Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China.

BACKGROUND: Cadonilimab is a bispecific antibody targeting PD-1 and CTLA-4, which has shown substantial clinical benefits in advanced cervical cancer. In the COMPASSION-16 trial, we aimed to evaluate the addition of cadonilimab to first-line standard chemotherapy in persistent, recurrent, or metastatic cervical cancer. METHODS: In this randomised, double-blind, multicentre, placebo-controlled phase 3 trial, women aged 18-75 years across 59 clinical sites in China with previously untreated persistent, recurrent, or metastatic cervical cancer were randomly assigned (1:1) to receive cadonilimab (10 mg/kg) or placebo plus platinum-based chemotherapy with or without bevacizumab every 3 weeks for six cycles, followed by maintenance therapy every 3 weeks for up to 2 years. Randomisation was performed centrally through an interactive web-response system. Stratification factors were the use of bevacizumab (yes or no) and previous concurrent chemoradiotherapy (yes or no). The dual primary outcomes were progression-free survival as assessed by blinded independent central review and overall survival in the full analysis set. This study is registered with ClinicalTrials.gov, NCT04982237; the study has completed enrolment and is ongoing for treatment and follow-up. FINDINGS: 445 eligible women were enrolled between Sept 11, 2021, and June 23, 2022. Median progression-free survival was 12·7 months (95% CI 11·6-16·1) in the cadonilimab group and 8·1 months (7·7-9·6) in the placebo group (hazard ratio 0·62 [95% CI 0·49-0·80], p<0·0001); median overall survival was not reached (27·0 months to not estimable) versus 22·8 months (17·6-29·0), respectively (hazard ratio 0·64 [0·48-0·86], p=0·0011). The most common grade 3 or higher adverse events were decreased neutrophil count, decreased white blood cell count, and anaemia. INTERPRETATION: The addition of cadonilimab to first-line standard chemotherapy significantly improved progression-free survival and overall survival with a manageable safety profile in participants with persistent, recurrent, or metastatic cervical cancer. The data support the use of cadonilimab plus chemotherapy as an efficacious first-line therapy in persistent, recurrent, or metastatic cervical cancer. FUNDING: Akeso Biopharma.

Cancer screening and prevention education in standardized training residents: A cross-sectional survey in single center.

BACKGROUND: Standardized residency training is an essential aspect of enhancing the ability of cancer prevention and screening of residents. The current study was performed to investigate tumor prevention, screening literacy and the training demands of standardized training residents and explore related influencing factors. METHODS: A cross-sectional survey was conducted among 320 residents of The First Hospital of Lanzhou University. An online, self-designed questionnaire was employed to investigate tumor prevention and screening, training status, and the requirements of residents. Data were analyzed using Fisher's exact test. RESULTS: The mean age of the 320 participants was 26.04 ± 1.85 years;133, 83, and 104 were in the 1st, 2nd and 3rd year of standardized training, respectively. Among the common carcinogenic factors, smoking, infectious agents, and drinking were more correlated with tumors by 72.19, 66.57, and 64.38% of the physicians, respectively. Excess body weight, an insufficient intake of fruits and dietary fiber, and a lack of exercise were correlated with tumors by only 26.56, 25, and 23.44% of the physicians, respectively. The proportion of physicians providing an accurate answer to the tumor screening question ranged from 23.13 to 93.13%. The lowest accuracy was 23.13% for the initial age of regular breast cancer screening in general-risk women. The maximum rate of the primary liver cancer screening methods was 93.13%. Postgraduates and residents of oncology practitioners considered excess body weight and the insufficient intake of fruits and dietary fiber more relevant to cancer (P < 0.05). Male residents viewed more associations between tumors and a lack of exercise and air pollution (P < 0.05). Overall, 71.26% of participants felt that their tumor prevention and screening knowledge was poor and 95.31% thought they needed standardized tumor prevention and screening training. CONCLUSION: Tumor prevention and screening literacy of standardized training residents should be further improved. There is a huge knowledge demand for tumor prevention and screening. Therefore, it is vital to build a training program in line with the requirements of cancer prevention and control efforts that focus on improving literacy among residents.

Is there a role for carbon therapy in the treatment of gynecological carcinomas? A systematic review.

This Systematic Review summarizes the literatures of clinical trials on the efficacy and safety of carbon ion therapy for gynecological carcinomas. The protocol is detailed in the online PROSPERO database, registration no. CRD42019121424, and a final set of eight studies were included. In the treatment of cervical carcinomas, both carbon ion therapy alone and carbon ion therapy concurrent chemotherapy have presented good efficacy. Besides, the efficacy of inoperable endometrial carcinomas and gynecological melanoma are similar to that of surgical treatment. In terms of safety, gastrointestinal and genitourinary toxicities are low and could be controlled by limiting the volume and dose of intestinal tract and bladder. Carbon ion radiotherapy could be considered a safe, effective and feasible therapy for gynecological carcinomas.

Correlation between patient-specific quality assurance in volumetric modulated arc therapy and 2D dose image features.

In radiotherapy, air-filled ion chamber detectors are ubiquitously used in routine dose measurements for treatment planning. However, its use has been restricted by intrinsic low spatial resolution barriers. We developed one procedure for patient-specific quality assurance (QA) in arc radiotherapy by coalescing two adjacent measurement images into a single image to improve spatial resolution and sampling frequency, and investigated how different spatial resolutions affect the QA results. PTW 729 and 1500 ion chamber detectors were used for dosimetric verification via coalescing two measurements with 5 mm-couch shift and the isocenter, and only isocenter measurement, which we call coalescence and standard acquisition (SA). Statistical process control (SPC), process capability analysis (PCA), and receiver operating characteristic (ROC) curve were used to compare the performance of the two procedures in determining tolerance levels and identifying clinically relevant errors. By analyzing 1256 γ values calculated on interpolated data points, our results indicated that detector 1500 showed higher averages in coalescence cohorts at different tolerance criteria and the dispersion degrees were spread out smaller. Detector 729 yielded a slightly lower process capability of 0.79, 0.76, 1.10, and 1.34, but detector 1500 exhibited somewhat different results of 0.94, 1.42, 1.19, and 1.60 in magnitude. The results of SPC individual control chart showed that cases in coalescence cohorts with γ values lowering its lower control limit (LCL) were greater than those in SA cohorts for detector 1500. A combination of the width of multi-leaf collimator (MLC) leaf, the cross-sectional area of the single detector, and the spacing between adjacent detectors might lead to discrepancies in percent γ values across diverse spatial resolution scenarios. The accuracy of reconstructed volume dose is mainly determined by the interpolation algorithm used in dosimetric systems. The magnitude of filling factor in the ion chamber detectors determined its ability to detect dose deviations. SPC and PCA results indicated that coalescence procedure could detect more potential failure QA results than SA while enhancing action thresholds.

Landscape of Alternative Splicing Events Related to Prognosis and Immune Infiltration in Glioma: A Data Analysis and Basic Verification.

Background: Glioma is a prevalent primary brain cancer with high invasiveness and typical local diffuse infiltration. Alternative splicing (AS), as a pervasive transcriptional regulatory mechanism, amplifies the coding capacity of the genome and promotes the progression of malignancies. This study was aimed at identifying AS events and novel biomarkers associated with survival for glioma. Methods: RNA splicing patterns were collected from The Cancer Genome Atlas SpliceSeq database, followed by calculating the percentage of splicing index. Expression profiles and related clinical information of glioma were integrated based on the UCSC Xena database. The AS events in glioma were further analyzed, and glioma prognosis-related splicing factors were identified with the use of bioinformatics analysis and laboratory techniques. Further immune infiltration analysis was performed. Results: Altogether, 9028 AS events were discovered. Upon univariate Cox analysis, 425 AS events were found to be related to the survival of patients with glioma, and 42 AS events were further screened to construct the final prognostic model (area under the curve = 0.974). Additionally, decreased expression of the splicing factors including Neuro-Oncological Ventral Antigen 1 (NOVA1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), heterogeneous nuclear ribonucleoprotein L-like protein (HNRNPLL), and RNA-Binding Motif Protein 4 (RBM4) contributed to the poor survival in glioma. The immune infiltration analysis demonstrated that AS events were related to the proportion of immune cells infiltrating in glioma. Conclusions: It is of great value for comprehensive consideration of AS events, splicing networks, and related molecular subtype clusters in revealing the underlying mechanism and immune microenvironment remodeling for glioma, which provides clues for the further verification of related therapeutic targets.

Clinical features, treatment and outcomes in patients with tracheal adenoid cystic carcinoma: a systematic literature review.

BACKGROUND: Primary tracheal adenoid cystic carcinoma (TACC) is rare and originates from the minor salivary gland. Biologically, TACC results in delayed presentation, and the therapeutic effects of multimodal treatment differ across individuals. This study aimed to review cases of TACC to identify clinical features, imaging modalities, treatment, and patient outcomes across follow-ups. METHODS: The PubMed, Web of Science and MEDLINE databases were searched to identify articles reporting cases of TACC. The study variables included in the analysis were patient demographics, biological characteristics, presenting symptoms, imaging modalities, treatments, follow-up times and survival outcomes. RESULTS: A total of 76 articles and 1252 cases were included in this review. The most common presenting symptom was dyspnoea (86.0%), followed by cough (58.0%). Surgery alone (40.9%), surgery with postoperative radiotherapy (36.4%) and radiotherapy alone (19.2%) were used most frequently treatments modalities. Of the 1129 cases with disease control and survival data, there was no evidence of disease in 78.7%, local recurrence was reported in 3.8%. Distant metastasis rate was 24.9% of 418 reported cases, lung (44.2%) was the most commonly involved organ. The 5, 10 years survival rate of patients treated with surgery alone and surgery with postoperative radiotherapy were 86.4%, 55.6% and 97.3%, 44.4%, respectively. CONCLUSION: TACC most common presenting symptoms were dyspnoea, cough and shortness of breath. Surgery alone and surgery with postoperative radiotherapy are predominant treatment modalities. Both seems to provide a good result in term of disease control and long-term survival rate in patients with TACC.

Irradiation-Induced Changes in the Immunogenicity of Lung Cancer Cell Lines: Based on Comparison of X-rays and Carbon Ions.

Increasing the immunogenicity of tumors is considered to be an effective means to improve the synergistic immune effect of radiotherapy. Carbon ions have become ideal radiation for combined immunotherapy due to their particular radiobiological advantages. However, the difference in time and dose of immunogenic changes induced by Carbon ions and X-rays has not yet been fully clarified. To further explore the immunogenicity differences between carbon ions and X-rays induced by radiation in different "time windows" and "dose windows." In this study, we used principal component analysis (PCA) to screen out the marker genes from the single-cell RNA-sequencing (scRNA-seq) of CD8+ T cells and constructed a protein-protein interaction (PPI) network. Also, ELISA was used to test the exposure levels of HMGB1, IL-10, and TGF-ß under different "time windows" and "dose windows" of irradiation with X-rays and carbon ions for A549, H520, and Lewis Lung Carcinoma (LLC) cell lines. The results demonstrated that different marker genes were involved in different processes of immune effect. HMGB1 was significantly enriched in the activated state, while the immunosuppressive factors TGF-ß and IL-10 were mainly enriched in the non-functional state. Both X-rays and Carbon ions promoted the exposure of HMGB1, IL-10, and TGF-ß in a time-dependent manner. X-rays but not Carbon ions increased the HMGB1 exposure level in a dose-dependent manner. Besides, compared with X-rays, carbon ions increased the exposure of HMGB1 while relatively reduced the exposure levels of immunosuppressive factors IL-10 and TGF-ß. Therefore, we speculate that Carbon ions may be more advantageous than conventional X-rays in inducing immune effects.

MiR-192-5p inhibits proliferation, migration, and invasion in papillary thyroid carcinoma cells by regulation of SH3RF3.

BACKGROUND: The decreased level of miR-192-5p has been reported in several kinds of cancers, including bladder, colon, ovarian, and non-small cell lung cancer. However, the expression and function of miR-192-5p in papillary thyroid carcinoma/cancer (PTC) remains unknown. OBJECTIVE: The present study aimed to explore the function and underlying mechanism of miR-192-5p in PTC development. METHODS: PTC tissues and relative normal controls from PTC patients were collected. qRT-PCR analysis was performed to measure miR-192-5p and SH3RF3 mRNA level in PTC tissues and cell lines. CCK-8 method and FCM assay were used to test cell proliferation and apoptosis in TPC-1 cells, respectively. The abilities of cell migration and invasion were detected by wound healing and transwell assays, respectively. The protein expression was evaluated by Western blot. The interaction between miR-192-5p and Src homology 3 (SH3) domain containing ring finger 3 (SH3RF3) were confirmed by dual-luciferase reporter assay. RESULTS: MiR-192-5p level was obviously decreased in PTC tissues and cell lines. Overexpression of miR-192-5p suppressed proliferation, migration, invasion, and EMT process, while induced apoptosis in TPC-1 cells. In addition, miR-192-5p negatively modulated SH3RF3 expression by binding to its 3'-untranslated region (3'UTR). Silencing SH3RF3 inhibited the migration, invasion, and EMT of TPC-1 cells. In the meantime, matrine, an alkaloid extracted from herb, exerted its anti-cancer effects in PTC cells dependent on increase in miR-192-5p expression and decrease in SH3RF3 expression. CONCLUSION: We firstly declared that miR-192-5p played a tumor suppressive role in PTC via targeting SH3RF3. Moreover, matrine exerted its anti-cancer effects in PTC via regulating miR-192-5p/SH3RF3 pathway.

Evaluation of tumor microenvironmental immune regulation and prognostic in lung adenocarcinoma from the perspective of purinergic receptor P2Y13.

Tumor-infiltrating immune cells (TICs) can serve as an important indicator to evaluate the prognosis and therapeutic response in lung adenocarcinoma (LUAD). The identification of mutated genes that can affect the abundance of TICs and prognosis has practical implications. In the presented study, tumor microenvironment (TME) scoring was performed by the ESTIMATE scoring system on 598 RNA transcripts selected from the TCGA database to determine the proportions of immune cells and stromal cells. The infiltration difference of TICs in LUAD samples was obtained by CIBERSORT. The 'immuneeconv' R software package, which integrates six latest algorithms, including TIMER, xCell, MCP-counter, CIBERSORT, EPIC and quanTIseq were used to verify the correlation between purinergic receptor P2Y13 (P2RY13) and immune cells. Based on RNA sequencing analysis of the Lewis lung cancer-bearing model in C57BL/6 mice and immunohistochemistry (IHC) of human LUAD tissues, the expression of P2RY13 and associated pathways were verified. It was shown that differentially expressed genes (DEGs) obtained by interactive analysis based on Immunescore and Stromalscore were significantly enriched in immune-related pathways. The expression of P2RY13 was significantly associated with prognosis and clinicopathological characteristics of LUAD patients. More importantly, this gene played an important role in maintaining the immune dominant environment and changing the regulation of TICs. P2RY13 expression was positively correlated with the infiltration of dendritic cells (DCs) in various of tumor tissues as validated by the PanglaoDB scRNA-seq database. Therefore, P2RY13 is expected to be a potential biomarker for predicting TME and the prognosis of LUAD after verification.

Carbon ion (12C6+) irradiation induces the expression of Klrk1 in lung cancer and optimizes the tumor microenvironment based on the NKG2D/NKG2D-Ls pathway.

With the identification of "negative immune regulation" defects in the immune system and the continuous improvement of immunotherapy, natural killer cells (NK) have received more attention, especially as tools in combined immunotherapy. Carbon ions (12C6+) have become the ideal radiation for combined immunotherapy due to their significant radiobiological advantages and synergistic effects. The purpose of this study was to explore the NK cell-mediated cytotoxicity pathway and related mechanisms in lung cancer induced by carbon ion irradiation. KLRK1, which specifically encodes the NKG2D receptor, was significantly correlated with the prognosis, clinical stage, functional status of NK cells, and the immune microenvironment of lung cancer, as shown by bioinformatics analysis. Based on RNA-seq data of Lewis lung cancer in C57BL/6 mice, carbon ion irradiation was found to significantly induce Klrk1 gene expression and activate the NKG2D/NKG2D-Ls pathway. The Treg inhibition pathway combined with carbon ion radiotherapy could significantly increase the infiltration and function of NK cells in the tumor microenvironment of lung cancer and prolong the survival time of C57BL/6 mice. In conclusion, carbon ions have significant radiobiological advantages, especially under conditions of combined immunotherapy. Carbon ions combined with Treg inhibitors can significantly improve the infiltration and functional status of NK cells.

Construction of a novel ceRNA network and identification of lncRNA ADAMTS9-AS2 and PVT1 as hub regulators of miRNA and coding gene expression in gastric cancer.

BACKGROUND: Studies on the interactions of single long non-coding RNA, microRNA, and mRNA have many limitations; therefore, it is necessary to study the complex regulatory network of gastric cancer (GC) pathogenesis systematically. METHODS: In this study, gene and miRNA expression data for GC were downloaded from The Cancer Genome Atlas and used for transcriptome profiling, differential gene analysis, and construction of an lncRNA-miRNA-mRNA regulatory network in conjunction with an online database to identify the key genes and subnetworks in GC pathogenesis. Real-time quantitative polymerase chain reaction was used to detect the expression of hub lncRNAs in 54 paired GC and matched normal mucosal tissues. RESULTS: We constructed an lncRNA-miRNA-mRNA competitive endogenous RNA regulatory network containing 1,626 network nodes and 2,704 interactions. LncRNA ADAMTS9-AS2 and PVT1 were identified as key node genes in this competitive endogenous RNA network. Quantitative reverse transcription-polymerase chain reaction revealed ADAMTS9-AS2 downregulation and PVT1 upregulation in 54 pairs of GC and normal tissues adjacent to the cancer tissues. CONCLUSIONS: This study systematically analysed the lncRNA-miRNA-mRNA regulatory network in GC and identified ADAMTS9-AS2 and PVT1 as key regulatory genes in this network, providing new understanding of GC pathogenesis and insights for its early diagnosis and treatment.

Intensity modulated radiation therapy may improve survival for tracheal-bronchial adenoid cystic carcinoma: A retrospective study of 133 cases.

PURPOSES: This study aimed to evaluate the role of radiotherapy (RT) and intensity modulated radiation therapy (IMRT) in adjuvant and definitive settings of tracheal-bronchial adenoid cystic carcinoma (TACC) treatment. MATERIALS/METHODS: TACC patients (n = 133) treated with surgery and/or RT curatively in our institution between January 1st, 1984 and December 31st, 2017 were analyzed retrospectively. RESULTS: Among the 116 patients undergoing surgery, 50 (43.1 %) achieved complete resections and 66 (56.9 %) had positive surgical margins. For patients with positive margins, overall adjuvant RT was correlated with no significantly improved OS (10-year: 58.0 % vs. 47.9 %; P =  0.340) and a slight LRFS benefit (5-year: 81.9 % vs.75.6 %; P =  0.056), but adjuvant IMRT showed significant superiority in both OS (10-year: 82.9 % vs. 47.9 %; P =  0.031) and LRFS (5-year: 100.0 % vs. 75.6 %; P =  0.001) in comparison with no postoperative RT. Multivariate analysis also identified adjuvant IMRT as a significant favorable factor with OS (HR = 0.186, 95 %CI: 0.039-0.883; P =  0.034). For 17 patients receiving definitive RT, IMRT achieved promising 5-year OS of 88.9 % and LRFS of 64.3 %, yet no significant difference from non-IMRT group was reached (P = 0.447 and 0.706). Different therapies presented no significantly different impact on DMFS, whilst DMFS explained more of the OS variances (P < 0.001, R2 = 0.480) than LRFS (P < 0.001, R2 = 0.323). CONCLUSION: IMRT could confer greatly improved OS and LRFS in postoperative setting for TACC patients with positive surgical margins. IMRT was also a good therapeutic option for definitive TACC with promising survival and local control.

The impact of pelvic radiotherapy on the gut microbiome and its role in radiation-induced diarrhoea: a systematic review.

Pelvic radiotherapy is the key treatment for pelvic malignancies, usually including pelvic primary tumour lesions and lymphatic drainage areas in the pelvic region. Therefore, the intestinal tract in the radiation field is inevitably damaged, a phenomenon clinically referred to as radiation enteritis, and diarrhoea is the most common clinical symptom of radiation enteritis. Therefore, it is necessary to study the mechanism of radiation-induced diarrhoea. It has been found that the gut microbiome plays an important role in the development of diarrhoea in response to pelvic radiotherapy, and the species and distribution of intestinal microbiota are significantly altered in patients after pelvic radiotherapy. In this study, we searched for articles indexed in the Cochrane Library, Web of Science, EMBASE and PubMed databases in English and CNKI, Wanfang data and SINOMED in Chinese from their inception dates through 13 March 2020 to collect studies on the gut microbiome in pelvic radiotherapy patients. Eventually, we included eight studies: one study report on prostatic carcinoma, five studies on gynaecological carcinoma and two papers on pelvic carcinomas. All studies were designed as self-controlled studies, except for one that compared toxicity to nontoxicity. The results from all the studies showed that the diversity of intestinal flora decreased during and after pelvic radiotherapy, and the diversity of intestinal flora decreased significantly in patients with diarrhoea after radiotherapy. Five studies observed that the community composition of the gut microbiota changed at the phylum, order or genus level before, during, and after pelvic radiotherapy at different time points. In addition, the composition of the gut microbiota before radiotherapy was different between patients with postradiotherapy diarrhoea and those without diarrhoea in five studies. However, relevant studies have not reached consistent results regarding the changes in microbiota composition. Changes in the intestinal flora induced by pelvic radiotherapy and their relationship between changes in intestinal flora and the occurrence of radiation-induced diarrhoea (RID) are discussed in this study, providing a theoretical basis for the causes of RID after pelvic radiotherapy.

Construction prognosis model based on autophagy-related gene signatures in hepatocellular carcinoma.

Aim: To develop robust and accurate prognostic biomarkers to help clinicians optimize therapeutic strategies. Materials & methods: Differentially prognosis-related autophagy genes were identified by bioinformatics analysis method. Results: Seven prognosis-related autophagy genes were more significantly related to the prognosis of hepatocellular carcinoma (HCC). Functional enrichment analysis demonstrated that these genes were mainly enriched in the autophagy pathway. BIRC5, HSPB8 and TMEM74 exhibited significant prognostic value for HCC. Besides, the risk score and BIRC5 have significant significance with clinicopathological significance of HCC. Conclusion: The research has identified a number of prognosis-related autophagy genes that associated with the survival and clinical stage of HCC. In addition, the prognostic model can be used to calculate the patient's risk score and these prognosis-related autophagy genes might serve as therapeutic targets.

LINC02381 Promoted Cell Viability and Migration via Targeting miR-133b in Cervical Cancer Cells.

BACKGROUND: It has been proved that lncRNAs could function as CeRNA for miRNAs in tumor growth and metastasis for cervical cancer. This paper aims to identify the role of LINC02381 in cervical cancer cells. MATERIALS AND METHODS: RT-qPCR was utilized to measure the expression levels of LINC02381 in cervical cancer tissues and cells. MTT, colony formation assay, transwell assay, RT-qPCR, and Western blotting were performed to investigate the roles of LINC02381 in cervical cancer cells. RegRNA 2.0 was used to predict the miRNA-binding sites of LINC02381. Luciferase reporter assay and RT-qPCR were employed to confirm the sponging effect between miR-133b and LINC02381. RESULTS: This study showed that LINC02381 was up-regulated in cervical cancer cells and acted as an oncogene in the development of cervical cancer. LINC02381 promoted cell viability and metastasis via sponging miR-133b. Moreover, miR-133b could target its downstream mediator of RhoA and inhibit its expression. CONCLUSION: Overall, our results indicated that LINC02381 functions as an oncogene in cervical cancer and could serve as a novel target for cervical cancer therapies in the future.

Mechanism of Asbt (Slc10a2)-related bile acid malabsorption in diarrhea after pelvic radiation.

Background: Radiation is a mode of treatment for many pelvic malignancies, most of which originate in the gynecologic, gastrointestinal, and genitourinary systems. However, the healthy gut is unavoidably included in the irradiation volume, resulting in undesirable results that manifest as radiation-induced diarrhea (RID), which is the most common side effect of radiation therapy and significantly affects the patients' quality of life. This study aimed to investigate the potential mechanism of diarrhea after pelvic radiotherapy in rats based on the effect of radiation on bile acid homeostasis and sodium-dependent bile acid transporter (Asbt).Methods: In this experimental study, male Sprague-Dawley rats were divided into the following groups - pelvic irradiation, cholestyramine-concurrent radiation, and control groups. The rats in the pelvic irradiation group were irradiated in the pelvic region with 2 Gy per day for five consecutive days. The total bile acid (TBA) levels in the ileum, colon, and feces were measured using automatic biochemical analyzer, and the levels of individual bile acids were evaluated by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The mRNA and protein expression of Asbt in ileum were assessed by qRT-PCR and Western blot assay. The rats in the cholestyramine-concurrent radiation group were administered with cholestyramine, a bile acid-chelating resin, and concurrent radiation for 5 days. The body weight of rats was monitored daily, and the degree of diarrhea was scored.Results: Diarrhea was observed at 2 and 3 days post-pelvic radiation. The TBA levels were significantly decreased at 4 and 5 days post-radiation in the ileum (p < .01, p < .01) and increased at 4 and 5 days post-radiation in the colon (p < .05, p < .05). The fecal excretions of TBA were significantly increased at 3, 4, and 5 days post-radiation (p < .05). The levels of individual bile acids were significantly decreased in the ileum and increased in the colon and feces, post-radiation. The mRNA and protein expression of Asbt in the ileum gradually decreased with increasing days of pelvic radiation and significantly decreased at 3 and 5 days post-radiation, respectively. Furthermore, a significant decrease in body weight was observed post-pelvic radiation, and cholestyramine administration did not reverse the weight loss. However, the incidence of RID was decreased after administration of cholestyramine.Conclusions: Bile acid malabsorption is partially responsible for RID post-pelvic radiation in rats, and the potential mechanism is related to the downregulation of the ileal Asbt.

[Celecoxib induces apoptosis and inhibits angiogenesis in gastric cancer].

OBJECTIVE: The aim of this study was to explore the effect of celecoxib, a cyclooxygenase-2 inhibitor, on induction of apoptosis and inhibition of angiogenesis in gastric cancer. METHODS: Fifty nine gastric cancer patients were randomly divided into 2 groups: celecoxib group (n = 37) and control group (n = 22). The patients in the celecoxib group were treated orally with celecoxib 200 mg twice daily for 7 days before resection. The patients in the control group received surgical resection alone. Another group of 20 healthy subjects were recruited as normal control. The number of apoptotic tumor cells was measured by terminal deoxynucleotidyl transferse-mediated dUTP nick end labeling (TUNEL). The expression of COX-2, VEGF and the microvessel density (MVD) were evaluated by immunohistochemistry. RESULTS: The TUNEL results showed an increase of apoptosis in the tumor cells after celecoxib treatment in comparison with that in the control group (7.1% +/- 1.0% vs. 6.2% +/- 0.9%, P < 0.05). The expression level of COX-2 and VEGF in the gastric cancer tissues was significantly decreased in the celecoxib group compared with those in the control group (P < 0.05). Furthermore, MVD was also significantly lower in the celecoxib group when compared with that in the control group (30.48 +/- 5.02 vs. 38.98 +/- 4.58, P < 0.05). CONCLUSION: Oral intake of celecoxib can induce apoptosis and suppress angiogenesis in gastric cancer. It may become an effective agent in the treatment of gastric cancer.

Effect of celecoxib on E-cadherin, VEGF, Microvessel density and apoptosis in gastric cancer.

Cyclooxygenase-2 (COX-2) plays a crucial role in the development and invasion of gastric cancer. COX-2 inhibitors have been shown to be chemopreventive against gastrointestinal cancers. In vitro studies have suggested that the mechanisms may be related to induction of apoptosis and inhibition of angiogenesis. COX-2 may also have impact on E-cadherin. In our study we investigate the effect of Celecoxib on expression of E-cadherin and serum soluble E-cadherin, as well as on apoptosis and angiogenesis in patients with gastric cancer. Fifty nine gastric cancer patients were randomly divided into two groups: Surgery group (n = 22), in which patients underwent surgical resection after diagnosis, and Celecoxib + Surgery group (n = 37), in which patients received oral Celecoxib 200 mg twice daily for 7 days before curative resection. Twenty healthy subjects (Healthy controls) were recruited as normal controls. After curative resection, COX-2, E-cadherin, VEGF, and MVD were detected by immunohistochemistry. Serum soluble E-cadherin was quantitatively measured using a commercially available enzyme-linked immunosorbent assay kit. Apoptosis was determined by TUNEL assay. Significantly decreased expression of COX-2, increased E-cadherin and apoptosis, decreased VEGF and MVD were observed in gastric cancer tissues from patients receiving Celecoxib compared to Surgery group. Compared to Healthy controls, the serum soluble E cadherin levels were higher in gastric cancer patients which were decreased by Celecoxib. This in vivo study demonstrated that Celecoxib induces apoptosis and inhibit angiogenesis of gastric cancer. Its impact on E-cadherin may suggest that this agent may suppress the invasion of advanced gastric cancer.

Effects of nociceptin/orphanin FQ on rats with cathartic colon.

AIM: To demonstrate the change and effect of nociceptin/orphanin FQ in the colon of rats with cathartic colon. METHODS: The cathartic colon model was established by feeding rats rhubarb for 3 mo, the changes of colonic electromyography were investigated by both suspension muscle strips test and serosal recordings of colonic myoelectrical activity. Immunohistochemical staining (S-P methods) and image analysis were used to determine the changes of nociceptin/orphanin FQ in the proximal colon and distal colon of rats with cathartic colon. RESULTS: Suspension muscle strips test in vitro showed OFQ (10(-9)-10(-6) mol/L) concentration dependently caused an immediate tonic contraction in the isolated colon. But the increase of tension in cathartic colon was less than control groups (P < 0.01). Intravenous administration of OFQ (1 microg/kg) caused phasic contractions in the proximal colon, while the amplitude of phasic contractions caused by OFQ in cathartic colon was much lower than that in the control groups (2.58 +/- 0.41 vs 4.16 +/- 0.53, t = -2.6, P = 0.012). OFQ was highly expressed in the myenteric plexus of the rat colon but not in the muscle cells. The immunoreactivity of OFQ in the proximal colon in cathartic colon rats decreased significantly compared with the control group (P = 0.001). CONCLUSION: Colonic smooth muscle of cathartic colon showed low sensitivity to the stimulation of OFQ, suggesting that it might be caused by the abnormal distribution of OFQ or the abnormalities of receptors, leading to the disorganization of dynamic and incoordinated contractions.