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https://www.readbyqxmd.com/read/28319448/rationale-and-design-of-a-phase-1-clinical-trial-to-evaluate-hsv-g207-alone-or-with-a-single-radiation-dose-in-children-with-progressive-or-recurrent-malignant-supratentorial-brain-tumors
#1
Alicia M Waters, James M Johnston, Alyssa T Reddy, John Fiveash, Avi Madan-Swain, Kara Kachurak, Asim K Bag, G Yancey Gillespie, James M Markert, Gregory K Friedman
Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer-related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy, and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor-specific tropism and potential efficacy in the treatment of malignant brain tumors...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28319088/reference-component-analysis-of-single-cell-transcriptomes-elucidates-cellular-heterogeneity-in-human-colorectal-tumors
#2
Huipeng Li, Elise T Courtois, Debarka Sengupta, Yuliana Tan, Kok Hao Chen, Jolene Jie Lin Goh, Say Li Kong, Clarinda Chua, Lim Kiat Hon, Wah Siew Tan, Mark Wong, Paul Jongjoon Choi, Lawrence J K Wee, Axel M Hillmer, Iain Beehuat Tan, Paul Robson, Shyam Prabhakar
Intratumoral heterogeneity is a major obstacle to cancer treatment and a significant confounding factor in bulk-tumor profiling. We performed an unbiased analysis of transcriptional heterogeneity in colorectal tumors and their microenvironments using single-cell RNA-seq from 11 primary colorectal tumors and matched normal mucosa. To robustly cluster single-cell transcriptomes, we developed reference component analysis (RCA), an algorithm that substantially improves clustering accuracy. Using RCA, we identified two distinct subtypes of cancer-associated fibroblasts (CAFs)...
March 20, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28319069/the-branched-chain-amino-acid-transaminase-1-sustains-growth-of-antiestrogen-resistant-and-er%C3%AE-negative-breast-cancer
#3
V Thewes, R Simon, M Hlevnjak, M Schlotter, P Schroeter, K Schmidt, Y Wu, T Anzeneder, W Wang, P Windisch, M Kirchgäßner, N Melling, N Kneisel, R Büttner, U Deuschle, H P Sinn, A Schneeweiss, S Heck, S Kaulfuss, H Hess-Stumpp, J G Okun, G Sauter, A E Lykkesfeldt, M Zapatka, B Radlwimmer, P Lichter, M Tönjes
Antiestrogen-resistant and triple-negative breast tumors pose a serious clinical challenge because of limited treatment options. We assessed global gene expression changes in antiestrogen-sensitive compared with antiestrogen-resistant (two tamoxifen resistant and two fulvestrant resistant) MCF-7 breast cancer cell lines. The branched-chain amino acid transaminase 1 (BCAT1), which catalyzes the first step in the breakdown of branched-chain amino acids, was among the most upregulated transcripts in antiestrogen-resistant cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28316008/cytogenetic-analysis-of-metaplastic-squamous-cell-carcinoma-of-the-breast-inter-and-intratumoral-heterogeneity
#4
Masahiro Oikawa, Akiko Igawa, Kenichi Taguchi, Kimiko Baba, Mayumi Ishida, Sayuri Akiyoshi, Hiroshi Yano, Takeshi Nagayasu, Shinji Ohno, Eriko Tokunaga
BACKGROUND: Squamous cell carcinoma (SCC) of the breast is a rare and generally aggressive disease that accounts for less than 0.1% of all breast carcinomas. Although SCCs have distinct morphological features, their origin and cytogenetic profile are not well understood. METHODS: Five patients with SCC were studied. The tumor area that was predominantly composed of SCC components was macrodissected and DNA was extracted. In three cases, an invasive or noninvasive ductal carcinoma of no special type (NST) component was also present...
March 18, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28315938/the-relationship-between-breast-cancer-molecular-subtypes-and-mast-cell-populations-in-tumor-microenvironment
#5
Anna Glajcar, Joanna Szpor, Agnieszka Pacek, Katarzyna Ewa Tyrak, Florence Chan, Joanna Streb, Diana Hodorowicz-Zaniewska, Krzysztof Okoń
Mast cells (MCs) are a part of the innate immune system. The MC functions toward cancer are partially based on the release of chymase and tryptase. However, the MC effect on breast cancer is controversial. The aim of our study was to investigate the presence of MCs in breast cancer tumors of different molecular subtypes and their relationships with other pathological prognostic factors. Tryptase- and chymase-positive mast cell densities were evaluated by immunohistochemistry in 108 primary invasive breast cancer tissue samples...
March 18, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28314739/intratumorous-heterogeneity-for-ras-mutations-in-a-treatment-na%C3%A3-ve-colorectal-tumour
#6
Sebastian Lunke, Belinda Lee, Sevastjan Kranz, Peter Gibbs, Paul Waring, Michael Christie
Activating mutations in KRAS and NRAS genes in patients with colorectal cancer (CRC) are associated with a lack of response to treatment with anti-epidermal growth factor receptor (EGFR) therapies. Mutations in these genes are thought to be mutually exclusive, however reports have described CRCs with two activating rat sarcoma (RAS) mutations. This has fuelled discussion about whether these mutations are the result of intratumorous heterogeneity, or if they are co-occurring in the same cancer cell clone. We present a case of a colorectal tumour with three RAS mutations detected during routine diagnostic testing...
March 17, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28306552/precise-determination-of-the-heat-delivery-during-in-vivo-magnetic-nanoparticle-hyperthermia-with-infrared-thermography
#7
Harley Rodrigues, Gustavo Capistrano, Francyelli Mello, Nicholas Zufelato, Elisangela Silveira-Lacerda, Andris F Bakuzis
Monitoring noninvasively and in real-time the heat delivery during magnetic nanoparticle hyperthermia is of fundamental importance to predict clinical outcome for cancer treatment. Infrared thermography (IRT) can inform the surface temperature due to three-dimensional heat delivery inside a subcutaneous tumor, an argument that is supported by numerical simulations. However, for precise temperature determination, it is of crucial relevance to use a correct experimental configuration. This work reports a magnetic nanoparticle hyperthermia study (MNH) using a sarcoma 180 murine tumor containing 3...
March 17, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28303203/a-case-of-acute-subdural-hematoma-due-to-bleeding-from-metastatic-chondrosarcoma-of-the-skull
#8
Kenzo Kosugi, Satoshi Takahashi, Hikaru Sasaki, Ryota Tamura, Kentaro Ohara, Kazunari Yoshida
BACKGROUND: Intra or peritumoral hemorrhage of brain and skull tumors sometimes presents as stroke. Skull metastasis of chondrosarcoma is relatively rare, and furthermore, a case of intratumoural hemorrhage of skull metastasis of chondrosarcoma has not been reported. CASE DESCRIPTION: A 73-year-old man underwent right lower leg amputation in the past because of chondrosarcoma and was operated for a skull metastasis. He presented with a sudden headache, and head computed tomography revealed a right acute subdural hematoma (SDH) adjacent to the recurrent skull metastatic tumor...
2017: Surgical Neurology International
https://www.readbyqxmd.com/read/28302680/genomic-and-epigenomic-heterogeneity-of-hepatocellular-carcinoma
#9
De-Chen Lin, Anand Mayakonda, Huy Q Dinh, Pinbo Huang, Lehang Lin, Xiaoping Liu, Ling-Wen Ding, Jie Wang, Benjamin Berman, Erwei Song, Dong Yin, H Phillip Koeffler
Understanding the intratumoral heterogeneity of hepatocellular carcinoma (HCC) is instructive for developing personalized therapy and identifying molecular biomarkers. Here we applied whole-exome sequencing to 69 samples from 11 patients to resolve the genetic architecture of subclonal diversification. Spatial genomic diversity was found in all 11 HCC cases, with 29% of driver mutations being heterogeneous, including TERT, ARID1A, NOTCH2, and STAG2. Similar with other cancer types, TP53 mutations were always shared between all tumor regions i...
February 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28302530/regorafenib-overcomes-chemotherapeutic-multidrug-resistance-mediated-by-abcb1-transporter-in-colorectal-cancer-in-vitro-and-in-vivo-study
#10
Yi-Jun Wang, Yun-Kai Zhang, Guan-Nan Zhang, Sweilem B Al Rihani, Meng-Ning Wei, Pranav Gupta, Xiao-Yu Zhang, Suneet Shukla, Suresh V Ambudkar, Amal Kaddoumi, Zhi Shi, Zhe-Sheng Chen
Chemotherapeutic multidrug resistance (MDR) is a significant challenge to overcome in clinic practice. Several mechanisms contribute to MDR, one of which is the augmented drug efflux induced by the upregulation of ABCB1 in cancer cells. Regorafenib, a multikinase inhibitor targeting the RAS/RAF/MEK/ERK pathway, was approved by the FDA to treat metastatic colorectal cancer and gastrointestinal stromal tumors. We investigated whether and how regorafenib overcame MDR mediated by ABCB1. The results showed that regorafenib reversed the ABCB1-mediated MDR and increased the accumulation of [(3)H]-paclitaxel in ABCB1-overexpressing cells by suppressing efflux activity of ABCB1, but not altering expression level and localization of ABCB1...
March 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28302144/a-dosimetric-model-for-the-heterogeneous-delivery-of-radioactive-nanoparticles-in-vivo-a-feasibility-study
#11
Andrew B Satterlee, Peter Attayek, Bentley Midkiff, Leaf Huang
ᅟ: Accurate and quantitative dosimetry for internal radiation therapy can be especially challenging, given the heterogeneity of patient anatomy, tumor anatomy, and source deposition. Internal radiotherapy sources such as nanoparticles and monoclonal antibodies require high resolution imaging to accurately model the heterogeneous distribution of these sources in the tumor. The resolution of nuclear imaging modalities is not high enough to measure the heterogeneity of intratumoral nanoparticle deposition or intratumoral regions, and mathematical models do not represent the actual heterogeneous dose or dose response...
March 17, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28300564/contrasting-roles-of-the-abcg2-q141k-variant-in-prostate-cancer
#12
Kathryn M Sobek, Jessica L Cummings, Dean J Bacich, Denise S O'Keefe
ABCG2 is a membrane transport protein that effluxes growth-promoting molecules, such as folates and dihydrotestosterone, as well as chemotherapeutic agents. Therefore it is important to determine how variants of ABCG2 affect the transporter function in order to determine whether modified treatment regimens may be necessary for patients harboring ABCG2 variants. Previous studies have demonstrated an association between the ABCG2 Q141K variant and overall survival after a prostate cancer diagnosis. We report here that in patients with recurrent prostate cancer, those who carry the ABCG2 Q141K variant had a significantly shorter time to PSA recurrence post-prostatectomy than patients homozygous for wild-type ABCG2 (P=0...
March 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28299887/fibroepithelial-lesions-in-the-breast-of-adolescent-females-a-clinicopathological-study-of-54-cases
#13
Dara S Ross, Dilip D Giri, Muzaffar M Akram, Jeffrey P Catalano, Cristina Olcese, Kimberly J Van Zee, Edi Brogi
Fibroepithelial lesions (FELs) are the most frequent breast tumors in adolescent females. The pubertal hormonal surge could impact the growth and microscopic appearance of FELs in this age group. In this study, we evaluate the morphology and clinical behavior of FELs in adolescents. We searched the 1992-2012 pathology data base for FELs in females 18 years old or younger (F ≤18 years). Seven FELs from 1975 to 1983 were also included. Three pathologists reviewed all available material. Patient (pt) characteristics and follow-up information were obtained from electronic medical records...
March 2017: Breast Journal
https://www.readbyqxmd.com/read/28297689/-a-case-of-subcortical-intracerebral-hemorrhage-caused-by-underlying-oligodendroglioma-diagnosed-through-long-term-follow-up
#14
Masamune Kidoguchi, Makoto Isozaki, Satoshi Hirose, Ryuhei Kitai, Ken-Ichiro Kikuta
We report on a case of an oligodendroglioma that caused intracerebral hemorrhage, which was diagnosed by long-term follow-up. An 82-year-old man with underlying hypertrophic cardiomyopathy presented with weakness in the right upper extremity. Computed tomography and magnetic resonance imaging(MRI)showed intracerebral hemorrhage and focal brain edema. Since there was a discrepancy between hematoma and focal brain edema, we first diagnosed cardiogenic cerebral embolism. Six months later, MRI results showed an improvement of the brain edema; however, the lesion developed after a year...
March 2017: No Shinkei Geka. Neurological Surgery
https://www.readbyqxmd.com/read/28297623/clinical-implications-of-novel-genomic-discoveries-in-chronic-lymphocytic-leukemia
#15
Gregory Lazarian, Romain Guièze, Catherine J Wu
Chronic lymphocytic leukemia (CLL) is a common B-cell malignancy with a remarkably heterogeneous course, ranging from indolent disease with no need for immediate therapy to rapidly progressive disease associated with therapeutic resistance. The recent US Food and Drug Administration approvals of novel targeted therapies such as inhibitors of B-cell receptor signaling and B-cell lymphoma 2 have opened up new opportunities in the clinical management of patients with CLL and heralded a new era in the clinical treatment of this disease...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28296675/eosinophilic-esophagitis-and-esophageal-granular-cell-tumor-an-unexpected-association
#16
Mary Ellen Riffle, Alexandros D Polydorides, Jessica Niakan, Mirna Chehade
Esophageal granular cell tumors (GCTs) are rare. Eosinophilic esophagitis (EoE) is an immune-mediated disease characterized by esophageal eosinophilia despite proton pump inhibitor (PPI) therapy. Given that GCTs occur at sites of scarring and inflammation, we sought to determine the prevalence of EoE in patients with esophageal GCTs. Our center's pathology database was searched for GCT specimens from 1995 to 2014. Slides were blindly rereviewed. GCTs were scored for atypical cytological features. Presence and number of eosinophils in the tumor and the surrounding esophageal epithelium and any EoE features were recorded...
March 14, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28296559/the-irony-of-highly-effective-bacterial-therapy-of-a-patient-derived-orthotopic-xenograft-pdox-model-of-ewing-s-sarcoma-which-was-blocked-by-ewing-himself-80%C3%A2-years-ago
#17
Takashi Murakami, Tasuku Kiyuna, Kei Kawaguchi, Kentaro Igarashi, Arun S Singh, Yukihiko Hiroshima, Yong Zhang, Ming Zhao, Kentaro Miyake, Scott D Nelson, Sarah M Dry, Yunfeng Li, Jonathan C DeLong, Thinzar M Lwin, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Fritz C Eilber, Robert M Hoffman
William B. Coley developed bacterial therapy of cancer more than 100 years ago and had clinical success. James Ewing, a very famous cancer pathologist for whom the Ewing sarcoma is named, was Coley's boss at Memorial Hospital in New York and terminated Coley's bacterial therapy of cancer. A tumor from a patient with soft-tissue Ewing's sarcoma, who failed doxorubicin (DOX) therapy, was previously implanted in nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. In the present study, the Ewing's sarcoma PDOX was treated with tumor-targeting S...
March 15, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28292923/aspirin-use-reduces-the-risk-of-aggressive-prostate-cancer-and-disease-recurrence-in-african-american-men
#18
Cheryl J Smith, Tiffany H Dorsey, Wei Tang, Symone V Jordan, Christopher A Loffredo, Stefan Ambs
BACKGROUND: Men of African descent experience a disproportionately high prostate cancer mortality. Intratumoral inflammation was found to be associated with aggressive prostate cancer. We and others have shown that prostate tumors in African-American (AA) patients harbor a distinct immune and inflammation signature when compared with European-American (EA) patients. These observations suggest that inflammation could be a driver of aggressive disease in men of African descent, leading to the hypothesis that an anti-inflammatory drug like aspirin could prevent disease progression...
March 14, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28291360/in-situ-gelling-liquid-crystalline-system-as-local-sirna-delivery-system
#19
Livia N Borgheti-Cardoso, Sander A A Kooijmans, Marcel H A M Fens, Roy van der Meel, Fabiana T M C Vicentini, Marcia C A Fantini, Maria Vitória L B Bentley, Raymond M Schiffelers
An effective short interfering RNA (siRNA) delivery system protects the siRNA from degradation, facilitates its cellular uptake and promotes its release into the cytoplasm. Local administration of siRNA presents advantages over systemic administration, such as the possibility to use lower doses and allow local and sustained release. In this context, in situ solidifying organogels based on monoglycerides (MO), polyethylenimine (PEI), propylene glycol (PG) and tris buffer are an attractive strategy for intratumoral delivery of siRNA...
March 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28290464/blocking-the-recruitment-of-naive-cd4-t-cells-reverses-immunosuppression-in-breast-cancer
#20
Shicheng Su, Jianyou Liao, Jiang Liu, Di Huang, Chonghua He, Fei Chen, LinBing Yang, Wei Wu, Jianing Chen, Ling Lin, Yunjie Zeng, Nengtai Ouyang, Xiuying Cui, Herui Yao, Fengxi Su, Jian-Dong Huang, Judy Lieberman, Qiang Liu, Erwei Song
The origin of tumor-infiltrating Tregs, critical mediators of tumor immunosuppression, is unclear. Here, we show that tumor-infiltrating naive CD4(+) T cells and Tregs in human breast cancer have overlapping TCR repertoires, while hardly overlap with circulating Tregs, suggesting that intratumoral Tregs mainly develop from naive T cells in situ rather than from recruited Tregs. Furthermore, the abundance of naive CD4(+) T cells and Tregs is closely correlated, both indicating poor prognosis for breast cancer patients...
March 14, 2017: Cell Research
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