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https://www.readbyqxmd.com/read/28095146/phase-i-first-in-human-study-of-venetoclax-in-patients-with-relapsed-or-refractory-non-hodgkin-lymphoma
#1
Matthew S Davids, Andrew W Roberts, John F Seymour, John M Pagel, Brad S Kahl, William G Wierda, Soham Puvvada, Thomas J Kipps, Mary Ann Anderson, Ahmed Hamed Salem, Martin Dunbar, Ming Zhu, Franklin Peale, Jeremy A Ross, Lori Gressick, Monali Desai, Su Young Kim, Maria Verdugo, Rod A Humerickhouse, Gary B Gordon, John F Gerecitano
Purpose B-cell leukemia/lymphoma-2 (BCL-2) overexpression is common in many non-Hodgkin lymphoma (NHL) subtypes. A phase I trial in patients with NHL was conducted to determine safety, pharmacokinetics, and efficacy of venetoclax, a selective, potent, orally bioavailable BCL-2 inhibitor. Patients and Methods A total of 106 patients with relapsed or refractory NHL received venetoclax once daily until progressive disease or unacceptable toxicity at target doses from 200 to 1,200 mg in dose-escalation and safety expansion cohorts...
January 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28093523/cutting-edge-nanog-activates-autophagy-under-hypoxic-stress-by-binding-to-bnip3l-promoter
#2
Meriem Hasmim, Bassam Janji, Mehdi Khaled, Muhammad Zaeem Noman, Fawzia Louache, Didier Bordereaux, Abdou Abderamane, Veronique Baud, Fathia Mami-Chouaib, Salem Chouaib
Hypoxia upregulates the core pluripotency factors NANOG, SOX2, and OCT4, associated with tumor aggressiveness and resistance to conventional anticancer treatments. We have previously reported that hypoxia-induced NANOG contributed in vitro to tumor cell resistance to autologous-specific CTL and in vivo to the in situ recruitment of immune-suppressive cells. In this study, we investigated the mechanisms underlying NANOG-mediated tumor cell resistance to specific lysis under hypoxia. We demonstrated the tumor-promoting effect of hypoxia on tumor initiation into immunodeficient mice using human non-small lung carcinoma cells...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28092804/enhancement-of-nk-cell-mediated-lysis-of-non-small-lung-cancer-cells-by-npkc-activator-ingenol-3-20-dibenzoate
#3
Chenyuan Gong, Chao Yao, Zihang Xu, Zhongya Ni, Xiaowen Zhu, Lixin Wang, Xuewei Yan, Wuxiong Zhou, Shiguo Zhu
The IFN-γ production is crucial for NK cell-mediated lysis of cancer cells. Thus increasing the IFN-γ production by NK cells may be an ideal strategy to improve their tumoricidal effect. Since the focus on new drug development has shifted towards natural products, limited information is out there about natural products that enhance the IFN-γ production by NK cells. In this study, through a high-throughput screening, we have identified a natural product ingenol 3,20 dibenzoate (IDB), an activator of tumor suppressor protein kinase C (PKC) isozymes, could increase the IFN-γ production and degranulation by NK cells, especially when NK cells were stimulated by non-small lung cancer (NSCLC) cells...
January 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28079265/chimeric-antigen-receptor-t-cells-in-hematologic-malignancies
#4
Brandon R Shank, Bryan Do, Adrienne Sevin, Sheree E Chen, Sattva S Neelapu, Sandra B Horowitz
Patients with B cell hematologic malignancies who progress through first or second line chemotherapy have a poor prognosis. Early clinical trials with autologous anti-CD19 chimeric antigen receptor (CAR) T cells have demonstrated promising results for patients who have relapsed or refractory disease. Lymphodepleting conditioning regimens including cyclophosphamide, fludarabine, pentostatin, bendamustine, interleukin-2, and total body irradiation are often administered prior to infusion of CAR T cells, allowing for greater T cell expansion...
January 12, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28078984/rasburicase-induced-methemoglobinemia-in-a-patient-with-glucose-6-phosphate-dehydrogenase-deficiency
#5
Maliha Khan, Shilpa Paul, Saad Farooq, Thein Hlaing Oo, Priya Ramshesh, Nitin Jain
BACKGROUND: Rasburicase is commonly used in patients with hematologic malignancies for tumor lysis syndrome prophylaxis and management. Methemoglobinemia is a serious rare adverse effect of rasburicase, more common in patients with G6PD deficiency. Prompt diagnosis and appropriate management of this condition can make the difference between successful recovery and significant morbidity. Here we discuss the link of rasburicase with methemoglobinemia and the pathophysiology behind increased incidence of this side effect in G6PD deficient patients...
January 11, 2017: Current Drug Safety
https://www.readbyqxmd.com/read/28077046/rational-use-of-rasburicase-for-the-treatment-and-management-of-tumor-lysis-syndrome
#6
Suhail A Shaikh, Bernard L Marini, Shannon M Hough, Anthony J Perissinotti
Purpose There is a lack of high-level evidence identifying meaningful outcomes and the optimal place in therapy of rasburicase in patients with, or at high risk for tumor lysis syndrome. The primary objective of this study was to evaluate and characterize outcomes resulting from an institution-specific guideline emphasizing supportive care, xanthine oxidase inhibitors, and lower doses of rasburicase. Methods In this retrospective chart review, we compared conservative rasburicase dosing, in accordance with newly developed UMHS tumor lysis syndrome guidelines, with aggressive rasburicase in adult patients (≥ 18 years of age) with hematological or solid tumor malignancies, and a uric acid level between 8 and 15 mg/dL...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28062698/monoclonal-antibodies-against-epidermal-growth-factor-receptor-acquire-an-ability-to-kill-tumor-cells-through-complement-activation-by-mutations-that-selectively-facilitate-the-hexamerization-of-igg-on-opsonized-cells
#7
Annalina Tammen, Stefanie Derer, Ralf Schwanbeck, Thies Rösner, Anna Kretschmer, Frank J Beurskens, Janine Schuurman, Paul W H I Parren, Thomas Valerius
Triggering of the complement cascade induces tumor cell lysis via complement-dependent cytotoxicity (CDC) and attracts and activates cytotoxic cells. It therefore represents an attractive mechanism for mAb in cancer immunotherapy development. The classical complement pathway is initiated by IgG molecules that have assembled into ordered hexamers after binding their Ag on the tumor cell surface. The requirements for CDC are further impacted by factors such as Ab epitope, valency, and affinity. Thus, mAb against well-validated solid tumor targets, such as the epidermal growth factor receptor (EGFR) that effectively induces complement activation and CDC, are highly sought after...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28060265/analysis-of-cap-binding-proteins-in-human-cells-exposed-to-physiological-oxygen-conditions
#8
Sara Timpano, Gaelan Melanson, Sonia L Evagelou, Brianna D Guild, Erin J Specker, James Uniacke
Translational control is a focal point of gene regulation, especially during periods of cellular stress. Cap-dependent translation via the eIF4F complex is by far the most common pathway to initiate protein synthesis in eukaryotic cells, but stress-specific variations of this complex are now emerging. Purifying cap-binding proteins with an affinity resin composed of Agarose-linked m(7)GTP (a 5' mRNA cap analog) is a useful tool to identify factors involved in the regulation of translation initiation. Hypoxia (low oxygen) is a cellular stress encountered during fetal development and tumor progression, and is highly dependent on translation regulation...
December 28, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28057026/advances-in-rare-cell-isolation-an-optimization-and-evaluation-study
#9
Stefan Schreier, Piamsiri Sawaisorn, Rachanee Udomsangpetch, Wannapong Triampo
BACKGROUND: Rare nucleated CD45 negative cells in peripheral blood may be malignant such as circulating tumor cells. Untouched isolation thereof by depletion of normal is favored yet still technological challenging. We optimized and evaluated a novel magnetic bead-based negative selection approach for enhanced enrichment of rare peripheral blood nucleated CD45 negative cells and investigated the problem of rare cell contamination during phlebotomy. METHODS: Firstly, the performance of the magnetic cell separation system was assessed using leukocytes and cultivated fibroblast cells in regard to depletion efficiency and the loss of cells of interest...
January 5, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28056525/venetoclax
#10
Amber C King, Tim J Peterson, Troy Z Horvat, Mabel Rodriguez, Laura A Tang
OBJECTIVE: To review the pharmacology, efficacy, and safety of venetoclax for treatment of lymphoid malignancies. DATA SOURCES: A literature search was performed of PubMed and MEDLINE databases (2005 to September 2016), abstracts from the American Society of Hematology and the American Society of Clinical Oncology, and ongoing studies from clinicaltrials.gov. Searches were performed utilizing the following key terms: venetoclax, ABT-199, GDC-199, obatoclax, GX15-070, BCL-2 inhibitor, navitoclax, ABT-263, and Venclexta...
December 1, 2016: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28053195/tcr-based-therapy-for-multiple-myeloma-and-other-b-cell-malignancies-targeting-intracellular-transcription-factor-bob1
#11
Lorenz Jahn, Pleun Hombrink, Renate S Hagedoorn, Michel G D Kester, Dirk M van der Steen, Tania Rodriguez, Tsvetelina Pentcheva-Hoang, Arnoud H de Ru, Marjolein P Schoonakker, Miranda H Meeuwsen, Marieke Griffioen, Peter A van Veelen, J H Frederik Falkenburg, Mirjam H M Heemskerk
Immunotherapy of hematological malignancies or solid tumors by administration of monoclonal antibodies or T-cells engineered to express chimeric antigen receptors or T-cell receptors (TCRs) has demonstrated clinical efficacy. However, antigen-loss tumor escape variants and the absence of currently targeted antigens on several malignancies hampers the widespread application of immunotherapy. We have isolated a TCR targeting a peptide of the intracellular B-cell specific transcription factor BOB1 presented in the context of HLA-B*07:02...
January 4, 2017: Blood
https://www.readbyqxmd.com/read/28050548/monostotic-fibrous-dysplasia-of-the-metacarpal-a-case-report
#12
Kátia Tôrres Batista, Hugo José de Araújo, Ulises Prieto Y Schwartzman
Fibrous dysplasia is a bone disease characterized by abnormal differentiation of fibrous tissue in the bones; it is often asymptomatic. It may affect one bone (monostotic) or several bones (polyostotic). The monostotic form primarily affects the ribs, but hardly ever affects the hand. It is important to make the differential diagnosis with malignant bone tumors. This article describes the treatment and outcome of a rare case of a patient admitted with a history of tumor growth in the right hand, diagnosed as fibrous dysplasia of the right second metacarpal...
November 2016: Revista Brasileira de Ortopedia
https://www.readbyqxmd.com/read/28046379/we-ab-bra-01-biodistribution-of-paclitaxel-loaded-nanodroplets-for-prostate-cancer-management-using-ultrasound-mediated-drug-delivery-under-mrguidance
#13
R Gupta, D Cvetkovic, B Wang, L Chen, C Ma
PURPOSE: To study the biodistribution of paclitaxel-loaded nanodroplets in vivo in order to evaluate the efficacy of focused ultrasound (FUS)-mediated drug delivery under MR-guidance to prostate tumor. METHODS: Poly {ethylene oxide}-co-poly {D, L-lactide} (PDLA) nanodroplets loaded with fluorescently labeled-paclitaxel (F-PTX) were synthesized using solid dispersion technique. Human prostate cancer, LNCaP cells were implanted orthotopically in prostates of male nude mice...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28040089/success-rate-and-risk-factors-of-failure-of-the-induced-membrane-technique-in-children-a-systematic-review
#14
Jean-Charles Aurégan, Thierry Bégué, Guillaume Rigoulot, Christophe Glorion, Stéphanie Pannier
The induced membrane technique was designed by Masquelet et al. to address segmental bone defects of critical size in adults. It has been used after bone defects of traumatic, infectious and tumoral origin with satisfactory results. Recently, it has been used in children but, after an initial enthusiasm, several cases of failure have been reported. The purpose of this study was to assess the success rate and the risk factors of failure of the induced membrane for children. We conducted a systematic review of all the studies reporting the results of the induced membrane technique to address bone defects of critical size in children...
December 2016: Injury
https://www.readbyqxmd.com/read/28027282/role-of-rifampin-in-reducing-inflammation-and-neuronal-damage-in-childhood-bacterial-meningitis-a-pilot-randomized-controlled-trial
#15
Lipi Uppal, Sunit Singhi, Pratibha Singhi, Ritu Aggarwal
BACKGROUND: Treatment of acute bacterial meningitis in children with bactericidal antibiotics causes cell wall lysis and a surge in inflammatory cascade, which in turn contributes to neuronal damage and morbidity. Pretreament with a non-bacteriolytic antibiotic, such as rifampin, has been shown to attenuate the inflammatory response in experimental models of bacterial meningitis. In a pilot study in children with bacterial meningitis we have studied markers of inflammatory response and neuronal damage in two groups of children with bacterial meningitis, one group received rifampin pretreatment with ceftriaxone, other group received ceftriaxone alone...
December 23, 2016: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28025583/a-novel-bcma-cd3-bi-specific-t-cell-engager-for-the-treatment-of-multiple-myeloma-induces-selective-lysis-in-vitro-and-in-vivo
#16
S Hipp, Y-T Tai, D Blanset, P Deegen, J Wahl, O Thomas, B Rattel, P J Adam, K Anderson, M Friedrich
B cell maturation antigen (BCMA) is a highly plasma cell selective protein that is expressed on malignant plasma cells of multiple myeloma (MM) patients and therefore is an ideal target for T cell redirecting therapies. We developed a bispecific T cell engager (BiTE(®)) targeting BCMA and CD3ɛ (BI 836909) and studied its therapeutic impacts on MM. BI 836909 induced selective lysis of BCMA-positive MM cells, activation of T cells, release of cytokines and T cell proliferation; whereas BCMA-negative cells were not affected...
December 27, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28011817/a-mechanism-for-evasion-of-ctl-immunity-by-altered-o-glycosylation-of-hla-class-i
#17
Mihoko Sutoh Yoneyama, Yuki Tobisawa, Shingo Hatakeyama, Misaki Sato, Kiyoshi Tone, Yota Tatara, Ikuko Kakizaki, Tomihisa Funyu, Minoru Fukuda, Senji Hoshi, Chikara Ohyama, Shigeru Tsuboi
Anti-tumor immunity by cytotoxic T-lymphocytes (CTLs) is essential to suppress tumor progression. Cancer cells that evade CTL immunity proliferate in the host, promoting metastasis, but mechanisms underlying this capacity remain unknown. Here we report that bladder cancer cells metastasized to lymph nodes evade CTL immunity by a new mechanism via altered glycosylation. CTLs normally recognize and kill cancer cells presenting antigenic peptides on human leukocyte antigen (HLA) class I. We show bladder cancer cells expressing the O-glycan processing enzyme, core2 β-1,6-N-acetylglucosaminyltransferase (C2GnT) exhibit HLA class I O-glycan modified with poly-N-acetyllactosamine and are highly susceptible to CTL...
December 22, 2016: Journal of Biochemistry
https://www.readbyqxmd.com/read/27993406/tumor-lysis-syndrome-in-solid-tumors-clinical-characteristics-and-prognosis
#18
Fernando Caravaca-Fontán, Olga Martínez-Sáez, Saúl Pampa-Saico, Maria Eugenia Olmedo, Antonio Gomis, Pilar Garrido
INTRODUCTION AND OBJECTIVE: Tumour lysis syndrome (TLS) is an uncommon complication in solid tumors following treatment initiation, and its spontaneous development (STLS) is exceptional. In this study, we analyse the main clinical and prognostic features of a case series with TLS and STLS. MATERIAL AND METHODS: Observational retrospective study in which we included all patients with solid tumours diagnosed with TLS and STLS over a period of 16 years, according to Cairo-Bishop criteria...
December 16, 2016: Medicina Clínica
https://www.readbyqxmd.com/read/27988837/talimogene-laherparepvec-t-vec-and-other-oncolytic-viruses-for-the-treatment-of-melanoma
#19
Praveen K Bommareddy, Anand Patel, Saamia Hossain, Howard L Kaufman
Many mammalian viruses have properties that can be commandeered for the treatment of cancer. These characteristics include preferential infection and replication in tumor cells, the initiation of tumor cell lysis, and the induction of innate and adaptive anti-tumor immunity. Furthermore, viruses can be genetically engineered to reduce pathogenicity and increase immunogenicity resulting in minimally toxic therapeutic agents. Talimogene laherparepvec (T-VEC; Imlygic™), is a genetically modified herpes simplex virus, type 1, and is the first oncolytic virus therapy to be approved for the treatment of advanced melanoma by the US FDA...
December 17, 2016: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/27967252/hyperleukocytosis-and-leukostasis-management-of-a-medical-emergency
#20
Sabrina Giammarco, Patrizia Chiusolo, Nicola Piccirillo, Alessia Di Giovanni, Elisabetta Metafuni, Luca Laurenti, Simona Sica, Livio Pagano
Hyperleukocytosis is defined as a white blood cell count greater than 100,000/mL in patients affected by acute leukemia and often it is associated with increased morbidity and mortality, that can be up to 40% if unrecognized. Areas covered: Risk factors include younger age, myelomonocytic or monocytic/monoblastic morphology, microgranular variant of acute promyelocitic leukemia and T-cell ALL, and some cytogenetic abnormalities. Poor prognosis due to high early death rate secondary to leukostasis. The mechanisms at the origin of leukostasis are still poorly understood...
December 26, 2016: Expert Review of Hematology
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