Circ-CCS enhances autophagy during imatinib resistance of gastrointestinal stromal tumor by regulating miR-197-3p/ATG10 signaling.

Context: Drug resistance in gastrointestinal stromal tumors (GISTs) is connected with autophagy activation. Accumulating data demonstrates the critical role of circular RNAs (circRNAs) dysregulation in this development. Aim: To explore the possible function of hsa_circ_0092306 (circ-CCS) in GIST imatinib resistance. Materials and Methods: Quantitative real-time reverse transcription PCR (RT-qPCR) was used to determine the expression levels of circ-CCS and miR-197-3p. The vitality and apoptosis of cells were determined using the Cell Counting Kit-8 and TUNEL assays, respectively. Western blot analysis was used to evaluate the relative protein expression. A dual-luciferase reporter assay was used to validate the link between circ-CCS, miR-197-3p, and ATG10. Statistical Analysis Used: Comparisons of two groups were analyzed using Student's t tests, and analysis of variance (ANOVA) with Tukey's post hoc test was used to compare three or more groups. Results: Circulating-CCS expression was considerably increased in the serum of imatinib-resistant GIST patients (P < 0.001). Circulating-CCS deficiency decreased cell proliferation and autophagy in GIST-882 and GIST-T1 cells, but promoted apoptosis (P < 0.05). Additionally, circ-CCS was predominantly found in the cytoplasm. Mechanically, circ-CCS targeted miR-197-3p, which may influence autophagy by downregulating ATG10, in order to modulate GIST cells' malignant tendencies. Moreover, silencing miR-197-3p reversed the effect of circ-CCS knockdown on apoptosis and autophagy in GIST cells. Conclusions: By modulating the miR-197-3p/ATG10 axis, circ-CCS increased imatinib resistance in GIST cells, establishing a potential target for reversing medication resistance in such patients.

CHINESE HERBAL DECOCTION AS A COMPLEMENTARY THERAPY FOR ATROPHIC GASTRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Chinese herbal decoction (CHD) has been extensively used in the treatment of atrophic gastritis (AG) in China and other Far Eastern countries. We conducted a systematic review and meta-analysis to estimate the efficacy and safety of CHD in AG. MATERIALS AND METHODS: Pubmed, Embase, Cochrane central register of controlled trials (central), VIP, China National Knowledge Infrastructure, Sinomed, Wanfang data were searched (up to December 2015). Randomized controlled trials recruiting patients with AG comparing CHD (alone or with western medicine (WM)) with WM were eligible. Dichotomous data were pooled to obtain relative risk (RR), with a 95% confidence interval (CI). RESULTS: Forty-two articles including 3,874 patients were identified. CHD, used alone or with WM, had beneficial effect over WM in the improvement of clinical manifestations (RR=1.28; 95% CI 1.22-1.34) and pathological change (RR=1.42; 95% CI 1.30-1.54) for AG patients. However, the H. pylori eradication effect of CHD was not supported by the existing clinical evidence, because of the significant study heterogeneity (I2>50%) and inconsistency between the primary results and sensitivity analysis. CONCLUSIONS: CHD, if prescribed as a complementary therapy to WM, may improve the clinical manifestations and pathological change for AG patients. But its monotherapy for H. pylori eradication is not supported by enough clinical evidence.

Prevalence of depression and anxiety in patients with chronic digestive system diseases: A multicenter epidemiological study.

AIM: To investigate the prevalence of depression and anxiety in patients with chronic digestive system diseases. METHODS: A total of 1736 patients with chronic digestive system diseases were included in this cross-sectional study, including 871 outpatients and 865 in-patients. A self-designed General Information for Patients of the Department of Gastroenterology of General Hospitals questionnaire was used to collect each patient's general information, which included demographic data (including age, sex, marital status, and education) and disease characteristics (including major diseases, disease duration, principal symptoms, chronic pain, sleep disorder, and limited daily activities). RESULTS: The overall detection rate was 31.11% (540/1736) for depression symptoms alone, 27.02% (469/1736) for anxiety symptoms alone, 20.68% (359/1736) for both depression and anxiety symptoms, and 37.44% (650/1736) for either depression or anxiety symptoms. Subjects aged 70 years or above had the highest detection rate of depression (44.06%) and anxiety symptoms (33.33%). χ2 trend test showed: the higher the body mass index (BMI), the lower the detection rate of depression and anxiety symptoms (χ2trend = 13.697, P < 0.001; χ2trend = 9.082, P = 0.003); the more severe the limited daily activities, the higher the detection rate of depression and anxiety symptoms (χ2trend = 130.455, P < 0.001, χ2trend = 108.528, P < 0.001); and the poorer the sleep quality, the higher the detection rate of depression and anxiety symptoms (χ2trend = 85.759, P < 0.001; χ2trend = 51.969, P < 0.001). Patients with digestive system tumors had the highest detection rate of depression (57.55%) and anxiety (55.19%), followed by patients with liver cirrhosis (41.35% and 48.08%). Depression and anxiety symptoms were also high in subjects with comorbid hypertension and coronary heart disease. CONCLUSION: Depression and anxiety occur in patients with tumors, liver cirrhosis, functional dyspepsia, and chronic viral hepatitis. Elderly, divorced/widowed, poor sleep quality, and lower BMI are associated with higher risk of depression and anxiety.

Effects of luteinizing hormone receptor signaling in prostate cancer cells.

BACKGROUND: The importance of androgen signaling in prostate cancer (PC) is well described and prostate cancer cells retain the ability to directly synthesize androgens. Luteinizing hormone (LH) can induce expression of steroidogenic enzymes and trigger androgen production, but the regulation of this process is not well-described. Here, we explored the impact of silencing LH receptor (LHR) silencing on androgen synthesis and on several relevant signaling pathways in PC. METHODS: LHR mRNA and protein expression was evaluated in LNCaP PC cells treated with LHR-siRNA. MTS assay was used to measure the effect of LHR-siRNA on proliferation in LNCaP and 22RV1 PC cells. Treated LNCaP and LAPC-3 cells were also assayed for differences in androgen synthesis and expression of steroidogenic enzymes, PSA, AR, and critical signaling molecules including PKA, ERK1/2, PI3K, AKT2, and HER2. RESULTS: We confirmed that functional LHR is expressed in both androgen-sensitive and castrate-resistant PC specimens. Treatment with LHR-siRNA effectively silenced LHR gene and protein expression and prevented LH-mediated proliferation and androgen synthesis in prostate cancer cells. LHR silencing also downregulated expression of AR, PSA, PKA, ERK1/2, PI3K, AKT2, and HER2. CONCLUSION: Collectively, these data demonstrate that silencing LHR expression suppresses androgen synthesis and signaling and the LH-LHR pathway may represent a viable therapeutic strategy in PC.

Endoscopic submucosal dissection of gastric fundus subepithelial tumors originating from the muscularis propria.

Endoscopic resection of gastric subepithelial tumors (SETs) carries a high risk of perforation, particularly for tumors located at the gastric fundus and originating from the muscularis propria. Based on our experience with endoscopic submucosal dissection (ESD) and a novel endoscopic device, namely the 'Resolution clip' for the endoscopic closure of iatrogenic upper gastrointestinal (upper GI) perforations, we evaluated the clinical feasibility and safety of ESD for gastric fundus subepithelial tumors originating from the muscularis propria. In this prospective study, 11 consecutive patients who presented with gastric SETs ≤3 cm in diameter were enrolled. Regardless of whether perforation occurred, the gastric wall defect was closed with clips. The patients were followed up after the surgery. Endoscopic resection was successfully performed in 10 patients; however, in one patient a pure endoscopic approach was impossible as the lesion was severely adhered to surrounding tissue, and a switch to laparoscopic wedge resection was necessary. The mean resected tumor size was 18.8×17.2 mm and the mean surgery time of the 10 patients with ESD was 81 min (range 45-130 min). Histological diagnosis was gastrointestinal stromal tumor (GIST) in eight lesions [very low risk according to the National Institutes of Health (NIH) risk classification] and leiomyoma in three lesions. Perforation occurred in 3/10 patients. Gastric closure with the Resolution clips was performed successfully in all cases. Early post-ESD bleeding (EPEB) occurred in one patient. Basic ferric sulfate solution was sprayed during the upper GI endoscopy examination and the bleeding stopped. No complications occurred and the follow-up was unremarkable. In this early study, ESD using the Resolution clip was demonstrated to be a feasible and minimally invasive treatment for gastric fundus subepithelial tumors originating from the muscularis propria.

Expression and significance of RKIP and E-cadherin in lung squamous cell carcinoma.

The purpose of this study was to investigate the expression of Raf kinase inhibitor protein (RKIP) and epithelial cadherin (E-cadherin) in lung squamous cell carcinoma tissue and its correlation with the clinical pathology of lung squamous cell carcinoma. RKIP and E-cadherin mRNA (by RT-PCR) and protein (by western blotting) levels were monitored in carcinoma tissues and surrounding normal tissues from 86 lung squamous cell carcinoma cases, and their positive rates were calculated. The rates of positive RKIP and E-cadherin mRNA expression were significantly lower in lung squamous cell carcinoma than in the surrounding normal tissues (P < 0.05). The positive expression rates were significantly lower in those with lymph node metastasis than in those without (P < 0.05). The lower the degree of tumor differentiation, the lower the E-cadherin mRNA positive expression rate (P < 0.05). The rates of positive RKIP and E-cadherin mRNA expression were significantly lower in patients at advanced (III, IV) stages than in patients at early (I, II) stages (p < 0.05); this rate, however, was independent of gender, age, and tumor size (P > 0.05). The protein levels of RKIP and E-cadherin were significantly lower in lung squamous cell carcinoma than in the surrounding normal tissues (P < 0.05). The levels were significantly lower in patients with lymph node metastasis than in those without it (P < 0.05). The lower the degree of tumor differentiation, the lower the protein level of E-cadherin (P < 0.05). Both RKIP and E-cadherin are tumor suppressors, their low expression levels may be associated with initiation, invasion and/or metastasis, as well as with the inhibition of lung squamous cell carcinoma differentiation.

Analysis of the causes and clinical characteristics of jejunoileal hemorrhage in China: a multicenter 10 year retrospective survey.

BACKGROUND: A retrospective study was performed to assess the causes, diagnostic methods for, and clinical features of, jejunoileal hemorrhage in Shandong province, China and to derive recommendations for management of this condition from these data. METHODS: We performed a retrospective systematic collection of data from between January 1999 and December 2008 in seven cities in Shandong province, China, identified 72 patients with jejunoileal hemorrhage and analyzed the relevant clinical data. RESULTS: Overall, tumors were the most common cause of jejunoileal hemorrhage (42 patients, 58.3%). The causes of this condition were significantly different (P < 0.05) in male and female patients. In male patients, the commonest factors were tumor (52.2%), enteritis (17.4%) and angiopathy (15.2%). However, in female patients, tumors accounted for a greater proportion of cases (18/26, 69.2%). In 38 cases (52.8%) the diagnosis was made by intraoperative enteroscopy or laparotomy, in 14 by capsule endoscopy and in the remainder by radiological methods. The most frequent presentation was melena (62.7%), followed by maroon stools (26.9%) and hematochezia (9.0%). Of the 72 patients,laparotomy is the main treatment method. CONCLUSION: Tumor, enteritis and angiopathy and diverticular disease are the most common causes of jejunoileal hemorrhage in Shandong province, China. The main clinical manifestations are bloody stools, most commonly in the form of melena, with or without abdominal pain. We recommend that female patients over the age of 40 with jejunoileal hemorrhage accompanied by abdominal pain should undergo urgent further assessment because of the strong probability of jejunoileal tumor.

Correlation between distribution of Helicobacter pylori in oral cavity and chronic stomach conditions.

In this study, the colonization and distribution of Helicobacter pylori (Hp) in patients with chronic gastric diseases were investigated and the relationship between the periodontal initial treatment and presence of Hp in oral cavity was examined to better understand the connection between Hp infection and chronic diseases. Primers for PCR amplification were designed according to ureC gene and cagA genes of Hp. Specimens were harvested from different sites of 96 patients with chronic gastric diseases and the specimens of dental plaques, gargles and dorsal mucosa were tested for Hp. The 96 patients were treated by bismuth triple therapy and among them, 52 subjects were additionally given periodontal initial therapy. The eradication rate of gastric Hp and oral Hp detection rate were determined 4 weeks and 1 year after the treatment. The results showed that the detection rates of oral specimens were in the order of dental plaques (82.3%), gargles (51.1%) and scrapings of dorsal mucosa of tongue (37.5%). One year after bismuth triple therapy or the triple therapy in combination with periodontal initial treatment, the eradication rate of gastric Hp was significantly higher in the combination treatment group than in group treated by the triple therapy alone (62.8% vs. 32.4%, P<0. 05). Moreover, the Hp detection rate was significantly lower in the combination group than in the group treated only with the triple therapy. We are led to conclude that Hp is present at various parts of oral cavity, oral Hp might be an important source of gastric Hp and the triple therapy plus periodontal initial treatment can enhance the long-term eradication rate of gastric Hp in patient with both chronic gastric diseases and chronic periodontitis.

Effect of luteinizing hormone on the steroidogenic pathway in prostate cancer.

BACKGROUND: Recent data has shown that prostate cancer (PCA) cells are capable of producing testosterone directly from cholesterol, which may contribute to the development of castration resistance. While up-regulation of steroidogenic enzymes has been previously described during castration-resistant prostate cancer (CRPC) progression, regulation of this process is poorly defined. These data examine the role of luteinizing hormone (LH) in the regulation of steroidogenic machinery in PCA cells. METHODS: PCA cell lines LNCaP, C4-2B, and 22RV1 were exposed to LH. Gene expression was quantified using real-time PCR and protein expression was characterized with standard Western blot analysis. Steroid analysis was performed using radioimmunoassay (RIA). Cell viability was measured using an MTS viability assay. RESULTS: Androgen-sensitive (LNCaP) and -independent PCA cells (C4-2B and 22RV1) express both mRNA and protein for LH and LH receptor (LHR). Exposure of these cells to LH for 4 hr increased the expression of several steroidogenic genes. Exposure for 10 days resulted in the increase of additional genes. At both time points, the upregulation of these genes was dose-dependent. This was mirrored by an increase in the expression of several key steroidogenic enzymes, including StAR, CYB5B, CYP11A, and 3ßHSD. LH stimulated the production of progesterone and testosterone in LNCaP cells as measured by RIA. We have also demonstrated that treatment of LNCaP cells with LH enhanced their viability. CONCLUSIONS: Our data show that LH-mediated activation of LHR significantly up-regulates the expression of genes and enzymes required for steroidogenesis and increases steroid production in PCA cells.

Correlation between Distribution of Helicobacter Pylori in Oral Cavity and Chronic Stomach Conditions / 华中科技大学学报（医学）（英德文版）

In this study,the colonization and distribution of Helicobacter pylori (Hp) in patients with chronic gastric diseases were investigated and the relationship between the periodontal initial treatment and presence of Hp in oral cavity was examined to better understand the connection between Hp infection and chronic diseases.Primers for PCR amplification were designed according to ureC gene and cagA genes of Hp.Specimens were harvested from different sites of 96 patients with chronic gastric diseases and the specimens of dental plaques,gargles and dorsal mucosa were tested for Hp.The 96 patients were treated by bismuth triple therapy and among them,52 subjects were additionally given periodontal initial therapy.The eradication rate of gastric Hp and oral Hp detection rate were determined 4 weeks and 1 year after the treatment.The results showed that the detection rates of oral specimens were in the order of dental plaques (82.3％),gargles (51.1％) and scrapings of dorsal mucosa of tongue (37.5％).One year after bismuth triple therapy or the triple therapy in com bination with periodontal initial treatment,the eradication rate of gastric Hp was significantly higher in the combination treatment group than in group treated by the triple therapy alone (62.8％ vs.32.4％,P＜0.05).Moreover,the Hp detection rate was significantly lower in the combination group than in the group treated only with the triple therapy.We are led to conclude that Hp is present at various parts of oral cavity,oral Hp might be an important source of gastric Hp and the triple therapy plus periodontal initial treatment can enhance the long-term eradication rate of gastric Hp in patient with both chronic gastric diseases and chronic periodontitis.

The disintegrin contortrostatin in combination with docetaxel is a potent inhibitor of prostate cancer in vitro and in vivo.

BACKGROUND: There are few available treatments for hormone refractory prostate cancer. Through the inhibition of integrins, contortrostatin (CN) effects tumor cell growth directly as well as through the inhibition of angiogenesis. The effect of CN in combination with docetaxel on prostate cancer cell lines in vitro and in vivo is evaluated in the present study. METHODS: FACS analysis of integrin expression, assessment of CN and docetaxel exposure on viability of plated cancer cells, and scratch test migration analysis were performed on PC-3 prostate cancer cells. CN and docetaxel inhibition of both PC-3 and CWR-22 prostate cancer cell lines were evaluated in a mouse xenograft bone model. Angiogenic activity in tumors were assessed using IHC with antibodies to CD31. RESULTS: Cell culture experiments indicate that the combination of docetaxel and CN inhibits growth in an additive fashion. FACS analysis of PC-3 cells shows expression of alpha5beta1 and alphavbeta5 integrins, but little expression of the alphavbeta3. CN showed complete inhibition of PC-3 migration in cultures grown on matrigel plates. In mice xenograft bone models, CN with docetaxel showed increased inhibition of both PC-3 and CWR-22 derived tumors. Analysis of treated xenograft tumors showed significantly decreased expression of CD31 indicating suppression of angiogenesis.

Gene profiling and pathway analysis of neuroendocrine transdifferentiated prostate cancer cells.

BACKGROUND: Neuroendocrine (NE) cells are present in both normal prostate and prostate cancer. In addition, NE differentiation can be induced by various factors, such as IL-6, in vitro and in vivo. However, the mechanism of this differentiation and the role of NE cells in prostate cancer are not well understood. In this study, we evaluated the gene expression and analyzed the pathways in prostate cancer cells exposed to various NE differentiation inducing factors in vitro. METHODS: Gene expression signatures between control LNCaP cells and each treatment induced NE cell line were compared using Affymetrix GeneChip with network and pathway analysis. RESULTS: All treatments were able to transdifferentiate LNCaP cells into NE phenotype as shown by morphology changes and NE marker measurements. Of the 54,675 oligonucleotide-based probe sets in microarray, 44,975 were mapped into the Ingenuity Pathway Analysis database and were filtered according to the t-test P value. At P < 0.002, the number of genes that were differentially expressed included 302 of the IL-6 treated cells, 201 of genistein, 233 of epinephrine, and 191 of the charcoal stripped serum ones. A pooled data approach also showed 346 differentially expressed genes at the same P value. Gene ontology analysis showed that cancer-related function had the highest significance. CONCLUSIONS: Despite some overlap, each NE transdifferentiation inducing treatment was associated with a changed expression of a unique set of genes, and such gene profiling may help to elucidate the molecular mechanisms involved in NE transdifferentiation of prostate cancer cells.

[Preliminary study of biweekly regimen of docetaxel, oxaliplatin, 5-fluorouracil and leucovorin for advanced gastric cancer].

OBJECTIVE: To evaluate the efficacy and toxicity of a biweekly DOF regimen consisting of docetaxel, oxaliplatin, 5-fluorouracil and leucovorin for advanced gastric cancer. METHODS: The biweekly DOF regimen was administered in 37 advanced gastric cancer patients. Docetaxel, oxaliplatin and leucovorin were given intravenously at a dose of 35 mg/m2, 85 mg/m2 and 200 mg/m2 for 1 h, 2 h and 2 h on D1, respectively, and 5-Fu was administered as continuous intravenous infusion for 48 h at a dose of 1500 mg/m2 on D1 and D2. This regimen was repeated every 2 weeks. The efficacy and toxicity were evaluated after completion of 3 cycles at least. RESULTS: The overall response rate (RR) of this series was 67.6%, complete response rate and partial response rate were 27.0% and 40.5%, respectively. The time to progression (TTP) was 9.2 months, and median survival time (MST) was 13.7 months. The RRs of 11 chemotherpy-naïve patients and 26 patients pre-treated with chemotherapy were 81.8% and 61.5%, respectively. CONCLUSION: Our preliminary results showed that this biweekly combination regimen of docetaxel, oxaliplatin, 5-fluorouracil and leucovorin is effective and tolerable for advanced gastric cancer. However, further investigation of this regimen is mandatory.

Both beta-actin and GAPDH are useful reference genes for normalization of quantitative RT-PCR in human FFPE tissue samples of prostate cancer.

BACKGROUND: Beta-actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) have been frequently considered as constitutive house keeping genes for RT-PCR and used to normalize changes in specific gene expressions. However, these expressions have been shown to be affected by the sample type and experimental conditions. We investigated which housekeeping gene is useful to study gene expression of paraffin embedded human tissue samples of prostate cancer. METHODS: Fifteen pairs of cancer and corresponding normal tissue were obtained from patients with prostate cancer. We evaluated gene expression of beta-actin, GAPDH, androgen receptor (AR), and heat-shock 70-kd protein 5 (HSPA5) using laser captured microdissection and quantitative RT-PCR. AR and HSPA5 gene expression were normalized to each of these reference genes using the 2(-DeltaDeltaCt) method of relative quantification. The quantity 2(Ct(normal)-Ct(cancer)) divided by ratio of cDNA(cancer)/cDNA (normal) was used for comparing differences between cancer and normal tissue in GAPDH and beta-actin expression. RESULTS: Ct value of beta-actin was significantly correlated with that of GAPDH (r = 0.443, P = 0.014). AR and HSPA5 gene expression levels using beta-actin for normalization were significantly correlated with these gene expression levels using GAPDH (AR; r = 0.689, P = 0.004, HSPA5; r = 0.879, P < 0.001). Both reference genes were expressed more highly in cancer tissue than in normal tissue, with that of GAPDH being significantly different between cancer tissue and normal tissue (P = 0.029). CONCLUSIONS: The good correlation between gene expression values obtained when using beta-actin and GAPDH as reference genes suggests that either gene is a valid denominator for gene expression studies in prostate cancer.

Prognostic value of the androgen receptor and its coactivators in patients with D1 prostate cancer.

BACKGROUND: Prostate cancer treated with androgen ablation eventually becomes resistant. Because the androgen receptor (AR) signaling axis affects disease progression, AR coactivator molecules could provide clinical prognostic value. This study investigates the association between AR coactivator molecules and clinical outcome measures in patients with prostate cancer. PATIENTS AND METHODS: Expression levels of AR and its coactivators, SRC1, TIF2, and Her2/neu were determined by quantitative RT-PCR in 148 prostatectomy specimens. AR protein expression was determined by immunohistochemistry. The prognostic value of these expression levels on clinical outcomes was examined. RESULTS: Increased gene and protein AR expression was not correlated with any of the clinical outcome measures. A non-monotonic correlation was observed between SRC1 and overall survival, as well as Her2/neu and time to prostate-specific PSA recurrence. CONCLUSION: Although no statistically significant relationships were found, the weak association between some clinical outcomes and two AR coactivators may help improve the current predictive nomogram for patients with prostate cancer.

[Influence of intravenous chemotherapy on cellular immunity in patients with advanced digestive tract cancer].

BACKGROUND & OBJECTIVE: Cancer patients have a poor immune response and chemotherapy could deteriorate their immune system further. Reasonable immune therapy is an important adjuvant remedy for tumors. This study was to monitor the changes of T-cell phenotypes in peripheral blood and interleukin-2 (IL-2) concentration in plasma in digestive tract cancer patients before and after chemotherapy. METHODS: The proportions of CD3+, CD4+, CD8+, CD4+CD28+, CD8+CD28+ and CD4+CD25+ T cells in peripheral blood of 104 patients with advanced digestive tract cancer, hospitalized from Sep. 2005 to Apr. 2006, were detected by flow cytometry (FCM). The concentration of IL-2 in plasma was measured by ELISA. RESULTS: The proportions of CD4+, CD4+CD28+, CD8+CD28+, CD4+CD25+ T cells and ratio of CD4/CD8 were (36.52+/-3.85)%, (32.87+/-4.98)%, (6.87+/-3.11)%, (9.68+/-3.42)% and 0.98+/-0.17 in digestive tract cancer patients, and (45.23+/-9.20)%, (40.12+/-5.85)%, (15.8+/-4.50)%, (5.67+/-2.90)% and 1.43+/-0.12 in healthy subjects. In the patients with response to chemotherapy, the proportions of CD4+CD28+ and CD8+CD28+ T cells and ratio of CD4/CD8 were (22.93+/-3.98)%, (7.08+/-1.23)% and 0.90+/-0.22 before chemotherapy, and (28.25+/-4.03)%, (12.10+/-3.45)% and 1.24+/-0.22 at 3 weeks after chemotherapy. In the patients with no response to chemotherapy, the proportions of CD4+CD28+, CD8+CD28+ and CD4+CD25+ T cells were (24.08+/-4.02)%, (6.35+/-1.23)% and (8.20+/-2.34)% before chemotherapy, and (16.45+/-3.27)%, (3.20+/-0.82)% and (20.34+/-3.69)% at 3 weeks after chemotherapy. CONCLUSIONS: The immunosuppression of digestive tract cancer patients would be enhanced early (about 1-2 weeks) after intravenous chemotherapy. The immunity of the patients with response to chemotherapy would be improved at 3 weeks after chemotherapy; while the immunity of the patients with no response to chemotherapy would not change, or even be suppressed.

Locus-wide chromatin remodeling and enhanced androgen receptor-mediated transcription in recurrent prostate tumor cells.

Prostate cancers (PCas) become resistant to hormone withdrawal through increased androgen receptor (AR) signaling. Here we show increased AR-mediated transcription efficiency in PCa cells that have acquired the ability to grow in low concentrations of androgen. Compared to androgen-dependent PCa cells, these cells showed increased activity of transiently transfected reporters and increased mRNA synthesis relative to levels of AR occupancy of the prostate-specific antigen (PSA) gene. The locus also displayed up to 10-fold-higher levels of histone H3-K9/K14 acetylation and H3-K4 methylation across the entire body of the gene. Although similar increased mRNA expression and locus-wide histone acetylation were also observed at another kallikrein locus (KLK2), at a third AR target locus (TMPRSS2) increased gene expression and locus-wide histone acetylation were not seen in the absence of ligand. Androgen-independent PCa cells have thus evolved three distinctive alterations in AR-mediated transcription. First, increased RNA polymerase initiation and processivity contributed to increased gene expression. Second, AR signaling was more sensitive to ligand. Third, locus-wide chromatin remodeling conducive to the increased gene expression in the absence of ligand was apparent and depended on sustained AR activity. Therefore, increased AR ligand sensitivity as well as locus-specific chromatin alterations contribute to basal gene expression of a subpopulation of specific AR target genes in androgen-independent PCa cells. These features contribute to the androgen-independent phenotype of these cells.

Genistein-induced neuroendocrine differentiation of prostate cancer cells.

BACKGROUND: Neuroendocrine (NE) cells are present in normal prostate and their number appears to be increased in advanced prostate cancer (PCA). In this study, we studied the effect of the phytoestrogen, genistein, on NE differentiation of LNCaP cells in vitro. METHODS: Neuroendocrine marker expression of LNCaP cells exposed to genistein was measured by immunohistochemistry, Western blot, and real-time PCR methods. Western blot analysis was used to study cell cycle and signaling pathways induced by genistein treatment. RESULTS: Six days after continuous genistein treatment, the majority of genistein-surviving cancer cells underwent transdifferentiation into a NE-like phenotype overexpressing the NE markers chromogranin A, synaptophysin, serotonin, and beta-III tubulin. This NE differentiation process was associated with upregulation of the cell cycle modulators p21, p27, and p53, and activation of the MAPK and STAT3 pathways. CONCLUSION: Our data indicate that genistein evokes not only apoptosis but also NE transdifferentiation of PCA cells.

[Effects of shading at blossoming and boll-forming stages on cotton fiber quality].

The study on the effects of different shading level at blossoming and boll-forming stages on cotton fiber quality of Zhongmiansuo No.41 and Lumianyan No. 18 showed that with increasing shading, the maximum fiber length of cotton decreased, while the elongation period increased. The fiber length in 70% shading treatment was 1.01 mm shorter than that in 40% shading treatment. Without shading, the fiber reached its maximum length 25 days after anthesis, while in shading treatments, the fiber reached its maximum length 35 days after anthesis. Fiber gauge tenacity was also decreased with increasing shading. Comparing with the control, both 40% and 70% shading significantly decreased the fiber maturation and maturity. Two test cotton varieties presented the same change trend under shading condition.

Discovery and preclinical evaluation of a novel class of small-molecule compounds in hormone-dependent and -independent cancer cell lines.

We discovered a series of salicylhydrazide class of compounds with remarkable anticancer activity against a panel of hormone receptor-positive and -negative cell lines. In the present study, we evaluated the in vitro activity of SC21 and SC23 against a range of human tumor cell types and the in vivo efficacy of compound SC21 in a PC3 human prostate cancer xenograft model in mice. We also determined the effects of SC21 on cell cycle regulation and apoptosis. Our in vitro results show that salicylhydrazides are highly potent compounds effective in both hormone receptor-positive and -negative cancer cells. SC21 induced apoptosis and blocked the cell cycle in G(0)/G(1) or S phase, depending on the cell lines used and irrespective of p53, p21, pRb, and p16 status. SC21 effectively reduced the tumor growth in mice without apparent toxicity. Although the mechanism of action of SC21 is not completely elucidated, the effect on cell cycle, the induction of apoptosis and the activity against a panel of tumor cell lines of different origins prompted us to carry out an in-depth preclinical evaluation of SC21.