Gene expression patterns and profile changes pre- and post-erlotinib treatment in patients with metastatic breast cancer.

PURPOSE: To delineate gene expression patterns and profile changes in metastatic tumor biopsies at baseline and 1 month after treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib in patients with metastatic breast cancer. EXPERIMENTAL DESIGN: Patients were treated with 150 mg of oral erlotinib daily. Gene expression profiles were measured with Affymetrix U133A GeneChip and immunohistochemistry was used to validate microarray findings. RESULTS: Estrogen receptor (ER) status by immunohistochemistry is nearly coincided with the two major expression clusters determined by expression of genes using unsupervised hierarchical clustering analysis. One of 10 patients had an EGFR-positive tumor detected by both microarray and immunohistochemistry. In this tumor, tissue inhibitor of metalloproteinases-3 and collagen type 1 alpha 2, which are the EGF-down-regulated growth repressors, were significantly increased by erlotinib. Gene changes in EGFR-negative tumors are those of G-protein-linked and cell surface receptor-linked signaling. Gene ontology comparison analysis pretreatment and posttreatment in EGFR-negative tumors revealed biological process categories that have more genes differentially expressed than expected by chance. Among 495 gene ontology categories, the significant differed gene ontology groups include G-protein-coupled receptor protein signaling (34 genes, P = 0.002) and cell surface receptor-linked signal transduction (74 genes, P = 0.007). CONCLUSIONS: ER status reflects the major difference in gene expression pattern in metastatic breast cancer. Erlotinib had effects on genes of EGFR signaling pathway in the EGFR-positive tumor and on gene ontology biological process categories or genes that have function in signal transduction in EGFR-negative tumors.     

多种血管新生指标在肝细胞肝癌中的表达及敏感性比较

目的　探讨血管新生指标CD34、CD31、vWF、Ⅳ型胶原纤维及层粘连蛋白在肝细胞肝癌(HCC)中的表达及意义 ,同时比较上述几种血管新生因子与增殖细胞核抗原 (PCNA)、病理指标及预后的相关性 ,以便筛选出有效的临床预后指标。方法　采用免疫组化方法 ,对 5 3例肝细胞肝癌的标本进行CD31、CD34、vWF、Ⅳ型胶原纤维及层粘连蛋白的染色、计数 ,并用检测数据与患者的临床资料进行统计分析。结果　统计染色的血管面积后发现 ,CD34与多种临床病理指标无相关性 ;CD31与肝内门静脉浸润相关 ;vWF与肿瘤的TNM分期及肝内门静脉浸润呈正相关 ;CollⅣ与肝内门静脉浸润呈正相关、与术后生存期呈负相关 ;Lam与肝硬化及术中出血量呈负相关、与术后生存期呈正相关。PCNA与肿瘤TNM分期有关。结论　在HCC中 ,CollⅣ、vWF、及CD31为肝细胞肝癌的有效血管新生及预后指标 ;Lam则与肝硬化及术中出血相关 ;PCNA指数肿瘤分期有关 ;CD34不能用作血管新生或预后指标     

Reduction of Immunosuppression for Transplant-Associated Skin Cancer: Rationale and Evidence of Efficacy

BACKGROUND: Solid organ transplant recipients may develop numerous or life-threatening skin cancers. In addition to aggressive standard treatment of skin cancer, reduction of immunosuppression has been considered an adjuvant therapeutic strategy, albeit without direct proof of efficacy. OBJECTIVE: To review the rationale for and evidence supporting the efficacy of reduction of immunosuppression for severe skin cancer in transplant recipients. METHODS: Review of the literature regarding direct and indirect evidence on reduction of immunosuppression for transplant-associated skin cancer. RESULTS: Although there are no randomized controlled trials of reduction of immunosuppression as a therapeutic intervention for transplant patients with skin cancer, multiple lines of evidence suggest that this strategy may be an effective adjuvant therapy. A randomized trial has demonstrated a lower incidence of skin cancer in transplant recipients after reduction of immunosuppression, albeit in a cohort not previously affected by skin cancer. Case series of reduction or cessation of immunosuppression demonstrate a lower incidence of skin cancer or improved outcomes of preexisting skin cancer. Lower overall immunosuppression is associated with a lower incidence of skin cancer. Multiple cancers affecting the skin have been shown to regress with reduction of immunosuppression. CONCLUSIONS: Reduction of immunosuppression may be an effective adjuvant therapeutic strategy when confronting severe transplant-associated skin cancer. The risks of reduction of immunosuppression must be better defined, and randomized trials of this strategy are necessary.     

Immunocytochemical identification of outer segment proteins in the rd chicken

Immunoreactivities of two monoclonal antibodies (MAbs) that recognize cone photopigments were tested in the retinas of congenitally blind retinal degenerate (rd) chicks and compared to normally sighted carrier chicks, heterozygous for the mutation. MAb OS-2 had been previously determined to label rod and most cone outer segment membranes in normal chick retinas and is believed to bind to an epitope that is common to several photopigments in chickens. MAb COS-1 labels specifically middle-to-long-wavelength-sensitive cone photopigments in a number of vertebrate species. In rd chicks MAb OS-2 labeled the same number of rod outer segments at the same densities as carrier chicks. However, cone outer segments were less frequently and significantly less heavily labeled with this MAb at all ages tested (1 day, 1 week and 2 weeks post hatching). MAb COS-1 labeled the same number of cone outer segments in both rd and carrier retinas at 1 day of age, however, those outer segments that were labeled in rd specimens had significantly fewer gold particles on them. At both 1 week and 2 weeks of age, rd chick retinas had a significant reduction in numbers of cone outer segments labeled by COS-1. These findings support the hypothesis that the cone photopigment protein is abnormal in the rd chick model of hereditary blindness and retinal degeneration.     

THE PITUITARY-LEYDIG CELL AXIS IN MEN WITH SEVERE DAMAGE TO THE GERMINAL EPITHELIUM

Eighteen men (mean age 27, range 18-30 years) treated for Hodgkin's disease with 6-8 courses of MVPP (Mustine, Vinblastine, Procarbazine and Prednisolone) have had Leydig cell function assessed by their steroidogenic responses to stimulation by a single bolus dose of HCG (1000 units intramuscularly). Normal age-matched men (n = 16) acted as controls. Baseline immunoreactive FSH was markedly raised in the patients (mean 18.1 +/- SD 6.9 vs 2.0 +/- 1.5 IU/l, P less than 0.0001) reflecting damage to the germinal epithelium. Immunoreactive LH was also greater in patients (10.3 +/- 3.9 IU/l) than in controls (3.9 +/- 1.9 IU/l, P less than 0.0001). There were no differences between the baseline testosterone, androstenedione, oestradiol, oestrone and sex hormone binding globulin (SHBG) concentrations. The testosterone/SHBG ratios were similar in the two groups and there was no correlation between baseline LH and testosterone concentrations or testosterone/SHBG ratios. Testosterone, androstenedione, oestradiol and oestrone secretion in response to HCG stimulation were similar at 24 h and 96 h in both groups. In order to explain the paradox of elevated immunoreactive LH in the face of normal testicular steroidogenesis in such patients, LH biological activity (B) as well as LH immunoreactivity (I) and FSH and testosterone were estimated in a second similar group of patients (n = 17, mean age 27, range 17-43 years) and in a further age-matched control group (n = 17). Bioactive and immunoreactive LH levels were significantly increased (P less than 0.005 and P less than 0.001, respectively) in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)