Cancer detection and prevention最新文献

Nuclear grade (NG) was studied in cytologic material obtained from 120 fine-needle aspiration biopsies of breast lesions and compared with the NG observed in the nuclear grade of surgical biopsies of the same lesions. All lesions included were invasive breast carcinomas diagnosed cytologically and confirmed histologically. Cytologic aspirates and tissue sections were graded by cytologists and pathologists, respectively, using a multiheaded microscope. Fisher's modification of Black's NG scheme was used. An agreement was observed between the NG of cytologic material and that of surgical biopsies in 93.33% of tumors, and an interesting exercise would be to correlate the NG with other significant factors for the prognosis of breast carcinomas. The purpose of this study was to assign and correlate the NG of ductal carcinomas of the breast in fine-needle aspiration biopsies and tissue specimens from the same patients.

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.

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.

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.

Some effects of recombinant p14, a protein encoded by the tat gene of immunodeficiency virus type 1 (HIV-1), were investigated on T lymphocytic cell cultures. In particular, we detected p14 adsorption to cells, the rate of cell replication, the expression of fibronectin (FN) and its receptor (FNR) and of cell surface CD4 antigen in HIV-1-infected or uninfected MT-4 and H9 cells, treated with p14. Moreover, we evaluated the proportion of apoptotic cells in uninfected and chronically infected H9 cells in the presence of p14 and the modulation of interferon (IFN) production induced by p14 in PBMC of healthy subjects. The results obtained demonstrate that p14 exerts multifunctional activities on HIV-1 infected and uninfected cells. In particular, this protein interacts in a specific manner with cell surface, especially with that of infected cells, and enhances the expression of FN and FNR but not that of the CD4 lymphocyte antigen. Moreover, p14 increases cell replication, IFN production and can exert a slight modulation of apoptosis. We also propose a model to explain a possible role in HIV-1 infection of the effects of exogenous p14.

Pancreatic cancer (pancreatic ductal carcinoma) is one of the most malignant solid tumors with poor prognosis. There is accumulating evidence that cellular reduction/oxidation (redox) status is deeply involved in the growth promotion and drug resistance of cancer cells. We therefore investigated the expression of redox-regulating proteins, such as thioredoxin (TRX) and glutaredoxin (GRX) in surgically resected pancreatic tissues and cis-diamminedichloroplatinum (CDDP)-resistant cells. Plasma levels of TRX were also measured in subjects with pancreatic diseases. Pancreatic ductal carcinoma tissues were immunohistochemically more positive for TRX (24/32 cases) and GRX (29/32 cases) than pancreatic cystadenocarcinoma or normal pancreas tissues. Plasma levels of TRX (mean +/- SD) measured by ELISA were significantly higher in patients with pancreatic ductal carcinoma (54.8 +/- 37.6 ng/ml, n = 60) than in healthy controls (24.4 +/- 12.9 ng/ml, n = 81). CDDP-resistant subclones of HeLa cells, HeLa-CP5 cells, had higher expression of TRX (1.5 fold) and GRX (1.6 fold) compared with parental HeLa cells by immunoblotting. These results indicate the possible association of TRX and GRX with malignant potential of pancreatic ductal carcinoma.

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.

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.