Cancer detection and prevention最新文献

The distribution of altered G-actin was investigated in prostatic cells obtained by fine needle aspiration (FNA) from 27 excised prostate glands obtained during radical prostatectomy. FNA, which was used to obtain single cells for image analysis, sampled in the region of any nodules and in grossly normal areas of the contralateral lobes. Quantitative fluorescence-image analysis was used to assay the amount of G-actin in individual cells. Abnormal G-actin, a precursor cytoskeletal protein representing cytoskeletal rearrangements accompanying cellular transformation, was associated with the presence of adenocarcinoma in 22 of 27 specimens from the dominant nodule, but only 3 of 20 in the grossly normal specimens (P<.0001). The mean G-actin content of all samples from the dominant nodule was 113.2+/-6.87 and 69.57+/-4.47 from the grossly normal area, the difference being significant at P<.0001. Altered G-actin was not associated with Gleason score (P = .95), grade (P = .26), stage (P = .058), or tumor volume (P = .32), thereby indicating it is a general marker for prostate adenocarcinoma.

The objective of this study was to determine cancer-related knowledge and attitudes among American Samoans, a population seldom studied by cancer researchers. Such information is necessary to develop culturally sensitive cancer control interventions. Specially trained personnel conducted face-to-face interviews with randomly selected respondents in the US Territory of American Samoa; Oahu, HI; and Los Angeles, CA, using a survey based on the National Health Interview Survey Cancer Control Supplement and focus group findings. The survey included questions concerning knowledge of risk factors for cancers (breast, cervical, colon, lung, stomach, and prostate), family resources (health insurance coverage, employment status, and family income), and demographic characteristics. Participants could complete the survey in English or Samoan. Analysis of data included the chi-squared test and logistic regression analysis. Participants included 1,834 noninstitutionalized English- or Samoan-speaking women and men (609 from American Samoa, 610 from Hawaii, and 615 from Los Angeles). The majority of residents had some positive attitudes about cancer prevention and treatment but often also had misconceptions about risk factors for cancer. Logistic regression analysis revealed that site of residence was an important predictor of attitudes. For example, being residents of American Samoa or Hawaii predicted that the respondents would rather not know that they had cancer (odds ratio [OR], 1.5, 2.1, respectively); that cancer can be caused by aitu, or spirits (OR, 1.9, 2.1, respectively); that cancer is a punishment from God (OR, 2.0, 2.2, respectively); and that cancer can be cured by fofo, or traditional Samoan healers (OR, 2.0, 3. 1, respectively). This study documented cancer-related knowledge and attitudes among American Samoans and set the stage for culturally sensitive interventions aimed at improving cancer control in this population. It also identified many issues that should be addressed in such interventions.

Fenretinide is a vitamin A derivative under investigation in cancer prevention trials. Because all available pharmacologic and toxicologic data were obtained from breast cancer patients, we measured plasma drug, metabolite, and vitamin A levels and studied their relationship with visual and ocular symptoms in a cohort formed mostly by male subjects belonging to a bladder cancer prevention trial. After 1 year, the mean plasma retinol levels (+/- standard deviation [SD]) were 168.2 +/- 75.8 ng/ml in 31 subjects treated with fenretinide and 594.5 +/- 168.4 ng/ml in 36 control subjects (P < .001). Plasma retinol levels were correlated inversely to drug and metabolite concentrations, which in turn were correlated inversely to the interval from last drug intake. The decline of plasma vitamin A levels accounted for a 41.7% cumulative incidence of diminished dark adaptability in the retinoid arm as compared to 6.8% in the control arm (odds ratio = 13.8; 95% confidence interval, 2.9-66.1). Although compliance as assessed by capsule count was high, three subjects originally assigned to the treatment group who proved to be noncompliers (8.8%, or 3 of 34) had no detectable plasma drug or metabolite levels. Our data confirm the specific pharmacologic and visual effects of fenretinide also in a male population and strengthen the importance of multiple blood measurements to monitor treatment compliance in prevention trials.

Poor survival in patients following resection for early stage colorectal cancer is thought to be due in part to the presence of occult micrometastases at the time of surgery. The MUC2 mucin gene is highly expressed in the colon and associated colorectal tumors and may be a candidate marker for colorectal cancer micrometastases. We have used RT-PCR to detect expression of MUC2 mRNA transcripts in order to identify possible lymph node micrometastases in node negative (Stage I and II, or Dukes A and B) colorectal cancer patients. A total of 396 nodes (histologic stage N0) from 34 colon and nine rectal cancers were studied by RT-PCR analysis with nested primers for MUC2 (an average of 7.6 nodes per case). In the primary tumors, 42/43 (98.1%) were positive for MUC2 by RT-PCR. Evidence of the presence of MUC2 was demonstrated in nodes from 0 of 10 (0%) patients with Tis or T1, one of six (16.7%) from T2, 10 of 25 (40.0%) from T3, and one of two (50%) from T4 tumors. MUC2 RT-PCR was negative in six nodes from three patients with non-malignant colon disease and positive in histologically positive lymph nodes from six of six (100%) stage III colon cancers. In this study, using RT-PCR to detect the presence of MUC2 transcripts, we have found preliminary evidence for possible micrometastatic disease in approximately a third of histologically negative N0 colorectal cancer patients. The increased presence of MUC2 expression also correlated with more advanced T stage. We conclude that MUC2 RT-PCR may be a sensitive and specific marker for occult micrometastases. This technique has the potential to identify a group of colorectal cancer patients at risk for early cancer recurrence.

Some patients with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome develop carcinoma despite surveillance. The aim of this study was to determine whether survival was greater in colorectal cancer (CRC) cases detected by surveillance than in patients who had disease diagnosed on the basis of symptoms. All 150 CRC cases detected in 57 HNPCC families over the last 15 years were divided into two groups depending on whether they had been included in the surveillance program (n = 35) or not (n = 115). The stage distribution of the tumors in the group that underwent surveillance (Dukes' A, 50%; B, 35%; C, 15%; D, 0%) was significantly more favorable (P < .001) than in the group without surveillance (Dukes' A, 17%; B, 50%; C, 16%; D, 17%). CRC-specific 10-year survival was 93% in the surveillance group, significantly better than the 68% in the nonsurveillance group (P < .02). The overall survival did not differ significantly between the two groups despite a tendency in favor of the surveillance group. Colonoscopic surveillance enables early detection of CRC in HNPCC and reduces CRC mortality.

To place the choice of therapy (endoscopic resection or radical surgery) in early invasive carcinoma (EIC) of colon and rectum on a more rational basis, this study sought to identify molecular predictors of metastasis. Several morphologic risk factors (histologic type, degree of tumor invasion, lymphatic and venous invasion) and expression of p53 and p27 proteins in the primary tumor were compared in 80 patients with EIC, including 12 (15%) with metastasis or recurrence (or both). Of the factors enumerated, deeper invasion of the submucosal layer, lymphatic-venous invasion, p53 overexpression, and decreased expression of p27 were correlated significantly with metastasis. The results also indicated that altered expression of p53 or p27 is independently relevant to metastasis of EIC. Analysis of these markers, together with determination of the morphologic risk factors, could complement the identification of patients with metastasis on the basis of known morphologic risk factors. Because the molecular factors can be assessed more objectively than can the morphologic parameters, they may strengthen the ability to identify EIC that has undergone, or will undergo, metastasis.

The purpose of this study was to examine whether tumor DNA content correlated with prognosis in nasopharyngeal carcinoma (NPC). DNA flow-cytometric analysis in fresh specimens of nasopharyngeal biopsy from 123 patients with clinical suspicion of NPC was collected initially. Histopathologic study and successful flow-cytometric analysis had 28 lymphoid hyperplasias and 87 NPCs. Seventeen NPC patients were treated elsewhere and were excluded. A total of 98 patients, including 28 lymphoid hyperplasias and 70 NPCs, formed the materials of this study. There were 34 (49%) diploid and 36 (51%) aneuploid in NPC patients. No lymphoid hyperplasias were aneuploid. The mean of S-phase fraction was higher in NPC than in lymphoid hyperplasia (P < .001), indicating higher cellular activity in NPC. DNA content failed to associate with age, gender, pathology, distant metastasis, and stage, indicating that DNA content was an independent prognostic indicator and possibly a clinical parameter. The log-rank test of overall survival curves was significant for stage (P = .002) and DNA ploidy (P = .042); it was almost significant for S-phase fraction (P = .057). Because the follow-up duration was not long enough, univariate and multivariate analysis were not significant for stage, ploidy, and S-phase fraction, except for distant metastasis. It is also most likely colinearity of clinical stage and distant metastasis that explained why clinical stage could not show significance in prognosis. Interestingly, the DNA content appeared to be a potential prognostic parameter in overall survival, although it was not statistically significant (P = .052). Our data suggested that NPC patients with aneuploid DNA and high S-phase fraction tend to have poor prognosis and should be treated more aggressively, even in the early stage of the disease.

Formalin-fixed, paraffin-embedded tumor specimens from 64 human meningiomas of various histologic types were immunostained using a streptavidin-peroxidase method and monoclonal antibodies for estrogen receptors (ER) and progesterone receptors (PgR) and hormone-induced proteins PS2 and heat shock protein 27 (Hsp27). The immunohistochemical analysis was scored in a semiquantitative fashion incorporating both the intensity and distribution of specific staining (score). Strong PgR nuclear immunoreactivity (mean score, 54.2) was observed in 51 of 64 meningiomas (80%). Meningiomas with atypical features were negative for PgR. Low Hsp27 cytoplasmic immunoreactivity (mean score, 9.8)--irrespective of histologic type--was observed in 26 of 64 meningiomas (40%). Whor1 formations in transitional meningiomas were Hsp27-positive. Hsp27 immunoreactivity was observed in tumor blood vessels. All neoplasms were negative for ER and PS2. Normal arachnoid tissue was positive for PgR and negative for ER, PS2, and Hsp27. Compared with previously reported data on gliomas, the results of this study indicate that meningiomas show a clear out difference concerning the expression of PgR and Hsp27.

Cervical intraepithelial neoplasia (CIN) is common in patients positive for human immunodeficiency virus (HIV). The questions are whether the management of CIN in these patients should be different from that of HIV-negative women, whether there are any prognostic factors to indicate the course of CIN, and whether the latter is influenced by antiretroviral therapy. A total of 267 HIV-seropositive women were counseled and examined in our colposcopic clinic. Of that number, 53 patients died during the observation period; 74% of these patients were immunosuppressed (CD4 count < 200 cells/mm3), and 45% were given diagnoses of CIN. The incidence of CIN was significantly higher in patients with CD4 less than 200 cells/mm3. Neither the route of HIV infection nor the HPV status nor smoking habits correlated with CIN. CIN relapse was histologically confirmed in 28% of patients who underwent complete surgical removal. Immune status plays an important role in HIV-positive women not only with respect to survival but with respect to CIN.

We developed a real-time one-step reverse transcriptase-polymerase chain reaction (RT-PCR) method for the routine quantification of c-erbB-2 oncogene expression in breast cancer, using a 7700 ABI PRISM Sequence Detector System (Perkin Elmer-Applied Biosystems, Courtaboeuf, France). The real-time quantification of the polymerase chain reaction products is based on the TaqMan 5' nuclease assay. The optimal experimental conditions we determined were as follows: 6 mM MgCl2, 200 nM of fluorogenic probe, 200 nM of each primer, and 12.5 units MuLV reverse transcriptase. The GAPDH housekeeping gene was used for normalization of c-erbB-2 expression. In human breast cancer cell lines, the normalized expression of c-erbB-2 ranged from 8 x 10(-6) to 2,600 x 10(-6), the two highest values corresponding to the c-erbB-2 overexpressing cells MDA-MB-453 and SK-BR-3. In a series of 100 breast cancer samples, c-erbB-2 normalized expression was found to range from 0.4 x 10(-6) to 350 x 10(-6). A close correlation was observed between this real-time one-step quantitative RT-PCR method and both semiquantitative conventional RT-PCR (N = 22; r = 0.8543; P < .0001) and c-erbB-2 protein expression (p185) quantified by an enzyme immunoassay (EIA) (N = 27; r = 0.71; P < .0001). The current realtime RT-PCR assay is rapid, sensitive, and reproducible and appears particularly suitable to quantify gene expression in large series of samples.