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https://www.readbyqxmd.com/read/28649131/blocking-the-utilization-of-glucose-induces-the-switch-from-senescence-to-apoptosis-in-pseudolaric-acid-b-treated-human-lung-cancer-cells-in-vitro
#1
Guo-Dong Yao, Jing Yang, Xiu-Xiu Li, Xiao-Yu Song, Toshihiko Hayashi, Shin-Ichi Tashiro, Satoshi Onodera, Shao-Jiang Song, Takashi Ikejima
Pseudolaric acid B (PAB), a diterpene acid isolated from the root bark of Pseudolarix kaempferi Gordon, exerts anti-tumor effects in several cancer cell lines. Our previous study showed that PAB mainly induced senescence via p53-p21 activation rather than apoptosis in suppression of the growth of human lung cancer A549 cells (p53 wild-type). In p53-null human lung cancer H1299 cells, however, PAB caused apoptosis without senescence. In this study we investigated what mechanism was responsible for the switch from senescence to apoptosis in PAB-treated human lung cancer cell lines...
June 26, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28649094/current-management-of-pregnancy-associated-breast-cancer
#2
H Hy Yu, P Sy Cheung, R Cy Leung, T N Leung, W H Kwan
Pregnancy-associated breast cancer is the most common malignancy during pregnancy with an expected rise in incidence. The belief in the need for termination of pregnancy and that chemotherapy is contra-indicated during pregnancy is challenged by recent evidence. Patients can consider breast-conserving surgery and sentinel lymph node biopsy with acceptably low fetal risk from radiation exposure. A range of chemotherapeutics is possible in the second trimester in terms of drug class and frequency. Hormone therapy and monoclonal antibody therapy are contra-indicated during pregnancy and lactation...
June 26, 2017: Hong Kong Medical Journal, Xianggang Yi Xue za Zhi
https://www.readbyqxmd.com/read/28648699/prognostic-factors-and-outcomes-in-metastatic-uveal-melanoma-treated-with-programmed-cell-death-1-or-combined-pd-1-cytotoxic-t-lymphocyte-antigen-4-inhibition
#3
Markus V Heppt, Lucie Heinzerling, Katharina C Kähler, Andrea Forschner, Michael C Kirchberger, Carmen Loquai, Markus Meissner, Friedegund Meier, Patrick Terheyden, Beatrice Schell, Rudolf Herbst, Daniela Göppner, Felix Kiecker, David Rafei-Shamsabadi, Sebastian Haferkamp, Margit A Huber, Jochen Utikal, Mirjana Ziemer, Irmgard Bumeder, Christiane Pfeiffer, Susanne G Schäd, Christoph Schmid-Tannwald, Julia K Tietze, Thomas K Eigentler, Carola Berking
BACKGROUND: Uveal melanoma (UM) is an ocular malignancy with high potential for metastatic spread. In contrast to cutaneous melanoma, immunotherapy has not yet shown convincing efficacy in patients with UM. Combined immune checkpoint blockade with checkpoint programmed cell death-1 (PD-1) and checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibition has not been systematically assessed for UM to date. PATIENTS AND METHODS: Patients with metastatic UM treated with either PD-1 inhibitor monotherapy or combined PD-1 inhibitor and ipilimumab (an anti-CTLA-4 monoclonal antibody) were included from 20 German skin cancer centres...
June 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28646020/mcam-mediates-chemoresistance-in-small-cell-lung-cancer-via-the-pi3k-akt-sox2-signaling-pathway
#4
Satyendra C Tripathi, Johannes F Fahrmann, Muge Celiktas, Mitzi Aguilar, Kieren D Marini, Mohit Kumar Jolly, Hiroyuki Katayama, Hong Wang, Eunice N Murage, Jennifer B Dennison, D Neil Watkins, Herbert Levine, Edwin J Ostrin, Ayumu Taguchi, Samir M Hanash
Despite favorable responses to initial therapy, small cell lung cancer (SCLC) relapse occurs within a year and exhibits resistance to multiple drugs. Due to limited accessibility of patient tissues for research purposes, SCLC-patient derived xenografts (PDX) have provided the best opportunity to address this limitation. Here we sought to identify novel mechanisms involved in SCLC chemoresistance. Through in-depth proteomic profiling, we identified MCAM as a markedly upregulated surface receptor in chemoresistant SCLC cell lines and in chemoresistant PDX compared to matched treatment-naïve tumors...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28644842/investigation-of-discriminant-metabolites-in-tamoxifen-resistant-and-choline-kinase-alpha-downregulated-breast-cancer-cells-using-1h-nuclear-magnetic-resonance-spectroscopy
#5
Hoe Suk Kim, Lianji Tian, Hyeonjin Kim, Woo Kyung Moon
Metabolites linked to changes in choline kinase-α (CK-α) expression and drug resistance, which contribute to survival and autophagy mechanisms, are attractive targets for breast cancer therapies. We previously reported that autophagy played a causative role in driving tamoxifen (TAM) resistance of breast cancer cells (BCCs) and was also promoted by CK-α knockdown, resulting in the survival of TAM-resistant BCCs. There is no comparative study yet about the metabolites resulting from BCCs with TAM-resistance and CK-α knockdown...
2017: PloS One
https://www.readbyqxmd.com/read/28644754/expression-of-enzymes-related-to-glucose-metabolism-in-non-small-cell-lung-cancer-and-prognosis
#6
Alexandra Giatromanolaki, Efthimios Sivridis, Stella Arelaki, Michael I Koukourakis
Purpose/Aim: Cancer cells are addicted to glycolytic anaerobic pathways, in presence or in absence of a functional Krebs' cycle (phenomenon Warburg). This metabolic predilection relies on both extracellular (impaired vascularization and oxygenation) and intracellular (oncogenic activation of genes) causes. MATERIALS AND METHODS: We investigated the expression and prognostic relevance of enzymes involved in the glucose absorption and metabolism, monocarboxylate transporter (MCT) expression, MCT1 and MCT2, pentose pathway (Glucose-6-phospahte dehydrogenase G6PD), glycogene synthesis (glycogene synthase GYS1), glycolysis (Hexokinase HXKII, phosphofructokinase PFK1, fructose biphosphate aldolase), fate of pyruvate (pyruvate dehydrogenase PDH, phosphorylated pPDH, PDH kinase PDK1, lactate dehydrogenase LDH5 and LDH1) and key Kreb's cycle enzymes (citrate synthase CSynth and isocitrate dehydrogenase IDH)...
June 23, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28643510/characterization-of-the-saffron-derivative-crocetin-as-an-inhibitor-of-human-lactate-dehydrogenase-5-in-the-antiglycolytic-approach-against-cancer
#7
Carlotta Granchi, Serena Fortunato, Serena Meini, Flavio Rizzolio, Isabella Caligiuri, Tiziano Tuccinardi, Hyang Yeon Lee, Paul J Hergenrother, Filippo Minutolo
Inhibition of lactate dehydrogenase (LDH) represents an innovative approach to tackle cancer because this peculiar glycolytic metabolism is characteristic of most invasive tumor cells. An investigation into the biological properties of saffron extracts led to the discover of their LDH-inhibition properties. In particular, the most important saffron components, crocetin, was found to inhibit LDH (IC50 = 54.9 ± 4.7 µM). This carotenoid was independently produced by chemical synthesis, and its LDH-inhibition properties manifested via its antiproliferative activity against two glycolytic cancer cell lines (A549 and HeLa, IC50 = 114...
June 23, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28643047/trace-elements-in-pleural-effusion-correlates-with-smokers-with-lung-cancer
#8
Kang-Yun Lee, Po-Hao Feng, Hsiao-Chi Chuang, Sheng-Ming Wu, Wen-Te Liu, Kuan-Yuan Chen, Chien-Ying Liu, Shu-Chuan Ho
Smoking leads to the presence of various elements, including toxic metals and metalloids, in tissues and fluids, thus contributing to cancer risk. This study assessed the concentrations of 14 elements (Ag, Al, As, Co, Cr, Cu, Fe, Ni, Mn, Mo, Pb, Sn, V, and Zn) and biochemical parameters (glucose, lactate dehydrogenase, and total protein) in the pleural effusion (PE) of patients with lung cancer. The potential association of these parameters with smoking was assessed. Total of 48 patients with lung cancer (26 non-smokers and 22 smokers) received thoracocentesis for PE removal...
June 22, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28639665/isolation-and-identification-of-l-d-lactate-conjugated-bufadienolides-from-toad-eggs-revealing-lactate-racemization-in-amphibians
#9
Shiwen Zhou, Qingfei Zheng, Xiuyong Huang, Yong Wang, Sifan Luo, Renwang Jiang, Lei Wang, Wencai Ye, Haiyan Tian
Three pairs of bufadienolide l/d-lactate epimers (1-6) were isolated from the eggs of the toad Bufo bufo gargarizans. The structures were elucidated by using spectroscopic methods, X-ray diffraction analysis and a modified Mosher's method. Compounds 1-6 represent the first occurrence of lactate-conjugated bufadienolides in nature, and illustrate the existence of an enzyme-controlled epimerization from l- to d-lactate in amphibians. The biosynthetic pathways, in which two key enzymes might be involved (i.e., lactate racemase and acyltransferase), were proposed...
June 22, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28639409/anti-pd-1-antibodies-in-metastatic-uveal-melanoma-a-treatment-option
#10
Carolin Bender, Alexander Enk, Ralf Gutzmer, Jessica C Hassel
Uveal melanomas (UMs) are a rare form of cancer with clinical and pathological characteristics distinct from cutaneous melanomas. Ipilimumab has shown efficacy and safety in the treatment of metastatic UM. This provides a rationale for treatment with other immune checkpoint inhibitors. This is a retrospective review of 15 patients with metastatic UM treated between June 2014 and February 2016, who received treatment with the anti-PD-1 Abs pembrolizumab or nivolumab. Patients were treated at two German university hospitals...
June 21, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28638795/potential-prognostic-biomarkers-in-pancreatic-juice-of-resectable-pancreatic-ductal-adenocarcinoma
#11
REVIEW
Shefali Agrawal
Despite potentially curative surgery pancreatic cancer has a dismal prognosis. Serum cancer antigen 19-9 (CA 19-9) correlates with tumor burden, resectability and survival in patients with pancreatic ductal adenocarcinoma. Identification of novel biomarkers may facilitate early diagnosis of pancreatic cancer and improve survival. Pancreatic juice is a rich source of cancer-specific proteins rendering it a promising tool for identifying biomarkers. Recent proteomic and microRNA expression analyses have identified several biomarkers of potential diagnostic and prognostic value...
June 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28638455/the-prognostic-and-predictive-value-of-carbohydrate-antigen-19-9-in-metastatic-colorectal-cancer-patients-with-first-line-bevacizumab-containing-chemotherapy
#12
Chang Jiang, Shousheng Liu, Wenzhuo He, Bei Zhang, Liangping Xia
Objective: We had previously demonstrated that the carbohydrate antigen 19-9 (CA19-9), lactate dehydrogenase (LDH), neutrophil lymphocyte ratio (NLR) are prognostic factors for patients with metastatic colorectal cancer (mCRC). In this study, we try to analysis the association of these blood-based biomarkers with bevacizumab efficacy in the first line setting. Methods: A total of 284 eligible consecutive mCRC patients who received first-line chemotherapy with or without bevacizumab were studied from 2007 to 2014 at Sun Yat-Sen University Cancer Center...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28630385/low-dose-of-lenalidomide-enhances-nk-cell-activity-possible-implication-as-an-adjuvant
#13
Kiandokht Borhani, Taravat Bamdad, Tayebeh Hashempour
BACKGROUND: Lenalidomide, a synthetic immunomodulatory drug, has a wide range of features including anti-angiogenic and anti-proliferative properties. To date, researchers have shown that lenalidomide is capable of ameliorating the immune system factors and antitumor responses. Most researchers have reported that lenalidomide enhances the immune response in certain cancer patients through several pathways including the stimulation of Natural Killer cells; notwithstanding, it is still crucial to investigate the effect of lenalidomide on the activity of NK cell cytotoxicity both in vitro and in vivo...
June 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28630053/glucose-catabolism-in-liver-tumors-induced-by-c-myc-can-be-sustained-by-various-pkm1-pkm2-ratios-and-pyruvate-kinase-activities
#14
Andrés Méndez-Lucas, Xiaolei Li, Junjie Hu, Li Che, Xinhua Song, Jiaoyuan Jia, Jingxiao Wang, Chencheng Xie, Paul C Driscoll, Darjus F Tschaharganeh, Diego F Calvisi, Mariia Yuneva, Xin Chen
Different pyruvate kinase isoforms are expressed in a tissue-specific manner, with pyruvate kinase M2 (PKM2) suggested to be the predominant isoform in proliferating cells and cancer cells. Due to differential regulation of enzymatic activities, PKM2 but not PKM1 has been thought to favor cell proliferation. However, the role of PKM2 in tumorigenesis has been recently challenged. Here we report that increased glucose catabolism through glycolysis and increased pyruvate kinase activity in c-MYC-driven liver tumors are associated with increased expression of both PKM1 and PKM2 isoforms and decreased expression of the liver-specific isoform of pyruvate kinase, PKL...
June 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28624442/loss-of-fructose-1-6-bisphosphatase-induces-glycolysis-and-promotes-apoptosis-resistance-of-cancer-stem-like-cells-an-important-role-in-hexavalent-chromium-induced-carcinogenesis
#15
Jin Dai, Yanli Ji, Wei Wang, Donghern Kim, Leonard Yenwong Fai, Lei Wang, Jia Luo, Zhuo Zhang
Hexavalent chromium (Cr(VI)) compounds are confirmed human carcinogens for lung cancer. Our previous studies has demonstrated that chronic exposure of human bronchial epithelial BEAS-2B cells to low dose of Cr(VI) causes malignant cell transformation. The acquisition of cancer stem cell-like properties is involved in the initiation of cancers. The present study has observed that a small population of cancer stem-like cells (BEAS-2B-Cr-CSC) exists in the Cr(VI)-transformed cells (BEAS-2B-Cr). Those BEAS-2B-Cr-CSC exhibit extremely reduced capability of generating reactive oxygen species (ROS) and apoptosis resistance...
June 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28623396/assessment-of-the-circulating-cell-free-dna-marker-association-with-diagnosis-and-prognostic-prediction-in-patients-with-lymphoma-a-single-center-experience
#16
Mao Li, Yongqian Jia, Juan Xu, Xiaomin Cheng, Caigang Xu
Circulating cell-free DNA (ccfDNA) has been shown to be associated with the clinical characteristics and prognosis of cancer patients. Our objective was to assess whether the concentration and integrity index of ccfDNA in plasma may be useful for diagnosing and monitoring the progression of patients with lymphoma. We included plasma samples from 174 lymphoma patients and 80 healthy individuals. The total concentration of ccfDNA was determined using a fluorometry method, and the DNA integrity index (DII), which is the ratio of longer to shorter DNA fragments, for the APP gene was detected using real-time quantitative PCR...
August 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28622713/mir-142-5p-promotes-development-of-colorectal-cancer-through-targeting-sdhb-and-facilitating-generation-of-aerobic-glycolysis
#17
Shaojun Liu, Zhiming Xiao, Feiyan Ai, Fen Liu, Xiong Chen, Ke Cao, Weiguo Ren, Xuemei Zhang, Peng Shu, Decai Zhang
Aberrant expression of miRNAs contributes to the development of human malignancies. A recent study revealed that miR-142-5p is increased in the serum of colorectal cancer (CRC) patients compared to health people. Using starBase v2.0, we found that succinate dehydrogenase-B (SDHB) is a potential target of miR-142-5p, while SDHB is negatively correlated to cancer development through regulating energetic metabolism. Based on these information, this study further examined the expression profiles of miR-142-5p and SDHB in CRC tissues and cell lines using PCR and Western blotting...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28621491/outcome-of-patients-older-than-80%C3%A2-years-with-diffuse-large-b-cell-lymphoma-dlbcl-treated-with-standard-immunochemotherapy-a-large-retrospective-study-from-4-institutions
#18
Stefania Gobba, Alden A Moccia, Wiebke Gulden-Sala, Annarita Conconi, Stefan Diem, Luciano Cascione, Gloria Iacoboni, Gloria Margiotta-Casaluci, Kathrin Aprile von Hohenstaufen, Anastasios Stathis, Felicitas Hitz, Graziella Pinotti, Gianluca Gaidano, Emanuele Zucca
Little information is available on the very elderly patients with diffuse large B-cell lymphoma (DLBCL). We performed a retrospective analysis of 281 patients >80 years old with newly diagnosed DLBCL treated in 4 referral institutions in Switzerland and Northern Italy. Primary end points were overall survival, progression-free survival, and cause-specific survival. Systemic chemotherapy was given to 239 patients, and 119 of them received rituximab in their initial treatment. At a median follow-up of 5.5 years, 5-year progression-free survival was 26% (95% confidence interval [CI], 20-32%), 5-year overall survival was 31% (95% CI, 25-37%), and 5-year cause-specific survival was 48% (95% CI, 41-55%) for the entire cohort...
June 16, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28619042/metabolic-targeting-of-hif-dependent-glycolysis-reduces-lactate-increases-oxygen-consumption-and-enhances-response-to-high-dose-single-fraction-radiotherapy-in-hypoxic-solid-tumors
#19
Eric Leung, Rob A Cairns, Naz Chaudary, Ravi N Vellanki, Tuula Kalliomaki, Eduardo H Moriyama, Hilda Mujcic, Brian C Wilson, Bradly G Wouters, Richard Hill, Michael Milosevic
BACKGROUND: A high rate of glycolysis leading to elevated lactate content has been linked to poor clinical outcomes in patients with head and neck and cervical cancer treated with radiotherapy. Although the biological explanation for this relationship between lactate and treatment response remains unclear, there is a continued interest in evaluating strategies of targeting metabolism to enhance the effectiveness of radiotherapy. The goal of this study was to investigate the effect of metabolic-targeting through HIF-1α inhibition and the associated changes in glycolysis, oxygen consumption and response on the efficacy of high-dose single-fraction radiotherapy (HD-SFRT)...
June 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28611673/reversing-egfr-mediated-immunoescape-by-targeted-monoclonal-antibody-therapy
#20
REVIEW
Fernando Concha-Benavente, Robert L Ferris
Uncontrolled growth is a signature of carcinogenesis, in part mediated by overexpression or overstimulation of growth factor receptors. The epidermal growth factor receptor (EGFR) mediates activation of multiple oncogenic signaling pathways and escape from recognition by the host immune system. We discuss how EGFR signaling downregulates tumor antigen presentation, upregulates suppressive checkpoint receptor ligand programmed death ligand (PD-L1), induces secretion of inhibitory molecules such as transforming growth factor beta (TGFβ) and reprograms the metabolic pathways in cancer cells to upregulate aerobic glycolysis and lactate secretion that ultimately lead to impaired cellular immunity mediated by natural killer (NK) cell and cytotoxic T lymphocytes (CTL)...
2017: Frontiers in Pharmacology
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