We evaluated a 72-year-old woman who was experiencing dysphagia. Esophageal leiomyosarcoma was diagnosed by barium meal study, upper gastrointestinal endoscopy, endoscopic ultrasonography (EUS), by computed tomography (CT). A barium meal study and esophagoscopy performed 3 months before the diagnosis of esophageal leiomyosarcoma showed no abnormalities. Therefore, the tumor appeared to have grown rapidly during the 3-month period.

Aged↗

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Effect of fluvastatin, an inhibitor of 3-hydroxy-3-methyl glutaryl CoA reductase, on drug-metabolizing enzymes in rats.

Fluvastatin (FV), a new cholesterol-lowering agent, has been studied for its effects on hepatic microsomal drug-metabolizing enzymes in male rats. FV was orally administered in dosages of 1, 5, and 30 mg/kg/day for 7 consecutive days. 3-Hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activities were markedly decreased at all dose levels. The amount of microsomal protein and the contents of cytochromes P450 and b5 did not change. No induction of aniline hydroxylase, aminopyrine N-demethylase, testosterone hydroxylases (15 alpha-, 7 alpha-, 6 beta-, 16 alpha-, and 16 beta-), and UDP-glucuronosyltransferase were found. On the other hand, 7-ethoxycoumarin o-deethylase activity was slightly increased and lauric acid omega-1-hydroxylase activity tended to be decreased after treatment with FV.

Animals↗

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Phase I and pharmacologic study of oral (E)-2'-deoxy-2'-(fluoromethylene) cytidine: on a daily x 5-day schedule.

(E)-2'-deoxy-2'-(fluoromethylene)cytidine (FMdC), one of the most potent inhibitors of ribonucleoside diphosphate reductase, was selected for clinical development because of its novel mechanisms of action, and strong antitumor activity against experimental tumor models. This study was designed to determine the toxicities, maximum-tolerated dose (MTD), and pharmacokinetic profile of FMdC. FMdC was given orally for 5 consecutive days every 3 or 4 weeks in patients with advanced solid tumors. The starting dose was 8 mg/m2/day. Pharmacokinetic studies were carried out on days 1 through 5 of the first cycle. Ten patients with non-small cell lung cancer received 15 courses of FMdC at doses which were de-escalated from 8 mg/m2/day to 2 mg/m2/day because of unexpected severe toxicities at the starting dose level. Neutropenia was the dose-limiting toxicity. Thrombocytopenia and anemia were mild. Flu-like symptoms and fever were the common non-hematologic toxicities. The MTD was 4 mg/m2/day, since four of six patients developed grade 3-4 neutropenia. At the 4 mg/m2/day dose level, the mean terminal half-life, maximum plasma concentration (Cmax), plasma clearance, and mean residence time on day 1 were 3.20 h, 15.8 ng/ml, 2.91 l/h/kg, and 4.03 h, respectively. The recommended dose for phase II studies with this schedule is also 4 mg/m2/day for 5 days. Further investigations are necessary to establish optimal dosing schedules and routes for the administration of FMdC.

Administration, Oral↗

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Effect of dextranase prepared from Spicaria violacea on dental caries in the hamster.

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Animals↗

PubMedDate not supplied

RB protein status and chemosensitivity in non-small cell lung cancers.

The retinoblastoma gene product (RB protein), one of the tumor suppressor proteins has been found as wild-type in most non-small cell lung cancer (NSCLC) cells, usually showing multidrug chemoresistance. Recently, carboplatin (CBDCA) and etoposide (VP-16) have been introduced for the treatment of NSCLC as well as small cell lung cancer (SCLC). We examined the correlation of RB protein expression levels and chemosensitivities of a panel of NSCLC cell lines with wild-type RB for CBDCA and VP-16 in order to clarify the role of RB protein in chemoresistance of NSCLC cells. There was significant correlation between chemosensitivity and high level of RB protein expression (P=0.049 for VP-16, P=0.016 for CBDCA). We next examined the effect of VP-16 on RB protein status and cell cycle phases of two NSCLC cell lines (Ma-12, the most chemosensitive cell line; Ma-31, the most chemoresistant cell line). VP-16 suppressed RB protein expression level of Ma-12 cells but did not suppress that of Ma-31 cells, following 24 h exposure at 0.1-10 microM. And the alteration of phosphorylation status of Rb protein expression were quite different in these cells. After the treatment of VP-16, dephosphorylated RB protein became dominant in Ma-12 cells, but phosphorylated RB protein became dominant in Ma-31. High sensitive non-small lung cancer Ma-12 cells were accumulated in G2/M phases of the cell cycle. But no major changes were found in low sensitive non-small lung cancer Ma-31 cells. This shows that phosphorylation status of RB protein might be useful for the assessment for the sensitivity to VP-16 and for the cell cycle inhibition.

Adult↗

PubMedDate not supplied

Identification of a 7-cM region of frequent allelic loss on chromosome band 16p13.3 that is specifically associated with anaplastic thyroid carcinoma.

A total of 17 primary thyroid cancer specimens including seven anaplastic cancers, two papillary cancers adjacent to the anaplastic cancers, and eight papillary cancers were analyzed for loss of heterozygosity (LOH) on chromosome arm 16p. All tumors of anaplastic cancer showed LOHs at one or more loci, and a 7-cM region of the smallest deleted region was found on 16p13.3 between D16S423 and D16S406. This LOH was specifically found in the anaplastic cancer and not in the papillary thyroid cancer. Our present results suggest localization of the putative tumor suppressor gene on 16p13.3, which is likely to play an important role in the anaplastic transformation of thyroid cancer.

Adult↗

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Selection of mRNA markers for detection of lymph node micrometastases in breast cancer patients.

The aim of this study was to search for specific and sensitive mRNA markers or a combination of markers for RT-PCR detection of micrometastases in axillary lymph nodes (LNs) from patients with breast cancer. LNs (n=177) from 17 patients were examined with Cytokeratin20 (CK20), melanoma-associated genes (MAGE1, MAGE3), carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), mammaglobin (MGB1) and mammaglobin B (MGB2) as molecular markers. CK20, MAGE1 and MAGE3 were slightly positive in primary tumors and CEA, PSA, MGB1 and MGB2 were highly positive. MGB1 and MGB2 were 100% positive in HE-positive LNs while CEA and PSA were only 35.7% and 57.1% positive. MGB1 and MGB2 were also 30.1% and 17.8% positive in HE-negative nodes. Thus, MGB1 and MGB2 are specific and a combination of the two should be useful for detection of micrometastases in axillary LNs of breast cancer patients.

Biomarkers, Tumor↗

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An immunohistochemical study of p16, pRb, p21 and p53 proteins in human esophageal cancers.

BACKGROUND: Cell cycle-associated proteins, p16, pRb, p21 and p53 are important in regulating the G1-S checkpoint in the cell cycle, and their functional alterations play key roles in carcinogenesis and cell proliferation. MATERIALS AND METHODS: We immunohistochemically examined the expression of p16, pRb, p21 and p53 proteins by using surgically resected tissues from 35 patients with primary esophageal cancers. RESULTS: In 35 esophageal cancers, the expressions of p16, pRb, p21 and p53 proteins were detectable in 4(11.4%), 25(71.4%), 11(31.4%) and 20(57.1%) respectively. Interestingly, 24 of 25 pRb positive cancers (96.0%) had negative p16, whereas three of ten pRb-negative cancers (30.0%) had high levels of p16 (p < 0.05). In 11 cases of p21 positive immunostaining, there was lymph node metastasis (pN1) in 9 (81.8%). CONCLUSIONS: These results suggest that abnormalities of p16 protein may be closely associated with the carcinogenesis or cell proliferation of esophageal cancers.

Adult↗

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↗

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Expression of nitrotyrosine is associated with angiogenesis in esophageal squamous cell carcinoma.

BACKGROUND: In our previous study, it was suggested that nitrotyrosine, a product of nitrogen species, found in esophageal squamous cell carcinoma (ESCC), may contribute to the progression of esophageal cancer. MATERIALS AND METHODS: To clarify whether nitrotyrosine expression is associated with apoptosis and/or angiogenic factors in ESCC, we have analyzed the relationship between nitrotyrosine presence and the apoptosis-related proteins, Bcl-2 and Bax, or CD34, the marker of vascular endothelial cells, by an immunohistochemical approach. RESULTS: Nitrotyrosine was detected in 21 out of 55 esophageal cancers. The correlation between nitrotyrosine presence and Bcl-2, Bax expression or apoptotic index (AI) was not significant. In contrast, nitrotyrosine presence was significantly correlated with the microvessel density (MVD); nitrotyrosine-positive specimens tended to show a high MAD, while nitrotyrosine-negative specimens tended to be associated with a low MVD (p<0.05). CONCLUSION: Our data suggest that NO induces progression of esophageal carcinoma through its effect on angiogenesis, rather than its effect on tumor apoptosis.

Adult↗

PubMedDate not supplied

Telomerase activity in endoscopically visible lung cancer.

To examine the correlation between telomerase activity and clinical features in patients with lung cancer, we examined 86 patients with endoscopically visible lung cancer including 61 with non-small cell lung cancer (NSCLC) and 25 with small cell lung cancer (SCLC). Telomerase activity was detected by using Telomerase ELISA Kit (Böhringer Manheim, Germany). The median and interquartile ranges of telomerase activity in normal lung, NSCLC and SCLC were 65 and 51-75, 106 and 58-349 and 285 and 117-2214, respectively. Normal lung, NSCLC and SCLC had significantly different telomerase activity (p < or = 0.0001). Between NSCLC and SCLC, SCLC exhibited higher telomerase activity than did NSCLC (p=0.0029). A cut-off level of absorbance [A450nm-A690nm] of 86 derived from 90% specificity in normal lung was used; sensitivity for overall lung cancer, NSCLC and SCLC was 62.8%, 54.1% and 84.0%, respectively. There was no significant difference in telomerase activity between each stage in NSCLC (p=0.9243). In SCLC, however, the median and interquartile range of telomerase activity in extensive disease (2128 and 292-2681) was significantly higher than those in limited disease (207 and 97-252) (p=0.0285).

Adult↗

PubMedDate not supplied

Potassium channel-opening and vasorelaxant profiles of a novel compound YM099 in rat isolated portal vein and rabbit isolated aorta.

The potassium channel-opening and vasorelaxant profiles of YM099, a newly synthesized benzoxadiazol derivative K channel opener, were evaluated in vitro. In the rat isolated portal vein, YM099 and a benzopyran derivative K channel opener levcromakalim concentration-dependently inhibited the frequency of spontaneous rhythmic contractions, with IC50 values of 104 and 38 nM, respectively. In the rabbit isolated aorta, YM099 (10(-7)-3 x 10(-5) M) and levcromakalim (10(-7)-3 x 10(-5) M) also concentration-dependently relaxed the contractions induced by 20 mM KCl, but they were ineffective against the contractions induced by 50 mM KCl. These effects of YM099 and levcromakalim were competitively antagonized by a K channel blocker glibenclamide (10(-7)-3 x 10(-6) M). In the rabbit isolated aorta, YM099 (3 x 10(-8)-3 x 10(-6) M), but not the calcium antagonist nifedipine (10(-8)-3 x 10(-6) M), relaxed the contractions induced by norepinephrine (10(-6) M) or prostaglandin F2 alpha (3 x 10(-6) M). These vasorelaxant effects of YM099 were also antagonized by glibenclamide. In conclusion, YM099 is a potent vascular smooth muscle-relaxant agent and possesses a vasorelaxant effect different from that of nifedipine. These effects of YM099 may be mediated, like those of levcromakalim, by the opening of glibenclamide-sensitive K channels.

Animals↗

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↗