Genes and Cancer最新文献_第10页

Deregulated expression of microRNA-200b/c and SUZ12, a Polycomb repressive complex 2 subunit, in chemoresistant colorectal cancer cells. microRNA-200b/c和Polycomb抑制复合体2亚基SUZ12在化疗耐药结直肠癌细胞中的表达失调

Genes and Cancer Pub Date : 2017-07-01 DOI: 10.18632/genesandcancer.152

KayKay San, Megan Horita, Aravinda Ganapathy, G Chinnadurai, Uthayashanker R Ezekiel

{"title":"Deregulated expression of microRNA-200b/c and SUZ12, a Polycomb repressive complex 2 subunit, in chemoresistant colorectal cancer cells.","authors":"KayKay San, Megan Horita, Aravinda Ganapathy, G Chinnadurai, Uthayashanker R Ezekiel","doi":"10.18632/genesandcancer.152","DOIUrl":"https://doi.org/10.18632/genesandcancer.152","url":null,"abstract":"In colorectal cancer, chemotherapy and/or radiotherapy can lead to the formation of resistant cells that become metastatic through Epithelial-Mesenchymal Transition (EMT). Invasive and metastatic characteristics of carcinoma cells in primary tumors are mediated by EMT. During EMT, the primary tumor cells lose cell-cell adhesion, have increased intercellular separation, and gain an elongated shape with pseudopodia. There is also dysregulation of Polycomb group proteins (such as BMI1, SUZ12, and EZH2), and changes in the expression of microRNA-200 (miR-200) family. In this study, we developed a chemoresistant colorectal cancer cell line (DLD-1-OxR) by exposing DLD-1 colorectal cancer cells to increasing concentrations of oxaliplatin (a chemotherapy drug used for colorectal cancer), and tested for EMT characteristics. We found that DLD-1-OxR exhibited EMT characteristics by morphologic, biochemical and molecular markers. SUZ12, a Polycomb repressive complex 2 subunit, was upregulated in DLD-1-OxR. The miRNA-200 family members that target SUZ12 were downregulated. Drug resistance is an impediment to chemotherapy and understanding the molecular mechanisms of chemoresistance can lead to its reversal and improvement of chemotherapy outcomes.","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35562664","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}

引用次数: 10

Origins of cancer: tackling provocative questions 癌症的起源：解决挑衅性问题

Genes and Cancer Pub Date : 2017-07-01 DOI: 10.18632/genesandcancer.150

A. Solitro, Nicole A. Vander Schaaf

引用次数: 0

Identification of candidate genes associated with triple negative breast cancer. 三阴性乳腺癌相关候选基因的鉴定。

Genes and Cancer Pub Date : 2017-07-01 DOI: 10.18632/genesandcancer.147

Audrey Player, Nissi Abraham, Kayla Burrell, Iria Ondo Bengone, Anthony Harris, Lisa Nunez, Telisa Willaims, Sharon Kwende, Wiley Walls

{"title":"Identification of candidate genes associated with triple negative breast cancer.","authors":"Audrey Player, Nissi Abraham, Kayla Burrell, Iria Ondo Bengone, Anthony Harris, Lisa Nunez, Telisa Willaims, Sharon Kwende, Wiley Walls","doi":"10.18632/genesandcancer.147","DOIUrl":"https://doi.org/10.18632/genesandcancer.147","url":null,"abstract":"When triple negative breast cancer (TNBC) are analyzed by gene expression profiling different subclasses are identified, at least one characterized by genes related to immune signaling mechanisms supporting the role of these genes in the cancers. In an earlier study we observed differences in TNBC cell lines with respect to their expression of the cytokine IL32. Our analyses showed that certain cell lines expressed higher levels of the cytokine compared to others. Because TNBC are heterogeneous and immune-related genes appear to play a pivotal role in these cancers, we chose to examine the transcriptomes of the different cell lines based on IL32 expression. We performed group analyses of TNBC cell lines demonstrating high IL32 compared to low IL32 levels and identified IL32, GATA3, MYBL1, ETS1, PTX3 and TMEM158 as differentially associated with a subpopulation of TNBC. The six candidate genes were validated experimental and in different patient datasets. The genes distinguished a subset of TNBC from other TNBC, and TNBC from normal, luminal A, luminal B, and HER2 patient samples. The current project serves as a preliminary study in which we outline the discovery and validation of our list of six candidate genes.","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35562663","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}

引用次数: 18

Correlation between c-Met and ALDH1 contributes to the survival and tumor-sphere formation of ALDH1 positive breast cancer stem cells and predicts poor clinical outcome in breast cancer. c-Met与ALDH1的相关性有助于ALDH1阳性乳腺癌干细胞的存活和肿瘤球的形成，并预测乳腺癌临床预后不良。

Genes and Cancer Pub Date : 2017-07-01 DOI: 10.18632/genesandcancer.148

Yuka Nozaki, Shoma Tamori, Masahiro Inada, Reika Katayama, Hiromi Nakane, Osamu Minamishima, Yuka Onodera, Makoto Abe, Shota Shiina, Kei Tamura, Daichi Kodama, Keiko Sato, Yasushi Hara, Ryo Abe, Ryoko Takasawa, Atsushi Yoshimori, Nariyoshi Shinomiya, Sei-Ichi Tanuma, Kazunori Akimoto

{"title":"Correlation between c-Met and ALDH1 contributes to the survival and tumor-sphere formation of ALDH1 positive breast cancer stem cells and predicts poor clinical outcome in breast cancer.","authors":"Yuka Nozaki, Shoma Tamori, Masahiro Inada, Reika Katayama, Hiromi Nakane, Osamu Minamishima, Yuka Onodera, Makoto Abe, Shota Shiina, Kei Tamura, Daichi Kodama, Keiko Sato, Yasushi Hara, Ryo Abe, Ryoko Takasawa, Atsushi Yoshimori, Nariyoshi Shinomiya, Sei-Ichi Tanuma, Kazunori Akimoto","doi":"10.18632/genesandcancer.148","DOIUrl":"https://doi.org/10.18632/genesandcancer.148","url":null,"abstract":"c-Met is a receptor-type tyrosine kinase, which is involved in a wide range of cellular responses such as proliferation, motility, migration and invasion. It has been reported to be overexpressed in various cancers. However, the role of c-Met in breast cancer stem cells (CSCs) still remains unclear. We herein, show that c-Met expression is significantly elevated in Basal-like type of breast cancer in comparison with other subtypes. High expression of c-Met strongly correlated with the expression of two CSC markers, ALDH1A3 and CD133 in breast cancers. In addition, breast cancers at tumor stage III-IV expressing both c-Methigh and ALDH1A3high had poor prognosis. Furthermore, treatment with c-Met inhibitors (Crizotinib, Foretinib, PHA-665752 and Tivantinib) in MDA-MB157 cells with high c-Met protein expression resulted in significant suppression in cell viability, contrary to MDA-MB468 cells with low c-Met protein expression. These c-Met inhibitors also suppressed cell viability and tumor-sphere formation of ALDH1high breast cancer cells with high c-Met expression. These results suggest that c-Met in ALDH1 positive CSCs seems to play an important role in breast cancer repopulation. Therefore, we conclude that c-Met is a potential therapeutic target in ALDH1 positive breast CSCs.","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35562661","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}

引用次数: 34

Pathological and prognostic role of mdig in pancreatic cancer. mdig在胰腺癌中的病理及预后作用。

Genes and Cancer Pub Date : 2017-07-01 DOI: 10.18632/genesandcancer.149

Srinivas Ashok Kumar, Chitra Thakur, Lingzhi Li, Hongjuan Cui, Fei Chen

{"title":"Pathological and prognostic role of mdig in pancreatic cancer.","authors":"Srinivas Ashok Kumar, Chitra Thakur, Lingzhi Li, Hongjuan Cui, Fei Chen","doi":"10.18632/genesandcancer.149","DOIUrl":"https://doi.org/10.18632/genesandcancer.149","url":null,"abstract":"Pancreatic cancer is a highly aggressive malignant disease having very limited therapeutic options that ultimately results in its poor prognosis. It is still elusive on the etiology and tumorigenic mechanisms of pancreatic cancer. In the present report, we provide evidence showing involvement of the mineral dust-induced gene (mdig) in the pathogenesis and prognosis of the pancreatic cancer. Using immunohistochemistry approach on human pancreatic cancer tissue microarray, we found differential expression of mdig in pancreatic adenocarcinoma and normal pancreas. Based on the staining intensities of mdig in these tissue samples, we found that 12% of the cancer tissues were strongly positive for mdig, 39% and 31% were moderately and weakly positive respectively. Several alternatively spliced mdig mRNAs were detected in the selected pancreatic cancer cell lines. Through R2 platform for the patient survival analysis (http://r2.amc.nl), we found that enrichment of some specific exon of mdig predicates different survival rate of the pancreatic cancer patients. In summary, our findings may help in assessing the role of mdig in the pathogenesis of the pancreatic cancer and the prognosis of the pancreatic cancer patients.","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35562662","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}

引用次数: 3

PRAJA is overexpressed in glioblastoma and contributes to neural precursor development. PRAJA 在胶质母细胞瘤中过度表达，有助于神经前体的发育。

Genes and Cancer Pub Date : 2017-07-01 DOI: 10.18632/genesandcancer.151

Joshua Shin, Viveka Mishra, Eric Glasgow, Sobia Zaidi, Jian Chen, Kazufumi Ohshiro, Bhargava Chitti, Amee A Kapadia, Neha Rana, Lopa Mishra, Chu-Xia Deng, Shuyun Rao, Bibhuti Mishra

{"title":"PRAJA is overexpressed in glioblastoma and contributes to neural precursor development.","authors":"Joshua Shin, Viveka Mishra, Eric Glasgow, Sobia Zaidi, Jian Chen, Kazufumi Ohshiro, Bhargava Chitti, Amee A Kapadia, Neha Rana, Lopa Mishra, Chu-Xia Deng, Shuyun Rao, Bibhuti Mishra","doi":"10.18632/genesandcancer.151","DOIUrl":"10.18632/genesandcancer.151","url":null,"abstract":"PRAJA, a RING-H2 E3 ligase, is abundantly expressed in brain tissues such as the cerebellum and frontal cortex, amongst others, and more specifically in neural progenitor cells as well as in multiple cancers that include glioblastomas. However, the specific role that Praja plays in neural development and gliomas remains unclear. In this investigation, we performed bioinformatic analyses to examine Praja1 and Praja2 expression across 29 cancer types, and observed raised levels of Praja1 and Praja2 in gliomas with an inverse relationship between Praja1 and apoptotic genes and Praja substrates such as Smad3. We analyzed the role of Praja in the developing brain through loss of function studies, using morpholinos targeting Praja1 in embryonic zebrafish, and observed that Praja1 is expressed prominently in regions enriched with neural precursor cell subtypes. Antisense Praja morpholinos resulted in multiple embryonic defects including delayed neural development likely through increased apoptosis. Further studies revealed high levels of Cdk1 with loss of Praja1 in TGF-β or insulin treated cells, supporting the link between Praja1 and cell cycle regulation. In summary, these studies underscore Praja's role in mammalian brain development and Praja1 deregulation may lead to gliomas possibly through the regulation of cell cycle and/or apoptosis.","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35562660","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}

引用次数: 0

Extracellular LDLR repeats modulate Wnt signaling activity by promoting LRP6 receptor endocytosis mediated by the Itch E3 ubiquitin ligase. 细胞外LDLR重复通过促进痒E3泛素连接酶介导的LRP6受体内吞作用来调节Wnt信号活性。

Genes and Cancer Pub Date : 2017-07-01 DOI: 10.18632/genesandcancer.146

Sapna Vijayakumar, Guizhong Liu, Huei-Chi Wen, Yaa Abu, Robert Chong, Horacio Nastri, Gadi G Bornstein, Zhen-Qiang Pan, Stuart A Aaronson

{"title":"Extracellular LDLR repeats modulate Wnt signaling activity by promoting LRP6 receptor endocytosis mediated by the Itch E3 ubiquitin ligase.","authors":"Sapna Vijayakumar, Guizhong Liu, Huei-Chi Wen, Yaa Abu, Robert Chong, Horacio Nastri, Gadi G Bornstein, Zhen-Qiang Pan, Stuart A Aaronson","doi":"10.18632/genesandcancer.146","DOIUrl":"https://doi.org/10.18632/genesandcancer.146","url":null,"abstract":"The LOW-density lipoprotein related protein 6 (LRP6) receptor is an important effector of canonical Wnt signaling, a developmental pathway, whose dysregulation has been implicated in various diseases including cancer. The membrane proximal low-density lipoprotein (LDL) receptor repeats in LRP6 exhibit homology to ligand binding repeats in the LDL receptor (LDLR), but lack known function. We generated single amino acid substitutions of LRP6-LDLR repeat residues, which are highly conserved in the human LDLR and mutated in patients with Familial Hypercholesteremia (FH). These substitutions negatively impacted LRP6 internalization and activation of Wnt signaling. By mass spectrometry, we observed that the Itch E3 ubiquitin ligase associated with and ubiquitinated wild type LRP6 but not the LDLR repeat mutants. These findings establish the involvement of LRP6-LDLR repeats in the regulation of canonical Wnt signaling.","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.18632/genesandcancer.146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35562659","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}

引用次数: 5

Telomere length regulation through epidermal growth factor receptor signaling in cancer. 肿瘤中表皮生长因子受体信号对端粒长度的调控。

Genes and Cancer Pub Date : 2017-05-01 DOI: 10.18632/genesandcancer.140

Titto Augustine, Radhashree Maitra, Sanjay Goel

引用次数: 14

The chemokine scavenging receptor D6/ACKR2 is a target of miR-146a in thyroid cancer. 趋化因子清除受体D6/ACKR2是miR-146a在甲状腺癌中的靶标。

Genes and Cancer Pub Date : 2017-05-01 DOI: 10.18632/genesandcancer.141

Francesco Pacifico, Alessio Lepore, Stefano Mellone, Luca Sanguigno, Giorgia Federico, Adelaide Greco, Arturo Brunetti, Antonio Leonardi

{"title":"The chemokine scavenging receptor D6/ACKR2 is a target of miR-146a in thyroid cancer.","authors":"Francesco Pacifico, Alessio Lepore, Stefano Mellone, Luca Sanguigno, Giorgia Federico, Adelaide Greco, Arturo Brunetti, Antonio Leonardi","doi":"10.18632/genesandcancer.141","DOIUrl":"https://doi.org/10.18632/genesandcancer.141","url":null,"abstract":"We have previously shown that miR-146a, a NF-κB-regulated microRNA, is strongly expressed in human specimens and cell lines derived from anaplastic thyroid carcinomas (ATC) where it mediates some of the NF-κB pro-tumorigenic functions. By using a bioinformatic analysis, we identified the chemokine scavenger receptor D6/ ACKR2 as a target of miR146a in human ATC. We found that the expression of D6/ ACKR2 was up-regulated in miR-146a-null ATC cell lines and that the 3' UTR of D6/ ACKR2 mRNA was able to inhibit its expression in parental, but not in miR-146a-null ATC cells. Since human specimens from primary ATC showed a low expression of D6/ ACKR2 compared to normal thyroid tissues, we analyzed the effects of D6/ACKR2 over-expression in ATC cells. Different chemokines added to the conditioned medium of D6/ACKR2 over-expressing ATC cells partially failed to drive in vitro monocyte migration, and tumors derived from the injection of the same cells in nude mice showed a decreased number of infiltrating macrophages. Taken together, these results indicate that ATC cells down-regulate D6/ACKR2 expression through miR-146a activity to sustain leukocyte trafficking inside tumor microenvironment and shed light on a novel mechanism by which NF-κB indirectly inhibits the expression and the function of anti-tumorigenic gene in thyroid cancer.","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35195126","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}

引用次数: 6

Phase I/II study of erlotinib, carboplatin, pemetrexed, and bevacizumab in chemotherapy-naïve patients with advanced non-squamous non-small cell lung cancer harboring epidermal growth factor receptor mutation. 厄洛替尼、卡铂、培美曲塞和贝伐单抗治疗含有表皮生长因子受体突变的晚期非鳞状非小细胞肺癌chemotherapy-naïve患者的I/II期研究

Genes and Cancer Pub Date : 2017-05-01 DOI: 10.18632/genesandcancer.145

Takayasu Kurata, Aya Nakaya, Takashi Yokoi, Maiko Niki, Kayoko Kibata, Yuki Takeyasu, Yoshitaro Torii, Yuichi Katashiba, Makoto Ogata, Takayuki Miyara, Shosaku Nomura

{"title":"Phase I/II study of erlotinib, carboplatin, pemetrexed, and bevacizumab in chemotherapy-naïve patients with advanced non-squamous non-small cell lung cancer harboring epidermal growth factor receptor mutation.","authors":"Takayasu Kurata, Aya Nakaya, Takashi Yokoi, Maiko Niki, Kayoko Kibata, Yuki Takeyasu, Yoshitaro Torii, Yuichi Katashiba, Makoto Ogata, Takayuki Miyara, Shosaku Nomura","doi":"10.18632/genesandcancer.145","DOIUrl":"https://doi.org/10.18632/genesandcancer.145","url":null,"abstract":"Background: Epidermal growth factor receptor tyrosine kinase inhibitors significantly prolong the progression-free survival of patients with non-squamous non-small cell lung cancer (NSCLC). However, most patients develop tumor regrowth and their prognosis remains poor. A new treatment strategy for NSCLC harboring EGFR mutation is therefore necessary.Methods: In phase I, eligible patients were administered oral erlotinib daily and intravenous pemetrexed, carboplatin, and bevacizumab every 3 weeks for four cycles with maintenance of pemetrexed and bevacizumab until progressive disease was observed. The dose of erlotinib was 100 mg for dose level 1 and 150 mg for dose level 2. The doses of pemetrexed, carboplatin, and bevacizumab were fixed at 500 mg/m2, area under the concentration-time curve of 6 mg/mL · min, and 15 mg/kg, respectively. The dose-limiting toxicities were grade 3/4 neutropenia with fever or infection, grade 4 leukopenia lasting for ≥7 days, grade 4 thrombocytopenia, grade 3/4 uncontrollable nonhematological toxicity, and delayed administration of the subsequent cycle by >2 weeks because of adverse events.Results: Six patients were enrolled in phase I (dose level 1, n = 3; dose level 2, n = 3). During the induction phase, grade 3 neutropenia without fever was observed in one patient at dose level 1 and two patients at dose level 2. Grade 3 anemia was reported in one patient at dose level 1 and grade 3 thrombocytopenia was reported in two patients at dose level 1 and dose level 2, respectively.Conclusion: Four-drug combination therapy is a feasible and promising.","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35195681","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}

引用次数: 5