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https://www.readbyqxmd.com/read/28423550/quantitative-proteomic-analysis-of-gastric-cancer-tissue-reveals-novel-proteins-in-platelet-derived-growth-factor-b-signaling-pathway
#1
Fang Liu, Yuan Zhang, Tingting Men, Xingyue Jiang, Chunhua Yang, He Li, Xiaodan Wei, Dong Yan, Gangming Feng, Jianke Yang, Jonas Bergquist, Bin Wang, Wenguo Jiang, Jia Mi, Geng Tian
Gastric cancer is one of the most common cancers in Asian countries. Searching for reliable biomarkers involving the development of gastric cancer is important for clinical practice. Quantitative proteomics has become an important method contributed to the discovery of novel diagnostic or therapeutic targets for the management of cancer. Here, we identified differently expressed proteins in gastric cancer and normal gastric tissues by using the high resolution mass spectrometer. Among the total of 2280 identified proteins, 87 were differentially expressed between gastric cancer and normal gastric tissues...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422716/sequential-evaluation-of-calr-mutant-burden-in-patients-with-myeloproliferative-neoplasms
#2
Chiara Cavalloni, Elisa Rumi, Virginia V Ferretti, Daniela Pietra, Elisa Roncoroni, Marta Bellini, Michele Ciboddo, Ilaria C Casetti, Benedetta Landini, Elena Fugazza, Daniela Troletti, Cesare Astori, Mario Cazzola
We investigated the variation of CALR-mutant burden during follow-up in 105 CALR-mutant MPN and compared it to the variation of JAK2-mutant burden in 226 JAK2-mutant MPN.The median allele burden at last evaluation was significantly higher than at first evaluation in essential thrombocythemia (ET) (49.5% vs 45%, P < .001) but not in primary myelofibrosis (PMF) (52% vs 51%, P 0.398). Median values of slope were positive both in ET (0.071) and in PMF (0.032). In CALR-mutant ET there was a difference between natural and therapy-related slope (P 0...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415571/increased-b-cell-activation-is-present-in-jak2v617f-mutated-calr-mutated-and-triple-negative-essential-thrombocythemia
#3
Ken-Hong Lim, Caleb Gon-Shen Chen, Yu-Cheng Chang, Yi-Hao Chiang, Chen-Wei Kao, Wei-Ting Wang, Chiao-Yi Chang, Ling Huang, Ching-Sung Lin, Chun-Chia Cheng, Hung-I Cheng, Nai-Wen Su, Johnson Lin, Yi-Fang Chang, Ming-Chih Chang, Ruey-Kuen Hsieh, Huan-Chau Lin, Yuan-Yeh Kuo
Essential thrombocythemia (ET) is a BCL-ABL1-negative myeloproliferative neoplasm. We have reported that increased activated B cells can facilitate platelet production mediated by cytokines regardless JAK2 mutational status in ET. Recently, calreticulin (CALR) mutations were discovered in ~30% JAK2/MPL-unmutated ET and primary myelofibrosis. Here we sought to screen for CALR mutations and to evaluate B cell immune profiles in a cohort of adult Taiwanese ET patients. B cell populations, granulocytes/monocytes membrane-bound B cell-activating factor (mBAFF) levels, B cells toll-like receptor 4 (TLR4) expression and intracellular levels of interleukin (IL)-1β/IL-6 and the expression of CD69, CD80, and CD86 were quantified by flow cytometry...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411309/calreticulin-mutations-in-bulgarian-mpn-patients
#4
Ivan Pavlov, Evgueniy Hadjiev, Tzvetan Alaikov, Sylva Spassova, Angel Stoimenov, Elissaveta Naumova, Velizar Shivarov, Milena Ivanova
Somatic mutations in JAK2, MPL and CALR are recurrently identified in most of the cases with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs). We applied four molecular genetic methods for identification of CALR exon 9 mutations, including high resolution melt (HRM) analysis, Sanger sequencing, semiconductor target genes sequencing and whole exome sequencing. A total of 78 patients with myeloid malignancies were included in the study. We identified 14 CALR exon 9 mutated cases out of 78 studied patients with myeloid malignancies...
April 14, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28406068/clinical-and-hematological-relevance-of-jak2-v617f-and-calr-mutations-in-bcr-abl-negative-et-patients
#5
N Limsuwanachot, B Rerkamnuaychoke, S Chuncharunee, T Pauwilai, R Singdong, P Rujirachaivej, T Chareonsirisuthigul, T Siriboonpiputtana
BACKGROUND: Classical BCR-ABL1-negative myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia (ET), and primary myelofibrosis frequently harbor JAK2, MPL, and CALR somatic mutations. METHODS: AS-PCR for JAK2 V617F, pyrosequencing for MPL W515L/K, and PCR-fragment analysis for CALR exon 9 mutations were established to analyze genomic DNA isolated from peripheral blood samples of 58 newly diagnosed ET patients in Thailand. RESULTS: JAK2 V617F was detected in 41 patients (71%) and CALR exon 9 mutation was positive in eight patients (14%), whereas no mutation of MPL W515L/K was observed in this study...
April 13, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28405618/efficacy-of-alk5-inhibition-in-myelofibrosis
#6
Lanzhu Yue, Matthias Bartenstein, Wanke Zhao, Wanting Tina Ho, Ying Han, Cem Murdun, Adam W Mailloux, Ling Zhang, Xuefeng Wang, Anjali Budhathoki, Kith Pradhan, Franck Rapaport, Huaquan Wang, Zonghong Shao, Xiubao Ren, Ulrich Steidl, Ross L Levine, Zhizhuang Joe Zhao, Amit Verma, Pearlie K Epling-Burnette
Myelofibrosis (MF) is a bone marrow disorder characterized by clonal myeloproliferation, aberrant cytokine production, extramedullary hematopoiesis, and bone marrow fibrosis. Although somatic mutations in JAK2, MPL, and CALR have been identified in the pathogenesis of these diseases, inhibitors of the Jak2 pathway have not demonstrated efficacy in ameliorating MF in patients. TGF-β family members are profibrotic cytokines and we observed significant TGF-β1 isoform overexpression in a large cohort of primary MF patient samples...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28402197/minimal-residual-disease-or-cure-in-mpns-rationales-and-perspectives-on-combination-therapy-with-interferon-alpha2-and-ruxolitinib
#7
Mads Emil Bjørn, Hans Carl Hasselbalch
The therapeutic landscape of the Philadelphia-negative myeloproliferative neoplasms (MPNs) is markedly changing consequent to the development of JAK-inhibitors and the use of ruxolitinib (RUX) in patients with myelofibrosis (MF) and patients with polycythemia vera (PV) who develop refractoriness or intolerance to hydroxyurea. The use of Interferon-alpha2 (IFN) is rapidly expanding in several countries, based upon favourable safety and efficacy profiles in several single-arm studies during the last 30 years, displaying complete hematological remissions in a large proportion of patients, a reduction in the JAK2V617 F and CALR mutational burden and in a subset of patients with PV with normalisation of the bone marrow after long-term treatment - even being sustained for several years after discontinuation of IFN...
April 12, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28389907/targeted-next-generation-sequencing-identified-novel-mutations-in-triple-negative-myeloproliferative-neoplasms
#8
Yu-Cheng Chang, Huan-Chau Lin, Yi-Hao Chiang, Caleb Gon-Shen Chen, Ling Huang, Wei-Ting Wang, Chun-Chia Cheng, Johnson Lin, Yi-Fang Chang, Ming-Chih Chang, Ruey-Kuen Hsieh, Shu-Jen Chen, Ken-Hong Lim, Yuan-Yeh Kuo
Mutations in JAK2, MPL and CALR genes have been identified in the majority of myeloproliferative neoplasm (MPN) patients, and patients negative for these three mutations are the so-called triple-negative (TN) MPN. In this study, we examined the mutational profiles of 16 triple-negative MPN patients including 7 essential thrombocythemia (ET), 1 primary myelofibrosis and 8 polycythemia vera (PV). Targeted next-generation sequencing was performed using the ACTOnco Comprehensive Cancer Panel (Ion AmpliSeq Comprehensive Cancer Panel, Life Technologies) to target all coding exons of 409 cancer-related genes...
May 2017: Medical Oncology
https://www.readbyqxmd.com/read/28389256/impact-of-molecular-genetics-on-outcome-in-myelofibrosis-patients-after-allogeneic-stem-cell-transplantation
#9
Nicolaus Kröger, Victoria Panagiota, Anita Badbaran, Tatjana Zabelina, Ioanna Triviai, Michelle Maria Araujo Cruz, Rabia Shahswar, Francis Ayuk, Marten Gehlhaar, Christine Wolschke, Robin Bollin, Carolin Walter, Martin Dugas, Lutz Wiehlmann, Ulrich Lehmann, Christian Koenecke, Anuhar Chaturvedi, Haefaa Alchalby, Michael Stadler, Matthias Eder, Max Christopeit, Gudrun Göhring, Michael Koenigsmann, Brigitte Schlegelberger, Hans-Heinrich Kreipe, Arnold Ganser, Carol Stocking, Boris Fehse, Felicitas Thol, Michael Heuser
Molecular genetics may influence outcome for patients with myelofibrosis. To determine the impact of molecular genetics on outcome after allogeneic stem cell transplantation, we screened 169 patients with primary myelofibrosis (n = 110), post-ET/PV myelofibrosis (n = 46), and myelofibrosis in transformation (n = 13) for mutations in 16 frequently mutated genes. The most frequent mutation was JAK2V617F (n = 101) followed by ASXL1 (n = 49), calreticulin (n = 34), SRSF2 (n = 16), TET2 (n = 10), U2AF1 (n = 11), EZH2 (n = 7), MPL (n = 6), IDH2 (n = 5), IDH1 (n = 4), and CBL (n = 1)...
April 4, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28378143/calr-is-required-for-the-expression-of-t6ss2-and-the-adhesion-of-vibrio-parahaemolyticus-to-hela-cells
#10
Lingyu Zhang, George Osei-Adjei, Ying Zhang, He Gao, Wenhui Yang, Dongsheng Zhou, Xinxiang Huang, Huiying Yang, Yiquan Zhang
Vibrio parahaemolyticus expresses one major virulence determinant T6SS2, which is constituted into three putative operons, i.e., VPA1027-1024, VPA1043-1028, and VPA1044-1046. CalR, a LysR-type transcriptional regulator, was originally identified as a repressor of the swarming motility and T3SS1 gene expression. As shown in this study, CalR binds to the promoter-proximal region of each of the three operons to activate their transcription, and moreover, CalR activates the adhesion of V. parahaemolyticus to HeLa cells...
April 4, 2017: Archives of Microbiology
https://www.readbyqxmd.com/read/28347227/comparative-proteomics-network-analysis-of-proteins-responsible-for-ursolic-acid-induced-cytotoxicity-in-colorectal-cancer-cells
#11
Qiaoyan Cai, Jing Lin, Ling Zhang, Jiumao Lin, Lili Wang, Daxin Chen, Jun Peng
Ursolic acid is a key active compound present in many medicinal herbs that have been widely used in traditional Chinese medicine for the clinical treatment of various cancers. However, the precise mechanisms of its antitumor activity have been poorly understood. To identify the cellular targets of ursolic acid, two-dimensional gel electrophoresis combined with mass spectrometry was performed in this study, which identified 15 proteins with significantly altered levels in protein expression. This demonstrated that ursolic acid-induced cytotoxicity in colorectal cancer cells involves dysregulation in protein folding, signal transduction, cell proliferation, cell cycle, and apoptosis...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28340692/calr-gene-mutational-profile-in-myeloproliferative-neoplasms-with-non-mutated-jak2-in-moroccan-patients-a-case-series-and-germline-in-frame-deletion
#12
W Smaili, Y Doubaj, F Z Laarabi, J Lyahyai, M Kerbout, M Mikdame, A Sefiani
BACKGROUND: The discovery of somatic mutations within the gene encoding calreticulin (CALR) in 2013 represented a major milestone in the molecular diagnosis of BCR-ABL negative myeloproliferative neoplasms (MPN). In fact, exome sequencing revealed that most patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF) lacking JAK2 or MPL mutations, harbor somatic insertion and/or deletion in exon 9 of CALR gene. In this study, we identified the first CALR gene mutational landscape in Moroccan patients with MPN nonmutated for the JAK2 gene...
January 2017: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/28335073/clinical-characteristics-and-whole-exome-transcriptome-sequencing-of-coexisting-chronic-myeloid-leukemia-and-myelofibrosis
#13
Malathi Kandarpa, Yi-Mi Wu, Dan Robinson, Patrick William Burke, Arul M Chinnaiyan, Moshe Talpaz
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell (HSC) disorders that can be classified on the basis of genetic, clinical, phenotypic features. Genetic lesions such as JAK2 mutations and BCR-ABL translocation are often mutually exclusive in MPN patients and lead to essential thrombocythemia, polycythemia vera or myelofibrosis (ET/PV/MF) or chronic myeloid leukemia, respectively. Nevertheless, coexistence of these genetic aberrations in the same patient has been reported. Whether these aberrations occur in the same stem cell or a different cell is unclear, but an unstable genome in the HSCs seems to be the common antecedent...
March 23, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28332377/hb-heathrow-%C3%AE-103-g5-phe%C3%A2-leu-a-first-report-in-an-asian-patient-with-erythrocytosis
#14
Sang Yong Shin, Hyun Young Kim, Hee Jin Kim, Hoon Gu Kim
Congenital erythrocytosis (CE) is a rare and heterogeneous disease. The high oxygen affinity hemoglobin (Hb) variants are the most common cause of CE. Herein, we report a Korean patient with isolated erythrocytosis. A 25-year-old man was referred to our hospital for evaluation of high Hb level (Hb 20.4 g/dL, hematocrit 58%, reticulocyte count 2.90%, white blood cell count 6.83×10⁹/L, and platelet count 195×10⁹/L). Bone marrow biopsy revealed normocellular marrow without myeloproliferative features. JAK2 (V617F, exon 12), CALR (exon 9), and MPL W515K/L mutations were not detected...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28318117/transcriptional-regulation-of-cpsq-mfpabc-and-mfpabc-by-calr%C3%A2-in-vibrio-parahaemolyticus
#15
He Gao, Lingyu Zhang, George Osei-Adjei, Wenhui Yang, Dongsheng Zhou, Xinxiang Huang, Huiying Yang, Zhe Yin, Yiquan Zhang
The cpsQ-mfpABC locus is transcribed as two operons, i.e., cpsQ-mfpABC and mfpABC, in Vibrio parahaemolyticus, and both of them are all required for biofilm formation. CalR belongs to the LysR-type transcriptional regulator family, and was originally identified as a repressor of the swarming motility and T3SS1 genes expression in V. parahaemolyticus. In the present work, a combination of qRT-PCR, primer extension, LacZ fusion expression, electrophoretic mobility shift assay, and DNase I footprinting assays were employed to elucidate the regulatory mechanisms of cpsQ-mfpABC and mfpABC by CalR...
March 20, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28314843/quantitative-proteome-heterogeneity-in-myeloproliferative-neoplasm-subtypes-and-association-with-jak2-mutation-status
#16
Nuria Socoro-Yuste, Cokic Vladan P, Julie Mondet, Isabelle Plo, Pascal Mossuz
Apart from well-known genetic abnormalities, several studies have reported variations in protein expression in Philadelphia negative (Ph-) Myeloproliferative Neoplasm (MPN) patients that could contribute towards their clinical phenotype. In this context, a quantitative mass spectrometry proteomics protocol was used to identify differences in the granulocyte proteome with the goal to characterize the pathogenic role of aberrant protein expression in MPNs. LC MS/MS (LTQ Orbitrap) coupled to iTRAQ labeling showed significant and quantitative differences in protein content among various MPN subtypes [polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF)], and according to the genetic status of JAK2 (JAK2V617F presence and JAK2V617F allele burden)...
March 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28302866/genomic-profiling-of-patient-derived-xenografts-for-lung-cancer-identifies-b2m-inactivation-impairing-immunorecognition
#17
Carolina Pereira, Pol Gimenez-Xavier, Eva Pros, Maria J Pajares, Massimo Moro, Antonio Gomez, Alejandro Navarro, Enric Condom, Sebastian Moran, Gonzalo Gomez-Lopez, Osvaldo Graña, Miriam Rubio-Camarillo, Alex Martinez-Martí, Jun Yokota, Julian Carretero, Jose M Galbis, Ernest Nadal, David Pisano, Gabriella Sozzi, Enriqueta Felip, Luis M Montuenga, Luca Roz, Alberto Villanueva, Montse Sanchez-Cespedes
Purpose: We aimed to maximize the performance of detecting genetic alterations in lung cancer using high-throughput sequencing for patient-derived xenografts (PDXs).Experimental Design: We undertook an integrated RNA and whole-exome sequencing of 14 PDXs. We focused on the genetic and functional analysis of β2-microglobulin (B2M), a component of the HLA class-I complex.Results: We identified alterations in genes involved in various functions, such as B2M involved in immunosurveillance. We extended the mutational analysis of B2M to about 230 lung cancers...
March 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28273188/-treatment-options-and-limitations-in-the-management-of-myelofibrosis
#18
Gábor Körösmezey, Gabriella Gyõri, Gábor Rudas, Hanna Eid, Zsolt Nagy, Judit Demeter
Primary myelofibrosis has the worst outcome among classical chronic myeloproliferative neoplasms. The past decade has brought numerous discoveries elucidating the role of proliferative mutations in disease pathogenesis. Mutations of the genes JAK2, MPL and CALR are present in about 90 percent of all primary myelofibrosis cases. The prognosis of myelofibrosis is considered heterogeneous, the expected survival of patients may range from one year to more than a decade based on several prognostic factors. Estimated survival can be assessed based on clinical prognostic scores...
March 8, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28273187/-the-role-of-driver-and-subclonal-mutations-in-pathogenesis-of-primary-myelofibrosis
#19
Réka Mózes, Ambrus Gángó, Zsófia Boha, Judit Csomor, Csaba Bödör
Primary myelofibrosis (PMF) is a Philadelphia chromosome negative, clonal myeloproliferative neoplasm characterised by a progressive nature. Morphologically, the bone marrow biopsy shows features of abnormal proliferation of terminally differentiated megakaryocytes and subsequent bone marrow fibrosis. The molecular landscape of PMF includes phenotypic driver mutations (JAK2 V617F, CALR and MPL) which represent major diagnostic criteria, and subclonal mutations that also occur in several other myeloid diseases, but have a prognostic value in disease progression of MF...
March 8, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28268179/vibrio-parahaemolyticus-calr-down-regulates-the-thermostable-direct-hemolysin-tdh-gene-transcription-and-thereby-inhibits-hemolytic-activity
#20
Yiquan Zhang, Ying Zhang, He Gao, Lingyu Zhang, Zhe Yin, Xinxiang Huang, Dongsheng Zhou, Huiying Yang, Wenhui Yang, Li Wang
TDH, encoded by tdh gene, is a major virulent determinant of V. parahaemolyticus that controls various biological activities, such as hemolytic activity, cytotoxicity, and enterotoxicity. The hemolytic activity on Wagatsuma agar ascribed to TDH is called Kanagawa phenomenon (KP). All KP positive strains contain tdh1 and tdh2 genes, but tdh2 is predominantly responsible for KP. CalR is a regulatory protein that was originally identified as a repressor of swarming motility and T3SS1 gene expression in V. parahaemolyticus...
May 20, 2017: Gene
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