Epidermal growth factor receptor tyrosine kinase inhibitor does not improve paclitaxel effect in an orthotopic mouse model of lung cancer.

PURPOSE: The purpose is to evaluate whether inhibition of epidermal growth factor receptor (EGFR) activation by PKI166, an EGFR-tyrosine kinase inhibitor, affects growth of human lung cancer implanted orthotopically into the lungs of nude mice. EXPERIMENTAL DESIGN: Lungs of mice were injected with NCI-H358 human bronchioloalveolar cancer cells. In three experiments, groups of mice (n = 10 per group) were randomized 7 days after tumor implantation to receive one of the following treatments: i.p. paclitaxel 100 or 200 microg (4 or 8 mg/kg) once per week, oral PKI166 100 or 200 mg/kg three times per week, paclitaxel plus PKI166, or i.p. saline and oral PKI166-vehicle (control) for 5 weeks. Mice were killed 6.5 to 8 weeks after tumor implantation. The experiments were repeated with PC14PE6 human lung adenocarcinoma cells to assess effect on survival. RESULTS: Immunohistochemical analyses revealed the expression and phosphorylation of EGFR in the growing tumors. Treatment with PKI166 alone or in combination with paclitaxel diminished activation of EGFR on tumor cells, yet maximal therapeutic effect was observed in mice treated with paclitaxel alone. Activated mitogen-activated protein kinase and basic fibroblast growth factor expression were similar in all treatment groups. Survival in mice treated with the combination of paclitaxel and PKI166 was shorter than in those treated with paclitaxel alone. CONCLUSIONS: Our results suggest that concurrent administration of EGFR-tyrosine kinase inhibitor and chemotherapy is equivalent and may indeed be inferior to chemotherapy alone, even if EGFR is functional and its phosphorylation effectively inhibited. Our data show that the interaction of EGFR-TKIs and chemotherapy is complex and suggest that other growth factors may activate the downstream signaling events.     

卵巢癌高频转移细胞模型中nm23-H1基因表达的相关性研究

目的 筛选高频转移卵巢恶性肿瘤细胞，研究不同转移潜能的细胞和nm23的相关性。方法 通过反复动物接种和体外培养，观察动物肺转移状况，筛选高频转移细胞株，比较原发肿瘤和转移肿瘤的特征，并应用Northera-blot方法测定各类肿瘤细胞nm23 mRNA表达水平。结果 8株卵巢恶性肿瘤细胞中4株有较高转移潜能。多次培养接种可筛选出高频转移细胞亚群。测定各类细胞nm23 mRNA表达水平与肿瘤转移特性呈负相关。结论 由基因分子水平决定的肿瘤转移趋势在不同肿瘤种类及细胞亚群中有明显差异；卵巢癌中nm23 mRNA和蛋白的表达与其转移能力的降低有密切关系，可作为判定卵巢癌预后的敏感指标。     

人前列腺癌细胞PC-3M亚系u-PAR基因表达的分析

目的 为研究与人前列腺癌细胞(PC-3M)侵袭能力相关的靶分子。方法 采用有限稀释法分离单克隆细胞株，并应用单层细胞侵袭等实验鉴定各亚系的体外侵袭能力；借助RT-PCR和免疫组化的方法，分别在转录和翻译水平检测5株侵袭能力不同的PC-3M亚系尿激酶型纤溶酶原激活物受体(u-PAR)的表达。结果 高侵袭亚系u-PAR基因mRNA的表达和蛋白质水平均明显高于低侵袭亚系。结论 PC-3M亚系u-PAR的高表达与其较强的侵袭能力密切相关，而u-PAR可能是抑制高侵袭亚系侵袭效应的一个重要靶分子。     

Continuous care in the cancer patient: palliative care in the 21<Superscript>st</Superscript> century

Continuous care for the cancer patient is an open concept that is not only applicable only to the terminal stage. Such a simplification could generate inequities of therapy and discrimination. Historically, oncology services have been structured as networks dispensing chemotherapy and radiotherapy rather than services dedicated to the integrated care of the cancer patient. This situation has changed in a continuous and progressive manner over the past few years, as reflected in the latest Spanish Libro Blanco de Oncología. We are still far from reaching the optimum level of integrated care, possibly because we have not, as yet, achieved services that are structured and appropriate for the care-needs of the patient and, perhaps, to the lack of the necessary personnel. We must always make sure that cancer patients receive the best possible treatment, irrespective of whet-her the disease is in relapse. Oncologists must not “give up”, indicating that, in addition to using the most effective anticancer treatments available, they should deploy their best knowledge and experience to control the symptoms of cancer while providing psycho-social help to the patient and family. This is best conducted with a communication that is adjusted to the changing needs of the patient over the longterm clinical process, and should be provided by a multidisciplinary team, according to the needs of the patient and the family. Within a program of integrated care, it is possible to coordinate the existing care structures without creating parallel health networks so as to cover the needs of the greatest number of cancer patients in advanced stage of the disease.     

Nuclear Pedigree Criteria for the Identification of Individuals Suspected to Be at Risk of an Inherited Predisposition to Gastric Cancer

Gastric cancer is the second most frequently diagnosed malignancy worldwide and therefore represents a significant healthcare burden. Environmental and genetic factors are involved in the development of gastric cancer. To date only one clear genetic predisposition has been identified involving mutations in the E-cadherin gene. The disease phenotype in patients harbouring E-cadherin mutations appears to be specifically related to diffuse gastric cancer. Little is known genetically about the other forms of gastric cancer. Since there is a growing awareness about the necessity of early intervention criteria have been developed that aid the identification of hereditary forms of gastric cancer. The aim of the current study was to identify minimal inclusion criteria so that nuclear pedigree families can be provided with risk assessment and/or genetic testing.The results reveal that inclusion features described herein such as (a) gastric cancer diagnosed before 46 years of age; (b) two gastric cancers among first degree relatives diagnosed over the age of 50 are useful in identifying suspected hereditary gastric cancer patients.