Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells

The incidence of distant metastases is higher in the tumours with low oxygen pressure than in those with high oxygen pressure. It is well known that hypoxia induces the transcription of various genes involved in angiogenesis and anaerobic metabolism necessary for the growth of tumour cells in vivo, suggesting that hypoxia may also induce the transcription of metastasis-associated genes. We sought to identify the metastasis-associated genes differentially expressed in tumour cells under hypoxic conditions with the use of a DNA microarray system. We found that hypoxia enhanced the expression of autocrine motility factor mRNA in various cancer cells and also enhanced the random motility of pancreatic cancer cells. Autocrine motility factor inhibitors abrogated the increase of motility under hypoxic conditions. In order to explore the roles of hypoxia-inducible factor-1α, we established hypoxia-inducible factor-1α-transfectants and dominant negative hypoxia-inducible factor-1α-transfectants. Transfection with hypoxia-inducible factor-1α and dominant-negative hypoxia-inducible factor-1α enhanced and suppressed the expression of autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA and the random motility, respectively. These results suggest that hypoxia may promote the metastatic potential of cancer cells through the enhanced autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA expression and that the disruption of the hypoxia-inducible factor-1 pathway may be an effective treatment for metastasis

Assesment of placement of the esophageal self-expandable metallic stent in esophageal cancer in patients with or without citorreduction therapy Avaliação do emprego de prótese metálica auto-expansível no câncer avançado do esôfago em pacientes com ou sem terapia citorredutora

BACKGROUND: Placement of self-expanding metallic esophageal stent in patients with advanced esophageal cancer offers excellent palliation of dysphagia and tracheo-esophageal fistulas. However, the safety of stent in patients undergoing radio and/or chemotherapy is controversial, in terms of the greater risk of complications in cases where these two treatments are used in conjunction. AIM: To assess the use of stent in patients with advanced cancer of the mid-thoracic esophagus, by comparing patients undergoing cytoreductive therapy with patients who have not undergone this treatment, in relation to improvement in the dysphagia, rate of complications, period of effectiveness and survival time. METHODS: Fifty seven patients were evaluated retrospectively (16 women and 41 men, with an average age 62 years) with advanced squamous cell carcinoma of the mid-thoracic esophagus who underwent placement of the Ultraflex™ self-expandable metallic coated stent, at the Gastrointestinal Endoscopy Unit of São Paulo University Medical School between October 1988 and October 2004. Out of the 57 patients, 24 patients received adjuvant cytoreductive therapy, and 33 patients were only treated with the stent placement. RESULTS: After stent placement, there was improvement in dysphagia in both groups; there were no differences in the rate of complications, such as migration, pain, fistula, obstruction and compression of the airways; the period of effectiveness was significantly higher in the group submitted to cytoreductive therapy (average 123 days compared to 63 days), as was the survival time (average of 210 days, compared with 120 days). CONCLUSIONS: Improvement in dysphagia was statistically significant in both groups, irrespective of whether the patient had undergone adjuvant cytoreductive therapy; there were no differences in the rate of complications between the two groups and both the period of effectiveness of the stent treatment and the survival time were higher in the group with adjuvant cytoreductive therapy.<br>RACIONAL: A colocação de stent esofágico metálico e auto-expansível em pacientes com câncer esofágico avançado oferece boa paliação para disfagia e fístulas traqueoesofágicas. No entanto, a segurança do stent em pacientes submetidos à rádio e/ou quimioterapia é controversa, podendo gerar maior risco de complicações em casos onde estes dois tratamentos são utilizados em conjunto. OBJETIVO: Avaliar o uso de stent em pacientes com câncer médio-torácico de esôfago avançado, comparando os pacientes submetidos à terapia citoredutora aos que não foram submetidos a este tratamento, com relação a melhora da disfagia, índice de complicações, período de efetividade e tempo de sobrevivência. MÉTODOS: Foram avaliadaos retrospectivamente 57 pacientes (16 mulheres e 41 homens, com idade média de 62 anos) com carcinoma de células escamosas avançado na região esofágica médio-torácica. Estes foram submetidos à colocação do stent metálico auto-expansível Ultraflex™, na Unidade de Endoscopia Gastrointestinal do Hospital de Clínicas da Universidade de São Paulo durante outubro de 1988 a outubro de 2004. De um total de 57 pacientes, 24 receberam terapia citoredutora adjuvante e 33 somente o tratamento através da colocação de stent. RESLTADOS: Após a colocação do stent, houve melhora com relação a displasia em ambos os grupos; não houve diferenças com relação ao índice de complicações, como enxaquecas, dores, fístulas, obstrução e compressão das vias aéreas; o período de efetividade foi significativamente maior no grupo submetido à terapia citoredutora (média de 123 dias comparados à 63 dias), assim como no tempo de sobrevivência (média de 210 dias comparados a 120). CONCLUSÃO: Melhora estatisticamente significante foi encontrada em ambos os grupos com relação à displasia, independentemente se o paciente foi submetido ou não à terapia citoredutora adjuvante; não houve diferenças quanto ao índice de complicações entre os dois grupos e tanto o período de efetividade do tratamento com stent como o tempo de sobrevivência foram maiores no grupo com terapia citoredutora adjuvante