Miiru Izumi

Expression of tumor-associated antigen RCAS1 correlates significantly with poor prognosis in nonsmall cell lung carcinoma

RCAS1 is a recently discovered antigen molecule expressed on the membrane of cancer cells, and it acts as a ligand for a putative receptor present on immune cells such as T, B and NK cells. It has been suggested that RCAS1 expression is related to the escape of tumors from immune surveillance. In this study, the relation between RCAS1 expression and various clinicopathologic variables, including patient prognosis, was investigated in lung carcinoma through immunohistochemical analysis.

Diagnostic value of bone‐turnover metabolites in the diagnosis of bone metastases in patients with lung carcinoma

Several biochemical markers of bone formation and bone resorption have been developed recently. The authors evaluated the usefulness of new biomarkers, such as urinary deoxypyridinoline (D‐PYD), serum pyridinoline cross‐linked C‐telopeptides of Type I collagen (1CTP), and urinary pyridinoline cross‐linked N‐telopeptides of Type I collagen (NTx), in the assessment of bone metastases in patients with lung carcinoma.

Incidence of hypertrophic pulmonary osteoarthropathy associated with primary lung cancer

Background and objective:  Although the association of hypertrophic pulmonary osteoarthropathy (HPO) with lung cancer was investigated in the 1960s, the recent incidence of clinically apparent HPO is not known. Data from a large series of patients with lung cancer were analysed, in order to assess the incidence of possible HPO, based on bone scintigraphy, as well as the incidence of clinically confirmed HPO. The clinical features of confirmed HPO were also evaluated.

Enhancement of antigen-presenting capacity and antitumor immunity of dendritic cells pulsed with autologous tumor-derived RNA in mice.

Dendritic cells (DCs) are antigen-presenting cells that play an important role in antitumor immunity. Several studies have reported that DCs pulsed with RNA from tumor cells have the ability to suppress tumors, but the details regarding the function and the immune-mechanism of DCs transfected with RNA remain to be elucidated. In this study, we investigated the transfection efficiency of RNA into DCs, and the functional modification and the antitumor efficacy of DCs pulsed with tumor-derived RNA. After the transfection of tumor-derived RNA into DCs cultured from the bone marrow of mice, pulsed DCs exhibited a high expression of both MHC antigens and CD86 on the cell surface as well as cultured DCs, and had a stronger ability both to present antigen on the MHC antigens and to stimulate T cells compared with DCs without transfection. DCs could sufficiently translate luciferase encoding RNA into luciferase proteins, and luciferase protein was expressed up to 12 hours in pulsed DCs. The DCs pulsed with tumor-derived RNA could elite a potent induction of cytotoxic T lymphocytes against autologous tumors, but not lysis against syngeneic normal cells. RNA-pulsed DCs exhibited a significant antitumor immunity in animal model. In conclusion, DCs could sufficiently uptake exogenous tumor-derived RNA, and consequently grow to be an intermediate maturate type, and induce potent T-cell stimulation and fully cause an antitumor effect in vivo. Therapy with DCs pulsed with tumor-derived RNA is sufficiently effective and safe, and thus it is considered to be clinically useful for tumor-immunotherapy.

Phase II study of uracil‐tegafur plus cisplatin in patients with previously untreated advanced non‐small cell lung cancer

Background and objective:  A multi‐institutional phase II trial combining uracil‐tegafur (UFT) and cisplatin (CDDP) was conducted in patients with previously untreated advanced non‐small cell lung cancer (NSCLC) to evaluate the safety and efficacy of this combined treatment regimen.

Prognostic value of serial serum KL-6 measurements in patients with idiopathic pulmonary fibrosis

BACKGROUND The prognostic significance of serial measurements of serum KL-6 levels in patients with idiopathic pulmonary fibrosis (IPF) is unclear; hence, it was assessed in this study. METHODS Medical records of 66 patients with IPF, who were not treated with pirfenidone prior to enrollment, were retrospectively reviewed for information on clinical progress, forced vital capacity (FVC), survival, and serum KL-6 levels. We assessed initial serum levels of KL-6, serial changes in serum KL-6 levels, yearly decline in FVC (ΔFVC), and the rate of decline (%ΔFVC). RESULTS Patients with increased serum KL-6 levels during follow-up had a significantly steeper decline in ΔFVC than those with no KL-6 increase (-201 vs. -50.7ml/year; p=0.0001). Patients with both initial serum KL-6 ≥1000U/ml and serial increases in serum KL-6 had the steepest decline, while those with both initial serum KL-6 <1000ml and no serial increases in KL-6 had the least decline in ΔFVC and %ΔFVC. Relative to the non-increased KL-6 group, survival in the increased KL-6 group tended to be poorer (p=0.0530). Patients with both initial serum KL-6 values <1000U/ml and no serial increase in KL-6 had more favorable prognoses than those with serial increases in KL-6 or initial serum KL-6 values ≥1000U/ml (p<0.0044). Prognosis was significantly poorer in patients with serial KL-6 changes >51.8U/ml/year than in those with serial KL-6 changes <51.8U/ml/year (p=0.0009). CONCLUSION Thus, serial serum KL-6 measurements can be useful for assessing prognosis in patients with IPF.

Phase I study of weekly irinotecan combined with weekly cisplatin in patients with advanced solid tumors.

Background: Previous studies have reported a synergistic effect between irinotecan and cisplatin. We have conducted a phase I trial combining these agents to find the optimal dose of irinotecan in combination with a fixed dose of cisplatin. Methods: Patients with advanced solid tumors, aged ≤75 years, performance status ≤2, and adequate organ function were enrolled in this study. They were treated at 4-week intervals with irinotecan plus 20 mg/m2 cisplatin on days 1, 8, and 15. The starting dose of irinotecan of 40 mg/m2 was escalated in 10 mg/m2 increments until a maximum dose of 90 mg/m2 was reached. Results: The recommended dose for phase II studies is 90 mg/m2 of irinotecan and 20 mg/m2 of cisplatin on days 1, 8, and 15. Overall response to the chemotherapy was 35% (95% confidential interval, 19.2–54.6%). Conclusion: This combination seems to be active against lung cancer with acceptable toxicity. A phase II study is now ongoing.

Patients with MAC Lung Disease Have a Low Visceral Fat Area and Low Nutrient Intake

Objective. This study aimed to examine the nutritional status and nutrient intake of patients with MAC lung disease with a focus on visceral fat area. Patients and Methods. Among 116 patients of our hospital with nontuberculous mycobacteriosis who were registered between May 2010 and August 2011, 103 patients with MAC lung disease were included in this study. In all patients, nutritional status and nutrient intake were prospectively examined. Results. Patients were 23 men and 80 women (mean age, 72.3 ± 10.9 years). BMI (kg/m2) at the time of registration was 20.4 ± 2.7 in men and 19.2 ± 2.9 in women. Visceral fat area (cm2) was significantly lower in women (35.7 ± 26.6) than in men (57.5 ± 47.4) (p = 0.0111). The comparison with general healthy adults according to age revealed a markedly reduced visceral fat area among patients with MAC lung disease. With respect to nutrient intake, energy adequacy (86.1 ± 15.7%), protein adequacy (82.4 ± 18.2%), lipid adequacy (78.1 ± 21.8%), and carbohydrate adequacy (89.6 ± 19.2%) ratios were all low at the time of registration. BMI was significantly correlated with protein adequacy (p = 0.0397) and lipid adequacy (p = 0.0214) ratios, while no association was found between visceral fat area and nutrient intake. Conclusion. Patients with MAC lung disease had a low visceral fat area and low nutrient intake.

Prognostic factors in patients with miliary tuberculosis

Background and purpose Acute respiratory distress syndrome (ARDS) complication has long been considered a factor associated with poor prognosis in patients with miliary tuberculosis. However, few reports exist on the prognostic factors of miliary tuberculosis including those complicating ARDS. Subjects and methods We retrospectively examined prognoses and other clinical information obtained from medical records of a total of 68 patients diagnosed with miliary tuberculosis. Clinical findings were compared between patients who died within three months (non-survivor group) and those who survived beyond three months (survivor group), and risk factors for death within three months of diagnosis were examined using logistic regression analysis. Results Fifteen of 68 patients diagnosed with miliary tuberculosis died within three months. Most patients were aged 60 years or older (63 patients; 91.2%), with a peak in the 80 s (32 patients; 47.1%). Of the 68 patients with miliary tuberculosis, 13 (19%) had ARDS. The risk of death within three months increased with increasing age and ARDS onset during the disease course. The results of multivariate analysis revealed that, in addition to age (odd ratio (OR): 15.5) and the presence/absence of ARDS (OR: 12.0), consciousness disturbance (OR: 81.53) and high BUN levels (OR: 5.71) were independent factors for death within three months. Conclusion In patients with miliary tuberculosis, old age, ARDS, consciousness disturbance, and high BUN levels were factors associated with poor prognosis.