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Cancer immunity cycle

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https://www.readbyqxmd.com/read/28333208/soluble-vcam-1-soluble-icam-1-ratio-is-a-promising-biomarker-for-diagnosing-endometriosis
#1
L Kuessel, R Wenzl, K Proestling, S Balendran, P Pateisky, Yotova, G Yerlikaya, B Streubel, H Husslein
STUDY QUESTION: Do cell adhesion molecules play a role in endometriosis, and can they be used as a biomarker for diagnosing endometriosis? SUMMARY ANSWER: Altered expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in the endometrium and peritoneum may play a key role in endometriosis and the soluble VCAM-1/soluble ICAM-1 ratio is a promising biomarker. WHAT IS KNOWN ALREADY: Cell adhesion molecules are cell surface proteins that mediate cellular adherence, inflammatory and immune responses, and cancer-related biological processes...
February 23, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28330929/the-role-of-pias-sumo-e3-ligases-in-cancer
#2
REVIEW
Andrea Rabellino, Cristina Andreani, Pier Paolo Scaglioni
SUMOylation modifies the interactome, localization, activity, and lifespan of its target proteins. This process regulates several cellular machineries, including transcription, DNA damage repair, cell-cycle progression, and apoptosis. Accordingly, SUMOylation is critical in maintaining cellular homeostasis, and its deregulation leads to the corruption of a plethora of cellular processes that contribute to disease states. Among the proteins involved in SUMOylation, the protein inhibitor of activated STAT (PIAS) E3-ligases were initially described as transcriptional coregulators...
March 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28327944/a-phase-2-randomized-double-blind-placebo-%C3%A2-controlled-study-of-chemo-immunotherapy-combination-using-motolimod-with-pegylated-liposomal-doxorubicin-in-recurrent-or-persistent-ovarian-cancer-a-gynecologic-oncology-group-partners-study
#3
B J Monk, M F Brady, C Aghajanian, H A Lankes, T Rizack, J Leach, J M Fowler, R Higgins, P Hanjani, M Morgan, R Edwards, W Bradley, T Kolevska, P Foukas, E Swisher, K S Anderson, R Gottardo, J K Bryan, M Newkirk, K L Manjarrez, R S Mannel, R M Hershberg, G Coukos
Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28325688/current-and-emerging-molecular-tests-for-human-papillomavirus-related-neoplasia-in-the-genomic-era
#4
REVIEW
Sixto M Leal, Margaret L Gulley
Laboratory tests have a key role in preventing human papillomavirus (HPV)-driven carcinomas and in guiding therapeutic interventions. An understanding of the virology, immunology, and carcinogenesis of HPV is essential for choosing appropriate diagnostic test modalities and developing new and even more effective cancer prevention strategies. HPV infects basal epithelial cells on multiple surfaces and induces carcinoma primarily in the cervix and the oropharynx. HPV types are stratified as high risk or low risk based on their carcinogenic potential, driven largely by viral interference with cell cycle regulation and the DNA damage response to promote continuous cell division while thwarting apoptosis, which enables mutation accumulation...
March 18, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28323497/potential-mechanisms-underlying-cdk5-related-osteosarcoma-progression
#5
Hang-Xing Bao, Qing Bi, Yong Han, Chen Zhao, Hai Zou
OBJECTIVES: Identification of new prognostic biomarkers and therapeutic targets is of crucial importance for patients with osteosarcoma. Cyclin-dependent kinase 5 (CDK5) is overexpressed in several tumor types. However, the exact role CDK5 plays in osteosarcoma is still unknown. METHODS: In this study, we explored the association between CDK5 expression and the prognosis of osteosarcoma patients using publicly available gene expression datasets. Potential molecular mechanisms underlying its pro-malignant role in cancer progression were also discussed...
March 21, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28303530/a-randomized-open-label-multicenter-phase-ii-study-evaluating-the-efficacy-and-safety-of-bth1677-1-3-1-6-beta-glucan-imprime-pgg-in-combination-with-cetuximab-and-chemotherapy-in-patients-with-advanced-non-small-cell-lung-cancer
#6
M Thomas, P Sadjadian, J Kollmeier, J Lowe, P Mattson, J R Trout, M Gargano, M L Patchen, R Walsh, M Beliveau, J F Marier, N Bose, K Gorden, F Schneller
Introduction BTH1677, a 1,3-1,6 beta-glucan immunomodulator, stimulates a coordinated anti-cancer immune response in combination with anti-tumor antibody therapies. This phase II study explored the efficacy, pharmacokinetics (PK), and safety of BTH1677 combined with cetuximab/carboplatin/paclitaxel in untreated stage IIIB/IV non-small cell lung cancer (NSCLC) patients. Methods Patients were randomized 2:1 to the BTH1677 arm (N=60; BTH1677, 4 mg/kg, weekly; cetuximab, initial dose 400 mg/m(2) and subsequent doses 250 mg/m(2), weekly; carboplatin, 6 mg/mL/min AUC (area-under-the-curve) by Calvert formula, once each 3-week cycle [Q3W]); and paclitaxel, 200 mg/m(2), Q3W) or Control arm (N=30; cetuximab/carboplatin/paclitaxel as above)...
March 16, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28293794/do-all-patients-in-the-phase-i-oncology-trials-need-to-be-hospitalized-domestic-but-outstanding-issues-for-globalization-of-drug-development-in-japan
#7
Akihiko Shimomura, Shunsuke Kondo, Noriko Kobayashi, Satoru Iwasa, Shigehisa Kitano, Kenji Tamura, Yutaka Fujiwara, Noboru Yamamoto
INTRODUCTION: Most trials investigating new drugs around the world, including phase I trials, are conducted in outpatient clinics. However, in Japan, regulatory authority requirements and traditional domestic guidelines often require hospitalization of phase I study participants. PATIENTS AND METHODS: Patients participating in single-agent phase I clinical trials at National Cancer Center Hospital between December 1996 and August 2014 were monitored. Toxicity requiring hospitalization is defined as toxicity that needs intensive treatment...
March 14, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28289863/a-phase-ii-study-of-reolysin-%C3%A2-pelareorep-in-combination-with-carboplatin-and-paclitaxel-for-patients-with-advanced-malignant-melanoma
#8
Devalingam Mahalingam, Christos Fountzilas, Jennifer Moseley, Nicole Noronha, Hue Tran, Romit Chakrabarty, Giovanni Selvaggi, Matthew Coffey, Brad Thompson, John Sarantopoulos
REOLYSIN(®) (pelareorep) is an investigational new drug, consisting of a live, replication-competent, Reovirus Type 3 Dearing strain in a proprietary formulation. Several preclinical and clinical trials with REOLYSIN(®) on a wide range of cancer indications have demonstrated antineoplastic activity on cells with activated RAS-signaling pathway. Furthermore, long-term survival benefits were evident in post-treatment patients indicating a potential antitumor immune response triggered by REOLYSIN(®). Numerous mono and/or combination therapy studies with the agent showed a consistent safety profile...
March 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28289079/deletion-of-f4l-ribonucleotide-reductase-in-vaccinia-virus-produces-a-selective-oncolytic-virus-and-promotes-anti-tumor-immunity-with-superior-safety-in-bladder-cancer-models
#9
Kyle G Potts, Chad R Irwin, Nicole A Favis, Desmond B Pink, Krista M Vincent, John D Lewis, Ronald B Moore, Mary M Hitt, David H Evans
Bladder cancer has a recurrence rate of up to 80% and many patients require multiple treatments that often fail, eventually leading to disease progression. In particular, standard of care for high-grade disease, Bacillus Calmette-Guérin (BCG), fails in 30% of patients. We have generated a novel oncolytic vaccinia virus (VACV) by mutating the F4L gene that encodes the virus homolog of the cell-cycle-regulated small subunit of ribonucleotide reductase (RRM2). The F4L-deleted VACVs are highly attenuated in normal tissues, and since cancer cells commonly express elevated RRM2 levels, have tumor-selective replication and cell killing...
March 13, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28286742/persistent-exposure-to-porphyromonas-gingivalis-promotes-proliferative-and-invasion-capabilities-and-tumorigenic-properties-of-human-immortalized-oral-epithelial-cells
#10
Fengxue Geng, Junchao Liu, Yan Guo, Chen Li, Hongyang Wang, Hongyan Wang, Haijiao Zhao, Yaping Pan
Recent epidemiological studies revealed a significant association between oral squamous cell carcinoma (OSCC) and Porphyromonas gingivalis, a major pathogen of periodontal disease. As a keystone pathogen of periodontitis, P. gingivalis is known not only to damage local periodontal tissues, but also to evade the host immune system and eventually affect systemic health. However, its role in OSCC has yet to be defined. To explore the underlying effect of chronic P. gingivalis infection on OSCC and to identify relevant biomarkers as promising targets for therapy and prevention, we established a novel model by exposing human immortalized oral epithelial cells (HIOECs) to P...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28283885/anti-inflammatory-effects-of-atorvastatin-by-suppressing-traf3ip2-and-il-17ra-in-human-glioblastoma-spheroids-cultured-in-a-three-dimensional-model-possible-relevance-to-glioblastoma-treatment
#11
Neda Bayat, Somayeh Ebrahimi-Barough, Abbas Norouzi-Javidan, Hooshang Saberi, Mohammad Mehdi Mokhtari Ardakan, Arman Ai, Mostafa Soleimannejad, Jafar Ai
Glioblastoma multiform (GBM) is a primary malignant brain tumor with a few therapeutic targets available for it. The interaction between the immune system and glioma is an important factor that could lead to novel therapeutic approaches to fight glioma. In this study, we investigated in vitro anti-inflammatory and apoptotic activity of atorvastatin in different concentrations 1, 5, and 10 μM on glioma spheroid cells cultured in a three-dimensional model in fibrin gel that indicate the complex in vivo microenvironment better than a simple two-dimensional cell culture...
March 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28271657/dna-damage-response-is-hijacked-by-human-papillomaviruses-to-complete-their-life-cycle
#12
Shi-Yuan Hong
The DNA damage response (DDR) is activated when DNA is altered by intrinsic or extrinsic agents. This pathway is a complex signaling network and plays important roles in genome stability, tumor transformation, and cell cycle regulation. Human papillomaviruses (HPVs) are the main etiological agents of cervical cancer. Cervical cancer ranks as the fourth most common cancer among women and the second most frequent cause of cancer-related death worldwide. Over 200 types of HPVs have been identified and about one third of these infect the genital tract...
2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/28267050/nivolumab-causing-a-polymyalgia-rheumatica-in-a-patient-with-a-squamous-non-small-cell-lung-cancer
#13
Marjorie Bernier, Cyril Guillaume, Nathalie Leon, Joachim Alexandre, Lea Hamel-Senecal, Basile Chretien, Florian Lecaignec, Xavier Humbert, Sophie Fedrizzi, Jeannick Madelaine, Marion Sassier
The anti-programmed cell-death-1 antibody, nivolumab, has been recently approved for the treatment of advanced non-small cell lung cancer. Although, today, immune-related adverse effects such as dermatologic, digestive, hepatic, and endocrine toxicities are well-known with immune checkpoint inhibitors, rheumatic diseases are less well described. Herein, we report the case of a patient without a history of arthritis who developed polymyalgia rheumatica after 13 cycles of nivolumab used for the treatment of advanced non-small cell lung cancer...
March 6, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28260922/metronomic-treatment-of-advanced-non-small-cell-lung-cancer-with-daily-oral-vinorelbine-a-phase-i-trial
#14
Sylvia Guetz, Amanda Tufman, Joachim von Pawel, Achim Rittmeyer, Astrid Borgmeier, Pierre Ferré, Birgit Edlich, Rudolf Maria Huber
MICRO-ABSTRACT: In a Phase I dose-finding study of metronomic daily oral vinorelbine in advanced non-small-cell lung cancer, a recommended dose was established for this therapeutic approach. In addition, this trial revealed promising efficacy data and an acceptable tolerability profile. The observed vinorelbine blood concentrations suggest continuous anti-angiogenic coverage. INTRODUCTION: We present a Phase I dose-finding study investigating metronomic daily oral vinorelbine (Navelbine(®) Oral, NVBo) in advanced non-small-cell lung cancer (NSCLC)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28257957/the-cancer-immunity-cycle-as-rational-design-for-synthetic-cancer-drugs-novel-dc-vaccines-and-car-t-cells
#15
REVIEW
Mohanraj Ramachandran, Anna Dimberg, Magnus Essand
Cell therapy is an advanced form of cancer immunotherapy that has had remarkable clinical progress in the past decade in the search for cure of cancer. Most success has been achieved for chimeric antigen receptor (CAR) T-cells where CAR T-cells targeting CD19 show very high complete response rates for patients with refractory acute B-cell acute lymphoblastic leukemia (ALL) and are close to approval for this indication. CD19 CAR T-cells are also effective against B-cell chronic lymphoblastic leukemia (CLL) and B-cell lymphomas...
February 28, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28256603/exome-sequencing-identifies-potentially-druggable-mutations-in-nasopharyngeal-carcinoma
#16
Yock Ping Chow, Lu Ping Tan, San Jiun Chai, Norazlin Abdul Aziz, Siew Woh Choo, Paul Vey Hong Lim, Rajadurai Pathmanathan, Noor Kaslina Mohd Kornain, Chee Lun Lum, Kin Choo Pua, Yoke Yeow Yap, Tee Yong Tan, Soo Hwang Teo, Alan Soo-Beng Khoo, Vyomesh Patel
In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28255845/anti-pd-l1-atezolizumab-induced-autoimmune-diabetes-a-case-report-and-review-of-the-literature
#17
REVIEW
Laura Hickmott, Hugo De La Peña, Helen Turner, Fathelrahman Ahmed, Andrew Protheroe, Ashley Grossman, Avinash Gupta
Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors trigger an immune-mediated anti-tumour response by promoting the activation of cytotoxic T lymphocytes. Although proven to be highly effective in the treatment of several malignancies they can induce significant immune-related adverse events (irAEs) including endocrinopathies, most commonly hypophysitis and thyroid dysfunction, and rarely autoimmune diabetes. Here we present the first case report of a patient with a primary diagnosis of urothelial cancer developing PD-L1 inhibitor-induced autoimmune diabetes...
March 2, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28254412/bromodomain-inhibitors-jq1-and-i-bet-762-as-potential-therapies-for-pancreatic-cancer
#18
Ana S Leal, Charlotte R Williams, Darlene B Royce, Patricia A Pioli, Michael B Sporn, Karen T Liby
Bromodomain inhibitors (JQ1 and I-BET 762) are a new generation of selective, small molecule inhibitors that target BET (bromodomain and extra terminal) proteins. By impairing their ability to bind to acetylated lysines on histones, bromodomain inhibitors interfere with transcriptional initiation and elongation. BET proteins regulate several genes responsible for cell cycle, apoptosis and inflammation. In this study, JQ1 and I-BET 762 decreased c-Myc and p-Erk 1/2 protein levels and inhibited proliferation in pancreatic cancer cells...
February 27, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28253720/the-potential-roles-of-vesicle-enclosed-mirnas-in-communication-between-macrophages-and-cancer-cells-in-tumor-microenvironment
#19
M Korabecna, L Koutova, P Tesarova
Functional microRNA (miRNA) molecules are transported in extracellular vesicles among tumor cells and cells of the immune system. Macrophages as integral components of tumor microenvironment are known as potential contributors to tumor growth and progression. We searched for studies which could provide a direct link between the particular miRNAs transported between cancer cells and macrophages and experimental evidence of subsequent alterations in biological functions of target cells. The validated targets of such microRNAs were found using miRWalk database...
March 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/28248240/global-proteome-changes-in-liver-tissue-6-weeks-after-folfox-treatment-of-colorectal-cancer-liver-metastases
#20
Jozef Urdzik, Anna Vildhede, Jacek R Wiśniewski, Frans Duraj, Ulf Haglund, Per Artursson, Agneta Norén
(1) Oxaliplatin-based chemotherapy for colorectal cancer liver metastasis is associated with sinusoidal injury of liver parenchyma. The effects of oxaliplatin-induced liver injury on the protein level remain unknown. (2) Protein expression in liver tissue was analyzed-from eight patients treated with FOLFOX (combination of fluorouracil, leucovorin, and oxaliplatin) and seven controls-by label-free liquid chromatography mass spectrometry. Recursive feature elimination-support vector machine and Welch t-test were used to identify classifying and relevantly changed proteins, respectively...
October 14, 2016: Proteomes
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