TERT promotor region rearrangements analyzed in high-risk neuroblastomas by FISH method and whole genome sequencing.

BACKGROUND: Unfavorable neuroblastomas (NBLs) achieve telomere stabilization via telomerase activation through MYCN amplification, TERT promoter region (TERT-PR) rearrangements, or alternative telomere lengthening of telomeres. No well-established methods are available for investigating TERT-PR rearrangements. We examined the relationship between and prognosis by fluorescence in situ hybridization (FISH) upstream and downstream of TERT to establish a simple analysis method. PROCEDURE: TERT-PR rearrangements were analyzed in 3 M MYCN amplified cases and, 11MYCN non-amplified cases (1 MS case, 1 L2 case and 2 M cases less than 18 months, and 1 L2 case and  6 M cases over 18 months old at diagnosis) to determine if MYCN and TERT-PR rearrangement were independent prognostic factors. In total, 14 patients (11 males, 3 females; median age 36.4 months, range 1-122 months) with NBLs were evaluated at Hiroshima University. We identified MYCN amplification, TERT expression, and TERT-PR rearrangements. TERT-PR rearrangement was detected by FISH upstream and downstream of TERT on Chr5.p15.33. For TERT-PR rearranged cases, we characterized the fusion partners by whole genome sequencing. RESULTS: We detected TERT-PR rearrangements in two NBL samples. Both samples were high-risk NBLs and MYCN single NBLs, and their TERT expression levels were extremely higher than in the other samples. Genomic translocation occurred at chromosome 5p15.33 according to whole genome sequencing, agreeing with the FISH results. One case showed translocation of the chr5.p15.33 SLCA6A19 gene to 22q12.3, and another case showed chr5p15.33 to chr5q33.3. CONCLUSIONS: FISH is a useful diagnostic tool for evaluating high-risk NBLs in which TERT-PR rearrangements have occurred.

Risk Factors for Problem Drinking among Evacuees in Fukushima following the Great East Japan Earthquake: The Fukushima Health Management Survey.

Many studies have consistently reported the bidirectional relationship between problem drinking and psychological distress following a disaster, but the risk factors of problem drinking following a disaster remain unclear. In this study, we therefore aimed to explore the risk factors associated with the incidence of problem drinking among evacuees after the Great East Japan Earthquake of March 11, 2011. We used the data for evacuees of the Fukushima Daiichi nuclear power plant accident, obtained from the Mental Health and Lifestyle Survey. A total of 12,490 individuals from 13 municipalities, which included the evacuation order areas after the accident, completed surveys between 2012 and 2013. The CAGE (Cutting down, Annoyed by criticism, Guilty feeling, and Eye-opener) questionnaire was used to screen the participants for alcohol dependence, and a score ≥ 2 indicated problem drinking. Logistic regression models were applied to investigate the possible predictors of problem drinking. The results showed that insufficient sleep and heavy drinking (≥ 4 drinks per day) were significant risk factors for the incidence of problem drinking in both men and women. Additional risk factors included family financial issues due to the disaster and trauma symptoms among men and a diagnosed history of mental illness among women. Other remaining variables were not significantly associated with problem drinking. The present study is the first to identify the risk factors for problem drinking following a compound disaster. Our findings could be used to develop a primary intervention program to improve evacuees' health and lives following a disaster.

Drinking Behavior and Mental Illness Among Evacuees in Fukushima Following the Great East Japan Earthquake: The Fukushima Health Management Survey.

BACKGROUND: Recent evidence from alcohol and trauma studies suggests that disasters are associated with increases in the consumption of alcohol. The Great East Japan Earthquake and the associated nuclear disaster have continued to affect the mental health of evacuees from Fukushima. This study aimed to extend these findings by examining the relationship between drinking behaviors and the risk of mental illness after the compound disaster. METHODS: We conducted the Mental Health and Lifestyle Survey with 56,543 evacuees. Kessler's K6 was used to assess the risk of mental illness, and logistic regression models were applied to analyze how drinking behavior patterns influence the risk of serious mental illness after adjustment for confounding variables. RESULTS: Logistic regression analysis evidenced that beginning heavy and light drinkers had the highest and a higher risk of serious mental illness, respectively. Individuals who were nondrinkers pre- and postdisaster had the lowest proportional risk of mental illness. Abstainers also had some risk to their mental health after the compound disaster. CONCLUSIONS: The results of this study highlight that beginning drinkers have a high risk of serious mental illness. Thus, mental health professionals should pay attention to the drinking behaviors of evacuees, which might predict increased risk of serious mental illness and consequently indicate a need for psychological intervention.

Phenotypes of gene disruptants in relation to a putative mitochondrial malate-citrate shuttle protein in citric acid-producing Aspergillus niger.

The mitochondrial citrate transport protein (CTP) functions as a malate-citrate shuttle catalyzing the exchange of citrate plus a proton for malate between mitochondria and cytosol across the inner mitochondrial membrane in higher eukaryotic organisms. In this study, for functional analysis, we cloned the gene encoding putative CTP (ctpA) of citric acid-producing Aspergillus niger WU-2223L. The gene ctpA encodes a polypeptide consisting 296 amino acids conserved active residues required for citrate transport function. Only in early-log phase, the ctpA disruptant DCTPA-1 showed growth delay, and the amount of citric acid produced by strain DCTPA-1 was smaller than that by parental strain WU-2223L. These results indicate that the CTPA affects growth and thereby citric acid metabolism of A. niger changes, especially in early-log phase, but not citric acid-producing period. This is the first report showing that disruption of ctpA causes changes of phenotypes in relation to citric acid production in A. niger.

Impact of supervised cardiac rehabilitation on urinary albumin excretion in patients with cardiovascular disease.

Urinary albumin excretion is a predictor of cardiovascular death. Cardiac rehabilitation (CR) with exercise training (ET) has been shown to improve exercise capacity and prognosis in patients with cardiovascular disease (CVD). However, it remains unclear whether CR reduces urinary albumin excretion in CVD patients. We performed a retrospective, observational study using data obtained from 98 male CVD patients without macroalbuminuria and estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m(2) who participated in CR with ET during hospitalization. Twenty-three patients continued supervised ET for 6 months (supervised group) and 75 patients quit supervised ET (non-supervised group). The supervised ET program consisted of 60 minutes of supervised sessions 1-3 times a week and 30-60 minutes of home exercise at least twice a week. Urinary albumin/creatinine ratio (ACR) was significantly decreased in the supervised group at 6 months after enrollment (43 ± 71 mg/g to 17 ± 20 mg/g creatinine, P < 0.05) but not in the non-supervised group. eGFR was unchanged in the supervised group but was significantly decreased in the non-supervised group (72 ± 18 mL/minute/1.73 m(2) to 67 ± 17 mL/minute/1.73 m(2), P < 0.001). The results of multiple regression analysis showed that only supervised ET was an independent contributor to ΔACR. CR with supervised ET decreased urinary albumin excretion without deterioration of renal function. These findings suggest that continuation of a supervised ET program is associated with reduction in the development of CVD and reduction in cardiovascular morbidity and mortality in CVD patients.

Androgen receptor promotes sex-independent angiogenesis in response to ischemia and is required for activation of vascular endothelial growth factor receptor signaling.

BACKGROUND: Hypoandrogenemia is associated with an increased risk of ischemic diseases. Because actions of androgens are exerted through androgen receptor (AR) activation, we studied hind-limb ischemia in AR knockout mice to elucidate the role of AR in response to ischemia. METHODS AND RESULTS: Both male and female AR knockout mice exhibited impaired blood flow recovery, more cellular apoptosis, and a higher incidence of autoamputation after ischemia. In ex vivo and in vivo angiogenesis studies, AR-deficient vascular endothelial cells showed reduced angiogenic capability. In ischemic limbs of AR knockout mice, reductions in the phosphorylation of the Akt protein kinase and endothelial nitric oxide synthase were observed despite a robust increase in hypoxia-inducible factor 1α and vascular endothelial cell growth factor (VEGF) gene expression. In in vitro studies, siRNA-mediated ablation of AR in vascular endothelial cells blunted VEGF-stimulated phosphorylation of Akt and endothelial nitric oxide synthase. Immunoprecipitation experiments documented an association between AR and kinase insert domain protein receptor that promoted the recruitment of downstream signaling components. CONCLUSIONS: These results document a physiological role of AR in sex-independent angiogenic potency and provide evidence of novel cross-talk between the androgen/AR signaling and VEGF/kinase insert domain protein receptor signaling pathways.

Cardiac rehabilitation reduces serum levels of oxidized low-density lipoprotein.

BACKGROUND: Oxidized low-density lipoprotein (oxLDL) levels have been found to play an important role in the progression of atherosclerosis. However, methods for effectively reducing oxLDL levels have not been established. Comprehensive cardiac rehabilitation (CR) with exercise training prevents the progression of atherosclerosis, and might reduce oxLDL levels. METHODS AND RESULTS: We measured the serum levels of malondialdehyde-modified LDL (MDA-LDL), a marker of oxLDL, in 136 patients who were enrolled in a 6-month CR program. Peak oxygen consumption (V̇O2) and MDA-LDL levels were analyzed, before and 6 months after enrolment. In total, 67 patients completed the CR program (CR group) and 69 patients failed to complete the program (non-CR group). Peak V̇O2increased significantly in the CR group (P<0.01). The levels of MDA-LDL decreased significantly in the CR group (P<0.01) but not in the non-CR group. ∆V̇O2(peak V̇O2after CR-peak V̇O2before CR) was negatively associated with ∆MDA-LDL (MDA-LDL after CR-MDA-LDL before CR) (R(2)=0.11, P=0.01). Multiple regression analysis showed that continuing CR was an independent determining factor for lowering MDA-LDL levels. CONCLUSIONS: CR decreases oxLDL levels in patients with cardiovascular diseases. Moreover, CR may prevent cardiovascular events through an antioxidative effect.

Pentraxin 3 is a local inflammatory marker in atrial fibrillation.

Increasing evidence indicates that inflammation contributes to the pathogenesis of atrial fibrillation (AF). Pentraxin 3 (PTX3) is produced abundantly in local inflammatory lesions while C-reactive protein (CRP) is produced mainly in the liver. In this study, we investigated whether a local level of PTX3 might be a sensitive marker for the local inflammation of AF. Blood from the periphery and left atrial appendage (LAA) was sampled from 23 patients with AF undergoing pulmonary vein isolation, and from 10 control subjects with Wolff-Parkinson-White syndrome. We measured peripheral and LAA plasma concentrations of CRP, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and PTX3. Plasma PTX3 concentrations in both locations were higher in patients with AF than in control subjects. PTX3 concentrations were significantly higher in the LAA than the periphery in patients with AF (3.7 ± 1.4 vs 3.3 ± 1.2 ng/ml, P < 0.01), but not in control subjects (2.4 ± 0.5 vs 2.4 ± 0.5 ng/ml, not significant). Patients and controls showed no significant differences in CRP, IL-6, or TNF-α concentrations between the periphery and LAA. Interestingly, there was a significant positive correlation between LAA plasma concentrations of PTX3 and left atrial volume (r = 0.55, P < 0.01). These data demonstrate that local PTX3 production in the left atrium might reflect the local inflammation of AF.

Ghrelin protects the heart against ischemia-induced arrhythmias by preserving connexin-43 protein.

Vagal nerve stimulation has been postulated to confer an antifibrillatory effect. We studied whether ghrelin administration would exert an antiarrhythmic effect via modulation of autonomic nerve activity in rats after acute myocardial ischemia (MI). Male Sprague-Dawley rats were exposed to 30 min of ischemia following ligation of the left coronary artery. Animals were then randomized to receive either ghrelin (n = 26) or saline (n = 26) during the period of coronary ligation. Power spectral analysis of heart-rate variability revealed that the administration of ghrelin increased the high-frequency (HF) power and decreased the low-frequency (LF)/HF ratio. Ventricular tachyarrhythmias were less frequent in rats after MI who received ghrelin in comparison with rats that received saline. Immunoblotting and immunohistochemistry revealed that rats given saline alone during MI exhibited a marked reduction in phosphorylated connexin-43 within the left ventricle, whereas those that received ghrelin displayed only minor reductions in comparison with sham-operated rats. These effects of ghrelin were diminished by the coadministration of atropine or the blockade of vagal afferents. These data demonstrate that the beneficial effect of ghrelin might be mediated by modulation of cardiac autonomic nerve activity.

Detection of MYCN amplification using blood plasma: noninvasive therapy evaluation and prediction of prognosis in neuroblastoma.

PURPOSE: Amplification of neuroblastoma derived (avian)v-myc myelocytomatosis viral related oncogene (MYCN) is an important risk-stratified indicator in neuroblastoma. To evaluate the feasibility of noninvasive measurement of MYCN amplification, we analyzed MYCN amplification in stored blood plasma samples. METHODS: We used quantitative real-time PCR to determine MYCN copy numbers in plasma-derived DNA of 10 healthy volunteers and 50 neuroblastoma cases. The copy number was calculated as the ratio of copies of MYCN to those of a reference gene. Plasma samples obtained after surgery or neoadjuvant therapy were also analyzed in five cases and four cases, respectively. RESULTS: In 34 neuroblastoma cases, MYCN was nonamplified in both tumor tissue and blood plasma. In 16 neuroblastoma cases, MYCN was amplified in both tumor tissue and blood plasma; 13 of the 16 cases showed poor outcomes. MYCN amplification was undetectable in blood plasma shortly after surgery or neoadjuvant therapy. The correlation coefficient between MYCN copy numbers in tumor tissue and in blood plasma was approximately 0.9. CONCLUSION: We can detect MYCN amplification of tumor tissue noninvasively and quantitatively by measuring the MYCN copy number in blood plasma. Determination of MYCN copy number in plasma may be useful when evaluating surgery and neoadjuvant chemotherapy.

A cisplatin plus pirarubicin-based JPLT2 chemotherapy for hepatoblastoma: experience and future of the Japanese Study Group for Pediatric Liver Tumor (JPLT).

INTRODUCTION: The Japanese Study Group for Pediatric Liver Tumor (JPLT) has conducted cooperative treatment studies on hepatoblastoma (HBL) since 1991. The JPLT2 protocol was launched in 1999 to evaluate the efficacy of cisplatin/pirarubicin (CITA) under risk stratification. European and North American groups showed the improvement of HBL patients by pre- and postoperative chemotherapeutic regimens. Therefore, we evaluated the results of JPLT study and considered the future aspect of JPLT. METHODS: A total of 389 children with malignant hepatic tumors were enrolled in JPLT-2 until 2010. Data from 331 HBL cases were analyzed. RESULTS AND DICUSSION: Of the 331 patients enrolled, their 5-year overall survival and event-free survival rates were 83.3 and 68.0%, respectively. While outcomes of standard-risk cases (tumors involving 3 or fewer sectors of the liver) were excellent, those of high-risk cases (tumors involving 4 sectors of the liver or with distant metastases) remained poor. For 26 high-risk or relapse/refractory HBL cases, high-dose chemotherapy (HDC) with stem cell transplantation (SCT) was carried out. Among them, 6 of 12 relapse or refractory cases died. Compared with other regimens, the CITA regimen achieved similar or superior rates of survival among children with standard-risk HBL, while HDC with SCT was not effective in patients with high-risk HBL. Presently, a global Children's Hepatic Tumor International Consortium (CHIC) project is ongoing, with a focus on international cooperation and risk stratification in the field of rare liver cancers in children. More promising strategies, including liver transplantation and new targeting drugs under global risk stratification, are being proposed.

Eosinophilic myocarditis due to Churg-Strauss syndrome with markedly elevated eosinophil cationic protein.

A 67-year-old woman with asthma visited our hospital with increasing dyspnea and new-onset paresthesia and purpura in her legs. Physical examination showed a wheeze, pretibial edema, and surrounding purpura. Chest X-rays showed cardiac decompensation and an electrocardiogram revealed a new ST-T change. Laboratory data showed leukocytosis, hypereosinophilia (10,450/µL), troponin T(+), elevated BNP, and markedly elevated eosinophil cationic protein (ECP) (> 150 ng/mL). Echocardiography revealed diffuse left ventricular hypokinesis (ejection fraction 30%) with increased wall thickness. Coronary angiography was normal. Cardiac magnetic resonance imaging implied diffuse myocardial edema and subendocardial late gadolinium enhancement. Skin biopsy of purpura showed superfi cial perivascular dermatitis with remarkable eosinophilic infiltrations. No evidence of drug allergies, parasitic infection, or myeloproliferative disorder was detected. Based on these findings, a diagnosis of eosinophilic myocarditis due to Churg-Strauss syndrome was considered. She was administered prednisolone at a dose of 1 mg/kg, cyclophosphamide, and diuretics. Several markers of eosinophilic myocarditis and heart failure gradually improved, including ECP. She was discharged 30 days later with no cardiac event. Eosinophilic myocarditis is characterized by predominantly eosinophilic infi ltration. Eosinophilic granule proteins, such as ECP and major basic protein, play important roles in the pathogenesis of eosinophilic myocarditis. We experienced a rare case of eosinophilic myocarditis due to Churg-Strauss syndrome. Markedly elevated ECP played an important role in the early diagnosis and subsequent reduction in ECP served as a marker of monitoring. In an asthmatic patient with dyspnea, hypereosinophilia, and vasculitis, Churg-Strauss syndrome with eosinophilic myocarditis should be considered.

Pharmacology of Aldosterone and the Effects of Mineralocorticoid Receptor Blockade on Cardiovascular Systems.

UNLABELLED: It is well-known that aldosterone plays an important role in reabsorption of sodium and fluid, and in potassium excretion in kidneys via epithelial mineralocorticoid receptor (MR) activation. Recent studies have shown that aldosterone causes cardiovascular remodeling not only in a blood pressure-dependent manner, but also in a blood pressure-independent manner by decreasing nitric oxide bioavailability and modulating oxidative stress, leading to vascular inflammation. In addition, MR blockade does provide beneficial effects associated with cardiovascular protection, resulting in a reduction of cardiovascular morbidity and mortality. A growing body of evidence suggests that MR blockade is a promising therapeutic target to help prevent cardiovascular events. KEY WORDS: Aldosterone; Mineralocorticoid receptor; Nitrix oxide; Renin-angiotensin-aldosterone system.

A Six-Year Prospective Study on Problem Drinking among Evacuees of the Great East Japan Earthquake: The Fukushima Health Management Survey.

Evacuees of the Great East Japan Earthquake have experienced adverse, long-term physical and psychological effects, including problem drinking. This study examined the risk and recovery factors for problem drinking among evacuees between fiscal years (FY) 2012 and 2017 using data on residents in the evacuation area from the Mental Health and Lifestyle Survey. With the FY 2012 survey as a baseline, a survey comprising 15,976 men and women was conducted in the evacuation area from FY 2013 to FY 2017, examining the risk and protective factors for problem drinking. Particularly, the Cutting down, Annoyed by criticism, Guilty feeling, and Eye-opener (CAGE) questionnaire was used to evaluate problem drinking. Univariate and multivariate Cox proportional hazard models were constructed to identify the risk and recovery factors of problem drinking. The findings indicated that the male gender, insufficient sleep, job change, trauma symptoms, mental illness, family financial issues, and heavy drinking (≥4 drinks per day) were significant risk factors for the incidence of problem drinking among the evacuees. Furthermore, a high blood pressure diagnosis could exacerbate problem drinking among men, while younger age and a diabetes mellitus diagnosis could increase problem drinking among women. Trauma symptoms and heavy drinking inhibited recovery from problem drinking after the disaster. Understanding these factors can shape effective long-term intervention strategies to physically and psychologically support evacuees.

The Usefulness of Brief Telephonic Intervention After a Nuclear Crisis: Long-Term Community-Based Support for Fukushima Evacuees.

The Fukushima Daiichi Nuclear Power Station accident in 2011 produced over 100000 evacuees. In order to deal with an increased need of mental health care, brief, transdiagnostic Telephonic Interventions (TI) have been provided for those at risk of different mental health problems identified based on results of the Mental Health and Lifestyle Survey (MHLS). This study aimed to examine usefulness of TI with focusing on evacuees' subjective estimation assessed in individual follow-up interviews. The sample comprised 484 persons who had been evacuated from 13 municipalities in Fukushima Prefecture to 8 safer regions in and out of Fukushima. We conducted semi-structured interviews for participants receiving TI (intervention group) and those not receiving TI despite being identified as high risk (non-intervention group). The intervention group was older, had a higher proportion of self-reported mental illness, and higher unemployment compared with the non-intervention group. The satisfaction proportion of those who underwent TI was as high as 74.6%. Satisfaction was significantly associated with advance knowledge of TI availability (OR = 3.00, 95% CI: 1.59-5.64), and advice on health-related practices (OR = 2.15, 95% CI: 1.12-4.13). Thus, TI is considered to be feasible and useful for public health management practices in major disasters.

Outcome and Late Complications of Hepatoblastomas Treated Using the Japanese Study Group for Pediatric Liver Tumor 2 Protocol.

PURPOSE: We report here the outcomes and late effects of the Japanese Study Group for Pediatric Liver Tumors (JPLT)-2 protocol, on the basis of cisplatin-tetrahydropyranyl-adriamycin (CITA) with risk stratification according to the pretreatment extent of disease (PRETEXT) classification for hepatoblastoma (HB). PATIENTS AND METHODS: From 1999 to 2012, 361 patients with untreated HB were enrolled. PRETEXT I/II patients were treated with up-front resection, followed by low-dose CITA (stratum 1) or received low-dose CITA, followed by surgery and postoperative chemotherapy (stratum 2). In the remaining patients, after 2 cycles of CITA, responders received the CITA regimen before resection (stratum 3), and nonresponders were switched to ifosfamide, pirarubicin, etoposide, and carboplatin (ITEC; stratum 4). Intensified chemotherapeutic regimens with autologous hematopoietic stem-cell transplantation (SCT) after resection were an optional treatment for patients with refractory/metastatic disease. RESULTS: The 5-year event-free and overall survival rates of HB patients were 74.2% and 89.9%, respectively, for stratum 1, 84.8% and 90.8%%, respectively, for stratum 2, 71.6% and 85.9%%, respectively, for stratum 3, and 59.1% and 67.3%%, respectively, for stratum 4. The outcomes for CITA responders were significantly better than those for nonresponders, whose outcomes remained poor despite salvage therapy with a second-line ITEC regimen or SCT. The late effects, ototoxicity, cardiotoxicity, and delayed growth, occurred in 61, 18, and 47 patients, respectively. Thirteen secondary malignant neoplasms (SMNs), including 10 leukemia, occurred, correlating with higher exposure to pirarubicin and younger age at diagnosis. CONCLUSION: The JPLT-2 protocol achieved up-front resectability in PRETEXT I/II patients with no annotation factors, and satisfactory survival in patients who were CITA responders in the remaining patients. However, outcomes for CITA nonresponders were unsatisfactory, despite therapy intensification with ITEC regimens and SCT. JPLT-2 had a relatively low incidence of cardiotoxicity but high rates of SMNs.

Ion-pair chromatographic separation of glycoprotein derived oligosaccharides as their 8-aminopyrene-1,3,6-trisulfonic acid derivatives.

A reversed-phase ion-pair gradient liquid chromatographic method has been developed for separation of 8-aminopyrene-1,3,6-trisulfonic acid (APTS) labeled oligosaccharides derived from some glycoproteins. This separation mode has high capability for structural recognition of oligosaccharide isomers, which are usually difficult to separate using commonly used partition chromatography. In addition, some glycoprotein-derived complex-type oligosaccharides that have linkage isomers in one lactosamine arm and neuraminic acids existing in fetuin, as well as differences in the numbers of lactosamine branches, are separable using this mode. The ion-pair mode is promising for simple analyses of glycoprotein-derived oligosaccharides that are labeled with APTS.

Phase I study of paclitaxel, carboplatin and UFT in chemo-naive patients with advanced non-small cell lung cancer (NSCLC).

OBJECTIVE: We conducted a phase I study of paclitaxel (PTX), carboplatin (CBDCA), and UFT in chemo-naive patients with advanced non-small cell lung cancer (NSCLC). METHOD: Twenty-one chemo-naive patients with advanced NSCLC were enrolled. The study was conducted as a phase I dose-escalation study of various doses of systemic PTX followed by CBDCA on day 1 and oral UFT (400 mg/m2) on days 1-5 and 8-12, with the cycle repeated at 21-day intervals. At least three patients were enrolled in each step. RESULTS: The main toxicities were neutropenia and paresthesia, but were tolerable and reversible in all cases. Overall response rate was 57% (12 out of 21). The MTD was not reached at the highest dose level after the first cycle. Given previous recommends of PTX at 225 mg/m2 and CBDCA AUC 6 for two-drug therapy, the recommended dose for the phase II study under our regimen was set at PTX 225 mg/m2 on day 1, CBDCA AUC 6 on day 1, and UFT 400 mg/m2 on days 1-5 and 8-12. CONCLUSION: The combination of PTX, CBDCA, and UFT showed promising activity and acceptable toxicity in these chemo-naive patients, supporting the development of this combination as a feasible chemotherapeutic option for advanced NSCLC.