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https://www.readbyqxmd.com/read/29691296/tryptophan-metabolism-contributes-to-radiation-induced-immune-checkpoint-reactivation-in-glioblastoma
#1
Pravin Kesarwani, Antony Prabhu, Shiva Kant, Praveen Kumar, Stewart F Graham, Katie L Buelow, George D Wilson, Christopher Ryan Miller, Prakash Chinnaiyan
PURPOSE: Immune checkpoint inhibitors designed to revert tumor-induced immune suppression have emerged as potent anti-cancer therapies. Tryptophan metabolism represents an immune checkpoint and targeting this pathway's rate limiting enzyme IDO1 is actively being investigated clinically. Here, we studied the intermediary metabolism of tryptophan metabolism in glioblastoma and evaluated the activity of the IDO1 inhibitor GDC-0919, both alone and in combination with radiation (RT).  Experimental Design: LC/GC-MS and expression profiling was performed for metabolomic and genomic analyses of patient-derived glioma...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29691252/high-usp6nl-levels-in-breast-cancer-sustain-chronic-akt-phosphorylation-and-glut1-stability-fueling-aerobic-glycolysis
#2
Daniele Avanzato, Emanuela Pupo, Nadia Ducano, Claudio Isella, Giovanni Bertalot, Chiara Luise, Salvatore Pece, Alejandra Bruna, Oscar M Rueda, Carlos Caldas, Pier Paolo Di Fiore, Anna Sapino, Letizia Lanzetti
USP6NL, also named RN-tre, is a GTPase activating protein (GAP) involved in control of endocytosis and signal transduction. Here we report that USP6NL is overexpressed in breast cancer (BC), mainly of the basal-like/integrative cluster 10 subtype. Increased USP6NL levels were accompanied by gene amplification and were associated with worse prognosis in the METABRIC dataset, retaining prognostic value in multivariable analysis. High levels of USP6NL in BC cells delayed endocytosis and degradation of the epidermal growth factor receptor (EGFR), causing chronic AKT activation...
April 24, 2018: Cancer Research
https://www.readbyqxmd.com/read/29691196/clinical-characteristics-and-outcomes-of-older-women-with-breast-cancer-in-mexico
#3
Paula Cabrera-Galeana, Enrique Soto-Perez-de-Celis, Nancy Reynoso-Noverón, Cynthia Villarreal-Garza, Claudia Arce-Salinas, Juan Matus-Santos, María Teresa Ramírez-Ugalde, Alberto Alvarado-Miranda, Abelardo Meneses-García, Fernando Lara-Medina, Juan Torres-Dominguez, Enrique Bargalló-Rocha, Alejandro Mohar
INTRODUCTION: Although the epidemiology of breast cancer in older women has been widely described before, little is known about the clinical characteristics and prognosis of older patients living in developing countries. Here, we studied older women with breast cancer treated at a public cancer center in Mexico City, and compared their outcomes with their younger counterparts. MATERIALS AND METHODS: We retrospectively analyzed a database of 5488 women treated for breast cancer at a single institution...
April 21, 2018: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/29691090/myeloid-derived-suppressor-cells-in-lymphoma-the-good-the-bad-and-the-ugly
#4
REVIEW
A Betsch, O Rutgeerts, S Fevery, B Sprangers, G Verhoef, D Dierickx, M Beckers
Lymphomas cause significant morbidity and mortality worldwide. A substantial number of patients ultimately relapse after standard treatment. However, the efficacy of these therapies can be counteracted by the patients' immune system, more specifically by myeloid-derived suppressor cells (MDSC). MDSC are a heterogeneous group of immature myeloid cells that suppress the innate and adaptive immune system via different mechanisms and accumulate under pathological conditions, such as cancer. MDSC play a role in the induction and progression of cancer and immune evasion...
April 19, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29690797/atezolizumab-for-the-treatment-of-breast-cancer
#5
Debora Basile, Giacomo Pelizzari, Maria Grazia Vitale, Camilla Lisanti, Marika Cinausero, Donatella Iacono, Fabio Puglisi
Breast cancer (BC) is the most common cancer diagnosed among women. The development of new personalized therapeutic strategies has reshaped the landscape in this field. However, BC is still the first cause of death among women. Interestingly, several preclinical studies and some clinical evidences are focused their attention on the role of immune system and immunotherapy on cancer control, also in BC. Areas covered: Usually, BC has been considered a not immunogenic tumor for its low mutational load. However, recent studies have evidenced that some subtypes, triple negative and HER-2 positive BC, are "hot" tumors, thus more immunogenic...
April 24, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29690599/clinicopathological-characteristics-and-mutations-driving-development-of-early-lung-adenocarcinoma-tumor-initiation-and-progression
#6
REVIEW
Kentaro Inamura
Lung cancer is the leading cause of cancer-related deaths worldwide, with lung adenocarcinoma representing the most common lung cancer subtype. Among all lung adenocarcinomas, the most prevalent subset develops via tumorigenesis and progression from atypical adenomatous hyperplasia (AAH) to adenocarcinoma in situ (AIS), to minimally invasive adenocarcinoma (MIA), to overt invasive adenocarcinoma with a lepidic pattern. This stepwise development is supported by the clinicopathological and molecular characteristics of these tumors...
April 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29687728/exposure-to-permethrin-and-cancer-risk-a-systematic-review
#7
Paolo Boffetta, Vimi Desai
No systematic reviews are available on data from humans on cancer risk from exposure to permethrin, a widely used insecticide for which some animal studies have reported positive findings based on mechanisms that may not be relevant to humans. We identified potentially relevant articles through a search of electronic databases which included all studies of pesticide exposure and human cancer. A total of 18 articles were selected, including six identified from the list of references of other articles. Most articles were based on analyzes of the Agriculture Health Study (AHS); they provided no evidence of an increased risk of cancers of colon, rectum, pancreas, lung, melanoma, female breast, prostate, urinary bladder, as well as non-Hodgkin lymphoma (including its main subtypes), and leukemia...
April 24, 2018: Critical Reviews in Toxicology
https://www.readbyqxmd.com/read/29687205/the-impact-of-hormonal-contraceptives-on-breast-cancer-pathology
#8
Jesse A Dorchak, Sifat Maria, Joseph L Guarinoni, Anette Duensing, Stella Somiari, Jane Cavanaugh, Brenda Deyarmin, Hai Hu, Joji Iida, Craig D Shriver, Paula A Witt-Enderby
This retrospective case series study, using data obtained through questionnaires and histopathological diagnoses from 656 patients enrolled in the Department of Defense (DoD) Clinical Breast Care Project (CBCP), evaluated associations between hormonal contraceptive use and breast cancer pathology including benign breast pathologies. Three combination hormonal contraceptive agents (COCs) Lo Ovral (LO), Ortho Novum (ON), and Ortho Tri-Cyclen (OTC) were evaluated as they represented the most commonly used hormonal contraceptives in our cohort...
April 23, 2018: Hormones & Cancer
https://www.readbyqxmd.com/read/29686080/systemic-surfaceome-profiling-identifies-target-antigens-for-immune-based-therapy-in-subtypes-of-advanced-prostate-cancer
#9
John K Lee, Nathanael J Bangayan, Timothy Chai, Bryan A Smith, Tiffany E Pariva, Sangwon Yun, Ajay Vashisht, Qingfu Zhang, Jung Wook Park, Eva Corey, Jiaoti Huang, Thomas G Graeber, James Wohlschlegel, Owen N Witte
Prostate cancer is a heterogeneous disease composed of divergent molecular and histologic subtypes, including prostate adenocarcinoma (PrAd) and neuroendocrine prostate cancer (NEPC). While PrAd is the major histology in prostate cancer, NEPC can evolve from PrAd as a mechanism of treatment resistance that involves a transition from an epithelial to a neurosecretory cancer phenotype. Cell surface markers are often associated with specific cell lineages and differentiation states in normal development and cancer...
April 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29685789/integrative-epi-genomic-analysis-to-predict-response-to-androgen-deprivation-therapy-in-prostate-cancer
#10
Sukanya Panja, Sheida Hayati, Nusrat J Epsi, James Scott Parrott, Antonina Mitrofanova
Therapeutic resistance is a central problem in clinical oncology. We have developed a systematic genome-wide computational methodology to allow prioritization of patients with favorable and poor therapeutic response. Our method, which integrates DNA methylation and mRNA expression data, uncovered a panel of 5 differentially methylated sites, which explain expression changes in their site-harboring genes, and demonstrated their ability to predict primary resistance to androgen-deprivation therapy (ADT) in the TCGA prostate cancer patient cohort (hazard ratio = 4...
April 12, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29684800/ethnic-disparity-in-breast-cancer-survival-in-southern-thai-women
#11
Shama Virani, Elizabeth C Wetzel, Suphawat Laohawiriyakamol, Pleumjit Boonyaphiphat, Alan Geater, Celina G Kleer, Judy Pang, Katie M Rentschler, Justin A Colacino, Carlos F Mendes de Leon, Laura S Rozek, Hutcha Sriplung
BACKGROUND: Breast cancer has the highest incidence in women of all cancers and its burden is expected to continue to increase worldwide, especially in middle-income countries such as Thailand. The southern region of Thailand is unique in that it is comprised of 30% Muslims, whereas the rest of Thailand is 95% Buddhist. Breast cancer incidence and survival differ between these religious groups, but the association between clinical subtype of breast cancer and survival has not yet been assessed...
April 20, 2018: Cancer Epidemiology
https://www.readbyqxmd.com/read/29684420/novel-cancer-gene-variants-and-gene-fusions-of-triple-negative-breast-cancers-tnbcs-reveal-their-molecular-diversity-conserved-in-the-patient-derived-xenograft-pdx-model
#12
Jaeyun Jung, Kiwon Jang, Jung Min Ju, Eunji Lee, Jong Won Lee, Hee Jung Kim, Jisun Kim, Sae Byul Lee, Beom Seok Ko, Byung Ho Son, Hee Jin Lee, Gyungyup Gong, Sei Yeon Ahn, Jung Kyoon Choi, Shree Ram Singh, Suhwan Chang
Despite the improved 5-year survival rate of breast cancer, triple-negative breast cancer (TNBC) remains a challenge due to lack of effective targeted therapy and higher recurrence and metastasis than other subtypes. To identify novel druggable targets and to understand its unique biology, we tried to implement 24 patient-derived xenografts (PDXs) of TNBC. The overall success rate of PDX implantation was 45%, much higher than estrogen receptor (ER)-positive cases. Immunohistochemical analysis revealed conserved ER/PR/Her2 negativity (with two exceptions) between the original and PDX tumors...
April 20, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29683140/liquid-biopsy-in-the-omics-era-of-tumor-medicine
#13
Yi Jiang, Denong Wang
Liquid biopsy uses noninvasive blood test to assess tumor heterogeneity and evolution in real time. It looks for tumor components in the blood circulation, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), to provide tumor-specific information. By detecting multiplex tumor biomarkers, including nucleic acids, proteins, carbohydrates, and other tumor-derived substances, liquid biopsy helps with early tumor diagnosis, tumor evolution monitoring, and prognosis prediction. With the development of high-throughput OMICS tools like carbohydrate microarray and high-speed fiber-optic array scanning technology (FAST scan), it is now practical to identify glycan markers of CTCs and cancer stem cells (CSCs), especially those that are cell-surface exposed and readily accessible for immune recognition and targeting...
2018: Open access journal of biomedical engineering and its applications
https://www.readbyqxmd.com/read/29682521/immune-escape-mechanisms-and-future-prospects-for-immunotherapy-in-neuroblastoma
#14
REVIEW
Thitinee Vanichapol, Somchai Chutipongtanate, Usanarat Anurathapan, Suradej Hongeng
Neuroblastoma (NB) is the most common extracranial solid tumor in childhood with 5-year survival rate of 40% in high-risk patients despite intensive therapies. Recently, adoptive cell therapy, particularly chimeric antigen receptor (CAR) T cell therapy, represents a revolutionary treatment for hematological malignancies. However, there are challenges for this therapeutic strategy with solid tumors, as a result of the immunosuppressive nature of the tumor microenvironment (TME). Cancer cells have evolved multiple mechanisms to escape immune recognition or to modulate immune cell function...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29682196/testosterone-metabolites-inhibit-proliferation-of-castration-and-therapy-resistant-prostate-cancer
#15
Felix Bremmer, Hubertus Jarry, Valerie Unterkircher, Silke Kaulfuss, Peter Burfeind, Heinz-Joachim Radzun, Philipp Ströbel, Paul Thelen
Novel treatments for castration-resistant prostate cancer (CRPC) such as abiraterone acetate (AA) or enzalutamide effectively target the androgen pathway to arrest aberrant signalling and cell proliferation. Testosterone is able to inhibit tumour cell growth in CRPC. Estrogen receptor-beta (ERβ) binds the testosterone-metabolites 3β-androstanediol and 3α-androstanediol in parallel to the canonical estradiol. In the prostate it is widely accepted that ERβ regulates estrogen signalling, mediating anti-proliferative effects...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29682102/expression-of-pentose-phosphate-pathway-related-proteins-in-breast-cancer
#16
Junjeong Choi, Eun-Sol Kim, Ja Seung Koo
Purpose: The purpose of this study was to assess the expression of pentose phosphate pathway- (PPP-) related proteins and their significance in clinicopathologic factors of breast cancer. Methods: Immunohistochemical staining for PPP-related proteins (glucose-6-phosphate dehydrogenase [G6PDH], 6-phosphogluconolactonase [6PGL], 6-phosphogluconate dehydrogenase [6PGDH], and nuclear factor-erythroid 2-related factor 2 [NRF2]) was performed using tissue microarray (TMA) of 348 breast cancers...
2018: Disease Markers
https://www.readbyqxmd.com/read/29681821/genomic-profiling-of-two-histologically-distinct-rare-urothelial-cancers-in-a-clinical-setting-to-identify-potential-therapeutic-options-for-treatment-and-management-of-disease
#17
Andrew N Hesse, William Fabricius, Christian A Thomas, Ramesh Gaindh, Robert Christman, Pavalan Selvam, Matthew Prego, Gregory Lewis, Jasmina Uvalic, Daniel Bergeron, Shelbi Burns, Bridgette Sisson, Kevin Kelly, Jens Rueter, Honey V Reddi
Molecular profiling of urothelial cancers for therapeutic and prognostic potential has been very limited due to the absence of cancer-specific targeted therapies. We describe here 2 clinical cases with a histological diagnosis of an invasive sarcomatoid and a poorly differentiated carcinoma favoring urothelial with some neuroendocrine differentiation, two of the rarer types of urothelial cancers, which were evaluated for mutations in 212 genes for single-nucleotide variants and copy-number variants and 53 genes for fusions associated with solid tumors...
January 2018: Case Reports in Oncology
https://www.readbyqxmd.com/read/29681456/chemoresistance-evolution-in-triple-negative-breast-cancer-delineated-by-single-cell-sequencing
#18
Charissa Kim, Ruli Gao, Emi Sei, Rachel Brandt, Johan Hartman, Thomas Hatschek, Nicola Crosetto, Theodoros Foukakis, Nicholas E Navin
Triple-negative breast cancer (TNBC) is an aggressive subtype that frequently develops resistance to chemotherapy. An unresolved question is whether resistance is caused by the selection of rare pre-existing clones or alternatively through the acquisition of new genomic aberrations. To investigate this question, we applied single-cell DNA and RNA sequencing in addition to bulk exome sequencing to profile longitudinal samples from 20 TNBC patients during neoadjuvant chemotherapy (NAC). Deep-exome sequencing identified 10 patients in which NAC led to clonal extinction and 10 patients in which clones persisted after treatment...
April 13, 2018: Cell
https://www.readbyqxmd.com/read/29680230/percutaneous-ablative-cryoimmunotherapy-for-micrometastaic-abscopal-effect-no-complications
#19
Erik Soule, Mark Bandyk, Jerry Matteo
Recent studies have shown efficacy of nivolumab, a monoclonal antibody specific for an immunoregulatory protein termed programmed death 1 (PD-1), against metastatic renal cell carcinoma. PD-1 is a transmembrane protein expressed on T cells that suppresses activation upon binding to its ligands, which may be secreted paraneoplastically by various cancers. Inhibition of PD-1 signaling via nivolumab may sensitize tumor-specific T lymphocytes in the immunosuppressive tumor microenvironment. Systemic elimination of micrometastases requires robust activation and proliferation of tumor antigen stimulated T cells...
April 19, 2018: Cryobiology
https://www.readbyqxmd.com/read/29680210/the-cadm2-akt-pathway-is-involved-in-the-inhibitory-effect-of-mir-21-5p-downregulation-on-proliferation-and-apoptosis-in-esophageal-squamous-cell-carcinoma-cells
#20
Xiaohui Li, Dong Chen, Mengfei Li, Xiang Gao, Gongning Shi, Hui Zhao
Esophageal squamous cell carcinoma (ESCC), the main subtype of esophageal cancer, is the eighth most common cancer worldwide. Cell adhesion molecule 2 (CADM2) has been reported to be a tumor suppressor and is usually downregulated in several cancers. However, the role of CADM2 in ESCC remains unknown. The aim of the present study was to evaluate the potential role and underlying action mechanism of CADM2 in ESCC. Herein, we found that CADM2 was low-expressed in ESCC tissues and cell lines. CADM2 overexpression inhibited proliferation and induced apoptosis of ESCC cells...
April 19, 2018: Chemico-biological Interactions
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