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https://www.readbyqxmd.com/read/28336527/a-phase-i-clinical-trial-of-single-agent-selinexor-in-acute-myeloid-leukemia
#1
Ramiro Garzon, Michael Savona, Rachid Baz, Michael Andreeff, Nashat Gabrail, Martin Gutierrez, Lynn Savoie, Morten Mau-Sorensen, Nina Wagner-Johnston, Karen Yee, T J Unger, Jean Richard Saint-Martin, Robert Carlson, Tami Rashal, Trinayan Kashyap, Boris Klebanov, Sharon Shacham, Michael Kauffman, Richard Stone
Selinexor is a novel, first-in-class, Selective Inhibitor of Nuclear Export (SINE) compound, which blocks XPO1 function, leads to nuclear accumulation of tumor suppressor proteins (TSPs) and induces cancer cell death. A phase I dose-escalation study was initiated to examine the safety and efficacy of selinexor in patients with advanced hematological malignancies. Ninety-five patients with relapsed or refractory acute myeloid leukemia (AML) were enrolled between January 2013 and June 2014 to receive 4, 8 or 10 doses of selinexor in 21- or 28-day cycle...
March 23, 2017: Blood
https://www.readbyqxmd.com/read/28325150/managing-expectations-in-the-transition-to-proof-of-concept-studies
#2
Thomas Kieber-Emmons, Issam Makhoul, Angela Pennisi, Eric R Siegel, Peter D Emanuel, Bejotaloh Monzavi-Karbassi, Zenon Steplewski, J Thaddeus Beck, Laura F Hutchins
BACKGROUND: As we are moving away from the traditional chemotherapy era to targeted therapy, the validity of old assessment paradigms associated with therapeutics are being raised in the context of immunotherapy. The old paradigm required elaborate assessment of toxicity with no expectation of efficacy in early phase trials. Safety data from Phase 1 and 2 studies with many immunotherapeutics show that they display limited toxicities and draw attention to the need to demonstrate efficacy in the early evaluation of new agents...
March 21, 2017: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/28319455/joint-model-imputation-to-estimate-the-treatment-effect-on-long-term-survival-using-auxiliary-events
#3
Audrey Mauguen, Stefan Michiels, Virginie Rondeau
Clinical trial duration may be a concern in clinical research, especially in cancer trials where the endpoint is overall survival. A surrogate endpoint can be used as an auxiliary variable to analyze the treatment effect earlier. At an early time point, the high number of censored observations can be compensated by the imputation of the unobserved deaths times. We propose to use predictions of the risk of death from a joint model for a recurrent event and a terminal event, which account for disease relapse information...
February 16, 2017: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/28297624/genomics-of-acute-myeloid-leukemia-diagnosis-and-pathways
#4
Lars Bullinger, Konstanze Döhner, Hartmut Döhner
In recent years, our understanding of the molecular pathogenesis of myeloid neoplasms, including acute myeloid leukemia (AML), has been greatly advanced by genomics discovery studies that use novel high-throughput sequencing techniques. AML, similar to most other cancers, is characterized by multiple somatically acquired mutations that affect genes of different functional categories, a complex clonal architecture, and disease evolution over time. Patterns of mutations seem to follow specific and temporally ordered trajectories...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28291693/synthesis-and-evaluation-of-a-ligand-targeting-the-%C3%AE-and-%C3%AE-opioid-receptors-for-drug-delivery-to-lung-cancer
#5
Guo Li, Philip S Low
A well-established approach to developing new imaging agents and treatments for cancer begins with the recognition of receptors that are overexpressed in cancer cells. Ideally, these same receptors would also be absent, or minimally expressed, in healthy tissue. The mu (μ) and delta (δ) opioid receptors (MOR and DOR respectively) match these criteria, with expression in cancer cells that is higher than primary lung epithelial cells. Naltrexone is a drug approved by the U.S. Food and Drug Administration (FDA) for treatment of alcohol dependence or prevention of relapse from opioid addiction...
June 28, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28270069/pathological-and-therapeutic-aspects-of-long-noncoding-rnas-in-osteosarcoma
#6
Kaixiu Wang, Wei Jiang, Chao Cheng, Yusheng Li, Min Tu
BACKGROUND: Osteosarcoma (OS) is a common bone malignant tumor, which is the eighth leading form of pediatric cancer. Despite the modern chemotherapeutic development of OS, a number of patients with OS have a high risk of lung metastasis and local relapse after chemotherapy. OBJECTIVE: This review study focused on the role of long non coding RNAs (lncRNAs) in OS progression, and presented update reports on OS treatment by targeting specific lncRNAs. METHOD: We have acquired information on OS and lncRNAs from scientific databases like google scholar, pubmed and scopus, and reviewed for this study...
February 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28269454/prediction-of-oral-cancer-recurrence-using-dynamic-bayesian-networks
#7
Konstantina Kourou, George Rigas, Konstantinos P Exarchos, Costas Papaloukas, Dimitrios I Fotiadis
We propose a methodology for predicting oral cancer recurrence using Dynamic Bayesian Networks. The methodology takes into consideration time series gene expression data collected at the follow-up study of patients that had or had not suffered a disease relapse. Based on that knowledge, our aim is to infer the corresponding dynamic Bayesian networks and subsequently conjecture about the causal relationships among genes within the same time-slice and between consecutive time-slices. Moreover, the proposed methodology aims to (i) assess the prognosis of patients regarding oral cancer recurrence and at the same time, (ii) provide important information about the underlying biological processes of the disease...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28261344/a-nomogram-for-predicting-the-probability-of-recurrence-in-patients-with-carcinomas-located-in-the-ampulla-of-vater
#8
Keng-Hao Liu, Chih-Ho Hsu, Jun-Te Hsu, Chun-Yi Tsai, Yu-Yin Liu, Tsann-Long Hwang, Ta-Sen Yeh, Yu-Shin Hung, Wen-Chi Chou
Background and Objectives: The standard treatment for carcinomas of the ampulla of Vater (CAV) is surgical resection. Nevertheless, recurrence is observed in half of the patients within five years after cancer surgery. In this study, we aimed to identify predictive factors and develop a nomogram capable of predicting the risk of recurrence in post-resection CAV patients. Methods: Our study cohort was composed of two hundred and twelve patients who had undergone radical surgery for CAV between 2000 and 2012...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28240420/clinical-utility-of-multipolar-ablation-with-a-three-dimensional-simulator-system-for-patients-with-liver-cancer
#9
Masashi Hirooka, Yohei Koizumi, Yusuke Imai, Yoshiko Nakamura, Atsushi Yukimoto, Takao Watanabe, Osamu Yoshida, Yoshio Tokumoto, Masanori Abe, Yoichi Hiasa
BACKGROUND AND AIM: To confirm the efficacy of multipolar ablation with a new simulator system, 3D sim-Navigator, for patients with hepatocellular carcinoma by assessing relapse-free survival and shape of the ablation volume under clinical conditions. METHODS: All participants provided written, informed consent, and study protocols were approved by the institutional ethics committee. Twenty-seven patients with 27 nodules were treated by no-touch ablation using the new simulator system...
February 27, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28227700/prediction-of-oral-cancer-recurrence-using-dynamic-bayesian-networks
#10
Konstantina Kourou, George Rigas, Konstantinos P Exarchos, Costas Papaloukas, Dimitrios I Fotiadis, Konstantina Kourou, George Rigas, Konstantinos P Exarchos, Costas Papaloukas, Dimitrios I Fotiadis, George Rigas, Konstantinos P Exarchos, Dimitrios I Fotiadis, Costas Papaloukas, Konstantina Kourou
We propose a methodology for predicting oral cancer recurrence using Dynamic Bayesian Networks. The methodology takes into consideration time series gene expression data collected at the follow-up study of patients that had or had not suffered a disease relapse. Based on that knowledge, our aim is to infer the corresponding dynamic Bayesian networks and subsequently conjecture about the causal relationships among genes within the same time-slice and between consecutive time-slices. Moreover, the proposed methodology aims to (i) assess the prognosis of patients regarding oral cancer recurrence and at the same time, (ii) provide important information about the underlying biological processes of the disease...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28218784/mutations-in-codons-12-and-13-of-k-ras-exon-2-in-colorectal-tumors-of-saudi-arabian-patients-frequency-clincopathological-associations-and-clinical-outcomes
#11
J Zekri, A Al-Shehri, M Mahrous, S Al-Rehaily, T Darwish, S Bassi, H El Taani, A Al Zahrani, S Elsamany, J Al-Maghrabi, B B Sadiq
Mutations in codons 12/13 of K-ras exon 2 are associated with reduced benefit from anti-epidermal growth factor receptor antibody treatment for metastatic colorectal cancer (CRC). Here, we evaluated the frequency of K-ras mutations and their relationship with clinicopathological features and treatment outcomes in Saudi Arabian patients with CRC. The genetic status of K-ras was determined in 300 patients diagnosed with CRC. Clinical information was collected retrospectively. K-ras was wild-type in 58% and mutated in 42% of the tumors...
February 16, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28197383/analysis-of-the-prognostic-role-of-an-immune-checkpoint-score-in-resected-non-small-cell-lung-cancer-patients
#12
Marta Usó, Eloísa Jantus-Lewintre, Silvia Calabuig-Fariñas, Ana Blasco, Eva García Del Olmo, Ricardo Guijarro, Miguel Martorell, Carlos Camps, Rafael Sirera
Tumors develop mechanisms to recruit tolerogenic immune cells and to induce the expression of molecules that act as immune checkpoints. This regulation of the immune microenvironment favors immune tolerance to the neoplastic cells. In this study, we have investigated the prognostic role of immune-checkpoint expression markers in a cohort of resectable non-small cell lung cancer (NSCLC) patients. RNA was isolated from fresh-frozen lung specimens (tumor and normal lung) (n = 178). RTqPCR was performed to analyze the relative expression of 20 immune-related genes that were normalized by the use of endogenous genes selected by GeNorm algorithm...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28195905/value-of-intratumoral-metabolic-heterogeneity-and-quantitative-18f-fdg-pet-ct-parameters-to-predict-prognosis-in-patients-with-hpv-positive-primary-oropharyngeal-squamous-cell-carcinoma
#13
Esther Mena, Mehdi Taghipour, Sara Sheikhbahaei, Abhinav K Jha, Arman Rahmim, Lilja Solnes, Rathan M Subramaniam
OBJECTIVE: The aim of this study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative FDG PET/CT imaging parameters for predicting patient outcomes in primary oropharyngeal squamous cell cancer (OPSCC). PATIENTS AND METHODS: We retrospectively investigated 105 patients with HPV-positive OPSCC. SUVmax and metabolic tumor volume (MTV) were measured for the primary tumors and when available for the metastatic sites. Primary tumor intratumoral metabolic heterogeneity was calculated as the area under a cumulative SUV volume histograms curve (AUC-CSH)...
February 13, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28151712/integration-of-novel-agents-into-the-care-of-patients-with-multiple-myeloma
#14
EDITORIAL
Robert Z Orlowski, Sagar Lonial
The pace of therapeutic drug development in multiple myeloma has reached unprecedented levels, with five regulatory approvals for relapsed and/or refractory disease of either new drugs or new drug regimens in 2015, one already in 2016, and still others anticipated. This has provided a wide array of options to be considered by patients and their health care providers in the event of relapse after or progression on front-line therapy. Most of these agents are currently being evaluated in earlier patient populations, including as parts of induction, consolidation, and maintenance therapy approaches, where their benefits may be even greater...
November 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28151709/progress-and-paradigms-in-multiple-myeloma
#15
EDITORIAL
Kenneth C Anderson
Remarkable progress has been achieved in multiple myeloma, and patient median survival has been extended 3- to 4-fold. Specifically, there have been 18 newly approved treatments for multiple myeloma in the past 12 years, including seven in 2015, and the treatment paradigm and patient outcome have been transformed. The definition of patients benefitting from these therapies has been broadened. Response criteria now include minimal residual disease (MRD), assessed in bone marrow by multicolor flow cytometry or sequencing, and by imaging for extramedullary disease...
November 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28150408/clinical-significance-and-predicting-indicators-of-post-cancer-treatment-survival-in-terminally-ill-patients-with-ovarian-cancer
#16
Fumi Utsumi, Hiroaki Kajiyama, Kaoru Niimi, Ryuichiro Sekiya, Jun Sakata, Shiro Suzuki, Kiyosumi Shibata, Mika Mizuno, Fumitaka Kikkawa
AIM: Women with ovarian cancer (OC) often experience relapse and receive further repetitive chemotherapy. The objective of this study was to overview the remaining survival time after the final chemotherapy and to examine influential clinicopathologic indicators in those patients. METHODS: The medical charts of deceased OC patients who had died of the disease between 2003 and 2012 were retrospectively reviewed. We investigated post-cancer-treatment survival (PCS) defined as the interval between the date of the final chemotherapy and death...
February 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28123750/accuracy-of-transbronchial-biopsy-as-a-rebiopsy-method-for-patients-with-relapse-of-advanced-non-small-cell-lung-cancer-after-systemic-chemotherapy
#17
Hidenobu Ishii, Koichi Azuma, Kazuhiko Yamada, Norikazu Matsuo, Masayuki Nakamura, Takaaki Tokito, Takashi Kinoshita, Tomoaki Hoshino
INTRODUCTION: Rebiopsy in patients with advanced non-small-cell lung cancer (NSCLC) resistant to systemic chemotherapy may yield information on the mechanisms of resistance and planning of subsequent treatment. Transbronchial biopsy (TBB) using a flexible bronchoscope has been commonly used for establishing the initial diagnosis of lung cancer. The aim of this study was to assess the accuracy and safety of TBB in patients with NSCLC relapse, and the factors affecting its diagnostic yield...
2017: BMJ Open Respiratory Research
https://www.readbyqxmd.com/read/28108818/association-between-bone-scan-index-and-activities-of-daily-living-in-patients-with-advanced-non-small-cell-lung-cancer
#18
Ikuno Ito, Kimiteru Ito, Shinichi Takahashi, Mitsuko Horibe, Rui Karita, Chika Nishizaka, Takako Nagai, Kohei Hamada, Hiroyuki Sato, Naoko Shindo
PURPOSE: The aim of this retrospective cross-sectional study was to investigate the association between the bone scan index (BSI) and activities of daily living (ADL) in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Among patients with advanced NSCLC, subjects who underwent bone scintigraphy were recruited from this study. Clinical information about patients, including the Barthel Index of ADL, was extracted from their medical charts. Variables including the age, sex, BSI, presence/absence skeletal-related events (SREs), diagnostic state (initial vs...
January 20, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28097046/molecular-classification-of-tissue-from-a-transformed-non-hogkin-s-lymphoma-case-with-unexpected-long-time-remission
#19
Julie Støve Bødker, Marianne Tang Severinsen, Tarec Christoffer El-Galaly, Rasmus Froberg Brøndum, Maria Bach Laursen, Steffen Falgreen, Mette Nyegaard, Alexander Schmitz, Lasse Hjort Jakobsen, Anna Amanda Schönherz, Hanne Due, Linn Reinholdt, Martin Bøgsted, Karen Dybkær, Hans Erik Johnsen
BACKGROUND: The concept of precision medicine in cancer includes individual molecular studies to predict clinical outcomes. In the present N = 1 case we retrospectively have analysed lymphoma tissue by exome sequencing and global gene expression in a patient with unexpected long-term remission following relaps. The goals were to phenotype the diagnostic and relapsed lymphoma tissue and evaluate its pattern. Furthermore, to identify mutations available for targeted therapy and expression of genes to predict specific drug effects by resistance gene signatures (REGS) for R-CHOP as described at http://www...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28092963/mathematical-modeling-of-continuous-and-intermittent-androgen-suppression-for-the-treatment-of-advanced-prostate-cancer
#20
Alacia M Voth, John G Alford, Edward W Swim
Prostate cancer is one of the most prevalent types of cancer among men. It is stimulated by the androgens, or male sexual hormones, which circulate in the blood and diffuse into the tissue where they stimulate the prostate tumor to grow. One of the most important treatments for advanced prostate cancer has become androgen deprivation therapy (ADT). In this paper we present three different models of ADT for prostate cancer: continuous androgen suppression (CAS), intermittent androgen suppression (IAS), and periodic androgen suppression...
June 1, 2017: Mathematical Biosciences and Engineering: MBE
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