Cancer detection and prevention最新文献

Androstene-3beta, 17alpha-diol (17alpha-AED) inhibits DNA synthesis and induces apoptosis in several myeloid cancer cell lines. The purpose of this study was to determine if 17alpha-AED inhibition of human breast carcinoma cell proliferation is dependent on the estrogen or androgen receptor. At concentrations of 12.5 to 50 x 10(-9) M 17alpha-AED inhibited the proliferation of ZR75-1, estrogen receptor-positive (ER+) cells, by 54% to 68%. Further, 17alpha-AED inhibited MDA-MB231, estrogen receptor-negative (ER-) cells, by 33.6% to 56.0%. The inhibitory effect was dose dependent with a minimal effective inhibitory dose at 12.5x10(-9) M for both cell lines. Both 17beta-AED and estradiol potentiate the inhibitory effect of 17alpha-AED on ER+ cells at lower doses (3.13 to 6.25 x 10(-9) M) where 17alpha-AED alone was not inhibitory. The inhibitory action of 17alpha-AED on human mammary carcinomas appears to be independent of either the alpha estrogen or the androgen receptors.

The purpose of this study was to determine whether prostate cancer mortality conforms to gompertzian analysis and, if so, what conclusions can be made regarding increasing prostate cancer mortality in Japan by the application of longitudinal gompertzian analysis. Data regarding 77,492 prostate cancer deaths reported during the period 1955 to 1996 were obtained from death certificate records in Japan. Age-adjusted prostate cancer mortality rates increased 6.4-fold during that period. The changing patterns in the mortality rate was explained by a constantly increasing number of elderly people. Age-specific mortality rate distributions between the ages of 50 and 84 years were highly gompertzian for each year during that period. The environmental factor for prostate cancer mortality increased 80% for that period. Gompertzian analysis suggests that rising mortality from prostate cancer may be related to rapidly changing lifestyles among Japanese. Intake of animal proteins was the most strongly correlated parameter considered with the mortality from prostate cancer.

Mitogenic and growth-inhibitory signals influence cell-cycle progression through their action on a family of cyclin-dependent kinases (cdks). The activity of cdk complexes is regulated in part by the association of a cyclin partner that acts as a positive effector and by two families of cdk inhibitors, the kinase inhibitor proteins (KIP) and the inhibitors of cdk4 (INK4), which act as negative effectors. In human malignancies, increased expression of cyclins is frequently observed. Cyclin D1 and E are frequently overexpressed in breast cancers, and cyclin E overexpression has been correlated with a poor prognostic outcome. The abrogated expression or the acquisition of mutations that render cdk inhibitors functionally inactive have similarly been found in human malignancies. The p16 gene is frequently deleted or mutated in cancers. Although normal epithelial cells express high levels of p27 protein, reduced levels of p27 have been observed in several human cancers, and this has been consistently correlated with a poor prognostic outcome. In this review, we will provide a brief overview of the cell cycle regulators and then discuss their deregulation in cancers.

The aim of this study was to examine the prognostic value of the alpha-L-fucosidase enzyme to determine whether it can help in the early recognition of colorectal cancer cases at high risk of tumor recurrence. One hundred and twenty-three colorectal carcinoma patients treated by curative surgery were studied. The alpha-L-fucosidase activity was assayed in the tumor and in normal mucosa from each patient using a fluorometric method. Seven other clinical and pathologic features were also studied. To evaluate the impact of each variable over the disease-free interval, a postoperative 30-month follow-up of patients was performed, and a statistical survival analysis was carried out. The recurrence appearance was higher when the relative decrease of alpha-L-fucosidase activity was more than 52% (log-rank test, P = .0261). The results of this work indicate that alpha-L-fucosidase activity appears to be a good independent prognostic factor of tumoral recurrence in colorectal carcinoma.

Recently, we presented evidence for the role of MGN-3, an enzymatically modified arabinoxylan extracted from rice bran, in potent activation of human natural killer (NK) cell function in vivo and in vitro. In the current study, we examined the mechanism by which MGN-3 elevated NK cytotoxic activity. We did this by testing the action of MGN-3 on the levels of both tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) secretions and MGN-3 function on the expression of key cell surface receptors. Peripheral blood lymphocytes were treated with MGN-3 at concentrations of 0.1 mg/ml and 1 mg/ml, and supernatants were subjected to enzyme-linked immunosorbent assay. Results showed that MGN-3 is a potent TNF-alpha inducer. The effect was dose-dependent. MGN-3 concentration at 0.1 and 1 mg/ml increased TNF-alpha production by 22.8- and 47. 1-fold, respectively. MGN-3 also increased production of IFN-gamma but at lower levels as compared to TNF-alpha With respect to key cell surface receptors, MGN-3 increases the expression of CD69, an early activation antigen at 16 hours after treatment. Furthermore, the interleukin-2 receptor CD25 and the adhesion molecule ICAM-1 (CD54) were upregulated after treatment with MGN-3. Treating highly purified NK cells with MGN-3 also resulted in increased levels of TNF-alpha and IFN-gamma secretion in conjunction with augmentation of NK cell cytotoxic function. Furthermore, addition of MGN-3 to interleukin-2-activated NK cells resulted in a synergistic induction of TNF-alpha and IFN-gamma secretion. Overall, our data suggest that MGN-3, a novel biological response modifier, can be used as a safe alternative or as an adjuvant to the existing immunotherapeutic modalities.

We investigated biosynthesis of Vicia graminea lectin (VGA)- and Vicia unijuga lectin (VUA)-binding (Vgu) glycoproteins, which are human malignant tumor-associated antigens, in cultured human tumor and non-tumor cells by pulse-labeling experiments with [35S]-methionine, followed by immunoprecipitation using immobilized VUA, SDS-PAGE and autofluorography. It was shown that Vgu glycoproteins synthesized by tumor cells were 15-30 times greater than those of non-tumor cells. It was also shown that about 40-70% of Vgu glycoproteins synthesized by non-tumor cells were secreted from the cells while more than 80% of the antigen synthesized by tumor cells was not secreted, and that Vgu glycoproteins consisted of multiple molecular species with the same epitope. To estimate the epitope structure of Vgu glycoproteins, in preliminary experiments we prepared sialoglycoproteins and/or sialoglycopeptides from purified human glycophorin A. Human glycophorins A(M) and A(N) (GPs-A(M) and A(N)) were treated with Clostridium perfringens neuraminidase to remove all sialic acid residues linked to carbohydrate chains, with Newcastle disease virus (NDV) to remove alpha2-3 linked sialic acid residues, and by Edman's degradation to eliminate N-terminal amino acid of GP-As. Partial or complete desialylation reactions resulted in disappearance of the reactivity of GP-A(M) and GP-A(N) with corresponding antisera and in appearance of reactivities with VUA and VGA. Elimination of N-terminal amino acid of GP-As also resulted in appearance of reactivities with VUA. These results show that sialoglycoproteins with similar serological properties of Vgu glycoprotein could be prepared from GP-As, and suggest that the epitope structure of Vgu glycoprotein may be related to the MN blood type-epitope structure and its sialic acid residues at N-terminal moiety of GP-As.

The jack bean lectin, concanavalin A (Con A), was modified with 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chloro-s-triazine, activated PEG2, to form PEG-Con A. The immunoreactivity of PEG-Con A towards anti-Con A antibodies was reduced by increasing the degree of modification of amino groups in the Con A molecule. PEG-Con A had a complete reduction of the immunogenicity in mice and prolonged the clearance-time in blood. Although the mitogenic activity of Con A towards murine spleen cells was reduced by the conjugation with activated PEG2, the administration of PEG-Con A to mice enhanced the anti-tumor cytotoxicity of peripheral lymphocytes against melanoma B16 cells.

We explored the relationship between insulin-like growth factor-1 (IGF-1) concentrations and breast cancer risk. Also, we examined whether obesity, sex hormone-binding globulin (SHBG), and estradiol influenced IGF-1 concentrations. A pilot study of 60 postmenopausal African-American women (30 cases and 30 controls) was used. Plasma concentrations of IGF-1 were higher among the cases, as compared to the controls. A negative trend was seen for plasma concentrations of IGF-1 and TNM (tumor-node-metastasis) stage and IGF-1 and body mass index. IGF-1 was found to be associated negatively with SHBG. After adjustment, plasma concentrations of IGF-1 remained significantly and positively associated with breast cancer risk (odds ratio, 1.183; 95% confidence interval, 1.167-1.201). No significant associations for breast cancer risk were observed for estradiol, SHBG, and body mass index. Further research with a larger sample is needed to clarify the relationships between obesity and IGF-1 concentrations to breast cancer risk in this population.

The usefulness of fluorescence in situ hybridization (FISH) analysis to detect minimal residual disease (MRD) in autologous bone marrow and peripheral blood stem-cell harvests has been tested in three patients with hematologic malignancies. Conventional cytogenetics and FISH were used to characterize the leukemic clones identifying the specific chromosomal abnormalities (monosomy 7 in a myelodysplastic patient and trisomy 8 in two acute myeloid leukemic patients). Such analysis was useful to monitor the MRD persistent after treating these patients with intensive chemotherapy. The myelodysplastic patient underwent eight peripheral blood-stem cell harvests in which FISH detected the persistence of monosomy 7 cells, precluding their use for autologous transplantation. This patient relapsed and died. In two acute myeloid leukemia patients who underwent an autologous marrow harvest, FISH did not show a significant proportion of trisomy 8 cells. Nevertheless, autologous transplantation was not performed, owing to an insufficient CD34 cell content in the harvests. One of these patients relapsed with the reappearance of trisomy 8 and died. The other patient, on the contrary, is alive in complete remission 3 years after the bone marrow harvest. The usefulness and applicability of MRD quantification in stem-cell harvests is discussed on the basis of the sensitivity of the methodology applied.

Patients with unresectable non-small-cell lung cancer (NSCLC) usually have undergone chemotherapy; however, such problems as resistance to chemotherapeutic agents occur during the treatments. Recent studies have indicated that glutathione S-transferase-pi (GST-pi) may play an important role in the resistance of cancer cells to alkylating agents, including cisplatin compounds. We examined a possible relationship between immunohistochemical expression of GST-pi and the response to cisplatin plus etoposide chemotherapy in patients with untreated and unresectable primary NSCLC. Of the 89 patients, 50 (56.2%) were GST-pi-positive and 39 (43.8%) were GST-pi-negative. For the patients with negative GST-pi expression, the response rate was 66.7% (26 of 39 patients). In the patients with positive GST-pi expression, the response rate was 26% (13 of 50 patients). This difference was statistically significant (P = .0019). The results suggest that GST-pi expression in NSCLC tissues is related to response to cisplatin plus etoposide chemotherapy and may be useful as a predictor of chemotherapy response.