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Sapan J Patel, Costel C Darie, Bayard D Clarkson
Tumors contain heterogeneous cell populations and achieve dominance by functioning as collective systems. The mechanisms underlying the aberrant growth and interactions between cells are not very well understood. The pre-B acute lymphoblastic leukemia cells we studied were obtained directly from a patient with Ph+ ALL. A new Ph+ ALL cell line (ALL3) was established from the leukemic cells growing as ascitic cells in his pleural fluid. The patient died of his disease shortly after the cells were obtained. ALL3 cells grow well at high cell densities (HD), but not at low cell densities...
2016: American Journal of Translational Research
Jessica T Leonard, Wendy Stock
No abstract text is available yet for this article.
November 2016: Biology of Blood and Marrow Transplantation
(no author information available yet)
Dual targeting of the ABL and LYN kinases and BCL2 synergizes to promote Ph(+)ALL cell apoptosis.
October 2016: Cancer Discovery
Ebrahem M Eid, Ahmed F El-Bebany, Sulaiman A Alrumman, Abd El-Latif Hesham, Mostafa A Taher, Khaled F Fawy
In this study, we present the response of spinach to different amendment rates of sewage sludge (0, 10, 20, 30, 40 and 50 g kg(-1)) in a greenhouse pot experiment, where plant growth, biomass and heavy metal uptake were measured. The results showed that sewage sludge application increased soil EC, organic matter, chromium and zinc concentrations and decreased soil pH. All heavy metal concentrations of the sewage sludge were below the permissible limits for land application of sewage sludge recommended by the Council of the European Communities...
September 3, 2016: International Journal of Phytoremediation
Jessica T Leonard, Joelle S J Rowley, Christopher A Eide, Elie Traer, Brandon Hayes-Lattin, Marc Loriaux, Stephen E Spurgeon, Brian J Druker, Jeffrey W Tyner, Bill H Chang
Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) remains a challenge. Although the addition of targeted tyrosine kinase inhibitors (TKIs) to standard cytotoxic therapy has greatly improved upfront treatment, treatment-related morbidity and mortality remain high. TKI monotherapy provides only temporary responses and renders patients susceptible to the development of TKI resistance. Thus, identifying agents that could enhance the activity of TKIs is urgently needed. Recently, a selective inhibitor of B cell lymphoma 2 (BCL-2), ABT-199 (venetoclax), has shown impressive activity against hematologic malignancies...
August 31, 2016: Science Translational Medicine
Xavier Thomas, Maël Heiblig
In Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL), the BCR-ABL translocation is the main transforming event; consequently, it is targeted by ABL-tyrosine kinase inhibitors (TKIs), the first of which to be identified was imatinib mesylate. There are now four newer TKIs, three so-called second-generation inhibitors and one third generation inhibitor, all of which are more potent than imatinib in in vitro assays. Areas covered: This paper reviews the current knowledge on the function of BCR-ABL...
November 2016: Expert Opinion on Drug Discovery
Yoshimasa Kamoda, Kiyotaka Izumi, Futoshi Iioka, Takashi Akasaka, Fumihiko Nakamura, Chiyuki Kishimori, Katsuyo Tsuda, Katsuhiro Fukutsuka, Atsuko Okumura, Masahiko Hayashida, Hitoshi Ohno
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) may include the lymphoid blast crisis of chronic myeloid leukemia (CML-BC). We applied fluorescence in situ hybridization (FISH) of the BCR-ABL fusion gene to peripheral blood and/or bone marrow smears to determine whether the fusion was restricted to mononuclear cell nuclei or if segmented cell nuclei representing mature neutrophils also carried the fusion (Seg-FISH). Among 20 patients with Ph+ ALL without a prior diagnosis of CML, 9 were Seg-FISH+ and 11 were Seg-FISH-...
2016: Acta Haematologica
Laura L Reimers, Supriya D Mehta, L Stewart Massad, Robert D Burk, Xianhong Xie, Jacques Ravel, Mardge H Cohen, Joel M Palefsky, Kathleen Weber, Xiaonan Xue, Kathryn Anastos, Howard Minkoff, Jessica Atrio, Gypsyamber D'Souza, Qian Ye, Christine Colie, Christine P Zolnik, Gregory T Spear, Howard D Strickler
BACKGROUND:  Bacterial vaginosis (BV) is characterized by low abundance of Lactobacillus spp., high pH, immune cell infiltration, and has been associated with increased risk of human papillomavirus (HPV) infection. We molecularly assessed the cervicovaginal microbiota over time in HIV-infected and HIV-uninfected women to more comprehensively study the HPV-microbiota relationship, controlling for immune status. METHODS:  16S rRNA gene amplicon pyrosequencing and HPV DNA testing was conducted annually in serial cervicovaginal lavage specimens obtained over 8-10 years in African American women from Chicago: (i) N=22 HIV-uninfected, (ii) N=22 HIV-infected with stable CD4 >500 cells/mm(3), (iii) N=20 HIV-infected women with progressive immunosuppression...
August 11, 2016: Journal of Infectious Diseases
Takanobu Morishita, Fumihiko Hayakawa, Keiki Sugimoto, Mizuho Iwase, Hideyuki Yamamoto, Daiki Hirano, Yuki Kojima, Naoto Imoto, Tomoki Naoe, Hitoshi Kiyoi
Cell lines have been used for drug discovery as useful models of cancers; however, they do not recapitulate cancers faithfully, particularly from the viewpoints of microenvironmental independence. Patient-derived xenografts (PDX) are established by the transfer of primary tumor cells directly from patients into immunodeficient mice and can provide primary-like tumor cells of the amount needed at the desired time. We developed a high-throughput drug screening system using PDX cells and performed drug screening using the PDX cells of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)...
August 2, 2016: Oncotarget
Federico Lussana, Tamara Intermesoli, Francesca Gianni, Cristina Boschini, Arianna Masciulli, Orietta Spinelli, Elena Oldani, Manuela Tosi, Anna Grassi, Margherita Parolini, Ernesta Audisio, Chiara Cattaneo, Roberto Raimondi, Emanuele Angelucci, Irene Maria Cavattoni, Anna Maria Scattolin, Agostino Cortelezzi, Francesco Mannelli, Fabio Ciceri, Daniele Mattei, Erika Borlenghi, Elisabetta Terruzzi, Claudio Romani, Renato Bassan, Alessandro Rambaldi
Allogeneic stem cell transplantation (alloHSCT) in first complete remission (CR1) remains the consolidation therapy of choice in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). The prognostic value of measurable levels of minimal residual disease (MRD) at time of conditioning is a matter of debate. We analyzed the predictive relevance of MRD levels before transplantation on the clinical outcome of Ph+ ALL patients treated with chemotherapy and imatinib in 2 consecutive prospective clinical trials...
November 2016: Biology of Blood and Marrow Transplantation
Koji Sasaki, Elias J Jabbour, Farhad Ravandi, Nicholas J Short, Deborah A Thomas, Guillermo Garcia-Manero, Naval G Daver, Tapan M Kadia, Marina Y Konopleva, Nitin Jain, Ghayas C Issa, Vicki Jeanis, Haim G Moore, Rebecca S Garris, Naveen Pemmaraju, Jorge E Cortes, Susan M O'Brien, Hagop M Kantarjian
BACKGROUND: The clinical efficacy of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD) plus ponatinib has not been compared with that of HCVAD plus dasatinib in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in a randomized clinical trial. METHODS: The authors analyzed 110 patients with newly diagnosed Ph+ ALL who were enrolled in 2 consecutive, prospective, phase 2 clinical trials of frontline HCVAD with either dasatinib (63 patients) or ponatinib (47 patients)...
August 1, 2016: Cancer
Z N Cisneros-García, V F Mara Non-Ruiz, J G Rodríguez-Zavala
The main absorption peaks were obtained for 1-(1-hydroxy-4-methyl-2-phenylazo)-2-naphthol-4-sulfonic acid. Generalized gradient approximation, hybrid, semi-empirical, and Coulomb attenuating methods were utilized to compare theoretical electronic transitions and experimental absorption spectra at different pH. The main peaks and shoulders observed in experimental spectra were assigned to its correct conformer. In order to find the most populated conformer, thermal effects on stability calculations were investigated to obtain molar fractions of possible isomers present at room and higher temperature...
August 2016: Journal of Molecular Modeling
Hyun-Jong Cho, Ju-Hwan Park, Dae-Duk Kim, In-Soo Yoon
Docetaxel (DCT) is one of anti-mitotic chemotherapeutic agents and has been used for the treatment of gastric cancer as well as head and neck cancer, breast cancer and prostate cancer. Poly(lactic- co-glycolic) acid (PLGA) is one of representative biocompatible and biodegradable polymers, and polyoxyl 15 hydroxystearate (Solutol HS15) is a nonionic solubilizer and emulsifying agent. In this investigation, PLGA/Solutol HS15-based nanoparticles (NPs) for DCT delivery were fabricated by a modified emulsification-solvent evaporation method...
February 2016: Journal of Nanoscience and Nanotechnology
J S Jia, S M Yang, J Wang, H Jiang, T Zhao, L Bao, H X Shi, J Lu, H H Zhu, Y Y Lai, B Jiang, X J Huang, Q Jiang
OBJECTIVE: To investigate the prognostic significance of proportion of the blasts in bone marrow on day 14 (D14) during induction chemotherapy in patients with adult Ph-negative acute lymphoblastic leukemia (Ph (-) ALL). METHODS: Newly diagnosed Ph (-) ALL patients with bone marrow morphology analysis on day 14 during induction chemotherapy were analyzed retrospectively. The proportion of the D14 blasts which had an impact on achieving a CR by the first induction chemotherapy and outcomes were determined by ROC curve...
June 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Sapan J Patel, Su Dao, Costel C Darie, Bayard D Clarkson
Quorum sensing (QS) is a generic term used to describe cell-cell communication and collective decision making by bacterial and social insects to regulate the expression of specific genes in controlling cell density and other properties of the populations in response to nutrient supply or changes in the environment. QS mechanisms also have a role in higher organisms in maintaining homeostasis, regulation of the immune system and collective behavior of cancer cell populations. In the present study, we used a p190(BCR-ABL) driven pre-B acute lymphoblastic leukemia (ALL3) cell line derived from the pleural fluid of a terminally ill patient with ALL to test the QS hypothesis in leukemia...
2016: American Journal of Cancer Research
Mohammed Alcharakh, Seongseok Yun, Yimin Dong, Nicole D Vincelette, Madiha Daud, Saima Manzoor, Irbaz Bin Riaz, Faiz Anwer
Post-stem cell transplantation (SCT) relapsed acute lymphoblastic leukemia (ALL) has extremely poor prognosis with median survival of less than 1 year. Donor lymphocyte infusion, second transplantation, chemotherapy or cytokine treatment have been tried as a salvage regimen without significant clinical benefit. Recently, blinatumomab, a bispecific monoclonal antibody targeting CD3-expressing T cells and CD19-expressing B-cell lineage malignant cells demonstrated promising outcomes in relapsed/refractory ALL patients...
July 2016: Immunotherapy
Ibrahim Aldoss, Karl Gaal, Monzr M Al Malki, Haris Ali, Ryotaro Nakamura, Stephen J Forman, Vinod Pullarkat
The tyrosine kinase inhibitor dasatinib is often used after allogeneic hematopoietic cell transplantation to treat minimal residual disease in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Colitis, sometimes hemorrhagic, has occasionally been described with the use of dasatinib for both chronic myeloid leukemia and Ph+ ALL. The pathogenesis of dasatinib-induced colitis is unclear but may be related to effects of dasatinib on immune function. We describe a series of 5 patients who had 7 episodes of colitis during dasatinib use...
October 2016: Biology of Blood and Marrow Transplantation
Moe Tamaura, Fuminori Iwasaki, Tomoko Yokosuka, Kunio Fukuda, Satoshi Hamonoue, Hiroaki Goto
Children with Down syndrome (DS) are at high risk of developing acute lymphoblastic leukemia (ALL), but Philadelphia chromosome-positive (Ph+) ALL is rare in DS children. We report a case of Ph+ALL with DS complicated by chronic heart failure. Complete molecular remission was obtained after imatinib-combined chemotherapy, although infectious episodes during the neutropenic period worsened the heart condition. After two courses of intensification chemotherapy, the patient underwent reduced intensity stem cell transplantation from an HLA-identical sibling donor followed by post-transplant imatinib...
August 2016: Pediatrics International: Official Journal of the Japan Pediatric Society
C Witte, J U Meyer Zur Heide Genannt Meyer-Arend, R Andrié, J W Schrickel, C Hammerstingl, J O Schwab, G Nickenig, D Skowasch, C Pizarro
A growing body of evidence indicates that sudden cardiac death constitutes a major cause of mortality in pulmonary hypertension (PH). As validated method to evaluate cardiac autonomic system dysfunction, alterations in heart rate variability (HRV) are predictive of arrhythmic events, particularly in left ventricular disease. Here, we sought to determine the clinical value of HRV assessment in PH. Sixty-four patients were allocated to different PH-subgroups in this prospectively conducted trial: 25 patients with pulmonary arterial hypertension (PAH), 11 patients with chronic thromboembolic PH (CTEPH), and 28 patients with COPD-induced PH...
2016: Advances in Experimental Medicine and Biology
Wang-Chou Sung, Chiung-Wen Chang, Sheng-Yu Huang, Ting-Yu Wei, Yi-Li Huang, Yu-Hua Lin, Han-Min Chen, Sung-Fang Chen
Disulfide linkages play an important role in protein stability and activity. Thus, it is critical to characterize disulfide bonds to ensure the quality and function of protein pharmaceuticals. There are, however, problems associated with maintaining disulfide linkages in the conventional procedures that are used to digest a protein. In order to preserve enzyme activity during the digestion of a protein, it is commonly carried out at neutral to basic environment which increases the possibilities of disulfide bond scrambling...
September 2016: Biochimica et Biophysica Acta
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