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Bao-Zhu Yang, Shizhong Han, Henry R Kranzler, Abraham A Palmer, Joel Gelernter
Sex influences risk for opioid dependence (OD). We hypothesized that sex might interact with genetic loci that influence the risk for OD. Therefore we performed an analysis to identify sex-specific genomic susceptibility regions for OD using linkage. Over 6,000 single nucleotide polymorphism (SNP) markers were genotyped for 1,758 African- and European-American (AA and EA) individuals from 739 families, ascertained via affected sib-pairs with OD and/or cocaine dependence. Autosomewide non-parametric linkage scans, stratified by sex and population, were performed...
October 20, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Xunian Zhou, Grace Gar-Lee Yue, Minghua Liu, Zhili Zuo, Julia Kin-Ming Lee, Mingyue Li, Stephen Kwok-Wing Tsui, Kwok-Pui Fung, Handong Sun, Jianxin Pu, Clara Bik-San Lau
Eriocalyxin B (EriB), a natural ent-kaurane diterpenoid isolated from the plant Isodon eriocalyx var. laxiflora, has emerged as a promising anticancer agent. The effects of EriB on angiogenesis were explored in the present study. Here we demonstrated that the subintestinal vein formation was significantly inhibited by EriB treatment (10, 15 μM) in zebrafish embryos, which was resulted from the alteration of various angiogenic genes as shown in transcriptome profiling. In human umbilical vein endothelial cells, EriB treatment (50, 100 nM) could significantly block vascular endothelial growth factors (VEGF)-induced cell proliferation, tube formation, cell migration and cell invasion...
October 14, 2016: Oncotarget
A R L de Aquino, C F W Nonaka, C H P de Carvalho, C F Demeda, L B de Souza, L P Pinto
The purpose of this study was to evaluate the immunoexpression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor 3 (VEGFR-3) and their correlation with intratumoural lymphatic density (ILD) and peritumoural lymphatic density (PLD) in metastatic and non-metastatic lower lip squamous cell carcinoma (LLSCC). Twenty-five LLSCC with regional nodal metastasis and 25 LLSCC without metastasis were selected. The percentages of VEGF-C and VEGFR-3 staining in each tumour core and at the deep invasive front were assessed...
October 10, 2016: International Journal of Oral and Maxillofacial Surgery
Na Zhou, Cong Min Liu, He Lei Hou, Chuan Tao Zhang, Dong Liu, Guan Qun Wang, Ke Wei Liu, Jing Juan Zhu, Hong Ying Lv, Tian Jun Li, Xiaochun Zhang
Spindle cell carcinoma of the breast is a rare subtype of metaplastic carcinoma, and no effective chemotherapy special for metaplastic carcinoma exists until now. As spindle cell carcinomas of the breast are typically "Triple Negative", endocrine therapy and molecular therapy targeted to Her2 might not be favorable, resulting in poor prognosis. Apatinib is currently being tested in patients with breast or lung cancers. Here we report a successful case using Apatinib to treat spindle cell carcinoma of breast...
October 11, 2016: Oncotarget
Hidenori Fujita, Akira Gomori, Yayoi Fujioka, Yuki Kataoka, Kenji Tanaka, Akihiro Hashimoto, Takamasa Suzuki, Kenjiro Ito, Tomonori Haruma, Hiromi Yamamoto-Yokoi, Naomoto Harada, Motomu Sakuragi, Nobuyuki Oda, Kenichi Matsuo, Masaki Inada, Kazuhiko Yonekura
Approximately 25-40% of patients with lung cancer show bone metastasis. Bone modifying agents reduce skeletal-related events (SREs), but they do not significantly improve overall survival. Therefore, novel therapeutic approaches are urgently required. In this study, we investigated the anti-tumor effect of TAS-115, a VEGFRs and HGF receptor (MET)-targeted kinase inhibitor, in a tumor-induced bone disease model. A549-Luc-BM1 cells, an osteo-tropic clone of luciferase-transfected A549 human lung adenocarcinoma cells (A549-Luc), produced aggressive bone destruction associated with tumor progression after intra-tibial (IT) implantation into mice...
2016: PloS One
M Moore, S Gill, T Asmis, S Berry, R Burkes, K Zbuk, T Alcindor, A Jeyakumar, T Chan, S Rao, J Spratlin, P A Tang, J Rothenstein, E Chan, J Bendell, F Kudrik, J Kauh, S Tang, L Gao, S R P Kambhampati, F Nasroulah, L Yang, N Ramdas, P Binder, E Strevel
BACKGROUND: Icrucumab and ramucirumab are recombinant human IgG1 monoclonal antibodies that bind VEGF receptors 1 and 2 (VEGFR-1 and -2), respectively. This randomized phase II study evaluated the antitumor activity and safety of icrucumab and ramucirumab each in combination with mFOLFOX-6 in patients with metastatic colorectal cancer after disease progression on first-line therapy with a fluoropyrimidine and irinotecan. PATIENTS AND METHODS: Eligible patients were randomly assigned to receive mFOLFOX-6 alone (mFOLFOX-6) or in combination with ramucirumab 8 mg/kg IV (RAM+mFOLFOX-6) or icrucumab 15 mg/kg IV (ICR+mFOLFOX-6) every 2 weeks...
October 11, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Anna Cecília Dias Maciel Carneiro, Isadora Caixeta da Silveira, Arthur Silva Rezende, Bruna Raphaela Oliveira Silva, Virgínia Oliveira Crema
BACKGROUND: Oral squamous cell carcinoma is extremely invasive, this behavior is regulated by binding of extracellular molecules to the cell membrane receptors. The TKI-258 inhibits phosphorylation of FGFRs VEGFRs and PDGFRs. Our aim was to analyze the effect of TKI-258 treatment in cell movement by using SCC-4 cell line from human oral squamous cell carcinoma. METHODS: F-actin was stained with rhodamine phalloidin and confocal analysis was performed. The migration and invasion (membrane covered with Matrigel(TM) ) three-dimensional assays were performed, control and cells treated with TKI-258 that migrated through the membrane were counted after 24 h...
October 12, 2016: Journal of Oral Pathology & Medicine
Andrea Maria Mess, Ana Claudia Oliveira Carreira, Cláudia Marinovic de Oliveira, Paula Fratini, Phelipe Oliveira Favaron, Rodrigo da Silva Nunes Barreto, Christiane Pfarrer, Flávio Vieira Meirelles, Maria Angelica Miglino
Reproductive technologies are widely used in cattle, although many are associated with high-embryonic mortality, especially during early gestation, when the yolk sac undergoes macroscopic changes in structure. We hypothesized that vasculogenesis and angiogenesis are affected, thereby affecting embryonic and placental differentiation. To test this, we studied yolk sac development and gene expression of the vascular endothelial growth factor system (VEGF-A, VEGFR-1/Flt-1, VEGFR-2/KDR). Samples from Days 25 to 40/41 of pregnancy from control cattle (n = 8) and from pregnancies established with IVF, (n = 7) or somatic cell nuclear transfer/clones (n = 5) were examined by histology, immunohistochemistry, and quantitative reverse transcriptase PCR...
September 13, 2016: Theriogenology
Naoto Takahashi
BCR-ABL tyrosine kinase inhibitor (TKI) has dramatically improved the prognosis of CML patients. Now, one of the most important factors with a marked effect on prognosis in CML patients is having a comorbidity. Recently, cardiovascular events (CVE) have been reported in some clinical trials as a late toxicity of TKI, which might be associated with off-target of TKI, ABL/ARG, PDGFR and VEGFR. Because TKI-associated CVE is one of the potentially lethal adverse events associated with TKI administration, hematologists must practice the "ABCDE steps" for CML patients treated with second generation TKI in collaboration with cardiologists...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Jin Hee Kim, Ji-Yeon Suh, Dong-Cheol Woo, Yu Sub Sung, Woo-Chan Son, Yoon Seok Choi, Sang Joon Pae, Jeong Kon Kim
Contrast enhancement by an extracellular-fluid contrast agent (CA) (Gd-DOTA) depends primarily on the blood-brain-barrier permeability (bp), and transverse-relaxation change caused by intravascular T2 CA (superparamagnetic iron oxide nanoparticles, SPIONs) is closely associated with the blood volume (BV). Pharmacokinetic (PK) vascular characterization based on single-CA-using dynamic contrast-enhanced MRI (DCE-MRI) has shown significant measurement variation according to the molecular size of the CA. Based on this recognition, this study used a dual injection of Gd-DOTA and SPIONs for tracing the changes of bp and BV in C6 glioma growth (Days 1 and 7 after the tumor volume reached 2 mL)...
October 10, 2016: NMR in Biomedicine
Mingzhu Yin, Xia Li, Shu Tan, Huanjiao Jenny Zhou, Weidong Ji, Stefania Bellone, Xiaocao Xu, Haifeng Zhang, Alessandro D Santin, Ge Lou, Wang Min
Tumor-associated macrophages (TAMs) can influence ovarian cancer growth, migration, and metastasis, but the detailed mechanisms underlying ovarian cancer metastasis remain unclear. Here, we have shown a strong correlation between TAM-associated spheroids and the clinical pathology of ovarian cancer. Further, we have determined that TAMs promote spheroid formation and tumor growth at early stages of transcoelomic metastasis in an established mouse model for epithelial ovarian cancer. M2 macrophage-like TAMs were localized in the center of spheroids and secreted EGF, which upregulated αMβ2 integrin on TAMs and ICAM-1 on tumor cells to promote association between tumor cells and TAM...
October 10, 2016: Journal of Clinical Investigation
Christoph Schliemann, Joachim Gerss, Stefanie Wiebe, Jan-Henrik Mikesch, Nicola Knoblauch, Tim Sauer, Linus Angenendt, Tobias Kewitz, Marc Urban, Trude Butterfass-Bahloul, Sabine Edemir, Kerstin Vehring, Carsten Müller-Tidow, Wolfgang E Berdel, Utz Krug
: Nintedanib (BIBF 1120), a potent multikinase inhibitor of VEGFR-1/-2/-3, FGFR-1/-2/-3 and PDGFR-α/-β, exerts growth inhibitory and pro-apoptotic effects in myeloid leukemic cells, especially when used in combination with cytarabine. This phase I study evaluated nintedanib in combination with low-dose cytarabine (LDAC) in elderly patients with untreated or relapsed/refractory acute myeloid leukemia (AML) ineligible for intensive chemotherapy in a 3+3 design. Nintedanib (dose levels 100, 150, and 200 mg orally twice daily) and LDAC (20 mg subcutaneous injection twice daily for 10 days) were administered in 28-day cycles...
2016: PloS One
Claudia Karnthaler-Benbakka, Diana Groza, Bettina Koblmüller, Alessio Terenzi, Katharina Holste, Melanie Haider, Dina Baier, Walter Berger, Petra Heffeter, Christian R Kowol, Bernhard K Keppler
Tyrosine kinase inhibitors (TKIs), which have revolutionized cancer therapy over the past 15 years, are limited in their clinical application due to serious side effects. Therefore, we converted two approved TKIs (sunitinib and erlotinib) into 2-nitroimidazole-based hypoxia-activatable prodrugs. Kinetics studies showed very different stabilities over 24 h; however, fast reductive activation via E. coli nitroreductase could be confirmed for both panels. The anticancer activity and signaling inhibition of the compounds against various human cancer cell lines were evaluated in cell culture...
October 5, 2016: ChemMedChem
Alessio D'Alessio, Gabriella Proietti, Gina Lama, Filippo Biamonte, Libero Lauriola, Umberto Moscato, Angelo Vescovi, Annunziato Mangiola, Cristiana Angelucci, Gigliola Sica
The formation of new blood vessels represents a crucial event under both physiological and pathological circumstances. In this study, we evaluated by immunohistochemistry, and/or Western blotting and/or quantitative real time-PCR the expression of HIF1α, HIF2α, VEGF, VEGFR1 and VEGFR2 in surgical glioblastoma multiforme (GBM) and peritumoral tissue samples obtained from 50 patients as well as in cancer stem cells (CSCs) isolated from GBM (GCSCs) and peritumoral tissue (PCSCs) of 5 patients. We also investigated the contribution of both GCSCs and PCSCs on the behavior of endothelial cells (ECs) in vitro...
October 1, 2016: Oncotarget
Eun-Joo Jeon, Munkhtugs Davaatseren, Jin-Taek Hwang, Jae Ho Park, Haeng Jeon Hur, Ae Sin Lee, Mi Jeong Sung
In patients with inflammatory bowel disease (IBD), inflammation is induced and maintained by lymphangiogenesis and angiogenesis. 3,3'-Diindolylmethane (DIM) is a natural product formed in acidic conditions from indole-3-carbinol in cruciferous vegetables, and it is known for its chemotherapeutic activity. This study evaluated DIM's effects on angiogenesis, lymphangiogenesis, and inflammation in a mouse colitis model. Experimental colitis was induced in mice by administering 3% dextran sulfate sodium (DSS) via drinking water...
October 4, 2016: Journal of Agricultural and Food Chemistry
Nikolaos Koufos, John Syrios, Despina Michailidou, Ioannis D Xynos, Andreas Lazaris, Nicolaos Kavantzas, Periclis Tomos, Stamatis Kakaris, Christos Kosmas, Nikolas Tsavaris
The expression of various angiogenic factors was assessed in tumour samples of patients with stage III non-small-cell lung cancer (NSCLC) and further evaluated in terms of response to induction paclitaxel-ifosfamide-cisplatin chemotherapy. Freshly isolated lung tumour specimens obtained by bronchoscopy from 70 stage IIIA NSCLC chemotherapy-naïve patients were sampled and analysed for vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2 and VEGFR-3. Microvessel density was assessed through evaluating the angiogenic markers CD34 and CD105...
October 2016: Molecular and Clinical Oncology
Hai-Tao Du, Ping Liu
The aim of the present study was to investigate the roles of matrix metalloproteinase 14 (MMP-14) in corneal inflammatory lymphangiogenesis. The expression of MMP-14 in vivo was detected by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays, under various corneal conditions. pCMV-MMP-14 or empty pCMV vectors were injected into mouse corneal stroma, 3 days after suture placement in a standard suture-induced inflammatory corneal neovascularization assay...
October 2016: Experimental and Therapeutic Medicine
Hai-Lang He, Dan Wang, Jie Tang, Xian-Mei Zhou, Jian-Xin Li, Ling Xu
Lung cancer is the leading cause of cancer-related deaths worldwide. Jin Fu Kang (JFK), an oral liquid prescription of Chinese herbal drugs, has been clinically available for the treatment of non-small cell lung cancer (NSCLC). Lymphangiogenesis is a primary event in the process of cancer development and metastasis, and the formation and migration of lymphatic endothelial cells (LECs) play a key role in the lymphangiogenesis. To assess the activity of stromal cell-derived factor-1 (SDF-1) and the coeffect of SDF-1 and vascular endothelial growth factor-C (VEGF-C) on the formation and migration of LECs and clarify the inhibitory effects of JFK on the LECs, the LECs were differentiated from CD34(+)/VEGFR-3(+) endothelial progenitor cells (EPCs), and JFK-containing serums were prepared from rats...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Jianfeng Liang, Qinghua Meng, Wanni Zhao, Pan Tong, Ping Li, Yuanli Zhao, Xiaodong Zhao, Hua Li
Proper regulation of neuronal gene expression is crucial for the development and differentiation of the central nervous system. The transcriptional repressor REST (repressor element-1 silencing transcription factor) is a key regulator in differentiation of pluripotent stem cells to neuronal progenitors and mature neurons. Dysregulated REST activity has been implicated in various diseases, among which the most deadly is glioblastoma multiforme (GBM). Here we have developed an expression-based REST signature (EXPREST), a device providing quantitative measurements of REST activity for GBM tumors...
October 4, 2016: Scientific Reports
Shotaro Maehana, Masaki Nakamura, Fumihiro Ogawa, Rimika Imai, Rei Murakami, Fumiaki Kojima, Masataka Majima, Hidero Kitasato
The vascular endothelial growth factor (VEGF) family has a key role in the formation of blood vessels and lymphatics. Among the members of this family, VEGF-C is one of the most important factors involved in lymphangiogenesis via binding with two receptors (vascular endothelial growth factor receptor-2 and -3: VEGFR-2 and VEGFR-3). Soluble VEGFR-2 (sVEGFR-2) has a role in maintaining the alymphatic state of the cornea associated with binding to VEGF-C, and selectively inhibits lymphangiogenesis but not angiogenesis...
September 30, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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