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https://www.readbyqxmd.com/read/28812378/bevacizumab-in-advanced-lung-cancer-state-of-the-art
#1
Sandra Assoun, Solenn Brosseau, Christelle Steinmetz, Valérie Gounant, Gérard Zalcman
Despite recent advances in metastatic lung cancer treatment with the advent of immune checkpoint inhibitors and molecules targeting addictive genomic abnormalities, prognosis of most of the patients remains unfavorable. Combination approaches with older drugs, such as bevacizumab, should be thus envisioned. Bevacizumab is a monoclonal anti-VEGF antibody, approved by the US FDA and the EMA in first-line and maintenance settings of advanced nonsquamous non-small-cell lung cancer (NSCLC) treatment, in association with platinum-based chemotherapy...
August 16, 2017: Future Oncology
https://www.readbyqxmd.com/read/28812304/management-of-castration-resistant-taxane-resistant-prostate-cancer
#2
Tomasz M Beer
Metastatic castration-resistant prostate cancer that is progressing despite docetaxel chemotherapy is difficult to treat and often aggressive. If not previously used, modern androgen signaling inhibitors have established clinical activity in this setting. Cabazitaxel and radium-223 have also been shown to extend survival in appropriately selected patients. Carboplatin-containing chemotherapy regimens have not been studied in randomized trials with a survival endpoint, but they have demonstrated activity in phase II trials and are occasionally considered in the post-docetaxel setting...
August 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28811332/de-novo-lipid-synthesis-facilitates-gemcitabine-resistance-through-endoplasmic-reticulum-stress-in-pancreatic-cancer
#3
Saber Tadros, Surendra K Shukla, Ryan J King, Venugopal Gunda, Enza Vernucci, Jaime Abrego, Nina CHaika, Fang Yu, Audrey J Lazenby, Lyudmyla Berim, Jean L Grem, Aaron Sasson, Pankaj K Singh
Pancreatic adenocarcinoma is moderately responsive to gemcitabine-based chemotherapy, the most widely used single agent therapy for pancreatic cancer. While the prognosis in pancreatic cancer remains grim in part due to poor response to therapy, previous attempts at identifying and targeting the resistance mechanisms have not been very successful. By leveraging TCGA dataset, we identified lipid metabolism as the metabolic pathway that most significantly correlated with poor gemcitabine response in pancreatic cancer patients...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28810651/kanglaite-inhibits-the-expression-of-drug-resistance-genes-through-suppressing-pvt1-in-cisplatin-resistant-gastric-cancer-cells
#4
Xian-Wen Zhang, Liang Liu, Xi-Zhi Zhang, Ping Bo
Kanglaite (KLT) was shown to alleviate the development of multidrug resistance (MDR) clinically. The purpose of this study is to examine the mechanism of KLT for chemotherapy resistance in gastric cancer cells involving the regulation of MDR-related proteins. The cisplatin-resistant BGC823/DPP and SGC7901/DDP cells were treated with 1, 2.5 and 5 µl/ml of KLT for 24, 36 and 48 h. Cell Counting Kit-8 (CCK-8) assay and flow cytometry were performed to detect the cell viability and cell apoptosis, respectively...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810525/in-vitro-anticancer-activities-of-osthole-against-renal-cell-carcinoma-cells
#5
Lei Liu, Jun Mao, Qifei Wang, Zhiwei Zhang, Guangzhen Wu, Qizhen Tang, Bin Zhao, Lianhong Li, Quanlin Li
Renal cell carcinoma (RCC) is a common urinary malignancy that is resistant to chemotherapy and radiotherapy. Osthole, a monomer compound extracted from a traditional Chinese herb, has potent anti-tumor effects on various types of cancer cells. However, the therapeutic effects of osthole on RCC remain unclear. In our study, osthole could suppress the proliferation and colony formation of two RCC cell lines, ACHN and 786-O cells, in a dose-dependent manner. Treatment with osthole resulted in a significant, dose-dependent increase in the expression of pro-apoptotic proteins (cleaved caspase-3 and Bax) and decreased expression of anti-apoptotic proteins (Bcl-2 and survivin), which were consistent with evidence of apoptotic nuclear morphology revealed by DAPI staining...
August 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28808338/a-dynamical-framework-for-complex-fractional-killing
#6
Richard Ballweg, Andrew L Paek, Tongli Zhang
When chemotherapy drugs are applied to tumor cells with the same or similar genotypes, some cells are killed, while others survive. This fractional killing contributes to drug resistance in cancer. Through an incoherent feedforward loop, chemotherapy drugs not only activate p53 to induce cell death, but also promote the expression of apoptosis inhibitors which inhibit cell death. Consequently, cells in which p53 is activated early undergo apoptosis while cells in which p53 is activated late survive. The incoherent feedforward loop and the essential role of p53 activation timing makes fractional killing a complex dynamical challenge, which is hard to understand with intuition alone...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808163/a-role-for-fimh-in-extraintestinal-pathogenic-escherichia-coli-invasion-and-translocation-through-the-intestinal-epithelium
#7
Nina M Poole, Sabrina I Green, Anubama Rajan, Luz E Vela, Xi-Lei Zeng, Mary K Estes, Anthony W Maresso
The translocation of bacteria across the intestinal epithelium of immunocompromised patients can lead to bacteremia and life-threatening sepsis. Extraintestinal Pathogenic Escherichia coli (ExPEC), so named because this pathotype infects tissues distal to the intestinal tract, is a frequent cause of such infections, is often multidrug resistant, and chronically colonizes a sizable portion of the healthy population. Although several virulence factors and their roles in pathogenesis are well described for ExPEC that cause urinary tract infections and meningitis, they have not been linked to translocation through intestinal barriers, a fundamentally distant yet important clinical phenomenon...
August 14, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28807911/systematic-review-and-meta-analyses-of-the-effect-of-chemotherapy-on-pulmonary-mycobacterium-abscessus-outcomes-and-disease-recurrence
#8
Jotam G Pasipanodya, Deborah Ogbonna, Beatriz E Ferro, Gesham Magombedze, Shashikant Srivastava, Devyani Deshpande, Tawanda Gumbo
Background. In pharmacokinetic/pharmacodynamics models of pulmonary Mycobacterium abscessus complex, the recommended macrolide-containing combination therapy has poor kill rates. However, clinical outcomes are unknown.Methods We searched the literature for studies published between 1990-2017 that reported microbial outcomes in patients treated for pulmonary M. abscessus disease. Good outcome was defined as sustained sputum culture conversion (SSCC) without relapse. Random effects models were used to pool studies and estimate proportions of patients with good outcomes...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28805931/mrp1-protein-expression-in-leukemic-stem-cells-as-a-negative-prognostic-marker-in-acute-myeloid-leukemia-patients
#9
Maria Paprocka, Aleksandra Bielawska-Pohl, Joanna Rossowska, Agnieszka Krawczenko, Danuta Duś, Marek Kiełbiński, Olga Haus, Maria Podolak-Dawidziak, Kazimierz Kuliczkowski
BACKGROUND: It is well established that expression of multi-drug resistance (MDR) proteins (MDR1, BCRP, MDR3, MRP1 and LRP) in leukemic blasts correlates with AML patients clinical response. Assuming that leukemic stem cells (LSC) are resistant to chemotherapy and responsible for relapse it might be clinically relevant to evaluate the expression level of MDR proteins in LSC and relate it to the clinical outcome. METHODS: Bone marrow samples from 26 patients with de novo AML were labeled with antibodies to distinguish CD34+CD38-CD123+ LSC population and with antibodies against MDR1, BCRP, MDR3, MRP1 or LRP proteins...
August 14, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28805111/chemoresistance-in-cancer-cells-exosomes-as-potential-regulators-of-therapeutic-tumor-heterogeneity
#10
Aman Sharma
Drug resistance in cancer cells remains a fundamental challenge. Be it nontargeted or targeted drugs, the presence of intrinsic or acquired cancer cell resistance remains a great obstacle in chemotherapy. Conventionally, a spectrum of cellular mechanisms defines drug resistance including overexpression of antiapoptotic proteins and drug efflux pumps, mutations in target and synergistic activation of prosurvival pathways in tumor cells. In addition to these well-studied routes, exosome-induced chemoresistance is emerging as a novel mechanism...
August 14, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28804908/influence-of-abiraterone-acetate-on-neuroendocrine-differentiation-in-chemotherapy-naive-metastatic-castration-resistant-prostate-cancer
#11
Baijun Dong, Liancheng Fan, Yanqing Wang, Chenfei Chi, Xiaowei Ma, Rui Wang, Wen Cai, Xiaoguang Shao, Jiahua Pan, Yinjie Zhu, Xun Shangguan, Zhixiang Xin, Jianian Hu, Shaowei Xie, Xiaonan Kang, Lixin Zhou, Wei Xue
BACKGROUND: To determine the influence of abiraterone Acetate (AA) on neuroendocrine differentiation (NED) in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC). METHODS: We conducted an analysis in 115 chemotherapy-naïve mCRPC patients who would be treated with chemotherapy. The serum levels of chromogranin A (CgA), neurone-specific enolase (NSE) were measured in 67 mCRPC patients without AA treatment and 48 patients after the failure of AA treatment, in which these markers were also measured in 34 patients before and after 6 months of AA treatment...
August 14, 2017: Prostate
https://www.readbyqxmd.com/read/28804523/tri-methylation-of-h3k79-is-decreased-in-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-lung-cancer
#12
Emilie Evanno, Julie Godet, Nathalie Piccirilli, Joëlle Guilhot, Serge Milin, Jean Marc Gombert, Benoit Fouchaq, Joëlle Roche
BACKGROUND: The epithelial-to-mesenchymal transition (EMT) enables epithelial cancer cells to acquire mesenchymal features and contributes to metastasis and resistance to treatment. This process involves epigenetic reprogramming for gene expression. We explored global histone modifications during TGF-β1-induced EMT in two non-small cell lung cancer (NSCLC) cell lines and tested different epigenetic treatment to modulate or partially reverse EMT. RESULTS: Loss of classical epithelial markers and gain of mesenchymal markers were verified in A549 and H358 cell lines during TGF-β1-induced EMT...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28803687/predictors-of-asymptomatic-radiation-induced-abdominal-atherosclerosis
#13
L Cella, R Liuzzi, P Romanelli, M Conson, V D'Avino, M Ottaviano, V Damiano, G Palmieri, R Pacelli, M Mancini
AIMS: To identify predictors of asymptomatic radiation-induced abdominal atherosclerosis in patients treated with radiotherapy and evaluated by abdominal vascular ultrasonography. MATERIALS AND METHODS: Forty-two testicular classic seminoma patients (median age 34 years, range 16-56) undergoing radical inguinal orchiectomy were analysed. Twenty-six patients underwent post-surgery radiotherapy (median total dose 25 Gy, range 25-43), two of them also received chemotherapy (CHT) and 16 patients were treated with surgery alone or by surgery followed by CHT (control group)...
August 10, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28803675/the-yale-fitness-intervention-trial-in-female-cancer-survivors-cardiovascular-and-physiological-outcomes
#14
M Tish Knobf, Sangchoon Jeon, Barbara Smith, Lyndsay Harris, Siobhan Thompson, Mitchel R Stacy, Karl Insogna, Albert J Sinusas
BACKGROUND: Induced premature menopause and cardio-toxic therapy increase cardiovascular disease risk in female cancer survivors. OBJECTIVE: To compare the effects of a 12 month aerobic-resistance fitness center intervention to home based physical activity on cardiovascular function and metabolic risk factors. METHODS: Subjects (N = 154) who had completed primary and/or adjuvant chemotherapy (past 3 years) were randomized to a fitness center intervention or a home based group...
August 10, 2017: Heart & Lung: the Journal of Critical Care
https://www.readbyqxmd.com/read/28803259/opportunities-and-challenges-in-the-immunological-therapy-of-pediatric-malignancy-a-concise-snapshot
#15
REVIEW
Francesco Ceppi, Maja Beck-Popovic, Jean-Pierre Bourquin, Raffaele Renella
Over the last 50 years, collaborative clinical trials have reduced the number of children dying from pediatric cancer significantly. Unfortunately, certain tumor types have remained resistant to conventional surgical, radiotherapy and chemotherapy combinations, and relapsing and/or refractory disease remains associated with dismal outcomes. Recently, renewed attention has been given to the role for immunotherapies in pediatric oncology. In fact, these combine several attractive features, including (but possibly not limited to) the specificity for cancer cells, potentially in vivo persistence and longevity, and potency against refractory disease...
August 12, 2017: European Journal of Pediatrics
https://www.readbyqxmd.com/read/28802152/comparison-and-analysis-of-the-structures-and-binding-modes-of-antifungal-se-and-cyp51-inhibitors
#16
Bin Sun, Wanxu Huang, Min Liu, Kang Lei
With the abuse of clinical broad-spectrum antimicrobial agents, immunosuppressive agents, chemotherapy drugs, the emergence of pathogenic fungi resistance is more and more frequent. However, there is still no effective treatment for the fungal resistance. Squalenee epoxidase (SE) and 14 α-demethylase (CYP51) are important antifungal drug targets. In order to achieve a deeper insight into the structural characteristics and the action modes of SE and CYP51inhibitors, the homology model of SE (Candida albicans) was constructed using monooxygenase of Pseudomonas aeruginosa as template, and the reliability of model was confirmed by Ramachandran plots and Verify 3D...
August 1, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28801914/blockade-of-transforming-growth-factor-%C3%AE-signaling-enhances-oncolytic-herpes-simplex-virus-efficacy-in-patient-derived-recurrent-glioblastoma-models
#17
Shinichi Esaki, Fares Nigim, Esther Moon, Samantha Luk, Juri Kiyokawa, William Curry, Daniel P Cahill, Andrew S Chi, A John Iafrate, Robert L Martuza, Samuel D Rabkin, Hiroaki Wakimoto
Despite the current standard of multimodal management, glioblastoma (GBM) inevitably recurs and effective therapy is not available for recurrent disease. A subset of tumor cells with stem-like properties, termed GBM stem-like cells (GSCs), are considered to play a role in tumor relapse. Although oncolytic herpes simplex virus (oHSV) is a promising therapeutic for GBM, its efficacy against recurrent GBM is incompletely characterized. Transforming growth factor beta (TGF-β) plays vital roles in maintaining GSC stemness and GBM pathogenesis...
August 12, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28801675/targeting-p-glycoprotein-investigation-of-piperine-analogs-for-overcoming-drug-resistance-in-cancer
#18
Safiulla Basha Syed, Hemant Arya, I-Hsuan Fu, Teng-Kuang Yeh, Latha Periyasamy, Hsing-Pang Hsieh, Mohane Selvaraj Coumar
P-glycoprotein (P-gp) is a drug transporter that effluxes chemotherapeutic drugs and is implicated in the development of resistance of cancer cells to chemotherapeutic drugs. To date, no drug has been approved to inhibit P-gp and restore chemotherapy efficacy. Moreover, majority of the reported inhibitors have high molecular weight and complex structures, making it difficult to understand the basic structural requirement for P-gp inhibition. In this study, two structurally simple, low molecular weight piperine analogs Pip1 and Pip2 were designed and found to better interact with P-gp than piperine in silico...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801626/hif1%C3%AE-regulates-glioma-chemosensitivity-through-the-transformation-between-differentiation-and-dedifferentiation-in-various-oxygen-levels
#19
Pan Wang, Wenwu Wan, Shuanglong Xiong, Junwei Wang, Dewei Zou, Chuan Lan, Shuangjiang Yu, Bin Liao, Hua Feng, Nan Wu
Chemotherapy plays a significant role in glioma treatment; however, it has limited effectiveness in extending the life expectancies of glioma patients. Traditional studies have attributed this lack of efficacy to glioma stem cells (GSCs) and their high resistance to chemotherapy, and hypoxia worsens this issue. In contrast, hyperoxia effectively alleviates hypoxia in glioma and sensitizes glioma cells to chemotherapy. In a summary of traditional studies, the majority of researchers overlooked the influence of hypoxia on differentiated cells because they only focused on the maintenance of GSCs stemness, which thus resulted in chemoresistance...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801308/egfr-mutations-compromise-hypoxia-associated-radiation-resistance-through-impaired-replication-fork-associated-dna-damage-repair
#20
Mohammad Saki, Haruhiko Makino, Prashanthi Javvadi, Nozomi Tomimatsu, Lianghao Ding, Jennifer E Clark, Elaine Gavin, Kenichi Takeda, Joel Andrews, Debabrata Saha, Michael D Story, Sandeep Burma, Chaitanya Nirodi
Epidermal growth factor receptor (EGFR) signaling has been implicated in hypoxia-associated resistance to radiation or chemotherapy. Non-small cell lung carcinomas (NSCLC) with activating L858R or ΔE746-E750 EGFR mutations exhibit elevated EGFR activity and downstream signaling. Here, relative to wild type (WT) EGFR, mutant (MT) EGFR expression significantly increases radiosensitivity in hypoxic cells. Gene expression profiling in human bronchial epithelial cells (HBEC) revealed that MT-EGFR expression elevated transcripts related to cell cycle and replication in aerobic and hypoxic conditions and down-regulated RAD50, a critical component of non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA repair pathways...
August 11, 2017: Molecular Cancer Research: MCR
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