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https://www.readbyqxmd.com/read/27908881/pre-clinical-studies-of-gilteritinib-a-next-generation-flt3-inhibitor
#1
Lauren Y Lee, Daniela Hernandez, Trivikram Rajkhowa, Samuel C Smith, Jayant Ranganathan Raman, Bao Nguyen, Donald Small, Mark Levis
Activating mutations in the receptor tyrosine kinase FLT3 comprise approximately one-third of genetic lesions in acute myeloid leukemia (AML) and are associated with a poor prognosis. Internal tandem duplication (FLT3-ITD) mutations in particular are associated with a high relapse rate. Although FLT3 tyrosine kinase inhibitors (TKIs) appear to improve clinical outcomes for patients with FLT3-ITD AML, the development of early-generation FLT3 TKIs has been impeded by several obstacles such as low potency and selectivity, myelosuppression, and the emergence of resistance-conferring point mutations...
December 1, 2016: Blood
https://www.readbyqxmd.com/read/27906584/effects-of-the-transforming-growth-factor-beta-signaling-pathway-on-the-differentiation-of-chicken-embryonic-stem-cells-into-male-germ-cells
#2
Yani Zhang, Yingjie Wang, Qisheng Zuo, Dong Li, Wenhui Zhang, Chao Lian, Beibei Tang, Tianrong Xiao, Man Wang, Kehua Wang, Bichun Li
The objectives of the present study were to screen for key gene and signaling pathways involved in the production of male germ cells in poultry and to investigate the effects of the transforming growth factor beta (TGF-β) signaling pathway on the differentiation of chicken embryonic stem cells (ESCs) into male germ cells. The ESCs, primordial germ cells, and spermatogonial stem cells (SSCs) were sorted using flow cytometry for RNA sequencing (RNA-seq) technology. Male chicken ESCs were induced using 40 ng/mL of bone morphogenetic protein 4 (BMP4)...
November 2016: Cellular Reprogramming
https://www.readbyqxmd.com/read/27900093/primary-gastrointestinal-stromal-tumour-of-the-ileum-pre-operatively-diagnosed-as-an-abdominal-abscess
#3
Patrizia Rubini, Francesco Tartamella
The present case report described the acute presentation, diagnosis and management of a primary gastrointestinal stromal tumour (GIST) of the ileum. A male patient (age, 51 years) was admitted to Maggiore Hospital (Parma, Italy) due to presenting with fever, dysuria and lower abdominal pain. Ultrasonography and computed tomography showed a 7,5×5,5-cm pelvic mass containing air and purulent fluid indicative of an intraperitoneal abscess. The patient was subjected to diagnostic laparoscopy, which revealed a huge, soft cystic mass arising from the small bowel...
November 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27899264/cyclic-ferrocenylnaphthalene-diimide-derivative-as-a-new-class-of-g-quadruplex-dna-binding-ligand
#4
Md Monirul Islam, Shinobu Sato, Shingo Shinozaki, Shigeori Takenaka
To identify an effective ligand that binds to a G-quadruplex structure but not a double-stranded DNA (dsDNA), a set of biophysical and biochemical experiments were carried out using newly synthesized cyclic ferrocenylnaphthalene diimide (cFNDI, 1) or the non-cyclic derivative (2) with various structures of G-quadruplex DNAs and dsDNA. Compound 1 bound strongly to G-quadruplexes DNAs (10(6)M(-1) order) with diminished binding to dsDNA (10(4)M(-1) order) in 100mM AcOH-AcOK buffer (pH 5.5) containing 100mM KCl...
November 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27890929/extended-time-lapse-in-vivo-imaging-of-tibia-bone-marrow-to-visualize-dynamic-hematopoietic-stem-cell-engraftment
#5
S Kim, L Lin, G A J Brown, K Hosaka, E W Scott
Homing, engraftment and proliferation of hematopoietic stem/progenitor cell (HSC/HPCs) are crucial steps required for success of a bone marrow transplant. Observation of these critical events is limited by the opaque nature of bone. Here we demonstrate how individual HSCs engraft in long bones by thinning one side of the tibia for direct and unbiased observation. Intravital imaging enabled detailed visualization of single Sca-1(+), c-Kit(+), Lineage(-) (SKL) cell migration to bone marrow niches and subsequent proliferation to reconstitute hematopoiesis...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27890784/identifying-residues-that-determine-scf-molecular-level-interactions-through-a-combination-of-experimental-and-in-silico-analyses
#6
Eitan Rabinovich, Michael Heyne, Anna Bakhman, Mickey Kosloff, Julia M Shifman, Niv Papo
The stem cell factor (SCF)/c-Kit receptor tyrosine kinase complex - with its significant roles in hematopoiesis and angiogenesis - is an attractive target for rational drug design. There is thus a need to map, in detail, the SCF/c-Kit interaction sites and the mechanisms that modulate this interaction. While most residues in the direct SCF/c-Kit binding interface can be identified from the existing crystal structure of the complex, other residues that affect binding through protein unfolding, intermolecular interactions, or allosteric or long-distance electrostatic effects cannot be directly inferred...
November 24, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27879307/unusual-cause-of-profound-weight-loss-in-a-young-woman
#7
Ashu Rastogi, Pavan Uppula, Kanchan Kumar Mukherjee, Anil Bhansali
A 27-year-old woman presented with anorexia, weight loss and psychiatric symptoms for the past 4 years. She did not have history of headache, visual disturbances or symptoms of raised intracranial pressure. She was sarcopenic with body mass index of 10.16 kg/m(2)Her systemic examination was normal except for temporal hemianopia suggesting a sellar/suprasellar lesion. Hormonal evaluation revealed pan-hypopituitarism with central diabetes insipidus. Subsequent neuroimaging revealed sellar-suprasellar mass lesion with intense contrast enhancement and leptomeningeal metastases...
November 22, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27876094/nitric-oxide-has-contrasting-age-dependent-effects-on-the-functionality-of-murine-hematopoietic-stem-cells
#8
Sapana Jalnapurkar, Shweta Singh, Moirangthem Ranjita Devi, Lalita Limaye, Vaijayanti Kale
BACKGROUND: The success of hematopoietic stem cell (HSC) transplantation is dependent on the quality of the donor HSCs. Some sources of HSCs display reduced engraftment efficiency either because of inadequate number (e.g., fetal liver and cord blood), or age-related dysfunction (e.g. in older individuals). Therefore, use of pharmacological compounds to improve functionality of HSCs is a forefront research area in hematology. METHODS: Lineage negative (Lin(-)) cells isolated from murine bone marrow or sort-purified Lin(-)Sca-1(+)c-Kit(+)CD34(-) (LSK-CD34(-)) were treated with a nitric oxide donor, sodium nitroprusside (SNP)...
November 22, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27868139/clinical-genetic-and-innate-immunity-characteristics-of-melanoma-in-organ-transplant-recipients
#9
Anabelle Brocard, Anne-Chantal Knol, Céline Bossard, Marc G Denis, Gaëlle Quéreux, Mélanie Saint-Jean, Lucie Peuvrel, Amir Khammari, Gilles Blancho, Jacques Dantal, Brigitte Dréno
The aims of this study were to determine the clinical and histological characteristics of melanoma in transplant recipients, the mutation profile (BRAF, NRAS and c-KIT genes), and the immune tolerance of the tumour microenvironment by immunohistochemical study of the expression of IDO, PD1, PD-L1, CD8 and FoxP3. The study population comprised patients who had undergone a renal transplant in Nantes University Hospital who developed post-transplantation melanoma. Twenty cases of melanoma out of 4,663 transplant recipients were studied...
November 10, 2016: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/27864904/an-update-on-the-current-management-of-head-and-neck-mucosal-melanoma
#10
REVIEW
Ben Green, Ahmed Elhamshary, Ricardo Gomez, Siavash Rahimi, Peter A Brennan
Primary mucosal melanomas of the head and neck are rare and aggressive tumours that arise in the nasal cavity, paranasal sinuses and more rarely, in the oral cavity. The current treatment options include radical surgical resection with adjuvant external beam radiotherapy being offered in high risk patients. Although the latter can improve regional control, it does not reduce overall survival. Elective neck dissection is recommended for nodular oral mucosal melanoma but its role in the clinically node negative neck is controversial...
November 19, 2016: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/27860388/enhanced-tissue-remodeling-efficacy-of-adipose-derived-mesenchymal-stem-cells-using-injectable-matrices-in-radiation-damaged-salivary-gland-model
#11
Jeong-Seok Choi, Hye-Young An, Hyun-Soo Shin, Young-Mo Kim, Jae-Yol Lim
The present study was conducted to introduce the use of a delivery carrier for local transplantation of human adipose tissue-derived mesenchymal stem cells (AdMSCs) into the salivary gland (SG) and analyze its ability to enhance radioprotection of AdMSCs against irradiation (IR)-induced damage. An injectable porcine small intestinal submucosa (SIS) matrix was used as a cell delivery carrier and human AdMSCs were contained within SIS hydrogel (AdMSC/SIS). After local injection into SGs of mice following local IR, morphological and functional changes were evaluated in the sham, vehicle (PBS), SIS, AdMSC, and AdMSC/SIS groups...
November 12, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27860245/telocytes-a-potential-defender-in-the-spleen-of-npc1-mutant-mice
#12
Bichao Zhang, Ciqing Yang, Liang Qiao, Qiuling Li, Congrui Wang, Xin Yan, Juntang Lin
Niemann-Pick disease, type C1 (Npc1), is an atypical lysosomal storage disorder caused by autosomal recessive inheritance of mutations in Npc1 gene. In the Npc1 mutant mice (Npc1(-/-) ), the initial manifestation is enlarged spleen, concomitant with free cholesterol accumulation. Telocytes (TCs), a novel type of interstitial cell, exist in a variety of tissues including spleen, presumably thought to be involved in many biological processes such as nursing stem cells and recruiting inflammatory cells. In this study, we found that the spleen is significantly enlarged in Npc1(-/-) mice, and the results from transmission electron microscopy examination and immunostaining using three different TCs markers, c-Kit, CD34 and Vimentin revealed significantly increased splenic TCs in Npc1(-/-) mice...
November 18, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27860185/sildenafil-attenuates-hypoxic-pulmonary-remodelling-by-inhibiting-bone-marrow-progenitor-cells
#13
Shirley Favre, Elisa Gambini, Patrizia Nigro, Alessandro Scopece, Paola Bianciardi, Anna Caretti, Giulio Pompilio, Antonio F Corno, Giuseppe Vassalli, Ludwig K von Segesser, Michele Samaja, Giuseppina Milano
The recruitment of bone marrow (BM)-derived progenitor cells to the lung is related to pulmonary remodelling and the pathogenesis of pulmonary hypertension (PH). Although sildenafil is a known target in PH treatment, the underlying molecular mechanism is still elusive. To test the hypothesis that the therapeutic effect of sildenafil is linked to the reduced recruitment of BM-derived progenitor cells, we induced pulmonary remodelling in rats by two-week exposure to chronic hypoxia (CH, 10% oxygen), a trigger of BM-derived progenitor cells...
November 18, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27858882/pigmented-perivascular-epithelioid-cell-tumor-pecoma-arising-from-kidney-a-case-report
#14
Hexi Du, Jun Zhou, Lingfan Xu, Cheng Yang, Li Zhang, Chaozhao Liang
INTRODUCTION: Perivascular epithelioid cell tumor (PEComa) is a mesenchymal neoplasm composed of perivascular epithelioid cells with clear to eosinophilic cytoplasm. Pigmented PEComa arising from kidney is extraordinarily rare and sometimes can exhibit aggressive biological behavior. CASE REPORT: We present here a rare case of pigmented renal PEComa in a 46-year-old female. The patient had complained of lumbago complicated with nausea and vomiting for 2 weeks and therefore was referred to our department...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27857005/polypoid-anal-melanoma-a-case-report-and-review-of-the-literature
#15
Roberta Tutino, Giuseppe Clerico, Alberto Realis Luc, Gaetano Gallo, Mario Trompetto
INTRODUCTION: Ano-rectal melanoma is an uncommon finding in patients complaining of rectal bleeding and/or anal mass often misinterpreted as a haemorroidal pile. CASE REPORT: A 55-years-old woman, complaining of rectal bleeding, frequent anal pain and anal mass suspected for haemorroidal thrombosis was referred for evaluation and possible treatment. A brown polypoid mass arising from the anal canal/lower rectum with a maximum diameter of 6 cm was diagnosed. The hystological examination of the neoplasm, transanally removed, revealed the presence of a polypoid melanoma partially involving the resection margin...
November 12, 2016: Annali Italiani di Chirurgia
https://www.readbyqxmd.com/read/27856608/reversal-of-bone-marrow-mobilopathy-and-enhanced-vascular-repair-by-angiotensin-1-7-in-diabetes
#16
Goutham Vasam, Shrinidh Joshi, Sean E Thatcher, Stephen H Bartelmez, Lisa A Cassis, Yagna Pr Jarajapu
Ang-(1-7)/MasR pathway activates vascular repair-relevant functions of bone marrow progenitor cells. We tested the effects of Ang-(1-7) on mobilization and vasoreparative functions of progenitor cells that are impaired in diabetes. Study was carried out in streptozotocin-induced diabetic or db/db mice. Diabetes resulted in decreased number of Lineage(-) Sca-1(+) c-Kit(+) (LSK) cells in the circulation, which was normalized by Ang-(1-7). Diabetes-induced depletion of LSK cells in the bone marrow was reversed by Ang-(1-7)...
November 17, 2016: Diabetes
https://www.readbyqxmd.com/read/27856257/maternal-diabetes-and-high-glucose-in-vitro-trigger-sca1-cardiac-progenitor-cell-apoptosis-through-foxo3a
#17
Penghua Yang, Wendy W Yang, Xi Chen, Sunjay Kaushal, Daoyin Dong, Wei-Bin Shen
Recent controversies surrounding the authenticity of c-kit(+) cardiac progenitor cells significantly push back the advance in regenerative therapies for cardiovascular diseases. There is an urgent need for research in characterizing alternative types of cardiac progenitor cells. Towards this goal, in the present study, we determined the effect of maternal diabetes on Sca1(+) cardiac progenitor cells. Maternal diabetes induced caspase 3-dependent apoptosis in Sca1(+) cardiac progenitor cells derived from embryonic day 17...
November 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27855694/cd274-promotes-cell-cycle-entry-of-leukemia-initiating-cells-through-jnk-cyclin-d2-signaling
#18
Xia Fang, Chiqi Chen, Fangzhen Xia, Zhuo Yu, Yaping Zhang, Feifei Zhang, Hao Gu, Jiangbo Wan, Xiaocui Zhang, Wei Weng, Cheng Cheng Zhang, Guo-Qiang Chen, Aibing Liang, Li Xie, Junke Zheng
BACKGROUND: CD274 (programmed death ligand 1, also known as B7H1) is expressed in both solid tumors and hematologic malignancies and is of critical importance for the escape of tumor cells from immune surveillance by inhibiting T cell function via its receptor, programmed death 1 (PD-1). Increasing evidence indicates that functional monoclonal antibodies of CD274 may potently enhance the antitumor effect in many cancers. However, the role of CD274 in leukemia-initiating cells (LICs) remains largely unknown...
November 17, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27854307/mast-cells-density-positive-to-tryptase-correlate-with-microvascular-density-in-both-primary-gastric-cancer-tissue-and-loco-regional-lymph-node-metastases-from-patients-that-have-undergone-radical-surgery
#19
Michele Ammendola, Rosario Sacco, Valeria Zuccalà, Maria Luposella, Rosa Patruno, Pietro Gadaleta, Nicola Zizzo, Cosmo Damiano Gadaleta, Giovambattista De Sarro, Giuseppe Sammarco, Mihai Oltean, Girolamo Ranieri
Mast Cells (MCs) play a role in immune responses and more recently MCs have been involved in tumoral angiogenesis. In particular MCs can release tryptase, a potent in vivo and in vitro pro-angiogenic factor via proteinase-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase (MAPK) phosphorylation. MCs can release tryptase following c-Kit receptor activation. Nevertheless, no data are available concerning the relationship among MCs Density Positive to Tryptase (MCDPT) and Microvascular Density (MVD) in both primary gastric cancer tissue and loco-regional lymph node metastases...
November 15, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27846844/a-rare-case-with-synchronous-gastric-gastrointestinal-stromal-tumor-pancreatic-neuroendocrine-tumor-and-uterine-leiomyoma
#20
Elena Arabadzhieva, Atanas Yonkov, Sasho Bonev, Dimitar Bulanov, Ivanka Taneva, Alexandrina Vlahova, Tihomir Dikov, Violeta Dimitrova
BACKGROUND: Although gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, they comprise less than 1% of all gastrointestinal tumors. Neuroendocrine tumors (NET) of the gastro-enteropancreatic system are also rare, representing about 2% of all gastrointestinal neoplasms. Pancreatic localization of NET is extremely uncommon-these tumors are only 1-5% of all pancreatic cancers. CASE PRESENTATION: We describe an unusual case with triple tumor localization-a gastric tumor, a formation in the pancreas, which involves the retroperitoneal space, and a uterine leiomyoma...
November 15, 2016: World Journal of Surgical Oncology
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