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https://www.readbyqxmd.com/read/29446828/novel-insights-on-testicular-volume-and-testosterone-replacement-therapy-in-klinefelter-patients-undergoing-testicular-sperm-extraction-a-retrospective-clinical-study
#1
Andrea Garolla, Riccardo Selice, Massimo Menegazzo, Umberto Valente, Filiberto Zattoni, Massimo Iafrate, Tommaso Prayer-Galetti, Marina Gardiman Paola, Alberto Ferlin, Andrea Di Nisio, Carlo Foresta
STUDY QUESTION: To investigate whether sperm recovery is related to clinical features, hormone parameters and testosterone replacement therapy (TRT) in patients with Klinefelter syndrome (KS). SUMMARY ANSWER: This study provides three interesting insights: i) the probability to retrieve sperm is not related to testicular volume; ii) TRT does not affect sperm retrieval rate (SRR); iii) reduced levels of LH and FSH represent a negative predictor of sperm retrieval in patients with TRT...
February 15, 2018: Clinical Endocrinology
https://www.readbyqxmd.com/read/29431697/convergent-therapeutic-strategies-to-overcome-the-heterogeneity-of-acquired-resistance-in-brafv600e-colorectal-cancer
#2
Mehlika Hazar-Rethinam, Marianna Kleyman, G Celine Han, David Liu, Leanne G Ahronian, Heather A Shahzade, Lifeng Chen, Aparna R Parikh, Jill N Allen, Jeffrey W Clark, Eunice L Kwak, Jason E Faris, Janet E Murphy, Theodore S Hong, Emily E Van Seventer, Brandon Nadres, Catriona B Hong, Joseph M Gurski, Nicholas A Jessop, Dora Dias-Santagata, A John Iafrate, Eliezer M Van Allen, Ryan B Corcoran
Clonal heterogeneity associated with acquired resistance presents a critical therapeutic challenge. Whole-exome sequencing of paired tumor biopsies and targeted sequencing of cell-free DNA (cfDNA) from BRAFV600E colorectal cancer patients receiving BRAF inhibitor combinations identified 14 distinct alterations in MAPK pathway components driving acquired resistance, with as many as eight alterations in a single patient. We developed a novel pooled clone system to study clonal outgrowth during acquired resistance, in vitro and in vivo...
February 5, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29376144/tracking-the-evolution-of-resistance-to-alk-tyrosine-kinase-inhibitors-through-longitudinal-analysis-of-circulating-tumor-dna
#3
Ibiayi Dagogo-Jack, A Rose Brannon, Lorin A Ferris, Catarina D Campbell, Jessica J Lin, Katherine R Schultz, Jennifer Ackil, Sara Stevens, Leila Dardaei, Satoshi Yoda, Harper Hubbeling, Subba R Digumarthy, Markus Riester, Aaron N Hata, Lecia V Sequist, Inga T Lennes, A John Iafrate, Rebecca S Heist, Christopher G Azzoli, Anna F Farago, Jeffrey A Engelman, Jochen K Lennerz, Cyril H Benes, Rebecca J Leary, Alice T Shaw, Justin F Gainor
Purpose: ALK rearrangements predict for sensitivity to ALK tyrosine kinase inhibitors (TKIs). However, responses to ALK TKIs are generally short-lived. Serial molecular analysis is an informative strategy for identifying genetic mediators of resistance. Although multiple studies support the clinical benefits of repeat tissue sampling, the clinical utility of longitudinal circulating tumor DNA analysis has not been established in ALK-positive lung cancer. Methods: Using a 566-gene hybrid-capture next-generation sequencing (NGS) assay, we performed longitudinal analysis of plasma specimens from 22 ALK-positive patients with acquired resistance to ALK TKIs to track the evolution of resistance during treatment...
2018: JCO Precision Oncology
https://www.readbyqxmd.com/read/29373100/impact-of-eml4-alk-variant-on-resistance-mechanisms-and-clinical-outcomes-in-alk-positive-lung-cancer
#4
Jessica J Lin, Viola W Zhu, Satoshi Yoda, Beow Y Yeap, Alexa B Schrock, Ibiayi Dagogo-Jack, Nicholas A Jessop, Ginger Y Jiang, Long P Le, Kyle Gowen, Philip J Stephens, Jeffrey S Ross, Siraj M Ali, Vincent A Miller, Melissa L Johnson, Christine M Lovly, Aaron N Hata, Justin F Gainor, Anthony J Iafrate, Alice T Shaw, Sai-Hong Ignatius Ou
Purpose Advanced anaplastic lymphoma kinase ( ALK) fusion-positive non-small-cell lung cancers (NSCLCs) are effectively treated with ALK tyrosine kinase inhibitors (TKIs). However, clinical outcomes in these patients vary, and the benefit of TKIs is limited as a result of acquired resistance. Emerging data suggest that the ALK fusion variant may affect clinical outcome, but the molecular basis for this association is unknown. Patients and Methods We identified 129 patients with ALK-positive NSCLC with known ALK variants...
January 26, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29275311/quality-of-life-in-patients-with-bladder-cancer-undergoing-ileal-conduit-a-comparison-of-women-versus-men
#5
Salvatore Siracusano, Carolina D'Elia, Maria Angela Cerruto, Omar Saleh, Sergio Serni, Mauro Gacci, Stefano Ciciliato, Alchiede Simonato, Antonio Porcaro, Vincenzo DE Marco, Renato Talamini, Laura Toffoli, Francesco Visalli, Mauro Niero, Cristina Lonardi, Ciro Imbimbo, Paolo Verze, Vincenzo Mirone, Marco Racioppi, Massimo Iafrate, Giovanni Cacciamani, Davide DE Marchi, Pierfrancesco Bassi, Walter Artibani
BACKGROUND/AIM: Studies comparing health-related quality of life (HR-QoL) between patients who underwent radical cystectomy (RC) and those who underwent a different form of urinary diversion has not reached yet univocal and reliable conclusions. The aim of our study was to evaluate bladder-specific long-term HR-QoL after radical cystectomy and ileal conduit. PATIENTS AND METHODS: A multicenter study was carried out on 145 consecutive patients (112 males and 33 females) undergoing RC and ileal conduit (IC)...
January 2018: In Vivo
https://www.readbyqxmd.com/read/29242214/expressed-gene-fusions-as-frequent-drivers-of-poor-outcomes-in-hormone-receptor-positive-breast-cancer
#6
Karina J Matissek, Maristela L Onozato, Sheng Sun, Zongli Zheng, Andrew Schultz, Jesse Lee, Kristofer Patel, Piiha-Lotta Jerevall, Srinivas V Saladi, Allison MacLeay, Mehrad Tavallai, Tanja Badovinac-Crnjevic, Carlos Barrios, Nuran Beşe, Arlene Chan, Yanin Chavarri-Guerra, Marcio Debiasi, Elif Demirdogen, Unal Egeli, Sehsuvar Gökgöz, Henry Gomez, Pedro Liedke, Ismet Tasdelen, Sahsine Tolunay, Gustavo Werutsky, Jessica St Louis, Nora Horick, Dianne M Finkelstein, Long Phi Le, Aditya Bardia, Paul E Goss, Dennis C Sgroi, A John Iafrate, Leif W Ellisen
We sought to uncover novel genetic drivers of hormone-receptor positive (HR+) breast cancer, employing a targeted next-generation sequencing approach for detecting expressed gene rearrangements without prior knowledge of the fusion partners. We identified intergenic fusions involving driver genes including PIK3CA, AKT3, RAF1 and ESR1 in 14% (24/173) of unselected patients with advanced HR+ breast cancer. Fluorescence in situ hybridization (FISH) confirmed the corresponding chromosomal rearrangements in both primary and metastatic tumors...
December 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29236940/polyclonal-rb1-mutations-and-acquired-resistance-to-cdk-4-6-inhibitors-in-patients-with-metastatic-breast-cancer
#7
R Condorelli, L Spring, J O'Shaughnessy, L Lacroix, C Bailleux, V Scott, J Dubois, R J Nagy, R B Lanman, A J Iafrate, F Andre, A Bardia
Background: While deregulation of the cyclin D1-CDK4/6-retinoblastoma pathway is common in hormone receptor positive (HR+) breast cancer, Rb is usually intact in HR+ breast cancer, and targeted CDK 4/6 inhibitors that act upstream of Rb, are routinely being utilized in clinical practice. However, factors that can lead to clinical resistance to CDK 4/6 inhibitors are not known. Patients and methods: We identified patients who had pre and post genotyping in tissue and peripheral blood samples after receiving CDK 4/6 inhibitors...
December 11, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29021774/corrigendum-marital-satisfaction-sex-age-marriage-duration-religion-number-of-children-economic-status-education-and-collectivistic-values-data-from-33-countries
#8
Piotr Sorokowski, Ashley K Randall, Agata Groyecka, Tomasz Frackowiak, Katarzyna Cantarero, Peter Hilpert, Khodabakhsh Ahmadi, Ahmad M Alghraibeh, Richmond Aryeetey, Anna Bertoni, Karim Bettache, Marta Błazejewska, Guy Bodenmann, Tiago S Bortolini, Carla Bosc, Marina Butovskaya, Felipe N Castro, Hakan Cetinkaya, Diana Cunha, Daniel David, Oana A David, Fahd A Dileym, Alejandra C Domínguez Espinosa, Silvia Donato, Daria Dronova, Seda Dural, Maryanne Fisher, Aslihan Hamamcıoğlu Akkaya, Takeshi Hamamura, Karolina Hansen, Wallisen T Hattori, Ivana Hromatko, Evrim Gülbetekin, Raffaella Iafrate, Bawo James, Feng Jiang, Charles O Kimamo, Firat Koç, Anna Krasnodębska, Amos Laar, Fívia A Lopes, Rocio Martinez, Norbert Meskó, Natalya Molodovskaya, Khadijeh Moradi Qezeli, Zahrasadat Motahari, Jean C Natividade, Joseph Ntayi, Oluyinka Ojedokun, Mohd S B Omar-Fauzee, Ike E Onyishi, Barış Özener, Anna Paluszak, Alda Portugal, Anu Realo, Ana P Relvas, Muhammad Rizwan, Agnieszka L Sabiniewicz, Svjetlana Salkicević, Ivan Sarmány-Schuller, Eftychia Stamkou, Stanislava Stoyanova, Denisa Šukolová, Nina Sutresna, Meri Tadinac, Andero Teras, Edna L T Ponciano, Ritu Tripathi, Nachiketa Tripathi, Mamta Tripathi, Maria E Yamamoto, Gyesook Yoo, Agnieszka Sorokowska
[This corrects the article on p. 1199 in vol. 8, PMID: 28785230.].
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/29016871/cost-effectiveness-of-idh-testing-in-diffuse-gliomas-according-to-the-2016-who-classification-of-tumors-of-the-central-nervous-system-recommendations
#9
John C DeWitt, Justin T Jordan, Matthew P Frosch, Wesley R Samore, A John Iafrate, David N Louis, Jochen K Lennerz
Background: Due to the decreasing prevalence of IDH1 mutations in older patients, the 2016 World Health Organization (WHO) classification of brain tumors proposed not to perform sequencing for isocitrate dehydrogenase (IDH) in glioblastoma patients ≥55 years old. We present a cost-effectiveness analysis to estimate the financial impact of these guidelines. Methods: From 2010 to 2015 we performed 1023 IDH tests in gliomas, amounting to ~$1.09 million in direct laboratory test costs...
November 29, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28954285/phase-ii-study-of-proton-based-stereotactic-body-radiation-therapy-for-liver-metastases-importance-of-tumor-genotype
#10
Theodore S Hong, Jennifer Y Wo, Darrell R Borger, Beow Y Yeap, Erin I McDonnell, Henning Willers, Lawrence S Blaszkowsky, Eunice L Kwak, Jill N Allen, Jeffrey W Clark, Shyam Tanguturi, Lipika Goyal, Janet E Murphy, John A Wolfgang, Lorraine C Drapek, Ronald S Arellano, Harvey J Mamon, John T Mullen, Kenneth K Tanabe, Cristina R Ferrone, David P Ryan, A John Iafrate, Thomas F DeLaney, Andrew X Zhu
Background: We evaluated the efficacy and safety of risk-adapted, proton-based stereotactic body radiation therapy (SBRT) for liver metastases from solid tumors. Methods: This single-arm phase II single institutional study (NCT01239381) included patients with limited extrahepatic disease, 800 mL or greater of uninvolved liver, and no cirrhosis or Child-Pugh A, who had received proton-based SBRT to one to four liver metastases from solid tumors. Treatment comprised 30 to 50 Gray equivalent (GyE) in five fractions based on the effective volume of liver irradiated...
September 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28801914/blockade-of-transforming-growth-factor-%C3%AE-signaling-enhances-oncolytic-herpes-simplex-virus-efficacy-in-patient-derived-recurrent-glioblastoma-models
#11
Shinichi Esaki, Fares Nigim, Esther Moon, Samantha Luk, Juri Kiyokawa, William Curry, Daniel P Cahill, Andrew S Chi, A John Iafrate, Robert L Martuza, Samuel D Rabkin, Hiroaki Wakimoto
Despite the current standard of multimodal management, glioblastoma (GBM) inevitably recurs and effective therapy is not available for recurrent disease. A subset of tumor cells with stem-like properties, termed GBM stem-like cells (GSCs), are considered to play a role in tumor relapse. Although oncolytic herpes simplex virus (oHSV) is a promising therapeutic for GBM, its efficacy against recurrent GBM is incompletely characterized. Transforming growth factor beta (TGF-β) plays vital roles in maintaining GSC stemness and GBM pathogenesis...
December 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28776576/gnas-mutations-in-primary-mucinous-and-non-mucinous-lung-adenocarcinomas
#12
Lauren L Ritterhouse, Marina Vivero, Mari Mino-Kenudson, Lynette M Sholl, A John Iafrate, Valentina Nardi, Fei Dong
GNAS mutations have been described in mucinous and non-mucinous epithelial neoplasms of the appendix, pancreas, and colon, with hotspot GNAS mutations found in up to two-thirds of pancreatic intraductal papillary mucinous neoplasms. Additionally, many GNAS-mutated tumors have concurrent mutations in the Ras/Raf pathway. The clinicopathologic features of GNAS-mutated lung carcinomas, however, have not yet been characterized. Primary lung carcinomas from Brigham and Women's Hospital (n=1282) or Massachusetts General Hospital (n=1070) were genotyped on a targeted massively parallel sequencing panel of oncogenes and tumor suppressor genes including GNAS...
August 4, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28710865/neoadjuvant-chemotherapy-in-triple-negative-breast-cancer-a-multicentric-retrospective-observational-study-in-real-life-setting
#13
Teresa Gamucci, Laura Pizzuti, Isabella Sperduti, Lucia Mentuccia, Angela Vaccaro, Luca Moscetti, Paolo Marchetti, Luisa Carbognin, Andrea Michelotti, Laura Iezzi, Alessandra Cassano, Antonino Grassadonia, Antonio Astone, Andrea Botticelli, Emanuela Magnolfi, Luigi Di Lauro, Domenico Sergi, Paola Fuso, Nicola Tinari, Maddalena Barba, Marcello Maugeri-Saccà, Elisabetta Landucci, Francesca Conti, Giuseppe Sanguineti, Michele De Tursi, Gianni Iafrate, Antonio Giordano, Gennaro Ciliberto, Clara Natoli, Patrizia Vici
We aimed to assess the efficacy of neoadjuvant chemotherapy (NACT) in a cohort of 213 triple-negative breast cancer (TNBC) patients treated in real-world practice at 8 Italian cancer centres. We computed descriptive statistics for all the variable of interest. Factors testing significant in univariate analysis were included in multivariate models. Survival data were compared by Kaplan-Meier curves and log-rank test. The median follow-up was 45 months. We observed 60 (28.2%) pathological complete response (pCR)...
July 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28658208/recurrent-and-functional-regulatory-mutations-in-breast-cancer
#14
Esther Rheinbay, Prasanna Parasuraman, Jonna Grimsby, Grace Tiao, Jesse M Engreitz, Jaegil Kim, Michael S Lawrence, Amaro Taylor-Weiner, Sergio Rodriguez-Cuevas, Mara Rosenberg, Julian Hess, Chip Stewart, Yosef E Maruvka, Petar Stojanov, Maria L Cortes, Sara Seepo, Carrie Cibulskis, Adam Tracy, Trevor J Pugh, Jesse Lee, Zongli Zheng, Leif W Ellisen, A John Iafrate, Jesse S Boehm, Stacey B Gabriel, Matthew Meyerson, Todd R Golub, Jose Baselga, Alfredo Hidalgo-Miranda, Toshi Shioda, Andre Bernards, Eric S Lander, Gad Getz
Genomic analysis of tumours has led to the identification of hundreds of cancer genes on the basis of the presence of mutations in protein-coding regions. By contrast, much less is known about cancer-causing mutations in non-coding regions. Here we perform deep sequencing in 360 primary breast cancers and develop computational methods to identify significantly mutated promoters. Clear signals are found in the promoters of three genes. FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding...
July 6, 2017: Nature
https://www.readbyqxmd.com/read/28652163/health-related-quality-of-life-after-radical-cystectomy-a-cross-sectional-study-with-matched-pair-analysis-on-ileal-conduit-vs-ileal-orthotopic-neobladder-diversion
#15
Maria Angela Cerruto, Carolina D'Elia, Salvatore Siracusano, Omar Saleh, Mauro Gacci, Giovanni Cacciamani, Vincenzo De Marco, Antonio Benito Porcaro, Matteo Balzarro, Mauro Niero, Cristina Lonardi, Massimo Iafrate, Pierfrancesco Bassi, Ciro Imbimbo, Marco Racioppi, Renato Talamini, Stefano Ciciliato, Sergio Serni, Marco Carini, Paolo Verze, Walter Artibani
OBJECTIVE: To examine the different and health-related quality of life (HR-QoL) outcomes between ileal conduit (IC) and ileal orthotopic neobladder (IONB) in patients who underwent radical cystectomy (RC), by using validated self-reported cancer-specific instruments. PATIENTS AND METHODS: This retrospective, cross-sectional, multicenter cohort study included 148 and 171 patients with either IC or IONB. HR-QoL was evaluated with Quality of Life Core Questionnaire and bladder module (BLM)-30 European Organisation for Research and Treatment of Cancer questionnaires...
June 23, 2017: Urology
https://www.readbyqxmd.com/read/28641066/free-to-love-the-role-of-intrusive-parenting-for-young-adult-children-s-romantic-relationship-quality
#16
Miriam Parise, Claudia Manzi, Silvia Donato, Raffaella Iafrate
Intrusive parenting is a form of boundary disturbance in the parent-child relationship which has been consistently associated with children's maladjustment. The present study examines the role of intrusive parenting for young adult children's romantic relationship quality. Relying on data from a two-wave longitudinal study among young couples in transition to marriage in Italy, we investigated the link between young adults' perceived intrusive parenting and change in their romantic relationship quality from 6 months before marriage to 18 months after marriage, as well as the mediating role of change in the capacity to include the partner in the self...
July 2017: Journal of Prevention & Intervention in the Community
https://www.readbyqxmd.com/read/28641064/a-qualitative-evaluation-of-a-preventive-intervention-for-parents-the-groups-for-family-enrichment_parent-version-gfe_p
#17
Anna Bertoni, Silvia Donato, Antonella Morgano, Raffaella Iafrate, Rosa Rosnati
The traditional objective of parenting enrichment programs is to train parents' abilities and specific competences, but less attention is paid to promoting participants' reflection on their parental identity. These programs are generally delivered to groups of parents, though the group is rarely considered a specific tool to promote changes in participants' relational functioning. The Groups for Family Enrichment_Parent version (GFE_P; Iafrate, Donato, & Bertoni, 2010 ; Iafrate & Rosnati, 2007 ) focus on parental identity in addition to parental competences and skills and purposely use the group of parents as an educational tool, adopting a semistructured format...
July 2017: Journal of Prevention & Intervention in the Community
https://www.readbyqxmd.com/read/28625978/the-alkylating-chemotherapeutic-temozolomide-induces-metabolic-stress-in-idh1-mutant-cancers-and-potentiates-nad-depletion-mediated-cytotoxicity
#18
Kensuke Tateishi, Fumi Higuchi, Julie J Miller, Mara V A Koerner, Nina Lelic, Ganesh M Shankar, Shota Tanaka, David E Fisher, Tracy T Batchelor, A John Iafrate, Hiroaki Wakimoto, Andrew S Chi, Daniel P Cahill
IDH1-mutant gliomas are dependent upon the canonical coenzyme NAD(+) for survival. It is known that PARP activation consumes NAD(+) during base excision repair (BER) of chemotherapy-induced DNA damage. We therefore hypothesized that a strategy combining NAD(+) biosynthesis inhibitors with the alkylating chemotherapeutic agent temozolomide could potentiate NAD(+) depletion-mediated cytotoxicity in mutant IDH1 cancer cells. To investigate the impact of temozolomide on NAD(+) metabolism, patient-derived xenografts and engineered mutant IDH1-expressing cell lines were exposed to temozolomide, in vitro and in vivo, both alone and in combination with nicotinamide phosphoribosyltransferase (NAMPT) inhibitors, which block NAD(+) biosynthesis...
August 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28611373/is-there-any-clinical-relevant-difference-between-non-mosaic-klinefelter-syndrome-patients-with-or-without-androgen-receptor-variations
#19
Umberto Valente, Cinzia Vinanzi, Savina Dipresa, Riccardo Selice, Massimo Menegazzo, Massimo Iafrate, Carlo Foresta, Andrea Garolla
Klinefelter Syndrome (KS) is the most common chromosomal disorder in men leading to non-obstructive azoospermia. Spermatozoa can be found by TESE in about 50% of adults with KS despite severe testicular degeneration. We evaluated AR variations and polymorphism length in 135 non-mosaic KS patients, aimed to find possible correlation with clinical features, sex hormones and sperm retrieval. Among 135 KS patients we found AR variations in eight subjects (5.9%). All variations but one caused a single amino acid substitution...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28391773/kif13b-nrg1-gene-fusion-and-kras-amplification-in-a-case-of-natural-progression-of-lung-cancer
#20
Daniel Xia, Long Phi Le, Anthony John Iafrate, Jochen Lennerz
An 85-year-old woman with a history of several primary lung cancers presented with liver metastases. The primary lung cancers were all managed surgically and the patient did not receive adjuvant or neoadjuvant therapy prior to presenting with metastases. Comparison of molecular testing results from the most recent primary and the liver metastases demonstrated ( a) a clonal relationship between the 2 cancers and ( 2) the presence of a KIF13B-NRG1 fusion and KRAS amplification unique to the metastases. When integrated, the molecular surgical pathology findings in this case illustrate the extent of "oncogenic drive" in preterminal lung cancer...
May 2017: International Journal of Surgical Pathology
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