The present study was undertaken to investigate whether or not radical scavengers can inhibit platelet aggregation in humans. Toward this end, nicaraven was selected for this study because it has been shown to specifically scavenge hydroxyl radicals that are implicated in platelet aggregation. Ten healthy volunteers and 10 patients with cerebral thrombosis were enrolled in this study. The antiplatelet activities in vitro of nicaraven were examined. The concentrations of nicaraven tested were 3.50 x 10(-5) mol/L, 1.75 x 10(-4) mol/L, 3.50 x 10(-4) mol/L, and 1.75 x 10(-3) mol/L, respectively. The maximum aggregation rate induced by adenosine diphosphate (ADP) was significantly inhibited by nicaraven at concentration ranges of 3.50 x 10(-4) mol/L or higher in the healthy volunteer platelets. The maximum aggregation rate induced by collagen was significantly inhibited by 1.75 x 10(-3) mol/L of nicaraven. Using platelets from patients with cerebral thrombosis, the maximum aggregation rate induced by ADP was significantly inhibited by 1.75 x 10(-3) mol/L of nicaraven. Furthermore, the maximum aggregation rate induced by collagen were significantly reduced by 1.75 x 10(-3) mol/L of nicaraven. Nicaraven induces dose-dependent inhibition of platelet aggregation in both healthy volunteers and patients with cerebral thrombosis.

Aged↗

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Fibromuscular dysplasia complicated by primary thrombocythemia presenting recurrent ischemic cerebrovascular accidents: a case report.

A patient with fibromuscular dysplasia associated with primary thrombocythemia is reported. The patient, a 46-year-old female, had recurrent episodes of ischemic cerebrovascular accidents. Cranial CT scans revealed multiple low density areas in the right frontal and parietal lobes, and cerebral angiograms showed evidence of multiple embolisms. In addition, occlusion of the right internal carotid artery developed. To our knowledge, this is the first report on fibromuscular dysplasia complicated by essential thrombocythemia. The pathogenesis of the severe thrombotic tendency is discussed.

Angiography, Digital Subtraction↗

PubMedDate not supplied

Induction of apoptosis in human stomach cancer cells by green tea catechins.

The exposure of human stomach cancer KATO III cells to green tea catechin extract and epigallocatechin gallate (EGCG), a main component of the extract led to both growth inhibition and the induction of programmed cell death (apoptosis). Morphological changes showing apoptotic body were observed in the cells treated with green tea catechin extract and EGCG. The fragmentation of DNA to oligonucleosomal-sized fragments, characteristic of apoptosis was determined to be concentration- and time-dependent. These data suggest that drinking of green tea in large amounts is recommended possibly to protect humans from stomach cancer.

Antineoplastic Agents↗

PubMedDate not supplied

GPI-anchored molecule-like protein (GML) expression in non-small cell lung cancer (NSCLC).

BACKGROUND: GPI-anchored molecule-like protein (GML) has been identified as a new target molecule of p53. In esophageal cancer cell lines, expression of GML mRNA, which was found to be significantly correlated with in vitro anti-cancer drug sensitivity, was observed only in the presence of wild-type p53. MATERIALS AND METHODS: The relationship between expression of GML mRNA and p53 gene status in 24 non-small cell lung cancer (NSCLC) cell lines was examined using RT-PCR and PCR-SSCP followed by direct DNA sequencing. RESULTS: Expression of GML mRNA was observed in only 3 of 24 cell lines. In contrast to previous studies showing p53-dependent GML expression, of the 3 cell lines expressing GML mRNA, one had a p53 gene mutation (codon 245: Gly to Cys). CONCLUSION: These findings suggest that the expression of GML mRNA is infrequent and regulated in a p53-independent manner in NSCLC.

Carcinoma, Non-Small-Cell Lung↗

PubMedDate not supplied

Prognostic significance of telomeric repeat length alterations in pathological stage I-IIIA non-small cell lung cancer.

This study was performed to evaluate the prognostic significance of alteration in telomere length in pathological stage (p-stage) I-IIIA non-small cell lung cancer (NSCLC). Paired cancer and normal lung tissues were obtained from 72 patients with histologically confirmed p-stage I-IIIA NSCLC. Terminal restriction fragment (TRF) length, which indicates telomere length, was measured by Southern blot analysis. Tumor telomerase activity was also assayed by non-radioactive PCR-ELISA in 55 patients. TRF length (mean +/- SD) in normal tissue was 6.2 +/- 1.1 Kb. Therefore, upper and lower limits of normal range in TRF length was set at 8.4 (mean + 2SD) Kb and 4.0 (mean-2SD) Kb, respectively. A tumor showing TRF length over normal range was defined as positive for the alteration. In 72 patients, 25 (34.7%) with alteration in TRF length had significantly shorter survival durations than those of the others. Telomerase activity did not correlate with survival duration. In multivariate analysis, alteration in TRF length (P = 0.0033) was second to p-stage (P = 0.0004) in importance among the various parameters.

Adult↗

PubMedDate not supplied

Induction of programmed cell death (apoptosis) in human lymphoid leukemia cells by catechin compounds.

The need for antitumor compounds with novel mechanisms of action is great. The exposure of human lymphoid leukemia Molt 4B cells to epigallocatechin (EGC), epigallocatechin gallate (EGCG), and persimmon extract (PS) led to both growth inhibition and the induction of programmed cell death (apoptosis). The fragmentation of DNA to oligonucleosomal-sized fragments, characteristic of programmed cell death, was determined to be concentration- and time-dependent. These data provide the first evidence that catechin compounds and persimmon extract containing all these catechin compounds induce programmed cell death.

Apoptosis↗

PubMedDate not supplied

Prognostic significance of serum p53 antibodies in squamous cell carcinoma of the lung.

BACKGROUND: The prognostic significance of serum p53-Abs positivity for non-small cell lung cancer (NSCLC) is still unknown. PATIENTS AND METHODS: To determine the prognostic value of serum p53-Abs status, we determined serum p53-Abs and immunohistochemistry in 140 patients with stage I-IIIA NSCLC. RESULTS: p53-Abs were detected in 12.1% of all patients and in 17.6% of those with squamous cell carcinoma (SCC). Neither p53-Abs nor p53 overexpression alone was correlated with survival for all patients. When these factors were combined for SCC, seronegative patients with tumors overexpressing p53 survived significantly longer than did those with p53-Abs or p53-nonexpressing tumors. In multivariate analysis, p53-Abs status and p53 overexpression were independent prognostic factors for SCC (p = 0.0337). CONCLUSIONS: These findings suggest that the combination of p53Abs seropositivity and p53 overexpression may be a prognostic factor for SCC.

Aged↗

PubMedDate not supplied

Clinical significance of p53 in non-small-cell lung cancer.

p53 abnormalities appear to play critical roles in human carcinogenesis. Many studies have indicated that p53 alteration is responsible for the differences in clinical characteristics of non-small cell lung cancer (NSCLC). The purpose of this review is to evaluate and summarize the significance of p53 alteration in the diagnosis and therapy of NSCLC. After assessing the principles of each approach to detecting p53 alteration, we reviewed the literature describing the impact of p53 alteration on clinical modalities such as diagnosis, prediction of prognosis, and response to treatment. We also reviewed p53 gene replacement therapy for NSCLC. Although p53 appears to be the most important gene in the development of NSCLC, it is not known whether p53 abnormalities are useful markers for clinicians. A multicenter, prospective study of p53 immunohistochemistry should therefore be performed. Replacement of the p53 gene has been shown to be effective in a clinical trial for patients with NSCLC. In addition to simple gene replacement, combination treatments of gene transfer and chemotherapy are now being tested in clinical trials.

Apoptosis↗

PubMedDate not supplied

Prognostic significance of CYFRA 21-1 in non-small cell lung cancer.

Between July 1991 and February 1993, CYFRA 21-1 levels of 149 newly diagnosed patients with histologically proven non-small cell lung cancer (NSCLC) at Osaka Prefectural Habikino Hospital were measured with an enzyme immunoassay method developed by Boeringer Mannheim (Enzymun-Test CYFRA 21-1). NSCLC patients with CYFRA 21-1 serum levels over 3.5 ng/ml had a significantly poorer prognosis than did patients with normal CYFRA 21-1 levels (P < 0.001). Univariate analysis revealed that CYFRA 21-1 levels above 3.5 ng/ml, poor PS, advanced stage and serum LDH over 450 U/l strongly correlated with survival period. In multivariate analysis, however, only CYFRA 21-1 was found to be an independent prognostic factor compatible with Stage and PS (P = 0.0040 for CYFRA 21-1, P < 0.001 for PS, P = 0.0052 for Stage).

Adult↗