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https://www.readbyqxmd.com/read/28740459/dosimetric-predictors-of-treatment-related-lymphopenia-induced-by-palliative-radiotherapy-predictive-ability-of-dose-volume-parameters-based-on-body-surface-contour
#1
Tetsuo Saito, Ryo Toya, Tomohiko Matsuyama, Akiko Semba, Natsuo Oya
BACKGROUND: Radiation-related lymphopenia has been associated with poor patient outcome. Our aim was to identify predictors of lymphopenia after palliative radiotherapy, with a focus on dose-volume parameters. PATIENTS AND METHODS: To retrospectively assess patients with various cancers who had undergone palliative radiotherapy, we delineated three organs at risk: the volume enclosed by the body surface contour (body A), the volume left after excluding air, pleural effusion, ascites, bile, urine, and intestinal content (body B), and the volume of the bone marrow (BM)...
June 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/28736763/immunologic-effects-of-maraviroc-in-hiv-infected-patients-with-severe-cd4-lymphopenia-starting-antiretroviral-therapy-a-sub-study-of-the-cadiris-trial
#2
Pablo F Belaunzarán-Zamudio, Livio Azzoni, David H Canaday, Yanink N Caro-Vega, Brian Clagget, Mohammed S Rassool, Benigno Rodriguez, Ian Sanne, Irini Sereti, Juan G Sierra-Madero, Michael M Lederman
BACKGROUND: We aimed to describe the mechanisms of immunological recovery and the effects of blocking CCR5 in patients starting ART with advanced HIV-infection. METHODS: This was a sub-study of a 48 week double-blind, clinical trial where patients starting ART with CD4+ cell counts <100 cells/uL were randomized to receive maraviroc or a placebo. CD4+ and CD8+ cell maturation phenotypes, expression of PD-1 and CCR5, and activation indices were measured at weeks 0, 4, 12, 24, and 48...
2017: Pathogens & Immunity
https://www.readbyqxmd.com/read/28736761/phase-ii-study-of-dovitinib-in-patients-progressing-on-anti-vascular-endothelial-growth-factor-therapy
#3
Thomas J Semrad, Edward J Kim, Michael S Tanaka, Jacob Sands, Chris Roberts, Rebekah A Burich, Yu Li, David R Gandara, Primo Lara, Philip C Mack
BACKGROUND: Prior work identified the fibroblast growth factor (FGF) pathway as a mediator of resistance to anti-vascular endothelial growth factor (VEGF) therapy. We tested dovitinib, an inhibitor of both FGF and VEGF receptors, in patients progressing on anti-VEGF treatment. METHODS: Patients with measurable advanced colorectal or non-small cell lung cancer with progression despite anti-VEGF treatment within 56 days, good performance status and adequate organ function were eligible...
2017: Cancer Treat Res Commun
https://www.readbyqxmd.com/read/28736642/gemcitabine-nab-paclitaxel-as-second-line-therapy-following-folfirinox-in-metastatic-advanced-pancreatic-cancer-retrospective-analysis-of-response
#4
Khanh T Nguyen, Aparna Kalyan, H Scott Beasley, Aatur D Singhi, Weijing Sun, Herbert J Zeh, Daniel Normolle, Nathan Bahary
BACKGROUND: Given the tolerability of nPG in first-line therapy, we desired to evaluate the response and toxicity profiles of second-line gemcitabine with nab-paclitaxel (nPG) following FOLFIRINOX. Methods: We retrospectively identified 30 patients who received first-line FOLFIRINOX for unresectable or metastatic pancreatic adenocarcinoma followed by second-line nPG. Response was evaluated by RECIST criteria and carbohydrate antigen 19-9 (CA19-9) change. RESULTS: Median age was 63 years with 77% percent having metastatic disease...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28724986/core-shell-lipid-polymer-hybrid-nanoparticles-with-combined-docetaxel-and-molecular-targeted-therapy-for-the-treatment-of-metastatic-prostate-cancer
#5
Qi Wang, Heba Alshaker, Torsten Böhler, Shyam Srivats, Yimin Chao, Colin Cooper, Dmitri Pchejetski
Many prostate cancers relapse after initial chemotherapy treatment. Combining molecular and chemotherapy together with encapsulation of drugs in nanocarriers provides effective drug delivery and toxicity reduction. We developed core shell lipid-polymer hybrid nanoparticles (CSLPHNPs) with poly (lactic-co-glycolic acid) (PLGA) core and lipid layer containing docetaxel and clinically used inhibitor of sphingosine kinase 1 (SK1) FTY720 (fingolimod). We show for the first time that FTY720 (both free and in CSLPHNPs) re-sensitizes castrate resistant prostate cancer cells and tumors to docetaxel, allowing a four-fold reduction in effective dose...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710747/phase-i-study-of-chimeric-antigen-receptor-modified-t-cells-in-treating-her2-positive-advanced-biliary-tract-cancers-and-pancreatic-cancers
#6
Kaichao Feng, Yang Liu, Yelei Guo, Jingdan Qiu, Zhiqiang Wu, Hanren Dai, Qingming Yang, Yao Wang, Weidong Han
This phase I clinical trial (NCT01935843) is to evaluate the safety, feasibility, and activity of chimeric antigen receptor-engineered T cell (CART) immunotherapy targeting human epidermal growth factor receptor 2 (HER2) in patients with advanced biliary tract cancers (BTCs) and pancreatic cancers (PCs). Eligible patients with HER2-positive (>50%) BTCs and PCs were enrolled in the trial. Well cultured CART-HER2 cells were infused following the conditioning treatment composed of nab-paclitaxel (100-200 mg/m(2)) and cyclophosphamide (15-35 mg/kg)...
July 14, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28704707/a-founder-mutation-underlies-a-severe-form-of-phosphoglutamase-3-pgm3-deficiency-in-tunisian-patients
#7
Leila Ben-Khemis, Najla Mekki, Imen Ben-Mustapha, Karen Rouault, Fethi Mellouli, Monia Khemiri, Mohamed Bejaoui, Leila Essaddam, Saayda Ben-Becher, Lamia Boughamoura, Saida Hassayoun, Meriem Ben-Ali, Mohamed-Ridha Barbouche
Phosphoglucomutase 3 (PGM3) protein catalyzes the conversion of N-acetyl-d-glucosamine-6-phosphate (GlcNAc-6-P) to N-acetyl-d-glucosamine-1-phosphate (GlcNAc-1-P), which is required for the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) an important precursor for protein glycosylation. Mutations in PGM3 gene have been recently shown to underlie a new congenital disorder of glycosylation often associated to elevated IgE. Herein, we report twelve PGM3 deficient patients. They belong to three highly consanguineous families, originating from a rural district in the west central Tunisia...
July 10, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28695300/new-fty720-docetaxel-nanoparticle-therapy-overcomes-fty720-induced-lymphopenia-and-inhibits-metastatic-breast-tumour-growth
#8
Heba Alshaker, Qi Wang, Shyam Srivats, Yimin Chao, Colin Cooper, Dmitri Pchejetski
PURPOSE: Combining molecular therapies with chemotherapy may offer an improved clinical outcome for chemoresistant tumours. Sphingosine-1-phosphate (S1P) receptor antagonist and sphingosine kinase 1 (SK1) inhibitor FTY720 (FTY) has promising anticancer properties, however, it causes systemic lymphopenia which impairs its use in cancer patients. In this study, we developed a nanoparticle (NP) combining docetaxel (DTX) and FTY for enhanced anticancer effect, targeted tumour delivery and reduced systemic toxicity...
July 10, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28694137/idiopathic-t-cell-lymphopenia-identified-in-new-york-state-newborn-screening
#9
Stephanie Albin-Leeds, Juliana Ochoa, Harshna Mehta, Beth H Vogel, Michele Caggana, Vincent Bonagura, Heather Lehman, Mark Ballow, Arye Rubinstein, Subhadra Siegel, Leonard Weiner, Geoffrey A Weinberg, Charlotte Cunningham-Rundles
Quantification of T-cell receptor excision circles (TRECs) for newborn screening for SCID has advanced the diagnosis of severe combined immune deficiency (SCID). However, it has led to the identification of infants with T cell lymphopenia without known cause. The clinical characteristics, appropriate laboratory monitoring, and outcomes of patients remain unclear. We performed a retrospective review of clinical and laboratory studies for 26 infants collected from 7 New York State referral centers from 2010 to 2016 with low TRECs (mean, 70copies/μl) and subnormal CD3 counts (mean, 1150/cubicmm)...
July 8, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28691750/human-neonatal-thymectomy-induces-altered-b-cell-responses-and-auto-reactivity
#10
Theo Broek, Asaf Madi, Eveline M Delemarre, Alvin W L Schadenberg, Kiki Tesselaar, José A M Borghans, Stefan Nierkens, Frank A Redegeld, Henny G Otten, Maura Rosetti, Salvatore Albani, Rachel Sorek, Irun R Cohen, Nicolaas J G Jansen, Femke van Wijk
An association between T-cell lymphopenia and autoimmunity has long been proposed, but it remains to be elucidated whether T-cell lymphopenia affects B-cell responses to auto-antigens. Human neonatal thymectomy results in a decrease in T-cell numbers and we used this model to study the development of auto-reactivity. Two cohorts of neonatally thymectomized individuals were examined, a cohort of young (1-5 years post-thymectomy, n = 10-27) and older children (>10years,n = 26), and compared to healthy age-matched controls...
July 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28684537/pomalidomide-bortezomib-and-dexamethasone-pvd-for-patients-with-relapsed-lenalidomide-refractory-multiple-myeloma
#11
Jonas Paludo, Joseph R Mikhael, Betsy R LaPlant, Alese E Halvorson, Shaji Kumar, Morie A Gertz, Suzanne R Hayman, Francis K Buadi, Angela Dispenzieri, John A Lust, Prashant Kapoor, Nelson Leung, Stephen J Russell, David Dingli, Ronald S Go, Yi Lin, Wilson I Gonsalves, Rafael Fonseca, P Leif Bergsagel, Vivek Roy, Taimur Sher, Asher A Chanan-Khan, Sikander Ailawadhi, A Keith Stewart, Craig B Reeder, Paul G Richardson, S Vincent Rajkumar, Martha Q Lacy
This phase I/II trial evaluated the maximum tolerated doses (MTD), safety and efficacy of pomalidomide, bortezomib and dexamethasone (PVD) combination in patients with relapsed, lenalidomide refractory, MM. In the phase I, dose level 1 consisted of pomalidomide 4mg PO days 1-21, bortezomib 1.0 mg/m(2) IV or SQ days 1,8,15,22 and dexamethasone 40mg PO days 1,8,15,22 given every 28 days. Bortezomib was increased to 1.3 mg/m(2) for dose level 2 and adopted in the phase 2 expansion cohort. We describe the results of 50 patients...
July 6, 2017: Blood
https://www.readbyqxmd.com/read/28679644/a-phase-ii-multi-center-study-of-bevacizumab-in-combination-with-ixabepilone-in-subjects-with-advanced-renal-cell-carcinoma
#12
Mauricio Burotto, Maureen Edgerly, Margarita Velarde, Sanjeeve Balasubramaniam, Harry Drabkin, Juan G Gormaz, Ciara O'Sullivan, Ravi Madan, Tito Fojo
LESSONS LEARNED: Accrual to renal cell carcinoma trials remains a challenge despite the lack of prolonged response to the available treatments.The observation of three responses among the 30 patients with median progression-free survival and overall survival of 8.3 and 15 months, respectively, indicates the combination has some activity, but it is not sufficient for further development. BACKGROUND: Treatment of metastatic renal cell carcinoma (mRCC) remains suboptimal...
July 5, 2017: Oncologist
https://www.readbyqxmd.com/read/28670575/cd8-memory-t-cell-inflation-renders-compromised-cd4-t-cell-dependent-cd8-t-cell-immunity-via-na%C3%A3-ve-t-cell-anergy
#13
Aizhang Xu, Andrew Freywald, Yufeng Xie, Zejun Li, Jim Xiang
Whether inflation of CD8(+) memory T (mT) cells, which is often derived from repeated prime-boost vaccinations or chronic viral infections in the elderly, would affect late CD8(+) T-cell immunity is a long-standing paradox. We have previously established an animal model with mT-cell inflation by transferring ConA-stimulated monoclonal CD8(+) T cells derived from Ova-specific T-cell-receptor transgenic OTI mice into irradiation-induced lymphopenic B6 mice. In this study, we also established another two animal models with mT-cell inflation by transferring, 1) ConA-stimulated monoclonal CD8(+) T cells derived from lymphocytic choriomeningitis virus glycoprotein-specific T-cell-receptor transgenic P14 mice, and 2) ConA-stimulated polyclonal CD8(+) T cells derived from B6...
2017: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/28669012/report-of-safety-of-pulse-dosing-of-lapatinib-with-temozolomide-and-radiation-therapy-for-newly-diagnosed-glioblastoma-in-a-pilot-phase-ii-study
#14
Andrew Yu, Nadia Faiq, Stacey Green, Albert Lai, Richard Green, Jethro Hu, Timothy F Cloughesy, Ingo Mellinghoff, P Leia Nghiemphu
Epidermal growth factor receptor (EGFR) mutations are commonly observed in Glioblastoma (GBM) and have long posed as a target for new therapies. Trials involving erlotinib have shown mixed results, likely owing to a mechanism of the mutation that may instead favor other EGFR inhibitors, such as lapatinib. We aimed to determine whether or not pulse high-dose lapatinib was a safe and tolerable regimen in addition to standard therapy. We recruited adult patients with newly-diagnosed GBM who had Karnofsky Performance Status ≥60, normal baseline hematological, hepatic, and renal function tests, and no prior history of radiation or treatment with EGFR inhibitor...
July 1, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28668896/systemic-intravenous-adoptive-transfer-of-autologous-lymphokine-activated-%C3%AE-%C3%AE-t-cells-improves-temozolomide-induced-lymphopenia-in-patients-with-glioma
#15
Yonehiro Kanemura, Miho Sumida, Yoshiko Okita, Ema Yoshioka, Atsuyo Yamamoto, Daisuke Kanematsu, Yukako Handa, Hayato Fukusumi, Yui Inazawa, A I Takada, Masahiro Nonaka, Shin Nakajima, Kanji Mori, Shigenori Goto, Takashi Kamigaki, Tomoko Shofuda, Shusuke Moriuchi, Mami Yamasaki
In this clinical study, we investigated the safety and clinical usefulness of systemic adoptive immunotherapy using autologous lymphokine-activated αβ T-cells (αβ T-cells), combined with standard therapies, in patients with malignant brain tumors. Twenty-three patients with different malignant brain tumors, consisting of 14 treated with temozolomide (TMZ group) and 9 treated without temozolomide (non-TMZ group), received systemic intravenous injections of αβ T-cells (mean=10.4 injections/patient for the TMZ group, and 4...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28666250/the-novel-sphingosine-1-phosphate-receptors-antagonist-ad2900-affects-lymphocyte-activation-and-inhibits-t-cell-entry-into-the-lymph-nodes
#16
Jing Song, Arie Dagan, Zhanna Yakhtin, Shimon Gatt, Sean Riley, Hugh Rosen, Reuven Or, Osnat Almogi-Hazan
Sphingolipid derivatives play key roles in immune cell migration and function. Synthetic sphingolipid analogues are used as therapeutics to intervene various inflammatory and malignant conditions. We hypothesize that different analogs have different effects on immune cells and therefore can be used as treatment for specific diseases. This study examines the properties of the novel synthetic sphingolipid analog, AD2900, and its effects on immune cell activation and lymphocyte localization in homeostasis. AD2900 is an antagonist for all sphingosine-1-phosphate (S1P) receptors...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28664499/romidepsin-in-japanese-patients-with-relapsed-or-refractory-peripheral-t-cell-lymphoma-a-phase-i-ii-and-pharmacokinetics-study
#17
Dai Maruyama, Kensei Tobinai, Michinori Ogura, Toshiki Uchida, Kiyohiko Hatake, Masafumi Taniwaki, Kiyoshi Ando, Kunihiro Tsukasaki, Takashi Ishida, Naoki Kobayashi, Kenichi Ishizawa, Yoichi Tatsumi, Koji Kato, Toru Kiguchi, Takayuki Ikezoe, Eric Laille, Tokihiro Ro, Hiromi Tamakoshi, Sanae Sakurai, Tomoko Ohtsu
This phase I/II multicenter study evaluated romidepsin treatment in Japanese patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL). Patients aged ≥20 years received romidepsin via a 4-h intravenous infusion on days 1, 8, and 15 of each 28-day cycle. Phase I used a 3 + 3 design to identify any dose-limiting toxicity (DLT) for regimens of romidepsin 9 and 14 mg/m(2). The primary endpoints for phase I and II were DLT and overall response rate (ORR), respectively...
June 29, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28662755/stress-leukogram-induced-by-acute-and-chronic-stress-in-zebrafish-danio-rerio
#18
Agata K Grzelak, Daniel J Davis, Susan M Caraker, Marcus J Crim, Jan M Spitsbergen, Charles E Wiedmeyer
The use of zebrafish (Danio rerio) as an animal model for experimental studies of stress has increased rapidly over the years. Although many physiologic and behavioral characteristics associated with stress have been defined in zebrafish, the effects of stress on hematologic parameters have not been described. The purpose of our study was to induce a rise in endogenous cortisol through various acute and chronic stressors and compare the effects of these stressors on peripheral WBC populations. Acutely stressed fish underwent dorsal or full-body exposure to air for 3 min, repeated every 30 min over the course of 90 min...
June 1, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28660549/safety-and-effectiveness-of-eribulin-in-japanese-patients-with-locally-advanced-or-metastatic-breast-cancer-a-post-marketing-observational-study
#19
Junichiro Watanabe, Yoshinori Ito, Shozo Ohsumi, Mitsuhiro Mizutani, Hideya Tashiro, Kenichi Sakurai, Masato Takahashi, Tsuyoshi Saito, Junji Tsurutani, Hirofumi Mukai, Tetsuhiro Yoshinami, Shintaro Takao, Yasuhisa Yamamoto, Toshiyuki Matsuoka, Hirotaka Iwase, Hiroji Iwata, Seigo Nakamura, Toshiaki Saeki
Background This large-scale study was conducted to evaluate the safety and effectiveness of eribulin for the treatment of inoperable or recurrent breast cancer in real-world settings in Japan. Methods Between July and December 2011, eligible patients with inoperable or recurrent breast cancer receiving eribulin for the first time were centrally registered and observed for 1 year. Eribulin was administered intravenously (1.4 mg/m(2)) on days 1 and 8 of every 3-week cycle. The primary endpoint was the frequency and intensity of adverse drug reactions (ADRs)...
June 29, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28653760/hepatitis-c-virus-reactivation-in-patients-receiving-cancer-treatment-a-prospective-observational-study
#20
Harrys A Torres, Jeff Hosry, Parag Mahale, Minas P Economides, Ying Jiang, Anna S Lok
Hepatitis C virus (HCV) reactivation in patients receiving cancer treatment has been reported in retrospective studies. We sought to determine prospectively the incidence, predictors, and clinical significance of HCV reactivation during cancer treatment. HCV-infected patients receiving cancer treatment at our institution (11/2012-07/2016) were studied. Reactivation was defined as an increase in HCV-RNA ≥1 log10 IU/mL over baseline and hepatitis flare as alanine aminotransferase (ALT) increase to ≥3 times the upper limit of normal...
June 27, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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