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Cancer Letters

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https://www.readbyqxmd.com/read/29054784/developing-a-xenograft-human-tumor-model-in-immunocompetent-mice
#1
Matthew T Basel, Sanjeev Narayanan, Chanran Ganta, Tej B Shreshta, Alejandro Marquez, Marla Pyle, Jennifer Hill, Stefan H Bossmann, Deryl L Troyer
Animal models are essential to cancer research, but current xenograft models are limited in their utility especially due to the lack of an immune system. Here we demonstrate that a xenograft tumor model can be developed in immunocompetent mice by tolerizing murine fetuses to human tumor cells. A375 human melanoma cells were injected into day E14 fetuses and after birth mice were challenged with A375 cells to determine their ability to develop tumors. Intravenous injections of cells resulted in metastatic-like lung tumors, which were verified to be human in origin by immunohistochemistry and PCR...
October 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29050983/precision-diagnosis-and-treatment-of-liver-cancer-in-china
#2
Jing Fu, Hongyang Wang
Liver cancer ranks the sixth in cancer incidence and the second in tumor related mortality worldwide, with over half of the new cases and deaths occur in China. Because of difficulties in early diagnosis, rapid progression and lack of targeted drugs, the survival rate of liver cancer is extremely low. The existence of extraordinary heterogeneity has greatly limited the progress in early detection, molecular classification and targeted therapy of live cancer, owing to its varied risk factors, genetic susceptibilities, morphological diversity and microenvironmental discrepancies...
October 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29050982/pharmacological-inhibition-of-dusp6-suppresses-gastric-cancer-growth-and-metastasis-and-overcomes-cisplatin-resistance
#3
Qi-Nian Wu, Yi-Fu Liao, Yun-Xin Lu, Yun Wang, Jia-Huan Lu, Zhao-Lei Zeng, Qi-Tao Huang, Hui Sheng, Jing-Ping Yun, Dan Xie, Huai-Qiang Ju, Rui-Hua Xu
Gastric cancer (GC) is the second cause of cancer-related death. Cisplatin (CDDP) is widely used as the standard GC treatment, but relapse and metastasis are common because of intrinsic or acquired drug resistance. The mitogen-activated protein kinase phosphatases (MAPK)-extracellular signal regulated kinases (ERK) pathway contributes to GC progression and drug resistance, but targeting the MAPK-ERK pathway is challenging in GC therapy. Here, we demonstrated that dual-specificity phosphatases 6 (DUSP6) was overexpressed in GC and predicted poor overall survival and progression-free survival...
October 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29037867/costunolide-specifically-binds-and-inhibits-thioredoxin-reductase-1-to-induce-apoptosis-in-colon-cancer
#4
Weishan Zhuge, Ruijie Chen, Katanaev Vladimir, Xidan Dong, Khan Zia, Xiangwei Sun, Xuanxuan Dai, Miao Bao, Xian Shen, Guang Liang
Colon cancer is one of the leading causes of cancer-related deaths. A natural sesquiterpene lactone, costunolide (CTD), showed inhibition of cancer development. However, the underlying mechanisms are not known. Here, we have examined the therapeutic activity and novel mechanisms of the anti-cancer activities of CTD in colon cancer cells. Using SPR analysis and enzyme activity assay on recombinant TrxR1 protein, our results show that CTD directly binds and inhibits the activity of TrxR1, which caused enhanced generation of ROS and led to ROS-dependent endoplasmic reticulum stress and cell apoptosis in colon cancer cells...
October 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29031566/high-nrf2-expression-controls-endoplasmic-reticulum-stress-induced-apoptosis-in-multiple-myeloma
#5
Yu Sun, Amina Abdul Aziz, Kristian Bowles, Stuart Rushworth
Multiple myeloma (MM) is an incurable disease characterized by clonal plasma cell proliferation. The stress response transcription factor Nuclear factor erythroid 2 [NF-E2]-related factor 2 (NRF2) is known to be activated in MM in response to proteasome inhibitors (PI). Here, we hypothesize that the transcription factor NRF2 whose physiological role is to protect cells from reactive oxygen species via the regulation of drug metabolism and antioxidant gene plays an important role in MM cells survival and proliferation...
October 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29031565/quantified-postsurgical-small-cell-size-ctcs-and-epcam-circulating-tumor-stem-cells-with-cytogenetic-abnormalities-in-hepatocellular-carcinoma-patients-determine-cancer-relapse
#6
Liang Wang, Yilin Li, Jing Xu, Aiqun Zhang, Xuedong Wang, Rui Tang, Xinjing Zhang, Hongfang Yin, Manting Liu, Daisy Dandan Wang, Peter Ping Lin, Lin Shen, Jiahong Dong
Detection of hepatocellular carcinoma circulating tumor cells performed with conventional strategies, is significantly limited due to inherently heterogeneous and dynamic expression of EpCAM, as well as degradation of cytokeratins during epithelial-to-mesenchymal transition, which inevitably lead to non-negligible false negative detection of such "uncapturable and invisible" CTCs. A novel SE-iFISH strategy, improved and optimized for detection of HCC-CTCs in this study, was applied to comprehensively detect, phenotypically and karyotypically characterize hepatocellular and cholangiocarcinoma CTCs in patients subjected to surgical resection...
October 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29031586/complement-c5a-c5ar-pathway-potentiates-the-pathogenesis-of%C3%A2-gastric-cancer-by-down-regulating-p21-expression
#7
Jian Chen, Gui-Qing Li, Li Zhang, Ming Tang, Xu Cao, Gui-Lian Xu, Yu-Zhang Wu
Although the complement C5a/C5aR pathway is suggested to play a critical role in tumor pathogenesis, the underlying mechanism has yet to be fully elucidated. In the present study, we found that in patients with gastric cancer in different clinical stages (from stageⅠto stage Ⅳ), both C5aR and p-PI3K/AKT levels were significantly higher in tumoral tissues than in adjacent non-tumoral tissues. In contrast, p21/p-p21 levels were significantly lower in tumoral tissues than in adjacent non-tumoral tissues. In vitro recombinant C5a administration remarkably promoted p-PI3K/p-AKT expression, but inhibited p21/p-p21 expression...
October 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29031564/eif3a-a-new-anticancer-drug-target-in-the-eif-family
#8
Ji-Ye Yin, Jian-Ting Zhang, Wei Zhang, Hong-Hao Zhou, Zhao-Qian Liu
eIF3a is the largest subunit of eIF3, which is a key player in all steps of translation initiation. During the past years, eIF3a is recognized as a proto-oncogene, which is an important discovery in this field. It is widely reported to be correlated with cancer occurrence, metastasis, prognosis, and therapeutic response. Recently, the mechanisms of eIF3a action in the carcinogenesis are unveiled gradually. A number of cellular, physiological, and pathological processes involving eIF3a are identified. Most importantly, it is emerging as a new potential drug target in the eIF family, and some small molecule inhibitors are being developed...
October 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29024815/identification-of-a-novel-autophagic-inhibitor-cepharanthine-to-enhance-the-anti-cancer-property-of-dacomitinib-in-non-small-cell%C3%A2-lung-cancer
#9
Zheng-Hai Tang, Wen-Xiang Cao, Xia Guo, Xiao-Yang Dai, Jia-Hong Lu, Xiuping Chen, Hong Zhu, Jin-Jian Lu
Inhibition of autophagy is a promising strategy for non-small cell lung cancer (NSCLC) treatment, which is in the clinical trials. However, only chloroquine is used in clinic as an autophagic inhibitor and the inhibitory effect of chloroquine on autophagy is finite. Therefore, the development of an alternative autophagic inhibitor for NSCLC therapy becomes necessary. In the present study, cepharanthine (CEP), an alkaloid extracted from Stephania cepharantha Hayata, was identified as a novel autophagic inhibitor in NSCLC cells...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29024814/anti-tumor-effects-of-nvp-bkm120-alone-or-in-combination-with-mek162-in-biliary-tract-cancer
#10
Ling Jin, Mei-Hua Jin, Ah-Rong Nam, Ji-Eun Park, Ju-Hee Bang, Do-Youn Oh, Yung-Jue Bang
There are currently no clinically validated therapeutic targets for biliary tract cancer (BTC). Despite promising results in other cancers, compounds targeting the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, alone or in combination with Ras/Raf/MEK pathway inhibitors, have not been evaluated in BTC. Here, we examined the effects of a pan-PI3K inhibitor (BKM120) with or without a MEK inhibitor (MEK162), on eight human BTC cell lines carrying mutations in K-Ras and/or the PI3K catalytic subunit, PI3KCA...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29024813/a-prodrug-of-green-tea-polyphenol-epigallocatechin-3-gallate-pro-egcg-serves-as-a-novel-angiogenesis-inhibitor-in-endometrial-cancer
#11
Jianzhang Wang, Gene Chi Wai Man, Tak Hang Chan, Joseph Kwong, Chi Chiu Wang
Anti-angiogenesis effect of a prodrug of green tea polyphenol (-)-epigallocatechin-3-gallate (Pro-EGCG) in malignant tumors is not well studied. Here, we investigated how the treatment with Pro-EGCG inhibited tumor angiogenesis in endometrial cancer. Tumor xenografts of human endometrial cancer were established and subjected to microarray analysis after Pro-EGCG treatment. First, we showed Pro-EGCG inhibited tumor angiogenesis in xenograft models through down-regulation of vascular endothelial growth factor A (VEGFA) and hypoxia inducible factor 1 alpha (HIF1α) in tumor cells and chemokine (C-X-C motif) ligand 12 (CXCL12) in host stroma by immunohistochemical staining...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29024812/inhibition-of-pyruvate-carboxylase-by-1%C3%AE-25-dihydroxyvitamin-d-promotes-oxidative-stress-in-early-breast-cancer-progression
#12
Tomasz Wilmanski, Xuanzhu Zhou, Wei Zheng, Aparna Shinde, Shawn S Donkin, Michael Wendt, John R Burgess, Dorothy Teegarden
Maintaining reductive-oxidative (redox) balance is an essential feature in breast cancer cell survival, with cellular metabolism playing an integral role in maintaining redox balance through its supply of reduced NADPH. In the present studies, the effect of 1,25-dihydroxyvitamin D (1,25(OH)2D) on redox balance was investigated in early stages of breast cancer. Treatment with 1,25(OH)2D promoted oxidative stress in MCF10A-ras and MCF10A-ErbB2 breast epithelial cells, as measured by the decreased ratios of NADPH/NADP+ and reduced to oxidized glutathione (GSH/GSSG)...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29024811/cnot2-promotes-proliferation-and-angiogenesis-via-vegf-signaling-in-mda-mb-231-breast-cancer-cells
#13
Eun Jung Sohn, Deok-Beom Jung, HyoJung Lee, In Han, Jihyun Lee, Hyemin Lee, Sung-Hoon Kim
Here the underlying role of CNOT2, a subunit of CCR4-NOT complex, was elucidated in cancer progression. CNOT2 was overexpressed in HIT-T15, ASPC-1, BXPC-3, PC-3, LNCaP, MCF-7 and MDA-MB-231 cell lines, which was confirmed by Tissue array in various human tumor tissues. Also, CNOT2 depletion suppressed proliferation and colony formation of MDA-MB-231 cells. Of note, microarray revealed decreased expression of CNOT2, VEGF-A, HIF2 alpha (<0.5 fold) and increased expression of UMOD1, LOC727847, MMP4, hCG and other genes (>2...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29024810/magea6-promotes-human-glioma-cell-survival-via-targeting-ampk%C3%AE-1
#14
Si-Jian Pan, Jie Ren, Hong Jiang, Wei Liu, Liang-Yun Hu, Yi-Xin Pan, Bomin Sun, Qing-Fang Sun, Liu-Guan Bian
Melanoma antigen A6 (MAGEA6)/TRIM28 complex is a cancer-specific ubiquitin ligase, which degradates tumor suppressor protein AMP-activated protein kinase (AMPK). We show that MAGEA6 is uniquely expressed in human glioma tissues and cells, which is correlated with AMPKα1 downregulation. It is yet absent in normal brain tissues and human astrocytes/neuronal cells. MAGEA6 knockdown by targeted-shRNA in glioma cells restored AMPKα1 expression, causing mTORC1 in-activation and cell death/apoptosis. Reversely, AMPKα1 knockdown or mutation ameliorated glioma cell death by MAGEA6 shRNA...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29017913/the-use-of-natural-compounds-for-the-targeting-and-chemoprevention-of-ovarian-cancer
#15
Francesca Pistollato, Ruben Calderón Iglesias, Roberto Ruiz, Silvia Aparicio, Jorge Crespo, Luis Dzul Lopez, Francesca Giampieri, Maurizio Battino
Among gynaecological cancers, ovarian cancer represents the leading cause of death in women. Current treatment for ovarian cancer entails surgery followed by combined chemotherapy with platinum and taxane, which are associated, particularly cisplatin, with severe side effects. While this treatment approach appears to be initially effective in a high number of patients, nearly 70% of them suffer a relapse within a few months after initial treatment. Therefore, more effective and better-tolerated treatment options are clearly needed...
October 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28989055/down-regulation-of-hectd3-by-her2-inhibition-makes-serous-ovarian-cancer-cells-sensitive-to-platinum-treatment
#16
Tong Shu, Yi Li, Xiaowei Wu, Bin Li, Zhihua Liu
Resistance to platinum-based chemotherapy is a major cause of treatment failure in patients with epithelial ovarian cancer and predicts a poor prognosis. Previously, we found that HECTD3 confers cancer cell resistance to apoptosis. However, the significance of HECTD3 expression in ovarian cancer and its regulatory mechanisms were unknown. Here, we found that HECTD3 depletion promotes carboplatin-induced apoptosis in both an ovarian cancer cell model and a xenograft mouse model. Moreover, high HECTD3 expression is significantly associated with poor platinum response and prognosis in ovarian cancer patients...
October 6, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28989054/nuclear-met-promotes-hepatocellular-carcinoma-tumorigenesis-and-metastasis-by-upregulation-of-tak1-and-activation-of-nf-%C3%AE%C2%BAb-pathway
#17
Sze Keong Tey, Edith Yuk Ting Tse, Xiaowen Mao, Frankie Chi Fat Ko, Alice Sze Tsai Wong, Regina Cheuk-Lam Lo, Irene Oi-Lin Ng, Judy Wai Ping Yam
Presence of Met receptor tyrosine kinase in the nucleus of cells has been reported. However, the functions of Met which expresses in the nucleus (nMet) remain elusive. In this study, we found that nMet was increased in 89% of HCC tumorous tissues when compared with the corresponding non-tumorous liver tissues. nMet expression increased progressively along HCC development and significantly correlated with cirrhosis, poorer cellular differentiation, venous invasion, late stage HCC and poorer overall survival...
October 6, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28987389/environmental-tobacco-smoke-exposure-and-egfr-and-alk-alterations-in-never-smokers-lung-cancer-results-from-the-lcrins-study
#18
María Torres-Durán, Alberto Ruano-Ravina, Karl T Kelsey, Isaura Parente-Lamelas, Virginia Leiro-Fernández, Ihab Abdulkader, Mariano Provencio, José Abal-Arca, Olalla Castro-Añón, Carmen Montero-Martínez, Iria Vidal-García, Margarita Amenedo, Antonio Golpe-Gómez, Cristina Martínez, Rosirys Guzmán-Taveras, María José Mejuto-Martí, Alberto Fernández-Villar, Juan Miguel Barros-Dios
Environmental tobacco smoke (ETS) exposure is a main risk factor of lung cancer in never smokers. Epidermal Growth Factor Receptor (EGFR) mutations and ALK translocations are more frequent in never smokers' lung cancer than in ever-smokers. We performed a multicenter case-control study to assess if ETS exposure is associated with the presence of EGFR mutations and its types and if ALK translocations were related with ETS exposure. All patients were never smokers and had confirmed lung cancer diagnosis. ETS exposure during childhood showed a negative association on the probability of EGRF mutation though not significant...
October 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28987386/autophagy-in-the-inflammation-carcinogenesis-pathway-of-liver-and-hcc-immunotherapy
#19
Sizhe Yu, Yu Wang, Li Jing, F X Claret, Qing Li, Tao Tian, Xuan Liang, Zhiping Ruan, Lili Jiang, Yu Yao, Kejun Nan, Yi Lv, Hui Guo
Autophagy plays a dual role in many types of cancer, such as hepatocellular carcinoma (HCC). Autophagy seems to be inhibited and functions as a tumor-suppression mechanism in the "inflammation-carcinogenesis" pathway of the liver, including hepatitis B virus and hepatitis C virus, alcoholic steatohepatitis and non-alcoholic steatohepatitis related HCC. However, in established tumors, autophagy plays a tumor-promoting role. Because of the varied function of autophagy in HCC, we hypothesized p62 as a marker to evaluate the autophagic level...
October 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28987385/sumoylation-of-iqgap1-promotes-the-development-of-colorectal-cancer
#20
Ziwei Liang, Yanfang Yang, Yu He, Pengbo Yang, Xixi Wang, Gu He, Peng Zhang, Hongxia Zhu, Ningzhi Xu, Xia Zhao, Shufang Liang
IQGAP1 is a conserved multifunctional protein implicated in tumorigenesis. An aberrant expression of IQGAP1 widely exists in many cancers, but the SUMOylation modification of IQGAP1 in carcinogenesis is unknown by now. Here we first time explore biological functions of IQGAP1 SUMOylation in promoting colorectal cancer progression in vitro and in vivo. The expression of IQGAP1 and its SUMOylation level are both increased in human colorectal carcinoma (CRC) cells and tissues. IQGAP1 is mainly SUMOylated by SUMO1 at the K1445 residue, which could stabilize IQGAP1 by reducing protein ubiquitination...
October 5, 2017: Cancer Letters
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