Cancer detection and prevention最新文献

Based on a theory of behavior, the interaction of a motivational message and external barriers on mammography utilization was tested. Participants (N = 101) had not had mammograms annually, and were identified from an urban clinic serving a disproportionally high percentage of indigent clients. Fifty-five percent were Caucasian; 45% were African-American. In an experimental design, half of the sample received a telephone discussion about rationale, feelings, and beliefs regarding mammograms, and half did not receive this contact. Four months later, nurses assessed women's recent mammography utilization and external barriers (e.g., affordability and accessibility). A logistic regression revealed an interaction between the intervention and barriers on postintervention mammography utilization (odds ratio: 2.12; p < 0.05). As proposed, the intervention was associated with a 64% rate of mammography utilization among women without barriers, but only a 26% rate among women with barriers. Not only should clinicians offer motivational messages about mammography, but also administrators should address external barriers to maximize mammography among socioeconomically disadvantaged groups.

The objective of the present study was to examine the effects of the well-known tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on the morphology of cultured Sertoli cells from immature rats. The cells were cultured for 5 days and the TPA was added at the end of the culture period for 8 h at a concentration of 10-7 M. Viability tests showed that controls as well as TPA-treated cells remained viable during the culture period and no deleterious effects were observed as a result. Application of computerized morphometry at both light and electron microscopic levels revealed that TPA caused important changes in cell morphology in vitro. Statistical analysis of the results indicated that compared to the controls, Sertoli cells treated with TPA exhibited fewer astrocytic-type cytoplasmic extensions and a smaller size. Our results support the conclusion that the tumor promoter TPA, when applied to immature Sertoli cells in vitro, causes significant morphological alterations.

Tumor necrosis factor (TNF-alpha) has a cytotoxic or cytostatic effect when tested with various malignant cell lines. Clinical trials in cancer patients, however, revealed high systemic toxicity of TNF-alpha. The existence of two types of receptor may partially explain the pleiotropic activity of TNF-alpha. The purpose of this study was to characterize the relative cytotoxic activity of TNF-alpha and TNF mutants on the mouse fibrosarcoma L929 cells in a standard cytotoxicity test, on human larynx carcinoma HEp-2 cells, and on human monoblastoid leukemic cells U937. TNF mutants were obtained by site-directed mutagenesis. The purity of TNF-alpha was established by capillary electrophoresis. TNF-alpha and TNF mutants were analysed by Western blot analysis using monoclonal antibodies against TNF-alpha. The results show that TNF mutants can recognize the different TNF-receptors (TNF-R) selectivity. It is generally believed that activation of TNF-R75 is responsible for the systemic toxicity of TNF-alpha. Hence, the development of TNF mutants, binding selectively to TNF-R55, could lead to new option for an anticancer treatment that would be devoid of the deleterious effect of TNF-alpha.

Flow cytometric DNA ploidy analysis for human bladder cancers may provide significant diagnostic and prognostic potential. We have previously reported that combined use of histologic and flow cytometric parameters may offer additional information regarding the clinical outcome for bladder cancer patients. However, the evaluation included both superficial and muscle-invasive tumors. In the present manuscript, we present our study on whether flow cytometric determination yields significant prognosticators beyond the classical histologic evaluation only in the patient with superficial bladder cancer. A total of 217 patients with untreated bladder cancer were evaluated, using fresh bladder tumor specimens. Tumor grading (grade 1, 2, and 3) and stage (pTa + pT1a and pT1b) served as the histologic prognostic parameters. Multiple flow cytometric parameters assessed included DNA index, percentage S-phase cells, percentage G2/M-phase cells, and hypertetraploid cell presence. Multivariate survival analysis was performed using the SAS proportional hazard regression procedure to study statistical individual prognostic values of both the histologic and the flow cytometric parameters. Clinical follow-up of more than 60 months was required, with the mean follow-up being 116.3 +/- 18.6 months. Hypertetraploid cell presence was the single most important prognostic factor (p < 0.01; risk ratio: 14.3), with the second being tumor grade (p < 0.05; risk ratio: 4.6). No other parameters, including tumor stage, the DNA index, and cell phase fractions, contributed to the model. These results indicate that hypertetraploid cell presence found by flow cytometric determination may provide additional information regarding the clinical outcome for superficial bladder cancer patients, and can be used as an indicator for decision making in treatment of superficial bladder cancer patients.

The etiology of the Carney's triad (gastrointestinal stromal tumors, pulmonary chondromas, and paragangliomas) is unknown, and only 57 cases have been reported since its identification in 1977. We report the clinical course of a female with the complete triad and some additional tumors. Bilateral vagal paragangliomas were treated surgically and with radiotherapy between the ages of 24 and 26 years. Subsequently she underwent surgery for a gastric leiomyosarcoma (27 years), a pleomorphic adenoma of the parotid gland (49 years) and a multifocal breast cancer with axillary spread (50 years). A calcified lesion was also noticed in the left lung, the radiologic diagnosis of which was consistent with chondroma. A mediastinal paraganglioma, detected at 56 years on a control X-ray of the chest, was partially excised at 63 years. At the last control, performed at 66 years, the patient was alive with residual cervical and mediastinal paraganglioma. Her younger brother was affected by Hirschsprung's disease and died at 54 years of rectal cancer. Her daughter is 33 and has been suffering since birth with severe constipation. In conclusion, this is one of the longest followed-up patients with Carney's triad. Her case illustrates the need for early recognition of the setting in order to detect the component tumors at a stage when surgery may be curative, and careful and life-long follow-up, both because the multicentricity of the classic components tends to manifest metachronously and because of the tendency to develop other tumors, some of which may be malignant. Furthermore, the presence of Hirschsprung's disease in the patient's family, coupled with the alleged common origin of two component lesions from derivatives of the neural crest, open new avenues for the understanding of this disorder.

Gastric adenomas are often detected in the stomach resected for gastric cancer. Previous investigation have revealed that the prevalence of their malignant transformation is generally low, but the frequent coexistence with carcinoma suggests that they may share some common processes with gastric cancer in tumorigenesis. In contrast to the cumulative information about genetic alterations in gastric cancer, inquiries into the genetic changes of adenoma and coexisting carcinoma in the same individual's stomach are still few. We investigated microsatellite instability (MSI) and K-ras point mutations in codons 12 and 13 in 50 lesions of gastric adenomas in 43 cases, and 31 lesions of gastric cancers that coexisted with these adenomas. In gastric adenomas, we found seven lesions (14.0%) to have microsatellite instability (MSI) at one or more loci, and most of them (six cases) had MSI at only one locus and were not associated with alterations in presumable target molecules. MSI was detected more frequently (11/31, 35.5%) and more extensively (five lesions at multiple loci) in accompanying gastric carcinomas. The prevalence of MSI in adenomas was more frequently found in those with synchronous gastric cancer (6/37, 16.2%, vs. 1/13, 7.6%) than without, and gastric adenoma accompanied by gastric cancer with multiple MSI tended to have MSI more frequently than that accompanied by cancer without MSI (4/5, 80%, vs. 1/24, 4.2%; p = 0. 01). In at least some individuals, MSI appears to represent one step in the pathway of gastric tumorigenesis, shared by adenoma and carcinoma. We found K-ras gene alteration in 8 lesions (16.0%) out of 50 gastric flat adenomas and no difference in its prevalence between adenoma with or without cancer. Only one gastric cancer, which had adenoma without K-ras mutation, had K-ras codon 12 mutation. Adenomas with a higher grade of atypia (p < 0.05) more frequently carried K-ras point mutation, which is consistent with the situation in colorectal adenoma. We conclude that MSI, not K-ras mutation, is a shared genetic alteration in adenoma and carcinoma of the individual stomach.

The treatment of prostate carcinoma is dependent on the stage of the disease. Patients who present with clinically localized cancer or locally advanced tumors can be potentially cured by radical prostatectomy, radiation, and hormonal therapy. However, disease progression can occur in 30-50% of patients diagnosed with clinically localized cancer. The bone is the predominant site of metastases. Metastatic prostate cancer is first treated by androgen blockade but within a few months becomes hormone refractory. Hormone refractory metastatic prostate cancer is not responsive to conventional treatments, and patients have an expected survival of less than a year. It is essential to develop new approaches for the treatment of hormone refractory metastatic disease. Immunotherapy, based on enhancement of the host immune response against the tumor, has been used as an alternative therapy for the treatment of metastatic cancers refractory to conventional therapy in particular for melanoma and renal cell carcinoma. In this review, we will summarize various immunotherapeutic approaches developed over the last 18 years, and we will address the potential of immunotherapy for the treatment of metastatic prostate carcinoma by reviewing preclinical studies and initial clinical trials performed in this field.

The purpose of this study was to determine the degree to which colon cancer treatment in rural North and South Carolina in 1991 and 1996 conformed to national treatment recommendations. Data came from medical records of colon cancer patients residing in rural North and South Carolina. The National Cancer Institute's Physician Data Query (PDQ) database was used to define state-of-the-art care and to categorize receipt of primary and/or adjuvant treatment. Changes in treatment over time, location, and stage and bivariate relationships between treatment and selected covariates were assessed with chi-square and Fisher's exact tests. Regression was used to control for possible interactions between patient and/or disease characteristics and treatment. The majority of colon cancer cases received primary therapy as suggested by the PDQ which was not significantly related to other factors examined. There was variation in provision of adjuvant therapy. Stage III patients received adjuvant therapy significantly more often than did stage II patients (p

Increased expression and elevated serum levels of tumor necrosis factor-alpha (TNF-alpha) have been shown to be associated with the presence of constitutional B symptoms and poor prognosis in non-Hodgkin's lymphoma (NHL) patients. Soluble TNF receptors (sTNF-R) are suggested to act as biological buffers in inflammatory conditions by binding and inactivating increased circulating TNF. Whereas studies have shown elevated TNF to be correlated with B symptoms, similar studies showing the status of soluble receptor release in these patients have not been conducted. Here, we show that there is increased soluble p75 TNF receptor release from peripheral blood mononuclear cells (PBMNC) in NHL patients in the early stages of the disease but it is severely depressed in patients with advanced disease. Decreased release is associated with presence of B symptoms in these patients. All NHL patients also show increased TNF secretion and a decreased rate of receptor release with time compared with healthy controls. These findings imply that decreased sTNF-R receptor release, in addition to increased TNF secretion, is also important in predisposing the patients to B symptoms. This opens up the possibility of the use of sTNF-Rs as a therapeutic tool to counter increased TNF and alleviate systemic symptoms in these patients and also as a marker for the progression of the disease.

Mer+ HeLa S3 tumor cells with high levels of O6-methylguanine-DNA methyltransferase (MGMT) gene expression were transduced by retroviral-mediated MGMT antisense RNA. The MGMT mRNA, MGMT protein, and MGMT activity in transduced cells were only 28.7%, 32.7%, and 39. 1% of that in HeLa S3 cells, respectively. The transduced cells showed more sensitive to ACNU than HeLa S3 cells both in cell survival and in nude mice experiments. Pathologic examination confirmed that transduced grafts were killed by ACNU. Our results suggested that MGMT gene expression could be modulated by retroviral-mediated antisense RNA and that Mer+ tumor drug resistance to ACNU could be reversed by modulation of MGMT gene expression.