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https://www.readbyqxmd.com/read/29352732/long-term-effects-of-crizotinib-in-alk-positive-tumors-excluding-nsclc-a-phase-1b-open-label-study
#1
Carlo Gambacorti-Passerini, Sergey Orlov, Li Zhang, Fadi Braiteh, Huiqiang Huang, Taito Esaki, Keizo Horibe, Jin-Seok Ahn, Joseph T Beck, William Jeffrey Edenfield, Yuankai Shi, Matthew Taylor, Kenji Tamura, Brian A Van Tine, Shang-Ju Wu, Jolanda Paolini, Paulina Selaru, Tae Min Kim
Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK-positive or ROS1-positive advanced non-small-cell lung cancer (NSCLC). However, ALK rearrangements are also implicated in other malignancies, including anaplastic large-cell lymphoma and inflammatory myofibroblastic tumors (IMTs). In this ongoing, multicenter, single-arm, open-label phase 1b study (PROFILE 1013; NCT01121588), patients with ALK-positive advanced malignancies other than NSCLC were to receive a starting dose of crizotinib 250 mg twice daily...
January 20, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29352718/consolidative-radiotherapy-to-residual-masses-after-chemotherapy-is-associated-with-improved-outcome-in-diffuse-large-b-cell-lymphoma-a-retrospective-population-based-study
#2
Øystein Fluge, Bård Mannsåker, Anders Torp, Ingvil Mjaaland, Lars Helgeland, Jan Klos, Olav Mella, Sigbjørn Berentsen, Peter Meyer
BACKGROUND: The role of consolidative radiotherapy (RT) in advanced diffuse large B-cell lymphoma (DLBCL) is not established. PATIENTS AND METHODS: In a population-based retrospective analysis of patients with DLBCL in Western Norway during 2003 to 2008, 170 consecutive patients admitted to Haukeland University Hospital (HUS) and 94 to Stavanger University Hospital (SUS) were included. The mean age was 64 years (range, 17-95 years), 147 patients (56%) were male, 80 patients (30%) had stage I/II, 126 patients (48%) stage III/IV, and 57 patients (22%) had primary extranodal disease...
December 24, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29352714/effect-of-single-agent-daily-prednisone-on-outcomes-and-toxicities-in-metastatic-castration-resistant-prostate-cancer-pooled-analysis-of-prospective-studies
#3
REVIEW
Pooja Ghatalia, Gregory R Pond, Arnoud J Templeton, Guru Sonpavde
The clinical effect of prednisone in metastatic castration-resistant prostate cancer (mCRPC) is unknown. We performed a pooled analysis of control arms of randomized controlled trials that had or had not administered single-agent prednisone. Randomized controlled trials with a control arm that included single-agent placebo (or no anticancer therapy) or single-agent prednisone (with or without placebo) were eligible for analysis. Patients receiving prednisone combined with other agents in the control arm were excluded...
December 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29352713/clinical-variables-associated-with-overall-survival-in-metastatic-castration-resistant-prostate-cancer-patients-treated-with-sipuleucel-t-immunotherapy
#4
Xiao X Wei, Jaselle Perry, Emily Chang, Li Zhang, Robert A Hiatt, Charles J Ryan, Eric J Small, Lawrence Fong
BACKGROUND: Sipuleucel-T is an autologous cell-based cancer immunotherapy for men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Its approval by the Food and Drug Administration was based on demonstration of an overall survival (OS) benefit in randomized placebo-controlled phase III trials. However, treatment was associated with a prostate-specific antigen (PSA) decline in only a small minority of patients. Understanding the clinical factors that are associated with OS could help guide treatment decisions, including patient selection and the timing of sipuleucel-T relative to other therapies...
December 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29352703/inotuzumab-ozogamicin-in-combination-with-low-intensity-chemotherapy-for-older-patients-with-philadelphia-chromosome-negative-acute-lymphoblastic-leukaemia-a-single-arm-phase-2-study
#5
Hagop Kantarjian, Farhad Ravandi, Nicholas J Short, Xuelin Huang, Nitin Jain, Koji Sasaki, Naval Daver, Naveen Pemmaraju, Joseph D Khoury, Jeffrey Jorgensen, Yesid Alvarado, Marina Konopleva, Guillermo Garcia-Manero, Tapan Kadia, Musa Yilmaz, Gautam Bortakhur, Jan Burger, Steven Kornblau, William Wierda, Courtney DiNardo, Alessandra Ferrajoli, Jovitta Jacob, Rebecca Garris, Susan O'Brien, Elias Jabbour
BACKGROUND: Inotuzumab ozogamicin, an anti-CD22 monoclonal antibody bound to a toxin, calicheamicin, has shown single-agent activity in relapsed or refractory acute lymphoblastic leukaemia. We aimed to assess the activity and safety of inotuzumab ozogamicin in combination with low-intensity chemotherapy in older patients with acute lymphoblastic leukaemia. METHODS: We did a single-arm, phase 2 study at the MD Anderson Cancer Center (Houston, TX, USA). Eligible patients were aged 60 years or older and had newly diagnosed, Philadelphia chromosome-negative, acute lymphoblastic leukaemia, and an Eastern Cooperative Oncology Group performance status of 3 or lower...
January 15, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29352660/clinical-significance-of-muc13-in-pancreatic-ductal-adenocarcinoma
#6
Sheema Khan, Nadeem Zafar, Shabia S Khan, Saini Setua, Stephen W Behrman, Zachary E Stiles, Murali M Yallapu, Peeyush Sahay, Hemendra Ghimire, Tomoko Ise, Satoshi Nagata, Lei Wang, Jim Y Wan, Prabhakar Pradhan, Meena Jaggi, Subhash C Chauhan
BACKGROUND: Poor prognosis of pancreatic cancer (PanCa) is associated with lack of an effective early diagnostic biomarker. This study elucidates significance of MUC13, as a diagnostic/prognostic marker of PanCa. METHODS: MUC13 was assessed in tissues using our in-house generated anti-MUC13 mouse monoclonal antibody and analyzed for clinical correlation by immunohistochemistry, immunoblotting, RT-PCR, computational and submicron scale mass-density fluctuation analyses, ROC and Kaplan Meir curve analyses...
January 15, 2018: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/29352585/adjuvant-chemotherapy-improves-survival-in-patients-with-completely-resected-t3n0-non-small-cell-lung-cancer-invading-the-chest-wall
#7
Justin A Drake, Jennifer L Sullivan, Benny Weksler
OBJECTIVE: Adjuvant chemotherapy prolongs survival in patients with non-small cell lung cancer with N1 disease or tumors larger than 4 cm. Patients with T3N0 disease due to chest wall invasion often receive adjuvant chemotherapy because their disease is classified as stage II non-small cell lung cancer. This study evaluated whether chemotherapy improves survival after complete resection of T3N0 non-small cell lung cancer with invasion of the chest wall. METHODS: Patients who underwent complete resection of N0 non-small cell lung cancer with invasion of the chest wall were identified in the National Cancer Database...
December 19, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/29352574/mismatch-repair-status-as-a-beneficial-predictor-of-fluorouracil-based-adjuvant-chemotherapy-for-pancreatic-cancer
#8
Dingkong Liang, Si Shi, Chen Liang, Qingcai Meng, Bo Zhang, Quanxing Ni, Jin Xu, Xianjun Yu
BACKGROUND: Prior studies have indicated that patients with colorectal cancer with deficient mismatch repair have particular clinicopathologic features that distinguish them from patients with tumors with proficient mismatch repair. However, the effect of the mismatch repair status on outcomes after adjuvant chemotherapy for pancreatic cancer is still unknown. METHODS: Pancreatic cancer patients who underwent R0 resection between January 2013 and December 2015 at Fudan University Shanghai Cancer Center were included in this study...
January 15, 2018: Surgery
https://www.readbyqxmd.com/read/29352444/activation-of-the-anti-aging-and-cognition-enhancing-gene-klotho-by-crispr-dcas9-transcriptional-effector-complex
#9
Ci-Di Chen, Ella Zeldich, Yuexuan Li, Andrea Yuste, Carmela R Abraham
Multiple lines of evidence show that the anti-aging and cognition-enhancing protein Klotho fosters neuronal survival, increases the anti-oxidative stress defense, and promotes remyelination of demyelinated axons. Thus, upregulation of the Klotho gene can potentially alleviate the symptoms and/or prevent the progression of age-associated neurodegenerative diseases such as Alzheimer's disease and demyelinating diseases such as multiple sclerosis. Here we used a CRISPR-dCas9 complex to investigate single-guide RNA (sgRNA) targeting the Klotho promoter region for efficient transcriptional activation of the Klotho gene...
January 19, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29352441/utility-of-tumor-burden-score-to-stratify-prognosis-of-patients-with-hepatocellular-cancer-results-of-4759-cases-from-ita-li-ca-study-group
#10
Alessandro Vitale, Quirino Lai, Fabio Farinati, Laura Bucci, Edoardo G Giannini, Lucia Napoli, Francesca Ciccarese, Gian Lodovico Rapaccini, Maria Di Marco, Eugenio Caturelli, Marco Zoli, Franco Borzio, Rodolfo Sacco, Giuseppe Cabibbo, Roberto Virdone, Fabio Marra, Martina Felder, Filomena Morisco, Luisa Benvegnù, Antonio Gasbarrini, Gianluca Svegliati-Baroni, Francesco Giuseppe Foschi, Gabriele Missale, Alberto Masotto, Gerardo Nardone, Antonio Colecchia, Mauro Bernardi, Franco Trevisani, Timothy M Pawlik
BACKGROUND: Dichotomous models like Milan Criteria represent the routinely used tools for predicting the outcome of patients with hepatocellular carcinoma (HCC). However, a paradigm shift from a dichotomous to continuous prognostic stratification should represent a good strategy for improving the prediction process. Recently, the tumor burden score (TBS) has been proposed for selecting patients with colorectal liver metastases. To date, TBS has not been validated in a large HCC population...
January 19, 2018: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/29352431/analysis-and-comparison-of-the-8th-edition-american-joint-committee-on-cancer-ajcc-nodal-staging-system-in-cutaneous-and-oral-squamous-cell-cancer-of-the-head-and-neck
#11
Nikolaus Moeckelmann, Ardalan Ebrahimi, Richard Dirven, Jessica Liu, Tsu-Hui Hubert Low, Ruta Gupta, Bruce Ashford, Sydney Ch'ng, Carsten E Palme, Jonathan R Clark
BACKGROUND: The American Joint Committee on Cancer (AJCC) uses the same nodal staging system for cutaneous and mucosal squamous cell carcinoma of the head and neck in its 8th edition (AJCC 8) despite differences in the etiology, risk factors, and clinical behavior of the two diseases. This study aims to evaluate the performance of the AJCC 8 nodal staging system by direct comparison of cutaneous (cSCC) versus oral squamous cell carcinoma (oSCC) patients. METHODS: Patients with metastatic cSCC (N = 382) and oSCC (N = 325) were identified from a prospective database (years 1987-2016)...
January 19, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29352306/prognostic-and-predictive-role-of-egfr-pathway-alterations-in-biliary-cancer-patients-treated-with-chemotherapy-and-anti-egfr
#12
Caterina Peraldo-Neia, Giuliana Cavalloni, Elisabetta Fenocchio, Celeste Cagnazzo, Loretta Gammaitoni, Stefano Cereda, Guglielmo Nasti, Maria Antonietta Satolli, Giuseppe Aprile, Michele Reni, Antonio Avallone, Rosella Spadi, Tiziana Venesio, Vittoria Martin, Claudio Doglioni, Milo Frattini, Massimo Aglietta, Francesco Leone
The association of anti-EGFR to gemcitabine and oxaliplatin (GEMOX) chemotherapy did not improve survival in biliary tract carcinoma (BTC) patients. Multiple mechanisms might be involved in the resistance to anti-EGFR. Here, we explored the mutation profile of EGFR extracellular domain (ECD), of tyrosine kinase domain (TKD), and its amplification status. EGFR mutational status of exons 12, 18-21 was analyzed in 57 tumors by Sanger sequencing. EGFR amplification was evaluated in 37 tumors by Fluorescent In Situ Hybridization (FISH)...
2018: PloS One
https://www.readbyqxmd.com/read/29352271/sex-disparity-in-cancer-roles-of-micrornas-and-related-functional-players
#13
REVIEW
Alessandra Carè, Maria Bellenghi, Paola Matarrese, Lucia Gabriele, Stefano Salvioli, Walter Malorni
A sexual dimorphism at the cellular level has been suggested to play a role in cancer onset and progression. In particular, very recent studies have unraveled striking differences between cells carrying XX or XY chromosomes in terms of response to stressful stimuli, indicating the presence of genetic and epigenetic differences determining sex-specific metabolic or phenotypic traits. Although this field of investigation is still in its infancy, available data suggest a key role of sexual chromosomes in determining cell life or death...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352232/the-silent-healer-mir-205-5p-up-regulation-inhibits-epithelial-to-mesenchymal-transition-in-colon-cancer-cells-by-indirectly-up-regulating-e-cadherin-expression
#14
Diana Gulei, Lorand Magdo, Ancuta Jurj, Lajos Raduly, Roxana Cojocneanu-Petric, Alin Moldovan, Cristian Moldovan, Adrian Florea, Sergiu Pasca, Laura-Ancuta Pop, Vlad Moisoiu, Liviuta Budisan, Cecilia Pop-Bica, Cristina Ciocan, Rares Buiga, Mihai-Stefan Muresan, Rares Stiufiuc, Calin Ionescu, Ioana Berindan-Neagoe
EMT represents the dominant program within advanced stages of colon cancer, where cells acquire migratory characteristics in order to invade secondary tissues and form metastasis. Where the majority of the therapeutic strategies are concentrated on the reduction of the tumor mass through different apoptotic mechanisms, the present study advocates an important role for miR-205-5p in impairment of colon cancer cells migration and restoration of the epithelial phenotype. Upon identification of a homogenous downregulated profile for miR-205-5p in colon adenocarcinoma patients, functional studies demonstrated that experimental upregulation of this sequence is able to significantly raise the levels of E-cadherin through direct inhibition of ZEB1...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352113/polo-like-kinase-4-mediates-epithelial-mesenchymal-transition-in-neuroblastoma-via-pi3k-akt-signaling-pathway
#15
Xiangdong Tian, Dejun Zhou, Lu Chen, Yao Tian, Benfu Zhong, Yanna Cao, Qiuping Dong, Meng Zhou, Jie Yan, Yalei Wang, Yanli Qiu, Lianmin Zhang, Zhongyuan Li, Huijuan Wang, Daowei Wang, Guoguang Ying, Qiang Zhao
Neuroblastoma (NB) is the most common malignant tumor in infancy and most common extracranial solid tumor in childhood. With the improvement of diagnosis and treatment, the survival rate of patients with low-risk and intermediate-risk NB can reach up to 90%. In contrast, for high-risk NBs, the long-term survival rate is still <40% because of heterogeneity of this tumor. The pathogenesis of NB is still not explicit, therefore it is of great significance to explore the mechanism of NB tumorigenesis and discover new therapeutic targets for NB...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352043/prognostic-implications-of-multiplex-detection-of-kras-mutations-in-cell-free-dna-from-patients-with-pancreatic-ductal-adenocarcinoma
#16
Min Kyeong Kim, Sang Myung Woo, Boram Park, Kyong-Ah Yoon, Yun-Hee Kim, Jungnam Joo, Woo Jin Lee, Sung-Sik Han, Sang-Jae Park, Sun-Young Kong
BACKGROUND: Cell-free DNA (cfDNA) is known to provide potential biomarkers for predicting clinical outcome, but its value in pancreatic ductal adenocarcinoma (PDAC) has not been fully evaluated. The aim of this study was to evaluate the clinical applicability of quantitative analysis of multiplex KRAS mutations in cell-free DNA from patients with PDAC. METHODS: A total of 106 patients with PDAC were enrolled in this prospective study. The concentration and fraction of KRAS mutations were determined through multiplex detection of KRAS mutations in plasma samples by use of a droplet digital PCR kit (Bio-Rad)...
January 19, 2018: Clinical Chemistry
https://www.readbyqxmd.com/read/29352019/opposing-roles-of-tgf%C3%AE-and-bmp-signaling-in-prostate-cancer-development
#17
Xin Lu, Eun-Jung Jin, Xi Cheng, Shan Feng, Xiaoying Shang, Pingna Deng, Shan Jiang, Qing Chang, Sharif Rahmy, Seema Chaudhary, Xuemin Lu, Ren Zhao, Y Alan Wang, Ronald A DePinho
SMAD4 constrains progression of Pten-null prostate cancer and serves as a common downstream node of transforming growth factor β (TGFβ) and bone morphogenetic protein (BMP) pathways. Here, we dissected the roles of TGFβ receptor II (TGFBR2) and BMP receptor II (BMPR2) using a Pten-null prostate cancer model. These studies demonstrated that the molecular actions of TGFBR2 result in both SMAD4-dependent constraint of proliferation and SMAD4-independent activation of apoptosis. In contrast, BMPR2 deletion extended survival relative to Pten deletion alone, establishing its promoting role in BMP6-driven prostate cancer progression...
December 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29351990/saa3-is-a-key-mediator-of-the-protumorigenic-properties-of-cancer-associated-fibroblasts-in-pancreatic-tumors
#18
Magdolna Djurec, Osvaldo Graña, Albert Lee, Kevin Troulé, Elisa Espinet, Lavinia Cabras, Carolina Navas, María Teresa Blasco, Laura Martín-Díaz, Miranda Burdiel, Jing Li, Zhaoqi Liu, Mireia Vallespinós, Francisco Sanchez-Bueno, Martin R Sprick, Andreas Trumpp, Bruno Sainz, Fátima Al-Shahrour, Raul Rabadan, Carmen Guerra, Mariano Barbacid
Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of abundant desmoplastic stroma primarily composed of cancer-associated fibroblasts (CAFs). It is generally accepted that CAFs stimulate tumor progression and might be implicated in drug resistance and immunosuppression. Here, we have compared the transcriptional profile of PDGFRα+ CAFs isolated from genetically engineered mouse PDAC tumors with that of normal pancreatic fibroblasts to identify genes potentially implicated in their protumorigenic properties...
January 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29351920/exceptional-response-to-pembrolizumab-in-a-metastatic-chemotherapy-radiation-resistant-ovarian-cancer-patient-harboring-a-cd274-pd-l1-genetic-rearrangement
#19
Stefania Bellone, Natalia Buza, Jungmin Choi, Luca Zammataro, Laurie Gay, Julia A Elvin, David L Rimm, Yuting Liu, Elena Ratner, Peter E Schwartz, Alessandro D Santin
PURPOSE: Ovarian carcinoma no longer responsive to surgery and chemotherapy remains an incurable disease. Alternative therapeutic options remain desperately needed. EXPERIMENTAL DESIGN: We describe a heavily pretreated ovarian cancer patient with recurrent disease experiencing a remarkable clinical response to treatment with the anti-PD1 immune check-point inhibitor pembrolizumab. The clinical, pathological, and genomic characteristics of this exceptional ovarian cancer responder were carefully investigated using immunohistochemistry (IHC), quantitative multiplex fluorescence methods (ie, automated quantitative analysis, AQUA) and whole exome sequencing (WES) techniques...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29351905/cancer-treatment-in-childhood-and-testicular-function-the-role-of-the-somatic-environment
#20
Jan-Bernd Stukenborg, Kirsi Jahnukainen, Marsida Hutka, Rod T Mitchell
Testicular function and future fertility may be affected by cancer treatment during childhood. Whilst survival of the germ (stem) cells is critical for ensuring the potential for fertility in these patients, the somatic cell populations also play a crucial role in providing a suitable environment to support germ cell maintenance and subsequent development. Regulation of the spermatogonial stem cell niche involves many signaling pathways with hormonal influence from the hypothalamo-pituitary-gonadal axis. In this review, we describe the somatic cell populations that comprise the testicular germ stem cell niche in human and how they may be affected by cancer treatment during childhood...
January 19, 2018: Endocrine Connections
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