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https://www.readbyqxmd.com/read/28936999/non-adherence-to-cml-therapy-and-its-clinical-implications-in-india
#1
REVIEW
Hari Menon
Clinical trials have shown that early and deeper cytogenetic/ molecular responses to tyrosine kinase inhibitors (TKIs) help in achieving improved long-term outcomes including lower rates of disease progression in chronic myeloid leukaemia (CML). However, the level of molecular responses achieved with TKI therapy in patients with CML is variable and this could be explained by differences in adherence to CML therapy. A systematic literature review of CML studies reporting adherence to BCR-ABL inhibitors from the USA, Asia and Europe (19 articles: 9 retrospective, 4 prospective, rest cross-sectional) showed that average adherence varies from 19% to 100% of the proportion of prescribed drug taken...
May 2017: National Medical Journal of India
https://www.readbyqxmd.com/read/28933694/ubiquilin1-promotes-antigen-receptor-mediated-proliferation-by-eliminating-mislocalized-mitochondrial-proteins
#2
Alexandra M Whiteley, Miguel A Prado, Ivan Peng, Alexander R Abbas, Benjamin Haley, Joao A Paulo, Mike Reichelt, Anand Katakam, Meredith Sagolla, Zora Modrusan, Dong Yun Lee, Merone Roose-Girma, Donald S Kirkpatrick, Brent S McKenzie, Steven P Gygi, Daniel Finley, Eric J Brown
Ubiquilins (Ubqlns) are a family of ubiquitin receptors that promote the delivery of hydrophobic and aggregated ubiquitinated proteins to the proteasome for degradation. We carried out a proteomic analysis of a B cell lymphoma-derived cell line, BJAB, that requires UBQLN1 for survival to identify UBQLN1 client proteins. When UBQLN1 expression was acutely inhibited, 120 mitochondrial proteins were enriched in the cytoplasm, suggesting that the accumulation of mitochondrial client proteins in the absence of UBQLN1 is cytostatic...
September 21, 2017: ELife
https://www.readbyqxmd.com/read/28933554/rational-targeting-of-cellular-cholesterol-in-diffuse-large-b-cell-lymphoma-dlbcl-enabled-by-functional-lipoprotein-nanoparticles-a-therapeutic-strategy-dependent-on-cell-of-origin
#3
Jonathan S Rink, Shuo Yang, Osman Cen, Tim Taxter, Kaylin M McMahon, Sol Misener, Amir Behdad, Richard Longnecker, Leo I Gordon, C Shad Thaxton
Cancer cells have altered metabolism and, in some cases, an increased demand for cholesterol. It is important to identify novel, rational treatments based on biology, and cellular cholesterol metabolism as a potential target for cancer is an innovative approach. Toward this end, we focused on diffuse large B-cell lymphoma (DLBCL) as a model because there is differential cholesterol biosynthesis driven by B-cell receptor (BCR) signaling in germinal center (GC) versus activated B-cell (ABC) DLBCL. To specifically target cellular cholesterol homeostasis, we employed high-density lipoprotein-like nanoparticles (HDL NP) that can generally reduce cellular cholesterol by targeting and blocking cholesterol uptake through the high-affinity HDL receptor, scavenger receptor type B-1 (SCARB1)...
September 21, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28931525/ectopic-ilt3-controls-bcr-dependent-activation-of-akt-in-b-cell-chronic-lymphocytic-leukemia
#4
Vanessa Zurli, Giuliana Wimmer, Francesca Cattaneo, Veronica Candi, Emanuele Cencini, Alessandro Gozzetti, Donatella Raspadori, Giuseppe Campoccia, Francesca Sanseviero, Monica Bocchia, Cosima Tatiana Baldari, Anna Kabanova
The high proportion of long-term non-progressors among chronic lymphocytic leukemia (CLL) patients suggests the existence of a regulatory network which restrains the proliferation of tumor B cells. The identification of molecular determinants composing such network is hence fundamental for our understanding of CLL pathogenesis. Based on our previous finding establishing a deficiency in the signaling adaptor p66Shc in CLL cells, we undertook to identify unique phenotypic traits caused by this defect. Here we show that a lack of p66Shc shapes the transcriptional profile of CLL cells and leads to an upregulation of the surface receptor ILT3, the immunoglobulin-like transcript 3 which is normally found on myeloid cells...
September 20, 2017: Blood
https://www.readbyqxmd.com/read/28929350/optimal-mri-sequences-for-68-ga-psma-11-pet-mri-in-evaluation-of-biochemically-recurrent-prostate-cancer
#5
Spencer T Lake, Kirsten L Greene, Antonio C Westphalen, Spencer C Behr, Ronald Zagoria, Eric J Small, Peter R Carroll, Thomas A Hope
BACKGROUND: PET/MRI can be used for the detection of disease in biochemical recurrence (BCR) patients imaged with (68)Ga-PSMA-11 PET. This study was designed to determine the optimal MRI sequences to localize positive findings on (68)Ga-PSMA-11 PET of patients with BCR after definitive therapy. Fifty-five consecutive prostate cancer patients with BCR imaged with (68)Ga-PSMA-11 3.0T PET/MRI were retrospectively analyzed. Mean PSA was 7.9 ± 12.9 ng/ml, and mean PSA doubling time was 7...
September 19, 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28929332/deeper-molecular-response-is-a-predictive-factor-for-treatment-free-remission-after-imatinib-discontinuation-in-patients-with-chronic-phase-chronic-myeloid-leukemia-the-jalsg-stim213-study
#6
Naoto Takahashi, Tetsuzo Tauchi, Kunio Kitamura, Koichi Miyamura, Yoshio Saburi, Yoshihiro Hatta, Yasuhiko Miyata, Shinichi Kobayashi, Kensuke Usuki, Itaru Matsumura, Yosuke Minami, Noriko Usui, Tetsuya Fukuda, Satoru Takada, Maho Ishikawa, Katsumichi Fujimaki, Hiroshi Gomyo, Osamu Sasaki, Kohshi Ohishi, Takaaki Miyake, Kiyotoshi Imai, Hitoshi Suzushima, Hideki Mitsui, Kazuto Togitani, Toru Kiguchi, Yoshiko Atsuta, Shigeki Ohtake, Kazunori Ohnishi, Yukio Kobayashi, Hitoshi Kiyoi, Yasushi Miyazaki, Tomoki Naoe
The objective of this prospective clinical trial (JALSG-STIM213, UMIN000011971) was to evaluate treatment-free remission (TFR) rates after discontinuation of imatinib in chronic myeloid leukemia (CML). CML patients who received imatinib treatment for at least 3 years and sustained deep molecular response for at least 2 years were eligible. Molecular recurrence was defined as loss of major molecular response (MMR). Of the 68 eligible patients, 38.2% were women, the median age was 55.0 years, and the median duration of imatinib treatment was 97...
September 19, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28928866/ct-721-a-potent-bcr-abl-inhibitor-exhibits-excellent-in-vitro-and-in-vivo-efficacy-in-the-treatment-of-chronic-myeloid-leukemia
#7
Yinghui Sun, Na Zhao, Huan Wang, Qiong Wu, Yunqi Han, Qichao Liu, Mangang Wu, Yuliang Liu, Fansheng Kong, He Wang, Ying Sun, Deguang Sun, Lutao Jing, Guojing Tang, Yuandong Hu, Dengming Xiao, Hong Luo, Yongxin Han, Yong Peng
Kinase inhibitors that target Bcr-Abl are highly effective in the treatment of chronic myeloid leukemia (CML). However, these inhibitors are often invalidated due to the drug resistance. Therefore, the discovery and development of novel Bcr-Abl inhibitors is required to overwhelm the drug resistance in the treatment of CML resistant to the currently used first-line Bcr-Abl inhibitors. Herein we have described a newly developed Bcr-Abl inhibitor CT-721, which displayed potent inhibitory effects on wild-type and T315I mutant Bcr-Abl...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928163/high-bcr-abl-gusis-levels-at-diagnosis-of-chronic-phase-cml-are-associated-with-unfavorable-responses-to-standard-dose-imatinib
#8
Paolo Vigneri, Fabio Stagno, Stefania Stella, Alessandra Cupri, Stefano Forte, Michele Massimino, Agostino Antolino, Sergio Siragusa, Donato Mannina, Stefana S Impera, Caterina Musolino, Alessandra Malato, Giuseppe Mineo, Carmela Tomaselli, Pamela Murgano, Maurizio Musso, Fortunato Morabito, Stefano Molica, Bruno Martino, Livia Manzella, Martin C Müller, Andreas Hochhaus, Francesco Di Raimondo
PURPOSE: The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first line treatment of chronic myeloid leukemia (CML) has generated an unmet need for baseline molecular parameters associated with inadequate Imatinib responses. EXPERIMENTAL DESIGN: We correlated BCR-ABL/GUSIS and BCR-ABL/ABLIS transcripts at diagnosis with the outcome - defined by the 2013 European LeukemiaNet recommendations - of 272 newly diagnosed CML patients receiving Imatinib 400 mg/daily...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28928012/frequency-and-prognostic-significance-of-incidental-prostate-cancer-at-radical-cystectomy-results-from-an-international-retrospective-study
#9
Rieken Malte, Luis A Kluth, Dharam Kaushik, Stephen A Boorjian, Mohammad Abufaraj, Beat Foerster, Michael Rink, Kilian Gust, Florian Roghmann, Joachim Noldus, Dimitri Vordos, Masayuki Hagiwara, Eiji Kikuchi, Masaomi Ikeda, Kazumasa Matsumoto, Pierre I Karakiewicz, Morgan Rouprêt, Alberto Briganti, Douglas S Scherr, Shahrokh F Shariat, Veronika Seebacher
OBJECTIVES: To analyze the frequency of incidental prostate cancer (PC) at radical cystoprostatectomy (RC) for urothelial carcinoma of the bladder (UCB) and its association with survival outcomes in an international cohort. PATIENTS AND METHODS: In this retrospective study, we included 2114 who underwent RC and lymphadenectomy for UCB between 1976 and 2012 male patients from seven institutions. Univariable and multivariable Cox regression models addressed the association of incidental PC with cancer-specific mortality and overall mortality after RC...
September 7, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28927784/safety-and-efficacy-of-blinatumomab-in-combination-with-a-tyrosine-kinase-inhibitor-for-the-treatment-of-relapsed-philadelphia-chromosome-positive-leukemia
#10
Rita Assi, Hagop Kantarjian, Nicholas J Short, Naval Daver, Koichi Takahashi, Guillermo Garcia-Manero, Courtney DiNardo, Jan Burger, Jorge Cortes, Nitin Jain, William Wierda, Salim Chamoun, Marina Konopleva, Elias Jabbour
OBJECTIVE: The treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia has been revolutionized with the introduction of tyrosine kinase inhibitors (TKIs) and the combination of these agents with chemotherapy. Blinatumomab is a bispecific anti-CD3/CD19 monoclonal antibody with clinical activity as single-agent in the relapsed setting and independent of BCR-ABL1 mutational status, including T315I. The combination of blinatumomab with a TKI may further improve outcomes for this high-risk population, including higher eradication of minimal residual disease and minimize the use of chemotherapy...
August 18, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28927158/regulation-of-htra2-on-wt1-gene-expression-under-imatinib-stimulation-and-its-effects-on-the-cell-biology-of-k562-cells
#11
Lixia Zhang, Yan Li, Xiaoyan Li, Qing Zhang, Shaowei Qiu, Qi Zhang, Min Wang, Haiyan Xing, Qing Rao, Zheng Tian, Kejing Tang, Jianxiang Wang, Yingchang Mi
The aim of the present study was to investigate the regulation of Wilms Tumor 1 (WT1) by serine protease high-temperature requirement protein A2 (HtrA2), a member of the Htr family, in K562 cells. In addition, the study aimed to observe the effect of this regulation on cell biological functions and its associated mechanisms. Expression of WT1 and HtrA2 mRNA, and proteins following imatinib and the HtrA2 inhibitor 5-[5-(2-nitrophenyl) furfuryl iodine]-1, 3-diphenyl-2-thiobarbituric acid (UCF-101) treatment was detected with reverse transcription-quantitative polymerase chain reaction and western blot analysis...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28924539/genetic-polymorphisms-of-hemostatic-factors-and-thrombotic-risk-in-non-bcr-abl-myeloproliferative-neoplasms-a-pilot-study
#12
R Dambrauskienė, R Gerbutavičius, R Ugenskienė, R Jankauskaitė, A Savukaitytė, R Šimoliūnienė, M Rudžianskienė, R Gerbutavičienė, E Juozaitytė
The most important complications of Philadelphianegagive (non BCR-ABL) myeloproliferative neoplasms (MPNs) are vascular events. Our aim was to evaluate the effects of single nucleotide polymorphisms (SNPs), platelet glycoproteins (GPs) (Ia/IIa, Ibα, IIb/IIIa and VI), von Willebrand factor (vWF), coagulation factor VII (FVII), β-fibrinogen, and the risk of thrombosis in patients with non BCR-ABL MPNs at the Lithuanian University of Health Sciences. Kaunas, Lithuania. Genotyping was done for 108 patients. The TT genotype of the GP Ia/IIa c...
June 30, 2017: Balkan Journal of Medical Genetics: BJMG
https://www.readbyqxmd.com/read/28923960/igh-isotype-specific-b-cell-receptor-expression-influences-b-cell-fate
#13
Pei Tong, Alessandra Granato, Teng Zuo, Neha Chaudhary, Adam Zuiani, Seung Seok Han, Rakesh Donthula, Akritee Shrestha, Debattama Sen, Jennifer M Magee, Michael P Gallagher, Cees E van der Poel, Michael C Carroll, Duane R Wesemann
Ig heavy chain (IgH) isotypes (e.g., IgM, IgG, and IgE) are generated as secreted/soluble antibodies (sIg) or as membrane-bound (mIg) B cell receptors (BCRs) through alternative RNA splicing. IgH isotype dictates soluble antibody function, but how mIg isotype influences B cell behavior is not well defined. We examined IgH isotype-specific BCR function by analyzing naturally switched B cells from wild-type mice, as well as by engineering polyclonal Ighγ1/γ1 and Ighε/ε mice, which initially produce IgG1 or IgE from their respective native genomic configurations...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923853/adaptation-to-tki-treatment-reactivates-erk-signaling-in-tyrosine-kinase-driven-leukemias-and-other-malignancies
#14
Joshua K Bruner, Hayley S Ma, Li Li, Alice Can Ran Qin, Michelle A Rudek, Richard J Jones, Mark J Levis, Keith W Pratz, Christine A Pratilas, Donald Small
FLT3 tyrosine kinase inhibitors (TKI) have been tested extensively to limited benefit in acute myeloid leukemia. We hypothesized that FLT3/ITD leukemia cells exhibit mechanisms of intrinsic signaling adaptation to TKI treatment that are associated with an incomplete response. Here we identified reactivation of ERK signaling within hours following treatment of FLT3/ITD AML cells with selective inhibitors of FLT3. When these cells were treated with inhibitors of both FLT3 and MEK in combination, ERK reactivation was abrogated and anti-leukemia effects were more pronounced compared to either drug alone...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28923044/cost-benefit-of-investment-on-quality-in-pharmaceutical-manufacturing-who-gmp-pre-and-post-certification-of-a-nigerian-pharmaceutical-manufacturer
#15
Chimezie Anyakora, Obinna Ekwunife, Faith Alozie, Mopa Esuga, Jonathan Ukwuru, Steve Onya, Jude Nwokike
BACKGROUND: Pharmaceutical companies in Africa need to invest in both facilities and quality management systems to achieve good manufacturing practice (GMP) compliance. Compliance to international GMP standards is important to the attainment of World Health Organization (WHO) prequalification. However, most of the local pharmaceutical manufacturing companies may be deterred from investing in quality because of many reasons, ranging from financial constraints to technical capacity. This paper primarily evaluates benefits against the cost of investing in GMP, using a Nigerian pharmaceutical company, Chi Pharmaceuticals Limited, as a case study...
September 18, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28923030/the-eef1a2-gene-expression-as-risk-predictor-in-localized-prostate-cancer
#16
Thomas Stefan Worst, Frank Waldbillig, Abdallah Abdelhadi, Cleo-Aron Weis, Maria Gottschalt, Annette Steidler, Jost von Hardenberg, Maurice Stephan Michel, Philipp Erben
BACKGROUND: Besides clinical stage and Gleason score, risk-stratification of prostate cancer in the pretherapeutic setting mainly relies on the serum PSA level. Yet, this is associated with many uncertainties. With regard to therapy decision-making, additional markers are needed to allow an exact risk prediction. Eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) was previously suggested as driver of tumor progression and potential biomarker. In the present study its functional and prognostic relevance in prostate cancer was investigated...
September 18, 2017: BMC Urology
https://www.readbyqxmd.com/read/28922958/post-prostatectomy-radiation-therapy-for-locally-recurrent-prostate-cancer
#17
Sudhir Isharwal, Andrew J Stephenson
Approximately 15-30% of men with localized prostate cancer will experience biochemical recurrence (BCR) after radical prostatectomy. Postoperative radiation therapy is used in men with adverse pathological features to reduce the risk of BCR or with curative intent in men with known BCR. In this study, we review the evidence for the adjuvant and salvage radiation therapy after radical prostatectomy. Areas covered: A literature review of the Medline and Embase databases was performed. The search strategy included the following terms: prostate cancer, adjuvant radiotherapy, salvage radiotherapy, radical prostatectomy, biochemical recurrence, and prostate cancer recurrence...
September 18, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28921505/nfatc1-activation-by-dna-hypomethylation-in-chronic-lymphocytic-leukemia-correlates-with-clinical-staging-and-can-be-inhibited-by-ibrutinib
#18
Christine Wolf, Angela Garding, Katharina Filarsky, Jasmin Bahlo, Sandra Robrecht, Natalia Becker, Manuela Zucknick, Arefeh Rouhi, Anja Weigel, Rainer Claus, Dieter Weichenhan, Barbara Eichhorst, Kirsten Fischer, Michael Hallek, Florian Kuchenbauer, Christoph Plass, Hartmut Döhner, Stephan Stilgenbauer, Peter Lichter, Daniel Mertens
B cell receptor (BCR) signaling is key for survival of chronic lymphocytic leukemia (CLL) cells, and BCR signaling inhibitors are clinically active. However, relapse and resistance to treatment require novel treatment options. In order to detect novel candidate therapeutic targets, we performed a genome-wide DNA methylation screen with custom arrays and identified aberrant promoter DNA methylation in 2192 genes. The transcription factor NFATC1 that is a downstream effector of BCR signaling was among the top hypomethylated genes and was concomitantly transcriptionally upregulated in CLL...
September 18, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28919770/swollen-lymph-nodes-may-not-be-clinical-manifestations-of-chronic-myeloid-leukemia-case-report-and-revision-of-literature
#19
Zhihe Liu, Siyun Li, Ou Bai
We present here the case of a 33-year-old Chinese female patient with synchronous double primary malignant tumors (chronic myeloid leukemia [CML] and classic Hodgkin lymphoma). This patient was admitted to our hospital because of bilateral cervical lymph node enlargement and recurrent fever for 2 weeks. The complete blood cell count revealed white blood cell counts of 18.2×10(9)/L, hemoglobin of 9.6 g/dL, and platelet counts of 1,547×10(9)/L. Chromosome karyotype analysis demonstrated that t(9;22)(q34;q11) was positive in all 20 cells examined...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28917745/chlorine-determination-via-mgcl-molecule-in-environmental-samples-using-high-resolution-continuum-source-graphite-furnace-molecular-absorption-spectrometry
#20
Rina Lourena da S Medeiros, Sidnei Oliveira Souza, Rennan Geovanny Oliveira Araújo, Djalma Ribeiro da Silva, Tatiane de A Maranhão
This paper describes a method development for chlorine determination through the formation of MgCl molecule, applied for the first time for Cl quantification, by high resolution continuum source graphite furnace molecular absorption spectrometry (HR-CS GF MAS) in environmental samples. Pyrolysis and vaporization temperatures were optimized as well as the use of chemical modifier. Determinations were carried out at the wavelength of 377.010 and the compromise conditions of the graphite furnace temperature program were 500°C and 2500°C for pyrolysis and vaporization, respectively, using 10µg of chemical modifier Pd...
January 1, 2018: Talanta
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