Antileukinate, a hexapeptide inhibitor of CXC-chemokine receptor, suppresses bleomycin-induced acute lung injury in mice.

A hexapeptide, Ac-RRWWCR-NH(2) (Antileukinate), has been reported to be a potent inhibitor of CXC-chemokine receptor. However, the in vivo anti-inflammatory activity of this agent has not been tested except in a rabbit skin edema model. This study was undertaken to investigate the effect of subcutaneously administered Antileukinate on experimental bleomycin-induced acute lung injury in mice, in which CXC-chemokines have been reported to be involved.

Inhibitory effects of 14-membered ring macrolide antibiotics on bleomycin-induced acute lung injury.

14-membered ring macrolides have been reported to have anti-inflammatory effects and to decrease neutrophil infiltration into the airways in chronic lower respiratory tract diseases. This study investigated the potential inhibitory effects of macrolide antibiotics on bleomycin-induced acute lung injury. Four drugs were studied: two 14-membered ring macrolides, clarithromycin (CAM) and roxithromycin (RXM); a 15-membered ring macrolide, azithromycin (AZM); and a 16-membered ring macrolide, josamycin (JM).

Fourteen-membered ring macrolides as anti-angiogenic compounds.

Macrolide antibiotics have been widely used for infectious diseases since the 1950s. For the last decade, 14-membered ring macrolides, of which erythromycin is the prototype, have attracted a great deal of attention because of their additional therapeutical activities far beyond antibiotics. First, erythromycin has prokinetic effects on the gastrointestinal tract as a motilin receptor agonist.

[A case of desmoplastic malignant pleural mesothelioma].

A 71-year-old woman with no history of asbestos exposure was referred to our hospital for evaluation of mediastinal soft tissue density. Six months prior to the admission, she had developed back pain and had been diagnosed as having intercostal neuralgia. Since the symptoms progressed, she was referred to another hospital.

Increased interleukin-5 levels in bronchoalveolar lavage fluid is a major factor for eosinophil accumulation in acute eosinophilic pneumonia.

Background: Increased interleukin-5 (IL-5) levels have been reported in bronchoalveolar lavage fluid (BALF) from patients with acute eosinophilic pneumonia (AEP); however, it still remains to be determined whether IL-5 is responsible for the eosinophil accumulation in the lung.

Objective: We examined the effect of antibodies against cytokines on eosinophil chemotaxis induced by BALF from AEP patients to identify factors responsible for eosinophil accumulation.

Methods: We measured a series of specific cytokines, including IL-3, IL-4, IL-5, IL-6, IL-8, GM-CSF, RANTES, MCP-1, MIP-1alpha and eotaxin, in the BALF from 4 patients with AEP.

Antiangiogenic and antitumor effects of tranilast on mouse lung carcinoma cells.

We examined the effects of tranilast on tumor angiogenesis, tumor growth and metastasis in the mouse Lewis lung carcinoma and C57BL mouse system. Tranilast significantly reduced the dense capillary network induced by Lewis lung cancer cells in a mouse dorsal air sac angiogenesis model. Intraperitoneal administration of tranilast at 200 mg/kg/day reduced the tumor size of mouse Lewis lung carcinoma to about 63% of that of the control and suppressed pulmonary metastasis in a spontaneous system.

Roxithromycin and clarithromycin, 14-membered ring macrolides, potentiate the antitumor activity of cytotoxic agents against mouse B16 melanoma cells.

We previously reported antiangiogenic activity of roxithromycin and clarithromycin, 14-membered ring macrolide antibiotics. In the present study, we examined the antitumor effects of roxithromycin and clarithromycin, alone and in combination with several cytotoxic drugs, on mouse B16BL6 melanoma cells in vivo and in vitro. Both roxithromycin and clarithromycin potentiated the inhibition of tumor growth induced by cyclophosphamide, cis-diamminedichloroplatinum(II), Adriamycin and vindesine in vivo.

Antiangiogenic and antitumor effects of 14-membered ring macrolides on mouse B16 melanoma cells.

We examined the effects of macrolide antibiotics on tumor angiogenesis, tumor growth and metastasis in the B 16BL6 mouse melanoma and C57BL mouse system. Two 14-membered ring macrolide antibiotics, roxithromycin and clarithromycin, significantly reduced the dense capillary network area in a mouse dorsal air sac angiogenesis model, whereas a 15-membered ring macrolide, azithromycin, and a 16-membered ring macrolide, josamycin, did not show any inhibitory effect on angiogenesis at the same dose. Intraperitoneal administration of roxithromycin and clarithromycin at 50 mg/kg/day reduced the tumor size of B 16BL6 melanoma to about 41% and 56%, respectively, of that of the control, and significantly suppressed pulmonary metastasis of B16BL6 cells in a spontaneous system.

Inhibitory effects of roxithromycin on tumor angiogenesis, growth and metastasis of mouse B16 melanoma cells.

We examined the effects of roxithromycin, a 14-membered ring macrolide antibiotic, on tumor angiogenesis, tumor growth and metastasis of mouse B16BL6 melanoma cells. The inhibitory effect of roxithromycin on angiogenesis using mouse dorsal air sac model was dose-dependent, and 100 mg/kg of roxithromycin administered intraperitoneally twice a day reduced the dense capillary network area to about 20% of the control. Administration of roxithromycin histologically reduced the development of microvessels and mononuclear cell infiltration.

Inhibition of tumor angiogenesis by roxithromycin, a 14-membered ring macrolide antibiotic.

We examined the effects of roxithromycin, a 14-membered ring macrolide antibiotic, on tumor angiogenesis using a mouse dorsal air sac model. The inhibitory effect of roxithromycin was dose-dependent and 100 mg/kg of roxithromycin administered intraperitoneally twice a day reduced the dense capillary network area to about 20% of the control. However, at concentrations of up to 50 microM, roxithromycin had no effect on lung cancer cells and human vascular endothelial cell growth and lung cancer cell production of the angiogenesis-inducing factors interleukin-8 and vascular endothelial growth factor.

The levels of integrin alpha v beta 5 may predict the susceptibility to adenovirus-mediated gene transfer in human lung cancer cells.

Adenovirus mediated transfer of growth-inhibiting molecules, such as p53 shows promise as an effective method of suppressing the growth of cancer cells. As the basis for in vivo studies, we examined transfection efficiency using 15 human lung cancer cell lines that differ in their endogenous p53 status. When infected with an adenovirus expressing bacterial beta-galactosidase, the different cell lines showed different levels of beta-galactosidase activity.

Granulocyte-macrophage-colony stimulating factor stimulates tumor invasiveness in squamous cell lung carcinoma.

Background: Bronchial epithelial cells produce a significant amount of granulocyte-macrophage-colony stimulating factor (GM-CSF), which is believed to mediate both the host defense and inflammation. Recently, GM-CSF has been demonstrated to be produced by several tumor cells and also to be associated with tumor growth and metastasis. In the current study, the authors investigated the biologic role of GM-CSF produced by squamous cell lung carcinoma.

Interleukin-8 participates in angiogenesis in non-small cell, but not small cell carcinoma of the lung.

We examined interleukin-8 (IL-8) production in 17 lung cancer cell lines, IL-8 expression in tumor specimens and IL-8's contribution to tumor-induced angiogenesis in vivo. Eight of 13 non-small cell lung cancer cell lines constitutively produced high levels of IL-8. Four small cell lung cancer cell lines produced little or no IL-8.

[Expression of CD44 standard and CD44 variant 6 in human lung cancer].

We immunohistochemically examined the expression of CD44 standard (CD44 st) and CD44 variant 6 (CD44 v6) in 112 cases of primary lung cancer, and their relationship to the clinical milieu, including the clinical stage. In 46 cases of squamous cell carcinoma, expression of CD44 st was observed in 45.7% of the cases, and expression of CD44 v6 was observed in 60.

Phase II trial of dose intensification with cisplatin and carboplatin plus vindesine in patients with inoperable non-small cell lung cancer.

We conducted a phase II trial of a regimen that combined cisplatin (CDDP), carboplatin (CBDCA), and vindesine (VDS) in previously untreated patients with non-small cell lung cancer (NSCLC) to evaluate the efficacy and safety of the regimen. Thirty-five patients with inoperable NSCLC entered the study. Cisplatin (CDDP 80 mg/m2) was administered on day 1, and CBDCA 100 mg/m2 and VDS 2 mg/m2) were administered on days 2, 3, and 8.

The utility of p53 immunostaining of transbronchial biopsy specimens of lung cancer: p53 overexpression predicts poor prognosis and chemoresistance in advanced non-small cell lung cancer.

There are few reports on the p53 status of small cell lung cancer (SCLC) and advanced non-SCLC (NSCLC) because surgically resected specimens are generally not available. Therefore, we evaluated p53 immunostaining in 175 transbronchial biopsy (TBB) specimens obtained from patients with all stages of lung cancer and retrospectively evaluated the relationship between p53 status and clinical parameters. All of the specimens were obtained prior to therapy.

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.

Clarithromycin is a potent inhibitor of tumor-induced angiogenesis.

We investigated the inhibitory effect of clarithromycin, a 14-membered ring macrolide antibiotic, on tumor-induced angiogenesis in vivo using a mouse dorsal air sac model. The inhibitory effect of clarithromycin was dose-dependent, and 100 mg/kg of clarithromycin administered intraperitoneally twice a day reduced the area of dense capillary network to about 30% that of the control. However, in concentrations up to 50 microM clarithromycin had no effect on lung cancer cells and human vascular endothelial cell growth, endothelial cell migration, or lung cancer cell production of the angiogenesis-inducing factors interleukin-8 and vascular endothelial growth factor.

Granulocyte-colony stimulating factor promotes invasion by human lung cancer cell lines in vitro.

The effects of exogenous and endogenous granulocyte colony-stimulating factor (G-CSF) on invasion by cancer cells were studied, using lung cancer cell lines that produce G-CSF (NCI-H157) and lines that do not (PC-9 and NCI-H23). The invasive capacity of NCI-H157 cells was 26- to 27-fold higher than that of PC-9 and NCI-H23 cells. The invasiveness of PC-9 cells was stimulated by exogenous G-CSF, while that of NCI-H157 cells was not.

Empyema following the percutaneous instillation of antifungal agents in patients with aspergillosis.

We report two cases of empyema as a complication of the percutaneous instillation of antifungal drugs for pulmonary and pleural aspergillosis. Case 1 underwent percutaneous administration of amphotericin B and fluconazole for 2 months. Six months later, the patient was found to have an Aspergillus empyema with a bronchopleural fistula.

Immunohistochemical expression of glutathione S-transferase-Pi can predict chemotherapy response in patients with nonsmall cell lung carcinoma.

Background: Resistance to chemotherapy agents is a major problem in the treatment of patients with nonsmall cell lung carcinoma (NSCLC). 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.

Methods: The expression of GST-Pi in tissues obtained by bronchoscopic biopsy from 38 NSCLC patients was investigated immunohistochemically.

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).

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.

Tuberculosis following liver transplantation: report of a case and review of the literature.

We report on a 44-year-old man who developed tuberculosis 4 months after liver transplantation. The diagnosis was confirmed using a polymerase chain reaction (PCR) technique in bronchial alveolar lavage (BAL) fluid, and the patient was successfully treated by reducing his immunosuppression and administering antituberculous drugs. The patient became afebrile 20 days after starting antituberculous therapy and remains well at home.

Inhibition of pkc and pka by chemopreventive organoselenium compounds.

Numerous efficacy studies in rodents revealed that 1,4-phenylenebis(methylene)-selenocyanat (p-XSC) is a more effective chemopreventive organoselenium compound and less toxic than benzyl selenocyanate (BSC) or the inorganic compound Na2SeO3. To explore mechanisms which mediate chemopreventive activities of p-XSC we have tested its effect on protein kinase A and C using in vitro and cell culture systems. While p-XSC did completely inhibit PKC and PKA activity, BSC was less active and Na2SeO3 had no effect.