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cancer cell resistance

Georgios Pampalakis, Eleni Zingkou, Georgia Sotiropoulou
Vaginal cancer is rare and largely unexplored. We found here that KLK5 is coordinately expressed along with other KLKs in all stratified epithelia including vagina, pointing to potential role(s) in differentiation. Further, we propose that KLK5 could be implicated in vaginal cancer development based on the fact that Klk5-/- mice are prone to develop vaginal tumors when exposed to 7,12-dimethylbenz[a]anthracene. Nf-κb activation is markedly enhanced in Klk5-/- leading to increased resistance to apoptosis of mutated vaginal cells...
December 20, 2017: Biological Chemistry
Xiao-Ming Wang, Yang Liu, Yu-Xia Fan, Zheng Liu, Qing-Ling Yuan, Meng Jia, Geng Zu-Shi, Ling Gu, Xiu-Bo Lu
Background LncRNA PTCSC3 is a tumor suppressor in thyroid cancer, and its role in drug resistance of anaplastic thyroid cancer (ATC) to chemotherapy drug doxorubicin was investigated in this study. Methods Expression of RNA and protein was analyzed by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze the expression rate of CD133+ cells. The endogenous expression of related genes was modulated by recombinant plasmids and cell transfection. Combination condition and interaction between PTCSC3 and STAT3 were determined by RIP and RNA pull-down assay, respectively...
March 21, 2018: Cancer Biology & Therapy
Teng Lv, Kejuan Song, Lili Zhang, Weihua Li, Yulong Chen, Yuchao Diao, Qin Yao, Peishu Liu
This study was to explore the roles of miRNA-34a (miR-34a) in ovarian cancer (OC) cells and uncover possible mechanisms. The proliferation of OC cells was measured with MTT assay and soft agar colony formation assay. Targetscan analysis, real-time PCR and luciferase reporter assay were used to demonstrate the downstream target of miR-34a in OC cells. HDAC1 expression level was detected by immunoblot analysis. MiR-34a inhibited the proliferation of SKOV3 and OVCA433 cells and enhanced cisplatin sensitivity of cisplatin resistant SKOV3cp cells...
March 21, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Minji Jeon, Sunkyu Kim, Sungjoon Park, Heewon Lee, Jaewoo Kang
BACKGROUND: Drug combination therapy, which is considered as an alternative to single drug therapy, can potentially reduce resistance and toxicity, and have synergistic efficacy. As drug combination therapies are widely used in the clinic for hypertension, asthma, and AIDS, they have also been proposed for the treatment of cancer. However, it is difficult to select and experimentally evaluate effective combinations because not only is the number of cancer drug combinations extremely large but also the effectiveness of drug combinations varies depending on the genetic variation of cancer patients...
March 19, 2018: BMC Systems Biology
Ting-Ting Liu, Xi-Sheng Liu, Meng Zhang, Xue-Ni Liu, Fu-Xiang Zhu, Fang-Ming Zhu, Si-Wen Ouyang, Shan-Bao Li, Chen-Long Song, Hui-Min Sun, Su Lu, Yu Zhang, Jun Lin, Hua-Mei Tang, Zhi-Hai Peng
PURPOSE: Recent studies have determined that cartilage oligomeric matrix protein (COMP) plays a vital role in carcinogenesis. We sought to clarify the role of COMP in colon cancer. METHODS: We investigated gene expression data from The Cancer Genome Atlas (TCGA) dataset. Tissue microarrays (TMA) containing paired samples from 253 patients with colon cancer were subjected to immunostaining. COMP levels in serum of colon cancer patients and healthy donors were measured with ELISA...
March 20, 2018: Journal of Cancer Research and Clinical Oncology
Mohit Kumar Jolly, Prakash Kulkarni, Keith Weninger, John Orban, Herbert Levine
It is well known that genetic mutations can drive drug resistance and lead to tumor relapse. Here, we focus on alternate mechanisms-those without mutations, such as phenotypic plasticity and stochastic cell-to-cell variability that can also evade drug attacks by giving rise to drug-tolerant persisters. The phenomenon of persistence has been well-studied in bacteria and has also recently garnered attention in cancer. We draw a parallel between bacterial persistence and resistance against androgen deprivation therapy in prostate cancer (PCa), the primary standard care for metastatic disease...
2018: Frontiers in Oncology
Shaolin Ma, Sunila Pradeep, Wei Hu, Dikai Zhang, Robert Coleman, Anil Sood
Anti-angiogenic therapy has been demonstrated to increase progression-free survival in patients with many different solid cancers. Unfortunately, the benefit in overall survival is modest and the rapid emergence of drug resistance is a significant clinical problem. Over the last decade, several mechanisms have been identified to decipher the emergence of resistance. There is a multitude of changes within the tumor microenvironment (TME) in response to anti-angiogenic therapy that offers new therapeutic opportunities...
2018: F1000Research
Andrea Fabianova, Monika Barathova, Lucia Csaderova, Veronika Simko, Miriam Zatovicova, Martina Labudova, Jaromir Pastorek
Renal cell carcinoma is one of the most frequent cancer diseases with high resistance to radio- and chemotherapy. Mutation of VHL gene is frequent in these tumors leading to simulation of hypoxic conditions. Lymphocytic choriomeningitis virus, belonging to RNA viruses, is a neglected human pathogen and teratogen. We have found that infection of renal cell carcinoma cells by lymphocytic choriomeningitis virus strain MX causes a decrease of carbonic anhydrase IX protein and RNA level. Lower expression of carbonic anhydrase IX on the cell surface provides less target for carbonic anhydrase IX-targeted immunotherapy...
February 27, 2018: Oncotarget
Li Liu, Mingxing Miao, Yang Chen, Zhongjian Wang, Binbin Sun, Xiaodong Liu
This study investigated alterations in the function and expression of P-glycoprotein (P-GP), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP2) at the blood-brain barrier (BBB) of acute liver failure (ALF) mice and its clinical significance. ALF mice were developed using intraperitoneal injection of thioacetamide. P-GP, BCRP, and MRP2 functions were determined by measuring the ratios of brain-to-plasma concentration of rhodamine 123, prazosin, and dinitrophenyl- S -glutathione, respectively...
2018: Frontiers in Pharmacology
Alaa Abd-Elsayed, Samuel Lee, Markus Jackson
Background: Intercostal neuralgia is a complex and difficult-to-treat condition. We present 2 cases that demonstrate the safe and effective use of thermal radiofrequency ablation (RFA) to achieve significant pain relief. Case Reports: Our first patient was a 62-year-old female who developed chronic chest pain following lumpectomy for breast cancer and failed conservative management. Two intercostal diagnostic nerve blocks were performed with good results. One block provided pain relief for 3 weeks, and the other provided pain relief for 5 weeks...
2018: Ochsner Journal
Zhu Kun-Peng, Ma Xiao-Long, Zhang Chun-Lin
Circular RNAs (circRNAs) represent a widespread class of non-coding RNAs generated from back-splicing, with a circular loop structure. Many circRNAs have been reported to play essential roles in cancer development and have the potential to serve as a novel class of biomarkers for clinical diagnosis. However, the role of circRNA in osteosarcoma (OS) remains largely unknown. In the current study, we examined the expression level of circular RNA PVT1 (circPVT1), previously screened and identified the oncogenic role in gastric cancer, in OS and found that circPVT1 was significantly up-regulated in the OS tissues, serums and chemoresistant cell lines, correlated with poor prognosis of OS patients...
2018: International Journal of Biological Sciences
Zunyue Zhang, Guohong Lin, Yujing Yan, Xiang Li, Yibing Hu, Jing Wang, Bingjiao Yin, Yaqun Wu, Zhuoya Li, Xiang-Ping Yang
Chemoresistance remains a major obstacle to successful treatment of breast cancer. Although soluble tumor necrosis factor-α (sTNF-α) has been implicated in mediating drug-resistance in human cancers, whether transmembrane tumor necrosis factor-α (tmTNF-α) plays a role in chemoresistance remains unclear. Here we found that over 50% of studied patients expressed tmTNF-α at high levels in breast cancer tissues and tmTNF-α expression positively correlated with resistance to anthracycline chemotherapy. Alteration of tmTNF-α expression changed the sensitivity of primary human breast cancer cells and breast cancer cell lines to doxorubicin (DOX)...
March 21, 2018: Oncogene
Anne Mills, Sara Zadeh, Emily Sloan, Zachary Chinn, Susan C Modesitt, Kari L Ring
Mismatch repair-deficient endometrial carcinomas are optimal candidates for immunotherapy given their high neoantigen loads, robust lymphoid infiltrates, and frequent PD-L1 expression. However, co-opting the PD-1/PD-L1 pathway is just one mechanism that tumors can utilize to evade host immunity. Another immune modulatory molecule that has been demonstrated in endometrial carcinoma is indoleamine 2,3-dioxygenase (IDO). We herein evaluate IDO expression in 60 endometrial carcinomas and assess results in relation to PD-L1 and mismatch repair status...
March 20, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Fabricio Castro Machado, Caio Haddad Franco, Jose Vitorino Dos Santos Neto, Karina Luiza Dias-Teixeira, Carolina Borsoi Moraes, Ulisses Gazos Lopes, Bertal Huseyin Aktas, Sergio Schenkman
Some 1,3-diarylureas and 1-((1,4-trans)-4-aryloxycyclohexyl)-3-arylureas (cHAUs) activate heme-regulated kinase causing protein synthesis inhibition via phosphorylation of the eukaryotic translation initiation factor 2 (eIF2) in mammalian cancer cells. To evaluate if these agents have potential to inhibit trypanosome multiplication by also affecting the phosphorylation of eIF2 alpha subunit (eIF2α), we tested 25 analogs of 1,3-diarylureas and cHAUs against Trypanosoma cruzi, the agent of Chagas disease. One of them (I-17) presented selectivity close to 10-fold against the insect replicative forms and also inhibited the multiplication of T...
March 20, 2018: Scientific Reports
Nadège Bossuet-Greif, Julien Vignard, Frédéric Taieb, Gladys Mirey, Damien Dubois, Claude Petit, Eric Oswald, Jean-Philippe Nougayrède
Colibactins are hybrid polyketide-nonribosomal peptides produced by Escherichia coli , Klebsiella pneumoniae , and other Enterobacteriaceae harboring the pks genomic island. These genotoxic metabolites are produced by pks -encoded peptide-polyketide synthases as inactive prodrugs called precolibactins, which are then converted to colibactins by deacylation for DNA-damaging effects. Colibactins are bona fide virulence factors and are suspected of promoting colorectal carcinogenesis when produced by intestinal E...
March 20, 2018: MBio
Sana Hibino, Shunsuke Chikuma, Taisuke Kondo, Minako Ito, Hiroko Nakatsukasa, Setsuko Omata-Mise, Akihiko Yoshimura
Enhanced infiltration of regulatory T (Treg) cells into tumor tissue is detrimental to cancer patients and closely associated with poor prognosis as they create an immunosuppressive state that suppresses anti-tumor immune responses. Therefore, breaking Treg-mediated immune tolerance is important when considering cancer immunotherapy. Here we show that the Nr4a nuclear receptors, key transcription factors maintaining Treg cell genetic programs, contribute to Treg-mediated suppression of anti-tumor immunity in the tumor microenvironment...
March 20, 2018: Cancer Research
Anna Babayan, Klaus Pantel
Progress in sensitive analytical approaches has opened new avenues for the detection of cells or products such as circulating cell-free DNA released by tumors. These 'liquid biopsies' are being explored in clinical trials for early cancer detection, prediction of recurrent disease, and assessment of therapeutic resistance mechanisms.
March 20, 2018: Genome Medicine
Toshinori Ozaki, Meng Yu, Danjing Yin, Dan Sun, Yuyan Zhu, Youquan Bu, Meixiang Sang
BACKGROUND: Despite the remarkable advances in the early diagnosis and treatment, overall 5-year survival rate of patients with pancreatic cancer is less than 10%. Gemcitabine (GEM), a cytidine nucleoside analogue and ribonucleotide reductase inhibitor, is a primary option for patients with advanced pancreatic cancer; however, its clinical efficacy is extremely limited. This unfavorable clinical outcome of pancreatic cancer patients is at least in part attributable to their poor response to anti-cancer drugs such as GEM...
March 20, 2018: BMC Cancer
Mary Jo Fidler, Cristina L Fhied, Joanna Roder, Sanjib Basu, Selina Sayidine, Ibtihaj Fughhi, Mark Pool, Marta Batus, Philip Bonomi, Jeffrey A Borgia
BACKGROUND: The VeriStrat test is a serum proteomic signature originally discovered in non-responders to second line gefitinib treatment and subsequently used to predict differential benefit from erlotinib versus chemotherapy in previously treated advanced non-small cell lung cancer (NSCLC). Multiple studies highlight the clinical utility of the VeriStrat test, however, the mechanistic connection between VeriStrat-poor classification and poor prognosis in untreated and previously treated patients is still an active area of research...
March 20, 2018: BMC Cancer
Garcia-Chagollan Mariel, Carranza-Torres Irma Edith, Carranza-Rosales Pilar, Guzmán-Delgado Nancy Elena, Ramírez-Montoya Humberto, Martínez-Silva María Guadalupe, Mariscal-Ramirez Ignacio, Barrón-Gallardo Carlos Alfredo, Pereira-Suárez Ana Laura, Aguilar-Lemarroy Adriana, Jave-Suárez Luis Felipe
BACKGROUND: Currently, one of the most used strategies for the treatment of newly diagnosed patients with breast cancer is neoadjuvant chemotherapy based on the application of taxanes and anthracyclines. However, despite the high number of patients who develop a complete pathological clinical response, resistance and relapse following this therapy continue to be a clinical challenge. As a component of the innate immune system, the cytotoxic function of Natural Killer (NK) cells plays an important role in the elimination of tumor cells...
January 1, 2018: Technology in Cancer Research & Treatment
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