PubMed Health⌕ Search

Biomedical subjects

S Harita

Publications and source records attributed to S Harita.

13 recordsLinked to original sources

Continued gefitinib treatment after disease stabilisation prolongs survival of Japanese patients with non-small-cell lung cancer: Okayama Lung Cancer Study Group experience.

BACKGROUND: This study aimed to investigate the survival outcome of patients with non-small-cell lung cancer (NSCLC) who had obtained disease stabilisation with gefitinib treatment and to clarify the effect of continued treatment with gefitinib on prognosis. PATIENTS AND METHODS: We reviewed the clinical records of 365 Japanese patients with NSCLC who received gefitinib (250 mg/day). RESULTS: Of 324 (89%) patients assessable for response, 147 (45%) obtained disease stabilisation and 71 (22%) patients achieved an objective response. Overall survival in patients obtaining disease stabilisation was significantly longer than in patients with progressive disease (median survival time 12.1 versus 4.4 months; P <0.0001). In patients obtaining disease stabilisation, those who continued gefitinib treatment until disease progression tended to have longer overall and progression-free survival compared with those discontinuing gefitinib treatment (1-year survival rate 52.1% versus 36.6%, P = 0.08; 1-year progression-free survival rate 31.8% versus 5.2%, P = 0.001). Multivariate analysis showed discontinuing gefitinib was an independent risk factor for progression-free survival (hazard ratio 1.66; 95% confidence interval 1.07-2.56; P = 0.022) but not for overall survival. CONCLUSIONS: Our findings indicate the importance of achieving disease stabilisation with gefitinib treatment and continued gefitinib treatment in Japanese patients with disease stabilisation, although further studies are required to confirm these findings.

Adult↗

Phase I/II study of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small-cell lung cancer.

Recent studies have suggested the superiority of concomitant over sequential administration of chemotherapy and radiotherapy. Docetaxel and cisplatin have demonstrated efficacy in advanced non-small-cell lung cancer (NSCLC). This study evaluated the safety, toxicity, and antitumour activity of docetaxel/cisplatin with concurrent thoracic radiotherapy for patients with locally advanced NSCLC. Patients with locally advanced NSCLC (stage IIIA or IIIB), good performance status, age or=3 toxicities of 71, 60, 24, and 19%, respectively. Toxicity was significant, but manageable according to the dose and schedule modifications. Dose intensities of docetaxel and cisplatin were 86 and 87%, respectively. Radiotherapy was completed without a delay in 67% of 42 patients. The overall response rate was 79% (95% confidence interval (CI), 66-91%). The median survival time was 23.4+ months with an overall survival rate of 76% at 1 year and 54% at 2 years. In conclusion, chemotherapy with cisplatin plus docetaxel given on days 1, 8, 29, and 36 and concurrent thoracic radiotherapy is efficacious and tolerated in patients with locally advanced NSCLC and should be evaluated in a phase III study.

Adult↗

Fractionated administration of irinotecan and cisplatin for treatment of non-small-cell lung cancer: a phase II study of Okayama Lung Cancer Study Group.

A phase II study of fractionated administration of irinotecan (CPT-11) and cisplatin (CDDP) in patients with non-small-cell lung cancer (NSCLC) was conducted. Between January 1996 and January 1998, 44 previously untreated patients with stage IIIB or IV NSCLC were enrolled. CDDP at a dose of 60 mg x m(-2) was given first and followed by CPT-11 at a dose of 50 mg x m(-2). Both drugs were given by 1-hour infusion on days 1 and 8, and repeated every 4 weeks up to 4 cycles. 42 patients were evaluated for response and 44 for survival and toxicity. 20 patients (48%: 95% confidence interval 32-63%) achieved an objective response. The median duration of responses was 8 months, and the median survival time and the 1-year survival rate were 12.5 months and 56.8%, respectively. Major toxicities were neutropenia and diarrhoea. Grade 3 or 4 neutropenia occurred in 70.5% of the patients and one patient died of sepsis. Grade 3 or 4 diarrhoea was experienced in 25.0%, but manageable by conventional therapy. In conclusion, fractionated administration of CPT-11 and CDDP was highly effective for advanced NSCLC with manageable toxicities.

Adult↗

[Acute eosinophilic pneumonia with diffuse fine nodular shadows].

A 45-year-old man was admitted to our hospital because of high fever, dry cough, and respiratory distress. Chest roentgenograms and computed tomograms showed diffuse fine nodular shadows without any other interstitial or alveolar infiltrates. An examination of transbronchial lung biopsy specimens disclosed infiltration of eosinophils and lymphocytes in alveolar walls and perivascular areas. Bronchoalveolar lavage fluid revealed elevated total cell counts, mostly of eosinophils and lymphocytes. The patient was given a diagnosis of acute eosinophilic pneumonia (AEP), but his symptoms improved in a week without any medication. Although diffuse fine nodular shadows on x-ray films may sometimes be the only sign of AEP.

Acute Disease↗

Macrophage-chemotactic factor-producing T cell hybridomas reactive to phosphorylcholine in I-E-restricted manner.

Macrophage-chemotactic factor (MChF)-producing T cell hybridomas were established. These hybridomas produced MChF upon the specific antigenic stimulation with phosphorylcholine (PC)-conjugated protein in the presence of I-Ed-positive antigen-presenting cells. The hybridomas also secreted MChF after co-culture with concanavalin A in the absence of antigen-presenting cells. The MChF-secreting hybridomas were positive for Kd, Dd, Lyt-1.2 but negative for I-Ad, Lyt-2.2. The molecular weight of MChF produced by the hybridomas was 43000 and the factor was focused at pH 6.6-6.8 in the chromatofocusing procedure. The MChF was protease sensitive but resistant to neuraminidase treatment, and it was stable by heating at 80 degrees C for 15 min. The MChF-producing hybridomas established in this stud did not produce macrophage migration inhibitory factor (MIF), macrophage-activating factor (MAF) or interleukin 2, suggesting molecular nonidentity between MChF and these lymphokines. The MChF-producing T cell hybridomas reactive to specific antigens (PC) will be promising tools for analysis of molecular nature of MChF as well as molecular aspects of antigen recognition mechanism of T cells.

Animals↗

Lymphocyte chemotaxis in inflammation. IX. Further characterization of lymphocyte chemotactic lymphokines produced by purified protein derivative-stimulation in vitro and in vivo.

As recently reported, one lymphocyte chemotactic factor (beta-LCF, mol. wt. about 27,000) released from activated guinea-pig lymphocytes appeared to be identical to one of the LCFs (LCF-d) isolated from extract of purified protein derivative (PPD)-induced delayed-type hypersensitivity skin reaction sites in guinea-pigs with respect to antigenicity and chemotactic effect for T cells. However, the mol. wt. of LCF-d (about 300,000) was clearly distinct from beta-LCF. The experiments were undertaken to clarify the problem. beta-LCF appeared to be bound to some protein of normal guinea-pig serum (GPS) because the chemotactic activity was revealed in the fraction corresponding to that of LCF-d when the mixtures of beta-LCF with GPS were applied to a Sephadex G-200 column. Additionally, binding experiments using fluorescein isothiocyanate (FITC)-labelled beta-LCF were performed; fluorescence was only detected in the chemotactic fraction. It was thus assumed that the lymphokine (beta-LCF) would be released from activated lymphocytes around the inflammatory tissue, then bound with serum protein exuded in the site and function as LCF-d. The possibility was supported by the evidence that beta-LCF like-chemotactic substance (mol. wt. about 27,000) was dissociated from LCF-d under acid conditions. The factor dissociated from LCF-d was also bound with GPS protein under neutral conditions and converted to high molecular substance resembling LCF-d physiochemically. Furthermore, the chemotactic activity of LCF-d was almost completely absorbed by antibody against GPS. It is thus considered that the chemotactic activity of LCF-d may be attributed to beta-LCF released from activated lymphocytes and that some serum protein which binds beta-LCF may function as a carrier protein in the DTH sites.

Animals↗

Lymphocyte chemotaxis in inflammation. VII. Isolation and purification of chemotactic factors for T lymphocytes from PPD-induced delayed hypersensitivity skin reaction site in the guinea-pig.

Four types of lymphocyte chemotactic factor (LCF-a, -b, -c and -d) could be isolated from extract of 24-hr-old delayed-type hypersensitivity (DTH) skin reaction sites induced with purified protein derivative (PPD) in guinea-pigs by gel filtration on Sephadex G-100 followed by chromatography with DEAE-Sephadex. Partially purified LCF-b was thought to be a heat-stable protein with a molecular weight (mol. wt.) of about 14,000. LCF-c separated from LCF-d by chromatography with DEAE-Sephadex was highly purified by chromatography with CM-Sephadex, immunoadsorbent chromatography coupled with anti-IgG antibody, and chromatofocusing in that order. It was considered to be a heat-labile protein with a mol. wt. of about 160,000 and with pI of 8.1 +/- 0.2. LCF-d first separated from LCF-c was also highly purified by chromatography with CM-Sephadex followed by preparative isotachophoresis. The factor was considered to be a heat-labile protein with a mol. wt. of approximately 300,000 and with pI of 6.2 +/- 0.2. These factors were similarly active for non-adherent cells (mostly T cells) but not for cells (mostly B cells) adherent to anti-IgG antibody-coated petri-dishes. Since LCF-a was active for B cells as described earlier, it is thus suggested that LCF-b, LCF-c and LCF-d may be important for T cell migration in the DTH site to PPD.

Animals↗

Lymphocyte chemotaxis in inflammation. VIII. Demonstration of lymphocyte chemotactic lymphokines in PPD-induced delayed hypersensitivity skin reaction site in the guinea-pig.

The experiments were carried out to clarify whether lymphocyte chemotactic factors (LCFs) derived from activated lymphocytes, i.e. lymphocyte chemotactic lymphokines would exist in delayed-type hypersensitivity (DTH) reaction sites in guinea-pigs. To analyse the problem, we attempted to use an immunoadsorbent column conjugated with respective antibodies against LCFs (LCF-b, LCF-c and LCF-d) isolated from purified protein derivative (PPD)-induced DTH skin reaction sites in guinea-pigs. The chemotactic activity of culture supernatants from PPD- or concanavalin A (Con A)-stimulated lymph node (LN) cells was decreased to about 50% by the immunoadsorbent column with anti-LCF-c antibody or anti-LCF-d antibody, while its activity was little or not influenced by the columns with anti-LCF-b, anti-IgG or anti-IgM antibody. Further experiments using successive immunoadsorption with anti-LCF-c antibody followed by anti-LCF-d antibody showed almost the complete adsorption of the chemotactic activity in the above culture fluids. Additionally, the chemotactic lymphokine which was absorbed by anti-LCF-c antibody had a similar mol. wt. to that of LCF-c (mol. wt about 160,000). However, the chemotactic lymphokine which was absorbed by anti-LCF-d antibody had a mol. wt. of about 27,000; it was clearly distinct in mol. wt. from LCF-d (mol. wt. about 300,000). It is thus suggested that at least one of lymphocyte chemotactic lymphokines exists in the DTH reaction sites and functions as LCF-c.

Animals↗

Production of two lymphocyte chemotactic factors by antigen-stimulated guinea pig lymphocytes.

Lymph node cells from guinea pigs sensitized by BCG elaborated two chemotactic factors for lymphocytes when stimulated with purified protein derivative in vitro 4 weeks after immunization. Production of the factors occurred within 24 h of incubation. The two factors were termed alpha- and beta-lymphocyte chemotactic factors (alpha-LCF, beta-LCF), relative to their elution order on gel chromatography. The molecular weights were about 160,000 and 27,000, respectively. alpha-LCF was labile to heating at 56 degrees C for 30 min. Both factors were sensitive to digestion by trypsin, and were effective for T cells but not for B cells.

Animals↗

Lymphocyte chemotaxis in inflammation. III. Demonstration of lymphocyte chemotactic activity in extract from PPD-induced delayed hypersensitivity skin reaction site in the guinea-pig.

Various skin extracts from inflammatory lesions in guinea-pigs were assayed for chemotactic activity for guinea-pig lymphocytes; distinct chemotactic activity was shown in extract from PPD-induced delayed hypersensitivity reaction sites, and the time-course of chemotactic activity almost paralleled the intensity of lymphocyte reaction in skin sites. However, extracts obtained from various control sites or passive Arthus reaction sites exhibited little chemotactic activity for the cells. It is therefore suggested that lymphocyte chemotactic factor(s) was produced in the soluble form in the delayed hypersensitivity reaction.

Animals↗