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David L Elion, Rebecca S Cook
Cancer immunotherapies that remove checkpoint restraints on adaptive immunity are gaining clinical momentum. Approaches aimed at intrinsic cellular immunity in the tumor microenvironment are less understood, but are of intense interest, based on their ability to induce tumor cell apoptosis while orchestrating innate and adaptive immune responses against tumor antigens. The intrinsic immune response is initiated by ancient, highly conserved intracellular proteins that detect viral infection. For example, the RIG-I-like receptors (RLRs), a family of related RNA helicases, detect viral oligonucleotide patterns of certain RNA viruses...
June 22, 2018: Oncotarget
David M Goldenberg, Rhona Stein, Robert M Sharkey
TROP-2 is a glycoprotein first described as a surface marker of trophoblast cells, but subsequently shown to be increased in many solid cancers, with lower expression in certain normal tissues. It regulates cancer growth, invasion and spread by several signaling pathways, and has a role in stem cell biology and other diseases. This review summarizes TROP-2's properties, especially in cancer, and particularly its role as a target for antibody-drug conjugates (ADC) or immunotherapy. When the irinotecan metabolite, SN-38, is conjugated to a humanized anti-TROP-2 antibody (sacituzumab govitecan), it shows potent broad anticancer activity in human cancer xenografts and in patients with advanced triple-negative breast, non-small cell and small-cell lung, as well as urothelial cancers...
June 22, 2018: Oncotarget
Elsa Maitre, Philippe Bertrand, Catherine Maingonnat, Pierre-Julien Viailly, Margaux Wiber, Dina Naguib, Véronique Salaün, Edouard Cornet, Gandhi Damaj, Brigitte Sola, Fabrice Jardin, Xavier Troussard
Classical hairy cell leukemia (HCL-c) is a rare lymphoid neoplasm. BRAFV600E mutation, detected in more than 80% of the cases, is described as a driver mutation, but additional genetic abnormalities appear to be necessary for the disease progression. For cases of HCL-c harboring a wild-type BRAF gene, the differential diagnosis of the variant form of HCL (HCL-v) or splenic diffuse red pulp lymphoma (SDRPL) is complex. We selected a panel of 21 relevant genes based on a literature review of whole exome sequencing studies ( BRAF , MAP2K1 , DUSP2 , MAPK15 , ARID1A , ARID1B , EZH2 , KDM6A , CREBBP , TP53 , CDKN1B , XPO1 , KLF2 , CXCR4 , NOTH1 , NOTCH2 , MYD88 , ANXA1 , U2AF1 , BCOR , and ABCA8 )...
June 22, 2018: Oncotarget
Ishwaria M Subbiah, Chad Tang, Arvind Rao, Gerald S Falchook, Vivek Subbiah, Apostolia M Tsimberidou, Daniel Karp, Razelle Kurzrock, David S Hong
Background: Older adults aged 65 years and above remain underrepresented in cancer clinical trials. We hypothesized that older participation in early phase trials with VEGF/VEGFR (VEGF/R) inhibitors was lower than cancer prevalence in this group and lower than other age groups (middle age, adolescent/young adults [AYA]). Results: Of 1489 patients, 278 were older adults (18%, median age 68.9y), 220 AYA (15%, median age 32.6 y), 991 middle age (67%, median age 53...
June 22, 2018: Oncotarget
Shaojin Zhang, Qingwei Wang, Juanjuan He
[This corrects the article DOI: 10.18632/oncotarget.18549.].
June 22, 2018: Oncotarget
Antonella Rigo, Isacco Ferrarini, Giulio Innamorati, Fabrizio Vinante
CXCL12/CXCR4 axis relies on both heterotrimeric Gi protein and β-arrestin coupling to trigger downstream responses. G protein activation allows for calcium flux, chemotaxis and early extracellular-signal regulated kinases 1/2 (ERK1/2) phosphorylation, whereas β-arrestin recruitment leads to late signaling, receptor desensitization and internalization. Together they may regulate the balance between transactivation and transinhibition of epithelial growth factor receptor 1 (HER1). Since we have previously noted significant differences between CXCL12 and its structural variant [N33A]CXCL12 in CXCR4 signaling, we sought to better characterize them by performing cAMP inhibition and β-arrestin recruitment assays, as well as functional tests that separately investigate G protein and β-arrestin-induced responses...
June 22, 2018: Oncotarget
Mira Y Gökyildirim, Ulrich Grandel, Katja Hattar, Gabriele Dahlem, Elena Schuetz, Florian H Leinberger, Fabian Eberle, Ulf Sibelius, Friedrich Grimminger, Werner Seeger, Rita Engenhart-Cabillic, Ekkehard Dikomey, Florentine S B Subtil
Non-small cell lung cancer (NSCLC) has a very poor prognosis even when treated with the best therapies available today often including radiation. NSCLC is frequently complicated by pulmonary infections which appear to impair prognosis as well as therapy, whereby the underlying mechanisms are still not known. It was investigated here, whether the bacterial lipopolysaccharides (LPS) might alter the tumor cell radiosensitivity. LPS were found to induce a radioresistance but solely in cells with an active TLR-4 pathway...
June 22, 2018: Oncotarget
Yukie Yoshii, Mitsuyoshi Yoshimoto, Hiroki Matsumoto, Hideaki Tashima, Yuma Iwao, Hiroyuki Takuwa, Eiji Yoshida, Hidekatsu Wakizaka, Taiga Yamaya, Ming-Rong Zhang, Aya Sugyo, Sayaka Hanadate, Atsushi B Tsuji, Tatsuya Higashi
Peritoneal dissemination is a common cause of death from gastrointestinal cancers and is difficult to treat using current therapeutic options, particularly late-phase disease. Here, we investigated the feasibility of integrated therapy using 64 Cu-intraperitoneal radioimmunotherapy (ipRIT), alone or in combination with positron emission tomography (PET)-guided surgery using a theranostic agent (64 Cu-labeled anti-epidermal growth factor receptor antibody cetuximab) to treat early- and late-phase peritoneal dissemination in mouse models...
June 22, 2018: Oncotarget
Sami Sebastian Khaznadar, Martin Khan, Elke Schmid, Sebastian Gebhart, Eva-Tessina Becker, Thomas Krahn, Oliver von Ahsen
Background: Based on expression data, Epidermal Growth Factor Receptor (EGFR) emerged as therapeutic target in Head and Neck Cancer but clinical efficacy of EGFR inhibitors was very limited. We reinvestigated the EGFR expression and activation status necessary for response in cell lines and compared that to clinical samples. Methods: Clinical samples of head and neck squamous cell carcinoma (HNSCC, n=63), mostly from late stage (IV) and poorly or undifferentiated character and cultured cell lines (n=14) were tested by immunohistochemistry (IHC) (n=55) and sandwich immunoassays (n=63) for expression and phosphorylation of EGFR (Tyrosine-1173)...
June 22, 2018: Oncotarget
Roberta Fenoglio, Savino Sciascia, Giulietta Beltrame, Paola Mesiano, Michela Ferro, Giacomo Quattrocchio, Elisa Menegatti, Dario Roccatello
Minimal change disease (MCD) accounts for 15% of adult nephrotic syndrome (NS) cases. Adult-MCD patients may have more severe clinical features than pediatric patients. In children, Rituximab (RTX) has been used since 2006 to treat frequently relapsing NS. In adults, data about the efficacy of RTX for MCD are limited. We report our experience on the use of RTX in adult biopsy-proven MCD. Our series includes 6 adult patients (2 males and 4 females), age 45-73 years, treated with RTX (4 weekly doses of 375 mg/m2 )...
June 22, 2018: Oncotarget
Michael Constantin Kirchberger, Alvaro Moreira, Michael Erdmann, Gerold Schuler, Lucie Heinzerling
Dual immune-checkpoint blockade with the anti-PD-1 antibody nivolumab (1 mg/kg) and standard-dose ipilimumab (3 mg/kg) is the mainstay of immunotherapy in advanced melanoma and it is approved since 2016. However, severe side effects (grade 3/4) occur in up to 60% of the patients. Recently, clinical trials have shown similar anti-tumor activity with a more favorable toxicity profile in patients treated with low-dose ipilimumab (1 mg/kg) and standard-dose pembrolizumab (2 mg/kg). In this study we report on the real-world experience of this dosing regime in advanced melanoma patients not eligible for clinical trials...
June 22, 2018: Oncotarget
Dai Chihara, Nathan H Fowler, Yasuhiro Oki, Michelle A Fanale, Loretta J Nastoupil, Jason R Westin, Luis E Fayad, Sattva S Neelapu, Chan Yoon Cheah
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal presentation of lymphoma; however, the data for outcomes of patients with subtypes other than diffuse large B-cell lymphoma (DLBCL) are limited. Therefore, we analyzed overall survival (OS) of adult patients diagnosed with PCNSL by histologic subtype between 1998 and 2014 using the Surveillance, Epidemiology and End Results. A total of 4375 patients were identified. The median age of the patients was 64 years (range: 18-96)...
June 22, 2018: Oncotarget
Cory Pettit, Amy Webb, Steve Walston, Moumita Chatterjee, Wei Chen, Wendy Frankel, Carlo Croce, Terence M Williams
Purpose: There has been growing interest in using chemoradiation (CRT) for non-operative management of rectal cancer, and identifying patients who might benefit most from this approach is crucial. This study identified miRNAs (miRs) associated with clinical outcomes and treatment resistance by evaluating both pre- and post-CRT expression profiles. Methods: Forty patients, 9 with pathologic complete response (pCR) and 31 with pathologic incomplete response (pIR) were included...
June 22, 2018: Oncotarget
Andrew C Brown, Vishwanatha R A P Reddy, Joshua Lee, Venugopal Nair
Marek's disease (MD) is a neoplastic disease of poultry caused by Marek's disease virus (MDV), a highly contagious alphaherpesvirus. Meq, the major MDV oncoprotein, induces neoplastic transformation of T-cells through several mechanisms, including inhibition of apoptosis. In contrast, the chicken anemia virus (CAV)-encoded protein apoptin (VP3) is a powerful inducer of apoptosis of tumor cells, a property that is exploited for anticancer therapeutics. Although the molecular mechanisms of selective induction of tumor cell apoptosis by apoptin are not fully understood, its tumor cell-restricted nuclear translocation is thought to be important...
June 22, 2018: Oncotarget
Yamhilette Licon-Munoz, Colleen A Fordyce, Summer Raines Hayek, Karlett J Parra
Prostate Cancer (PCa) is the most commonly diagnosed cancer and the third leading cause of death for men in the United States. Suppression of androgen receptor (AR) expression is a desirable mechanism to manage PCa. Our studies showed that AR expression was reduced in LAPC4 and LNCaP PCa cell lines treated with nanomolar concentrations of the V-ATPase inhibitor concanamycin A (CCA). This treatment decreased PSA mRNA levels, indicative of reduced AR activity. V-ATPase-dependent repression of AR expression was linked to defective endo-lysosomal pH regulation and reduced AR expression at the transcriptional level...
June 22, 2018: Oncotarget
Janine Hensel, Antoinette Wetterwald, Ramzi Temanni, Irene Keller, Carsten Riether, Gabri van der Pluijm, Marco G Cecchini, George N Thalmann
Prostate and breast cancers frequently metastasize to bone. The physiological bone homeostasis is perturbed once cancer cells proliferate at the bone metastatic site. Tumors are complex structures consisting of cancer cells and numerous stroma cells. In this study, we show that osteolytic cancer cells (PC-3 and MDA-MB231) induce transcriptome changes in the bone/bone marrow microenvironment (stroma). This stroma transcriptome differs from the previously reported stroma transcriptome of osteoinductive cancer cells (VCaP)...
June 22, 2018: Oncotarget
Connie H M Ho, Chi-Leung Chiang, Francis A S Lee, Horace C W Choi, Jeffery C H Chan, Cynthia S Y Yeung, J J Huang, Mark K H Chan, Oliver Blanck, Frank C S Wong
Purpose: This work evaluated the prognostic performance of Child-Pugh (CP), albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) scores in hepatocellular carcinoma (HCC) patients undergoing radiotherapy (RT). Results: The study included 174 consecutive patients with 63% at CP A5 ( n = 110) and 34% at CP A6 ( n = 64). The median ALBI score was -2.39 (range: -3.61 to -1.41) with 34.5% at grade A1 ( n = 60) and 65.5% at grade A2 ( n = 114). The median PALBI score was -2...
June 22, 2018: Oncotarget
Tetsuya Idichi, Naohiko Seki, Hiroshi Kurahara, Haruhi Fukuhisa, Hiroko Toda, Masataka Shimonosono, Yasutaka Yamada, Takayuki Arai, Yoshiaki Kita, Yuko Kijima, Yuko Mataki, Kosei Maemura, Shoji Natsugoe
MicroRNAs (miRNAs) are unique in that a single miRNA molecule regulates a vast number of RNA transcripts. Thus, aberrantly expressed miRNAs disrupt tightly controlled RNA networks in cancer cells. Our functional screening showed that expression of miR-124-3p was downregulated in pancreatic ductal adenocarcinoma (PDAC) tissues. Here, we aimed to investigate the anti-tumor roles of miR-124-3p in PDAC cells and to identify miR-124-3p -mediated oncogenic signaling in this disease. Ectopic expression of miR-124-3p inhibited cancer cell migration and invasion in PDAC cells...
June 22, 2018: Oncotarget
Cristhian Manuel Durán-Acevedo, Aylen Lisset Jaimes-Mogollón, Oscar Eduardo Gualdrón-Guerrero, Tesfalem Geremariam Welearegay, Julián Davíd Martinez-Marín, Juan Martín Caceres-Tarazona, Zayda Constanza Sánchez-Acevedo, Kelvin de Jesus Beleño-Saenz, Umut Cindemir, Lars Österlund, Radu Ionescu
We present here the first study that directly correlates gastric cancer (GC) with specific biomarkers in the exhaled breath composition on a South American population, which registers one of the highest global incidence rates of gastric affections. Moreover, we demonstrate a novel solid state sensor that predicts correct GC diagnosis with 97% accuracy. Alveolar breath samples of 30 volunteers (patients diagnosed with gastric cancer and a controls group formed of patients diagnosed with other gastric diseases) were collected and analyzed by gas-chromatography/mass-spectrometry (GC-MS) and with an innovative chemical gas sensor based on gold nanoparticles (AuNP) functionalized with octadecylamine ligands...
June 22, 2018: Oncotarget
William Bruno, Claudia Martinuzzi, Bruna Dalmasso, Virginia Andreotti, Lorenza Pastorino, Francesco Cabiddu, Marina Gualco, Francesco Spagnolo, Alberto Ballestrero, Paola Queirolo, Federica Grillo, Luca Mastracci, Paola Ghiorzo
[This corrects the article DOI: 10.18632/oncotarget.23204.].
June 19, 2018: Oncotarget
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