Genes and Cancer最新文献

{"title":"Dialyl-sulfide with trans-chalcone prevent breast cancer prohibiting SULT1E1 malregulations and oxidant-stress induced HIF1a-MMPs induction.","authors":"Aarifa Nazmeen, Sayantani Maiti, Smarajit Maiti","doi":"10.18632/genesandcancer.237","DOIUrl":"10.18632/genesandcancer.237","url":null,"abstract":"<p><strong>Background: </strong>In some breast cancers, altered estrogen-sulfotransferase (SULT1E1) and its inactivation by oxidative-stress modifies E2 levels. Parallelly, hypoxia-inducible tissue-damaging factors (HIF1α) are induced. The proteins/genes expressions of these factors were verified in human-breast-cancer tissues. SULT1E1 inducing-drugs combinations were tested for their possible protective effects.</p><p><strong>Methods: </strong>Matrix-metalloproteases (MMP2/9) activity and SULT1E1-HIF1α protein/gene expression (Western-blot/RTPCR) were assessed in breast-cancers versus adjacent-tissues. Oxidant-stress neutralizer, chalcone (trans-1,3-diaryl-2-propen-1-ones) and SULT1E1-inducer pure dialyl-sulfide (garlic; <i>Allium sativum</i>) were tested to prevent cancer causing factors in rat, <i>in-vitro</i> and <i>in-vivo</i>. The antioxidant-enzymes SOD1/catalase/GPx/LDH and matrix-degenerating MMP2/9 activities were assessed (gel-zymogram). Histoarchitecture (HE-staining) and tissue SULT1E1-localization (immuno-histochemistry) were screened. Extensive statistical-analysis were performed.</p><p><strong>Results: </strong>Human cancer-tissue expresses higher SULT1E1, HIF1α protein/mRNA and lower LDH activity. Increase of MMP2/9 activities commenced tissue damage. However, chalcone and DAS significantly induced SULT1E1 gene/protein, suppressed HIF1α expression, MMP2/9 activities in rat tissues. Correlation and group statistics of t-test suggest significant link of oxidative-stress (MDA) with SULT1E1 (<i>p</i> = 0.006), HIF1α (<i>p</i> = 0.006) protein-expression. The non-protein-thiols showed negative correlation (<i>p</i> = 0.001) with HIF1α. These proteins and SULT1E1-mRNA expressions were significantly higher in tumor (<i>p</i> < 0.05). Correlation data suggest, SULT1E1 is correlated with non-protein-thiols.</p><p><strong>Conclusions: </strong>Breast cancers associate with SULT1E1, HIF1α and MMPs deregulations. For the first time, we are revealing that advanced cancer tissue with elevated SULT1E1-protein may reactivate in a reducing-state initiated by chalcone, but remain dormant in an oxidative environment. Furthermore, increased SULT1E1 protein synthesis is caused by DAS-induced mRNA expression. The combined effects of the drugs might decrease MMPs and HIF1α expressions. Further studies are necessary.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory effect of miR-377 on the proliferative and invasive behaviors of prostate cancer cells through the modulation of MYC mRNA via its interaction with BCL-2/Bax, PTEN, and CDK4.","authors":"Yasamin Azimi, Sara Hajibabaei, Ghazal Azimi, Fatemeh Rahimi-Jamnani, Masoumeh Azizi","doi":"10.18632/genesandcancer.236","DOIUrl":"https://doi.org/10.18632/genesandcancer.236","url":null,"abstract":"<p><p>The MYC gene is a regulatory and proto-oncogenic gene that is overexpressed in the majority of prostate cancers (PCa). Numerous studies have indicated that aberrant expression of microRNAs is involved in the initiation and progression of prostate cancer. In this investigation, we assessed the impact of miR-377 on MYC through luciferase assay. Real-time PCR was employed to determine whether miR-377 could reduce the levels of MYC mRNA in transfected PCa cell lines (PC-3 and DU145) and change in the mRNA levels of BCL-2/Bax, PTEN, and CDK4 as a consequence of MYC downregulation. Moreover, we analyzed the effects of miR-377 on apoptosis, proliferation, cell cycle, and wound healing. Our findings demonstrate that miR-377 effectively targets MYC mRNA, as confirmed by luciferase assay and Real-time PCR. We observed a significant reduction in BCL-2 and CDK4 expression, along with an increase in Bax and PTEN, in prostate cancer cell lines upon MYC suppression. Additionally, elevated levels of miR-377 in PCa cell lines induced apoptosis, inhibited proliferation and migration, and arrested the cell cycle. Taken together, these results unveil the inhibitory role of miR-377 in MYC function within PCa, thereby suggesting its potential as a therapeutic target for the treatment of this malignancy.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11098572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of USP1 in Ewing sarcoma.","authors":"Panneerselvam Jayabal, Xiuye Ma, Yuzuru Shiio","doi":"10.18632/genesandcancer.235","DOIUrl":"10.18632/genesandcancer.235","url":null,"abstract":"<p><p>Ewing sarcoma is a cancer of bone and soft tissue in children and young adults that is driven by the EWS-ETS fusion transcription factor, most commonly EWS-FLI1. We previously reported that Ewing sarcoma harbors two populations of cells, the CD133^high population displaying higher growth rate and the CD133^low population displaying chemotherapy resistance. We now find that the ubiquitin-specific protease 1 (USP1) is a transcriptional target of the EWS-FLI1 fusion oncoprotein, expressed at high and low levels in the CD133^high and the CD133^low populations, respectively, and determines chemo-sensitivity. We also find that USP1 inhibits cdc42, increases EWS-FLI1 transcriptional output, and simulates Ewing sarcoma growth. We show that chemo-sensitization by USP1 is independent of cdc42. A pharmacological inhibitor of USP1 was able to activate cdc42 and inhibit Ewing sarcoma growth. These results uncover critical roles for USP1 in Ewing sarcoma, which regulates growth and chemo-sensitivity via distinct mechanisms.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10843185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139698481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistically based blood proteomic markers in the TGF-β pathway stratify risk of hepatocellular cancer in patients with cirrhosis.","authors":"Xiyan Xiang, Krishanu Bhowmick, Kirti Shetty, Kazufumi Ohshiro, Xiaochun Yang, Linda L Wong, Herbert Yu, Patricia S Latham, Sanjaya K Satapathy, Christina Brennan, Richard J Dima, Nyasha Chambwe, Gulru Sharifova, Fellanza Cacaj, Sahara John, James M Crawford, Hai Huang, Srinivasan Dasarathy, Adrian R Krainer, Aiwu R He, Richard L Amdur, Lopa Mishra","doi":"10.18632/genesandcancer.234","DOIUrl":"10.18632/genesandcancer.234","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer worldwide but is often diagnosed at an advanced incurable stage. Yet, despite the urgent need for blood-based biomarkers for early detection, few studies capture ongoing biology to identify risk-stratifying biomarkers. We address this gap using the TGF-β pathway because of its biological role in liver disease and cancer, established through rigorous animal models and human studies. Using machine learning methods with blood levels of 108 proteomic markers in the TGF-β family, we found a pattern that differentiates HCC from non-HCC in a cohort of 216 patients with cirrhosis, which we refer to as TGF-β based Protein Markers for Early Detection of HCC (TPEARLE) comprising 31 markers. Notably, 20 of the patients with cirrhosis alone presented an HCC-like pattern, suggesting that they may be a group with as yet undetected HCC or at high risk for developing HCC. In addition, we found two other biologically relevant markers, Myostatin and Pyruvate Kinase M2 (PKM2), which were significantly associated with HCC. We tested these for risk stratification of HCC in multivariable models adjusted for demographic and clinical variables, as well as batch and site. These markers reflect ongoing biology in the liver. They potentially indicate the presence of HCC early in its evolution and before it is manifest as a detectable lesion, thereby providing a set of markers that may be able to stratify risk for HCC.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10843195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139698480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased expression of BRD4 isoforms long (BRD4-L) and short (BRD4-S) promotes chemotherapy resistance in high-grade serous ovarian carcinoma.","authors":"Ana Luiza Drumond-Bock, Luyao Wang, Lin Wang, Magdalena Cybula, Maria Rostworowska, Michael Kinter, Magdalena Bieniasz","doi":"10.18632/genesandcancer.233","DOIUrl":"10.18632/genesandcancer.233","url":null,"abstract":"<p><p>Chemoresistance in ovarian carcinoma is a puzzling issue that urges understanding of strategies used by cancer cells to survive DNA damage and to escape cell death. Expanding efforts to understand mechanisms driving chemoresistance and to develop alternative therapies targeting chemoresistant tumors are critical. Amplification of <i>BRD4</i> is frequently associated with chemoresistant ovarian carcinoma, but little is known about the biological effects of the overexpression of BRD4 isoforms in this malignancy. Here, we described the consequences of BRD4-L and BRD4-S overexpression in ovarian carcinoma shedding a light on a complex regulation of BRD4 isoforms. We demonstrated that the BRD4-L transcript expression is required to generate both isoforms, BRD4-L and BRD4-S. We showed that the BRD4-S mRNA expression positively correlated with BRD4-S protein levels, while BRD4-L isoform showed negative correlation between mRNA and protein levels. Moreover, we demonstrated that an overexpression of BRD4 isoforms is associated with chemoresistance in ovarian cancer.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10496930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10259601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VCP/p97, a pleiotropic protein regulator of the DNA damage response and proteostasis, is a potential therapeutic target in <i>KRAS</i>-mutant pancreatic cancer.","authors":"Ye S Lee, Jennifer E Klomp, Clint A Stalnecker, Craig M Goodwin, Yanzhe Gao, Gaith N Droby, Cyrus Vaziri, Kirsten L Bryant, Channing J Der, Adrienne D Cox","doi":"10.18632/genesandcancer.231","DOIUrl":"10.18632/genesandcancer.231","url":null,"abstract":"<p><p>We and others have recently shown that proteins involved in the DNA damage response (DDR) are critical for <i>KRAS</i>-mutant pancreatic ductal adenocarcinoma (PDAC) cell growth <i>in vitro</i>. However, the CRISPR-Cas9 library that enabled us to identify these key proteins had limited representation of DDR-related genes. To further investigate the DDR in this context, we performed a comprehensive, DDR-focused CRISPR-Cas9 loss-of-function screen. This screen identified valosin-containing protein (<i>VCP</i>) as an essential gene in <i>KRAS</i>-mutant PDAC cell lines. We observed that genetic and pharmacologic inhibition of VCP limited cell growth and induced apoptotic death. Addressing the basis for VCP-dependent growth, we first evaluated the contribution of VCP to the DDR and found that loss of VCP resulted in accumulation of DNA double-strand breaks. We next addressed its role in proteostasis and found that loss of VCP caused accumulation of polyubiquitinated proteins. We also found that loss of VCP increased autophagy. Therefore, we reasoned that inhibiting both VCP and autophagy could be an effective combination. Accordingly, we found that VCP inhibition synergized with the autophagy inhibitor chloroquine. We conclude that concurrent targeting of autophagy can enhance the efficacy of VCP inhibitors in <i>KRAS</i>-mutant PDAC.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10010283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9601074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging a powerful allogeneic dendritic cell line towards neoantigen-based cancer vaccines.","authors":"Dalil Hannani,&nbsp;Estelle Leplus,&nbsp;Karine Laulagnier,&nbsp;Laurence Chaperot,&nbsp;Joël Plumas","doi":"10.18632/genesandcancer.229","DOIUrl":"https://doi.org/10.18632/genesandcancer.229","url":null,"abstract":"<p><p>In recent years, immunotherapy has finally found its place in the anti-cancer therapeutic arsenal, even becoming standard of care as first line treatment for metastatic forms. The clinical benefit provided by checkpoint blockers such as anti-PD-1/PD-L1 in many cancers revolutionized the field. However, too many patients remain refractory to these treatments due to weak baseline anti-cancer immunity. There is therefore a need to boost the frequency and function of patients' cytotoxic CD8+ cellular effectors by targeting immunogenic and tumor-restricted antigens, such as neoantigens using an efficient vaccination platform. Dendritic cells (DC) are the most powerful immune cell subset for triggering cellular immune response. However, autologous DC-based vaccines display several limitations, such as the lack of reproducibility and the limited number of cells that can be manufactured. Here we discuss the advantages of a new therapeutic vaccine based on an allogeneic Plasmacytoid DC cell line, which is easy to produce and represents a powerful platform for priming and expanding anti-neoantigen cytotoxic CD8+ T-cells.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10643412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe herpesvirus infection beats adult T-cell leukemia/lymphoma.","authors":"Tatsuro Jo","doi":"10.18632/genesandcancer.228","DOIUrl":"https://doi.org/10.18632/genesandcancer.228","url":null,"abstract":"the confirmation of the","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10496929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10259605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CEACAMS 1, 5, and 6 in disease and cancer: interactions with pathogens.","authors":"Jerin Thomas,&nbsp;Addison Klebanov,&nbsp;Sahara John,&nbsp;Larry S Miller,&nbsp;Anil Vegesna,&nbsp;Richard L Amdur,&nbsp;Krishanu Bhowmick,&nbsp;Lopa Mishra","doi":"10.18632/genesandcancer.230","DOIUrl":"https://doi.org/10.18632/genesandcancer.230","url":null,"abstract":"<p><p>The CEA family comprises 18 genes and 11 pseudogenes located at chromosome 19q13.2 and is divided into two main groups: cell surface anchored CEA-related cell adhesion molecules (CEACAMs) and the secreted pregnancy-specific glycoproteins (PSGs). CEACAMs are highly glycosylated cell surface anchored, intracellular, and intercellular signaling molecules with diverse functions, from cell differentiation and transformation to modulating immune responses associated with infection, inflammation, and cancer. In this review, we explore current knowledge surrounding CEACAM1, CEACAM5, and CEACAM6, highlight their pathological significance in the areas of cancer biology, immunology, and inflammatory disease, and describe the utility of murine models in exploring questions related to these proteins.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9891707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10662302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel t (5; 17) (q35; q21) associated with t (8; 21) (q22; q22) in a patient with acute myeloid leukemia: case report and review of literature.","authors":"Kmira Zahra,&nbsp;Wided Cherif,&nbsp;Gereisha Ahmed,&nbsp;Haifa Regaieg,&nbsp;Ben Sayed Nesrine,&nbsp;Monia Zaier,&nbsp;Wided Mootamri,&nbsp;Yosra Ben Youssef,&nbsp;Nejia Brahem,&nbsp;Halima Sennana,&nbsp;Abderrahim Khelif","doi":"10.18632/genesandcancer.232","DOIUrl":"https://doi.org/10.18632/genesandcancer.232","url":null,"abstract":"<p><p>The t (8; 21) (q22; q22) with the resulting RUNX1- RUNX1T1 rearrangement is one of the most common cytogenetic abnormalities in acute myeloid leukemia (AML). It is associated with favorable prognosis. The t (5; 17) (q35; q21) is an uncommon translocation, fuses the gene for the nucleophosmin (NPM) to the retinoic acid receptor α(RARA) and was described essentially in acute promyelocytic leukemia (APL) variant. We present the case of a 19-year-old male patient who developed an AML with t (8; 21) (q22; q22) associated to t (5; 17) (q35; 21). Morphology and immunophenotype of the leukemic cells were compatible with AML. The patient received chemotherapy based on cytarabine and anthracycline without all-trans retinoic acid (ATRA) followed by allogenic stem cell transplantation in first remission. To the best of our knowledge, this is the first report of an association between a rare translocation t (5; 17) and t (8; 21) in AML. In this report, we will discuss the prognosis of this association as well as the treatment.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10328316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9809172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}