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https://www.readbyqxmd.com/read/28732382/novel-strategies-to-prevent-the-development-of-multidrug-resistance-mdr-in-cancer
#1
REVIEW
Jinglu Wang, Nicole Seebacher, Huirong Shi, Quancheng Kan, Zhenfeng Duan
The development of multidrug resistance (MDR) is one of the major challenges to the success of traditional chemotherapy treatment in cancer patients. Most studies to date have focused on strategies to reverse MDR following its development. However, agents utilizing this approach have proven to be of limited clinical use, failing to demonstrate an improvement in therapeutic efficacy with almost no significant survival benefits observed in cancer clinical trials. An alternative approach that has been applied is to prevent or delay MDR prior or early in its development...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732245/interleukin-4-receptor-targeted-delivery-of-bcl-xl-sirna-sensitizes-tumors-to-chemotherapy-and-inhibits-tumor-growth
#2
Padmanaban Guruprasath, Jihoon Kim, Gowri Rangaswamy Gunassekaran, Lianhua Chi, Soyoun Kim, Rang-Woon Park, Sang-Hyun Kim, Moon-Chang Baek, Sang Mun Bae, Sang-Yeob Kim, Dong-Kyu Kim, In-Kyu Park, Won-Jong Kim, Byungheon Lee
IL-4 receptor (IL-4R) is commonly up-regulated on tumor cells, and interactions between the receptor and Interleukin-4 (IL-4) can induce the expression of anti-apoptotic proteins, including Bcl-xL. This contributes to tumor cell survival and their resistance to chemotherapy. In this study, we exploited IL-4R-targeted delivery of Bcl-xL siRNA to IL-4R-expressing tumor cells in order to sensitize them to chemotherapy. To target IL-4R, an IL-4R-binding peptide, IL4RPep-1, was attached to branched polyethyleneimine-superparamagnetic iron oxide nanoparticles (BPEI-SPION)...
July 15, 2017: Biomaterials
https://www.readbyqxmd.com/read/28731456/upregulation-of-tet-activity-with-ascorbic-acid-induces-epigenetic-modulation-of-lymphoma-cells
#3
N Shenoy, T Bhagat, E Nieves, M Stenson, J Lawson, G S Choudhary, T Habermann, G Nowakowski, R Singh, X Wu, A Verma, T E Witzig
The Ten Eleven Translocation (TET) enzymes have been found to be mutated in both diffuse large B-cell (DLBCL) and peripheral T-cell (PTCL) lymphomas resulting in DNA hypermethylation. Recent studies in embryonal stem cells showed that ascorbic acid (AA) is a cofactor for TET with a binding site at the catalytic domain, and enhances TET activity. We hypothesized that AA could potentially enhance TET activity in lymphoma cells to cause DNA demethylation, reactivate expression of tumor suppressor genes and enhance chemosensitivity...
July 21, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28731185/snail-maintains-metastatic-potential-cancer-stem-like-properties-and-chemoresistance-in-mesenchymal-mouse-breast-cancer-tubo%C3%A2-p2j-cells
#4
Sun Young Ma, Jin-Hee Park, Hana Jung, Sung-Min Ha, Yeonye Kim, Dong Hyen Park, Deuk Hee Lee, Sooyong Lee, In-Ho Chu, So Young Jung, Il-Hwan Kim, Il-Whan Choi, Chang Soo Choi, Saegwang Park
Snail, a zinc-finger transcriptional repressor of E-cadherin expression, is one of the key inducers of epithelial-mesenchymal transition (EMT) in epithelial cancer. In breast cancer, EMT has been associated with malignancies, including metastasis, cancer stem-like properties, and resistance to chemotherapy and radiotherapy. In this study, we analysed the role of Snail in the highly metastatic mesenchymal TUBO‑P2J mouse breast cancer cells, by loss of function using short hairpin RNA. Though silencing Snail did not restore the E-cadherin expression or induce morphological changes, Snail silencing significantly ablated in vitro and in vivo metastatic potentials...
July 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28731184/bufalin-reverses-acquired-drug-resistance-by-inhibiting-stemness-in-colorectal-cancer-cells
#5
Jian Sun, Ke Xu, Yanyan Qiu, Hong Gao, Jianhua Xu, Qingfeng Tang, Peihao Yin
Drug resistance is an obstacle to chemotherapy in tumor patients. Recent studies have shown that the high stemness of cancer cells may be induced by chemotherapeutic drugs, which is correlated with drug resistance. In the present study, we investigated the effects of bufalin on the stemness of colorectal cancer. We found that cisplatin could induce high stemness through the tumorsphere formation assay in vitro and in vivo in the colorectal cancer cell lines HCT116 and LoVo. In addition, cisplatin-treated tumorsphere cells showed drug‑resistant properties...
July 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28731151/meg3-is-a-prognostic-factor-for-crc-and-promotes-chemosensitivity-by-enhancing-oxaliplatin-induced-cell-apoptosis
#6
Lixia Li, Jian Shang, Yupeng Zhang, Shi Liu, Yanan Peng, Zhou Zhou, Huaqing Pan, Xiaobing Wang, Lipng Chen, Qiu Zhao
A major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to oxaliplatin-based chemotherapy. Recently, studies have shown that long non-coding RNAs (lncRNAs) play an important role in drug resistance. Using HiSeq sequencing methods, we identified that lncRNAs show differential expression levels in oxaliplatin-resistant (OxR) and non-resistant CRC patients. RT-qPCR was then performed in tissues and serum samples, and lncRNA MEG3 was verified to be downregulated in non-responding patients and to have considerable discriminating potential to identify responding patients from non-responding patients...
July 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28731137/phosphorylation-of-bcl-2-plays-an-important-role-in-glycochenodeoxycholate-induced-survival-and-chemoresistance-in-hcc
#7
Maojun Zhou, Qi Zhang, Jinfeng Zhao, Mingmei Liao, Sailan Wen, Manyi Yang
Hepatocellular carcinoma (HCC) is a highly malignant tumor and can evolve rapidly to resistance to chemotherapies. Glycochenodeoxycholate (GCDA), which is toxic and hydrophobic, is the main ingredient in the bile and associated with carcinogenesis of gastrointenstinal tumors. Bcl-2 is the most important anti-apoptotic protein and overexpressed in various human tumors. In the present study, we found that GCDA can induce the chemoresistance of human liver cancer cells and specific depletion of Bcl-2 by RNA interference blocks GCDA-stimulated chemoresistance, which indicate the pivotal role of Bcl-2 in such process...
July 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28730960/protein-kinases-as-tumor-biomarkers-and-therapeutic-targets
#8
Chuntao Quan, Juanjuan Xiao, Lin Liu, Qiuhong Duan, Ping Yuan, Feng Zhu
Over the last three decades, neoplasms have become the largest cause of human mortality due to both high tumor incidence and mortality. Chemotherapy is one of the main therapies employed to treat neoplasms. Although classical genotoxic drugs, such as cyclophosphamide, 5-FU, cisplatin and doxorubicin have been applied in clinical settings and have achieved very good treatment efficacy, many cancer patients died of tumor metastasis, drug toxicity or drug resistance due to tumor heterogeneity. Targeted molecular treatments based on the genes, receptors, and kinases expressed by a tumor make individualized treatment possible...
July 20, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28730758/platinum-derivatives-a-multidisciplinary-approach
#9
Sinziana Gheorghe-Cetean, Calin Cainap, Luminita Oprean, Adriana Hangan, Piroska Virag, Eva Fischer-Fodor, Alexandra Gherman, Simona Cainap, Anne-Marie Constantin, Istvan Laszlo, Catalin Vlad, Radu Oprean
Cancer is one of the most difficult diseases to be treated. The particularities regarding the tumors' occurrence mechanism, their evolution under chemotherapy, disease-free interval, but also the increasing number of patients make cancer an intensively studied health domain. Although introduced in therapy since the early 80s, platinum derivatives play an essential role in anticancer therapy. Their use in therapy resulted in improving the patient quality of life and prolonging disease-free interval, which makes them still a benchmark for other anticancer compounds...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28729771/microarray-gene-expression-analysis-of-chemosensitivity-for-docetaxel-cisplatin-and-5-fluorouracil-tpf-combined-chemotherapeutic-regimen-in-hypopharyngeal-squamous-cell-carcinoma
#10
Meng Lian, Haizhou Wang, Jugao Fang, Jie Zhai, Ru Wang, Xixi Shen, Yifan Yang, Zhihong Ma, Honggang Liu
OBJECTIVE: To screen out a set of candidate genes which could help to determine whether patients with hypopharyngeal squamous cell carcinoma (HSCC) could benefit from docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy. METHODS: Gene-expression profiles in 12 TPF-sensitive patients were compared to 9 resistant controls by microarray analysis. Subsequently, expression levels of potential biomarkers in chemosensitive cell line FaDu after TPF treatment were observed by quantitative real-time polymerase chain reaction (qRT-PCR)...
June 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/28729402/wilms-tumor-ncam-expressing-cancer-stem-cells-as-potential-therapeutic-target-for-polymeric-nanomedicine
#11
Ela Markovsky, Einav Vax, Dikla Ben-Shushan, Anat Eldar-Boock, Rachel Shukrun, Eilam Yeini, Iris Barshack, Revital Caspi, Orit Harari-Steinberg, Naomi Pode-Shakked, Benjamin Dekel, Ronit Satchi-Fainaro
Cancer stem cells (CSC) form a specific population within the tumor that has been shown to have self-renewal and differentiation properties, increased ability to migrate and form metastases, and increased resistance to chemotherapy. Consequently, even a small number of cells remaining after therapy can repopulate the tumor and cause recurrence of the disease. CSCs in Wilms tumor, a pediatric renal cancer, were previously shown to be characterized by neural cell adhesion molecule (NCAM) expression. Therefore, NCAM provides a specific biomarker through which the CSC population in this tumor can be targeted...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28729067/real-world-characteristics-and-outcomes-of-patients-with-metastatic-castration-resistant-prostate-cancer-receiving-chemotherapy-versus-androgen-receptor-targeted-therapy-after-failure-of-first-line-androgen-receptor-targeted-therapy-in-the-community-setting
#12
William K Oh, Raymond Miao, Francis Vekeman, Jennifer Sung, Wendy Y Cheng, Marjolaine Gauthier-Loiselle, Ravinder Dhawan, Mei Sheng Duh
BACKGROUND: In metastatic castration-resistant prostate cancer (mCRPC), optimal treatment sequences are unknown. We assessed second-line taxane (TT) versus androgen receptor-targeted therapy (ART), after initial ART failure, in United States oncology community practices. PATIENTS AND METHODS: Using electronic medical records, patients with mCRPC receiving first-line ART and second-line therapy (TT, ART) were identified. Response and overall survival (OS) were evaluated from second-line therapy initiation...
June 19, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28729027/micrornas-as-multifaceted-players-in-glioblastoma-multiforme
#13
Neri Mercatelli, Silvia Galardi, Silvia Anna Ciafrè
Glioblastoma multiforme (GBM) is the most common and inevitably lethal primary brain tumor, with a median survival rate of only 15 months from diagnosis. The current standard treatment involves maximal surgical resection flanked by radiotherapy and chemotherapy with the alkylating agent temozolomide. However, even such aggressive treatment is never curative, and recurrent tumors always arise, commonly in more aggressive, chemo- and radio-resistant forms, leading to untreatable and deadly tumors. MicroRNAs, recognized major players in cancer, are deeply involved in GBM, as shown by more than a decade of studies...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28728967/impact-of-the-microbiota-on-bacterial-infections-during-cancer-treatment
#14
REVIEW
Jessica Galloway-Peña, Chelcy Brumlow, Samuel Shelburne
Patients being treated for cancer are at high risk for infectious complications, generally due to colonizing organisms that gain access to sterile sites via disrupted epithelial barriers. There is an emerging understanding that the ability of bacterial pathogens, including multidrug-resistant organisms, to colonize and subsequently infect humans is largely dependent on protective bacterial species present in the microbiome. Thus, herein we review recent studies demonstrating strong correlations between the microbiome of the oncology patient and infections occurring during chemotherapy...
July 17, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28728166/whole-genome-sequencing-revealed-novel-prognostic-biomarkers-and-promising-targets-for-therapy-of-ovarian-clear-cell-carcinoma
#15
Hiroaki Itamochi, Tetsuro Oishi, Nao Oumi, Satoshi Takeuchi, Kosuke Yoshihara, Mikio Mikami, Nobuo Yaegashi, Yasuhisa Terao, Kazuhiro Takehara, Kimio Ushijima, Hidemichi Watari, Daisuke Aoki, Tadashi Kimura, Toshiaki Nakamura, Yoshihito Yokoyama, Junzo Kigawa, Toru Sugiyama
BACKGROUND: Ovarian clear cell carcinoma (OCCC) is mostly resistant to standard chemotherapy that results in poor patient survival. To understand the genetic background of these tumours, we performed whole-genome sequencing of OCCC tumours. METHODS: Tumour tissue samples and matched blood samples were obtained from 55 Japanese women diagnosed with OCCC. Whole-genome sequencing was performed using the Illumina HiSeq platform according to standard protocols. RESULTS: Alterations to the switch/sucrose non-fermentable (SWI/SNF) subunit, the phosphatidylinositol-3-kinase (PI3K)/Akt signalling pathway, and the receptor tyrosine kinase (RTK)/Ras signalling pathway were found in 51%, 42%, and 29% of OCCC tumours, respectively...
July 20, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28726787/alkbh7-drives-a-tissue-and-sex-specific-necrotic-cell-death-response-following-alkylation-induced-damage
#16
Jennifer J Jordan, Sophea Chhim, Carrie M Margulies, Mariacarmela Allocca, Roderick T Bronson, Arne Klungland, Leona D Samson, Dragony Fu
Regulated necrosis has emerged as a major cell death mechanism in response to different forms of physiological and pharmacological stress. The AlkB homolog 7 (ALKBH7) protein is required for regulated cellular necrosis in response to chemotherapeutic alkylating agents but its role within a whole organism is unknown. Here, we show that ALKBH7 modulates alkylation-induced cellular death through a tissue and sex-specific mechanism. At the whole-animal level, we find that ALKBH7 deficiency confers increased resistance to MMS-induced toxicity in male but not female mice...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28726781/autophagy-inhibition-reduces-chemoresistance-and-tumorigenic-potential-of-human-ovarian-cancer-stem-cells
#17
Anna Pagotto, Giorgia Pilotto, Elena Laura Mazzoldi, Maria Ornella Nicoletto, Simona Frezzini, Anna Pastò, Alberto Amadori
Epithelial ovarian cancer (EOC) is one of the most malignant gynecological tumors with a high mortality rate owing to tumor relapse after anticancer therapies. It is widely accepted that a rare tumor cell population, known as cancer stem cells (CSC), is responsible for tumor progression and relapse; intriguingly, these cells are able to survive nutrient starvation (such as in vitro culture in the absence of glucose) and chemotherapy treatment. Recent data also indicated that chemotherapy resistance is associated with autophagy activation...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28726775/oroxylin-a-activates-pkm1-hnf4-alpha-to-induce-hepatoma-differentiation-and-block-cancer-progression
#18
Libin Wei, Yuanyuan Dai, Yuxin Zhou, Zihao He, Jingyue Yao, Li Zhao, Qinglong Guo, Lin Yang
Liver cancer is the second cause of death from cancer worldwide, without effective treatment. Traditional chemotherapy for liver cancer has big side effects for patients, whereas targeted drugs, such as sorafenib, commonly have drug resistance. Oroxylin A (OA) is the main bioactive flavonoids of Scutellariae radix, which has strong anti-hepatoma effect but low toxicity to normal tissue. To date, no differentiation-inducing agents have been reported to exert a curative effect on solid tumors. Here our results demonstrated that OA restrained the proliferation and induced differentiation of hepatoma both in vitro and in vivo, via inducing a high PKM1 (pyruvate kinase M1)/PKM2 (pyruvate kinase M2) ratio...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28725594/weekly-ascorbic-acid-infusion-in-castration-resistant-prostate-cancer-patients-a-single-arm-phase-ii-trial
#19
Torben K Nielsen, Martin Højgaard, Jon T Andersen, Niklas Rye Jørgensen, Bo Zerahn, Bent Kristensen, Trine Henriksen, Jens Lykkesfeldt, Kári J Mikines, Henrik E Poulsen
BACKGROUND: Ascorbic acid (AA) has in vivo cytotoxic properties at concentrations that can only be achieved through intravenous (IV) administration in humans. Treatment with intravenous AA is widely and increasingly used in complementary medicine despite a lack of clinical evidence for the efficacy of this treatment. METHODS: This non-comparative, single-center, phase II trial included patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer (mCRPC) from an outpatient clinic to evaluate the efficacy and safety of IV AA therapy...
June 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28724986/core-shell-lipid-polymer-hybrid-nanoparticles-with-combined-docetaxel-and-molecular-targeted-therapy-for-the-treatment-of-metastatic-prostate-cancer
#20
Qi Wang, Heba Alshaker, Torsten Böhler, Shyam Srivats, Yimin Chao, Colin Cooper, Dmitri Pchejetski
Many prostate cancers relapse after initial chemotherapy treatment. Combining molecular and chemotherapy together with encapsulation of drugs in nanocarriers provides effective drug delivery and toxicity reduction. We developed core shell lipid-polymer hybrid nanoparticles (CSLPHNPs) with poly (lactic-co-glycolic acid) (PLGA) core and lipid layer containing docetaxel and clinically used inhibitor of sphingosine kinase 1 (SK1) FTY720 (fingolimod). We show for the first time that FTY720 (both free and in CSLPHNPs) re-sensitizes castrate resistant prostate cancer cells and tumors to docetaxel, allowing a four-fold reduction in effective dose...
July 19, 2017: Scientific Reports
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