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https://www.readbyqxmd.com/read/29332347/genetically-engineered-bone-marrow-derived-mesenchymal-stem-cells-co-expressing-ifn-%C3%AE-and-il-10-inhibit-hepatocellular-carcinoma-by-modulating-mapk-pathway
#1
Hao Wang, Jun Wang, Xiaolei Shi, Yitao Ding
PURPOSE: One of the major challenges in delivering cytokines for the treatment of hepatocellular carcinoma (HCC) is the mode of delivery. This study hypothesized that genetically engineered bone marrow derived mesenchymal stem cells (BMSCs) co-expressing IFN-γ and IL-10 can serve as a potential therapeutic strategy in the treatment of HCC by inhibiting cell proliferation. METHODS: Male Sprague-Dawley rats (n=5, 200-250 g) for BMSCs isolation and Nude/SCID mice (n=35,12-20g) to develop liver cancer xenograft model were used...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29332262/tumor-expression-of-survivin-p53-cyclin-d1-osteopontin-and-fibronectin-in-predicting-the-response-to-neo-adjuvant-chemotherapy-in-children-with-advanced-malignant-peripheral-nerve-sheath-tumor
#2
Gabrielle Karpinsky, Malgorzata A Krawczyk, Ewa Izycka-Swieszewska, Aleksandra Fatyga, Agnieszka Budka, Walentyna Balwierz, Grazyna Sobol, Beata Zalewska-Szewczyk, Magdalena Rychlowska-Pruszynska, Teresa Klepacka, Bozenna Dembowska-Baginska, Bernarda Kazanowska, Anna Gabrych, Ewa Bien
PURPOSE: Selected cell-cycle regulators and extracellular matrix proteins were found to play roles in malignant peripheral nerve sheath tumor (MPNST) biology. We aimed to analyze whether initial tumor tissue expressions of survivin, p53, cyclin D1, osteopontin (OPN) and fibronectin (FN) correlate with the response to neo-adjuvant CHT (naCHT) in children with advanced inoperable MPNST. METHODS: The study included 26 children with MPNST (M/F 14/12, median age 130 months) treated in Polish centers of pediatric oncology between 1992 and 2013...
January 13, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29331888/a-longitudinal-analysis-of-ido-and-pdl1-expression-during-immune-or-targeted-therapy-in-advanced-melanoma
#3
Lukas Krähenbühl, Simone M Goldinger, Joanna Mangana, Katrin Kerl, Ines Chevolet, Liève Brochez, Christine Horak, Mitch Levesque, Reinhard Dummer, Phil F Cheng
A deepened understanding of the cellular and molecular processes in the tumor microenvironment is necessary for the development of precision immunotherapy (IT). We simultaneously investigated CD3, PDL1, and IDO by immunohistochemistry in paired biopsies from various organs of 43 metastatic melanoma patients treated with IT and targeted therapy (TT). Intraindividual biopsies taken after a period of weeks to months demonstrate discordant results in 30% of the cases. Overlap of IDO and PDL1 increased after therapy...
January 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29331886/anti-cancer-effects-of-hnha-and-lenvatinib-by-the-suppression-of-emt-mediated-drug-resistance-in-cancer-stem-cells
#4
Yong Sang Lee, Seok-Mo Kim, Bup-Woo Kim, Ho Jin Chang, Soo Young Kim, Cheong Soo Park, Ki Cheong Park, Hang-Seok Chang
Anaplastic thyroid cancer (ATC) constitutes less than 2% of total thyroid cancers but accounts for 20-40% of thyroid cancer-related deaths. Cancer stem cell drug resistance represents a primary factor hindering treatment. This study aimed to develop targeted agents against thyroid malignancy, focusing on individual and synergistic effects of HNHA (histone deacetylase), lenvatinib (FGFR), and sorafenib (tyrosine kinase) inhibitors. Patients with biochemically and histologically proven papillary thyroid cancer (PTC) and ATC were included...
January 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29331760/inotodiol-suppresses-proliferation-of-breast-cancer-in-rat-model-of-type-2-diabetes-mellitus-via-downregulation-of-%C3%AE-catenin-signaling
#5
Xia Zhang, Cuiyu Bao, Jingping Zhang
Breast cancer is amongst the most common cancers causing death of women worldwide. Breast cancer occurrence is more prominent in people with diabetes. A recent trend is management of diabetes and cancer has evolved to be natural remedy including single molecule therapy or combination. In this study, we investigated the effect of inotodiol on breast cancer growth in diabetic conditions. Inotodiol is a lanostane triterpenoid found in natural resources like edible mushroom Inonotus obliquus. We established a rat model of diabetic-breast cancer by treating female Sprague-Dawley rats with streptazotocin (STZ) at 35 mg/kg followed by induction of breast cancer by administration of 7,12-dimethylbenz(a)anthracene (DMBA) at 10 mg/kg...
January 10, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29331723/progesterone-arrested-cell-cycle-progression-through-progesterone-receptor-isoform-a-in-pancreatic-neuroendocrine-neoplasm
#6
Samaneh Yazdani, Atsuko Kasajima, Yoshiaki Onodera, Keely May McNamara, Kazue Ise, Yasuhiro Nakamura, Tomoyoshi Tachibana, Fuyuhiko Motoi, Michiaki Unno, Hironobu Sasano
In pancreatic neuroendocrine neoplasms (Pan-NEN) progesterone signaling has been shown to have both inhibitory and stimulatory effects on cell proliferation. The ability of progesterone to inhibit tumor proliferation is of particular interest and is suggested to be mediated through the less abundantly expressed progesterone receptor (PR) isoform A (PRA). To date the mechanistic processes underlying this inhibition of proliferation remain unclear. To examine the mechanism of PRA actions, the human Pan-NEN cell line QGP-1, that endogenously expresses PR isoform B (PRB) without PRA, was transfected with PRA...
January 10, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29331588/antagonism-of-cysteinyl-leukotriene-receptor-1-cysltr1-by-montelukast-suppresses-cell-senescence-of-chondrocytes
#7
Wei Song, Yumin Zhang, Jun Wang, Tao Ma, Linjie Hao, Kunzheng Wang
Aging is closely associated with osteoarthritis (OA). Although its underlying mechanisms remain unknown, cellular senescence in chondrocytes has become an important therapeutic target for the treatment of OA. Cysteinyl leukotriene receptors (cysLTRs) mediate the pathobiological function of cysteinyl leukotrienes (cysLTs). However, the roles of cysLTRs in the pathogenesis of OA have not been reported before. In the current study, we found that cysLTR1 but not cysLTR2 is expressed in human primary chondrocytes...
January 10, 2018: Cytokine
https://www.readbyqxmd.com/read/29330434/targeting-melanoma-stem-cells-with-the-vitamin-e-derivative-%C3%AE-tocotrienol
#8
Monica Marzagalli, Roberta Manuela Moretti, Elio Messi, Marina Montagnani Marelli, Fabrizio Fontana, Alessia Anastasia, Maria Rosa Bani, Giangiacomo Beretta, Patrizia Limonta
The prognosis of metastatic melanoma is very poor, due to the development of drug resistance. Cancer stem cells (CSCs) may play a crucial role in this mechanism, contributing to disease relapse. We first characterized CSCs in melanoma cell lines. We observed that A375 (but not BLM) cells are able to form melanospheres and show CSCs traits: expression of the pluripotency markers SOX2 and KLF4, higher invasiveness and tumor formation capability in vivo with respect to parental adherent cells. We also showed that a subpopulation of autofluorescent cells expressing the ABCG2 stem cell marker is present in the A375 spheroid culture...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330294/establishment-of-the-first-well-differentiated-human-pancreatic-neuroendocrine-tumor-model
#9
Daniel Benten, Yasmin Behrang, Ludmilla Unrau, Victoria Weissmann, Gerrit Wolters-Eisfeld, Susanne Burdak-Rothkamm, Felix R Stahl, Martin Anlauf, Patricia Grabowski, Markus Möbs, Jan Dieckhoff, Bence Sipos, Martina Fahl, Corinna Eggers, Daniel Perez, Maximilian Bockhorn, Jakob R Izbicki, Ansgar W Lohse, Joerg Schrader
Clinical options for systemic therapy of neuroendocrine tumors (NET) are limited. Development of new drugs requires suitable representative in vitro and in vivo model systems. So far, the unavailability of a human model with a well-differentiated phenotype and typical growth characteristics has impaired pre-clinical research in NET. Herein, we establish and characterize a lymph node-derived cell line (NT-3) from a male patient with well-differentiated pancreatic NET. Neuroendocrine differentiation and tumor biology was compared to existing NET cell lines BON and QGP-1...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330256/osteoprotegerin-is-associated-with-major-bleeding-but-not-with-cardiovascular-outcomes-in-patients-with-acute-coronary-syndromes-insights-from-the-plato-platelet-inhibition-and-patient-outcomes-trial
#10
Thor Ueland, Axel Åkerblom, Tatevik Ghukasyan, Annika E Michelsen, Pål Aukrust, Richard C Becker, Maria Bertilsson, Anders Himmelmann, Stefan K James, Agneta Siegbahn, Robert F Storey, Frederic Kontny, Lars Wallentin
BACKGROUND: Elevated levels of osteoprotegerin, a secreted tumor necrosis factor-related molecule, might be associated with adverse outcomes in patients with coronary artery disease. We measured plasma osteoprotegerin concentrations on hospital admission, at discharge, and at 1 and 6 months after discharge in a predefined subset (n=5135) of patients with acute coronary syndromes in the PLATO (Platelet Inhibition and Patient Outcomes) trial. METHODS AND RESULTS: The associations between osteoprotegerin and the composite end point of cardiovascular death, nonprocedural spontaneous myocardial infarction or stroke, and non-coronary artery bypass grafting major bleeding during 1 year of follow-up were assessed by Cox proportional hazards models...
January 12, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29330207/early-assessment-of-lung-cancer-immunotherapy-response-via-circulating-tumor-dna
#11
Sarah B Goldberg, Azeet Narayan, Adam J Kole, Roy H Decker, Jimmitti Teysir, Nicholas J Carriero, Angela Lee, Roxanne Nemati, Sameer K Nath, Shrikant M Mane, Yanhong Deng, Nitin Sukumar, Daniel Zelterman, Daniel J Boffa, Katerina Politi, Scott Gettinger, Lynn D Wilson, Roy S Herbst, Abhijit A Patel
PURPOSE: Decisions to continue or suspend therapy with immune checkpoint inhibitors are commonly guided by tumor dynamics seen on serial imaging.  However, immunotherapy responses are uniquely challenging to interpret because tumors often shrink slowly or can appear transiently enlarged due to inflammation.  We hypothesized that monitoring tumor cell death in real-time by quantifying changes in circulating tumor DNA (ctDNA) levels could enable early assessment of immunotherapy efficacy...
January 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29330202/high-risk-tp53-mutations-are-associated-with-extra-nodal-extension-ene-in-oral-cavity-squamous-cell-carcinoma-oscc
#12
Vlad C Sandulache, Chieko Michikawa, Pranav Kataria, Frederico O Gleber-Netto, Diana Bell, Sanchit Trivedi, Xiayu Rao, Jing Wang, Mei Zhao, Samar A Jasser, Jeffrey N Myers, Curtis R Pickering
PURPOSE:   Development of extra-nodal extension (ENE) has been associated with poor survival in patients with oral cavity squamous cell carcinoma (OSCC). Here we sought to confirm the role of ENE as a poor prognostic factor, and identify genomic and epigenetic markers of ENE in order to develop a predictive model and improve treatment selection. EXPERIMENTAL DESIGN: An institutional cohort (University of Texas MD Anderson Cancer Center) was utilized to confirm the impact of ENE on clinical outcomes and evaluate the genomic signature of primary and ENE containing tissue...
January 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29330143/breast-cancer-targeting-through-inhibition-of-the-endoplasmic-reticulum-based-apoptosis-regulator-nrh-bcl2l10
#13
Adrien Nougarede, Nikolay Popgeorgiev, Loay Kassem, Soleilmane Omarjee, Stephane Borel, Ivan Mikaelian, Jonathan Lopez, Rudy Gadet, Olivier Marcillat, Isabelle Treilleux, Bruno O Villoutreix, Ruth Rimokh, Germain Gillet
Drug resistance and metastatic relapse remain a top challenge in breast cancer treatment. In this study, we present preclinical evidence for a strategy to eradicate advanced breast cancers by targeting the BCL2 homolog Nrh/BCL2L10, which we discovered to be overexpressed in >45% of a large cohort of breast invasive carcinomas. Nrh expression in these tumors correlated with reduced metastasis-free survival and we determined it to be an independent marker of poor prognosis. Nrh protein localized to the endoplasmic reticulum (ER)...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29329997/clinical-log-data-analysis-for-assessing-the-accuracy-of-the-cyberknife-fiducial-free-lung-tumor-tracking-system
#14
Masao Nakayama, Hideki Nishimura, Hiroshi Mayahara, Masaki Nakamura, Kazuyuki Uehara, Shinji Tsudou, Aya Harada, Hiroaki Akasaka, Ryohei Sasaki
PURPOSE: The CyberKnife Xsight Lung Tracking (XLT) and 1-View tracking systems can synchronize beam targeting to a visible lung tumor with respiratory motion during irradiation without requiring internal fiducial markers. The systems use a correlation model that relates external marker positions to tumor positions as well as a prediction model that predicts the target's future position. In this study, the correlation and prediction model uncertainties related to the CyberKnife fiducial-free tumor tracking system were evaluated using clinical log data...
November 4, 2017: Practical Radiation Oncology
https://www.readbyqxmd.com/read/29329590/frequent-overexpression-of-amap1-an-arf6-effector-in-cell-invasion-is-characteristic-of-the-mmtv-pymt-rather-than-the-mmtv-neu-human-breast-cancer-model
#15
Yutaro Otsuka, Tsukasa Oikawa, Hinako Yoshino, Shigeru Hashimoto, Haruka Handa, Hiroki Yamamoto, Ari Hashimoto, Hisataka Sabe
BACKGROUND: The small GTPase Arf6 and its downstream effector AMAP1 (also called ASAP1/DDEF1) constitute a signaling pathway promoting cell invasion, in which AMAP1 interacts with several different proteins, including PRKD2, EPB41L5, paxillin, and cortactin. Components of this pathway are often overexpressed in human breast cancer cells, to be correlated with poor prognosis of the patients, whereas overexpression of the Arf6 pathway did not correlate with the four main molecular classes of human breast tumors...
January 5, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29329588/accuracy-of-four-mononucleotide-repeat-markers-for-the-identification-of-dna-mismatch-repair-deficiency-in-solid-tumors
#16
Yuko Takehara, Takeshi Nagasaka, Akihiro Nyuya, Tomoko Haruma, Junko Haraga, Yoshiko Mori, Keiichiro Nakamura, Toshiyoshi Fujiwara, C Richard Boland, Ajay Goel
BACKGROUND: To screen tumors with microsatellite instability (MSI) arising due to DNA mismatch repair deficiency (dMMR), a panel of five quasi-monomorphic mononucleotide-repeat markers amplified in a multiplex PCR (Pentaplex) are commonly used. In spite of its several strengths, the pentaplex assay is not robust at detecting the loss of MSH6-deficiency (dMSH6). In order to overcome this challenge, we designed this study to develop and optimize a panel of four quasi-monomorphic mononucleotide-repeat markers (Tetraplex) for identifying solid tumors with dMMR, especially dMSH6...
January 12, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29329562/granular-cell-tumors-of-the-tongue-fibroma-or-schwannoma
#17
Atsushi Musha, Masaru Ogawa, Satoshi Yokoo
BACKGROUND: Granular cell tumors are benign lesions that typically occur in the oral cavity, but can also be found in other sites. However, the characteristics of these tumors are unclear. Thus, the present study aimed to investigate the immunohistological characteristics of these tumors of the tongue. METHODS: Seven patients were treated for granular cell tumors of the tongue at our institution during 2003-2017. Paraffin-embedded specimens were available for all cases; thus, retrospective immunohistochemical analyses were performed...
January 3, 2018: Head & Face Medicine
https://www.readbyqxmd.com/read/29329556/cancer-immunotherapy-beyond-immune-checkpoint-inhibitors
#18
REVIEW
Julian A Marin-Acevedo, Aixa E Soyano, Bhagirathbhai Dholaria, Keith L Knutson, Yanyan Lou
Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized...
January 12, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29329547/microfluidic-co-culture-of-pancreatic-tumor-spheroids-with-stellate-cells-as-a-novel-3d-model-for-investigation-of%C3%A2-stroma-mediated-cell-motility-and-drug-resistance
#19
Ji-Hyun Lee, Seul-Ki Kim, Iftikhar Ali Khawar, Su-Yeong Jeong, Seok Chung, Hyo-Jeong Kuh
BACKGROUND: Pancreatic stellate cells (PSCs), a major component of the tumor microenvironment in pancreatic cancer, play roles in cancer progression as well as drug resistance. Culturing various cells in microfluidic (microchannel) devices has proven to be a useful in studying cellular interactions and drug sensitivity. Here we present a microchannel plate-based co-culture model that integrates tumor spheroids with PSCs in a three-dimensional (3D) collagen matrix to mimic the tumor microenvironment in vivo by recapitulating epithelial-mesenchymal transition and chemoresistance...
January 12, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29329541/a-role-for-endothelial-nitric-oxide-synthase-in-intestinal-stem-cell-proliferation-and-mesenchymal-colorectal-cancer
#20
Jon Peñarando, Laura M López-Sánchez, Rafael Mena, Silvia Guil-Luna, Francisco Conde, Vanessa Hernández, Marta Toledano, Victoria Gudiño, Michela Raponi, Caroline Billard, Carlos Villar, César Díaz, José Gómez-Barbadillo, Juan De la Haba-Rodríguez, Kevin Myant, Enrique Aranda, Antonio Rodríguez-Ariza
BACKGROUND: Nitric oxide (NO) has been highlighted as an important agent in cancer-related events. Although the inducible nitric oxide synthase (iNOS) isoform has received most attention, recent studies in the literature indicate that the endothelial isoenzyme (eNOS) can also modulate different tumor processes including resistance, angiogenesis, invasion, and metastasis. However, the role of eNOS in cancer stem cell (CSC) biology and mesenchymal tumors is unknown. RESULTS: Here, we show that eNOS was significantly upregulated in VilCre ERT2 Apc fl/+ and VilCre ERT2 Apc fl/fl mouse intestinal tissue, with intense immunostaining in hyperproliferative crypts...
January 10, 2018: BMC Biology
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