Pulmonary function tests were studied in 105 patients with cirrhosis of the liver who had no clinical or radiographical evidence of cardiopulmonary disease. Spirometric data such as VC, FRC, RV, TLC, RV/TLC and FEV1.0% were within normal limits in all subjects. However, flow-volume curve and closing volume curve were abnormal in the majority. In flow-volume curve, V25, was decreased and the V50/V25 value was increased; on the other hand, closing volume was markedly increased and FRC-CC value was reduced in the patients with hepatic cirrhosis. The closing capacity tended to exceed the FRC in the patients with arterial hypoxemia, indicating the presence of airway closure and gas trapping during resting ventilation. Therefore, ventilation-perfusion imbalance may be an important cause of arterial hypoxemia in patients with cirrhosis of the liver.

Adult↗

PubMedDate not supplied

PACAP reverses airway hyperresponsiveness induced by ozone exposure in guinea pigs.

BACKGROUND: We previously demonstrated that pituitary adenylate cyclase activating peptide (PACAP) inhibits airway smooth muscle contraction and plasma extravasation. OBJECTIVE: We thus hypothesized that PACAP may regulate airway responsiveness through these effects and examined the effects of exogenously applied PACAP on the airway hyperresponsiveness induced by ozone exposure. METHODS: Ozone exposure was carried out in awake, spontaneously breathing guinea pigs using 3 ppm for 2 h. Airway responsiveness to histamine was determined before and 30 and 90 min after the termination of ozone exposure for 2 h in anesthetized animals. Extravasation of Evans blue was measured before and 90 min after the termination of ozone exposure. Either PACAP (10(-6) mol/kg) or vehicle was administered intravenously 60 min after exposure. The airway responsiveness was expressed as the concentration of histamine required to produce a 200% increase in total pulmonary resistance (PC(200)). RESULTS: Ozone exposure caused a significant decrease in PC(200) (n = 5, p < 0.05) 30 min after ozone exposure which persisted 90 min thereafter, thus suggesting that ozone caused airway hyperresponsiveness. PACAP significantly suppressed the increase in airway hyperresponsiveness induced by ozone 90 min after exposure (n = 5, p < 0.05). In contrast, this peptide did not have any effect on plasma extravasation. CONCLUSION: We thus conclude that PACAP decreases ozone-induced airway responsiveness, and, therefore, intravenously administered PACAP may be useful in reversing airway hyperresponsiveness.

Animals↗

PubMedDate not supplied

Chemotherapy for advanced non-small cell lung cancer.

Less than 20% of all cases of non-small cell lung cancer are operable. The treatment option available for such patients is either radiotherapy or chemotherapy. Various combinations of chemotherapeutic agents have been tried. The combination of cisplatin and 5-fluorouracil (5-FU) has been proved to have a synergistic antitumour effect in many experimental and clinical studies. In this paper the authors report the results of a trial using tegafur (which is a prodrug of 5-FU; 1-[2-tetrahydrofuryl]-5-FU) and uracil along with cisplatin in inoperable non-small cell lung cancer. Thirty-one patients were entered into the study, all of whom were less than 75 years old (mean age 61 years). The patients (except for 2) had either stage IIIB (12) or stage IV (17) disease with adenocarcinoma and squamous cell carcinoma in equal proportions (15 each). A combination of uracil and tegafur (400 mg/m2) in 100 mg capsules (100 mg tegafur and 224 mg of uracil), was given orally for 21 days. Most of the patients received 300 mg of the combination tablets twice a day. Cisplatin (80 mg/m2) was given as an infusion over 90 minutes on day 8 after adequately hydrating the patients. This cycle was repeated every 4 weeks. At least 2 treatment cycles were given, unless there was disease progression or toxicity. The response and survival rates were assessed after a follow up period which ranged between 9 and 30 months. The patients received 1 to 4 cycles of therapy and the response rates were: complete response--nil,partial response--11, no change--11 and disease progression--9. The overall response rate was 35% (95% CI: range 19-52%). Five patients achieved at least 50% tumour reduction after 2 cycles. Of the 11 patients who showed partial response, 5 (35%) had stage IV disease and 6 (36%) had other stages; 6 (40%) had squamous cell carcinomas and 5 (31%) had tumours of other histological types. The median duration of response was 6 months (3-13 months). In stage III disease, the 1-year survival rate was 31%, with a median survival time of 11 months, while in stage IV disease it was 29% with a median survival time of 8 months. There was a low incidence of toxicity, with anaemia (10%), leukopenia (6%) and thrombocytopenia (6%) being the most common side-effects. There were also no treatment-related deaths. The authors concluded that oral uracil and tegafur were as effective as other combinations with cisplatin. They also caused very few side-effects. They suggest that a larger trial needs to be carried out.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Bcl-2 expression as a predictor of chemosensitivities and survival in small cell lung cancer.

PURPOSE: The bcl-2 gene belongs to a new category of oncogene that inhibits programmed cell death (apoptosis). No data are available on the frequency or clinical importance of its expression in patients with small cell lung cancer (SCLC), although its expression is reported in SCLC cell lines. We investigated the correlation between bcl-2 expression and prognosis, including response to chemotherapy, in SCLC patients and report our findings here. MATERIALS AND METHODS: Tumor specimens biopsied bronchoscopically in 38 SCLC patients were used for immunohistochemical study. Bcl-2 oncoprotein was detected by obtaining an immunostain using a specific monoclonal antibody, DAKO-bcl-2, 124. All patients received more than two courses of chemotherapy with 3- to 4-week intervals. RESULTS: We detected bcl-2 expression in 21 of the 38 SCLC patients (55%). In 17 patients with bcl-2-negative tumors, the objective response to chemotherapy was 76% with 12% complete response and in 21 patients with bcl-2-positive tumors it was 62% with 8% complete response. The difference in response rate was not significant. In patients with bcl-2-positive tumors, survival time tended to be shorter than in those with bcl-2-negative tumors. There was no significant correlation between bcl-2 expression and clinical factors (gender, age, smoking, performance score, staging). CONCLUSIONS: In 21 of the 38 SCLC patients bcl-2 oncoprotein was abnormally expressed and its expression may be associated with shorter survival times and poor response to chemotherapy.

Adult↗

PubMedDate not supplied

P53 immunostaining predicts chemosensitivity in non-small cell lung cancer: A preliminary report.

PURPOSE: Although resistance to chemotherapy is a major problem in cancer treatment, there is no predictor of treatment response. Recent reports suggest that p53 status may provide a genetic basis for drug resistance. METHODS: Transbronchial biopsy specimens from 18 patients with non-small cell lung cancer were evaluated for p53 expression using anti-p53 antibody (DO-1). After biopsy, these patients received more than two courses of identical chemotherapy including cisplatin, carboplatin, and vindesine. RESULTS: Ten of 18 (56%) patients responded to chemotherapy. The accumulation of p53 protein was detected in 10 of 18 (56%) patients. Positive staining for p53 was significantly correlated with unresponsiveness to chemotherapy. Other factors, including gender, performance status, body weight loss, serum albumin, and serum LDH, did not correlate with the immunohistochemical expression of p53. CONCLUSIONS: These results suggest that immunostaining with p53 can be a predictor of the response to chemotherapy in non-small cell lung cancer. Further studies are needed to confirm the relationship between p53 expression and chemosensitivity.

Adult↗

PubMedDate not supplied

Glutathione derivatives enhance adriamycin cytotoxicity in a human lung adenocarcinoma cell line.

We evaluated the effects of a panel of glutathione derivative (S-butyl, S-decyl, S-ethyl, S-heptyl, S-hexyl; S-methyl, S-nonyl, S-octyl, S-propyl and S-pentyl glutathiones) on glutathione-S-transferase activity in the cell lysates of a human lung cancer, PC-9. Glutathione derivatives inhibited glutathione-S-transferase activity in PC-9 cell lysates by up to 67%. When PC-9 cells were incubated with the IC50 concentration of adriamycin (200 nM) and with nontoxic concentrations (1 microM) of the glutathione derivatives, cytotoxicity ranged from -20% to +55% of the control levels. Enhancement of adriamycin toxicity by glutathione derivatives was significantly correlated with the inhibition of glutathione-S-transferase activity. S-decyl-glutathione, which was one of the most potent inhibitors of glutathione-S-transferase activity, significantly enhanced the adriamycin-induced antitumor effect in vivo. Findings suggest that some glutathione derivatives, including the S-decyl, S-octyl, and S-hexyl glutathiones, enhance adriamycin-induced cytotoxicity in part by inhibiting glutathione-S-transferase and that these agents may be useful as chemosensitizers for adriamycin therapy. In conclusion, the present results showed that some glutathione derivatives enhanced sensitivity of tumor cells to ADR by inhibiting GST activity. The use of BSO and EA as sensitizers to chemotherapy is currently being evaluated in clinical trials. The present data suggest that the use of GSH derivatives to modulate GST activity may improve the response to ADR.

Adenocarcinoma↗