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https://www.readbyqxmd.com/read/28334700/single-agent-pixantrone-as-a-bridge-to-autologous-stem-cell-transplantation-in-a-patient-with-refractory-diffuse-large-b-cell-lymphoma
#1
Lorena Appio, Carlo Landoni, Maria La Targia, Vanda Bertolli, Martina Chiarucci, Giovanni Crovetti, Elisabetta Vassenna, Giovanni Serio, Marco Bregni
Aggressive non-Hodgkin lymphoma is associated with poor long-term survival after relapse or resistance to chemotherapy. We report a case of aggressive non-Hodgkin lymphoma refractory to first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and second-line R-DHAP (rituximab, dexamethasone, cytarabine, and cisplatin) chemotherapy treatments. The patient achieved remission with single-agent pixantrone, and received a consolidation with high-dose BEAM (BCNU, etoposide, cytarabine, and melphalan) chemotherapy and autologous stem cell transplantation...
March 24, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28330997/igfbp3-modulates-lung-tumorigenesis-and-cell-growth-through-igf1-signaling
#2
Yong A Wang, Yunguang Sun, Joshua D Palmer, Charalambos Solomides, Li-Ching Huang, Yu Shyr, Adam P Dicker, Bo Lu
Insulin-like growth factor binding protein 3 (IGFBP3) modulates cell growth through IGF-dependent and -independent mechanisms. Reports suggest that the serum levels of IGFBP3 are associated with various cancers and that IGFBP3 expression is significantly decreased in cisplatin (CDDP)-resistant lung cancer cells. Based on these findings, we investigated whether Igfbp3 deficiency accelerates mouse lung tumorigenesis and if expression of IGFBP3 enhances CDDP response by focusing on the IGF1 signaling cascade. To this end, an Igfbp3-null mouse model was generated in combination with KrasG12D to compare the tumor burden...
March 22, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28328815/strobe-compliant-integrin-through-focal-adhesion-involve-in-cancer-stem-cell-and-multidrug-resistance-of-ovarian-cancer
#3
Luwei Wei, Fuqiang Yin, Wei Zhang, Li Li
Cancer stem cells (CSCs) are considered to be the root of carcinoma relapse and drug resistance in ovarian cancer. Hunting for the potential CSC genes and explain their functions would be a feasible strategy to meet the challenge of the drug resistance in ovarian cancer. In this study, we performed bioinformatic approaches such as biochip data extraction and pathway enrichment analyses to elucidate the mechanism of the CSC genes in regulation of drug resistance. Potential key genes, integrins, were identified to be related to CSC in addition to their associations with drug resistance and prognosis in ovarian cancer...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28328082/microrna-488-3p-sensitizes-malignant-melanoma-cells-to-cisplatin-by-targeting-prkdc
#4
Ning Li, Yue Ma, Li Ma, Yu Guan, Liang Ma, Daping Yang
Deregulation of microRNAs (miRNAs) has been implicated in drug resistance in various types of cancers, including malignant melanoma (MM). MiR-488-3p has been reported as a tumor suppressor in several cancers. However, the exact expression patterns of miR-488-3p and the precise molecular mechanisms underlying its role in MM remain largely unknown and require further investigation. In this study, we demonstrated that miR-488-3p is significantly down regulated in MM clinical specimens and cell lines. Ectopic expression of miR-488-3p resulted in markedly increased drug sensitivity of MM cells in vitro and in vivo...
March 22, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28326819/inflammation-and-nitrosative-stress-effects-in-ovarian-and-prostate-pathology-and-carcinogenesis
#5
Amy J Burke, Pablo Garrido, Carol Johnson, Francis J Sullivan, Sharon A Glynn
SIGNIFICANCE: Prostate and ovarian cancers are major contributors to cancer-related deaths worldwide. Recently, inflammation and nitrosative stress have been implicated in carcinogenesis, with the overexpression of NOS2 and concomitant release of nitric oxide (NO) associated with cancer initiation and progression. Recent Advances: An increasing body of evidence indicates an association between NOS2 expression and aggressive ovarian cancer. Research also indicates a role for NO in prostate disease pathology and prostate cancer...
March 22, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28326487/enhanced-stim1-expression-is-associated-with-acquired-chemo-resistance-of-cisplatin-in-osteosarcoma-cells
#6
Xilong Sun, Qiang Wei, Jie Cheng, Yanzhu Bian, Congna Tian, Yujing Hu, Huijie Li
Osteosarcoma is the most common primary malignant bone tumor. Although cisplatin is the primary chemotherapy used in osteosarcoma treatment, the cisplatin resistance remains a big challenge for improving overall survival. The store-operated calcium (Ca(2+)) entry (SOCE) and its major mediator Stim1 have been shown to be implicated in a number of pathological processes typical for cancer. In this study, we showed that Stim1 expression was significantly increased in chemo-resistant osteosarcoma tissues compared with chemo-sensitivity tissues...
March 22, 2017: Human Cell
https://www.readbyqxmd.com/read/28325293/a-pirna-like-small-rna-induces-chemoresistance-to-cisplatin-based-therapy-by-inhibiting-apoptosis-in-lung-squamous-cell-carcinoma
#7
Yuyan Wang, Tyler Gable, Mark Z Ma, David Clark, Jun Zhao, Yi Zhang, Wei Liu, Li Mao, Yuping Mei
Lung cancer is the leading cause of cancer-related death worldwide. Although advanced drugs have benefitted patients, therapeutic success has largely been hampered because of rapid development of resistance. Here we report that PIWI-interacting RNA likes (piR-Ls), a novel type of functional sncRNAs, play key roles in chemoresistance to cisplatin (CDDP)-based chemotherapy in lung squamous cell carcinoma (LSCC). piR-L-138 was upregulated upon CDDP-based chemotherapy both in LSCC cells and in patient-derived xenograft (PDX) LSCC models...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28323036/targeting-androgen-receptor-versus-targeting-androgens-to-suppress-castration-resistant-prostate-cancer
#8
Changcheng Guo, Shuyuan Yeh, Yuanjie Niu, Gonghui Li, Junhua Zheng, Lei Li, Chawnshang Chang
Prostate cancer (PCa) is the 2nd leading cause of cancer-related death among men in the United States and its progression is tightly associated with the androgen/androgen receptor (AR) signals. Men castrated before puberty (eunuchs) or men with inherited deficiency of type II 5α-reductase (with failure to convert testosterone to the more potent dihydrotestosterone) (DHT) do not develop PCa. To date, androgen deprivation therapy (ADT) with anti-androgen treatments to reduce or prevent androgens from binding to the AR remains the main therapeutic option for advanced PCa since its discovery by Huggins and Hodges in 1941...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28319809/abt-737-synergizes-with-cisplatin-bypassing-aberration-of-apoptotic-pathway-in-non-small-cell-lung-cancer
#9
Eun Young Kim, Ji Ye Jung, Arum Kim, Yoon Soo Chang, Se Kyu Kim
A subset of non-small cell lung cancer (NSCLC), which does not have a druggable driver mutation, is treated with platinum-based cytotoxic chemotherapy, but it develops resistance triggered by DNA damage responses. Here, we investigated the effect of activation of STAT3 by cisplatin on anti-apoptotic proteins and the effectiveness of a co-treatment with cisplatin and a BH3 mimetic, ABT-737. We analyzed the relationship between cisplatin and STAT3 pathway and effect of ABT-737, when combined with cisplatin in NSCLC cells and K-ras mutant mouse models...
March 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28319647/cancer-specific-intracellular-reductive-activation-of-anticancer-pt-iv-prodrugs
#10
Andriy Mokhir, Viktor Reshetnikov, Steffen Daum
Since cellular uptake of anticancer Pt(II)- and Pt(IV)-drugs occurs via different mechanisms, the latter ones can exhibit substantial activity towards cells, which have either intrinsic or acquired resistance towards Pt(II)-drugs. However, this positive effect is diminished due to reductive activation of Pt(IV)-drugs in extracellular space that can be one of the reasons why they were not yet approved for clinical use despite over 60 clinical trials conducted worldwide. Herein we suggest a solution to this problem by achieving highly specific intracellular versus extracellular prodrug reduction...
March 20, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28315871/effects-of-glycyrrhizin-in-a-mouse-model-of-lung-adenocarcinoma
#11
Qing-Ping Deng, Mao-Jie Wang, Xing Zeng, George Gong Chen, Run-Yue Huang
BACKGROUND: Currently, there is a global attempt to identify potential anti-cancer agents with low toxicity. Previous studies have found that glycyrrhizin exerts anti-cancer action with low toxicity through suppressing thromboxane A2 (TxA2) in lung cancer cell lines. However, these effects have not yet been determined in animal models of lung cancer. METHODS: Human lung adenocarcinoma xenografts were established in nude mice by the introduction of A549 cells with stable transfection of the TxA2 receptor (TPα)...
March 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28315428/p53-modulates-the-effect-of-ribosomal-protein-s6-kinase1-s6k1-on-cisplatin-toxicity-in-chronic-myeloid-leukemia-cells
#12
Ling-Yi Xiao, Wai-Ming Kan
Chronic myeloid leukemia (CML) is characterized by the expression of the oncoprotein, BCR-ABL. BCR-ABL inhibitors revolutionized CML chemotherapy while blast crisis (BC) CML patients are less responsive. Since suppression of ribosomal protein S6 kinase1 (S6K1) phosphorylation reverses the resistance to BCR-ABL inhibitor in CML cells and S6K1 inhibitors augment cisplatin toxicity in lung cancer cells, we speculated that combination of S6K1 inhibitor and cisplatin may be beneficial for eliminating BC CML cells...
March 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28301876/autophagy-inhibitor-chloroquine-increases-sensitivity-to-cisplatin-in-qbc939-cholangiocarcinoma-cells-by-mitochondrial-ros
#13
Xianzhi Qu, Jiyao Sheng, Luyan Shen, Jing Su, Yunjie Xu, Qi Xie, Yao Wu, Xuewen Zhang, Liankun Sun
The tumor cells have some metabolic characteristics of the original tissues, and the metabolism of the tumor cells is closely related to autophagy. However, the mechanism of autophagy and metabolism in chemotherapeutic drug resistance is still poorly understood. In this study, we investigated the role and mechanism of autophagy and glucose metabolism in chemotherapeutic drug resistance by using cholangiocarcinoma QBC939 cells with primary cisplatin resistance and hepatocellular carcinoma HepG2 cells. We found that QBC939 cells with cisplatin resistance had a higher capacity for glucose uptake, consumption, and lactic acid generation, and higher activity of the pentose phosphate pathway compared with HepG2 cells, and the activity of PPP was further increased after cisplatin treatment in QBC939 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28293855/growth-hormone-receptor-knockdown-sensitizes-human-melanoma-cells-to-chemotherapy-by-attenuating-expression-of-abc-drug-efflux-pumps
#14
Reetobrata Basu, Nicholas Baumgaertel, Shiyong Wu, John J Kopchick
Melanoma remains one of the most therapy-resistant forms of human cancer despite recent introductions of highly efficacious targeted therapies. The intrinsic therapy resistance of human melanoma is largely due to abundant expression of a repertoire of xenobiotic efflux pumps of the ATP-binding cassette (ABC) transporter family. Here, we report that GH action is a key mediator of chemotherapeutic resistance in human melanoma cells. We investigated multiple ABC efflux pumps (ABCB1, ABCB5, ABCB8, ABCC1, ABCC2, ABCG1, and ABCG2) reportedly associated with melanoma drug resistance in different human melanoma cells and tested the efficacy of five different anti-cancer compounds (cisplatin, doxorubicin, oridonin, paclitaxel, vemurafenib) with decreased GH action...
March 14, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28291769/downregulation-of-mir-33a-5p-in-hepatocellular-carcinoma-a-possible-mechanism-for-chemotherapy-resistance
#15
Wei Meng, Yan Tai, Hui Zhao, Binsheng Fu, Tong Zhang, Wei Liu, Hua Li, Yang Yang, Qi Zhang, Yuliang Feng, Guihua Chen
BACKGROUND Multi-drug resistance is one of the major problems limiting the efficacy of cisplatin (CDDP) in treatment of hepatocellular carcinoma (HCC), and abnormal microRNA (miRNA) expression in drug-resistant cell lines plays an important role in liver cancer chemotherapy resistance. MATERIAL AND METHODS We established stable Hep3B and 97L HCC cell strains resistant to CDDP, both in vitro and in vivo. A combination of microRNA microarray and RT-qPCR experiments were used to screen differentially expressed miRNAs in HCC cell strains...
March 14, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28290714/polymeric-micelles-for-targeted-tumor-therapy-of-platinum-anticancer-drugs
#16
Yuki Mochida, Horacio Cabral, Kazunori Kataoka
Platinum anticancer drugs are effective against a wide range of tumors, though their severe adverse effects and resistance remain unresolved. A breakthrough in these drawbacks could be achieved by using polymeric micelles, i.e. nanoassemblies having a drug loaded core and a protective hydrophilic shell, incorporating platinum drugs for tumor-targeted delivery. Areas covered: The development of cisplatin- (NC-6004) and DACHPt-loaded micelles (NC-4016) has been reviewed, particularly, from the viewpoint of the effect of their structural features on the tumor-targeting efficacy...
March 14, 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/28288821/reversal-of-cisplatin-resistance-in-human-gastric-cancer-cells-by-a-wogonin-conjugated-pt-iv-prodrug-via-attenuating-casein-kinase-2-mediated-nuclear-factor-%C3%AE%C2%BAb-pathways
#17
Feihong Chen, Xiaodong Qin, Gang Xu, Shaohua Gou, Xiufeng Jin
Pt(IV) prodrugs, with two additional coordination sites in contrast to Pt(II) drugs, have been actively studied nowadays, for they can perform well in enhancing the accumulation and retention of the corresponding Pt(II) drugs in cancer cells. Our designed Pt(II) drug, DN604, was recently found to exhibit significant anticancer activity and low toxicity. While, wogonin, a naturally O-methylated flavones, has been widely investigated for its tumor therapeutic potential. Thus, two Pt(IV)-based prodrugs were derived by addition of a wogonin unit to the axial position of DN604 and its analogue DN603 via a linker group...
March 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28286209/esophageal-adenocarcinoma-cells-and-xenograft-tumors-exposed-to-erb-b2-receptor-tyrosine-kinase-2-and-3-inhibitors-activate-transforming-growth-factor-beta-signaling-which-induces-epithelial-to-mesenchymal-transition
#18
Eva A Ebbing, Anne Steins, Evelyn Fessler, Phylicia Stathi, Willem Joost Lesterhuis, Kausilia K Krishnadath, Louis Vermeulen, Jan Paul Medema, Maarten F Bijlsma, Hanneke W M van Laarhoven
BACKGROUND & AIMS: Drugs that inhibit the erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2) are the standard treatment of patients with different types of cancer, including HER2-overexpressing gastroesophageal tumors. Unfortunately, cancer cells become resistant to these drugs, so overall these drugs provide little benefit to patients with these tumors. We investigated mechanisms that mediate resistance of esophageal adenocarcinoma (EAC) cells and patient-derived xenograft (PDX) tumors to ERBB inhibitors...
March 9, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28285905/targeting-bmi1-cancer-stem-cells-overcomes-chemoresistance-and-inhibits-metastases-in-squamous-cell-carcinoma
#19
Demeng Chen, Mansi Wu, Yang Li, Insoon Chang, Quan Yuan, Mari Ekimyan-Salvo, Peng Deng, Bo Yu, Yongxin Yu, Jiaqiang Dong, John M Szymanski, Sivakumar Ramadoss, Jiong Li, Cun-Yu Wang
Squamous cell carcinoma in the head and neck (HNSCC) is a common yet poorly understood cancer, with adverse clinical outcomes due to treatment resistance, recurrence, and metastasis. Putative cancer stem cells (CSCs) have been identified in HNSCC, and BMI1 expression has been linked to these phenotypes, but optimal treatment strategies to overcome chemotherapeutic resistance and eliminate metastases have not yet been identified. Here we show through lineage tracing and genetic ablation that BMI1(+) CSCs mediate invasive growth and cervical lymph node metastasis in a mouse model of HNSCC...
March 8, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28285878/stem-cell-factors-based-identification-and-functional-properties-of-in%C3%A2-vitro-selected-subpopulations-of-malignant-mesothelioma-cells
#20
Walter Blum, László Pecze, Emanuela Felley-Bosco, Licun Wu, Marc de Perrot, Beat Schwaller
Malignant mesothelioma (MM) is an aggressive neoplasm characterized by a poor patient survival rate, because of rapid tumor recurrence following first-line therapy. Cancer stem cells (CSCs) are assumed to be responsible for initiating tumorigenesis and driving relapse after therapeutic interventions. CSC-enriched MM cell subpopulations were identified by an OCT4/SOX2 reporter approach and were characterized by (1) increased resistance to cisplatin, (2) increased sensitivity toward the FAK inhibitor VS-6063 in vitro, and (3) a higher tumor-initiating capacity in vivo in orthotopic xenograft and allograft mouse models...
March 9, 2017: Stem Cell Reports
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