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https://www.readbyqxmd.com/read/28646408/a-mechanism-based-pk-pd-model-for-hematological-toxicities-induced-by-antibody-drug-conjugates
#1
Sihem Ait-Oudhia, Weiyan Zhang, Donald E Mager
Antibody-drug conjugates (ADCs) are complex drug platforms composed of monoclonal antibodies (mAbs) conjugated to potent cytotoxic drugs (payloads) via chemical linkers, enabling selective payload delivery to neoplastic cells, resulting in improved efficacy and reduced toxicity. Brentuximab vedotin (Adcetris®, SGN-35) and adotrastuzumab emtansine (Kadcyla®, T-DM1) are the two FDA-approved and commercially available ADCs, and both drugs exhibit ADC-related thrombocytopenia and neutropenia. A pharmacokinetic/pharmacodynamic (PK/PD) model for ADCs was developed to identify the analyte from each ADC that is most associated with the observed hematopoietic toxicities and to determine the role of the apparent in vivo payload release rate on the severity of thrombocytopenia and neutropenia...
June 23, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28642818/nivolumab-as-salvage-treatment-in-a-patient-with-hiv-related-relapsed-refractory-hodgkin-lymphoma-and-liver-failure-with-encephalopathy
#2
Jose D Sandoval-Sus, Francis Mogollon-Duffo, Ankita Patel, Nathan Visweshwar, Damian A Laber, Richard Kim, Michael V Jagal
BACKGROUND: We report the first case to our knowledge of a patient with relapsed/refractory classical hodgkin lymphoma and liver failure with encephalopathy along with human immunodeficiency virus/acquired immunodeficiency syndrome infection, successfully treated with nivolumab without major side effects and encouraging prolonged disease control. CASE PRESENTATION: In December 2015, at the time of the patient's progression from his Hodgkin lymphoma after fourth line treatment, he developed persistent fevers, abdominal distension, jaundice and worsening of his liver function tests...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28641637/-clinical-efficacy-and-safety-of-cmod-regimen-as-the-first-treatment-for-aged-new-diagnosed-patients-with-peripheral-t-cell-lymphoma
#3
Xiao-Lei Liu, Lei Gao, Na Cui
OBJECTIVE: To investigate clinical efficacy and safety of CMOD regimen as the first treatment for the aged new-diagnosed patients with peripheral T-cell lymphoma. METHODS: Seventy-six patients diagnosed as peripheral T cell lymphoma according to chemotherapy were divided into the 2 group: A and B groups. The patients in A group received CMOD regimen (38 cases) and the patients in B group received CHOP regiment (38 cases). The clinical efficacy, PFS (progression-free survival), OS and the adverse reactions in the 2 groups were compared...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641636/-short-and-long-term-clinical-efficacy-of-imrt-and-crt-for-treatment-of-patients-with-enktl
#4
Jian-Xiong Cui, Wu-Hua Lin
OBJECTIVE: To compare the short and long term clinical efficacy for treatment of patients with extranodal nasal-type NK/T-cell lymphoma(ENKTL) by intensity modulated radiotherapy(IMRT) and conventional radiotheraphy(CRT). METHODS: Sixty-three cases of early ENKTL were divided into the IMRT group of (33 cases) and CRT group(30 cases). The short effects, overall survival(OS) of 3 years, progression free survival(PFS) of 3 years, acute radiation injury and late adverse reactions to radiation were compared between 2 group...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28616753/gemcitabine-monotherapy-in-patients-with-heavily-treated-nasopharyngeal-cancer-a-case-series
#5
Tomohiro Enokida, Shinya Uozumi, Takao Fujisawa, Yuri Ueda, Susumu Okano, Makoto Tahara
BACKGROUND: Although gemcitabine is thought to play a critical role in the treatment of nasopharyngeal cancer, no research to evaluate the efficacy and toxicity of gemcitabine monotherapy has been conducted in Japan. METHODS: We retrospectively reviewed eight nasopharyngeal carcinoma patients treated with gemcitabine monotherapy at National Cancer Center Hospital East between May 2015 and August 2016. The main eligibility criteria were (1) histopathologically proven NPC; (2) tumor recurrence or an initial M1 TNM stage diagnosis; (3) at least two other types of systemic chemotherapy prior to gemcitabine; (4) no other active malignant tumor during treatment...
June 14, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28608578/cantharidin-inhibits-competitively-heme-fe-iii-binding-to-the-fa1-site-of-human-serum-albumin
#6
Fabio Polticelli, Loris Leboffe, Valentina Tortosa, Viviana Trezza, Gabriella Fanali, Mauro Fasano, Paolo Ascenzi
Cantharidin, a monoterpene isolated from the insect blister beetle, has long been used as a medicinal agent in the traditional Chinese medicine. Cantharidin inhibits a subgroup of serine/threonine phosphatases, thus inducing cell growth inhibition and cytotoxicity. Cantharidin has anticancer activity in vitro, since it is able of inducing p53-dependent apoptosis and double-strand breakage of DNA in cancer cells. Although the toxicity of cantharidin to the gastrointestinal and urinary tracts prevents its medical use, it is a promising lead compound for chemical modification to develop new anticancer therapeutics...
June 13, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28606468/protective-effect-of-rutin-on-humoral-and-cell-mediated-immunity-in-rat-model
#7
Aditya Ganeshpurkar, Ajay K Saluja
Diet and dietary intake can persuade the development, safeguard and proper functioning of immune system. Ruin, an important bioflavonoid, is abundantly found in various foodstuffs. Rutin has been acknowledged for its protective and beneficial effects on various aspects of the biological system. The present study was aimed to examine the effect of rutin on the regulation of the immune response in experimental animal models. Effect of rutin of cellular immunity was determined by delayed-type hypersensitivity (DTH) response, carbon clearance assay, leucocyte mobilization test, and cyclophosphamide-induced myelosuppression, whereas humoral immunity was analyzed by the haemagglutinating antibody (HA) titre assay...
June 9, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28601636/the-angiogenic-factor-egfl7-enhances-thymogenesis-by-activating-flt3-signaling
#8
Yousef Salama, Koichi Hattori, Beate Heissig
Thymic regeneration is a crucial function that allows for the generation of mature T cells after myelosuppression like irradiation. However molecular drivers involved in this process remain undefined. Here, we report that the angiogenic factor, epidermal growth factor-like domain 7 (Egfl7), is expressed on steady state thymic endothelial cells (ECs) and further upregulated under stress like post-irradiation. Egfl7 overexpression increased intrathymic early thymic precursors (ETPs) and expanded thymic ECs. Mechanistically, we show that Egfl7 overexpression caused Flt3 upregulation in ETPs and thymic ECs, and increased Flt3 ligand plasma elevation in vivo...
June 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28600037/continuous-oral-cyclophosphamide-as-salvage-or-maintenance-therapy-in-ovarian-primary-peritoneal-and-fallopian-tube-cancers-a%C3%A2-retrospective-single-institute-study
#9
Chui-Na Wong, Chui-Nguk Wong, Fu-Shing Liu
OBJECTIVE: Most patients with recurrent ovarian cancer are treated with multiple regimens of intravenous salvage chemotherapy. These anticancer agents often cause severe toxicities and offset their therapeutic effects. The present study assessed the experience of a single institute regarding the safety and treatment outcomes of continuous oral cyclophosphamide in patients with ovarian, primary peritoneal, and fallopian tube cancers. MATERIALS AND METHODS: A retrospective review was conducted on patients who received oral cyclophosphamide as salvage or maintenance therapy...
June 2017: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28599432/efficacy-and-tolerability-of-nanoparticle-albumin-bound-paclitaxel-in-combination-with-carboplatin-as-a-late-phase-chemotherapy-for-recurrent-and-advanced-non-small-cell-lung-cancer-a-multi-center-study-of-the-fukushima-lung-cancer-association-group-of-surgeons
#10
Mitsunori Higuchi, Hironori Takagi, Yuki Owada, Takuya Inoue, Yuzuru Watanabe, Takumi Yamaura, Mitsuro Fukuhara, Satoshi Muto, Naoyuki Okabe, Yuki Matsumura, Takeo Hasegawa, Atsushi Yonechi, Jun Osugi, Mika Hoshino, Yutaka Shio, Koichi Fujiu, Ryuzo Kanno, Akio Ohishi, Hiroyuki Suzuki, Mitsukazu Gotoh
The present retrospective multi-center study aimed to evaluate the efficacy and feasibility of nanoparticle albumin-bound (nab)-paclitaxel plus carboplatin as a second or late-phase chemotherapy in patients with non-small cell lung cancer (NSCLC). A total of 25 patients with recurrent or advanced NSCLC who had received previous chemotherapy were treated with nab-paclitaxel (70-100 mg/m(2), intravenously) on days 1, 8 and 15 every 28 days with a carboplatin area under the concentration-time curve of 4-6 on day 1...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28599428/bosutinib-as-a-fourth-line-therapy-for-a-patient-with-t315i-positive-lymphoid-blastic-phase-chronic-myeloid-leukemia-a-case-report
#11
Yukiko Komeno, Naoyuki Uchida, Yumiko Satoh, Hideki Uryu, Yuko Iwata, Akiko Masuda, Kuniko Iihara, Yutaka Yatomi, Shuichi Taniguchi, Tomiko Ryu
A 35-year-old male was diagnosed with chronic myeloid leukemia in the chronic phase and was prescribed 100 mg daily dasatinib. However, dasatinib was discontinued due to thrombocytopenia, and within six months, the disease progressed to the lymphoid blastic phase. Hyper-cyclophosphamide, vincristine, adriamycin and dexamethasone chemotherapy combined with 140 mg dasatinib or 600 mg imatinib was prescribed. The two inhibitors were soon discontinued due to severe thrombocytopenia and jaundice, respectively. Myelosuppression persisted subsequent to the nadir...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28594660/regulation-of-the-hematopoietic-stem-cell-lifecycle-by-the-endothelial-niche
#12
Pradeep Ramalingam, Michael G Poulos, Jason M Butler
PURPOSE OF REVIEW: Hematopoietic stem cells (HSCs) predominantly reside either in direct contact or in close proximity to the vascular endothelium throughout their lifespan. From the moment of HSC embryonic specification from hemogenic endothelium, endothelial cells (ECs) act as a critical cellular-hub that regulates a vast repertoire of biological processes crucial for HSC maintenance throughout its lifespan. In this review, we will discuss recent findings in endothelial niche-mediated regulation of HSC function during development, aging and regenerative conditions...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28586251/the-relationship-between-idiopathic-cytopenias-dysplasias-of-uncertain-significance-icus-idus-and-autoimmunity
#13
Wilma Barcellini
This review examines the several lines of evidence that support the relationship between myelodysplasia and autoimmunity, i.e. their epidemiologic association, the existence of common immune-mediated physiopathologic mechanisms, and the response to similar immunosuppressive therapies. The same relationship is reviewed here considering idiopathic cytopenia of uncertain significance (ICUS) and idiopathic dysplasia of uncertain significance (IDUS), two recently recognized provisional conditions characterized by isolated/unexplained cytopenia and/or dysplasia in <10% bone marrow cells...
June 15, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28575741/amino-functionalized-nano-vesicles-for-enhanced-anticancer-efficacy-and-reduced-myelotoxicity-of-carboplatin
#14
Xiumei Zhu, Yan Peng, Liyan Qiu
Carboplatin is one of the few platinum-based antitumor drugs used worldwide. Unfortunately, systemic carboplatin therapy is limited by its dose-related myelosuppression. In this study, a viable way to reduce the serious myelotoxicity of carboplatin while improving its therapeutic efficacy using amino-functionalized polyphosphazene vesicles is reported. First, three polyphosphazenes with different amino content were synthesized by amidating hydrophobic side groups; these polyphosphazenes could self-assemble into polymersomes with similar particle size and morphology...
May 15, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28566636/inhibition-of-methotrexate-uptake-via-organic-anion-transporters-oat1-and-oat3-by-glucuronides-of-nonsteroidal-anti-inflammatory-drugs
#15
Masahiro Iwaki, Hiroaki Shimada, Yuri Irino, Manami Take, Sachiko Egashira
Combination therapy of non-steroidal anti-inflammatory drugs (NSAIDs) and methotrexate (MTX) sometimes triggers adverse effects, such as liver injury, renal failure, gastrointestinal disorders, and myelosuppression, owing to the reduction of MTX clearance. Previous reports have suggested that NSAIDs inhibit renal MTX uptake via organic anion transporters (OATs) and reduced folate transporter (RFC)-1 and efflux via multidrug resistance-associated proteins (MRPs). Recently, our laboratory found inhibitory effects of NSAIDs-glucuronide (NSAIDs-Glu), a major metabolite of NSAIDs, on MRP-mediated MTX transport as a new site of interaction between MTX and NSAIDs...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28562379/dexrazoxane-added-to-doxorubicin-based-adjuvant-chemotherapy-of-breast-cancer-a-retrospective-cohort-study-with-a-comparative-analysis-of-toxicity-and-survival
#16
Esther Tahover, Amiel Segal, Rut Isacson, Ora Rosengarten, Tal Grenader, Maya Gips, Nathan Cherny, Norman I Heching, Lior Mesika, Raphael Catane, Alberto Gabizon
Dexrazoxane is indicated as a cardioprotective agent for patients receiving doxorubicin who are at increased risk for cardiotoxicity. Concerns have been raised on the use of dexrazoxane, particularly in adjuvant therapy, because of the risk of interference with the antitumor effect of doxorubicin. Two meta-analyses in metastatic breast cancer have rejected this hypothesis, but have shown an apparent increase in the severity of myelosuppression when dexrazoxane is used. Here, we analyzed retrospectively a cohort of our institute database to assess whether the addition of dexrazoxane causes more bone marrow suppression in breast cancer patients receiving doxorubicin-based adjuvant therapy...
May 30, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28557522/estimating-the-social-value-of-g-csf-therapies-in-the-united-states
#17
Jacqueline Vanderpuye-Orgle, Alison Sexton Ward, Caroline Huber, Chelsey Kamson, Anupam B Jena
OBJECTIVES: To provide a comprehensive estimate of the total social value (TSV) delivered by granulocyte-colony stimulating factor (G-CSF) therapies in the United States in 2014. STUDY DESIGN: Estimation of the TSV of G-CSF, based on a targeted literature review of pivotal studies. METHODS: A literature review was conducted to obtain estimates of the adverse outcomes associated with myelosuppressive chemotherapy-induced febrile neutropenia (FN) and the positive impacts of G-CSFs...
October 1, 2016: American Journal of Managed Care
https://www.readbyqxmd.com/read/28552060/thiopurine-s-methyltransferase-as-a-pharmacogenetic-biomarker-significance-of-testing-and-review-of-major-methods
#18
Chingiz Asadov, Gunay Aliyeva, Kamala Mustafayeva
Thiopurine S-methyltransferase (TPMT) enzyme metabolizes thiopurine drugs which are widely used in various disciplines as well as in leukemias. Individual enzyme activity varies depending on the genetic polymorphisms of TPMT gene located at chromosome 6. Up to 14% of population is known to have a decreased enzyme activity, and if treated with standard doses of thiopurines, these individuals are at the high risk of severe adverse drug reactions (ADR) as myelosuppression, gastrointestinal intolerance, pancreatitis and hypersensitivity...
May 28, 2017: Cardiovascular & Hematological Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28535087/cytotoxic-t-cells-in-chronic-idiopathic-neutropenia-express-restricted-antigen-receptors
#19
Semeli Mastrodemou, Evangelia Stalika, Anna Vardi, Katerina Gemenetzi, Michalis Spanoudakis, Maria Karypidou, Irene Mavroudi, Anastasia Hadzidimitriou, Catherine Stavropoulos-Giokas, Helen A Papadaki, Kostas Stamatopoulos
Chronic idiopathic neutropenia (CIN) is an acquired disorder of granulopoiesis characterized by female predominance and mostly uncomplicated course. Crucial to CIN pathophysiology is the presence of activated T lymphocytes with myelosuppressive properties in both peripheral blood (PB) and bone marrow (BM). We systematically profiled the T cell receptor beta chain (TRB) gene repertoire in CD8(+) cells of 34 CIN patients through subcloning/Sanger sequencing analysis of TRBV-TRBD-TRBJ gene rearrangements. Remarkable repertoire skewing and oligoclonality were observed, along with shared clonotypes between different patients, alluding to antigen selection...
May 23, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28533474/weekly-low-dose-versus-three-weekly-high-dose-cisplatin-for-concurrent-chemoradiation-in-locoregionally-advanced-non-nasopharyngeal-head-and-neck-cancer-a-systematic-review-and-meta-analysis-of-aggregate-data
#20
Petr Szturz, Kristien Wouters, Naomi Kiyota, Makoto Tahara, Kumar Prabhash, Vanita Noronha, Ana Castro, Lisa Licitra, David Adelstein, Jan B Vermorken
BACKGROUND: Three-weekly high-dose cisplatin (100 mg/m(2)) is considered the standard systemic regimen given concurrently with postoperative or definitive radiotherapy in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, due to unsatisfactory patient tolerance, various weekly low-dose schedules have been increasingly used in clinical practice. The aim of this meta-analysis was to compare the efficacy, safety, and compliance between these two approaches...
May 22, 2017: Oncologist
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