissue is Associated with Tumor Necrosis and Impaired Immune Response Within the Tumor, and is Decreased by Neoadjuvant Treatment." Gastroenterology 156, no. 6 (May 2019): S—1389. http://dx.doi.org/10.1016/s0016-5085(19)40507-6.

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18

Carroll, P. A., L. Healy, J. Lysaght, M. Griffin, B. Dunne, Mr T. Boyle, J. V. Reynolds, M. J. Kennedy, G. Pidgeon, and E. M. Connolly. "Mammary adipose tissue and cancer cell growth: The role of adipose tissue in the tumor microenvironment." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e22009-e22009. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e22009.

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e22009 Background: Worldwide, the prevalence of obesity is rapidly increasing, correlating with a direct increase in cancer rates1. Adipose tissue is considered an important endocrine organ producing several important hormones and cytokines including leptin and adiponectin. Mechanisms for the role of obesity in cancer states includes the excess or unregulated secretion of adipocytokines from adipose tissue, and potentially the metabolic syndrome (a cluster of co-morbidities linked to metabolic dysregulation). Mammary adipose tissue is proposed to play a vital role in the microenvironment of normal and tumour states within the breast2. Breast adipose tissue is a good candidate to investigate effects of obesity and metabolic disturbances on cancer states. Methods: Peritumoural (PT) adipose tissue adjacent to the tumour and distal adipose tissue (D) within the breast was sampled in 10 patients. The tissue was processed and cultured for 72hrs in serum free minimal cytokine media. A-MB-231 and MCF-7 breast cancer cell lines were then cultured with this adipocyte conditioned media (ACM) and cell proliferation response was then measured using BrDU assays. The adipocytokine profile at the mRNA and protein level was measured in ACM and adipose tissue for comparative differences using RT-PCR, ELISA and Cytokine Profiler technology. Results: ACM from both sites promoted tumour cell survival. There was however, a differential cell proliferation response noted between the peritumoural (PT) ACM and that from the distant (D) ACM. Pro-inflammatory mediators (VEGF, TNF-α, EGF) were also demonstrated a trend to be differentially expressed between the 2 sites. Conclusions: Proliferation of breast cancer cell lines occurs in response to ACM, with differential effects seen between peritumoural ACM and distant ACM. This may be mediated through increased pro-inflammatory or pro- mitogenic adipocytokine production in adipose tissue surrounding tumour. Further analysis will determine what role obesity and the metabolic syndrome plays in the results noted. No significant financial relationships to disclose.
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19

Neto, Nelson Inácio Pinto, Ariene Soares de Pinho Murari, Lila Missae Oyama, José Pinhata Otoch, Paulo Sérgio Martins Alcântara, Flavio Tokeshi, Raquel Galvão Figuerêdo, et al. "Peritumoural adipose tissue pro-inflammatory cytokines are associated with tumoural growth factors in cancer cachexia patients." Journal of Cachexia, Sarcopenia and Muscle 9, no. 6 (October 3, 2018): 1101–8. http://dx.doi.org/10.1002/jcsm.12345.

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20

Guaita-Esteruelas, S., J. Gumà, L. Masana, and J. Borràs. "The peritumoural adipose tissue microenvironment and cancer. The roles of fatty acid binding protein 4 and fatty acid binding protein 5." Molecular and Cellular Endocrinology 462 (February 2018): 107–18. http://dx.doi.org/10.1016/j.mce.2017.02.002.

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21

Okhunov, Z., C. Blair, F. Rahmatpanah, S. Shao, V. Huynh, D. Mercola, X. Zi, and J. Landman. "865 Higher levels of secreted S100 A8/9 levels from peritumor perirenal adipose tissues are associated with renal cell carcinoma (RCC)." European Urology Supplements 14, no. 2 (April 2015): e865. http://dx.doi.org/10.1016/s1569-9056(15)60853-3.

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22

Miracle, Cora E., Travis Salisbury, and Chelsea McCallister. "Abstract C096: Obese adipose derived secretome stimulates triple negative breast cancer via stimulation of the mTOR pathway." Cancer Epidemiology, Biomarkers & Prevention 32, no. 1_Supplement (January 1, 2023): C096. http://dx.doi.org/10.1158/1538-7755.disp22-c096.

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Abstract Background: Breast cancer remains the most common cancer amoung women with multipe risk factors including smoking, genetics, environmental factors, and obesity. Smoking and obesity are the top two risk factors for development of breast cancer, with smoking increasing the risk of development by 21% and obesity by 20-40%. Obesity increases the risk for all breast cancer subtypes, including triple negative breast cancer (TNBC) that is null for estrogen and progesterone receptors and the tyrosine kinase receptor, HER2. To this end, recent retrospective patient studies have shown that the majority of patients with TNBC were obese at the time of diagnosis. In addition, obese patients had a higher TNBC tumor grade and a higher staging. However, the signaling mechanisms that promote the progression of TNBC in obesity are not well understood. We published that adipose tissue (AT) derived secretome (ADS) in obesity promotes the invasiveness of estrogen receptor positive breast cancer cells. Based on these prior findings, we hypothesize ADS in obesity acts on TNBC cells to induce mTOR activity and in turn stimulates TNBC cell migration and invasiveness. Methods: De-identified peritumor (PT) breast AT samples were obtained with patient consent at the time of surgery for breast cancer treatment. Breast AT samples were cultured in serum free culture medium for 24 hours. After the incubation, the AT conditioned media was clarified by centrifugation. For this study, considered BMI less than 30 as lean-ADS (LADS) and BMI of 30 or greater as obese-ADS (OADS). ADS diluted 1:10 in serum free culture medium was applied to human MDA-MB-231 and MDA-MB-436 TNBC cells. Cell migration was assayed by the scratch assay. Images were taken at time 0, and 24 hours. Analysis was performed using image J. Western blot studies were performed to assay the levels of total and/or phosphorylated proteins. Results: OADS stimulated a statistically significant increase (1.5 fold) in TNBC cell migration compared with LADS. The increase in TNBC cell migration was associated with a significant increase (1.5 fold) in phosphorylated S6 in TNBC cells treated with OADS relative to LADS. Conclusion: Increases in mTOR activity in TNBC cells in response to OADS is associated with increased TNBC cell migration. Citation Format: Cora E. Miracle, Travis Salisbury, Chelsea McCallister. Obese adipose derived secretome stimulates triple negative breast cancer via stimulation of the mTOR pathway [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C096.
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23

Conti, G., L. Calderan, L. A. Quintero Sierra, A. Conti, R. Ossanna, F. Boschi, P. Marzola, et al. "Tumor and peritumoral adipose tissue crosstalk: de-differentiated adipocytes influence spread of colon carcinoma cells." Tissue and Cell, December 2022, 101990. http://dx.doi.org/10.1016/j.tice.2022.101990.

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24

Ferrando, Matías, Flavia Alejandra Bruna, Leonardo Rafael Romeo, David Contador, Daiana Lorena Moya-Morales, Flavia Santiano, Leila Zyla, et al. "Renal peritumoral adipose tissue undergoes a browning process and stimulates the expression of epithelial-mesenchymal transition markers in human renal cells." Scientific Reports 12, no. 1 (May 23, 2022). http://dx.doi.org/10.1038/s41598-022-12746-9.

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AbstractTumor cells can interact with neighboring adipose cells and adipocyte dedifferentiation appears to be an important aspect of tumorigenesis. We evaluated the size of adipocytes in human adipose explants from normal (hRAN) and kidney cancer (hRAT); changes in the expression of WAT and BAT/beige markers in hRAN and hRAT; the expression of epithelial-mesenchymal transition (EMT) cell markers in human kidney tumor (786-O, ACHN and Caki-1); and non-tumor (HK-2) epithelial cell lines incubated with the conditioned media (CMs) of hRAN and hRAT. We observed that hRAT adipocytes showed a significantly minor size compared to hRAN adipocytes. Also, we observed that both Prdm16 and Tbx1 mRNA and the expression of UCP1, TBX1, PPARγ, PCG1α, c/EBPα LAP and c/EBPα LIP was significantly higher in hRAT than hRAN. Finally, we found an increase in vimentin and N-cadherin expression in HK-2 cells incubated for 24 h with hRAT-CMs compared to hRAN- and control-CMs. Furthermore, desmin and N-cadherin expression also increased significantly in 786-O when these cells were incubated with hRAT-CMs compared to the value observed with hRAN- and control-CMs. We observed a significant decrease in E-cadherin expression in the ACHN cell line incubated with hRAT-CMs versus hRAN- and control-CMs. However, we did not observe changes in E-cadherin expression in HK-2, 786-O or Caki-1. The results obtained, together with the results previously published by our group, allow us to conclude that perirenal white adipose tissue browning contributes to tumor development in kidney cancer. In addition, hRAT-CMs increases the expression of mesenchymal markers in renal epithelial cells, which could indicate a regulation of EMT due to this adipose tissue.
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25

Motrescu, Elena Roza, and Marie-Christine Rio. "Cancer cells, adipocytes and matrix metalloproteinase 11: a vicious tumor progression cycle." Biological Chemistry 389, no. 8 (August 1, 2008). http://dx.doi.org/10.1515/bc.2008.110.

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Abstract This brief review focuses on the emerging role of matrix metalloproteinase 11 (MMP-11) in cancer progression. It has recently been shown that MMP-11 is induced in adipose tissue by cancer cells as they invade their surrounding environment. MMP-11 negatively regulates adipogenesis by reducing pre-adipocyte differentiation and reversing mature adipocyte differentiation. Adipocyte dedifferentiation in turn leads to the accumulation of non-malignant peritumoral fibroblast-like cells, which favor cancer cell survival and tumor progression. This MMP-11-mediated bi-directional cross-talk between invading cancer cells and adjacent adipocytes/pre-adipocytes highlights the central role that MMP-11 plays during tumor desmoplasia and represents a molecular link between obesity and cancer.
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26

Su, Fei, Alexes C. Daquinag, Songyeon Ahn, Achinto Saha, Yulin Dai, Zhongming Zhao, John DiGiovanni, and Mikhail G. Kolonin. "Progression of prostate carcinoma is promoted by adipose stromal cell-secreted CXCL12 signaling in prostate epithelium." npj Precision Oncology 5, no. 1 (March 22, 2021). http://dx.doi.org/10.1038/s41698-021-00160-9.

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AbstractAggressiveness of carcinomas is linked with tumor recruitment of adipose stromal cells (ASC), which is increased in obesity. ASC promote cancer through molecular pathways not fully understood. Here, we demonstrate that epithelial–mesenchymal transition (EMT) in prostate tumors is promoted by obesity and suppressed upon pharmacological ASC depletion in HiMyc mice, a spontaneous genetic model of prostate cancer. CXCL12 expression in tumors was associated with ASC recruitment and localized to stromal cells expressing platelet-derived growth factor receptors Pdgfra and Pdgfrb. The role of this chemokine secreted by stromal cells in cancer progression was further investigated by using tissue-specific knockout models. ASC deletion of CXCL12 gene in the Pdgfr + lineages suppressed tumor growth and EMT, indicating stroma as the key source of CXCL12. Clinical sample analysis revealed that CXCL12 expression by peritumoral adipose stroma is increased in obesity, and that the correlating increase in Pdgfr/CXCL12 expression in the tumor is linked with decreased survival of patients with prostate carcinoma. Our study establishes ASC as the source of CXCL12 driving tumor aggressiveness and outlines an approach to treatment of carcinoma progression.
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Yang, Li, Junyi Sun, Xianbo Yu, Yang Li, Min Li, Jing Liu, Xiangming Wang, and Gaofeng Shi. "Diagnosis of Serosal Invasion in Gastric Adenocarcinoma by Dual-Energy CT Radiomics: Focusing on Localized Gastric Wall and Peritumoral Radiomics Features." Frontiers in Oncology 12 (March 21, 2022). http://dx.doi.org/10.3389/fonc.2022.848425.

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ObjectivesTo build a radiomics model and combined model based on dual-energy CT (DECT) for diagnosing serosal invasion in gastric adenocarcinoma.Materials and methods231 gastric adenocarcinoma patients were enrolled and randomly divided into a training (n = 132), testing (n = 58), and independent validation (n = 41) cohort. Radiomics features were extracted from the rectangular ROI of the 120-kV equivalent mixed images and iodine map (IM) images in the venous phase of DECT, which was manually delineated perpendicularly to the gastric wall in the deepest location of tumor infiltration, including the peritumoral adipose tissue within 5 mm outside the serosa. The random forest algorithm was used for radiomics model construction. Traditional features were collected by two radiologists. Univariate and multivariate logistic regression was used to construct the clinical model and combined model. The diagnostic efficacy of the models was evaluated using ROC curve analysis and compared using the Delong’s test. The calibration curves were used to evaluate the calibration performance of the combined model.ResultsBoth the radiomics model and combined model showed high efficacy in diagnosing serosal invasion in the training, testing and independent validation cohort, with AUC of 0.90, 0.90, and 0.85 for radiomics model; 0.93, 0.93, and 0.89 for combined model. The combined model outperformed the clinical model (AUC: 0.76, 0.76 and 0.81).ConclusionThe radiomics model and combined model constructed based on tumoral and peritumoral radiomics features derived from DECT showed high diagnostic efficacy for serosal invasion in gastric adenocarcinoma.
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Mallikourti, Vasiliki, Sai Man Cheung, Tanja Gagliardi, Nicholas Senn, Yazan Masannat, Trevor McGoldrick, Ravi Sharma, Steven D. Heys, and Jiabao He. "Phased-array combination of 2D MRS for lipid composition quantification in patients with breast cancer." Scientific Reports 10, no. 1 (November 18, 2020). http://dx.doi.org/10.1038/s41598-020-74397-y.

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AbstractLipid composition in breast cancer, a central marker of disease progression, can be non-invasively quantified using 2D MRS method of double quantum filtered correlation spectroscopy (DQF-COSY). The low signal to noise ratio (SNR), arising from signal retention of only 25% and depleted lipids within tumour, demands improvement approaches beyond signal averaging for clinically viable applications. We therefore adapted and examined combination algorithms, designed for 1D MRS, for 2D MRS with both internal and external references. Lipid composition spectra were acquired from 17 breast tumour specimens, 15 healthy female volunteers and 25 patients with breast cancer on a clinical 3 T MRI scanner. Whitened singular value decomposition (WSVD) with internal reference yielded maximal SNR with an improvement of 53.3% (40.3–106.9%) in specimens, 84.4 ± 40.6% in volunteers, 96.9 ± 54.2% in peritumoural adipose tissue and 52.4% (25.1–108.0%) in tumours in vivo. Non-uniformity, as variance of improvement across peaks, was low at 21.1% (13.7–28.1%) in specimens, 5.5% (4.2–7.2%) in volunteers, 6.1% (5.0–9.0%) in peritumoural tissue, and 20.7% (17.4–31.7%) in tumours in vivo. The bias (slope) in improvement ranged from − 1.08 to 0.21%/ppm along the diagonal directions. WSVD is therefore the optimal algorithm for lipid composition spectra with highest SNR uniformly across peaks, reducing acquisition time by up to 70% in patients, enabling clinical applications.
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Lusch, Achim, Vien Nguyen, Christopher Blair, Molly Baker, Victor Huynh, Xiaolin Zi, and Jaime Landman. "311 SECRETED FACTORS FROM PERITUMOR ADIPOSE TISSUES OF CLEAR CELL RENAL CELL CARCINOMA INCREASED THE MOTILITY OF HUMAN CCRCC CELL LINE CAKI-2 VIA ENHANCEMENT OF WNT SIGNALING." Journal of Urology 189, no. 4S (April 2013). http://dx.doi.org/10.1016/j.juro.2013.02.1695.

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