keyword
https://read.qxmd.com/read/35907014/a-phase-i-dose-escalation-dose-expansion-and-pharmacokinetic-trial-of-gemcitabine-and-alisertib-in-advanced-solid-tumors-and-pancreatic-cancer
#21
JOURNAL ARTICLE
Justin A Chen, Jasmine C Huynh, Chun-Yi Wu, Ai-Ming Yu, Karen Matsukuma, Thomas J Semrad, David R Gandara, Tianhong Li, Jonathan W Riess, Kit Tam, Philip C Mack, Anthony Martinez, Nichole Mahaffey, Karen L Kelly, Edward J Kim
PURPOSE: Aurora Kinase A (AKA) inhibition with gemcitabine represents a potentially synergistic cancer treatment strategy via mitotic catastrophe. The feasibility, safety, and preliminary efficacy of alisertib (MLN8237), an oral AKA inhibitor, with gemcitabine was evaluated in this open-label phase I trial with dose escalation and expansion. METHODS: Key inclusion criteria included advanced solid tumor with any number of prior chemotherapy regimens in the dose escalation phase, and advanced pancreatic adenocarcinoma with up to two prior chemotherapy regimens...
July 30, 2022: Cancer Chemotherapy and Pharmacology
https://read.qxmd.com/read/35733515/wee1-kinase-inhibitor-adavosertib-with-radiation-in-newly-diagnosed-diffuse-intrinsic-pontine-glioma-a-children-s-oncology-group-phase-i-consortium-study
#22
JOURNAL ARTICLE
Sabine Mueller, Tabitha Cooney, Xiaodong Yang, Sharmistha Pal, Ralph Ermoian, Amar Gajjar, Xiaowei Liu, Komal Prem, Charles G Minard, Joel M Reid, Marvin Nelson, Daphne Haas-Kogan, Elizabeth Fox, Brenda J Weigel
Background: Children with diffuse intrinsic pontine gliomas (DIPG) have a dismal prognosis. Adavosertib (AZD1775) is an orally available, blood-brain barrier penetrant, Wee1 kinase inhibitor. Preclinical efficacy against DIPG is heightened by radiation induced replication stress. Methods: Using a rolling six design, 7 adavosertib dose levels (DLs) (50 mg/m2 alternating weeks, 50 mg/m2 alternating with weeks of every other day, 50 mg/m2 , then 95, 130, 160, 200 mg/m2 ) were assessed...
January 2022: Neuro-oncology advances
https://read.qxmd.com/read/35460753/isolation-characterization-and-structure-based-engineering-of-a-neutralizing-nanobody-against-sars-cov-2
#23
JOURNAL ARTICLE
Tingting Li, Bingjie Zhou, Yaning Li, Suqiong Huang, Zhipu Luo, Yuanze Zhou, Yanling Lai, Anupriya Gautam, Salome Bourgeau, Shurui Wang, Juan Bao, Jingquan Tan, Dimitri Lavillette, Dianfan Li
SARS-CoV-2 engages with human cells through the binding of its Spike receptor-binding domain (S-RBD) to the receptor ACE2. Molecular blocking of this engagement represents a proven strategy to treat COVID-19. Here, we report a single-chain antibody (nanobody, DL4) isolated from immunized alpaca with picomolar affinity to RBD. DL4 neutralizes SARS-CoV-2 pseudoviruses with an IC50 of 0.101 μg mL-1 (6.2 nM). A crystal structure of the DL4-RBD complex at 1.75-Å resolution unveils the interaction detail and reveals a direct competition mechanism for DL4's ACE2-blocking and hence neutralizing activity...
June 1, 2022: International Journal of Biological Macromolecules
https://read.qxmd.com/read/35112552/temsirolimus-combined-with-cyclophosphamide-and-etoposide-for-pediatric-patients-with-relapsed-refractory-acute-lymphoblastic-leukemia-a-therapeutic-advances-in-childhood-leukemia-consortium-trial-tacl-2014-001
#24
JOURNAL ARTICLE
Sarah K Tasian, Lewis B Silverman, James A Whitlock, Richard Sposto, Joseph P Loftus, Eric S Schafer, Kirk R Schultz, Raymond J Hutchinson, Paul S Gaynon, Etan Orgel, Caroline M Bateman, Todd M Cooper, Theodore W Laetsch, Maria Luisa Sulis, Yueh-Yun Chi, Jemily Malvar, Alan S Wayne, Susan R Rheingold
Phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling is commonly dysregulated in acute lymphoblastic leukemia (ALL). The TACL2014-001 phase I trial of the mTOR inhibitor temsirolimus in combination with cyclophosphamide and etoposide was performed in children and adolescents with relapsed/refractory ALL. Temsirolimus was administered intravenously (IV) on days 1 and 8 with cyclophosphamide 440 mg/m2 and etoposide 100 mg/m2 IV daily on days 1-5. The starting dose of temsirolimus was 7...
October 1, 2022: Haematologica
https://read.qxmd.com/read/34722685/electromagnetic-field-associated-with-dermoscope-magnets-may-affect-the-safety-of-cardiac-implanted-electronic-devices-patients
#25
JOURNAL ARTICLE
Grzegorz Sławiński, Martyna Sławińska, Zbigniew Usarek, Michał Sobjanek, Maciej Kempa, Aleksandra Liżewska-Springer, Ewa Lewicka, Roman J Nowicki, Grzegorz Raczak
Dermoscopy is currently used as an auxiliary tool in general dermatology. Since some commercially available dermoscopes have built-in magnets, electromagnetic interference (EMI) may occur when examining cardiac implantable electronic devices (CIED) patients. The aim of the study was to create maps of electromagnetic fields defining a safe distance in terms of EMI. The study was performed in laboratory conditions using measuring equipment specially designed for this purpose. The following dermoscopes have been tested: Illuco IDS-1100, Visiomed Luminis, Visiomed Luminis 2, Heine NC2 with and without a contact plate, DermLite DL4, and DermLite Handyscope...
2021: Frontiers in Cardiovascular Medicine
https://read.qxmd.com/read/34701486/phase-i-trial-of-dose-escalated-five-fraction-stereotactic-ablative-radiotherapy-for-early-stage-lung-squamous-cell-carcinoma
#26
JOURNAL ARTICLE
K Shiue, A Cerra-Franco, V Verma, M Arbab, M P Langer, C Deig, M E Tharp Ii, P A Anthony, M Shan, S Althouse, Y Zang, G K Bartlett, J A Holmes, C DesRosiers, P G Maxim, D Frye, F M Kong, J Y Jin, G Watson, R C Zellars, T Lautenschlaeger
PURPOSE/OBJECTIVE(S): We aimed to evaluate the safety of and maximum tolerated dose (MTD) for 5-fraction stereotactic ablative radiotherapy (SABR) for early-stage lung squamous cell carcinoma (SCC), for which local failure rates appears higher than that of early-stage adenocarcinomas. MATERIALS/METHODS: A single institution phase I study was conducted in pathologically confirmed early-stage lung SCC. The 3+3 design involved 4 dose levels of 11, 12, 13, and 14 Gy x 5 fractions delivered every other day (dose levels DL1, DL2, DL3, and DL4, respectively)...
November 1, 2021: International Journal of Radiation Oncology, Biology, Physics
https://read.qxmd.com/read/34408144/dl4-%C3%AE-beads-induce-t-cell-lineage-differentiation-from-stem-cells-in-a-stromal-cell-free-system
#27
JOURNAL ARTICLE
Ashton C Trotman-Grant, Mahmood Mohtashami, Joshua De Sousa Casal, Elisa C Martinez, Dylan Lee, Sintia Teichman, Patrick M Brauer, Jianxun Han, Michele K Anderson, Juan Carlos Zúñiga-Pflücker
T cells are pivotal effectors of the immune system and can be harnessed as therapeutics for regenerative medicine and cancer immunotherapy. An unmet challenge in the field is the development of a clinically relevant system that is readily scalable to generate large numbers of T-lineage cells from hematopoietic stem/progenitor cells (HSPCs). Here, we report a stromal cell-free, microbead-based approach that supports the efficient in vitro development of both human progenitor T (proT) cells and T-lineage cells from CD34+ cells sourced from cord blood, GCSF-mobilized peripheral blood, and pluripotent stem cells (PSCs)...
August 18, 2021: Nature Communications
https://read.qxmd.com/read/33627685/a-phase-i-dose-finding-pharmacokinetics-and-genotyping-study-of-olaparib-and-lurbinectedin-in-patients-with-advanced-solid-tumors
#28
JOURNAL ARTICLE
Andres Poveda, Ana Oaknin, Ignacio Romero, Angel Guerrero-Zotano, Lorena Fariñas-Madrid, Victor Rodriguez-Freixinos, Pedro Mallol, Raquel Lopez-Reig, Jose Antonio Lopez-Guerrero
The poly (ADP-Ribose) polymerase (PARP) inhibitor olaparib has shown antitumor activity in patients with ovarian or breast cancer with or without BRCA1/2 mutations. Lurbinectedin is an ecteinascidin that generates DNA double-strand breaks. We hypothesized that the combination of olaparib and lurbinectedin maximizes the DNA damage increasing the efficacy. A 3 + 3 dose-escalation study examined olaparib tablets with lurbinectedin every 21 days. The purpose of this phase I study is to determine the dose-limiting toxicities (DLTs) of the combination, to investigate the maximum tolerated dose (MTD), the recommended phase II dose (RP2D), efficacy, pharmacokinetics, in addition to genotyping and translational studies...
February 24, 2021: Scientific Reports
https://read.qxmd.com/read/33455336/gelatin-based-3d-microgels-for-in-vitro-t-lineage-cell-generation
#29
JOURNAL ARTICLE
Anisha B Suraiya, Michael L Hun, Vinh X Truong, John S Forsythe, Ann P Chidgey
T cells are predominantly produced by the thymus and play a significant role in maintaining our adaptive immune system. Physiological involution of the thymus occurs gradually with age, compromising naive T cell output, which can have severe clinical complications. Also, T cells are utilized as therapeutic agents in cancer immunotherapies. Therefore, there is an increasing need for strategies aimed at generating naive T cells. The majority of in vitro T cell generation studies are performed in two-dimensional (2D) cultures, which ignore the physiological thymic microenvironment and are not scalable; therefore, we applied a new three-dimensional (3D) approach...
April 13, 2020: ACS Biomaterials Science & Engineering
https://read.qxmd.com/read/32410799/phase-1-2-study-of-concurrent-chemoradiotherapy-with-weekly-irinotecan-hydrochloride-for-advanced-recurrence-uterine-cancer-a-multi-institutional-study-of-kansai-clinical-oncology-group
#30
JOURNAL ARTICLE
Satoshi Takeuchi, Haruo Kuroboshi, Taisuke Mori, Kimihiko Ito, Eiji Kondo, Tsutomu Tabata, Yoshio Itani, Ryuji Kawaguchi, Kyosuke Takeuchi, Toshinori Soejima, Ryohei Sasaki
OBJECTIVE: Concurrent chemoradiotherapy using cisplatin was thought to be standard treatment for squamous cell carcinoma of cervix, but it had not been effective for adenocarcinoma. Concurrent chemoradiotherapy using irinotecan hydrochloride (CPT-11) had been effective for colorectal cancer, thus, we chose CPT-11 as a candidate for gynecologic adenocarcinoma. To evaluate the maximum tolerated dose (MTD) of weekly CPT-11 with external pelvic radiotherapy, a phase 1/2 study was conducted according to modified Fibonacci method...
April 2020: Chinese Journal of Cancer Research
https://read.qxmd.com/read/32259040/dermoscopy-of-stage-lla-mycosis-fungoides
#31
JOURNAL ARTICLE
Melike Kibar Ozturk, Ilkin Zindancı, Ebru Zemheri
OBJECTIVE: Differential diagnosis of mycosis fungoides (MF) in the early stages can be challenging. Dermoscopy has been reported to be useful in the evaluation of early MF. However, to our knowledge, there is no study that specifies these early stages as stage IA, IB or IIA. The present study aims to evaluate the dermoscopic findings of stage IIA MF in comparison with plaque psoriasis (PP). METHODS: Thirty-four patients aged between 16-70 years with stage IIA MF (n=17) and PP (n=17) were evaluated in this prospective study...
2020: Northern Clinics of Istanbul
https://read.qxmd.com/read/32154188/antibiotic-resistance-profile-outer-membrane-proteins-virulence-factors-and-genome-sequence-analysis-reveal-clinical-isolates-of-enterobacter-are-potential-pathogens-compared-to-environmental-isolates
#32
JOURNAL ARTICLE
Mitali Mishra, Sasmita Panda, Susmita Barik, Arup Sarkar, Durg Vijai Singh, Harapriya Mohapatra
Outer membrane proteins (OMPs) of gram-negative bacteria play an important role in mediating antibacterial resistance, bacterial virulence and thus affect pathogenic ability of the bacteria. Over the years, prevalence of environmental antibiotic resistant organisms, their transmission to clinics and ability to transfer resistance genes, have been studied extensively. Nevertheless, how successful environmental bacteria can be in establishing as pathogenic bacteria under clinical setting, is less addressed. In the present study, we utilized an integrated approach of investigating the antibiotic resistance profile, presence of outer membrane proteins and virulence factors to understand extent of threat posed due to multidrug resistant environmental Enterobacter isolates...
2020: Frontiers in Cellular and Infection Microbiology
https://read.qxmd.com/read/31876107/a-phase-i-study-of-sirolimus-in-combination-with-metronomic-therapy-choanome-in-children-with-recurrent-or-refractory-solid-and-brain-tumors
#33
JOURNAL ARTICLE
Muna Qayed, Thomas Cash, Mourad Tighiouart, Tobey J MacDonald, Kelly C Goldsmith, Rachel Tanos, Leslie Kean, Benjamin Watkins, Yvonne Suessmuth, Cynthia Wetmore, Howard M Katzenstein
BACKGROUND/PURPOSE: To determine the maximum tolerated dose, toxicities, and response of sirolimus combined with oral metronomic therapy in pediatric patients with recurrent and refractory solid and brain tumors. PROCEDURE: Patients younger than 30 years of age with recurrent, refractory, or high-risk solid and brain tumors were eligible. Patients received six-week cycles of sirolimus with twice daily celecoxib, and alternating etoposide and cyclophosphamide every three weeks, with Bayesian dose escalation over four dose levels (NCT01331135)...
April 2020: Pediatric Blood & Cancer
https://read.qxmd.com/read/31675535/a-phase-i-study-of-weekly-doxorubicin-and-oral-topotecan-for-patients-with-relapsed-or-refractory-small-cell-lung-cancer-sclc-a-fred-and-pamela-buffet-cancer-center-clinical-trials-network-study
#34
JOURNAL ARTICLE
Vinicius Ernani, Rahat Jahan, Lynette M Smith, Alissa S Marr, Sarah E Kimbrough, Mary E Kos, Jolene Tijerina, Shannon Pivovar, Imayavaramban Lakshmanan, Marsha Ketcham, Sanchita Rauth, Kavita Mallya, Mohd W Nasser, Maneesh Jain, Anne Kessinger, Surinder K Batra, Apar Kishor Ganti
BACKGROUND: Relapsed/refractory small cell lung cancer (SCLC) has a poor prognosis, with no good options. We evaluated a novel combination of topotecan and doxorubicin, providing sequential topoisomerase I and II inhibition, in this setting. MATERIALS AND METHODS: Adult patients (>19 years) with relapsed/refractory SCLC, who had received at least one prior chemotherapy regimen were eligible. Patients received escalating doses of oral topotecan on days 1-5 of each three week cycle (maximum - 5 cycles)...
2020: Cancer Treatment and Research Communications
https://read.qxmd.com/read/31578237/a-new-role-for-notch-in-the-control-of-polarity-and-asymmetric-cell-division-of-developing-t-cells
#35
JOURNAL ARTICLE
Mirren Charnley, Mandy Ludford-Menting, Kim Pham, Sarah M Russell
A fundamental question in biology is how single cells can reliably produce progeny of different cell types. Notch signalling frequently facilitates fate determination. Asymmetric cell division (ACD) often controls segregation of Notch signalling by imposing unequal inheritance of regulators of Notch. Here, we assessed the functional relationship between Notch and ACD in mouse T cell development. To attain immunological specificity, developing T cells must pass through a pivotal stage termed β-selection, which involves Notch signalling and ACD...
October 2, 2019: Journal of Cell Science
https://read.qxmd.com/read/31431705/ex-vivo-generated-human-t-lymphoid-progenitors-as-a-tool-to-accelerate-immune-reconstitution-after-partially-hla-compatible-hematopoietic-stem-cell-transplantation-or-after-gene-therapy
#36
REVIEW
Isabelle André, Laura Simons, Kuiying Ma, Ranjita Devi Moirangthem, Jean-Sébastien Diana, Elisa Magrin, Chloé Couzin, Alessandra Magnani, Marina Cavazzana
Prolonged T-cell immunodeficiency following HLA- incompatible hematopoietic stem cell transplantation (HSCT) represents a major obstacle hampering the more widespread use of this approach. Strategies to fasten T-cell reconstitution in this setting are highly warranted as opportunistic infections and an increased risk of relapse account for high rates of morbidity and mortality especially during early month following this type of HSCT. We have implemented a feeder free cell system based on the use of the notch ligand DL4 and cytokines allowing for the in vitro differentiation of human T-Lymphoid Progenitor cells (HTLPs) from various sources of CD34+ hematopoietic stem and precursor cells (HSPCs)...
August 2019: Bone Marrow Transplantation
https://read.qxmd.com/read/30995924/hla-and-killer-cell-immunoglobulin-like-receptor-kirs-genotyping-in-patients-with-acute-ischemic-stroke
#37
JOURNAL ARTICLE
Antonino Tuttolomondo, Domenico Di Raimondo, Rosaria Pecoraro, Alessandra Casuccio, Danilo Di Bona, Anna Aiello, Giulia Accardi, Valentina Arnao, Giuseppe Clemente, Vittoriano Della Corte, Carlo Maida, Irene Simonetta, Calogero Caruso, Rosario Squatrito, Antonio Pinto
INTRODUCTION: In humans, a major component of natural killer (NK) and T cell target recognition depends on the surveillance of human leukocyte antigen (HLA) class I molecules by killer immunoglobulin-like receptors (KIRs). AIMS: To implement the knowledge about the immunological genetic background of acute ischemic stroke susceptibility in relation to the frequency of the KIR genes and HLA alleles. METHODS: Subjects with acute ischemic stroke and subjects without stroke were genotyped for the presence of KIR genes and of the three major KIR ligand groups, HLA-C1, HLA-C2, and HLA-Bw4, both HLA-B and HLA-A loci...
April 17, 2019: Journal of Neuroinflammation
https://read.qxmd.com/read/30633397/in-vitro-generated-mart-1-specific-cd8-t-cells-display-a-broader-t-cell-receptor-repertoire-than-ex-vivo-na%C3%A3-ve-and-tumor-infiltrating-lymphocytes
#38
JOURNAL ARTICLE
Patricia M Benveniste, Munehide Nakatsugawa, Linh Nguyen, Pamela S Ohashi, Naoto Hirano, Juan Carlos Zúñiga-Pflücker
The differentiation of human hematopoietic stem cells into CD8 T cells can be achieved in vitro with the OP9-DL4 system. We considered that in the absence of medullary thymic epithelial cells, which serve to restrict the breath of the T-cell receptor (TCR) repertoire by expressing tissue-restricted antigens, a distinct repertoire would be generated in vitro. To test this notion, we compared the TCR-Vα/Vβ (TRAV/TRBV) gene usage of major histocompatibility complex-restricted antigen (MART-1)-specific T cells generated in vitro to that from ex vivo naïve T cells and tumor-infiltrating lymphocytes (TILs) using high-throughput DNA sequencing...
April 2019: Immunology and Cell Biology
https://read.qxmd.com/read/30468144/sow-environment-during-gestation-part-i-influence-on-maternal-physiology-and-lacteal-secretions-in-relation-with-neonatal-survival
#39
JOURNAL ARTICLE
E Merlot, H Pastorelli, A Prunier, M-C Père, I Louveau, L Lefaucheur, M-H Perruchot, M C Meunier-Salaün, D Gardan-Salmon, F Gondret, H Quesnel
In pig husbandry, pregnant females are often exposed to stressful conditions, and their outcomes on maternal and offspring health have not been well evaluated. The present study aimed at testing whether improving the welfare of gestating sows could be associated with a better maternal health during gestation, changes in the composition of lacteal secretions and improvement in piglet survival. Two contrasted group-housing systems for gestating sows were used, that is, a French conventional system on slatted floor (C, 49 sows) and an enriched system using larger pens on deep straw (E, 57 sows)...
July 2019: Animal
https://read.qxmd.com/read/30442216/sow-environment-during-gestation-part-ii-influence-on-piglet-physiology-and-tissue-maturity-at-birth
#40
JOURNAL ARTICLE
H Quesnel, M-C Père, I Louveau, L Lefaucheur, M-H Perruchot, A Prunier, H Pastorelli, M C Meunier-Salaün, D Gardan-Salmon, E Merlot, F Gondret
Sow environment during gestation can generate maternal stress which could alter foetal development. The effects of two group-housing systems for gestating sows on piglet morphological and physiological traits at birth were investigated. During gestation, sows were reared in a conventional system on a slatted floor (C, 18 sows), demonstrated as being stressful for sows or in an enriched system in larger pens and on deep straw bedding (E, 19 sows). On gestation day 105, sows were transferred into identical individual farrowing crates on a slatted floor...
November 16, 2018: Animal
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