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https://www.readbyqxmd.com/read/28938696/the-molecular-mechanisms-of-chemoresistance-in-cancers
#1
REVIEW
Hua-Chuan Zheng
Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938672/comparing-the-clinical-efficacy-of-abiraterone-acetate-enzalutamide-and-orteronel-in-patients-with-metastatic-castration-resistant-prostate-cancer-by-performing-a-network-meta-analysis-of-eight-randomized-controlled-trials
#2
Minyong Kang, Chang Wook Jeong, Cheol Kwak, Ja Hyeon Ku, Hyeon Hoe Kim
Various novel androgen receptor (AR) targeting drugs have been developed recently and have shown beneficial effects on survival in patients with metastatic castration-resistant prostate cancer (mCRPC). However, no consensus has been reached regarding which of these agents provides the most favorable oncological outcomes. Here, we aimed to compare the efficacy of novel AR-targeted agents by performing a network meta-analysis of randomized controlled trials (RCTs). We included eight RCTs for men with mCRPC treated with one of the AR targeting agents: abiraterone acetate, enzalutamide, or orteronel...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938651/positive-transcription-elongation-factor-b-p-tefb-is-a-therapeutic-target-in-human-multiple-myeloma
#3
Yu Zhang, Liang Zhou, Yun Leng, Yun Dai, Robert Z Orlowski, Steven Grant
The role of the positive RNA Pol II regulator, P-TEFb (positive transcription elongation factor b), in maintenance of the anti-apoptotic protein Mcl-1 and bortezomib (btz) resistance was investigated in human multiple myeloma (MM) cells. Mcl-1 was up-regulated in all MM lines tested, including bortezomib-resistant lines, human MM xenograft mouse models, and primary CD138(+) MM cells. Mcl-1 over-expression significantly reduced bortezomib lethality, indicating a functional role for Mcl-1 in bortezomib resistance...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938627/prostate-tumor-overexpressed-1-ptov1-promotes-docetaxel-resistance-and-survival-of-castration-resistant-prostate-cancer-cells
#4
Verónica Cánovas, Yolanda Puñal, Valentina Maggio, Enric Redondo, Mercedes Marín, Begoña Mellado, Mireia Olivan, Matilde Lleonart, Jacques Planas, Juan Morote, Rosanna Paciucci
Metastatic prostate cancer is presently incurable. The oncogenic protein PTOV1, first described in prostate cancer, was reported as overexpressed and significantly correlated with poor survival in numerous tumors. Here, we investigated the role of PTOV1 in prostate cancer survival to docetaxel and self-renewal ability. Transduction of PTOV1 in docetaxel-sensitive Du145 and PC3 cells significantly increased cell survival after docetaxel exposure and induced docetaxel-resistance genes expression (ABCB1, CCNG2 and TUBB2B)...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938614/phenformin-enhances-the-therapeutic-effect-of-selumetinib-in-kras-mutant-non-small-cell-lung-cancer-irrespective-of-lkb1-status
#5
Jun Zhang, Sreenivas Nannapaneni, Dongsheng Wang, Fakeng Liu, Xu Wang, Rui Jin, Xiuju Liu, Mohammad Aminur Rahman, Xianghong Peng, Guoqing Qian, Zhuo G Chen, Kwok-Kin Wong, Fadlo R Khuri, Wei Zhou, Dong M Shin
MEK inhibition is potentially valuable in targeting KRAS-mutant non-small cell lung cancer (NSCLC). Here, we analyzed whether concomitant LKB1 mutation alters sensitivity to the MEK inhibitor selumetinib, and whether the metabolism drug phenformin can enhance the therapeutic effect of selumetinib in isogenic cell lines with different LKB1 status. Isogenic pairs of KRAS-mutant NSCLC cell lines A549, H460 and H157, each with wild-type and null LKB1, as well as genetically engineered mouse-derived cell lines 634 (kras(G12D/wt)/p53(-/-)/lkb1(wt/wt)) and t2 (kras(G12D/wt)/p53(-/-)/lkb1(-/-)) were used in vitro to analyze the activities of selumetinib, phenformin and their combination...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938602/activation-of-cancerous-inhibitor-of-pp2a-cip2a-contributes-to-lapatinib-resistance-through-induction-of-cip2a-akt-feedback-loop-in-erbb2-positive-breast-cancer-cells
#6
Ming Zhao, Erin W Howard, Amanda B Parris, Zhiying Guo, Qingxia Zhao, Zhikun Ma, Ying Xing, Bolin Liu, Susan M Edgerton, Ann D Thor, Xiaohe Yang
Lapatinib, a small molecule ErbB2/EGFR inhibitor, is FDA-approved for the treatment of metastatic ErbB2-overexpressing breast cancer; however, lapatinib resistance is an emerging clinical challenge. Understanding the molecular mechanisms of lapatinib-mediated anti-cancer activities and identifying relevant resistance factors are of pivotal significance. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that is overexpressed in breast cancer. Our study investigated the role of CIP2A in the anti-cancer efficacy of lapatinib in ErbB2-overexpressing breast cancer cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938593/endoplasmic-reticulum-stress-mediated-membrane-expression-of-crt-erp57-induces-immunogenic-apoptosis-in-drug-resistant-endometrial-cancer-cells
#7
Qin Xu, Chuanben Chen, An Lin, Yunqing Xie
OBJECTIVE: To investigate the role of endoplasmic reticulum (ER) stress-mediated CRT/ERp57 complex expression underlying the mechanism of resistance to doxorubicin (DOX) in endometrial carcinoma (EC) in vivo and in vitro. METHODS: The expression of CRT, ERp57, p-PERK, eIF2α, p-eIF2α in EC patients and EC cells was detected by Western blots and by immunofluorescence assay. MTT assay was used to determine the LC50 of EC cells to DOX and cell viability. Apoptosis was assayed using flow cytometer...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938421/bortezomib-alone-and-in-combination-with-salinosporamid-a-induces-apoptosis-and-promotes-pheochromocytoma-cell-death-in-vitro-and-in-female-nude-mice
#8
Petra Bullova, Antony Cougnoux, Geena Marzouca, Juraj Kopacek, Karel Pacak
Proteasome inhibitors have been frequently used in treating hematologic and solid tumors. They are administered individually or in combination with other regimens, to prevent severe side effects and resistance development. Since they have been shown to be efficient and are pharmaceutically available, we tested the first FDA-approved proteasome inhibitor bortezomib alone and in combination with another proteasome inhibitor, salinosporamid A, in pheochromocytoma cells. Pheochromocytomas/paragangliomas (PHEOs/PGLs) are neuroendocrine tumors for which no definite cure is yet available...
August 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938136/systemic-inflammatory-response-syndrome-in-the-course-of-status-epilepticus-7-year-two-center-observational-study
#9
Sebastian Szklener, Agnieszka Korchut, Magdalena Godek, Luiza Balicka-Adamik, Dariusz Bielecki, Robert Rejdak, Konrad Rejdak
OBJECTIVES: This study was aimed at identifying patients with systemic inflammatory response syndrome (SIRS) and determining whether the presence of SIRS on admission was associated with drug resistance and poor outcome in status epilepticus (SE) patients. METHODS: We conducted a prospective review of patients consecutively admitted to two territory centers over a 7-year period. SIRS was considered present if the necessary criteria persisted for 12h. Other potential outcome predictors in a cohort of patients with SE were also collected...
September 14, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28938109/investigating-mutation-specific-biological-activities-of-small-molecules-using-quantitative-structure-activity-relationship-for-epidermal-growth-factor-receptor-in-cancer
#10
P Anoosha, R Sakthivel, M Michael Gromiha
Epidermal Growth Factor Receptor (EGFR) is a potential drug target in cancer therapy. Missense mutations play major roles in influencing the protein function, leading to abnormal cell proliferation and tumorigenesis. A number of EGFR inhibitor molecules targeting ATP binding domain were developed for the past two decades. Unfortunately, they become inactive due to resistance caused by new mutations in patients, and previous studies have also reported noticeable differences in inhibitor binding to distinct known driver mutants as well...
August 26, 2017: Mutation Research
https://www.readbyqxmd.com/read/28937991/sociodemographic-correlates-of-hiv-drug-resistance-and-access-to-drug-resistance-testing-in-british-columbia-canada
#11
Genevieve Rocheleau, Conrado Franco-Villalobos, Natalia Oliveira, Zabrina L Brumme, Melanie Rusch, Jeannie Shoveller, Chanson J Brumme, P Richard Harrigan
Sociodemographic correlates of engagement in human immunodeficiency virus (HIV) care are well studied, however the association with accessing drug resistance testing (DRT) and the development of drug resistance have not been characterized. Between 1996-2014, 11 801 HIV patients accessing therapy in British Columbia were observed longitudinally. A subset of 9456 patients had testable viral load; of these 8398 were linked to census data. Sociodemographic (census tract-level) and clinical (individual-level) correlates of DRT were assessed using multivariable General Estimating Equation logistic regression adjusted odds ratios (aOR)...
2017: PloS One
https://www.readbyqxmd.com/read/28937965/artemin-promotes-oncogenicity-metastasis-and-drug-resistance-in-cancer-cells
#12
Kamal Hezam, Jiahao Jiang, Fumou Sun, Xinrong Zhang, Juan Zhang
Artemin (ARTN) is a member of glial cell line-derived neurotrophic factor (GDNF) family of ligands, and its signaling is mediated via a multi-component receptor complex including the glycosylphosphatidylinositol-anchored GDNF family receptors a (GFRa1, GFRa3) and RET receptor tyrosine kinase. The major mechanism of ARTN action is via binding to a non-signaling co-receptor. The major function of ARTN is to drive the molecule to induce migration and axonal projection from sympathetic neurons. It also promotes the survival, proliferation and neurite outgrowth of sympathetic neurons in vitro...
September 22, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28937793/investigating-the-antiangiogenic-anti-drug-resistance-and-apoptotic-effects-of-soy-isoflavone-extract-alone-or-in-combination-with-docetaxel-on-murine-4t1-breast-tumor-model
#13
Ehsan Hejazi, Maryam Tavakoli, Mahmood Jeddi-Tehrani, Masoud Kimiagar, Jalal Hejazi, Mohammad Houshyari, Zohre Amiri, Hale Edalatkhah, Javad Nasrollahzadeh, Farah Idali
BACKGROUND: One major concern in the treatment of cancer patients during chemotherapy is drug resistance. Here we investigated the effects of soy isoflavone extracts alone or in combination with Docetaxel on the drug resistance, angiogenesis, apoptosis, and tumor volume in mouse 4T1 breast tumor model. METHODS: Sixty female BALB/c mice were randomly divided into 4 groups: control, dietary soy isoflavone extract [Iso, 100 mg/kg diet (0.01%)], Docetaxel (10 mg/kg) injection, and the combination of dietary soy isoflavone extract and intravenous Docetaxel injection (Docetaxel + Iso)...
September 22, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28937624/therapeutic-mechanisms-of-vernonia-amygdalina-delile-in-the-treatment-of-prostate-cancer
#14
William Johnson, Paul B Tchounwou, Clement G Yedjou
Prostate cancer patients have been suffering from limited treatment options due to late diagnosis, poor drug tolerance, and multi-drug resistance to almost all the current drug treatments. Therefore, it is important to seek a new alternative therapeutic medicine that can effectively prevent the disease and even eradicate the progression and metastasis of prostate cancer. Vernonia amygdalina Delile (VAD) is a common edible vegetable in Cameroon that has been used as a traditional medicine for some human diseases...
September 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28937214/injectable-thermoresponsive-hydrogel-formed-by-alginate-g-poly-n-isopropylacrylamide-releasing-doxorubicin-encapsulated-micelles-as-smart-drug-delivery-system
#15
Min Liu, Xia Song, Yuting Wen, Jing-Ling Zhu, Jun Li
In this work, we have synthesized a thermoresponsive copolymer, alginate-g-poly(N-isopropylacrylamide) (alginate-g-PNIPAAm), by conjugating PNIPAAm to alginate, where PNIPAAm with different molecular weight and narrow molecular weight distribution was synthesized by atomic transfer radical polymerization (ATRP). The copolymer dissolved in water or PBS buffer solution at room temperature, and formed self-assembled micelles with low critical micellization concentrations when temperature increased to above their critical micellization temperatures...
September 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28936957/-pk-pd-of-vancomycin-in-patients-with-severe-acute-pancreatitis-combined-with-augmented-renal-clearance
#16
Juan He, Enqiang Mao, Feng Jing, Huiting Jiang, Wenyun Xu, Wanhua Yang, Erzhen Chen
OBJECTIVE: To evaluate the serum trough concentration and the pharmacokinetics/pharmacodynamics (PK/PD) of vancomycin in patients with severe acute pancreatitis (SAP), and analyze the effect of vancomycin continuous infusion for optimizing the characteristics of its PK/PD. METHODS: The inhospital patients with SAP received vancomycin treatment and admitted to emergency intensive care unit (EICU) of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2011 to December 2016 were enrolled...
September 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28936924/expression-of-cross-tolerance-to-a-wide-range-of-conditions-in-a-human-lung-cancer-cell-line-after-adaptation-to-nitric-oxide
#17
Zane Deliu, Timothy Tamas, Juel Chowdhury, Madeeha Aqil, Maaly Bassiony, James A Radosevich
Previously, we have shown that A549, a human lung adenocarcinoma, can be adapted to nitric oxide (NO(●)). NO(●) is a nitrogen-based free radical that is synthesized by a family of enzymes known as nitric oxide synthases. NO(●) has been shown to be overexpressed in patient populations of different cancers. In addition, it has been observed that patients who express high levels of nitric oxide synthases tend to have poorer clinical outcomes than those with low levels of expression. The original cell line A549 (parent) and the adapted A549-HNO (high nitric oxide) cell line serve as a useful model system to investigate the role of NO(●) in tumor progression and prognosis...
September 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28936851/-research-of-reversal-effect-of-pesv-to-multi-drug-resistance-of-leukemia-stem-cell
#18
Xiang-Dong Yang, Xing-Li Wang, Wen-Hua Yang, Lei Zhao, Tian-Gai Yan
Using the BALB/c mouse multidrug resistance model of leukemia, the effect of peptide extract from scorpion venom (PESV) to the upstream signal factors of P-gp of MDR leukemia stem cells on the mouse tumor block was observed, and the mechanism of PESV to reverse the MDR of LSC was studied. At the same time, the expression of P-gp, MDR1 mRNA and PI3-K, NF-κB were respectively detected through flow cytometry, RT-PCR, Western blot and Elisa, and the mouse liver, spleen were examined via histopathological methods...
December 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28936796/biosurfactants-produced-by-bacillus-subtilis-a1-and-pseudomonas-stutzeri-na3-reduce-longevity-and-fecundity-of-anopheles-stephensi-and-show-high-toxicity-against-young-instars
#19
Punniyakotti Parthipan, Raja Kumaresan Sarankumar, Anitha Jaganathan, Pandian Amuthavalli, Ranganathan Babujanarthanam, Pattanathu K S M Rahman, Kadarkarai Murugan, Akon Higuchi, Giovanni Benelli, Aruliah Rajasekar
Anopheles stephensi acts as vector of Plasmodium parasites, which are responsible for malaria in tropical and subtropical areas worldwide. Currently, malaria management is a big challenge due to the presence of insecticide-resistant strains as well as to the development of Plasmodium species highly resistant to major antimalarial drugs. Therefore, the present study focused on biosurfactant produced by two bacteria Bacillus subtilis A1 and Pseudomonas stutzeri NA3, evaluating them for insecticidal applications against malaria mosquitoes...
September 21, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28936409/current-scenario-of-hepatitis-b-and-its-treatment-in-india
#20
REVIEW
Gautam Ray
Hepatitis B is a significant public health problem in India, yet disease awareness is very low among the general population. The disease is mostly acquired horizontally, but the role of vertical transmission should not be underestimated. In spite of the fact that the majority of cases are e negative disease, most patients present in the advanced stage and even with hepatocellular carcinoma, the leading cause of which is hepatitis B. High-risk groups (especially tribals) also harbour significant disease burden and have a high prevalence of occult infection, supporting the potential of unknowingly spreading the disease...
September 28, 2017: Journal of Clinical and Translational Hepatology
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