Biomedical subjects

Keisuke Aoe

Publications and source records attributed to Keisuke Aoe.

32 records · Page 2Linked to original sources

PubMed2003

Diagnostic significance of interferon-gamma in tuberculous pleural effusions.

STUDY OBJECTIVES: Tuberculosis (TB), the single most frequent infectious cause of death worldwide, also is a major cause of pleural effusion, which in TB usually has lymphocytic and exudative characteristics. Differential diagnosis between TB and nontuberculous pleural effusion can be sometimes difficult, representing a critically important clinical problem. METHODS: We studied 46 patients presenting with pleural effusion to the National Sanyo Hospital between April 2000 and January 2001 (34 men and 12 women; mean age, 64 years). Ten patients (22%) had tuberculous pleurisy, 19 patients (41%) had malignant pleuritis, and 17 patients (37%) had pleural effusion due to an etiology other than tuberculosis or cancer. Pleural fluid concentrations of four suggested markers were measured using commercially available kits. RESULTS: The pleural fluid levels (mean +/- SE) of adenosine deaminase (83.3 +/- 18.2 U/L vs 25.8 +/- 20.4 U/L, p < 0.0001), interferon-gamma (137 +/- 230 IU/mL vs 0.41 +/- 0.05 IU/mL, p < 0.0001), immunosuppressive acidic protein (741 +/- 213 micro g/mL vs 445 +/- 180 micro g/mL, p < 0.001) and soluble interleukin 2 receptor (7,618 +/- 3,662 U/mL vs 2,222 +/- 1,027 U/mL, p < 0.0001) were significantly higher for tuberculous pleuritis than for other causes of effusion. Receiver operating characteristic analysis demonstrated that pleural fluid content INF-gamma was the best indicator of tuberculous pleurisy among four relevant biological markers. CONCLUSIONS: INF-gamma in pleural fluid is the most sensitive and specific among four biological markers for tuberculous pleuritis. Thus, our results suggest that determination of INF-gamma at the onset of pleural effusion is informative for the diagnosis of tuberculous pleuritis. Further studies including larger numbers of patients are needed to verify this result.

Adenosine Deaminase↗

PubMed2003

Relative abundance and patterns of correlation among six cytokines in pleural fluid measured by cytometric bead array.

Several cytokines play significant roles in the development and pathogenesis of pleural effusion. Little is known, however, about possible interactions between individual cytokines in terms of regulation of their relative abundance in the effusion. We studied 93 patients presenting with pleural effusion to the National Sanyo Hospital (68 men and 25 women; mean age, 64 years). Twenty-two patients had tuberculous pleurisy, 40 had malignant pleuritis, and 31 had effusions due to an etiology other than tuberculosis or cancer (miscellaneous). Pleural fluid concentrations of IL-2, IL-4, IL-5, IL-10, TNF-alpha, and INF-gamma were simultaneously measured by cytometric bead array (CBA). The ratios of IL-4/IL-5, IL-4/TNF-alpha, IL-2/TNF-alpha, and IL-10/TNF-alpha were lower in patients with tuberculosis pleurisy compared with other patients. In all three groups of patients significant correlation was seen between abundance of IL-2 vs. IL-4, IL-5, IL-10, or TNF-alpha, between IL-4 vs. IL-10, and between TNF-alpha vs. INF-gamma. In malignant pleural fluid patients, the significant correlation was between IL-2 vs. IL-4, TNF-alpha, or INF-gamma, between IL-4 vs. INF-gamma, and between TNF-alpha vs. INF-gamma. In tuberculosis pleural fluid patients, the significant correlation was between IL-2 vs. TNF-alpha, between IL-4 vs. IL-10, and between TNF-alpha vs. INF-gamma. In miscellaneous pleural fluid patients, the significant correlation was between IL-2 vs. IL-4, IL-10, or TNF-alpha, between IL-4 vs. IL-10, TNF-alpha, and between IL-10 vs. TNF-alpha. No significant correlation was observed between other pairs of cytokines. Strong correlation in abundance between particular cytokines in pleural fluids suggests cross-talk between them, in terms that an altered level of one of them provides a feedback mechanism regulating synthesis and/or secretion of another one. Such interactions may play important roles in pathogenesis and severity of the effusion. The CBA methodology provides a convenient tool to investigate these interactions.

Adenosine Deaminase↗

PubMed2003

[Rifampicin-induced severe thrombocytopenia in a patient with miliary tuberculosis].

A 74-year-old female visited a local clinic complaining of fever on January 21, 2002. A chest X-ray and a chest computed tomography (CT) showed diffuse micronodules in all lung fields, which strongly suggested miliary tuberculosis. On January 23, she was referred to our hospital for further examinations. Though sputum was negative on smear, culture, and polymerase chain reaction (PCR) for M. tuberculosis, bone marrow aspirate examined on admission revealed epithelioid granuloma. Therefore we diagnosed her as a miliary tuberculosis, and she was treated with 300 mg of Isoniazid (INH), 450 mg of Rifampicin, and 750 mg of Streptomycin (SM) daily. Five days later, severe thrombocytopenia (platelet count 0.3 x 10(4)/microliter) was observed. We immediately discontinued all antituberculous drugs and administered concentrated platelets and immune globulin. Platelet-associated IgG was detected, and megakaryocytes were slightly increased in moderately hypocellular marrow on the bone marrow aspirate examined again after the appearance of thrombocytopenia. Eleven days after discontinuing all antituberculous drugs, platelet count recovered to 10.2 x 10(4)/microliter. INH, SM, Levofloxacin (LV) were administered afterward, and these drugs did not induce thrombocytopenia. Though challenge administration of RFP was not performed, we concluded that the thrombocytopenia was immunologically induced by RFP. We should keep in mind that RFP-induced thromobocytopenia could appear in the first week after the initiation of therapy.

Aged↗

PubMed2002

Synergistic effects of topoisomerase I inhibitor, 7-ethyl-10-hydroxycamptothecin, and irradiation in a cisplatin-resistant human small cell lung cancer cell line.

7-ethyl-10-[4-(1-piperidyl)-1-piperidyl] carbonyloxy-camptothecin, a topoisomerase I (topo I) inhibitor, is one of the most active agent against lung cancer, and its radiosensitizing effect has been reported recently. We evaluated a combination in vitro effect of irradiation and 7-ethyl-10-hydroxy-CPT (SN-38), an active metabolite of 7-ethyl-10-[4- (1-piperidyl)-1-piperidyl] carbonyloxy-camptothecin, on a human small cell lung cancer cell line (SBC-3) and its cisplatin-resistant subline (SBC-3/CDDP). Growth-inhibitory effects of irradiation with or without SN-38 were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A modified isobologram method was used to evaluate the treatment interaction. The combination of irradiation and SN-38 showed a synergistic inhibitory effect on the growth of SBC-3/CDDP despite its cross-resistance to irradiation and SN-38. In contrast, the same combination showed only an additive effect on the growth of parental SBC-3 cells. There was no significant difference in topo I protein expression between these two cell lines. In SBC-3 cells, topo I catalytic activity was suppressed by 4 Gy of irradiation, without a decrease of nuclear topo I protein, whereas the exposure of SBC-3 cells to 1 microM SN-38 subsequent to irradiation showed no remarkable additional effects on both topo I activity and protein content. On the other hand, in SBC-3/CDDP cells, topo I activity was unchanged by irradiation, but the subsequent exposure to SN-38 gave rise to a decrease in topo I activity, which was accompanied by a significant decrease in the topo I protein content (P = 0.02). These observations may indicate that SN-38 induces sequestration of topo I onto DNA in radiation-treated SBC-3/CDDP cells and suggest that the synergistic effect of irradiation and SN-38 in SBC-3/CDDP cells was considered attributable to DNA repair-related enhanced recruitment of topo I onto the damaged DNA.

Antineoplastic Agents↗

PubMed2002

[Combination chemotherapy with carboplatin and etoposide for elderly patients aged 76 years or older with small cell lung cancer].

Eighteen elderly patients aged 76 years or older with small cell lung cancer were treated with carboplatin (AUC = 4 mg/ml.min, i.v. day 1) and etoposide (70 mg/m2 i.v. day 1-3) and 17 patients were evaluable. The median age of the study population was 77 years (range: 76-81). Eight patients had limited disease (LD) and nine did extensive disease (ED). The overall response rate was 88% for LD patients and 67% for ED patients. Median survival time was 219 days for LD patients and 158 days for ED patients. Grade 3 and 4 leukopenia, neutropenia, thrombocytopenia and anemia occurred in 41%, 76%, 24% and 6% of patients, respectively. There was one treatment-related death due to pneumonitis.

Aged↗

PubMedDate not supplied

Thrombocytosis as a useful prognostic indicator in patients with lung cancer.

BACKGROUND: Thrombocytosis can accompany various cancers including lung cancer. This finding has recently been suggested to indicate poor prognosis. OBJECTIVES AND METHODS: We retrospectively examined the clinical records of 611 patients with lung cancer to investigate whether there is a correlation between thrombocytosis, other clinicopathologic factors, and survival. RESULTS: Ninety-eight of the patients (16%) manifested thrombocytosis at the time of their first evaluation at our hospital. Thrombocytosis and age (p = 0.0006) and thrombocytosis and performance status (p = 0.0002) are significantly correlated, but thrombocytosis is not related to gender, tumor histology, clinical stage, or serum lactate dehydrogenase concentrations. Survival is significantly shorter in patients with thrombocytosis: [median survival time (MST) 7.5 months; n = 98] than without thrombocytosis (MST 10.1 months; n = 513; p = 0.0029). Multivariate analysis of prognostic factors using the Cox proportional hazards model indicated that thrombocytosis had independent prognostic significance. CONCLUSION: Thrombocytosis at the first patient evaluation is an independent prognostic factor in lung cancer.

Adult↗

PubMedDate not supplied

Malignant fibrous histiocytoma of the lung.

Primary malignant fibrous histiocytoma (MFH) of the lung is very rare. To date, only 32 reports of 63 cases of primary MFH of the lung have appeared in English, excluding tumors arising from the pulmonary arteries and pleura. We describe a patient with primary MFH of the lung who developed brain metastasis and involvement of pulmonary great vessels. In addition, we reviewed previously reported cases to establish the clinical characteristics and most appropriate management of primary pulmonary MFH. When disease is sufficiently limited, complete resection remains the mainstay of treatment.

Aged↗

PubMedDate not supplied

Gingival metastasis as initial presentation of small cell carcinoma of the lung.

We describe an 84-year-old man with small cell carcinoma of the lung (SCLC) initially manifesting as gingival metastasis. Although SCLC is well known for early and widespread dissemination, metastasis to the gingiva is extremely rare. We know of only two case reports describing gingival metastasis from SCLC and in these cases gingival metastasis was not the presenting occurrence. Physicians should be aware that, on rare occasions, gingival metastases can be the presenting event in SCLC.

Aged↗

PubMedDate not supplied

Stevens-Johnson syndrome induced by paclitaxel in a patient with squamous cell carcinoma of the lung: a case report.

We treated a 53-year-old man with advanced squamous cell carcinoma of the lung who had developed Stevens-Johnson syndrome, a life-threatening cutaneous reaction, after systemic chemotherapy consisting of carboplatin and paclitaxel. A critical assessment disclosed circumstantial evidence pointing to paclitaxel as the likely cause of this complication. As far as we are aware, this account is the first description of a paclitaxel-induced Stevens-Johnson syndrome. This case serves as an alert for the need to observe patients closely for potentially dangerous cutaneous reactions to paclitaxel therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

High frequency of allele-specific down-regulation of HLA class I expression in lung cancer cell lines.

Loss or down-regulation of HLA expression has been demonstrated in various types of solid tumors and is considered to be one of the mechanisms of tumor immunoescape. The effectiveness of immunotherapy using tumor-specific antigens (TSA) largely depends on the expression of the appropriate HLA class I alleles on the tumor cells. We analyzed the allele-specific HLA class I surface expression of six lung cancer cell lines using a broad panel of allele-specific monoclonal antibodies, as well as the effect of IFN-gamma on HLA expression. Flow cytometric analysis displayed a wide range, from minimal to a high degree of expression of monomorphic HLA class I among the studied cell lines. Allele-specific loss or down-regulation of HLA also was observed in 5 out of 6 cell lines. Our results suggest that lung cancer patients considered for specific immunotherapy should be examined with respect to the expression of specific HLA class I allele binding the TSA.

Alleles↗

PubMedDate not supplied

Primary choriocarcinoma of the lung.

Primary choriocarcinoma (PCC) of the lung is extremely rare, with about 25 cases previously reported. We describe here a patient with PCC of the lung and review previously described cases to establish the clinical characteristics and most appropriate management of this disease. Survival for patients treated with both surgery and chemotherapy was longer than for patients treated with surgery alone, chemotherapy alone, or optional supportive care. Multivariate analysis of prognostic factors revealed that treatment with both surgery and chemotherapy had independent prognostic significance. Our analysis including previous cases suggests that resection followed by adjuvant chemotherapy is the most effective treatment.

Adult↗

PubMedDate not supplied

Cisplatin down-regulates topoisomerase I activity in lung cancer cell lines.

Many clinical studies have reported that irinotecan has reproducible antitumor activity against lung cancer. Both cisplatin and SN-38 are key drugs in the treatment of lung cancer, and their combination is one of the most promising regimens available. Using lung cancer cell lines, ABC-1 and SBC-3, we examined the cytotoxic effect of the schedule, as well as the effect of cisplatin on topoisomerase I activity. Cytotoxicity was determined by MTT assay. ABC-1 or SBC-3 cells were incubated with or without various concentrations of both drugs in 96-well microplates for 72 or 96 hours in a humidified 5% CO2 atmosphere at 37 degrees C. Synergism was evaluated by median-effect plot analysis and a combination index isobologram method by Chou and Talalay. After ABC-1 or SBC-3 cells had been exposed to 10/microM cisplatin for one hour, topoisomerase I activities were determined by supercoiled-DNA relaxation assay. Synergism was observed in ABC-1 and SBC-3 cells when cisplatin was given first, followed by SN-38 (7-ethyl-10-hydroxycamptothecin) and cisplatin. Topoisomerase I activity decreased at 1-2 hours after exposure to cisplatin and recovered gradually after 4-5 hours of cisplatin exposure in both ABC-1 and SBC-3 cells. Accordingly, pretreatment with cisplatin will have an impact on the sensitivity to SN-38.

Adenocarcinoma↗

PubMedDate not supplied

Sudden onset of interstitial lung disease induced by gefitinib in a lung cancer patient with multiple drug allergy.

Gefitinib is an oral selective inhibitor of the epidermal growth factor receptor tyrosine kinase which is effective for patients with advanced non-small cell lung cancer. A 75-year-old man with advanced adenocarcinoma of the lung was treated with gefitinib. He had a history of allergy to several antibiotics and Welder's lung. Two days after initiation, he developed acute interstitial lung disease (ILD) and died of respiratory failure due to progression of ILD. Critical assessment pointed to gefitinib as the likely cause of this complication. This is the first report of rapid gefitinib-induced ILD. This case should alert physicians to the potential for dangerous pulmonary side-effects of gefitinib therapy, especially in patients with drug allergy.

Adenocarcinoma↗

PubMedDate not supplied

Expression of vascular endothelial growth factor in malignant mesothelioma.

Malignant mesothelioma is the most common primary pleural neoplasm. Angiogenesis is an important component of a variety of pathological processes, including carcinogenesis and tumor metastases. Vascular endothelial growth factor (VEGF) is the most potent known endothelial, cell specific mitogen. The authors assessed the relation between VEGF expression and clinicopathological variables or overall survival, in malignant mesothelioma. We studied 37 patients with malignant pleural mesothelioma and found that 36 out of 37 (97.3%) malignant mesothelioma samples were stained positively for VEGF. An increased expression of VEGF was observed in the epithelioid type compared with the other histological types of malignant mesothelioma, including the biphasic and sarcomatoid types. No statistically significant association was observed between VEGF expression and gender, age, or clinical stage. Furthermore, the expression of VEGF did not impact on the survival of patients with malignant mesothelioma. Although VEGF expression might be important for tumor development and maintenance, it was not identified as a prognostic factor in malignant mesothelioma.

Adult↗