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。     

Management of soft tissue sarcomas (STS) in first isolated local recurrence: a retrospective study of 83 cases.

PURPOSE: To analyze the management and clinical outcome of patients treated for a first isolated local recurrence of soft tissue sarcomas (trunk or extremities) and to identify prognosis factors. METHODS AND MATERIAL: Between 1980 and 1999, 83 adult patients were included in the study. Mean age was 61 years. Mean tumor size was 6 cm. Most sarcomas were located in extremities (n=74), were deep (n=60), and proximal (n=53); 30 involved nerves or vessels. Histologic subtypes were mainly grade 2 (42%) or 3 (36%) histiocytofibrosarcomas (49%) and liposarcomas (20%). Surgical treatment of recurrences consisted in wide excision (29 cases), marginal resection (43 cases), 5 patients requiring amputation. Final results were R0 (n=33), R1 (n=47) or R2 (n=3) resection. Besides surgery, 6 patients received neo-adjuvant and 7 others adjuvant chemotherapy. Twenty three patients received post-operative external beam radiotherapy (EBRT) (mean dose 55 Gy) and 26 interstitial 192Ir low dose rate brachytherapy (BCT) (mean dose 45 Gy for BCT alone, 22 Gy when associated with EBRT), 19 patients being re-irradiated. RESULTS: Mean follow up was 13 years. Thirty-seven (45%) patients relapsed, 62% of whom presenting an isolated local recurrence. Nineteen patients developed distant metastases. Multivariate analysis showed only tumor depth (P=0.05) and re-resection for primary R1 resection (P=0.018) being independent prognosis factors for tumor control, radiotherapy (EBRT and/or BCT) being significant in univariate analysis (P=0.05). Overall survival rate was 73%, 54%, and 47% at, respectively, 3.5 and 10 years, and was 65%, 35% and 32% after a further local recurrence. Multivariate analysis showed trunk (P=0.0001) or inferior extremity locations (P=0.023), symptomatic (P=0.001), high grade (P=0.01), deep (P=0.01) tumors, and the occurrence of a further local failure (P=0.004) as unfavorable characteristics for overall survival. CONCLUSIONS: A first isolated local recurrence of STS increases mainly the risk of a subsequent local relapse. Quality of local treatment is decisive. When a conservative treatment is feasible, it should combine surgical resection and radiotherapy, BCT being the best suited in previously irradiated patients. Efforts have to be pursued to increase quality of the treatment of primary tumors, at best performed in centers that have expertise in this field.     

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.     

Biomarker investigations from the ATAC trial: the role of TA01

cDNA arrays and proteomic analyses have allowed the rapid identification of specific genes and proteins implicated in multiple tumor types. These molecules must then be validated as clinically relevant prognostic and predictive markers, and this translational research is best conducted in the context of clinical trials. Outcomes data and clinical specimens collected in the ‘Arimidex’, Tamoxifen, Alone or in Combination (ATAC) study, for example, can now be used to compare the expression of biomarkers with clinical outcomes. In this study, adjuvant tamoxifen and anastrozole (‘Arimidex’) were compared alone and in combination in more than 9000 women with breast cancer. Anastrozole was found to be superior to tamoxifen in terms of disease-free survival, time to recurrence, and reduction in the incidence of contralateral tumors. Importantly, tissue specimens from surgical excision, local relapse, and contralateral breast cancer were collected and paraffin-embedded for storage. In the TA01 (TransATAC) program, these specimens will be studied (after obtaining patient consent) using tissue microarrays; tissue biopsy cores 0.6 mm in diameter will be removed from donor blocks and placed on recipient blocks, which will be sectioned to allow the simultaneous analysis of the same samples for multiple biomarkers. These analyses can help determine differential benefits of treatment with anastrozole or tamoxifen, depending on the expression of particular biomarkers in tumor cells. This research also should clarify de novo and acquired resistance mechanisms, and the validation of relevant molecular pathways could guide the development of new drugs. Ultimately, the TA01 program has the potential to favorably impact treatment choices for breast cancer. This revised version was published online in August 2006 with corrections to the Cover Date.