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81.
Evaluation of osteopontin as biomarker for pancreatic adenocarcinoma.   总被引:19,自引:0,他引:19  
OBJECTIVES: Pancreatic adenocarcinoma is a deadly disease with an overall 5-year patient survival of less than 5%. This dismal prognosis of pancreatic cancer is largely due to the advanced stage of the disease at presentation. If pancreatic cancer could be diagnosed more readily and accurately using serum markers, patient survival could theoretically be improved by enabling more patients to avail of surgical resection. One candidate tumor marker recently identified by global gene expression analysis of pancreatic cancer is the secreted glycophosphoprotein osteopontin (OPN). In this study, we evaluate OPN as a serum marker of pancreatic adenocarcinoma. METHODS: In situ hybridization for OPN was performed on a pancreatic adenocarcinoma tissue microarray. Serum OPN levels were determined in preoperative sera from 50 patients with pancreatic cancer and 22 healthy control individuals by competitive ELISA. RESULTS: In situ hybridization for OPN performed on a tissue microarray revealed strong OPN mRNA signal in tumor-infiltrating macrophages in 8 of 14 pancreatic adenocarcinomas. In contrast, OPN expression was not seen in the pancreatic cancer cells themselves, nor was it seen in normal pancreatic tissue or in the macrophages distant from the infiltrating cancer. Serum OPN levels, as measured by ELISA, were elevated in the sera of 50 patients with resectable pancreatic adenocarcinoma compared to 22 healthy control individuals (mean +/- SD for OPN was 482 +/- 170 ng/ml and 204 +/- 65 ng/ml, respectively; P < 0.001). Using a cutoff level of 2 SD above the mean for healthy individuals, elevated OPN had sensitivity of 80% and specificity of 97% for pancreatic cancer. In contrast, only 62% of these patients with resectable pancreatic cancer had elevated CA19-9. CONCLUSIONS: Serum OPN may have utility as a diagnostic marker in patients with pancreatic cancer.  相似文献   
82.
PURPOSE: Docetaxel, a taxane previously approved for the treatment of breast cancer and non-small cell lung cancer, was approved by the United States Food and Drug Administration on May 19, 2004 for use in combination with prednisone for the treatment of metastatic androgen-independent (hormone-refractory) prostate cancer. The purpose of this summary is to review the database supporting this approval. EXPERIMENTAL DESIGN: In a randomized, global study enrolling 1,006 patients, two schedules of docetaxel were compared with mitoxantrone + prednisone as follows: MTZ q 3w, mitoxantrone 12 mg/m2 every 21 days + prednisone 5 mg twice a day for a total of 10 cycles; TXT q 3w, docetaxel 75 mg/m2 every 21 days + prednisone 5 mg twice a day for a total of 10 cycles; and TXT qw, docetaxel 30 mg/m2 days 1, 8, 15, 22, and 29 every 6 weeks + prednisone 5 mg twice a day for a total of 5 cycles. RESULTS: There was a statistically significant overall survival advantage shown for the TXT q 3w arm over MTZ q 3w (median survival 18.9 months versus 16.5 months, P = 0.0094). No overall survival advantage was shown for TXT qw compared with MTZ q 3w. The most commonly occurring adverse events included anemia, neutropenia, infection, nausea, sensory neuropathy, fluid retention, alopecia, nail changes, diarrhea, and fatigue. CONCLUSIONS: This report describes the Food and Drug Administration review supporting this first approval of a combination therapy for hormone-refractory prostate cancer based on demonstration of a survival benefit.  相似文献   
83.
Effects of transforming growth factor beta-1 (TGF-beta1) and all-trans-retinoic acid (All-trans-RA) on development of bulbourethral glands (BUGs) of neonatal mice were investigated in vitro. BUGs from 0-day-old male mice were cultured for 6 days in serum-free, chemically defined medium containing transferrin and bovine serum albumin, supplemented with 5alpha-dihydrotestosterone (DHT; 10-8 M) and insulin (10 microg/mL) alone or in combination. Prior to culture, BUGs from 0-day-old mice consisted of a simple epithelial rudiment encapsulated by mesenchyme. Epithelial growth and ductal branching occurred in BUGs cultured in medium containing DHT and insulin or DHT alone, but epithelial branching did not occur in BUGs cultured in the presence of insulin alone. Addition of TGF-beta1 at concentrations of > 5 ng/mL (0.2 x 10-9 M) to medium containing both insulin and DHT, inhibited the expected increase in overall size of BUGs, epithelial area and ductal branching in a dose-dependent manner. TGF-beta1 also decreased [3H]-thymidine labelling indices of both epithelium and mesenchyme. TGF-beta1 at 10 ng/mL elicited these inhibitory effects on BUGs cultured in medium containing DHT alone. Addition of All-trans-RA (10-8 to 10-6 M) to the medium containing DHT plus insulin, or DHT alone did not exert significant effects on either overall size of BUGs or epithelial growth and ductal branching. All-trans-RA at 10-6 M decreased the [3H]-thymidine labelling index of mesenchyme of BUGs cultured in medium with DHT plus insulin or DHT alone, but did not decrease the [3H]-thymidine labelling index of epithelium. The present results indicate that TGF-beta1 inhibits androgen-induced epithelial and mesenchymal growth as well as epithelial morphogenesis of BUGs from neonatal mice. Such an inhibitory effect of TGF-beta1 is not mimicked by All-trans-RA at physiological concentrations.  相似文献   
84.
Traumatic injuries to the rectum although uncommon can result in virulent complications and even death. Diverting colostomy, presacral drainage, distal wash out and rectal repair, when feasible, have become the standard treatment for rectal injuries. We report an unusual case of rectal injury resulting in anorectal avulsion from skin and surrounding tissues.  相似文献   
85.
Objectives—To assess the level of cycle helmet wearing among young people in two counties in the South East of England in 1994, and to identify the factors associated with helmet wearing.  相似文献   
86.
Inherited susceptibility to ovarian cancer has been associated with germline defects at several loci. The major known ovarian cancer susceptibility gene is BRCA1 on chromosome 17q, which confers a risk of approximately 60% by the age of 70 years. Truncating mutations in BRCA2 on chromosome 13q also predispose to ovarian cancer, although they confer a lower risk than mutations in BRCA1. We have studied the molecular basis of ovarian cancer predisposition in a Finnish family with three affected sisters. Analysis of polymorphic markers provided evidence against linkage to BRCA1, but the sibship was consistent with linkage to BRCA2. Conformation-sensitive gel electrophoresis was used to screen the entire coding sequence of BRCA2. A G to A transition at nucleotide 8702 was observed, which is predicted to convert glycine 2901 to aspartate in the encoded protein. This sequence variant was not detected in 220 cancer-free Finnish control individuals, or in several hundred cancer families of many nationalities previously screened for BRCA2 mutations. Taken together with the fact that this amino acid residue and the surrounding region of BRCA2 is identical in mouse and chicken, the data suggest that this alteration is a disease-causing BRCA2 missense mutation. Previously published data indicate that the risks of breast and ovarian cancer conferred by BRCA2-truncating mutations varies with the position of the mutation in the gene. The missense mutation reported here suggests that the BRCA2 domain including and surrounding glycine 2901 may be more important in preventing neoplastic transformation in ovarian epithelium than in breast epithelium.  相似文献   
87.
This was an institutional study of all maternal deaths that occurred among 56422 total births at the King Faisal University Hospital, Al-Khobar, Saudi Arabia, between 1983 and 2002. The underlying cause of each maternal death and potentially avoidable factors were analysed. There were 16 maternal deaths in the hospital during the study period, giving a maternal mortality rate of 28.4/100,000 births. The leading cause of death was haemorrhage in seven (43.75%) patients, followed by pulmonary embolism in four (25%) and general anaesthesia in two (12.5%) mothers. The risk factors noted were maternal age 35 years and parity 5 coupled with iron deficiency anaemia. The main avoidable factors were failure of the patients to seek timely medical care and to follow medical advice. More than half the number of direct obstetrical causes of death was thought to be preventable. A rapidly changing attitude of women towards childbirth is occurring through progressively increasing female education and community health programmes in the region. Further reduction of maternal mortality rates in the community is envisaged through greater patient acceptance of medical advice, family spacing and proficient obstetric services.  相似文献   
88.
PURPOSE: This article summarizes data submitted to the U.S. Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome. EXPERIMENTAL DESIGN: In one phase 3 controlled trial, 191 study subjects were randomized to treatment with azacitidine or to observation; an additional 120 patients were treated with azacitidine in two phase 2 single arm studies. The primary efficacy end point was the overall response rate, defined as complete or partial normalization of peripheral blood counts and bone marrow blast percentages for at least 4 weeks. RESULTS: In the controlled trial, the overall response rate was 15.7% in the azacitidine treatment group; there were no responders in the observation group (P < 0.0001). Response rates were similar in the two single arm studies. During response patients stopped being red cell or platelet transfusion dependent. Median duration of responses was at least 9 months. An additional 19% of azacitidine-treated patients had less than partial responses, most becoming transfusion independent. The most common adverse events attributed to azacitidine were gastrointestinal, hematologic, local (injection site), and constitutional. There were no azacitidine-related deaths. CONCLUSIONS: On May 19, 2004 the U.S. Food and Drug Administration approved azacitidine as injectable suspension for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Full prescribing information is available at http://www.fda.gov/cder/foi/label/2004/050794lbl.pdf. Azacitidine is the first agent approved for treatment of myelodysplastic syndrome.  相似文献   
89.
The objective of this study was to investigate the prognostic significance of p53, and proliferative cell nuclear antigen (PCNA) in laryngeal squamous cell carcinoma (LSCC). Sixty pathologic specimens from the patients with LSCC were examined for the expression of the p53 and PCNA, with complete follow-up data. Sixty-three percent of the cases displayed nuclear p53 overexpression. There was a correlation between p53 overexpression and histological grades (p = 0.03), and localization site (p = 0.05). Median of PCNA index was 42.2 (range 5.9 to 85.2). There was no difference between the p53 overexpression group and the normal group in proliferative activity determined by PCNA (p = 0.73). In univariate analyses, localization site, grade, stage, invasion pattern, lymph node status, were significant factors in estimating disease free survival (DFS). Grade was the most important factor affecting recurrence (p = 0.002). In multivariate analyses, grade was the only significant predictor for DFS (p = 0.001). Grade (p = 0.001) and invasion pattern (p = 0.03) were found to be significant predictors of overall survival. In conclusion, the histological grade was the most reliable important prognostic factor. Further studies are necessary to facilitate understanding of the mechanisms of laryngeal carcinogenesis.  相似文献   
90.
HLA-G belongs to the nonclassical MHC class Ib group of molecules and has been implicated in mediating immune-responsiveness in various cancerous and non-cancerous cell types. We have examined HLA-G expression in a number of human gastrointestinal malignancies, including pancreatic ductal adenocarcinoma, ampullary cancer, biliary cancer, and colorectal cancer by immunolabeling analysis. We used indices of <5% (negative), 6–25%, 26–50%, 51–75%, and >75% (diffuse) to subclassify lesions based on percentage of positive cell labeling. Across all cancer subtypes, 52–79% of lesions demonstrated expression of HLA-G, with up to 33% of lesions demonstrating diffuse (>75%) expression. In addition, we utilized the neoplastic progression model of colorectal cancer to evaluate HLA-G protein expression in normal colon, tubulovillous adenomas, invasive cancer, and liver metastases arising from colorectal cancer. Focal HLA-G expression was detected in regions of normal colon adjacent to sites of adenomatous and cancerous lesions, as well as in all stages of cancer progression. Overall, the percentage of diffusely (>75%) labeled lesions appeared increased in preneoplastic and neoplastic conditions, as compared to normal colon. Specifically, tubulovillous adnenomas demonstrated pronounced diffuse labeling in 58% of lesions examined. No correlation with HLA-G expression and CD4+ or CD8+ T cells was identified. We propose that HLA-G expression is upregulated in a large percentage of gastrointestinal lesions and may serve to mediate immuneresponsiveness in certain instances.  相似文献   
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