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Identification of colorectal cancer metastasis markers by an angiogenesis-related cytokine-antibody array

世界胃肠病学杂志：英文版 2012年第7期18卷 637-645页

作者： ana abajo Nerea Bitarte Ruth Zarate Valentina Boni Ines Lopez Marisol Gonzalez-Huarriz Javier Rodriguez Eva Bandres Jesus Garcia-Foncillas Laboratory of Pharmacogenomics Division of OncologyCenter for Applied Medical ResearchUniversity of NavarraAvda Pio XII 5531008 PamplonaSpain Department of Oncology University Clinic of NavarraUniversity of NavarraAvda Pio XII 5531008 PamplonaSpain

AIM:To investigate the angiogenesis-related protein expression profile characterizing metastatic colorectal cancer (mCRC) with the aim of identifying prognostic markers.METHODS:The expression of 44 angiogenesissecreted factors was measured by a novel cytokine antibody array methodology.The study evaluated vascular endothelial growth factor (VEGF) and its soluble vascular endothelial growth factor receptor (sVEGFR)-1 protein levels by enzyme immunoassay (EIA) in a panel of 16 CRC cell lines.mRNA VEGF and VEGF-A isoforms were quantified by quantitative reverse-transcription polymerase chain reaction (Q-RT-PCR) and vascular endothelial growth factor receptor (VEGFR)-2 expression was analyzed by flow cytometry.RESULTS:Metastasis-derived CRC cell lines expressed a distinctive molecular profile as compared with those isolated from a primary tumor site.Metastatic CRC cell lines were characterized by higher expression of angiogenin-2 (Ang-2),macrophage chemoattractant proteins-3/4 (MCP-3/4),matrix metalloproteinase-1 (MMP-1),and the chemokines interferon γ inducible T cell α chemoattractant protein (I-TAC),monocyte chemoattractant protein I-309,and interleukins interleukin (IL)-2 and IL-1α,as compared to primary tumor cell lines.In contrast,primary CRC cell lines expressed higher levels of interferon γ (IFN-γ),insulin-like growth factor-1 (IGF-1),IL-6,leptin,epidermal growth factor (EGF),placental growth factor (PlGF),thrombopoietin,transforming growth factor β1 (TGF-β1) and VEGF-D,as compared with the metastatic cell lines.VEGF expression does not significantly differ according to the CRC cellular origin in normoxia.Severe hypoxia induced VEGF expression up-regulation but contrary to expectations,metastatic CRC cell lines did not respond as much as primary cell lines to the hypoxic stimulus.In CRC primary-derived cell lines,we observed a twofold increase in VEGF expression between normoxia and hypoxia as compared to metastatic cell lines.CRC cell lines express a similar pattern of VEGF isoforms (VEGF 121,VEGF 165 and VE

关键词：血管生成细胞因子血管内皮生长因子受体识别标记阵列抗体大肠癌逆转录聚合酶链反应

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Pharmacogenomics in colorectal cancer: The first step for individualized-therapy

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World Journal of Gastroenterology 2007年第44期13卷 5888-5901页

作者： Eva Bandrés Ruth Zárate Natalia Ramirez ana abajo Nerea Bitarte Jesus García-Foncillas Laboratory of Pharma-cogenomics Cancer Research Program (Center for Applied Medical Research) University of Navarra Navarra Spain

Interindividual differences in the toxicity and response to anticancer therapies are currently observed in practically all available treatment regimens. A goal of cancer therapy is to predict patient response and toxicity to drugs in order to facilitate the individualization of patient treatment. Identification of subgroups of patients that differ in their prognosis and response to treatment could help to identify the best available drug therapy according the genetic profile. Several mechanisms have been suggested to contribute to chemo-therapeutic drug resistance: amplification or overexpression of membrane transporters, changes in cellular proteins involved in detoxification or in DNA repair, apoptosis and activation of oncogenes or tumor suppressor genes. Colorectal cancer (CRC) is regarded as intrinsically resistant to chemotherapy. Several molecular markers predictive of CRC therapy have been included during the last decade but their results in different studies complicate their application in practical clinical. The simultaneous testing of multiple markers predictive of response could help to identify more accurately the true role of these polymorphisms in CRC therapy. This review analyzes the role of genetic variants in genes involved in the action mechanisms of the drugs used at present in colorectal cancer.

关键词：结肠癌化学治疗毒性多态现象

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Extracorporeal shock wave for plantar flexor spasticity in spinal cord injury:A case report and review of literature

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World Journal of Clinical Cases 2023年第1期11卷 127-134页

作者： Natalia Comino-Suárez Julio Gómez-Soriano Silvia Ceruelo-abajo Eduardo Vargas-Baquero ana Esclarín Juan Avendaño-Coy Toledo Physiotherapy Research Group Faculty of Physiotherapy and NurseryCastilla La Mancha UniversityToledo 45071ToledoSpain Department of Physical and Rehabilitation Medicine Hospital Nacional de ParapléjicosSescamToledo 45071ToledoSpain

BACKGROUND Approximately 65%-78%of patients with a spinal cord injury(SCI)develop any symptom of spasticity.The aim of this study was to investigate the tolerability and short-term effects of radial extracorporeal shock wave therapy(r ESWT)on plantar flexor spasticity in a patient with incomplete SCI.CASE SUMMARY An 18-year-old man with an incomplete SCI completed five sessions of r ESWT.The primary outcomes were the changes in ankle-passive range of motion(APROM)and passive resistive force to ankle dorsiflexion.The outcomes were assessed at baseline(T0),immediately after treatment(T1)and 1 wk after the end of treatment(T2).The A-PROM increased by 15 degrees at T1 and 25 degrees at T2 compared with T0.The passive resistive force to ankle dorsiflexion at low velocity decreased by 33%at T1 and 55%at T2 in the gastrocnemius muscle and by 41%at T1 and 39%at T2 in the soleus muscle compared with T0.At high velocity,it also decreased by 44%at T1 and 30%at T2 in the gastrocnemius muscle compared with T0.However,in the soleus muscle,the change was minor,with a decrease of 12%at T1 and increased by 39%at T2 compared with T0.CONCLUSION In this patient,the findings showed that r ESWT combined with conventional therapy was well-tolerated and could be effective in improving A-PROM and passive resistive force to ankle dorsiflexion in the short-term.Further randomized controlled clinical trials with longer period of follow-up are necessary to confirm the results obtained in patients with SCI.

关键词： Spasticity Spinal cord injury Radial extracorporeal shock wave therapy Rehabilitation Case report

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Low prevalence of germline hMSH6 mutations in colorectal cancer families from Spain

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World Journal of Gastroenterology 2005年第37期11卷 5770-5776页

作者： ana Sánchez de abajo Miguel de la Hoya Alicia Tosar Javier Godino Juan Manuel Fernández Jose Lopez Asenjo Beatriz Perez Villamil Pedro Perez Segura Eduardo Diaz-Rubio Trinidad Caldes Laboratorio de Oncología Molecular Hospital Clinico San Carlos Madrid Spain Servicio de anatomía Patológica Hospital Clinico San Carlos Madrid Spain Servicio de Oncología Médica Hospital Clinico San Carlos Madrid Spain

AIM: To investigate the prevalence and penetrance of hMSH6 mutations in Spanish HNPCC families that was negative for mutation in hMLH1 or hMSH2.METHODS: We used PCR-based DGGE assay and direct Sequencing to screen for hMSH6 gene in 91 HNPCC families.RESULTS: we have identified 10 families with germ-line mutations in the DNA sequence. These mutations included two intronic variation, three missense mutation, one nonsense mutation, and four silent mutations. Among the 10 germ-line mutations identified in the Spanish cohort,8 were novel, perhaps, suggesting different mutational spectra in the Spanish population. Detailed pedigrees were constructed for the three families with a possible pathogenic hMSH6 mutation. The two silent mutations H388H and L758L, detected in a person affected of colorectal cancer at age 29, produce loss of the wild-type allele in the tumor sample. Immunohistochemical analysis showed that expression of MSH6 protein was lost only in the tumors from the carriers of V878A and Q263X mutations.CONCLUSION: Altogether, our results indicate that disease-causing germ-line mutations of hMSH6 are very less frequent in Spanish HNPCC families.

关键词：基因突变 hMSH6 结肠癌直肠癌西班牙遗传因素

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