Inhibitor of apoptosis proteins (IAP) inhibitor APG-1387 monotherapy or in combination with programmed cell death 1 (PD-1) inhibitor toripalimab in patients with advanced solid tumors: results from two phase I trials.

BACKGROUND: APG-1387 is a novel second mitochondrial-derived activator of caspases mimetic, small-molecule inhibitor targeting inhibitor of apoptosis proteins. We report results from two phase I trials evaluating the tolerability, safety, and antitumor activity of APG-1387 monotherapy and APG-1387 plus toripalimab [a programmed cell death 1 (PD-1) inhibitor] for advanced solid tumors. PATIENTS AND METHODS: Participants aged ≥18 years who had histologically confirmed advanced solid tumors with no appropriate standard of care (or refractory to standard care) were eligible. Patients received escalating intravenous doses of APG-1387 alone or combined with fixed-dose toripalimab (240 mg every 3 weeks) in a '3 + 3' design. Primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) in the monotherapy trial, and recommended phase II dose (RP2D) in the combination therapy trial. Secondary endpoints included the pharmacokinetic and pharmacodynamic profiles and preliminary efficacy in both trials. RESULTS: In the monotherapy trial, 28 subjects were enrolled and received ≥1 treatment cycle. No DLT was reported among the 28 subjects, and the MTD was not reached. One participant (3.6%) had a grade ≥3 treatment-related adverse event (TRAE) of alanine aminotransferase elevation. In efficacy analysis of 23 participants, none achieved an objective response, and the disease control rate was 21.7%. In the combination trial, 22 subjects were enrolled and included in all analyses. There was one DLT of grade 3 lipase elevation. The MTD was not reached. Four grade ≥3 TRAEs occurred in three participants (13.6%), with the most common being lipase elevation (n = 2). The RP2D was 45 mg weekly. The objective response rate was 13.6%, with complete response achieved in one subject, and the disease control rate was 54.5%. CONCLUSIONS: APG-1387 45 mg weekly plus toripalimab was well tolerated and is recommended for further study, with preliminary clinical activity observed in study participants with advanced solid tumors.

[Clinical study of the efficacies of ruxolitinib plus low-dose PTCY for acute GVHD prevention after haploidentical transplantation in malignant hematological diseases].

Objective: To investigate and verify a novel acute graft versus host disease (aGVHD) prevention protocol in the context of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Patients who underwent haplo-HSCT in our center between January 2022 and December 2022 were included. All patients received reduced doses of cyclophosphamide, Rabbit anti-human tymoglobulin, ruxolitinib, methotrexate, cyclosporine, and MMF to prevent aGVHD. The transplantation outcomes, complications, and survival rate of all patients were investigated. Results: A total of 52 patients with haplo-HSCT were enrolled, 29 (55.8%) male and 23 (44.2%) female, with a median age of 28 (5-59) years. There were 25 cases of acute myeloid leukemia, 17 cases of acute lymphocyte leukemia, 6 cases of myelodysplastic syndrome, 2 cases of chronic myeloid leukemia and 2 cases of myeloproliferative neoplasms. 98.1% of patients had successful engraftment. The incidence of Ⅱ-Ⅳ aGVHD and Ⅲ-Ⅳ aGVHD was 19.2% (95% CI 8.2% -30.3% ) and 7.7% (95% CI 0.2% -15.2% ), respectively. No patients experienced severe gastrointestinal mucositis. The Epstein-Barr virus and CMV reactivation rates were 40.4% and 21.3%, respectively. 9.6% of patients relapsed during followup, with 1-year overall survival, progression-free survival, and non-relapse mortality rates of 86.5% (95% CI 76.9% -96.1% ), 78.8% (95% CI 67.4% -90.3% ) and 11.5% (95% CI 2.6% -20.5% ), respectively. Conclusion: Ruxolitinib combined with a low dose of PTCY is a safe and effective first-line aGVHD prevention strategy.

[Intervention effects of drugs on GSH and SOD enzyme activity of rats kidney acutely poisoned by nickel carbonyl].

Objective: To evaluate the intervention effect of various drugs on glutathione (GSH) and superoxide dismutase (SOD) enzyme activity of rats kidney with acute nickel carbonyl poisoning. Methods: In January 2019, The 250 SPF male SD rats were randomly divided into normal control group (n=10) , poisoned group (n=40) and treatment groups (n=200) according to the random number table method. And the treatment groups were divided into methylprednisolone group (20 mg/kg) , DDC group (100 mg/kg) , sodium selenite group (10 µmol/kg) , Shenfu huiyang decoction group (0.25 ml) and methylprednisolone combined with DDC group (100 mg/kg) , with 40 mice in each group. Except for the normal control group, rats in the other groups were exposed to nickel carbonyl for 30 min, at 4 h and 30 h after exposure, the rats in each treatment group were intraperitoneally injected with corresponding drugs, and kidney tissues were collected 3 d and 7 d after administration, with 10 mice in each group. The activities of GSH and SOD in kidney were measured by enzyme-linked immunosorbent assay, and using electron microscopy observe ultrastructure changes. Results: Compared to the control group, the activities of GSH and SOD enzyme of poisoned group were significantly decreased at 3 d or 7 d after 4 h or 30 h exposure, and the difference was statistically significant (P=0.000, 0.031, 0.001, 0.033) , the epithelial nuclei of proximal convoluted tubules were pyknosis and lysosome hyperplasia in the cytoplasm. And compared to poisoned group, the activities of GSH and SOD enzyme of methylprednisolone+DDC group were significantly increased at treatment with 7 d after 4 h exposure, the difference was statistically significant (P=0.022, 0.000) , and the activities of GSH and SOD enzyme of methylprednisolone and enzyme of methylprednisolone+DDC group were significantly higher at 7 days than at 3 days, the difference was statistically significant (P=0.020, 0.017, 0.018, 0.033) . The results of electron microscopy showed that the cell nuclei and cytoplasmic organelles of proximal convolute tubule were almost restored to normal tissue level of both methylprednisolone group and methylprednisolone+DDC group. Conclusion: The methylprednisolone and methylprednisolone+DDC have obvious repair effect on renal enzyme activity level of rats with acute nickel carbonyl poisoning, and the treatment effect is better for a long time of medication.

[A nested case-control study on relationship of traditional and combined lipid metabolism indexes with incidence of diabetes].

Objective: To explore the relationship between lipid indicators and the incidence of diabetes, and to compare the diabetes prediction and identification power of traditional lipid combined lipid indicators, in order to explore the best alternative indicators for identifying and predicting diabetes. Methods: Based on the Jinchang cohort, a nested case-control study was conducted in 1 025 new cases of diabetes after excluding patients with malignant tumor and related endocrine, circulatory system disease, then an age (±2 years), gender matched 1∶1 control group of 1 025 cases was set to analyze the relationship between the incidence of diabetes and lipid parameters. Results: Among the traditional lipid parameters, the fourth quartile of TG, TC, and LDL-C indicated higher risks of developing diabetes, which was 14.00 times (95%CI: 9.73-20.15), 2.15 times (95%CI: 1.65-2.79) and 1.66 times (95%CI: 1.29-2.14) than that of the first quartile, respectively. The risk of developing diabetes indicated by the fourth quartile of HDL-C was 0.21 times than that indicated by the first quartile (95%CI: 0.15-0.28). In the combined lipid parameters, the fourth quartile of TG/HDL-C, TC/HDL-C, LDL-C/HDL-C and non-HDL-C indicated higher risks of developing diabetes, which was 14.86 times (95%CI: 10.35-21.34), 8.12 times (95%CI: 5.94-11.01), 5.85 times (95%CI:4.34-7.88) and 5.20 times (95%CI: 3.85-7.03) than that indicated by the first quartile, respectively. The areas under the ROC curve of TG, TC, HDL-C, LDL-C, TG/HDL-C, TC/HDL-C, LDL-C/HDL-C and non-HDL-C were 0.76 (95%CI: 0.74-0.78), 0.59 (95%CI: 0.57-0.61), 0.67 (95%CI: 0.65-0.69), 0.57 (95%CI: 0.55-0.59), 0.77 (95%CI: 0.75-0.78), 0.73 (95%CI: 0.71-0.75), 0.69 (95%CI: 0.67-0.71) and 0.66 (95%CI: 0.64-0.68), respectively. The optimal diabetes predicting point cuts of TG, TC, HDL-C, LDL-C, TG/HDL-C, TC/HDL-C, LDL-C/HDL-C and non-HDL-C were 1.40, 4.70, 1.28, 3.25, 1.17, 3.43, 2.46, and 3.58 mmol/L, respectively. Conclusions: Lipid metabolic disorder is a risk factor for diabetes. TG and TG/HDL-C are the good lipid metabolism indicators for the prediction of diabetic.

[Retrospective investigation of patients receiving additional surgery after endoscopic non-curative resection for early colorectal cancer].

Objective: To investigate the clinical application of additional surgery after non-curative endoscopic resection for early colorectal cancer. Methods: A retrospectively descriptive cohort study was conducted. Inclusion criteria: (1) pathologically confirmed primary colorectal adenocarcinoma;(2) receiving additional surgery after endoscopic resection; (3) semi-elective operation. Exclusion criteria: familial adenomatous polyposis, appendiceal neoplasms, anal canal neoplasms, neuroendocrine tumors, and surgery because of perforation or bleeding after endoscopic resection. Indications of additional surgery: (1) pathologically positive lateral or basal resection margin; (2) submucosal invasion depth ≥ 1000 µm; (3) lymphovascular invasion; (4) poorly differentiated, undifferentiated or mucinous adenocarcinoma; (5) more than grade G2 in tumor budding; (6) incomplete resection or piecemeal specimen with margin impossible to evaluate; (7) patient's consent due to undetermined pathology. According to the above criteria, clinical data of 92 patients at the Colorectal Surgery Department, the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2018 were collected. Demographic data, pathological examinations, operative methods and outcomes were analyzed. Results: There were 61 (66.3%) male and 31 female (33.7%) patients with an average age of (58.2±10.7) years. The average BMI was (23.8±3.5) kg/m(2). The lesions located in the right-sided colon, left-sided colon and rectum in 19, 37 and 36 patients respectively. Sixteen patients received endoscopic snare resection, 45 received endoscopic mucosal resection and 31 received endoscopic submucosal dissection. Reasons for additional surgery included endoscopic specimen with pathologically positive margin (n=22, 23.9%), submucosal invasion depth ≥ 1000 µm (n=9, 9.8%), lymphovascular invasion (n=4, 4.3%), poorly differentiated, undifferentiated or mucinous adenocarcinoma (n=5, 5.4%), piecemeal resection (n=13, 14.1%), undetermined pathology (n=52, 56.5%). The median duration from endoscopic resection to additional surgery was 16 days. Thirty-four patients (37.0%) received preoperative endoscopic localization with carbon nanoparticles suspension injection and 5 (5.4%) were marked with titanium clip. Seventy-four patients (80.4%) received laparoscopic surgery, 17 (18.5%) received open surgery, while 1 patient (1.1%) was converted to open surgery due to missing titanium clip. Three patients (3.3%) were treated with transanal excision, 2 (2.2%) with bowel resection, and 87 (94.6%) with radical excision. After additional surgery, histopathological examination of surgical specimens revealed the presence of residual tumor in 5 patients (5.4%), lymph node metastasis in 8 (8.7%), lymphovascular invasion in 1 (1.1%) and tumor deposit in 1 (1.1%). Twelve patients (13.0%) developed postoperative complications, including 4 mid-low rectal cancer patients (4.3%) with anastomostic leakage or bleeding. After surgery, according to the TNM staging system, 83 patients (90.2%) were classified as TNM stage 0-I, 9 (9.8%) as TNM stage II-IV. One patient of stage IV with liver metastasis underwent concomitant hepatectomy. One patient of stage II received regular follow-up after operation. Seven cases of stage III and 1 of stage IV received postoperative chemotherapy. Eighty-five patients (92.4%) were followed up with a median time of 12.8 (IQR: 8.1, 24.3) months. No recurrence or metastasis was observed. Conclusions: Surgery is an effective salvage measure for non-curative endoscopic resection of early colorectal cancer. Since surgery may have complications, indications of the additional surgery should be considered carefully. Preoperative endoscopic localization should be performed in order to ensure the safety and efficacy of surgery.

[Incidence of chronic obstructive pulmonary disease and pneumoconiosis in different occupational positions among populations from jinchang cohort].

Objective: To investigate the incidence and rank of chronic obstructive pulmonary disease and pneumoconiosis to the workers in different occupational positions in Jinchang Cohort. Methods: In January 2014, a cohort of follow-up population in jinchang city was taken as the research object, 17843 individuals among follow-up populations in Jinchang Cohort Study, removed the individuals with chronic obstructive pulmonary disease and pneumoconiosis before 2013, and counted the new incidence individuals diagnosed by the A-Class hospital in Grade III in Jinchang City, Gansu Province, as the investigation objects to investigate the incidence rate & rank of chronic obstructive pulmonary disease and pneumoconiosis. The statistical significance was tested by chi-square test. Results: The 2-year incidence rate of Chronic Obstructive Pulmonary Disease and Pneumoconiosis in the population of Jinchang Cohort Study were 11.60‰, 13.51‰ for male and 8.46‰ for female. the ranks of 2-year incidence rates of chronic bronchitis, emphysema, pneumoconiosis and other phenotypes of chronic obstructive pulmonary disease were 7.06‰ã€3.42‰ã€0.84‰ã€0.34‰, respectively. Incidence rate of chronic bronchitis among administrators and executive staffs were 10.45‰; incidence rate of chronic bronchitis among service staffs were 10.45‰; incidence rate of pneumoconiosis among mining staffs were 3.44‰. Conclusion: The first incidence rank of chronic obstructive pulmonary disease and pneumoconiosis in Jinchang cohort is chronic bronchitis, and the risk factors are smoking and occupational exposure.

[Association between fatty liver and type 2 diabetes in the baseline population of Jinchang Cohort].

Objective: To explore the association between fatty liver and type 2 diabetes mellitus (T2DM) in the baseline-population of Jinchang cohort study. Methods: Data from all the participants involved in the baseline-population of Jinchang cohort study was used, to compare the risks of T2DM in fatty liver and non fatty liver groups and to explore the interaction between family history or fatty liver of diabetes and the prevalence of T2DM. Results: Among all the 46 861 participants, 10 574 were diagnosed as having fatty liver (22.56%), with the standardized rate as 20.66%. Another 3 818 participants were diagnosed as having T2DM (8.15%) with standardized rate as 6.90%. The prevalence of T2DM increased in parallel with the increase of age (trend χ(2)=2 833.671, trend P<0.001). The prevalence of T2DM in the fatty liver group was significantly higher than that in the non-fatty liver group, both in men or women and in the overall population. Compared with the group of non-fatty liver, the risks of T2DM in fatty liver group were seen 1.78 times higher in males, 2.33 times in women and 2.10 times in the overall population, after adjustment for factors as age, levels of education, smoking, drinking, physical exercise, BMI, family history of diabetes and some metabolic indicators (pressure, TC, TG, uric acid, ALT, AST, gamma-glutamyl transferase). Date from the interaction model showed that fatty liver and family history of diabetes present a positive additive interaction on T2DM (RERI=1.18, 95%CI: 0.59-1.78; AP=0.24, 95%CI: 0.14-0.34; S=1.43, 95%CI: 1.21-1.69). Conclusions: Fatty liver could significantly increase the risk of T2DM and a positive additive interaction was also observed between fatty liver and family history of diabetes on T2DM. It was important to strengthen the prevention program on T2DM, in order to effectively control the development of fatty liver.

A rare occurrence of intramasseteric schwannoma - case report and literature review.

A schwannoma is a benign, solitary, well-defined, painless, slowly-enlarging nerve sheath tumor, composed of Schwann cells. Intramasseteric localization is very unusual. We report the case of a 33-year-old male who developed an intramasseteric schwannoma. Tumor could be completely removed under general anesthesia. Histopathological examination made the diagnosis of intramasseteric schwannoma through the presence of Antoni A areas and Verocay bodies. The diagnosis of schwannoma should be taken into consideration in case of parotideomasseteric tumors.

[Correlation analysis between 18F-FDG uptake features and the prognosis in patients with pathologic stage â lung adenocarcinoma].

OBJECTIVE: To analyze the (18)F-FDG uptake features and the correlation between (18)F-FDG uptake and the prognosis in patients with pathologic stageⅠlung adenocarcinoma. METHODS: One hundred and seventeen patients with stageⅠlung adenocarcinoma proved by surgery, who underwent a preoperative (18)F-FDG PET-CT, were studied retrospectively. The tumors' SUVmax in different groups of clinicopathologic factors were compared. The correlations between the SUVmax and clinicopathologic factors were analyzed using Spearman rank correlation. The ROC was plotted to estimate the most discriminative cut-off point for SUVmax in predicting the recurrence or progression of tumor. The progression-free survival (PFS) in different clinicopathologic groups were estimated using the Kaplan-Meier method and Log-rank test. RESULTS: The SUVmax of pathologic stageⅠlung adenocarcinomas were significantly different in different groups of gender, tumor size, density, tumor differentiation grade and T staging, respectively (P<0.05 for all). Patients with a larger tumor size, a higher proportion of solid component, poorer grade of tumor differentiation had a higher SUVmax. The T1b group had a higher SUVmax than T1a and T2a groups. The male group had a higher SUVmax than the female group. The SUVmax was positively correlated with the size of the adenocarcinomas (P<0.01), and was negatively correlated with both the density and tumor differentiation grade (P<0.01). But there was no correlation between SUVmax and the T stage (P>0.05). The patients with an SUVmax of <3.0 had a much better PFS (75.1±3.0 month)than those with an SUVmax of ≥3.0 (52.7±5.9 month)(P<0.01). The tumor with a poorer differentiation grade was associated with reduced PFS (45.7±5.4 months) compared with those with well differentiated tumor (76.7±4.2 month)(P<0.05). The PFS showed no statistically significant differences in different gender, age, smoking history, tumor size, density and T staging groups (P>0.05). CONCLUSIONS: (18)F-FDG uptake is correlated with the tumor size, density, and differentiation grade, and has a prognostic value for predicting the PFS in the patients with pathologic stageⅠ lung-adenocarcinoma. Patients with an SUVmax of <3.0 have a much better PFS than those with an SUVmax of ≥3.0.

Single-agent capecitabine as maintenance therapy after induction of XELOX (or FOLFOX) in first-line treatment of metastatic colorectal cancer: randomized clinical trial of efficacy and safety.

BACKGROUND: The optimal strategy of maintenance therapy for patients with mCRC is controversial. This study was to evaluate the efficacy and safety of maintenance therapy with capecitabine versus observation following inductive chemotherapy in patients with metastatic colorectal cancer. PATIENTS AND METHODS: In this randomized, open-label, multicenter, phase III trial, patients who received 18-24 weeks of induction chemotherapy with XELOX or FOLFOX and achieved disease control were randomly assigned centrally (1:1) to receive maintenance therapy of capecitabine or only observation until disease progression. The primary end point was progression-free survival (PFS) from randomization; the secondary end points included overall survival (OS), PFS from induction treatment (PFS2) and safety. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02027363. RESULTS: Between 30 July 2010 and 15 September 2013, 274 patients were enrolled in the study from 11 sites in China and randomly assigned to maintenance group (n = 136) or observation group (n = 138). Clinicopathological characteristics were balanced in two groups. The median follow-up time from randomization was 29.0 months [interquartile range (IQR) 21-36 months]. The primary end point of PFS was statistically significantly longer in capecitabine maintenance group than in observation group {6.43 [95% confidence interval (CI) 5.26-7.71] versus 3.43 (2.83-4.16) months, HR 0.54 (0.42-0.70), P < 0.001}. The median OS of capecitabine maintenance group was longer than that of observation group, but not statistically significant [25.63 (22.46-27.80) versus 23.30 (19.68-26.92) months; HR 0.85 (0.64-1.11), P = 0.2247]. Similar safety profiles were observed in both arms. The most common grade 3 or 4 toxicities in capecitabine maintenance group versus observation group were neutropenia, hand-foot syndrome, and mucositis. CONCLUSIONS: Maintenance therapy with a single agent of capecitabine can be considered an appropriate option following the induction of XELOX or FOLFOX in mCRC patients with acceptable toxicities. CLINICAL TRIALS NUMBER: NCT02027363.

Effects of fluoride on proliferation and mineralization in periodontal ligament cells in vitro

Fluoride, which is often added to toothpaste or mouthwash in order to protect teeth from decay, may be a novel therapeutic approach for acceleration of periodontal regeneration. Therefore, we investigated the effects of fluoride on proliferation and mineralization in human periodontal ligament cells in vitro. The periodontal ligament cells were stimulated with various concentrations of NaF added into osteogenic inductive medium. Immunohistochemistry of cell identification, cell proliferation, alkaline phosphatase (ALP) activity assay, Alizarin red S staining and quantitative real-time-polymerase chain reaction (RT-PCR) were performed. Moderate concentrations of NaF (50-500 μmol/L) had pro-proliferation effects, while 500 μmol/L had the best effects. ALP activity and calcium content were significantly enhanced by 10 μmol/L NaF with osteogenic inductive medium. Quantitative RT-PCR data varied in genes as a result of different NaF concentrations and treatment periods. We conclude that moderate concentrations of NaF can stimulate proliferation and mineralization in periodontal ligament cells. These in vitro findings may provide a novel therapeutic approach for acceleration of periodontal regeneration by addition of suitable concentrations of NaF into the medication for periodontitis treatment, i.e., into periodontal packs and tissue patches.

Wnt1-induced MAFK expression promotes osteosarcoma cell proliferation.

Osteosarcoma is one of the most common primary bone tumors in children and young adults. In this study, we investigated the role of musculoaponeurotic fibrosarcoma oncogene homolog K (MAFK) in osteosarcoma cell proliferation in vitro and the possible pathways that contributed to MAFK-related osteosarcoma development. We first reported that MAFK was expressed at low levels in an osteosarcoma cell line. Furthermore, a significant correlation between MAFK and the Wnt signaling pathway was observed in osteosarcoma by using a gene microarray assay. We found that expression of MAFK could be induced by Wnt1 in a dose-dependent manner. Furthermore, Wnt1-induced MAFK expression caused a significant increase of cell viability, whereas a Wnt pathway inhibitor, IWR-1-endo, abolished Wnt1-induced effects on MAFK. Finally, cell cycle analysis showed that enhanced cell proliferation might be attributed to re-distribution of the cell cycle. Together, our results suggested that Wnt1-induced MAFK expression promoted cell proliferation in MG63 cells, and that the role of MAFK in osteosarcoma might be closely linked to the Wnt signaling pathway.

Effects of 5-aza-2′deoxycytidine on RECK gene expression and tumor invasion in salivary adenoid cystic carcinoma

Reversion-inducing cysteine-rich protein with kazal motifs (RECK), a novel tumor suppressor gene that negatively regulates matrix metalloproteinases (MMPs), is expressed in various normal human tissues but downregulated in several types of human tumors. The molecular mechanism for this downregulation and its biological significance in salivary adenoid cystic carcinoma (SACC) are unclear. In the present study, we investigated the effects of a DNA methyltransferase (DNMT) inhibitor, 5-aza-2′deoxycytidine (5-aza-dC), on the methylation status of the RECK gene and tumor invasion in SACC cell lines. Methylation-specific PCR (MSP), Western blot analysis, and quantitative real-time PCR were used to investigate the methylation status of the RECK gene and expression of RECK mRNA and protein in SACC cell lines. The invasive ability of SACC cells was examined by the Transwell migration assay. Promoter methylation was only found in the ACC-M cell line. Treatment of ACC-M cells with 5-aza-dC partially reversed the hypermethylation status of the RECK gene and significantly enhanced the expression of mRNA and protein, and 5-aza-dC significantly suppressed ACC-M cell invasive ability. Our findings showed that 5-aza-dC inhibited cancer cell invasion through the reversal of RECK gene hypermethylation, which might be a promising chemotherapy approach in SACC treatment.

Hepatitis B virus infection is associated with gastric cancer in China: an endemic area of both diseases.

BACKGROUND: Hepatitis B virus (HBV) infection was demonstrated to be a risk factor of several cancers of the digestive system. In addition, liver cirrhosis, which could possibly result from chronic HBV infection, was associated with a higher risk of gastric cancer. However, the association of HBV infection and gastric cancer has not been investigated. METHODS: A retrospective case-control study with 580 cases and 580 controls matched for age, sex and year of diagnosis was conducted. The associations between gastric cancer and HBV infection were explored with univariate and multivariate unconditional logistic regression analysis. RESULTS: Hepatitis B surface antigen (HBsAg) was positively associated with gastric cancer (AOR (95% CI): 1.49 (1.06-2.10)). This association remained significant in patients without family history of gastric cancer (AOR (95% CI): (1.06-2.11)). For HBsAg-negative population, being anti-HBc positive/anti-HBs negative, which possibly indicated occult HBV infection, was also found to have some associations with gastric cancer. In addition, some synergistic effects between HBV infection and blood type A in gastric cancer were identified. CONCLUSIONS: The HBV infection was positively related with gastric cancer, especially for patients without family history of gastric cancer. Further prospective studies are warranted to confirm this relationship.

Pemetrexed for previously treated patients with metastatic gastric cancer: a prospective phase II study.

BACKGROUND: Gastric cancer is one of the leading causes of cancer-related death worldwide. There were debates on the value of the second-line and beyond chemotherapy by the time we designed this trial. So we designed this phase II trial to assess the efficacy and safety of pemetrexed in patients with pretreated metastatic gastric cancer. METHODS: Thirty-four patients with pretreated metastatic gastric cancer were enroled in the study. Patients received pemetrexed 500 mg m(-2) every 21 days until the presence of progressive disease (PD) or unacceptable toxicity. RESULTS: A total of 34 patients were enroled in the study; 34 were eligible for toxicity and 30 for response. The response rate was 13.3%, 13.3% patients achieved a partial response, 50.0% achieved stable disease and 36.7% had a PD as the best response. The median overall survival time and median progression-free survival time was 6.4 months (95% confidence interval (CI) 5.8-9.5 months) and 2.2 months (95% CI 2.0-5.5 months), respectively. Most haematologic and non-haematologic toxicity were grade 1/2. Grade 3/4 toxicity included fatigue, neutropenia, thrombocytopenia, weight loss, anorexia and transaminase elevation. CONCLUSIONS: The monochemotherapy of pemetrexed is active and well tolerated when used in previously treated patients with metastatic gastric cancer.

Effects of 5-aza-2'deoxycytidine on RECK gene expression and tumor invasion in salivary adenoid cystic carcinoma.

Reversion-inducing cysteine-rich protein with kazal motifs (RECK), a novel tumor suppressor gene that negatively regulates matrix metalloproteinases (MMPs), is expressed in various normal human tissues but downregulated in several types of human tumors. The molecular mechanism for this downregulation and its biological significance in salivary adenoid cystic carcinoma (SACC) are unclear. In the present study, we investigated the effects of a DNA methyltransferase (DNMT) inhibitor, 5-aza-2'deoxycytidine (5-aza-dC), on the methylation status of the RECK gene and tumor invasion in SACC cell lines. Methylation-specific PCR (MSP), Western blot analysis, and quantitative real-time PCR were used to investigate the methylation status of the RECK gene and expression of RECK mRNA and protein in SACC cell lines. The invasive ability of SACC cells was examined by the Transwell migration assay. Promoter methylation was only found in the ACC-M cell line. Treatment of ACC-M cells with 5-aza-dC partially reversed the hypermethylation status of the RECK gene and significantly enhanced the expression of mRNA and protein, and 5-aza-dC significantly suppressed ACC-M cell invasive ability. Our findings showed that 5-aza-dC inhibited cancer cell invasion through the reversal of RECK gene hypermethylation, which might be a promising chemotherapy approach in SACC treatment.

Expression of beclin 1 in primary salivary adenoid cystic carcinoma and its relation to Bcl-2 and p53 and prognosis

Beclin 1 plays a critical role in autophagy and functions as a haploinsufficient tumor suppressor. The expression and prognostic significance of beclin 1 in head and neck adenoid cystic carcinoma (ACC) are largely unexplored. Therefore, we investigated the expression of beclin 1, Bcl-2, and p53 in head and neck ACC tissue. Tissue samples from 35 cases (15 females, 20 males) of head and neck ACC were utilized for immunohistochemistry. Beclin 1 expression was observed in 32 cases (91.4%) and considered to be high in 15 cases (42.9%) and low in 20 cases (57.1%). Beclin 1 expression was significantly correlated with a histological growth pattern (P=0.046) and histological grade (P=0.037). Beclin 1 expression was inversely correlated with Bcl-2 expression (P=0.013) and significantly associated with overall survival (P=0.006). Bcl-2 and p53 expression were observed in 21 cases (60.0%) and 16 cases (45.7%). Bcl-2 expression was significantly correlated with perineural invasion (P=0.041) and not associated with overall survival (P=0.053). p53 expression was directly correlated with beclin 1 expression (P=0.044). Our results indicated that beclin 1 may be a novel, promising prognostic factor for clinical outcome in head and neck ACC patients and may play a part in the development of head and neck ACC by interacting with Bcl-2 and p53.

Expression of beclin 1 in primary salivary adenoid cystic carcinoma and its relation to Bcl-2 and p53 and prognosis.

Beclin 1 plays a critical role in autophagy and functions as a haploinsufficient tumor suppressor. The expression and prognostic significance of beclin 1 in head and neck adenoid cystic carcinoma (ACC) are largely unexplored. Therefore, we investigated the expression of beclin 1, Bcl-2, and p53 in head and neck ACC tissue. Tissue samples from 35 cases (15 females, 20 males) of head and neck ACC were utilized for immunohistochemistry. Beclin 1 expression was observed in 32 cases (91.4%) and considered to be high in 15 cases (42.9%) and low in 20 cases (57.1%). Beclin 1 expression was significantly correlated with a histological growth pattern (P=0.046) and histological grade (P=0.037). Beclin 1 expression was inversely correlated with Bcl-2 expression (P=0.013) and significantly associated with overall survival (P=0.006). Bcl-2 and p53 expression were observed in 21 cases (60.0%) and 16 cases (45.7%). Bcl-2 expression was significantly correlated with perineural invasion (P=0.041) and not associated with overall survival (P=0.053). p53 expression was directly correlated with beclin 1 expression (P=0.044). Our results indicated that beclin 1 may be a novel, promising prognostic factor for clinical outcome in head and neck ACC patients and may play a part in the development of head and neck ACC by interacting with Bcl-2 and p53.

Aprepitant plus palonosetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy.

BACKGROUND: Chemotherapy-induced nausea and vomiting remain among the most feared adverse effects for cancer patients. AIM: The aim of this study was to evaluate the efficacy and safety of a combination of aprepitant, palonosetron and dexamethasone as antiemetic prophylaxis in patients receiving multiple-day cisplatin-based chemotherapy. METHODS: Forty-one solid cancer patients received aprepitant, palonosetron and dexamethasone during a 3-day cisplatin-based chemotherapy. Primary end-point was complete response in the overall phase (day 1 until 5 days after the end of chemotherapy). RESULTS: Aprepitant in combination with palonosetron and dexamethasone was safe, with hiccups (31.7%), fatigue (17.1%), headache (14.6%) and constipation (12.2%) the most common treatment-related adverse events, mostly mild. Complete response was seen in 58.5% of patients in the overall phase. In 23 patients receiving aprepitant in combination with palonosetron and dexamethasone more than one cycle (range: 2-5 cycles), the cumulative emetic protection rate after five cycles was 0.82. CONCLUSION: This study shows aprepitant in combination with palonosetron and dexamethasone is safe and effectively controls chemotherapy-induced nausea and vomiting in patients undergoing 3-day cisplatin-based chemotherapy, moreover, the efficacy is maintained during multiple cycles.