[Analysis of 14 cases of melanosis caused by 1, 8-dinitronaphthalene and 1, 8-diaminonaphthalene].

14 workers in the 1, 8-diaminonaphthalene workshop of a chemical company in Nantong City had symptoms or signs of varying degrees of pruritus and pigmentation of the face, neck and waist. Pathological examination of skin biopsies showed hyperkeratosis, the basal cells were liquefied and denatured. Seven workers were eventually diagnosed with occupational melanosis. To explore the causes of occupational melanosis caused by exposure to 1, 8-dinitronaphthalene and 1, 8-diaminonaphthalene, and to provide reference for the prevention and treatment of occupational melanosis in the future, this paper reported 14 cases of melanosis in the skin of workers in chemical industry.

Prednisolone dose during treatment of tuberculosis might be a risk factor for mortality in patients with systemic lupus erythematosus: a hospital-based cohort study.

Patients with systemic lupus erythematosus (SLE) are at high risk of tuberculosis (TB) because of their immunocompromised status and the use of immunosuppressive drugs. In endemic regions, TB complicates the diagnosis and treatment of SLE, but the risk factors of mortality in these patients have not been investigated. In this study, we reviewed medical records during 2006-2016. Patients who fulfilled the 1997 American College of Rheumatology SLE criteria and presented with definite TB were enrolled. The primary outcome was mortality during TB treatment. There were 5388 SLE patients screened, and 30 patients were enrolled. Seven patients died during follow-up. Compared with the survival group, patients in the mortality group had significantly more central nervous system involvement of TB, higher Systemic Lupus Erythematosus Disease Activity Index-2000 scores and more cyclophosphamide use before TB, and higher prednisolone dose before and during TB treatment. Cox regression showed that prednisolone dose during TB treatment was an independent risk factor for mortality (per 10 mg/day increase, hazard ratio (HR) 1.61, p = .019). For SLE patients, prednisolone dose during TB treatment is an independent risk factor for mortality. Keeping prednisolone dose at less than 25 mg per day during TB treatment might be a reasonable strategy in these patients.

[The role and mechanism of 2-deoxyglucose in reversing osimertinib-acquired resistance of non-small cell lung cancer cell line].

Objective: To explore the role and mechanism of 2-deoxyglucose (2-dg) in reversing osimertinib- acquired resistance of non-small cell lung cancer(NSCLC)cell line. Methods: The NSCLC line H1975 (purchased from the American Type Culture Collection) was conducted by induction method in vitro to construct the osimertinib-resistance NSCLC cell line H1975-OR. The osimertinib-resistance of H1975-OR cell line was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony-formation assay, Ki67 incorporation assay and the expression of apoptosis-related protein. The glycolysis level was assayed by the lactic acid production measured in the culture medium supernatant of H1975 and H1975-OR. The expression of glycolysis key enzymes (HK2, GLUT1, P-PKM2) and apoptosis-related protein (BIM, Bcl-2) were detected by Western blot. The cells were divided into control group, 2-deoxyglucose (4 mmol/L) monotherapy group, osimertinib (3 µmol/L) monotherapy group and 2-deoxyglucose (4 mmol/L)+ osimertinib (3 µmol/L) combination therapy group, then the apoptosis rate of cells was measured by flow cytometry to evaluate the pro-apoptotic ability of drugs. Date were analyzed by Independent-Samples t-test using SPSS 16.0 statistical software. Results: The glycolysis level of osimertinib-sensitive cell line H1975 was lower than that of osimertinib-resistance cell line H1975-OR [the yield of lactic acid, respectively, was (21.0±0.9) and (26.5±2.8) mmol·L(-1)·10(4)cells(-1), P<0.05]. The osimertinib- acquired resistance of H1975-OR could be reversed by 4 mmol/L 2-deoxyglucose(the IC(50) value of osimertinib in H1975-OR cell line decreased from (7.0±1.9) µmol/L to (1.4±0.1) µmol/L, which was close to the IC(50) value of osimertinib in H1975 cell line (1.0±0.2) µmol/L. The apoptosis rate of H1975-OR was significantly higher in 2-deoxyglucose + osimertinib combination therapy group (26.7±2.4)%, compared to control group (5.1±0.7)%, 2-deoxyglucose monotherapy group (6.1±2.5)% and osimertinib monotherapy group (11.4±2.7)%(all P<0.05). The expression of pro-apoptotic protein BIM in H1975-OR was significantly higher in 2-deoxyglucose+ osimertinib combination therapy group (177.8±28.1)% and the expression of anti-apoptotic protein Bcl-2 in H1975-OR was significantly lower in 2-deoxyglucose+ osimertinib combination therapy group (24.6±5.2)%, compared to control group (100±0)%, all P<0.05. Conclusion: 2-deoxyglucose can reverse the acquired resistance of NSCLC cell line to osimertinib, which may be related to the inhibition of cell glycolysis and the induction of apoptosis.

Nd3+/Yb3+ cascade-sensitized single-band red upconversion emission in active-core/active-shell nanocrystals.

Lanthanide-doped upconversion nanomaterials (UCNMs) have promoted extensive interest for its biological research and biomedical applications, benefiting from low autofluorescence background, deep light penetration depth, and minimal photo-damage to biological tissues. However, owing to the 980 nm laser-induced overheating issue and the attenuation effect associated with conventional multi-peak emissions, the usage of UCNMs as fluorescent bioprobes is still limited. To address these issues, an effective strategy has been proposed to tune both the excitation and emission peaks of UCNMs into the first biological window (650 âˆ¼ 900 nm), where the light absorption by water and hemoglobin in biological tissues is minimal. Based on the Nd3+/Yb3+ cascade-sensitized upconversion process and efficient exchange-energy transfer between Mn2+ and Er3+ in conjunction with the active-core@active-shell nanostructured design, we have developed a new class of upconversion nanoparticles (UCNPs) that exhibit strong single-band red emission upon excitation of an 808 nm near-infrared laser. Hopefully, the well-designed KMnF3:Yb/Er/Nd@ KMnF3:Yb/Nd core-shell nanocrystals will be considered a promising alternative to conventionally used UCNPs for biolabeling applications without the concern of the overheating issue and the attenuation constraints.

The impact of hepatitis B virus infection and vaccination on the development of non-Hodgkin lymphoma.

Hepatitis B virus (HBV) infection has been documented as a risk factor for non-Hodgkin lymphoma (NHL). However, there are few large cohort studies, and there is no report about the impact of HBV vaccination. We conducted this study to evaluate these issues. We used the nationwide cohort of the Taiwan National Health Insurance Research Database for 1997-2013. We compared the incidence and the risk of developing NHL and CD20+ aggressive lymphoma between HBV and non-HBV cohorts. The hazard ratios (HRs) were computed using Cox proportional hazards models. We matched these two large cohorts to reconfirm the data. We also compared the incidence of NHL between cohorts born before and after the inception of universal HBV vaccination. We found that HBV infection increased the risk for developing NHL and CD20+ aggressive lymphoma, with HRs of 4.14 and 5.52, with a higher incidence of 17.07 and 13.9 per 100 000 person-years, respectively, compared to the non-HBV cohort. The incidence of NHL in the cohort born in the era before universal HBV vaccination was higher with 1.85 per 100 000 person-years compared to 0.74 in the cohort born later aged younger than 20. Our study confirms that HBV confers a greater risk for developing NHL, especially CD20+ aggressive lymphoma. The impact of HBV vaccination is protective against lymphoma development in the teenagers in an endemic area, but longer follow-up is needed for older age.

[Effect and mechanism of silibinin on the inhibition of ALK positive NSCLC cells by sensitizing crizotinib].

Objective: To explore the synergistic effect of silibinin combined with crizotinib on anaplastic lymphoma kinase positive (ALK+ ) non-small cell lung cancer (NSCLC) cells and its mechanism. Methods: H2228 and H3122 cells were treated with silibinin, crizotinib alone or in combination. Cell proliferation was measured by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and colony formation assay. Migration or invasion ability was tested by wound healing assay or transwell assay, respectively. Expressions of E-Cadherin and vimentin protein were examined by immunofluorescence staining. The protein expressions of ALK, p-ALK, E-Cadherin and Vimentin were detected by western blotting.The anti-cancer effect of silibinin combined with crizotinib in vivo was determined by subcutaneously injecting 2×10(6) H2228 cells into immunodeficient nude mice. Results: The result of MTT assay showed that the cell viability of H2228 or H3122 treated with 100 µmol/L silibinin was (88.38±4.10)% or (72.27±3.62)%, respectively, marginally decreased compared with that of the control. The 50% inhibitory concentration (IC(50)) of H2228 cells treated with crizotinib alone or combined with 100 µmol/L silibinin was (917.10±7.75) nmol/L or (238.73±7.67) nmol/L, respectively. The IC(50) of H3122 cells treated with crizotinib alone or combined with 100 µmol/L silibinin was (472.50±15.70) nmol/L or (206.10±12.01) nmol/L, respectively. The IC(50s) of H2228 and H3122 cells were significantly decreased by combined treatment of crizotinib and silibinin compared to crizotinib treatment alone (P<0.01). When compared with the control group, colony forming ratios of H2228 cells were (83.34±2.72)% in 100 µmol/L silibinin treatment group, (69.42±3.06)% in 400 nmol/L crizotinib treatment group and (27.32±1.42)% in combined treatment group. When compared with the control group, colony forming ratios of H3122 cells were (84.45±5.67)% in 100 µmol/L silibinin treatment group, (45.02±5.83)% in 400 nmol/L crizotinib treatment group and (17.43±3.83)% in combined treatment group. Silibinin combined with crizotinib treatment significantly inhibited the colony formation ability of H2228 and H3122 cells (P<0.01). Migration and invasion results showed that combined treatment of crizotinib and silibinin markedly inhibited the migration and invasion ability of H2228 cells (P<0.01). Western blot results indicated that treated with silibinin alone or in combination of crozitinib for 48 hours, the protein level of E-cadherin in H2228 cells was upregulated, while the expressions of p-ALK and vimentin were downregulated, without obvious alteration of ALK protein expression. In the xenograft model, the mean tumor weight was (9.40±2.58)g in crizotinib treatment group and (4.58±1.07)g in the combined treatment group. The inhibitory effect of tumor growth in vivo of combined treatment was significantly superior to that of crizotinib treatment alone (P<0.05). Conclusion: Silibinin enhances the inhibitory effect of crizotinib on ALK positive NSCLC cells, which may be associated with suppression of ALK activity and mesenchymal-epithelial transition.

Effect of FUT3 gene silencing with miRNA on proliferation, invasion and migration abilities of human KATO-III gastric cancer cell line.

This study investigated the effects of FUT3 gene expression inhibition with miRNA on the proliferation, invasion and migration abilities of KATO-III cells. KATO-III cells were transfected with plasmid pcDNA™6.2-GW/EmGFP-FUT3-miR(FUT3-miRNA) and negative control plasmid in mediation of liposome, respectively, using untransfected cells as blank controls. Forty-eight hours after transfection, FUT3 mRNA levels were tested by RT-PCR. Levels of sLeA proteins were assayed by Western blot. The effects of FUT3-miRNA on the proliferation, invasion and migration of KATO-III cells were determined by CCK8 testing and Transwell assays, respectively. Results indicate that the transfection of FUT3-miRNA may down-regulate sLeA protein expression on the surface of KATO-III cells, and significantly inhibit cell proliferation (p<0.05). As compared to the negative and blank control groups, the number of invasion and migration cells in the FUT3-miRNA group decreased significantly (each p<0.05). Experimental results indicate that the miRNA expression vector which targets the FUT3 gene can effectively inhibit the proliferation, migration and invasion abilities of KATO-III cells.

Schwannomas of female genitalia from a gynaecologist's perspective: report of two cases and review of the literature.

BACKGROUND: Pelvic schwannomas are extremely rare. However, when located in the pelvic cavity, schwannomas are often encountered by a gynaecologist, not a general surgeon, and are misdiagnosed as gynaecologic masses. CASE REPORT: Here, the authors present two cases of pelvic schwannomas that were preoperatively misdiagnosed as broad ligament fibroid. One schwannoma occurred completely in the left broad ligament and was resected by laparoscopy without any complications. The other lesion was located in the retroperitoneum and had densely adhered to the surrounding tissues; this lesion was excised by laparotomy with considerable blood loss. CONCLUSIONS: Schwannomas of female genitalia are very scarce and difficulty to diagnose preoperatively. Literature review revealed 63 schwannomas arising from the female genital tract in total, 73.02% (46 cases) were located in the lower genital tract, and 26.98% (17 cases) were located in upper genital tract. The treatment modality is unique depending on the location of the tumor. Complete excision is benefical for diagnosis and treatment. The procedure can be performed safely under laparoscopy.

The value of serial plasma nuclear and mitochondrial DNA levels in acute spontaneous intra-cerebral haemorrhage.

BACKGROUND: Increased plasma nuclear and mitochondrial DNA levels may be connected to disease severity following spontaneous intra-cerebral haemorrhage (ICH). This study tested the hypothesis that plasma nuclear and mitochondrial DNA levels are substantially increased in acute ICH and can predict treatment outcomes. METHODS: Serial plasma nuclear and mitochondrial DNA levels were examined in 60 consecutive patients admitted within 24 h after onset of spontaneous ICH and in 60 volunteer control subjects. Additional samples were obtained on days 4, 7, 10, and 14 after onset of ICH regardless of clinical deterioration. RESULTS: Only plasma nuclear DNA, not plasma mitochondrial DNA, levels in patients with spontaneous ICH significantly correlated with Glasgow Coma Scale (GCS) (r = -0.467, P = 0.001) and ICH volume (r = 0.515, P ≤ 0.001) on presentation. Plasma nuclear DNA levels increased significantly from day 1 to day 7 in patients with poor outcome. Higher plasma nuclear DNA levels (cut-off value >18.7 ng/ml) on presentation were associated with poor outcomes in spontaneous ICH patients. CONCLUSION: Plasma nuclear DNA levels reflect the severity of cerebral damage such that higher levels are associated with poorer outcome. Plasma nuclear DNA level can be considered a neuropathologic marker of acute spontaneous ICH.

Efficacy and safety of dose-modified docetaxel plus cisplatin-based induction chemotherapy in Asian patients with locally advanced head and neck cancer.

WHAT IS KNOWN AND OBJECTIVE: The beneficial effects of docetaxel plus cisplatin-based induction chemotherapy for patients with unresectable, advanced head and neck cancer (HNC) have been documented in Western countries. However, the efficacy of such treatment has not been confirmed in Asian patients. We aimed to determine whether incorporation of dose-modified docetaxel into a cisplatin-based induction regimen would be both effective and tolerable in our Asian population of patients. METHODS: Thirty-six patients with stage III or IV HNC who had undergone cisplatin-based induction chemotherapy were included in the current analysis. Fifty-three percentage of the patients had received induction chemotherapy with bolus cisplatin and continuous 5-fluorouracil (PF group), while the remaining 47% had additionally received dose-modified docetaxel (TPF group). We assessed the relative impact of the two treatments on clinical outcomes and treatment-related toxicities. RESULTS AND DISCUSSION: The disease control rate was higher in the TPF group (92·9% vs. 76·5%), although the difference did not reach statistical significance (P = 0·217). Addition of docetaxel increased the median progression-free survival to 435 days, which was 2·3 times longer than that (188 days) of patients not receiving docetaxel (P = 0·019). Non-haematological toxicity profile was similar and acceptable in both treatment groups. Higher incidence of grade 3/4 neutropenia and more episodes of neutropenic fever-related hospitalization occurred in the docetaxel-treated patients, but most of them were managed uneventfully. WHAT IS NEW AND CONCLUSION: Addition of dose-modified docetaxel to cisplatin-based induction chemotherapy was both efficacious and generally safe. Docetaxel addition significantly prolonged progression-free survival and had an acceptable safety profile in our Asian population of patients with locoregionally advanced HNC.

Development and characterization of microsatellite markers for the endangered Chinese yew Taxus chinensis var. mairei (Taxaceae).

We isolated and characterized 11 microsatellite loci for the Chinese yew, Taxus chinensis var. mairei, an endangered tree species in China, by constructing a (CA)(12)-enriched library. The number of alleles per locus ranged from 5 to 10. The observed heterozygosities ranged from 0.2500 to 0.8333 and the expected heterozygosities ranged from 0.5196 to 0.8680. No significant linkage disequilibrium was detected at these loci. However, four loci significantly deviated from Hardy-Weinberg equilibrium. The null alleles were found to be present at locus Tach9 and locus Tach11 by the Micro-checker test (P < 0.001). These polymorphic loci could be employed in research of gene flow and spatial genetic patterns of T. chinensis var. mairei.

Adenomyosis completely encapsulated by muscle-like cavity in the mesorectum: a case report.

A case of adenomyosis, completely encapsulated and located in the mesentery between the sigmoid colon and rectum, was admitted our hospital. We have reported the symptoms, diagnosis, and treatment of the present case.

Impact of breast cancer patients' awareness on attendance at screening.

AIM: The purpose of this study is to investigate the impact of breast cancer awareness on the attendance for screening among women with breast cancer prior to diagnoses of breast cancer. BACKGROUND: Breast cancer is the most commonly diagnosed cancer for women in Taiwan and its incidence rate continues to increase. However, screening for breast cancer is still not common even if the incidence rate has topped the list from 2003 to 2010. METHODS: A cross-sectional study was conducted among women diagnosed with breast cancer. Subjects (535 women) were recruited from two medical centres in central Taiwan. Information on attendance for breast cancer screening was collected by self-report. Chi-square test and logistic regression were utilized to analyse the relationships between awareness of breast cancer and attendance at screening. FINDINGS: The results indicated that pre-diagnostic awareness of 'the concept of early treatment relating to higher cure rate'[odds ratio (OR): 4.09; 95% confidence interval (CI): 1.12-14.9], 'various breast cancer screening methods' (OR:3.00; 95% CI: 1.23-7.30), 'the coverage of breast cancer screening programme in the National Health Insurance' (OR:1.76; 95% CI: 1.03-3.02) and 'breast self-examination after each menstrual cycle' (OR:3.42; 95% CI: 1.99-5.87) were all significantly associated with the screening procedures performed. CONCLUSIONS: Findings of this study indicated that particular attention should be paid towards enhancement of women's knowledge for prevention and early detection of breast cancer through educational efforts by nurse professionals, medical institutions and/or civil organizations.

Nutritional Status and Renal Function in Relation to Frailty among the Community-Dwelling Elderly Taiwanese Population.

OBJECTIVES: Frailty is a significant public health and clinical issue among the elder population. This study aimed to evaluate the nutritional status and renal function in relation to frailty among elderly Taiwanese. DESIGN: We administered community-based health surveys to the elder population in Chiayi County, Taiwan, from 2017 to 2019. MEASUREMENTS: We measured nutritional status (including serum albumin and total protein levels), renal function (including serum blood urea nitrogen, creatinine, urine protein, and urine creatinine levels), hand grip strength (GS) and calculated appendicular muscle mass (AMM). RESULTS: The study recruited 3739 participants (2139 women). Participants of both sexes with normal GS had higher serum albumin levels and lower urine protein/creatinine ratios (UPCRs). For the men with normal and weak GS, serum albumin levels were 4.15 ± 0.2 and 4.10 ± 0.2 g/dL (p < 0.01), and UPCRs were 123.1 ± 219.6 and 188.7 ± 366.2 (p < 0.001), respectively. GS was positively correlated with serum albumin and urine creatinine levels (r = 0.136 and 0.177, both p < 0.001). AMM was also positively correlated with serum albumin and urine creatinine levels (r = 0.078 and 0.091, both p < 0.001). In the multivariate regression model, for every 1 g/dL increase in serum albumin level, there was a 1.9 and 1.7-kg increase in GS for men and women (p < 0.05 and p < 0.01), respectively. The final model for predicting GS included age, albumin, BUN, and UPCR (urine creatinine for women) which presented a variance of 22.1% and 13.8%, respectively. CONCLUSION: Proper dietary nutritional intake and maintaining renal function are key elements for preventing frailty among elder population in Taiwan.

Comparative study of percutaneous nephrostomy using catheters with and without locking strings.

BACKGROUND: Although it is generally felt that a catheter with a locking string can achieve better fixation and thus prevent catheter displacement, no formal study has ever substantiated this. METHODS: We retrospectively reviewed the charts from 80 patients (mean age of 64.6 ± 14.76 y) who underwent percutaneous nephrostomy (PCN) over a 1-year period. RESULTS: Most patients had catheters without locking strings and only 17 patients (21.3%) had catheters with locking strings. The median duration of catheter placement was 29 days (interquartile range 14 - 57 d). There were no significant differences in patients' characteristics or catheter outcomes between catheters with and catheters without locking strings (p > 0.05). In addition, no significant difference in the catheter 90-day survival between catheter types was found (log rank test, p = 0.638). On univariate analysis, tumor as an indication for PCN (p = 0.018), obstruction (p = 0.021) and displacement (p = 0.007) were associated with reduced catheter survival. The multivariate analysis indicated that tumor as an indication for PCN (HR: 0.28, 95% CI: 0.13 - 0.63, p = 0.002), obstruction (HR: 0.25, 95% CI: 0.08 - 0.77, p = 0.015) and catheter displacement (HR: 0.09, 95% CI: 0.03 - 0.31, p < 0.001) were independent hazard factors for reduced catheter 90-day survival. CONCLUSION: No significant difference in either complication rate or 90-day survival was found between catheters with or without locking strings. These findings may prove helpful to the clinician in deciding the type of catheter to use during PCN.

Linking Stage-Specific Plasma Biomarkers to Gray Matter Atrophy in Parkinson Disease.

BACKGROUND AND PURPOSE: The shortcomings of synucleinopathy-based Parkinson disease staging highlight the need for systematic clinicopathologic elucidation and biomarkers. In this study, we investigated associations of proteinopathy and inflammation markers with changes in gray matter volume that accompany Parkinson disease progression. MATERIALS AND METHODS: We prospectively enrolled 42 patients with idiopathic Parkinson disease, subdivided into early-/late-stage groups and 27 healthy controls. Parkinson disease severity and participants' functional and cognitive performance were evaluated. Peripheral plasma α-synuclein, ß-amyloid42, and tau were quantified with immunomagnetic reduction assays, and nuclear DNA by polymerase chain reaction, and regional gray matter volumes were determined by MR imaging. Statistical tests identified stage-specific biomarkers and gray matter volume patterns in the early-stage Parkinson disease, late-stage Parkinson disease, and control groups. Correlations between gray matter volume atrophy, plasma biomarkers, Parkinson disease severity, and cognitive performance were analyzed. RESULTS: Patients with Parkinson disease had significantly elevated α-synuclein, tau, and ß-amyloid42 levels compared with controls; nuclear DNA levels were similar in early-stage Parkinson disease and controls, but higher in late-stage Parkinson disease (all P < .01). We identified 3 stage-specific gray matter volume atrophy patterns: 1) control > early-stage Parkinson disease = late-stage Parkinson disease: right midfrontal, left lingual, and fusiform gyri, left hippocampus, and cerebellum; 2) control > early-stage Parkinson disease > late-stage Parkinson disease: precentral, postcentral, parahippocampal, left superior-temporal, right temporal, right superior-frontal, and left cingulate gyri, occipital lobe, and bilateral parts of the cerebellum; 3) control = early-stage Parkinson disease > late-stage Parkinson disease: left midfrontal, superior-frontal and temporal, amygdala, and posterior cingulate gyri, caudate nucleus, and putamen. We discovered stage-specific correlations among proteinopathy, inflammation makers, topographic gray matter volume patterns, and cognitive performance that accompanied Parkinson disease progression. CONCLUSIONS: Identifying associations linking peripheral plasma biomarkers, gray matter volume, and clinical status in Parkinson disease may facilitate earlier diagnosis and improve prognostic accuracy.

A phase II study of weekly docetaxel and cisplatin plus oral tegafur/uracil and leucovorin as first-line chemotherapy in patients with locally advanced or metastatic gastric cancer.

BACKGROUND: Docetaxel plus cisplatin and 5-fluorouracil has become a new standard for treating advanced gastric cancer. However, high rates of severe neutropenia limit its application. Modification of the regimen could be the solution to get similar activity but less myelosuppression. METHODS: Patients with histologically confirmed, locally advanced, or recurrent/metastatic gastric adenocarcinoma without previous chemotherapy were enrolled. This regimen consisted of docetaxel (Tyxan, TTY, Taipei, Taiwan) 30-min infusion at a dose of 36 mg m(-2), followed by cisplatin 30 mg m(-2) infusion over 1 h on days 1 and 8, and oral tegafur/uracil 300 mg m(-2) per day plus leucovorin 90 mg per day on days 1-14, every 3 weeks. Tumour response was evaluated after every 2 cycles of treatment. RESULTS: From August 2007 to March 2009, 45 patients were enrolled. The median age was 56 years (range: 22-75). Among the 40 patients evaluable for tumour response, one achieved a complete response, 22 had partial responses and 11 had stable disease. The overall response rates of the evaluable and intent-to-treat (ITT) populations were 58% (95% CI: 41-74%) and 53% (95% CI: 38-68%), respectively. The disease control rates in these populations were 85% (95% CI: 70-94%) and 82% (95% CI: 68-92%), respectively. In the ITT analysis, the median time to progression and overall survival were 6.8 and 13.9 months, respectively. Major grade 3-4 toxicities were neutropenia (51%), anaemia (22%), diarrhoea (16%), and infections (20%). No patient died of treatment-related toxicities. CONCLUSION: Concurrent weekly docetaxel and cisplatin plus oral tegafur/uracil and leucovorin are effective and well tolerated in the treatment of advanced gastric cancer.

Overexpression of transforming growth factor-beta1 in fetal monkey lung results in prenatal pulmonary fibrosis.

Altered transforming growth factor (TGF)-ß expression levels have been linked to a variety of human respiratory diseases, including bronchopulmonary dysplasia and pulmonary fibrosis. However, a causative role for aberrant TGF-ß in neonatal lung diseases has not been defined in primates. Exogenous and transient TGF-ß1 overexpression in fetal monkey lung was achieved by transabdominal ultrasound-guided fetal intrapulmonary injection of adenoviral vector expressing TGF-ß1 at the second or third trimester of pregnancy. The lungs were then harvested near term, and fixed for histology and immunohistochemistry. Lung hypoplasia was observed where TGF-ß1 was overexpressed during the second trimester. The most clearly marked phenotype consisted of severe pulmonary and pleural fibrosis, which was independent of the gestational time point when TGF-ß1 was overexpressed. Increased cell proliferation, particularly in α-smooth muscle actin-positive myofibroblasts, was detected within the fibrotic foci. But epithelium to mesenchyme transdifferentiation was not detected. Massive collagen fibres were deposited on the inner and outer sides of the pleural membrane, with an intact elastin layer in the middle. This induced fibrotic pathology persisted even after adenoviral-mediated TGF-ß1 overexpression was no longer evident. Therefore, overexpression of TGF-ß1 within developing fetal monkey lung results in severe and progressive fibrosis in lung parenchyma and pleural membrane, in addition to pulmonary hypoplasia.