[Treatment and prognosis of multiple primary malignant neoplasms complicated with renal cell carcinoma].

OBJECTIVE: To investigate the treatment and prognosis of multiple primary malignant neoplasms (MPMN) complicated with renal cell carcinoma (RCC), and to make risk stratification. METHODS: A retrospective study of 27 cases of MPMN with RCC in two centers, including the different tumors of MPMN, specific treatment methods, and the interval between primary cancers. At the same time, the survival conditions, including recurrence, metastasis and survival, were followed up for statistical analysis. The interval between the two kinds of primary cancer within 6 months was simultaneous MPMNs, and more than 6 months was metachronous MPMNs. For simple risk stratification of cases, as long as one of the MPMNs had a stage Ⅲ or higher malignancy, which was defined as high risk. RESULTS: Among the 27 patients, 20 were male and 7 were female, with age at the time of diagnosis was 42-82 years, with an average age of (61.3±11.7) years. The age at the diagnosis of renal cancer was 43-87 years, with an average age of (66.0±11.3) years. There were 21 cases with duplex primary malignant neoplasms, 4 cases with triple primary malignant neoplasms, and 2 cases with quadruple primary malignant neoplasms. The interval between first cancer and second cancer was 0-360 months, with a median of 18 months. There were 17 cases of metachronous multiple primary malignant neoplasms and 10 cases of simultaneous multiple primary malignant neoplasms. The most common system of MPMN with comorbid RCC involved urologic system, digestive system and respiratory system. The most common locations of MPMN with comorbid RCC were bladder cancer, lung cancer and colon cancer. Follow-up time calcu- lated from the last cancer was 2-156 months, with a median of 32 months. And 14 cases survived and 13 cases died, with 11 cases being tumor related. Tumor stage was the risk factor of prognosis. Any kind of tumor stage in stage Ⅲ or above had a relatively poor prognosis. CONCLUSION: MPMN complicated with RCC is relatively rare. Standard treatment should be used for each cancer type during the treatment process. The prognosis mainly depends on the highest stage of each tumor. Simple risk stratification shows that the prognosis of the high-risk group is worse. This simple stratification method may be helpful to predict the prognosis.

Using Rasch Analysis to Validate the Michigan Hand Outcomes Questionnaire from the Wrist and Radius Injury Surgical Trial.

BACKGROUND: The Michigan Hand Outcomes Questionnaire is a patient-reported outcome measure that has been validated in many upper extremity disorders using classic test theory. Rasch measurement analysis is a rigorous method of questionnaire validation that offers several advantages over classic test theory and was used to assess the psychometric properties of the Michigan Hand Outcomes Questionnaire. This study used Rasch analysis to evaluate the questionnaire for distal radius fractures in older adults. The incidence and costs of distal radius fractures are rising, and reliable assessment tools are needed to measure outcomes in this growing concern. METHODS: Rasch analysis was performed using 6-month assessment data from the Wrist and Radius Injury Surgical Trial. Each domain in the Michigan Hand Outcomes Questionnaire was independently analyzed for threshold ordering, person-item targeting, item fit, differential-item functioning, response dependency, unidimensionality, and internal consistency. RESULTS: After collapsing disordered thresholds and removing any misfitting items from the model, five domains (Function, Activities of Daily Living, Work, Pain, and Satisfaction) demonstrated excellent fit to the Rasch model. The Aesthetics domain demonstrated high reliability and internal consistency but had poor fit to the Rasch model. CONCLUSIONS: Rasch analysis further supports the reliability and validity of using the Michigan Hand Outcomes Questionnaire to assess hand outcomes in older adults following treatment for distal radius fractures. Results from this study suggest that questionnaire scores should be interpreted in a condition-specific manner, with more emphasis placed on interpreting individual domain scores, rather than the summary Michigan Hand Outcomes Questionnaire score.

[Targeted binding of rs1053005 locus of STAT3 with miR-452-3p and the association between STAT3 gene polymorphism and noise-induced hearing loss].

Objective: To investigate the relationship between rs1053005 of signal conversion and transcription activator 3 (STAT3) and miR-452-3p, and the association between STAT3 gene polymorphism and noise-induced hearing loss (NIHL) . Methods: In December 2017, 1220 workers were selected from an automobile manufacturing factory, an energy company and a chemical fiber factory in Jiangsu Province who had occupational noise exposure and working age of more than 3 years. The workers with the mean hearing threshold of ≥26 dB (A) of the two ear high frequency (3000, 4000 and 6000 Hz) were defined as case group (n=609) , and the rest were control group (n=611) . Five single nucleotide polymorphism (SNP) sites of STAT3 (rs4796793, rs1053023, rs1053005, rs1053004 and rs3744483) were selected to explore the association between STAT3 gene polymorphism and NIHL by analyzing the points. The double luciferase reporter gene verified whether miR-452-3p was targeted to bind STAT3, and overexpressed miR-452-3p in HEI-OC1 cells to explore the mechanism of STAT3 expression regulation. Results: There was no significant difference in gender, age, smoking and drinking between the two groups (P>0.05) . Compared with the control group[ (15.58±4.76) dB], the mean hearing threshold of the case group [ (37.50±12.39) dB] was higher, and the difference were statistically significant (P<0.05) . Compared with the control group, the C alleles of rs1053023 and rs1053005 were higher in the case group (OR=1.367, 1.370, P<0.05) . The risk of NIHL in men with TC/CC genotype were 1.545 and 1.531 times higher than that in men with TT genotype (P<0.05) . Compared with the control group, the mRNA expression of STAT3 in the case group was significantly increased (P<0.05) . The STAT3 mRNA expression of miR-452-3p group cells was significantly decreased (P<0.05) . Conclusion: The rs1053023 and rs1053005 polymorphism of STAT3 are related to NIHL. The C alleles of rs1053023 and rs1053005 may be biomarkers of workers exposed to noise.

[Targeted therapy of pyogenic sterile arthritis, pyoderma gangrenosum, and acne syndrome (PAPA): a case report and literature review].

Objective: To analyze the clinical course and targeted therapy of pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. Methods: The clinical history of a 6-year-old boy with PAPA syndrome, who was admitted to Hong Kong University Shenzhen Hospital in September 2017, was reviewed. His genetic diagnosis was confirmed by whole exome sequencing. The response to targeted therapy was evaluated by comparing the inflammatory markers (erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) and serum cytokines (interleukin (IL)-1, IL-6 and tumor necrosis factor-α (TNF-α)) before and after biological agents treatment. For literature review, "PAPA syndrome" and"PSTPIP1 gene"were used as keywords to retrieve papers published from January 1997 to December 2019 from Pubmed, Wanfang and CNKI database. Results: The patient was a 6-year-old boy, admitted to the hospital due to recurrent joint swelling and pain for more than 4 years. Before treatment, the CRP (256 mg/L), ESR (105 mm/1 h) and cytokines including serum TNF-α (7.43 ng/L), IL-1 (<5 ng/L), IL-6 (301 ng/L) were significantly elevated. Culture of the joint effusion was negative, but the IL-6 level was above 1 000 ng/L. MRI showed osteomyelitis at the lower end of the right femur. Gene detection found a heterozygous variation of PSTPIP1 gene (c.748G>A, p.E250K). Arthralgia once alleviated after the initiation of tocilizumab and infliximab, but recurred after 1 year of treatment. Thereafter, the anti-IL-1 receptor antagonist (Anakinra) was commenced, followed by a significant improvement of the arthralgia, and a complete remission during the follow-up. Besides, the level of CRP, ESR, serum TNF-α, IL-1 and IL-6 were all decreased to normal on the last followed up in December 2019. Literature review found 29 articles and 87 patients in total. The initial symptoms included those of arthritis (n=58), pyoderma gangrenosum (n=33), and acne (n=24). Among all the cases, 13 genotypes were confirmed, and 47 variations involved amino acid p.E250. Steroid and/or biological agents were used in most patients. Conclusions: PAPA syndrome should be suspected in children with recurrent pyogenic sterile arthritis, and an early diagnosis could be achieved by genetic test. Targeted treatment with biological agent may control the symptoms effectively. Biological agents can control symptoms of this disorder effectively.

[Usefulness of the indocyanine green fluorescence imaging technique in laparoscopic partial nephrectomy].

OBJECTIVE: To detail a novel technique for marking renal tumors with intravenous indocyanine green (ICG) during laparoscopic partial nephrectomy, and to investigate the feasibility and safety of this technique with the use of near-infrared fluorescence imaging. METHODS: Between July 2019 and January 2020, 25 consecutive cases with renal masses underwent intraoperative ICG tumor marking laparoscopic partial nephrectomy, at the department of urology in Peking University Third Hospital by the same surgeon. The key benefits included quick intraoperative identification of the mass with improved visualization and real-time control of resection margins by the ICG Immunofluorescence imaging technique. Clinical data were prospectively collected in our institutional database. Perioperative, pathological, and clinical outcomes of the partial nephrectomy were assessed. Measurement data with normal distribution and count data were respectively described as M(range) and percentage. Among these cases, 16 cases were male and 9 cases female, The median body mass index was 25.4 (20.0-35.4) kg/m2. The average age was 54 (29-77) years. The maximum tumor diameter was 2.75(1.30-5.20) cm. The R.E.N.A.L score was 7.5 (5.0-10.0).The tumor locations were distributed with upper pole (11, 42%), middle (6, 23%), and lower pole (9, 35%).The clinical stages of the tumor were described as follows: T1aN0M0 (23, 88.5%), T1bN0M0(2, 7.7%), T2aN0M0 (1, 3.8%). RESULTS: All the 25 cases were performed 26 times with intraoperative ICG tumor marking laparoscopic partial nephrectomy. There were no allergy, infection and other complications with intravenous indocyanine green. The surgical procedure was successful in all the patients. No conversion and blood transfusion were needed. All the cases of the surgical margin were negative. Overall the operative time was 136 (50-247) min and warm ischemia time was 14 (7-30) min.The estimated blood loss was 50 (10-400) mL and the hospital stay was 5.5 (3.0-31.0) days. One case with perirenal hematoma, one case with urine leak, one with respiratory failure and deep venous thrombosis. All of these cases were cured by the corresponding treatment. The others had no severe complications. There was no tumor recurrence and metastasis during the follow up with 4 to 10 months. CONCLUSION: ICG marking and near-infrared fluorescence imaging technology has now emerged as a safe, feasible and useful tool that may facilitate laparoscopic partial nephrectomy.

[Analysis of self-control trial results of narrow band imaging and white light in transurethral resection of bladder tumor].

OBJECTIVE: To investigate the effect of NBI assisted white light transurethral resection of bladder tumor (TURBT) in the treatment of bladder urothelial carcinoma and to summarize the experience of narrow band imaging (NBI) operation. METHODS: Patients with bladder urothelial carcinoma were selected, and TURBT was performed after anesthesia. First of all, the bladder tumor was found and resected under white light. Then we replaced with NBI, looked for suspicious lesions and resected them, The specimens excised under white light and NBI were collected separately. The number, location and pathological results of the lesions under white light were recorded, and the residual lesions under NBI were also recorded. To evaluate the effect of NBI, the ratio of residual bladder tumor was calculated. The cases were divided into three groups according to the time sequence. The clinical data of each group were collected and the learning curve of TURBT under NBI assisted white light was observed. RESULTS: A prospective study of 45 patients with bladder tumor from April 2018 to January 2020, including 32 males and 13 females, aged from 23 to 89 years, with an average age of 65.2 years. All the operations were successfully completed, without obvious complications after operation. Nine cases were single and 36 cases were multiple. The maximum diameter of the tumors was 0.5 to 4.0 cm, with an average of 2.2 cm. The histopathology of the resected tissue under white light was urothelial carcinoma, and 19 cases (42.2%) were pathologically positive by NBI resection. The 45 cases were divided into three groups according to the time sequence, 15 cases in each group. The true positive rate of NBI was 33.3%, 46.7% and 46.7%, respectively, and the false positive rate was 60.0%, 46.7% and 26.7%, respectively in the three groups. CONCLUSION: TURBT is an effective way to treat bladder urothelial cancer, NBI is an effective supplement of white light, which can increase the detection rate of bladder cancer and reduce post-operative recurrence. The NBI light source has a certain learning curve. With the increase of cases, the false-positive rate of NBI is gradually reduced. After the NBI operator has rich experience, the recognition degree of flat tumor is gradually improved under white light, and the residual rate of NBI is reduced after the removal under white light.

[Effect of silencing hepatocyte growth factor receptor c-Met expression on biological characteristics of colon cancer cells].

Objective: To investigate the effect of silencing hepatocyte growth factor receptor (c-Met) expression on the biological characteristics of HCT116 colon cancer cells. Methods: Cellular model of c-Met transient transfection was established by using small interfering RNA (siRNA), the expression of c-Met in colon cancer cells was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and western blot. The apoptosis assay, cell invasion assay, cell migration and other experiments were conducted to observe the effects of silencing c-Met on the biological characteristics of colon cancer cells. Results: RT-qPCR results showed that the relative expression levels of c-Met mRNA in siRNA-Met group, blank control group and siRNA negative control (siRNA-NC) group were 0.32±0.26, 1.01±0.03 and 1.05±0.23, respectively, and the difference was statistically significant (P<0.05). Western blot analysis showed that the expression level of c-Met protein in the siRNA-Met group was 0.24±0.03, significantly lower than 1.23±0.06 in the blank control group and 1.18±0.11 in the siRNA-NC group (P<0.05). The cell counting kit-8 (CCK8) results showed that the 72-hour absorbance (A) values of the siRNA-Met group, blank control group and the siRNA-NC group were 1.13±0.05, 1.48±0.08 and 1.53±0.07, respectively, and the difference was statistically significant (P<0.01). Cell cycle results showed that the proportion of cells in G(2)/M phase was (14.65±1.41)% in siRNA-Met group , (5.07±0.70)% in blank control group and (5.63±0.71)% in siRNA-NC group, and the difference was statistically significant (P<0.05). The expression levels of cell cycle regulatory proteins Cdc25c and cyclin B1 in siRNA-Met group were significantly decreased. The apoptotic rate in siRNA-Met group was (5.85±0.35)%, significantly higher than (1.00±0.17)% in blank control group and (0.91±1.14)% in siRNA-NC group (P<0.05). The expression level of apoptosis-related protein Bcl-2 in the siRNA-Met group was significantly decreased while Bcl-2 associated X protein (BAX) expression level was significantly increased. The cell scratching result showed that the cell migration abilities of the siRNA-Met group, blank control group and the siRNA-NC group were (51.33±8.62)%, (100.00±3.72)% and (102.33±6.43)%, respectively, and the difference was statistically significant (P<0.05). The number of cell penetrating into the basement membrane of the siRNA-Met group, blank control group and the siRNA-NC group were 47.50±10.60, 100.00±5.33 and 102.50±10.61, respectively, and the difference was statistically significant (P<0.05). The expressions of invasion related proteins including MMP-2 and MMP-9 in siRNA-Met group were decreased significantly. Conclusions: c-Met plays an important role in maintaining the biological characteristics of colon cancer cells. Inhibition of c-Met may have important values in the treatment of colon cancer.

[Expression of long-chain non-coding RNA LINC00152 in laryngeal squamous cell carcinoma and its clinical significance].

Objective:The aim of this study is to explore the relative expression level of LINC00152 in laryngeal squamous cell carcinoma（LSCC） and its clinical significance. Method:The relative expression levels of LINC00152 in LSCC cell lines and 36 paired LSCC specimens were measured by qRT-PCR method. And the correlations between the expression level of LINC00152 and the clinical features derived from LSCC patients were analyzed and compared through the independent sample t-test. Result:The relative expression level of LINC00152 was over-expressed in LSCC cell lines and cancerous tissues than that in paired adjacent normal tissues, and the difference was statistically significant（P=0.006）. Even the associations between LINC00152 expression level and clinicopathological features（P=0.044 for clinical stage, P=0.032 for pathological differentiation degree） were significantly. Conclusion:LINC00152 is highly expressed in LSCC and it may become a new tumor marker for the diagnosis and prognosis of LSCC.

[Epigenetic regulations in laryngeal squamous cell carcinoma].

Laryngeal cancer, which is mainly consisted of laryngeal squamous cell carcinoma(LSCC), is one of the common neoplasms in head and neck. In spite the advantages in diagnose and treatment, the mortality of LSCC is still high in the past 20 years. Epigenetic regulations play a important role in LSCC. The aim of this review is to provide an update on the epigenetic regulations in LSCC, such as the methylation of chromatin, the pre- and post-regulation of transcription by microRNAs and/or long noncoding RNAs. The gene methylation can represses the expression of genes, and some histone and DNA methylation are associated with LSCC. Histone deacetylases also play a role in LSCC. MicroRNAs are about 22 nt in length, which inhibit or facilite the occurrence and development of LSCC by different mechanisms.Long noncoding RNAs(lncRNAs) , more than 200 nt in length, can modulate the LSCC in different levels, such as gene methylation modification, microRNA regulation. Based on the differences of epigenetic regulation, some characteristics may serve as markers of diagnose, and even facilitate the treatment of LSCC.

MiR-425-5p promotes tumor progression via modulation of CYLD in gastric cancer.

OBJECTIVE: MicroRNAs (miRNAs) have emerged as important gene regulators and are recognized as key players in carcinogenesis. The present study investigated the role of miR-425-5p in the development and progression of gastric cancer (GC). PATIENTS AND METHODS: The miR-425-5p level in GC tissues and cells was assayed by qRT-PCR. Then, the effects of miR-425-5p expression on the biological behavior of GC cells were investigated. Analysis of target protein expression was determined by Western blotting. Bioinformatic prediction and luciferase assays were employed to identify the predicted miRNA which regulates CYLD. RESULTS: miR-425-5p was found to be up-regulated in GC tissues and cell lines. Knockdown of miR-425-5p in GC cells attenuated migration and invasion of GC cells, whereas overexpression of miR-425-5p promoted cell migration and invasion. The luciferase assay demonstrated that CYLD was a direct target of miR-425-5p. Furthermore, the miR-425-5p level was inversely correlated with levels of CYLD in Western blotting assay. CONCLUSIONS: Our findings indicate that miR-425-5p may contribute to the progression of GC through a mechanism involving CYLD, suggesting that miR-425-5p may have the potential to be a novel important alternative therapeutic target for GC.

[Effect of Δ40p53 isoform on enhancing the pro-apoptotic function of p53 in tumor cells].

Objective: To investigate the effect of Δ40p53, an alternative spliced isoform of p53 lacking the N-ter minus, on the pro-apoptotic function of p53. Methods: The wild-type p53 was ectopically expressed in HCT116-p53(-/-) (endogenous Δ40p53 expression), HCT116-p53(+ /+) (wild-type p53) and H1299 (p53-null) cells by adenoviral delivery, while Δ40p53 plasmid were transfected into these cells to overexpress Δ40p53. The levels of Δ40p53 and p53 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative PCR. The expression of related proteins was deter mined by Western blotting. The interaction of p53 and Δ40p53 was observed by co-immunoprecipitation assay. Calcein-AM/propidium iodide (PI) staining and flow cytometry were used to detect the apoptotic rate of tested cells in each group. Results: HCT116-p53(-/-) cells expressed endogenous Δ40p53 isoform. Neither transcription nor protein expression of wild-type p53 was interfered by the increased expression of Δ40p53. Full length p53 and Δ40p53 could bind to each other. Calcein-AM/PI staining showed that the apoptotic rates of H1299-Control, HCT116-p53(-/-) -Control, H1299+ p53, HCT116-p53(-/-)+ p53, H1299+ oxaliplatin (Oxa), HCT116-p53(-/-)+ Oxa, H1299+ p53+ Oxa and HCT116-p53(-/-)+ p53+ Oxa groups were (2.50±0.47)%, (2.40±0.32)%, (5.20±0.58)%, (4.10±0.18)%, (22.40±1.73)%, (19.30±1.11)%, (29.90±1.15)% and (39.30±2.26)%, respectively. It was statistically significant between H1299+ p53+ Oxa and HCT116-p53(-/-)+ p53+ Oxa groups (t=3.721, P=0.0205). Moreover, the apoptotic rates of H1299-Control, H1299+ Δ40p53, H1299+ p53, H1299+ p53+ Δ40p53, H1299+ Oxa, H1299+ Δ40p53+ Oxa, H1299+ p53+ Oxa and H1299+ p53+ Δ40p53+ Oxa groups were (2.60±0.35)%, (2.20±0.17)%, (4.80±0.49)%, (4.90±1.10)%, (20.30±1.10)%, (19.60±1.45)%, (27.90±1.39)%, (35.20±1.43)%, respectively. Furthermore, flow cytometry assay showed that the apoptotic rates of above cells were (2.70±0.32)%, (2.20±0.24)%, (4.60±0.48)%, (3.90±0.67)%, (19.30±1.11)%, (17.70±0.66)%, (28.30±2.76)% and (37.50±1.51)%, respectively. H1299+ p53+ Δ40p53+ Oxa cells showed higher cell apoptosis than H1299+ p53+ Oxa cells (t=2.930, P=0.042). Conclusion: Δ40p53 isoform can bind to full-length p53, and enhance its pro-apoptotic function in tumor cells.

[Study on the survival rate of random flap using pre-injection of ADSCs].

Objective: To determine the effects of adipose-derived stem cells (ADSCs) on the survival rate of flaps by transplanting ADSCs into the experimental flaps pre-operatively. Methods: ADSCs were isolated from fresh human fat and cultured in vitro. Their morphological characters were observed, and flowcytometry and differentiation test and evaluation were conducted. A total of 40 BALB/c mice were divided into 5 groups randomly with each of 8 mice. 1 cm×4 cm random skin flap was designed on the mice back, ADSCs were injected in advance into subcutaneous tissues of 3 groups, the operation was performed on the 2nd, 5th and 7th day after the ADSCs injection, meanwhile skin flap operation was conducted in the immediate injection group and control group. Survival condition of the skin flaps was observed and von willebrand factor (vWF) staining was used to detect the number of micro-vessels in the skin flap. The enzyme-linked immuno sorbent assay (ELISA) method was used to detect the concentration of vascular endothelial growth factor (VEGF) in the skin flap. Results: The immediate injection group had a significantly higher survival rate of skin flap than the pre-injection groups and the control group [(51.5±6.3)% vs (38.3±6.7)%, (21.0±2.9)%, (30.0±3.9)% and (34.5±4.2)%, all P<0.01]. The immediate injection group had a significantly higher number of micro-vessels in the skin flap than the pre-injection groups and the control group [(21.0±4.3) vs (17.5±3.9), (9.9±2.6), (13.9±2.6) and (16.1±3.3)/LPF, all P<0.01]. The laboratory results of the concentration of VEGF in skin flap kept a consistent tendency with the flap survival rate. Conclusion: Pre-injection with the ADSCs into the skin flap prevents the survival of the flap to a certain extend and does not show the function of promoting tissue angiogenesis.

Functional polymorphisms in microRNAs and susceptibility to liver cancer: a meta-analysis and meta-regression.

MicroRNAs (miRNAs) are small non-coding RNA molecules that play a fundamental role in controlling a variety of biological functions. Emerging evidence has shown that common genetic polymorphisms in miRNAs may be associated with the development of liver cancer; however, several individually published studies showed inconclusive results. This meta-analysis aimed to derive a more precise estimation of the association between functional polymorphisms in miRNAs and susceptibility to liver cancer. A literature search of PubMed, Embase, Web of Science, and China BioMedicine (CBM) databases was conducted on articles published before May 1, 2012. Crude odds ratios with 95% confidence intervals were calculated. Fourteen case-control studies were included with a total of 6824 liver cancer patients and 7674 healthy controls. Nine single nucleotide polymorphisms in miRNAs were assessed, including miR-146a G>C (rs2910164), miR-499 T>C (rs3746444), miR-218 A>G (rs11134527), miR-let-7c Ins/Del (rs6147150), miR-106b-25 A>G (rs999885), miR-34b/c T>C (rs4938723), miR-196a-2 C>T (rs11614913), miR-920 Ins/Del (rs16405), and miR-122 Ins/Del (rs3783553). The meta-analysis results showed that miR-let-7c Del, miR-34b/c C, and miR-122 Del variants may be associated with increased liver cancer risk. Conversely, miR-920*Del variant may decrease the risk of liver cancer. However, miR-146a G>C, miR-196a-2 C>T, miR-499 T>C, and miR-218 A>G polymorphisms showed no significant association with liver cancer risk. In conclusion, the current meta-analysis suggests that miR-let- 7c Del, miR-34b/c C and miR-122 Del variants may be associated with increased liver cancer risk, while miR-920 Del variant may be a protective factor against liver cancer.

Synergistic effects of glycated chitosan with high-intensity focused ultrasound on suppression of metastases in a syngeneic breast tumor model.

Stimulation of the host immune system is crucial in cancer treatment. In particular, nonspecific immunotherapies, when combined with other traditional therapies such as radiation and chemotherapy, may induce immunity against primary and metastatic tumors. In this study, we demonstrate that a novel, non-toxic immunoadjuvant, glycated chitosan (GC), decreases the motility and invasion of mammalian breast cancer cells in vitro and in vivo. Lung metastatic ratios were reduced in 4T1 tumor-bearing mice when intratumoral GC injection was combined with local high-intensity focused ultrasound (HIFU) treatment. We postulate that this treatment modality stimulates the host immune system to combat cancer cells, as macrophage accumulation in tumor lesions was detected after GC-HIFU treatment. In addition, plasma collected from GC-HIFU-treated tumor-bearing mice exhibited tumor-specific cytotoxicity. We also investigated the effect of GC on epithelial-mesenchymal transition-related markers. Our results showed that GC decreased the expression of Twist-1 and Slug, proto-oncogenes commonly implicated in metastasis. Epithelial-cadherin, which is regulated by these genes, was also upregulated. Taken together, our current data suggest that GC alone can reduce cancer cell motility and invasion, whereas GC-HIFU treatment can induce immune responses to suppress tumor metastasis in vivo.

Metabolic syndrome and insulin resistance in relation to biliary tract cancer and stone risks: a population-based study in Shanghai, China.

BACKGROUND: Serum lipids, diabetes, and obesity, individual components of metabolic syndrome, are associated with biliary tract cancer and stone risk, but the associations of metabolic syndrome or insulin resistance with biliary tract cancers and stones are not well studied. METHODS: In this population-based case-control study in Shanghai, China (627 biliary tract cancers, 1037 biliary stones, and 959 controls), metabolic syndrome was defined as the presence of any three of the five components, including high waist circumference, high triglycerides, low high-density lipoprotein cholesterol (HDL), high blood pressure, and diabetes. Insulin resistance and ß-cell function were assessed, using homeostasis assessment models. RESULTS: Metabolic syndrome was significantly associated with gallbladder cancer (odds ratio (OR)=2.75, 95% confidence interval (95% CI)=1.82-4.15) and biliary stones (OR=1.64, 95% CI=1.24-2.16), with a significant dose effect with increasing number of metabolic syndrome components (P trend <0.0001). The observed association persisted among subjects without a history of diabetes. The association between insulin resistance and gallbladder cancer was borderline (P trend=0.06). There was a significant inverse association between ß-cell function and gallbladder cancer risk (P trend <0.001). CONCLUSION: Our findings suggest that metabolic syndrome and insulin resistance have a role in the aetiology of biliary tract cancers and biliary stones, and if confirmed, they imply that lifestyle control of these factors may lower the risk of biliary stones and biliary tract cancer.

Diabetes in relation to biliary tract cancer and stones: a population-based study in Shanghai, China.

BACKGROUND: Biliary tract cancers are rare but fatal malignancies. Diabetes has been related to biliary stones, but its association with biliary tract cancers is less conclusive. METHODS: In a population-based case-control study of 627 cancers, 1037 stones, and 959 controls in Shanghai, China, we examined the association between diabetes and the risks of biliary tract cancer and stones, as well as the effect of potential mediating factors, including serum lipids and biliary stones (for cancer), contributing to the causal pathway from diabetes to biliary diseases. RESULTS: Independent of body mass index (BMI), diabetes was significantly associated with gallbladder cancer and biliary stones ((odds ratio (OR) (95% confidence interval)=2.6 (1.5-4.7) and 2.0 (1.2-3.3), respectively). Biliary stones and low serum levels of high-density lipoprotein (HDL) were significant mediators of the diabetes effect on gallbladder cancer risk, accounting for 60 and 17% of the diabetes effect, respectively. High-density lipoprotein was also a significant mediator of the diabetes effect on biliary stones, accounting for 18% of the diabetes effect. CONCLUSIONS: Independent of BMI, diabetes is a risk factor for gallbladder cancer, but its effect is mediated in part by biliary stones and serum HDL levels, suggesting that gallbladder cancer risk may be reduced by controlling diabetes, stones, and HDL levels.

Reproductive factors and risks of biliary tract cancers and stones: a population-based study in Shanghai, China.

BACKGROUND: Parity has been linked to gallbladder cancer and gallstones, but the effects of other reproductive factors are less clear. METHODS: We examined 361 incident biliary tract cancer cases, 647 biliary stone cases, and 586 healthy women in a population-based study in Shanghai. RESULTS: The effects of parity (odds ratios, OR(> or =3 vs 1 child)=2.0, 95% confidence interval (CI) 0.7-5.1), younger age at first birth (OR(per 1-year decrease)=1.2, 95% CI 0.99-1.6), and older age at menarche (OR(per 1-year increase)=1.4, 95% CI 1.1-1.8) on gallbladder cancer risk were more pronounced among women with stones, but the interactions were not significant. CONCLUSION: Our results provide support for high parity, younger age at first birth, and late age at menarche in the development of gallbladder cancer, particularly among women with biliary stones.