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https://www.readbyqxmd.com/read/29352660/clinical-significance-of-muc13-in-pancreatic-ductal-adenocarcinoma
#1
Sheema Khan, Nadeem Zafar, Shabia S Khan, Saini Setua, Stephen W Behrman, Zachary E Stiles, Murali M Yallapu, Peeyush Sahay, Hemendra Ghimire, Tomoko Ise, Satoshi Nagata, Lei Wang, Jim Y Wan, Prabhakar Pradhan, Meena Jaggi, Subhash C Chauhan
BACKGROUND: Poor prognosis of pancreatic cancer (PanCa) is associated with lack of an effective early diagnostic biomarker. This study elucidates significance of MUC13, as a diagnostic/prognostic marker of PanCa. METHODS: MUC13 was assessed in tissues using our in-house generated anti-MUC13 mouse monoclonal antibody and analyzed for clinical correlation by immunohistochemistry, immunoblotting, RT-PCR, computational and submicron scale mass-density fluctuation analyses, ROC and Kaplan Meir curve analyses...
January 15, 2018: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/29352488/understanding-intratumor-heterogeneity-by-combining-genome-analysis-and-mathematical-modeling
#2
REVIEW
Atsushi Niida, Satoshi Nagayama, Satoru Miyano, Koshi Mimori
Cancer is composed of multiple cell populations with different genomes. Each of the populations is called a clone (or subclone) and this phenomenon is called intratumor heterogeneity (ITH). ITH is observed in various types of cancers and presumed to be a major cause leading to therapeutic resistance. If a tumor harbors a major clone sensitive to a specific anti-cancer treatment, the tumor shrinks within a given period after the treatment. However, in most cases, a minor clone resistant to the chemotherapy exists in the tumor and predominantly regrows in spite of the intensive therapy...
January 20, 2018: Cancer Science
https://www.readbyqxmd.com/read/29352327/limk-cofilin-pathway-and-slingshot-are-implicated-in-human-colorectal-cancer-progression-and-chemoresistance
#3
Helen Aggelou, Panagiota Chadla, Sofia Nikou, Sofia Karteri, Ioannis Maroulis, Haralabos P Kalofonos, Helen Papadaki, Vasiliki Bravou
Cofilin phospho-regulation is important for actin filament turnover and is implicated in cancer. Phosphorylation of cofilin is mediated by LIM kinases (LIMKs) and dephosphorylation by Slingshot phosphatases (SSH). LIMKs and SSH promote cancer cell invasion and metastasis and represent novel anti-cancer targets. However, little is known regarding LIMK/cofilin and SSH in human colorectal cancer (CRC). In this study, we aimed to address their expression and significance in human CRC. We evaluated expression of non-phosphorylated (active) and phosphorylated cofilin, LIMK1, LIMK2, and SSH1 by immunohistochemistry in 143 human CRC samples in relation to clinicopathologic parameters, response of metastatic disease to chemotherapy, and epithelial-mesenchymal transition (EMT) markers β-catenin, E-cadherin, and ZEB...
January 19, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29352306/prognostic-and-predictive-role-of-egfr-pathway-alterations-in-biliary-cancer-patients-treated-with-chemotherapy-and-anti-egfr
#4
Caterina Peraldo-Neia, Giuliana Cavalloni, Elisabetta Fenocchio, Celeste Cagnazzo, Loretta Gammaitoni, Stefano Cereda, Guglielmo Nasti, Maria Antonietta Satolli, Giuseppe Aprile, Michele Reni, Antonio Avallone, Rosella Spadi, Tiziana Venesio, Vittoria Martin, Claudio Doglioni, Milo Frattini, Massimo Aglietta, Francesco Leone
The association of anti-EGFR to gemcitabine and oxaliplatin (GEMOX) chemotherapy did not improve survival in biliary tract carcinoma (BTC) patients. Multiple mechanisms might be involved in the resistance to anti-EGFR. Here, we explored the mutation profile of EGFR extracellular domain (ECD), of tyrosine kinase domain (TKD), and its amplification status. EGFR mutational status of exons 12, 18-21 was analyzed in 57 tumors by Sanger sequencing. EGFR amplification was evaluated in 37 tumors by Fluorescent In Situ Hybridization (FISH)...
2018: PloS One
https://www.readbyqxmd.com/read/29352292/rna-seq-of-kaposi-s-sarcoma-reveals-alterations-in-glucose-and-lipid-metabolism
#5
For Yue Tso, Andrew V Kossenkov, Salum J Lidenge, Owen Ngalamika, John R Ngowi, Julius Mwaiselage, Jayamanna Wickramasinghe, Eun Hee Kwon, John T West, Paul M Lieberman, Charles Wood
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). It is endemic in a number of sub-Saharan African countries with infection rate of >50%. The high prevalence of HIV-1 coupled with late presentation of advanced cancer staging make KS the leading cancer in the region with poor prognosis and high mortality. Disease markers and cellular functions associated with KS tumorigenesis remain ill-defined. Several studies have attempted to investigate changes of the gene profile with in vitro infection of monoculture models, which are not likely to reflect the cellular complexity of the in vivo lesion environment...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352272/nuclear-p53-mediated-repression-of-autophagy-involves-pink1-transcriptional-down-regulation
#6
Thomas Goiran, Eric Duplan, Lila Rouland, Wejdane El Manaa, Inger Lauritzen, Julie Dunys, Han You, Frédéric Checler, Cristine Alves da Costa
p53 is a transcription factor that is implicated in the control of both apoptotic and autophagic cell death. This tumor suppressor elicits both pro-autophagic and anti-autophagic phenotypes depending of its intracellular localization. The ability of p53 to repress autophagy has been exclusively associated to its cytoplasmic localization. Here, we show that transcriptional activity of p53 also contributes to autophagy down-regulation. Thus, nuclear p53 controls PINK1, a key protein involved in the control of mitophagy, by repressing its promoter activity, protein and mRNA levels, ex-vivo and in vivo...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352248/combined-use-of-epcam-and-fr%C3%AE-enables-the-high-efficiency-capture-of-circulating-tumor-cells-in-non-small-cell-lung-cancer
#7
Luojun Chen, Min Peng, Na Li, Qibin Song, Yi Yao, Bin Xu, Huali Liu, Peng Ruan
Circulating tumor cells (CTCs) provide a new approach for auxiliary diagnosis, therapeutic effect evaluation, and prognosis prediction for cancer patients. The epithelial cell adhesion molecule (EpCAM)-based separation method (CellSearch) showed good clinical use in multiple types of cancer. Nevertheless, some non-small cell lung cancer (NSCLC) tumor cells have a lower expression of EpCAM and are less frequently detected by CellSearch. Here, we present a highly sensitive immunomagnetic separation method to capture CTCs based on two cell surface markers for NSCLC, EpCAM and Folate receptor alpha (FRα)...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352243/nucleolin-and-erbb2-inhibition-reduces-tumorigenicity-of-erbb2-positive-breast-cancer
#8
Eya Wolfson, Shira Solomon, Eran Schmukler, Yona Goldshmit, Ronit Pinkas-Kramarski
ErbB2, a member of the ErbB family of receptor tyrosine kinases, is an essential player in the cell's growth and proliferation signaling pathways. Amplification or overexpression of ErbB2 is observed in ∼30% of breast cancer patients, and often drives cellular transformation and cancer development. Recently, we have shown that ErbB2 interacts with the nuclear-cytoplasmic shuttling protein nucleolin, an interaction which enhances cell transformation in vitro, and increases mortality risk and disease progression rate in human breast cancer patients...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352129/molecular-characterization-of-the-grape-seeds-extract-s-effect-against-chemically-induced-liver-cancer-in-vivo-and-in-vitro-analyses
#9
Alaaeldin Ahmed Hamza, Gehan Hussein Heeba, Hanan Mohamed Elwy, Chandraprabha Murali, Raafat El-Awady, Amr Amin
The purpose of this study was to investigate the anti-cancer property of grape seed extract (GSE) during early stages of developing liver cancer using a two-stage carcinogenic model combining diethylnitrosamine (DEN) and 2-Acetyl Aminofluorene (2-AAF). Administration of GSE at doses 25, 50 and 100 mg/kg per day started at the beginning of promotion periods and continued for 14 weeks. GSE dramatically inhibited pre-neoplastic foci formation as well as significantly decreased the number and the area of placental glutathione-S-transferase in livers of DEN-2AAF-treated rats by approximately 4 & 10 fold deductions, respectively...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352038/microenvironment-induced-cd44v6-promotes-early-disease-progression-in-chronic-lymphocytic-leukemia
#10
Julia C Gutjahr, Eva Szenes, Lisa Tschech, Daniela Asslaber, Michaela Schlederer, Simone Roos, Xiaobing Yu, Tamara Girbl, Christina Sternberg, Alexander Egle, Fritz Aberger, Ronen Alon, Lukas Kenner, Richard Greil, Veronique Orian-Rousseau, Tanja N Hartmann
Chronic lymphocytic leukemia (CLL) outgrowth depends on signals from the microenvironment. We have previously found that in vitro reconstitution of this microenvironment induces specific variant isoforms of the adhesion molecule CD44, which confer human CLL with high affinity to hyaluronan (HA). Here, we determined the in vivo contribution of standard CD44 and its variants to leukemic B-cell homing and proliferation in Tcl1 transgenic mice with a B-cell-specific CD44 deficiency. In these mice, leukemia onset was delayed and leukemic infiltration of spleen, liver, and lungs, but not of bone marrow was decreased...
January 19, 2018: Blood
https://www.readbyqxmd.com/read/29351987/cd83-is-a-new-potential-biomarker-and-therapeutic-target-for-hodgkin-lymphoma
#11
Ziduo Li, Xinsheng Ju, Kenneth Lee, Candice Clarke, Jennifer L Hsu, Edward Abadir, Christian E Bryant, Suzanne Pears, Neroli Sunderland, Scott Heffernan, Annemarie Hennessy, Tsun-Ho Lo, Geoffrey A Pietersz, Fiona Kupresanin, Phillip D Fromm, Pablo A Silveira, Con Tsonis, Wendy A Cooper, Ilona Cunningham, Christina Brown, Georgina J Clark, Derek N J Hart
Chemotherapy and hematopoietic stem cell transplantation are effective treatments for most Hodgkin lymphoma patients, however there remains a need for better tumor-specific target therapy in Hodgkin lymphoma patients with refractory or relapsed disease. We demonstrate that membrane CD83 is a diagnostic and therapeutic target, highly expressed in Hodgkin lymphoma cell lines and Hodgkin and Reed-Sternberg cells in 29/35 (82.9%) Hodgkin lymphoma patient lymph node biopsies. CD83 from Hodgkin lymphoma tumor cells was able to trogocytose to surrounding T cells and interestingly, the trogocytosing CD83+T cells expressed significantly more PD-1 compared to CD83- T cells...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29351920/exceptional-response-to-pembrolizumab-in-a-metastatic-chemotherapy-radiation-resistant-ovarian-cancer-patient-harboring-a-cd274-pd-l1-genetic-rearrangement
#12
Stefania Bellone, Natalia Buza, Jungmin Choi, Luca Zammataro, Laurie Gay, Julia A Elvin, David L Rimm, Yuting Liu, Elena Ratner, Peter E Schwartz, Alessandro D Santin
PURPOSE: Ovarian carcinoma no longer responsive to surgery and chemotherapy remains an incurable disease. Alternative therapeutic options remain desperately needed. EXPERIMENTAL DESIGN: We describe a heavily pretreated ovarian cancer patient with recurrent disease experiencing a remarkable clinical response to treatment with the anti-PD1 immune check-point inhibitor pembrolizumab. The clinical, pathological, and genomic characteristics of this exceptional ovarian cancer responder were carefully investigated using immunohistochemistry (IHC), quantitative multiplex fluorescence methods (ie, automated quantitative analysis, AQUA) and whole exome sequencing (WES) techniques...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29351904/er%C3%AE-mediated-nuclear-sequestration-of-rsk2-is-required-for-er-breast-cancer-tumorigenesis
#13
Katarzyna A Ludwik, Oliver Gene McDonald, David R Brenin, Deborah A Lannigan
Although ribosomal protein S6 kinase A3 (RSK) activation status positively correlates with patient responses to anti-estrogen hormonal therapies, the mechanistic basis for these observations is unknown. Using multiple in vitro and in vivo models of ER+ breast cancer, we report that ERα sequesters active RSK2 into the nucleus to promote neoplastic transformation and facilitate metastatic tumor growth. RSK2 physically interacted with ERα through its N-terminus to activate a pro-neoplastic transcriptional network critical to the ER+ lineage in the mammary gland, thereby providing a gene signature that effectively stratified patient tumors according to ERα status...
January 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29351887/synthesis-and-anti-tumor-activity-of-ef24-analogues-as-ikk%C3%AE-inhibitors
#14
Rong Jin, Qiuxiang Chen, Song Yao, Encheng Bai, Weitao Fu, Ledan Wang, Jiabing Wang, Xiaojing Du, Tao Wei, Haineng Xu, Chengxi Jiang, Peihong Qiu, Jianzhang Wu, Wulan Li, Guang Liang
EF24 is an IKKβ inhibitor (IC50: 72 μM) containing various anti-tumor activities. In this study, a series of EF24 analogs targeting IKKβ were designed and synthesized. Several IKKβ inhibitors with better activities than EF24 were screened out and B3 showed best IKKβ inhibitory (IC50: 6.6 μM). Molecular docking and dynamic simulation experiments further confirmed this inhibitory effect. B3 obviously suppressed the viability of Hela229, A549, SGC-7901 and MGC-803 cells. Then, in SGC-7901 and MGC-803 cells, B3 blocked the NF-κB signal pathway by inhibiting IKKβ phosphorylation, and followed arrested the cell cycle at G2/M phase by suppressing the Cyclin B1 and Cdc2 p34 expression, induced the cell apoptosis by down-regulating Bcl-2 protein and up-regulating cleaved-caspase3...
December 7, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29351747/combination-of-pelargonium-sidoides-and-coptis-chinensis-root-inhibits-nuclear-factor-kappa-b-mediated-inflammatory-response-in-vitro-and-in-vivo
#15
Sang Mi Park, Byung-Gu Min, Ji Yun Jung, Kyung Hwan Jegal, Chul Won Lee, Kwang Youn Kim, Young Woo Kim, Youn-Woong Choi, Il Je Cho, Sae Kwang Ku, Sang Chan Kim
BACKGROUND: Pelargonium sidoides (PS) and Coptis chinensis root (CR) have traditionally been used to treat various diseases, including respiratory and gastrointestinal infections, dysmenorrhea, and hepatic disorders. The present study was conducted to evaluate the anti-inflammatory effects of a combination of PS and CR in vitro and in vivo. METHODS: The in vitro effects of PS + CR on the induction of inflammation-related proteins were evaluated in lipopolysaccharide (LPS)-stimulated RAW 264...
January 19, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29351573/multicenter-french-harmonization-study-for-pd-l1-ihc-testing-in-non-small-cell-lung-cancer
#16
J Adam, N Le Stang, I Rouquette, A Cazes, C Badoual, H Pinot-Roussel, L Tixier, C Danel, F Damiola, D Damotte, F Penault-Llorca, S Lantuéjoul
Background: Various PD-L1 immunohistochemistry (IHC) assays have been developed and used in clinical trials in association with different drugs. In order to harmonize and make PD-L1 testing in non-small cell lung cancer (NSCLC) widely available, we conducted a multicenter study comparing PD-L1 standardized assays and laboratory-developed tests (LDT). Methods: IHC with five anti-PD-L1 monoclonal antibodies (28-8, 22C3, E1L3N, SP142 and SP263) was performed concomitantly on 41 NSCLC surgical specimens in 7 centers using Dako Autostainer Link 48 (3 centers), Leica Bond (2 centers) or Ventana BenchMark Ultra (2 centers), platforms...
January 16, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29351275/a-mathematical-model-for-il-6-mediated-stem-cell-driven-tumor-growth-and-targeted-treatment
#17
Fereshteh Nazari, Alexander T Pearson, Jacques Eduardo Nör, Trachette L Jackson
Targeting key regulators of the cancer stem cell phenotype to overcome their critical influence on tumor growth is a promising new strategy for cancer treatment. Here we present a modeling framework that operates at both the cellular and molecular levels, for investigating IL-6 mediated, cancer stem cell driven tumor growth and targeted treatment with anti-IL6 antibodies. Our immediate goal is to quantify the influence of IL-6 on cancer stem cell self-renewal and survival, and to characterize the subsequent impact on tumor growth dynamics...
January 19, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29351242/-vessels-in-the-storm-searching-for-prognostic-and-predictive-angiogenic-factors-in-colorectal-cancer
#18
REVIEW
Adriano Angelucci, Simona Delle Monache, Alessio Cortellini, Monica Di Padova, Ficorella Corrado
High expectations are placed upon anti-angiogenic compounds for metastatic colorectal cancer (mCRC), the first malignancy for which such type of treatment has been approved. Indeed, clinical trials have confirmed that targeting the formation of new vessels can improve in many cases clinical outcomes of mCRC patients. However, current anti-angiogenic drugs are far from obtaining the desirable or expected curative results. Many are the factors probably involved in such disappointing results, but particular attention is currently focused on the validation of biomarkers able to improve the direction of treatment protocols...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29351198/superoxide-dismutase-mimetic-gc4419-enhances-the-oxidation-of-pharmacological-ascorbate-and-its-anticancer-effects-in-an-h%C3%A2-o%C3%A2-dependent-manner
#19
Collin D Heer, Andrew B Davis, David B Riffe, Brett A Wagner, Kelly C Falls, Bryan G Allen, Garry R Buettner, Robert A Beardsley, Dennis P Riley, Douglas R Spitz
Lung cancer, together with head and neck cancer, accounts for more than one-fourth of cancer deaths worldwide. New, non-toxic therapeutic approaches are needed. High-dose IV vitamin C (aka, pharmacological ascorbate; P-AscH-) represents a promising adjuvant to radiochemotherapy that exerts its anti-cancer effects via metal-catalyzed oxidation to form H₂O₂. Mn(III)-porphyrins possessing superoxide dismutase (SOD) mimetic activity have been shown to increase the rate of oxidation of AscH-, enhancing the anti-tumor effects of AscH- in several cancer types...
January 19, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29351056/remediation-of-radiation-induced-cognitive-dysfunction-through-oral-administration-of-the-neuroprotective-compound-nsi-189
#20
Barrett Allen, Munjal M Acharya, Celine Lu, Erich Giedzinski, Nicole Chmielewski, David Quach, Mike Hefferan, Karl K Johe, Charles L Limoli
Clinical management of primary and secondary central nervous system (CNS) malignancies frequently includes radiotherapy to forestall tumor growth and recurrence after surgical resection. While cranial radiotherapy remains beneficial, adult and pediatric brain tumor survivors suffer from a wide range of debilitating and progressive cognitive deficits. Although this has been recognized as a significant problem for decades, there remains no clinical recourse for the unintended neurocognitive sequelae associated with these types of cancer treatments...
January 19, 2018: Radiation Research
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