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Molecular analysis of chemotherapy resistance

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https://www.readbyqxmd.com/read/28190862/acute-myeloid-leukemia-with-t-3-21-q13-q22-a-novel-simple-variant-of-the-21q22-runx1-translocation
#1
Yuka Tsuruoka, Hirotaka Sakai, Akiko Uchida, Yu Uemura, Kazuyuki Sato, Satoshi Yokoi, Yuji Nishio, Manabu Matsunawa, Yoshinori Suzuki, Yasushi Isobe, Masayuki Kato, Naoto Tomita, Yasuyuki Inoue, Ikuo Miura
A 69-year-old man diagnosed with leukocytosis was referred to our hospital in July 201X. The patient was diagnosed as having a myelodysplastic/myeloproliferative neoplasm. However, he presented with leukemia 2 months later. Chromosomal analysis of a bone marrow sample documented that this patient had a normal karyotype. The patient was successfully treated with idarubicin and cytarabine, and he underwent three courses of consolidation therapy. However, he suffered a relapse in May of the following year. A cytogenetic analysis revealed the presence of a t (3;21) (q13;q22) translocation, and fluorescence in situ hybridization of metaphase spreads detected three signals corresponding to the runt related transcription factor 1 (RUNX1) on the derivative chromosomes 3 and 21, besides the normal chromosome 21...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28187748/characterization-of-ovarian-clear-cell-carcinoma-using-target-drug-based-molecular-biomarkers-implications-for-personalized-cancer-therapy
#2
Mengjiao Li, Haoran Li, Fei Liu, Rui Bi, Xiaoyu Tu, Lihua Chen, Shuang Ye, Xi Cheng
BACKGROUND: It has long been appreciated that different subtypes (serous, clear cell, endometrioid and mucinous) of epithelial ovarian carcinoma (EOC) have distinct pathogenetic pathways. However, clinical management, especially chemotherapeutic regimens, for EOC patients is not subtype specific. Ovarian clear cell carcinoma (CCC) is a rare histological subtype of EOC, which exhibits high rates of recurrence and low chemosensitivity. We assessed potential therapeutic targets for ovarian CCC patients through analyzing the variation of drug-based molecular biomarkers expression between ovarian CCC and high-grade serous carcinoma (HGSC)...
February 10, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28186990/ube2l6-ubch8-and-isg15-attenuate-autophagy-in-esophageal-cancer-cells
#3
Chloe M Falvey, Tracey R O'Donovan, Shereen El-Mashed, Michelle J Nyhan, Seamus O'Reilly, Sharon L McKenna
Esophageal cancer remains a poor prognosis cancer due to advanced stage of presentation and drug resistant disease. To understand the molecular mechanisms influencing response to chemotherapy, we examined genes that are differentially expressed between drug sensitive, apoptosis competent esophageal cancer cells (OE21, OE33, FLO-1) and those which are more resistant and do not exhibit apoptosis (KYSE450 and OE19). Members of the ISG15 (ubiquitin-like) protein modification pathway, including UBE2L6 and ISG15, were found to be more highly expressed in the drug sensitive cell lines...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28154324/novel-mechanisms-of-resistance-to-investigational-molecularly-targeted-drugs
#4
Kohji Noguchi
 Drug resistance is a critical problem inhibiting the effective use of targeted molecular cancer therapies. Investigators have revealed a variety of resistance mechanisms, including alterations in drug targets, activation of pro-survival pathways, and the ineffective induction of cell death. The key alterations driving this resistance are likely condition-dependent, and a detailed analysis would be required to characterize these diverse alterations under a variety of conditions in order to facilitate practical precision medicine for treating individual cancer patients...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28153049/longitudinal-analysis-of-treatment-induced-genomic-alterations-in-gliomas
#5
E Zeynep Erson-Omay, Octavian Henegariu, S Bülent Omay, Akdes Serin Harmancı, Mark W Youngblood, Ketu Mishra-Gorur, Jie Li, Koray Özduman, Geneive Carrión-Grant, Victoria E Clark, Caner Çağlar, Mehmet Bakırcıoğlu, M Necmettin Pamir, Viviane Tabar, Alexander O Vortmeyer, Kaya Bilguvar, Katsuhito Yasuno, Lisa M DeAngelis, Joachim M Baehring, Jennifer Moliterno, Murat Günel
BACKGROUND: Glioblastoma multiforme (GBM) constitutes nearly half of all malignant brain tumors and has a median survival of 15 months. The standard treatment for these lesions includes maximal resection, radiotherapy, and chemotherapy; however, individual tumors display immense variability in their response to these approaches. Genomic techniques such as whole-exome sequencing (WES) provide an opportunity to understand the molecular basis of this variability. METHODS: Here, we report WES-guided treatment of a patient with a primary GBM and two subsequent recurrences, demonstrating the dynamic nature of treatment-induced molecular changes and their implications for clinical decision-making...
February 2, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28133295/-a-systematic-analysis-of-oncogene-and-tumor-suppressor-genes-for-panitumumab-resistant-rectal-cancer-with-wild-ras-gene-a-case-report
#6
Yosuke Tajima, Yoshifumi Shimada, Ryoma Yagi, Takuma Okamura, Masato Nakano, Hitoshi Kameyama, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Kohei Miura, Hiroshi Ichikawa, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Toshifumi Wakai
A 58-year-old man was admitted with the complaint of bloody stools. Colonoscopy and computed tomography revealed a rectal cancer with a liver metastasis and multiple lung metastases. After administering a regimen comprising 3 courses of XELOX plus bevacizumab chemotherapy, the sizes of the primary and metastatic lesions decreased remarkably. Abdominoperineal resection was performed for local control of the cancer; the specimen from the initial tumor was found to be KRAS wild type. After 14 courses of XELOX chemotherapy, brain metastases were detected...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28132960/selective-targeting-of-cancer-stem-cells-by-2-aminodihydroquinoline-analogs
#7
Heejoo Park, Yeongji Yu, Hyejin Kim, Eun Lee, Hani Lee, Raok Jeon, Woo-Young Kim
Many aminodihydroquinoline compounds have been studied to determine their cytotoxicity to cancer cells. However, anti- cancer stem cells (CSCs) activity of aminodihydroquinoline has not been tested in spite that CSC is believed to do an important roles in chemotherapy resistance and recurrence. The CSC selective targeting activities of 10 recently synthesized 2-aminodihydroquinoline analogs were examined on CSCs and bulk culture of a glioblastoma cell line. A diethylaminopropyl substituted aminodihydroquinoline, 5h, showed a strong anti-CSC effect and general cytotoxicity...
January 27, 2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28125325/in-vivo-gene-expression-profiling-for-chemosensitivity-to-docetaxel-cisplatin-5-fu-tpf-triplet-regimen-in-laryngeal-squamous-cell-carcinoma-and-the-effect-of-tpf-treatment-on-related-gene-expression-in-vitro
#8
Meng Lian, Qian Shi, Jugao Fang, Ling Feng, Hongzhi Ma, Haizhou Wang, Liang Zhang, Hong Wang, Zhihong Ma, Honggang Liu
CONCLUSION: These results provided a battery of genes relating to TPF chemotherapeutic sensitivity and might act as molecular targets in laryngeal squamous cell carcinoma (LSCC) treatment. Moreover, these candidate biomarkers could contribute to LSCC individualized treatment. OBJECTIVES: To screen out a set of candidate genes which could help to determine whether patients with LSCC could benefit from TPF induction chemotherapy. METHOD: Gene-expression profiles in seven TPF-sensitive patients were compared to four resistant controls by microarray analysis...
January 26, 2017: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/28106782/from-clinical-standards-to-translating-next-generation-sequencing-research-into-patient-care-improvement-for-hepatobiliary-and-pancreatic-cancers
#9
REVIEW
Ioannis D Kyrochristos, Georgios K Glantzounis, Demosthenes E Ziogas, Ioannis Gizas, Dimitrios Schizas, Efstathios G Lykoudis, Evangelos Felekouras, Anastasios Machairas, Christos Katsios, Theodoros Liakakos, William C Cho, Dimitrios H Roukos
Hepatobiliary and pancreatic (HBP) cancers are associated with high cancer-related death rates. Surgery aiming for complete tumor resection (R0) remains the cornerstone of the treatment for HBP cancers. The current progress in the adjuvant treatment is quite slow, with gemcitabine chemotherapy available only for pancreatic ductal adenocarcinoma (PDA). In the advanced and metastatic setting, only two targeted drugs have been approved by the Food & Drug Administration (FDA), which are sorafenib for hepatocellular carcinoma and erlotinib for PDA...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28098863/effect-and-mechanism-of-resveratrol-on-drug-resistance-in-human-bladder-cancer-cells
#10
Shanshan Wang, Qian Meng, Qing Xie, Man Zhang
Multidrug resistance (MDR) is a significant barrier to the effective treatment of bladder cancer. In order to improve the management of bladder cancer, it is crucial to identify strategies that may reverse MDR. The effects of three herbal medicines, ginsenoside Rh2, (‑)‑epigallocatechin gallate (EGCG) and resveratrol (RES) on bladder cancer were determined. The effect of these three herbal medicines against the drug resistance in adriamycin (ADM)‑resistant pumc‑91 cells (pumc‑91/ADM) was assessed using the Cell Counting Kit‑8 cell proliferation assay system...
January 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28097046/molecular-classification-of-tissue-from-a-transformed-non-hogkin-s-lymphoma-case-with-unexpected-long-time-remission
#11
Julie Støve Bødker, Marianne Tang Severinsen, Tarec Christoffer El-Galaly, Rasmus Froberg Brøndum, Maria Bach Laursen, Steffen Falgreen, Mette Nyegaard, Alexander Schmitz, Lasse Hjort Jakobsen, Anna Amanda Schönherz, Hanne Due, Linn Reinholdt, Martin Bøgsted, Karen Dybkær, Hans Erik Johnsen
BACKGROUND: The concept of precision medicine in cancer includes individual molecular studies to predict clinical outcomes. In the present N = 1 case we retrospectively have analysed lymphoma tissue by exome sequencing and global gene expression in a patient with unexpected long-term remission following relaps. The goals were to phenotype the diagnostic and relapsed lymphoma tissue and evaluate its pattern. Furthermore, to identify mutations available for targeted therapy and expression of genes to predict specific drug effects by resistance gene signatures (REGS) for R-CHOP as described at http://www...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28063788/response-to-chemotherapy-and-prognosis-in-metastatic-colorectal-cancer-with-dna-deficient-mismatch-repair
#12
Alexandra Khichfy Alex, Sheila Siqueira, Renata Coudry, Juliana Santos, Michel Alves, Paulo M Hoff, Rachel P Riechelmann
BACKGROUND: DNA deficient mismatch repair (dMMR) genes are associated with microsatellite instability and good prognosis in early-stage colorectal cancer (CRC). However dMMR is rare in metastatic CRC (mCRC) and little is known about its influence on treatment response rate (RR). The primary objective of this study was to compare the RR of patients with mCRC according to dMMR status. METHODS: This was a retrospective study that compared the RR by Response Evaluation Criteria In Solid Tumors 1...
November 26, 2016: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28062800/novel-allosteric-pathway-of-eg5-regulation-identified-through-multivariate-statistical-analysis-of-hx-ms-ligand-screening-data
#13
Joey G Sheff, Farshad Farshidfar, Oliver F Bathe, Karen Kopciuk, Francesco Gentile, Jack Tuszynski, Khaled Barakat, David C Schriemer
The mitotic kinesin Eg5 is an important target in cancer chemotherapy. A structurally diverse collection of canonical loop L5 inhibitors engage an allosteric pathway that includes elements of its microtubule binding region. However, recent evidence suggests that Eg5 may permit alternative allosteric mechanisms. Terpendole E, a natural-product Eg5 inhibitor, is active against mutants resistant to canonical loop L5 inhibitors and appears to offer a unique mode of inhibition. To investigate the variety of inhibitor responses, the structure-function properties of eighteen kinesin inhibitors were quantified with hydrogen-exchange mass spectrometry (HX-MS), functional analysis and molecular modeling...
January 5, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28009971/dacomitinib-a-new-pan-egfr-inhibitor-is-effective-in-killing-ovarian-cancer-cells
#14
Lei Xu, Huini Wu, Chao Jiang, Hongcai Wang, Bei Gao, Shumei Yan, Yushu Qi, Shufeng Zhou
OBJECTIVE: Aberrant epidermal growth factor receptor (EGFR) is involved in a variety of cancers and its inhibitors have been studied for over a decade. We aim to investigate the effects of dacomitinib, a second generation pan-EGFR inhibitor, on ovarian cancer cells. METHODS: By immunohistochemistry, we studied the clinical significance of EGFR expression in epithelial ovarian cancer (EOC). The correlations between EGFR expression and the clinicopathological variables of patients with EOC were assessed using Pearson's X2 test...
November 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27974547/molecular-epidemiology-of-clostridium-difficile-infection-in-hospitalized-patients-in-eastern-china
#15
Dazhi Jin, Yun Luo, Chen Huang, Jian Cai, Julian Ye, Yi Zheng, Liqian Wang, Peng Zhao, Anbing Liu, Weijia Fang, Xianjun Wang, Shichang Xia, Jianmin Jiang, Yi-Wei Tang
Few studies on risk factors and transmission of Clostridium difficile infection (CDI) have been reported from China. A cross-sectional study was conducted for three years in Eastern China. Consecutive stool specimens from hospitalized patients with diarrhea were cultured for C. difficile C. difficle isolates from these patients then were analyzed for toxin genes, genotypes and antimicrobial resistance. Severity of CDI was determined in each patient by a blinded review of the medical record and ranged from 1 to 6...
December 14, 2016: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/27959427/inhibiting-the-cytoplasmic-location-of-hmgb1-reverses-cisplatin-resistance-in-human-cervical-cancer-cells
#16
Jiyi Xia, Xiaolan Yu, Xueqin Song, Gang Li, Xiguang Mao, Yujiao Zhang
Cervical cancer is the fourth most common malignancy in women worldwide, and resistance to chemotherapy drugs is the biggest obstacle in the treatment of cervical cancers. In the present study, the molecular mechanisms underlying cisplatin resistance in human cervical cancer cells were investigated. When human cervical cancer cells were treated with 10 µg/ml of cisplatin for 24 and 48 h, high mobility group box 1 (HMGB1) protein expression levels significantly increased in a time‑dependent manner. Comparisons between cisplatin‑sensitive HeLa cells and cisplatin‑resistant HeLa/DDP cells revealed higher levels of HMGB1 in HeLa/DDP cells than in HeLa cells...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27926740/a-17-gene-stemness-score-for-rapid-determination-of-risk-in-acute-leukaemia
#17
Stanley W K Ng, Amanda Mitchell, James A Kennedy, Weihsu C Chen, Jessica McLeod, Narmin Ibrahimova, Andrea Arruda, Andreea Popescu, Vikas Gupta, Aaron D Schimmer, Andre C Schuh, Karen W Yee, Lars Bullinger, Tobias Herold, Dennis Görlich, Thomas Büchner, Wolfgang Hiddemann, Wolfgang E Berdel, Bernhard Wörmann, Meyling Cheok, Claude Preudhomme, Herve Dombret, Klaus Metzeler, Christian Buske, Bob Löwenberg, Peter J M Valk, Peter W Zandstra, Mark D Minden, John E Dick, Jean C Y Wang
Refractoriness to induction chemotherapy and relapse after achievement of remission are the main obstacles to cure in acute myeloid leukaemia (AML). After standard induction chemotherapy, patients are assigned to different post-remission strategies on the basis of cytogenetic and molecular abnormalities that broadly define adverse, intermediate and favourable risk categories. However, some patients do not respond to induction therapy and another subset will eventually relapse despite the lack of adverse risk factors...
December 15, 2016: Nature
https://www.readbyqxmd.com/read/27899771/-perspectives-of-individualized-treatment-by-genome-wide-analyses-in-ovarian-cancer
#18
Noriomi Matsumura, Ken Yamaguchi, Ryusuke Murakami, Masaki Mandai, Ikuo Konishi
Genome-wide analyses have recently been reported for ovarian cancer. High-grade serous ovarian carcinoma(HGSOC) almost exclusively harbor TP53 mutations and prominent copy number aberrations. Approximately 20% of HGSOCs harbor BRCA mutations, in which case PARP inhibitors may be effective. HGSOCs are classified into 4 molecular subtypes with distinct histopathological features by transcriptional profiling. These subtypes differ in prognosis and drug sensitivity. Additionally, a whole-genome analysis for HGSOC has revealed various factors that can induce resistance to chemotherapy...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27895763/small-cell-lung-cancer-transformation-and-the-t790m-mutation-a-case-report-of-two-acquired-mechanisms-of-tki-resistance-detected-in-a-tumor-rebiopsy-and-plasma-sample-of-egfr-mutant-lung-adenocarcinoma
#19
Greta Alì, Rossella Bruno, Mirella Giordano, Irene Prediletto, Letizia Marconi, Simonetta Zupo, Franco Fedeli, Alessandro Ribechini, Antonio Chella, Gabriella Fontanini
The present study describes the case of a 45-year-old man diagnosed with metastatic lung adenocarcinoma, which harbored a deletion within exon 19 of the epidermal growth factor receptor (EGFR) gene. The patient was subsequently treated with gefitinib (250 mg/day orally from May 2013 to March 2014), but developed acquired resistance to the drug following 11 months of treatment. Tumor burden molecular analysis was performed on a tumor rebiopsy and plasma sample, and histological analysis was also performed on the tumor rebiopsy...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27891677/staurosporine-scaffold-based-rational-discovery-of-the-wild-type-sparing-reversible-inhibitors-of-egfr-t790m-gatekeeper-mutant-in-lung-cancer-with-analog-sensitive-kinase-technology
#20
Xiaoyun Song, Xingcai Liu, Xi Ding
The human epidermal growth factor receptor (EGFR) has been established as an attractive target for lung cancer therapy. However, an acquired EGFR T790M gatekeeper mutation is frequently observed in patients treated with first-line anticancer agents such as gefitinib and erlotinib to cause drug resistance, largely limiting the application of small-molecule kinase inhibitors in EGFR-targeted chemotherapy. Previously, the reversible pan-kinase inhibitor staurosporine and its several analogs such as Gö6976 and K252a have been reported to selectively inhibit the EGFR T790M mutant (EGFR(T790M) ) over wild-type kinase (EGFR(WT) ), suggesting that the staurosporine scaffold is potentially to develop the wild-type sparing reversible inhibitors of EGFR(T790M) ...
November 28, 2016: Journal of Molecular Recognition: JMR
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