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https://www.readbyqxmd.com/read/28090501/clinical-implications-of-apex1-and-jagged1-as-chemoresistance-factors-in-biliary-tract-cancer
#1
Hong-Beum Kim, Won Jin Cho, Nam Gyu Choi, Sung-Soo Kim, Jun Hee Park, Hee-Jeong Lee, Sang Gon Park
PURPOSE: Biliary cancer is a highly malignant neoplasm with poor prognosis and most patients need to undergo palliative chemotherapy, however major clinical problem associated with the use of chemotherapy is chemoresistance. So far, we aimed at investigating clinical implications of apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) and Jagged1 as chemoresistance factors in biliary tract cancer. METHODS: We used 5 human biliary tract cancer cell lines (SNU-245, SNU-308, SNU-478, SNU-1079, and SNU-1196), and investigated the chemosensitivity of APEX1 and Jagged1 through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and Western blot...
January 2017: Annals of Surgical Treatment and Research
https://www.readbyqxmd.com/read/28090321/gm-csf-signalling-blockade-and-chemotherapeutic-agents-act-in-concert-to-inhibit-the-function-of-myeloid-derived-suppressor-cells-in-vitro
#2
Tessa Gargett, Susan N Christo, Timothy R Hercus, Nazim Abbas, Nimit Singhal, Angel F Lopez, Michael P Brown
Immune evasion is a recently defined hallmark of cancer, and immunotherapeutic approaches that stimulate an immune response to tumours are gaining recognition. However tumours may evade the immune response and resist immune-targeted treatment by promoting an immune-suppressive environment and stimulating the differentiation or recruitment of immunosuppressive cells. Myeloid-derived suppressor cells (MDSC) have been identified in a range of cancers and are often associated with tumour progression and poor patient outcomes...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28089756/glycan-alteration-imparts-cellular-resistance-to-a-membrane-lytic-anticancer-peptide
#3
Ken Ishikawa, Scott H Medina, Joel P Schneider, Amar J S Klar
Although resistance toward small-molecule chemotherapeutics has been well studied, the potential of tumor cells to avoid destruction by membrane-lytic compounds remains unexplored. Anticancer peptides (ACPs) are a class of such agents that disrupt tumor cell membranes through rapid and non-stereospecific mechanisms, encouraging the perception that cellular resistance toward ACPs is unlikely to occur. We demonstrate that eukaryotic cells can, indeed, develop resistance to the model oncolytic peptide SVS-1, which preferentially disrupts the membranes of cancer cells...
January 9, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28088372/nanoformulation-of-dual-bexarotene-tailed-phospholipid-conjugate-with-high-drug-loading
#4
Ruiyu He, Yawei Du, Longbing Ling, Muhammad Ismail, Yongpeng Hou, Chen Yao, Xinsong Li
Bexarotene (Bex), a synthetic retinoid X receptor-selective activator, has been proved to be an efficacious chemotherapeutic agent. But, its clinical application is limited due to the poor solubility. In this report, dual bexarotene-tailed phospholipid (DBTP) conjugate based nanovesicles were prepared in order to develop new nanoformulation. DBTP conjugate was first synthesized by conjugating two Bex molecules with glycerophosphorylcholine (GPC) through facial esterification. The amphiphilic DBTP nanovesicles were prepared without any additive by reverse-phase evaporation method...
January 11, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28088075/development-of-a-hypoxia-triggered-and-hypoxic-radiosensitized-liposome-as-a-doxorubicin-carrier-to-promote-synergetic-chemo-radio-therapy-for-glioma
#5
Hongmei Liu, Yandong Xie, Yafei Zhang, Yifan Cai, Baiyang Li, Honglin Mao, Yingguo Liu, Jun Lu, Longzhen Zhang, Rutong Yu
The treatment of malignant primary brain tumors is challenging. Concomitant radiochemotherapy has become the standard clinical treatment for malignant glioma, but there are two critical challenges to overcome in order to increase efficacy. First, glioma is known to have increased resistant to radiation due to its intra-tumoral hypoxia. In addition, the blood-brain barrier (BBB) restricts the distribution of the chemotherapeutic agent to the brain. Therefore, we developed a hypoxic radiosensitizer-prodrug liposome (MLP), in order to deliver DOX to the tumor and to overcome the above challenges, achieving a synergistic chemo-/radiotherapy treatment of malignant glioma...
January 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28086948/is-there-still-a-role-for-cytotoxic-chemotherapy-after-targeted-therapy-and-immunotherapy-in-metastatic-melanoma-a-case-report-and-literature-review
#6
Aurélien Simon, Hampig Raphael Kourie, Joseph Kerger
Metastatic melanoma has long been considered to have a very poor prognosis and to be chemo-resistant. However, a subgroup of patients with metastatic melanoma presents remarkable responses to chemotherapeutic agents, even in the absence of a response to modern targeted therapies and immunotherapies; accordingly, determining predictive biomarkers of the response to chemotherapies for metastatic melanoma remains a priority to guide treatment in these patients. We report a case study of a patient with B-Raf proto-oncogene serine/threonine kinase-mutated metastatic melanoma harbouring many genetic mutations...
January 13, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28079003/colorectal-cancer-chemotherapy-the-evolution-of-treatment-and-new-approaches
#7
Rachel M McQuade, Vanesa Stojanovska, Joel C Bornstein, Kulmira Nurgali
Colorectal cancer (CRC) is one the greatest contributors to cancer related mortality. Although 5 year survival rate for patients at the early stage of CRC (stages I and II) is above 60%, more than 50% of patients are diagnosed at or beyond stage III when distant metastasis has already occurred, in which case 5 year survival rate drops to 10%. Chemotherapeutic intervention coupled with surgery is the backbone of metastatic CRC treatment and the only means of enhanced survival. For decades following its discovery, an antimetabolite 5-fluorouracil (5-FU) was the only chemotherapeutic agent available to successfully improve 12 month survival in CRC patients...
January 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28078985/designing-isoform-selective-inhibitors-against-classical-hdacs-for-effective-anticancer-therapy-insight-and-perspectives-from-in-silico
#8
Shabir Ahmad Ganai
Histone deacetylase inhibitors, the small molecules modulating the biological activity of histone deacetylases are emerging as potent chemotherapeutic agents. Despite their considerable therapeutic benefits in disease models, the lack of isoform specificity culminates in debilitating off target effects, raising serious concerns regarding their applicability. This emphasizes the pressing and unmet medical need of designing isoform selective inhibitors for safe and effective anticancer therapy. Keeping these grim facts in view, the current article sheds light on structural basis of off-targeting...
12, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28078375/assessing-intra-arterial-complications-of-planning-and-treatment-angiograms-for-y-90-radioembolization
#9
Osman Ahmed, Mikin V Patel, Abdulrahman Masrani, Bradford Chong, Mohammed Osman, Jordan Tasse, Jayesh Soni, Ulku Cenk Turba, Bulent Arslan
PURPOSE: To report hepatic arterial-related complications encountered during planning and treatment angiograms for radioembolization and understand any potential-associated risk factors. MATERIALS AND METHODS: 518 mapping or treatment angiograms for 180 patients with primary or metastatic disease to the liver treated by Yttrium-90 radioembolization between 2/2010 and 12/2015 were retrospectively reviewed. Intra-procedural complications were recorded per SIR guidelines...
January 11, 2017: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/28076844/sulforaphane-inhibits-cancer-stem-like-cell-properties-and-cisplatin-resistance-through-mir-214-mediated-downregulation-of-c-myc-in-non-small-cell-lung-cancer
#10
Qian-Qian Li, You-Ke Xie, Yue Wu, Lin-Lin Li, Ying Liu, Xiao-Bo Miao, Qiu-Zhen Liu, Kai-Tai Yao, Guang-Hui Xiao
We herein report that sulforaphane (SFN), a potent anti-cancer and well-tolerated dietary compound, inhibits cancer stem-like cell (CSC) properties and enhances therapeutic efficacy of cisplatin in human non-small cell lung cancer (NSCLC). SFN exerted these functions through upregulation of miR-214, which in turn targets the coding region of c-MYC. This finding was further corroborated by our observations that plasmid or lentiviral vector-mediated expression of 3'UTR-less c-MYC cDNA and cisplatin- or doxorubicin-induced endogenous c-MYC accumulation was similarly suppressed by either SFN or miR-214...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076839/chemotherapy-can-induce-weight-normalization-of-morbidly-obese-mice-despite-undiminished-ingestion-of-high-fat-diet
#11
Cheryl E Myers, Dominique B Hoelzinger, Tiffany N Truong, Lindsey A Chew, Arpita Myles, Leena Chaudhuri, Jan B Egan, Jun Liu, Sandra J Gendler, Peter A Cohen
Morbidly obese patients who accomplish substantial weight loss often display a long-term decline in their resting metabolism, causing even relatively restrained caloric intake to trigger a relapse to the obese state. Paradoxically, we observed that morbidly obese mice receiving chemotherapy for cancer experienced spontaneous weight reduction despite unabated ingestion of their high fat diet (HFD). This response to chemotherapy could also be achieved in morbidly obese mice without cancer. Optimally dosed methotrexate (MTX) or cyclophosphamide (CY) enabled the mice to completely and safely normalize their body weight despite continued consumption of obesogenic quantities of HFD...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076683/modulation-of-cytotoxicity-by-transcription-coupled-nucleotide-excision-repair-is-independent-of-the-requirement-for-bioactivation-of-acylfulvene
#12
Claudia Otto, Graciela Spivak, Claudia Marie Nathalie Aloisi, Mirco Menigatti, Hanspeter Nägeli, Philip C Hanawalt, Marina Tanasova, Shana J Sturla
Bioactivation as well as DNA repair affect the susceptibility of cancer cells to the action of DNA-alkylating chemotherapeutic drugs. However, information is limited with regard to the relative contributions of these processes to the biological outcome of metabolically activated DNA alkylating agents. We evaluated the influence of cellular bioactivation capacity and DNA repair on cytotoxicity of the DNA alkylating agent, acylfulvene (AF). We compared cytotoxicity and RNA synthesis inhibition by AF and its synthetic activated analog iso-M0 in a panel of fibroblast cell lines with deficiencies in transcription-coupled (TC-NER) or global genome nucleotide excision repair (GG-NER)...
January 11, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28075477/escin-induces-apoptosis-in-human-renal-cancer-cells-through-g2-m-arrest-and-reactive-oxygen-species-modulated-mitochondrial-pathways
#13
Sheau-Yun Yuan, Chen-Li Cheng, Shian-Shiang Wang, Hao-Chung Ho, Kun-Yuan Chiu, Chuan-Shu Chen, Cheng-Che Chen, Ming-Yuh Shiau, Yen-Chuan Ou
Escin, a natural pentacyclic triterpenoid compound, exhibits antitumor effects on various types of human cancer cells, but its effect on human renal cancer cells has not been fully elucidated. In the present study, we demonstrated that escin elicits cytotoxic effects on human renal cancer cells (786-O and Caki-1) in a dose-dependent manner, as determined by MTT assay. Escin induced G2/M arrest, and then increased the sub-G1 population, Annexin V binding, activation of caspase-9/-3, cleavage of poly(ADP-ribose) polymerase (PARP) and Bax protein...
January 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28075466/co-delivery-of-doxorubicin-and-ph-sensitive-curcumin-prodrug-by-transferrin-targeted-nanoparticles-for-breast-cancer-treatment
#14
Tongxing Cui, Sihao Zhang, Hong Sun
The natural product curcumin and the chemotherapeutic agent doxorubicin have been used in the treatment of many cancers, including breast cancer. However, fast clearance and unspecific distribution in the body after intravenous injection are still challenges to be overcome by an ideal nano-sized drug delivery system in cancer treatment. In this study we design transferrin (Tf) decorated nanoparticles (NPs) to co-deliver CUR and DOX for breast cancer treatment. A pH-sensitive prodrug, transferrin-poly(ethylene glycol)-curcumin (Tf-PEG-CUR), was synthesized and used for the self‑assembling of NPs (Tf-PEG-CUR NPs)...
January 2, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28074721/-capecitabine-induced-ventricular-fibrillation
#15
A V van Capelle, J de Valk, D Schakenraad, T Germans, D Ten Oever
BACKGROUND: Capecitabine is an orally-administered chemotherapeutic agent used in the treatment of colorectal, gastric and breast carcinoma. Capecitabine has relatively mild side effects. Less known are its potential severe cardiotoxic effects. CASE DESCRIPTION: We report a case of a 61-year-old man recently diagnosed with rectal cancer. Six days after starting with capecitabine, he developed a cardiac arrest due to ventricular fibrillation (VF). Extensive additional diagnostics did not explain the cardiac arrest nor VF...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/28073914/serine-threonine-kinase-unc-51-like-kinase-1-ulk1-phosphorylates-the-co-chaperone-cdc37-and-thereby-disrupts-the-stability-of-cdc37-client-proteins
#16
Ran Li, Fengjie Yuan, Wan Fu, Luyao Zhang, Nan Zhang, Yanan Wang, Ke Ma, Xue Li, Lina Wang, Wei-Guo Zhu, Ying Zhao
The serine/threonine kinase Unc-51 like kinase-1 (Ulk1) is thought to be essential for induction of autophagy, an intracellular bulk degradation process that is activated by various stresses. Although several proteins have been suggested as Ulk1 substrates during autophagic process, it still remains largely unknown about Ulk1's physiological substrates. Here, by performing in vitro and in vivo phosphorylation assay, we report that the co-chaperone cell division cycle protein 37 (Cdc37) is an Ulk1 substrate...
January 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28073588/overexpression-of-cytochrome-p450-2a6-in-adrenocortical-carcinoma
#17
Timothy D Murtha, Taylor C Brown, Jill C Rubinstein, Felix Haglund, C Christofer Juhlin, Catharina Larsson, Reju Korah, Tobias Carling
BACKGROUND: Cytochrome P450-mediated metabolism of chemotherapeutic agents contributes to chemotherapy resistance in multiple malignancies. Adrenocortical carcinoma is known to have a poor response to adjuvant therapies; however, the mechanism remains unknown. Recent comprehensive genetic analyses of adrenocortical carcinomas demonstrated recurrent copy number gains in multiple cytochrome P450 genes prompting investigation into whether cytochrome P450 overexpression potentiates adrenocortical carcinoma chemoresistance...
January 7, 2017: Surgery
https://www.readbyqxmd.com/read/28073063/self-assembled-micelles-based-on-chondroitin-sulfate-poly-d-l-lactideco-glycolide-block-copolymers-for-doxorubicin-delivery
#18
Hui Zhang, Jiangkang Xu, Liang Xing, Jianbo Ji, Aihua Yu, Guangxi Zhai
Doxorubicin (DOX) is one of the most common chemotherapeutic agents for the treatment of various cancers, but its clinical usage is limited by dose-dependent cardiotoxicity. We have recently synthesized a series of Chondroitin sulfate/poly (d,l-lactideco-glycolide) block copolymers (Chs-b-PLGA) with different length of hydrophobic block by an end-to-end coupling strategy. The structure of the amphiphilic block copolymers with low critical micelle concentration (∼28mg/L) were confirmed by (1)H NMR. The copolymers could self-assemble into stable micelles in aqueous environment with homogeneous size distribution and negative zeta potential...
December 23, 2016: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28072762/giving-axl-the-axe-targeting-axl-in-human-malignancy
#19
Carl M Gay, Kavitha Balaji, Lauren Averett Byers
The receptor tyrosine kinase AXL, activated by a complex interaction between its ligand growth arrest-specific protein 6 and phosphatidylserine, regulates various vital cellular processes, including proliferation, survival, motility, and immunologic response. Although not implicated as an oncogenic driver itself, AXL, a member of the TYRO3, AXL, and MERTK family of receptor tyrosine kinases, is overexpressed in several haematologic and solid malignancies, including acute myeloid leukaemia, non-small cell lung cancer, gastric and colorectal adenocarcinomas, and breast and prostate cancers...
January 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28072604/epigenetic-upregulation-of-cxcl12-expression-mediates-anti-tubulin-chemotherapeutics-induced-neuropathic-pain
#20
Ting Xu, Xiao-Long Zhang, Han-Dong Ou-Yang, Zhen-Yu Li, Cui-Cui Liu, Zhen-Zhen Huang, Jing Xu, Jia-You Wei, Bi-Lin Nie, Chao Ma, Shao-Ling Wu, Wen-Jun Xin
Clinically, Microtubule-targeted agents-induced neuropathic pain hampers chemotherapeutics for cancer patients. Here, we found that application of paclitaxel or vincristine increased the protein and mRNA expression of CXCL12, and frequency and amplitude of miniature excitatory post synaptic currents (mEPSCs) in spinal dorsal horn neurons. Spinal local application of CXCL12 induced the long-term potentiation (LTP) of nociceptive synaptic transmission and increased the amplitude of mEPSCs. Inhibition of CXCL12 by using the transgenic mice (CXCL12) or neutralizing antibody or siRNA ameliorated the mEPSCs enhancement and mechanical allodynia...
January 7, 2017: Pain
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