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https://www.readbyqxmd.com/read/28446506/analytic-pre-analytic-and-clinical-validation-of-p53-immunohistochemistry-for-detection-of-tp53-missense-mutation-in-prostate-cancer
#1
Liana Guedes, Fawaz Almutairi, Michael C Haffner, Gaurav Rajoria, Zach Liu, Szczepan Klimek, Roberto Zoino, Kasra Yousefi, Rajni Sharma, Angelo M De Marzo, George Netto, William B Isaacs, Ashley E Ross, Edward M Schaeffer, Tamara L Lotan
PURPOSE:TP53 missense mutations may help to identify prostate cancer (PCa) with lethal potential. Here, we pre-analytically, analytically and clinically validated a robust immunohistochemistry (IHC) assay to detect subclonal and focal TP53 missense mutations in PCa. <p>EXPERIMENTAL DESIGN: The p53 IHC assay was performed in a CLIA-accredited laboratory on the Ventana Benchmark immunostaining system. p53 protein nuclear accumulation was defined as any p53 nuclear labeling in >10% of tumor cells. 54 formalin fixed paraffin embedded (FFPE) cell lines from the NCI-60 panel and 103 FFPE PCa tissues (88 primary adenocarcinomas, 15 metastases) with known TP53 mutation status were studied...
April 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28444227/incidence-and-prognosis-of-patients-with-brain-metastases-at-diagnosis-of-systemic-malignancy-a-population-based-study
#2
Daniel N Cagney, Allison M Martin, Paul J Catalano, Amanda J Redig, Nancy U Lin, Eudocia Q Lee, Patrick Y Wen, Ian F Dunn, Wenya Linda Bi, Stephanie E Weiss, Daphne A Haas-Kogan, Brian M Alexander, Ayal A Aizer
Background: Brain metastases are associated with significant morbidity and mortality. Population-level data describing the incidence and prognosis of patients with brain metastases are lacking. The aim of this study was to characterize the incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy using recently released data from the Surveillance, Epidemiology, and End Results (SEER) program. Methods: We identified 1,302,166 patients diagnosed with non-hematologic malignancies originating outside of the central nervous system between 2010-2013 and described the incidence proportion and survival of patients with brain metastases...
April 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28442277/prostate-brachytherapy-either-alone-or-in-combination-with-external-beam-radiation-is-associated-with-longer-overall-survival-in-men-with-favorable-pathologic-group-4-gleason-score-8-prostate-cancer
#3
Matthew W Jackson, Arya Amini, Bernard L Jones, Brian Kavanagh, Paul Maroni, Steven J Frank, Usama Mahmood, Rajat J Kudchadker, Thomas J Pugh
PURPOSE: Conventional prostate cancer risk stratification results in considerable heterogeneity within each prognostic group. Men with pathologic grade Group 4 (Gleason score 8) but otherwise low-risk features have been identified as a favorable subset of high-risk prostate cancer. Given recent randomized data supporting improved cancer outcome with brachytherapy in intermediate- and high-risk prostate cancer, we sought to evaluate brachytherapy utilization and overall survival (OS) for these patients...
April 23, 2017: Brachytherapy
https://www.readbyqxmd.com/read/28428707/advanced-pancreatic-ductal-adenocarcinoma-complexities-of-treatment-and-emerging-therapeutic-options
#4
REVIEW
Chandra Diwakarla, Katherine Hannan, Nadine Hein, Desmond Yip
Pancreatic ductal adenocarcinoma is a devastating disease with a poor prognosis regardless of stage. To date the mainstay of therapy for advanced disease has been chemotherapy with little incremental improvements in outcome. Despite extensive research investigating new treatment options the current practices continue to utilise fluorouracil or gemcitabine containing combinations. The need for novel therapeutic approaches is mandated by the ongoing poor survival rates associated with this disease. One such approach may include manipulation of ribosome biogenesis and the nucleolar stress response, which has recently been applied to haematological malignancies such as lymphoma and prostate cancer with promising results...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28427194/alternative-rna-splicing-of-the-meaf6-gene-facilitates-neuroendocrine-prostate-cancer-progression
#5
Ahn R Lee, Yinan Li, Ning Xie, Martin E Gleave, Michael E Cox, Colin C Collins, Xuesen Dong
Although potent androgen receptor pathway inhibitors (ARPI) improve overall survival of metastatic prostate cancer patients, treatment-induced neuroendocrine prostate cancer (t-NEPC) as a consequence of the selection pressures of ARPI is becoming a more common clinical issue. Improved understanding of the molecular biology of t-NEPC is essential for the development of new effective management approaches for t-NEPC. In this study, we identify a splice variant of the MYST/Esa1-associated factor 6 (MEAF6) gene, MEAF6-1, that is highly expressed in both t-NEPC tumor biopsies and neuroendocrine cell lines of prostate and lung cancers...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418352/-fatty-acid-synthase-in-the-diagnosis-of-prostate-neoplasms
#6
D O Allina, Yu Yu Andreeva, L E Zavalishina, L V Moskvina, G A Frank
The differential diagnosis of benign and malignant changes in the prostate presents still definite difficulties; the antibody panel existing for these purposes is imperfect. Fatty acid synthase (FASN) is an androgen-regulated enzyme required for de novo lipogenesis. A number of studies have noted increased expression of the gene encoding this protein in tumors and precancerous lesions of different locations. AIM: Тo estimate the diagnostic value of analyzing the expression of FASN in prostate neoplasias...
2017: Arkhiv Patologii
https://www.readbyqxmd.com/read/28417077/direct-extension-of-prostatic-adenocarcinoma-protruding-through-the-urethral-meatus
#7
Hasan Jhaveri, Kristen Combs, Faiyaaz Jhaveri
Prostate cancer involving the anterior urethra is rare with few cases describing isolated recurrence to the anterior urethra. This case describes a patient with a history of metastatic prostate cancer who subsequently developed advanced prostate cancer involving the entire urethra with extension from the prostatic urethra to the urethral meatus. This will help future healthcare providers recognize this metastatic pattern as a possibility and explore this option when presented with a bleeding mass at the urethral meatus of unknown origin...
July 2017: Urology Case Reports
https://www.readbyqxmd.com/read/28414305/spop-regulates-prostate-epithelial-cell-proliferation-and-promotes-ubiquitination-and-turnover-of-c-myc-oncoprotein
#8
C Geng, S Kaochar, M Li, K Rajapakshe, W Fiskus, J Dong, C Foley, B Dong, L Zhang, O-J Kwon, S S Shah, M Bolaki, L Xin, M Ittmann, B W O'Malley, C Coarfa, N Mitsiades
The E3 ubiquitin ligase adaptor speckle-type POZ protein (SPOP) is frequently dysregulated in prostate adenocarcinoma (PC), via either somatic mutations or mRNA downregulation, suggesting an important tumour suppressor function. To examine its physiologic role in the prostate epithelium in vivo, we generated mice with prostate-specific biallelic ablation of Spop. These mice exhibited increased prostate mass, prostate epithelial cell proliferation, and expression of c-MYC protein compared to littermate controls, and eventually developed prostatic intraepithelial neoplasia (PIN)...
April 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28412093/non-small-cell-lung-cancer-as-a-second-primary-among-patients-with-previous-malignancy-who-is-at-risk
#9
Geena X Wu, Rebecca A Nelson, Jae Y Kim, Dan J Raz
BACKGROUND: Patients with previous malignancies could be at increased risk of non-small cell lung cancer (NSCLC). However, the extent of the risk is unknown for many cancer types; thus, it is unclear who might benefit from screening. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results data set from 1992 to 2012 was used to identify patients with previous malignancies who received a diagnosis of NSCLC ≥ 6 months after their initial cancer diagnosis...
March 2, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28412047/patient-reported-quality-of-life-after-proton-beam-therapy-for-prostate-cancer-the-effect-of%C3%A2-prostate-size
#10
Anuj Goenka, Neil B Newman, Hiral Fontanilla, Oren Cahlon, Brian Chon, Henry Tsai, Eugen Hug, Carl Brown, Carlos Vargas, Rahul R Parikh
BACKGROUND: In the present study, we assessed the effect of prostate gland size on patient-assessed genitourinary and gastrointestinal (GI) quality of life (QOL) after definitive treatment of prostate adenocarcinoma with proton beam therapy. PATIENTS AND METHODS: As a part of a prospective outcome tracking protocol, 81 patients treated at a single center between with proton beam therapy completed the Expanded Prostate Cancer Index Composite (EPIC) questionnaire before treatment and at the follow-up examinations...
March 18, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28411366/anticancer-activity-of-some-polyamine-derivatives-on-human-prostate-and-breast-cancer-cell-lines
#11
Marta Szumilak, Malgorzata Galdyszynska, Kamila Dominska, Andrzej Stanczak, Agnieszka Piastowska-Ciesielska
The aim of this study was to expand our knowledge about anticancer activity of some polyamine derivatives with quinoline or chromane as terminal moieties. Tested compounds were evaluated in vitro towards metastatic human prostate adenocarcinoma (PC3), human carcinoma (DU145) and mammary gland adenocarcinoma (MCF7) cell lines. Cell viability was estimated on the basis of mitochondrial metabolic activity using water-soluble tetrazolium WST1 to establish effective concentrations of the tested compounds under experimental conditions...
April 14, 2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28411207/transdifferentiation-as-a-mechanism-of-treatment-resistance-in-a-mouse-model-of-castration-resistant-prostate-cancer
#12
Min Zou, Roxanne Toivanen, Antonina Mitrofanova, Nicolas Floc'h, Sheida Hayati, Yanping Sun, Clementine Le Magnen, Daniel Chester, Elahe A Mostaghel, Andrea Califano, Mark A Rubin, Michael M Shen, Cory Abate-Shen
Current treatments for castration-resistant prostate cancer (CPRC) that target androgen receptor (AR) signaling improve patient survival, yet ultimately fail. Here we provide novel insights into treatment response for the anti-androgen abiraterone by analyses of a genetically-engineered mouse model (GEMM) with combined inactivation of Trp53 and Pten, which are frequently co-mutated in human CRPC. These NPp53 mice fail to respond to abiraterone, and display accelerated progression to tumors resembling treatment-related CRPC with neuroendocrine differentiation (CRPC-NE) in humans...
April 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28409073/facial-paralysis-and-hearing-loss-a-rare-manifestation-of-prostate-cancer-metastases
#13
Uroosa Ibrahim, Amina Saqib, Farhan Mohammad, Muhammad R Raza, Nikhil Nalluri, Frank Forte
Dural prostate metastases (DPM) are a rare manifestation of metastatic prostate cancer seen in approximately one to six percent of cases. Presenting symptoms may include signs of elevated intracranial pressure, headache, altered mental status, or cranial nerve palsies. Hearing loss, sensory changes, dysarthria, and dysphagia are rare symptoms in DPM that were present in our patient. We present a case of a 58-year-old male with a known diagnosis of adenocarcinoma of the prostate presenting with symptoms of acute exacerbation of chronic obstructive pulmonary disease (COPD), sub-acute right-sided hearing loss, and right-sided facial paralysis...
March 3, 2017: Curēus
https://www.readbyqxmd.com/read/28399576/local-tumor-control-and-dna-pk-activity-of-peripheral-blood-lymphocytes-in-prostate-cancer-patients-receiving-radiotherapy
#14
Masanori Someya, Tomokazu Hasegawa, Masakazu Hori, Yoshihisa Matsumoto, Kensei Nakata, Naoya Masumori, Koh-Ichi Sakata
Repair of DNA damage is critical for genomic stability, and DNA-dependent protein kinase (DNA-PK) has an important role in repairing double-strand breaks. We examined whether the DNA-PK activity of peripheral blood lymphocytes (PBLs) was related to biochemical (prostate-specific antigen: PSA) relapse and radiation toxicity in prostate cancer patients who have received radiotherapy. A total of 69 patients with localized adenocarcinoma of the prostate participated in this study. Peripheral blood was collected 2 years or later after radiotherapy and centrifuged, then DNA-PK activity was measured by a filter binding assay...
March 1, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28398879/parthenolide-selectively-sensitizes-prostate-tumor-tissue-to-radiotherapy-while-protecting-healthy-tissues-in-vivo
#15
Katherine L Morel, Rebecca J Ormsby, Eva Bezak, Christopher J Sweeney, Pamela J Sykes
Radiotherapy is widely used in cancer treatment, however the benefits can be limited by radiation-induced damage to neighboring normal tissues. Parthenolide (PTL) exhibits anti-inflammatory and anti-tumor properties and selectively induces radiosensitivity in prostate cancer cell lines, while protecting primary prostate epithelial cell lines from radiation-induced damage. Low doses of radiation have also been shown to protect from subsequent high-dose-radiation-induced apoptosis as well as DNA damage. These properties of PTL and low-dose radiation could be used to improve radiotherapy by killing more tumor cells and less normal cells...
March 3, 2017: Radiation Research
https://www.readbyqxmd.com/read/28393575/using-circulating-cell-free-dna-to-monitor-personalized-cancer-therapy
#16
Michael Oellerich, Ekkehard Schütz, Julia Beck, Philipp Kanzow, Piers N Plowman, Glen J Weiss, Philip D Walson
High-quality genomic analysis is critical for personalized pharmacotherapy in patients with cancer. Tumor-specific genomic alterations can be identified in cell-free DNA (cfDNA) from patient blood samples and can complement biopsies for real-time molecular monitoring of treatment, detection of recurrence, and tracking resistance. cfDNA can be especially useful when tumor tissue is unavailable or insufficient for testing. For blood-based genomic profiling, next-generation sequencing (NGS) and droplet digital PCR (ddPCR) have been successfully applied...
April 10, 2017: Critical Reviews in Clinical Laboratory Sciences
https://www.readbyqxmd.com/read/28389666/molecular-classification-of-prostate-adenocarcinoma-by-the-integrated-somatic-mutation-profiles-and-molecular-network
#17
Lei Yang, Shiyuan Wang, Meng Zhou, Xiaowen Chen, Wei Jiang, Yongchun Zuo, Yingli Lv
Prostate cancer is one of the most common cancers in men and a leading cause of cancer death worldwide, displaying a broad range of heterogeneity in terms of clinical and molecular behavior. Increasing evidence suggests that classifying prostate cancers into distinct molecular subtypes is critical to exploring the potential molecular variation underlying this heterogeneity and to better treat this cancer. In this study, the somatic mutation profiles of prostate cancer were downloaded from the TCGA database and used as the source nodes of the random walk with restart algorithm (RWRA) for generating smoothed mutation profiles in the STRING network...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28389514/histopathology-of-prostate-cancer
#18
Peter A Humphrey
This review focuses on histopathological aspects of carcinoma of the prostate. A tissue diagnosis of adenocarcinoma is often essential for establishing a diagnosis of prostate cancer, and the foundation for a tissue diagnosis is currently light microscopic examination of hematoxylin and eosin (H&E)-stained tissue sections. Markers detected by immunohistochemistry on tissue sections can support a diagnosis of adenocarcinoma that is primary in the prostate gland or metastatic. Histological variants of carcinoma of the prostate are important for diagnostic recognition of cancer or as clinicopathologic entities that have prognostic and/or therapeutic significance...
April 7, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28385021/rhodium-catalyzed-3-2-annulation-of-cyclic-n-acyl-ketimines-with-activated-olefins-anticancer-activity-of-spiroisoindolinones
#19
Satyasheel Sharma, Yongguk Oh, Neeraj Kumar Mishra, Umasankar De, Hyeim Jo, Richa Sachan, Hyung Sik Kim, Young Hoon Jung, In Su Kim
The rhodium(III)-catalyzed redox-neutral coupling reaction of N-acyl ketimines generated in situ from 3-hydroxyisoindolinones with various activated olefins is described. This approach leads to the synthesis of bioactive spiroisoindolinone derivatives in moderate to high yields. In the case of internal olefins such as maleimides, maleates, fumarates, and cinnamates, spiroindanes were obtained by the [3 + 2] annulations reaction. In sharp contrast, acrylates and quinones displayed the β-H elimination followed by Prins-type cyclization furnishing spiroindenes...
April 7, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28384931/unusual-presentation-of-prostate-carcinoma-a-case-report
#20
Rohit Bhattar, Anuradha Maheshwari, Sher Singh Yadav, Vinay Tomar
Prostate cancer is a common cancer in elderly men and it frequently metastasizes to regional lymph nodes and sometimes to bone. Very rarely in some of the cases it also shows involvement of non-regional lymph nodes like supra-diaphragmatic lymph nodes. In our report, we present a 60-year-old male, initially misdiagnosed as Chronic Obstructive Pulmonary Disease (COPD) with cervical lymph node involvement may be due to infective region or inflammatory pathology, which was later found to have prostatic adenocarcinoma metastatic to supraclavicular lymph nodes...
February 2017: Journal of Clinical and Diagnostic Research: JCDR
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