Circular RNA ACACA negatively regulated p53-modulated mevalonate pathway to promote colorectal tumorigenesis via regulating miR-193a/b-3p/HDAC3 axis.

This study aimed to explore the biological functions and underlying mechanism of circRNA acetyl-CoA carboxylase alpha (circACACA) in colorectal cancer (CRC). The RNA and protein levels were detected by qRT-PCR and western blot assays. The malignant capacities of CRC cells were analyzed by cell counting kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays. The target relationship between miR-193a/b-3p and circACACA/histone deacetylase 3 (HDAC3) was determined by luciferase reporter assay and RNA immunoprecipitation. The binding of HDAC3 to the p53 promoter was validated by chromatin immunoprecipitation (ChIP). CRC cell growth and lung metastasis were evaluated in nude mice in vivo. High expression of circACACA was found in CRC tissues and cells, which was closely associated with the advanced tumor, lymph node, metastasis (TNM) stage, metastasis, and low overall survival rate. circACACA downregulation effectively delayed CRC cell proliferation and metastasis, but triggered apoptosis via inactivating the mevalonic acid (MVA) pathway. However, circACACA overexpression resulted in the opposite effects. Mechanistically, circACACA enhanced HDAC3 expression through sponging miR-193a/b-3p, which activated the MVA pathway via inhibiting the acetylation and transcription of p53. Moreover, rescue experiments confirmed that miR-193a/b-3p inhibition reversed the inhibitory effect of circACACA deficiency on CRC growth and metastasis. Moreover, circACACA overexpression-mediated malignant phenotypes of CRC cells were abrogated by HDAC3 knockdown. circACACA promoted CRC progression via regulating the miR-193a/b-3p/HDAC3/p53 axis to activate the MVA pathway, providing evidence for circACACA as a promising therapeutic target for CRC.

Pre-treatment CT-based radiomics nomogram for predicting microsatellite instability status in colorectal cancer.

OBJECTIVES: Stratification of microsatellite instability (MSI) status in patients with colorectal cancer (CRC) improves clinical decision-making for cancer treatment. The present study aimed to develop a radiomics nomogram to predict the pre-treatment MSI status in patients with CRC. METHODS: A total of 762 patients with CRC confirmed by surgical pathology and MSI status determined with polymerase chain reaction (PCR) method were retrospectively recruited between January 2013 and May 2019. Radiomics features were extracted from routine pre-treatment abdominal pelvic computed tomography (CT) scans acquired as part of the patients' clinical care. A radiomics nomogram was constructed using multivariate logistic regression. The performance of the nomogram was evaluated using discrimination, calibration, and decision curves. RESULTS: The radiomics nomogram incorporating radiomics signatures, tumor location, patient age, high-density lipoprotein expression, and platelet counts showed good discrimination between patients with non-MSI-H and MSI-H, with an area under the curve (AUC) of 0.74 [95% CI, 0.68-0.80] in the training cohort and 0.77 [95% CI, 0.68-0.85] in the validation cohort. Favorable clinical application was observed using decision curve analysis. The addition of pathological characteristics to the nomogram failed to show incremental prognostic value. CONCLUSIONS: We developed a radiomics nomogram incorporating radiomics signatures and clinical indicators, which could potentially be used to facilitate the individualized prediction of MSI status in patients with CRC. KEY POINTS: • There is an unmet need to non-invasively determine MSI status prior to treatment. However, the traditional radiological evaluation of CT is limited for evaluating MSI status. • Our non-invasive CT imaging-based radiomics method could efficiently distinguish patients with high MSI disease from those with low MSI disease. • Our radiomics approach demonstrated promising diagnostic efficiency for MSI status, similar to the commonly used IHC method.

SUMOylation of methyltransferase-like 3 facilitates colorectal cancer progression by promoting circ_0000677 in an m6 A-dependent manner.

BACKGROUND AND AIM: Colorectal cancer (CRC) is one of the major health issues in the world. Circ_0000677 has been shown to be upregulated in CRC with unclarified function and mechanism. Methyltransferase-like 3 (METTL3) acts as a regulator for gene expression via the mechanism of RNA N6 -methyladenosine (m6 A) in different types of cancer, which is under the control of SUMO1-based SUMOylation. We aim to investigate their roles in CRC progression. METHODS: Quantitative real-time polymerase chain reaction and Western blot were used to detect the expressions of METTL3, circ_0000677, and ATP binding cassette subfamily c member 1(ABCC1) in CRC patients' tissues and cell lines. The functions of ABCC1 and circ_0000677 in CRC were studied by manipulating their level via knocking down or overexpression. RNA pull-down and RNA immunoprecipitation assays were performed to identify the specific binding of target genes. The biological function of SUMOylation of METTL3 was investigated in vivo by xenograft mice tumor model. RESULTS: METTL3, circ_0000677, and ABCC1 were upregulated in CRC patients' samples and cell lines. Circ_0000677 positively regulates CRC cell proliferation and drug resistance via affecting ABCC1 expression. METTL3 facilitated circ_0000677 level via m6 A modification. METTL3 was regulated by SUMO1-mediated SUMOylation in CRC. Mutation of METTL3-K459 could suppress tumor growth in vivo via regulating circ_0000677/ABCC1 axis. CONCLUSIONS: Overall, our study revealed that circ_0000677 and its downstream target ABCC1 were upregulated in CRC cells, induced by the METTL3-mediated m6 A modification of circ_0000677 and SUMO1-mediated SUMOylation of METTL3. This work provided a new strategy for the therapeutic treatment of CRC.

Diterpenoids from Sauropus spatulifolius Leaves with Antimicrobial Activities.

As a plant used in both food and medicine, Sauropus spatulifolius is consumed widely as a natural herbal tea, food source, and Chinese medicine. Inspired by its extensive applications, we conducted a systematic phytochemical study of the leaves of S. spatulifolius. Thirteen new diterpenoids, sauspatulifols A-M (1-13), including four ent-cleistanthane-type diterpenoids (1-4), eight 15,16-di-nor-ent-cleistanthane-type diterpenoids (5-12), and one 17-nor-ent-pimarane-type diterpenoid (13) as well as one known diterpenoid, cleistanthol (14), were isolated. All of these diterpenoids feature a 2α,3α-dihydroxy unit within the A ring, and their structures were elucidated by spectroscopic data analysis, electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis. Compound 14 displayed moderate inhibitory activity against Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, and Shigella flexneri with the same minimum inhibitory concentration value of 12 µg/mL as well as activity against vesicular stomatitis virus and influenza A virus.

Oophorectomy for ovarian torsion - should this be abandoned?

BACKGROUND: Management of ovarian torsion ranges from de-torsion to oophorectomy and is dependent on various factors. Oophorectomy can have significant implications for fertility and general health, thus requiring careful consideration. AIMS: We evaluate the management of ovarian torsion at a tertiary hospital over a ten-year period and identify the predictors of oophorectomy in ovarian torsion cases. MATERIALS AND METHODS: Inpatient notes of patients who underwent surgical management for acute ovarian torsion at a tertiary hospital in Victoria, Australia, were reviewed, from January 2008 to June 2018. We reported the incidence and predictors of oophorectomy and ovarian ischaemia and current practices in oophoropexy. RESULTS: Our analysis included 159 patients. The incidence of oophorectomy was 47%. After confounders were adjusted, increasing age was the only significant predictor for oophorectomy. The adjusted odds ratio of having an oophorectomy based on age alone was 1.10 for each year increase in age between the ages of 15 and 68 (P = 0.001, 95% confidence interval 1.04-1.16). Of those with oophorectomy, 57% had ischaemia confirmed histologically. There were no significant predictors for ischaemia. CONCLUSION: The incidence of oophorectomy in this audit is comparable to reported incidences in current literature. However, with increasing evidence to support ongoing ovarian function even in cases where ischaemia is histologically confirmed, this incidence could be lowered. Age was the only variable that was found to have a significant effect on the incidence of oophorectomy.

Comparing neoadjuvant long-course chemoradiotherapy with short-course radiotherapy in rectal cancer.

BACKGROUND: The purpose of this study was to compare short-course radiotherapy (SC) or neoadjuvant long-course chemoradiotherapy (LC) treatment for locally advanced rectal cancer patients. METHODS: Patients with a diagnosis of locally advanced rectal cancer (LARC) who had undergone neoadjuvant radiotherapy before surgery between 2013 and 2018 at the medical center in China were included in this study. All patients' MRI confirmed T2N+M0 or T3-4N0-3M0 clinical stages. Patients in the SC group received pelvic radiotherapy with a dose of 5 × 5 Gy (with or without chemotherapy at any time), followed by immediate or delayed surgery. Patients in the LC group received a dose of 50-50.4 Gy in 25-28 fractions, concomitantly with FOLFOX or capecitabine-based chemotherapy, followed by surgery 4-6 weeks later. All clinical data were retrospectively collected, and long-term follow-up was completed and recorded at the same time. RESULTS: A total of 170 were eligible to participate in this study, 32 patients in the SC group, and 138 in the LC group. The median follow-up time of living patients was 39 months. The disease-free survival (DFS) and overall survival (OS) rates in the SC group and LC group at 3 years, were, 84.9% versus 72.4% (P = 0.273) and 96.2% versus 87.2% (P = 0.510), respectively. The complete pathological response (pCR) rates in the SC group and LC group were, 25% versus 18.1% (the difference was not statistically significant, P = 0.375), respectively. However, the SC group had better node(N) downstaging compared to the LC group (P = 0.011). CONCLUSIONS: There were no differences observed in DFS and OS between short-course radiotherapy and long-course chemoradiation, and both can be used as treatment options for patients with locally advanced rectal cancer.

Assessing the magnetic resonance imaging in determining the depth of invasion of tongue cancer.

OBJECTIVES: To assess the magnetic resonance imaging (MRI) in predicting tumour's depth of invasion (DOI) of tongue cancer by comparing to pathology and to determine the cut-off value of MRI-derived DOI for lymph node metastasis. PATIENTS AND METHODS: In a retrospective analysis, 156 patients with newly diagnosed tongue cancer were included. Tumour's DOI was compared between MRI measurement and pathology by Pearson correlation coefficient and paired t test. The accuracy of MRI-derived DOI was compared to the pathological DOI. The relationship between MRI-derived DOI and cervical lymph node metastasis was calculated by receiver operating characteristic curve. RESULTS: Tumour's DOI was well correlated between MRI measurement and pathology with correlation coefficients of 0.77. MRI-derived DOI was 3.4 mm (28%) larger than pathology. The accuracy of MRI in deciding pathological DOI was 67.9%. The cut-off value of MRI-derived DOI was 10.5 mm for lymph node metastasis of tongue cancer. CONCLUSION: Magnetic resonance imaging can be used as a reference to determine tumour's DOI of tongue cancer. Tumour with MRI-derived DOI larger than 10.5 mm deserves simultaneous neck dissection at initial surgery.

Association between adjuvant chemotherapy and survival in patients with rectal cancer and pathological complete response after neoadjuvant chemoradiotherapy and resection.

BACKGROUND: For patients with locally advanced rectal cancer (LARC), it is unclear whether neoadjuvant chemoradiotherapy-induced pathologic complete response (pCR) individuals would further benefit from adjuvant chemotherapy (ACT). METHODS: The pCR individuals who received different ACT cycles were paired by propensity score matching. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated by Kaplan-Meier and log-rank test. RESULTS: In total, 1041 pCR individuals were identified from 5567 LARC cases. Specifically, 303 pCR cases had no ACT treatment, and 738 pCR patients received fluoropyrimidine-based ACT (median, 4 cycles) treatment. After 1:3 propensity score matching, 297 cases without ACT treatment were matched to 712 cases who received ACT treatment. Kaplan-Meier analysis showed that pCR individuals treated with or without ACT had the similar 3-year outcome (OS, DFS, LRFS and DMFS) (all P > 0.05). Moreover, the pCR patients received different ACT cycle(s) (0 vs. 1-4 cycles, 0 vs. ≥5 cycles) had comparable 3-year OS, DFS, LRFS and DMFS (all P > 0.05). In stratified analysis, ACT treatment did not improve 3-year survival (OS, DFS, LRFS and DMFS) for the baseline high-risk (cT3-4/cN1-2) subgroup patients (all P > 0.05). CONCLUSION: ACT, which did not improve survival, is unnecessary to neoadjuvant treatment-induced pCR LARC patients. TRIAL REGISTRATION: 2019ZSLYEC-136 (24-6-2019).

Role of SSH1 in colorectal cancer prognosis and tumor progression.

BACKGROUND AND AIM: Slingshot 1 protein (SSH1) plays a critical role in cytoskeleton dynamic regulation. Increasing evidence suggest that SSH1 expression is upregulated in several cancers and relates to tumor progression and drug resistance. Here, we evaluated the role of SSH1 in colorectal cancer (CRC) development and its prognostic value in patients with CRC. METHODS: SSH1 expression was examined by quantitative real-time polymerase chain reaction, western blot analysis, or immunohistochemistry. The association between SSH1 expression and clinical characteristics and prognosis was evaluated. Stable SSH1 knockdown cells were used for in vitro assays and xenograft models. Correlation between SSH1 expression and epithelial-mesenchymal transition (EMT) was analyzed by western blot and online data analysis. RESULTS: SSH1 expression was upregulated in cancer tissue compared with paired non-cancerous tissue in patients with CRC. SSH1 expression level in CRC tissue was associated with tumor stage, lymph node metastasis, and correlated with poor prognosis as indicated by univariate and multivariate analyses. In vitro, loss of SSH1 impaired colony formation, migration, and invasion of CRC cells. In vivo data suggest that SSH1 could promote the progression and metastasis of CRC. Interestingly, E-cadherin, ZEB1, and Snail, which are markers of EMT, had a significant expression correlation with SSH1. CONCLUSIONS: SSH1 expression is associated with CRC progression and predicts poor prognosis. SSH1 may promote CRC tumor progression by regulating EMT.

The Main Bottleneck for Non-Metastatic Pancreatic Adenocarcinoma in Past Decades: A Population-Based Analysis.

BACKGROUND Despite recent advancements in surgical techniques, chemotherapy, and radiotherapy, the 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) remains an unsatisfactory ~8%. MATERIAL AND METHODS Data were extracted to identify patients with non-metastatic pancreatic adenocarcinoma diagnosed in the periods 1988-1996 and 2010-2014 in the Surveillance, Epidemiology, and End Results (SEER) database. The statistical analyses were performed with the log-rank test, Pearson's chi-square test, propensity score matching, and Cox regression model. RESULTS The hazard ratio (HR) of surgery was reduced from 0.454 to 0.302 in Cox regression modeling, and there was no overlapping about the 95% confidence intervals (CI) of surgery between the 2 periods. The HR values of radiotherapy, which were new prognostic factor for resectable PDAC in 2010-2014, were reduced in both the resectable and unresectable groups. The upgraded chemotherapy regimen reduced the HR values from 0.738 to 0.689 in all PADC patients, and from 0.656 to 0.588 in unresectable PDAC. The log-rank test results showed that advances in surgery significantly improved the median survival from 13 months to 32 months. Radiotherapeutic and chemotherapeutic advancements extended median survival by 12 months and 11 months, respectively, in resectable PDAC. The median survivals were extended by 3 months for both of radiotherapy and chemotherapy in unresectable PDAC. CONCLUSIONS The development of chemotherapy and radiotherapy has been slow, especially for unresectable PDAC. Although advances in surgery contributed significantly to improved survival for resectable PDAC, lack of early diagnostic tools, which lead to low resection rates, remain a barrier for all PDAC patients.

Isolation, Characterization, and Possible Anti-Alzheimer's Disease Activities of Bisabolane-Type Sesquiterpenoid Derivatives and Phenolics from the Rhizomes of Curcuma longa.

One new bisabolane-type sesquiterpenoid, together with four known bisabolane-type sesquiterpenoid derivatives and seven phenolics, was isolated from the rhizomes of Curcuma longa. Their structures were elucidated by extensive spectroscopic (IR, HR-ESI-MS, and NMR) data analysis. The possible anti-Alzheimer's disease (AD) activities of the isolated compounds were also evaluated using Caenorhabditis elegans AD pathological model, and 1ß-hydroxybisabola-2,10-dien-4-one had the highest possible anti-AD activity.

Matrix stiffness mediates stemness characteristics via activating the Yes-associated protein in colorectal cancer cells.

Matrix stiffness is an essential physical microenvironment in solid cancer. However, its influence on cancer stemness still remains elusive. Colorectal cancer (CRC) cell line HCT-116 was cultured in the matrix with various stiffness. The siYAP was applied to detect the changes of stemness markers. The cancer stemness markers, Yes-associated protein (YAP), Lamin A/C and downstream protein molecules, and their activation were measured after the treatment with anti-ß1-integrin and FAK inhibitors. In CRC tissue samples, collagen deposition and the expression of α-SMA and CD133 were detected. The study found that the expression level of stemness markers and Lamin A/C increased as the matrix stiffness raised and was regulated by YAP activation in CRC stem cells. Inhibition of ß1-integrin and FAK activation in a high stiffness cell culture medium significantly decreased the activation of YAP, PI3K, and AKT. Collagen was highly deposited in the CRC invasive tumor front (ITF), and the expression of CD133 was higher in ITF compared with normal tissue and the tumor cells. Moreover, the expression level of α-SMA was positively correlated with CD133 expression level. Together, our results suggest that activation of YAP in CRC plays an important role in the promotion of cancer stem cell properties by extracellular matrix stiffness in CRC.

[Association of NLRC3 with prognosis and tumor immunity in patients with stage III colorectal cancer].

OBJECTIVE: To explore the association of nucleotide binding oligomerization domain-like receptor family caspase recruitment domain containing 3 (NLRC3) with prognosis and tumor immunity in patients with stage III colorectal cancer.
 Methods: Data of 122 patients with stage III colorectal cancer, who underwent radical resection from 2012 to 2013 in Xiangya Hospital of Central South University, were retrospectively collected. The expressions of NLRC3 and CD8+ were examined by immumohistochemical (IHC) staining. The preoperative clinical data were used to obtain neutrophil to lymphocyte ratio (NLR), and the stability of microsatellite was determined. The relationship between NLRC3 and clinicopathological factors was analyzed by χ2 test, and the independent prognostic factors for patients with stage III colorectal cancer were determined by COX regression model.
 Results: The expression of NLRC3 was significantly associated with CD8+ T cells infiltration (χ2=27.79, P<0.01), NLR (χ2=6.35, P<0.05), lymph node metastasis (LN) (χ2=10.12, P<0.01) and microsatellite stability (χ2=6.05, P<0.05). NLRC3 (OR=0.066, 95% CI 0.020 to 0.218), vascular emboli (OR=3.119, 95% CI 1.547 to 6.286) and NLR (OR=5.103, 95% CI 2.465 to 10.563) had an effect on overall survival (OS) for patients with stage III colorectal cancer (all P<0.05). In addition, NLRC3 (OR=0.144, 95% CI 0.055 to 0.377), vascular emboli (OR=3.589, 95% CI 1.859 to 6.932) and NLR (OR=2.939, 95% CI 1.509 to 5.723) also had an effect on disease-free survival (DFS) for patients with stage III colorectal cancer (all P<0.05).
 Conclusion: NLRC3, intravascular emboli and NLR are independent prognostic factors for patients with stage III colorectal cancer. NLRC3 might be a good prognostic factor for patients with stage III colorectal cancer due to its capacity of inhibiting systemic inflammation and promoting local anti-tumor immunity.

Four novel sesquiterpenoids with their anti-Alzheimer's disease activity from Nardostachys chinensis.

Nardochinins A-D (1-4), four novel sesquiterpenoids, along with four known ones were isolated from the underground parts of Nardostachys chinensis Batal in ethanol. Their structures were determined by extensive spectroscopic methods and single-crystal X-ray diffraction. Nardochinin A (1) possessed a norsesquiterpene skeleton with an unusual 3/6/5/5 tetracyclic ring system, which had not appeared in natural products. Nardochinins B (2) and C (3) were the first time found naturally occurring sesquiterpenoids with a 4,5-seco-nardosinane skeleton. Besides, compound 3 represented an unprecedented 4,5-seco-nardosinane type norsesquiterpenoid with losing an isopropenyl at C-6 compared with 2 in the structural framework. Nardochinin D (4) was a novel, highly oxygenated valerenane-type sesquiterpenoid possessing a rare 3,12-epoxy group and an unusual 9,11-epoxy group. The anti-Alzheimer's disease (AD) activities of 1-4 were also evaluated using the Caenorhabditis elegans AD pathological model, and nardochinin B (2) had the highest anti-AD activity.

Norcrassin A, a novel C16 tetranorditerpenoid, and bicrotonol A, an unusual dimeric labdane-type diterpenoid, from the roots of Croton crassifolius.

A novel C16 tetranorditerpenoid, norcrassin A (1), and an unusual dimeric labdane-type diterpenoid, bicrotonol A (2), were isolated from the roots of Croton crassifolius. Norcrassin A (1) featured a new carbon skeleton with an unprecedented 5/5/5/6 tetracyclic system. Bicrotonol A (2) possessed an unusual tetrahydroxypyran ring linkage connecting two labdane diterpenoid monomers. The structures of all compounds, including the absolute configuration, were elucidated by the interpretation of their NMR spectroscopic data, high resolution mass spectrometry, and single-crystal X-ray diffraction. A plausible biosynthetic pathway of 1 is proposed. The anti-Alzheimer's Disease (AD) activities of 1 and 2 are also evaluated using the AD pathological model.

Phenolic compounds from Bletilla striata.

Two new malic acid derivatives, namely eucomic acid 1-methyl ester (2) and 6'''-acetylmilitaline (7), together with ten known compounds (1, 3-6, 8-12), were isolated from the dry tubers of Bletilla striata (Thunb.) Reichb. F., a perennial traditional Chinese medicinal herb, which was used for the treatment of pneumonophthisis, pneumonorrhagia, tuberculosis, and hemorrhage of the stomach or lung. Their structures were elucidated by spectroscopic analyses, including 1D-, 2D-NMR, and HR-ESI-MS.

Long Non-Coding RNA HOXA Transcript at the Distal Tip as a Putative Biomarker of Metastasis and Prognosis: a Meta-Analysis.

BACKGROUND: Many studies demonstrated that the expression level of HOTTIP in cancerous tissues was significantly higher than that in adjacent normal tissues. Increased expression of HOTTIP was associated with metastasis and a poor prognosis. METHODS: The current meta-analysis collected all relevant articles and explored the association of HOTTIP expression levels with lymph node metastasis (LNM), distant metastasis (DM), and overall survival (OS) in multiple cancers. Literature collections were conducted by searching a number of electronic databases (up to December 31, 2015). The Meta-analysis was conducted using RevMan5.3 software and Stata SE12.0. RESULTS: A total of 602 patients with cancer from seven studies were included. The Meta-analysis results showed that lymph node metastasis occurred more frequently in patients with high HOTTIP expression than in patients with low HOTTIP expression (OR = 2.22, 95% CI: 1.47 - 3.37, p = 0.0002, fixed-effects model), and a similar result was observed between HOTTIP expression and distant metastasis (OR = 3.30 (95% CI: 1.78 - 6.12, p = 0.0001, fixed-effects model). Moreover, we found that cancer patients with high HOTTIP expression had a poorer overall survival than those with low HOTTIP expression (HR = 2.23, 95% CI: 1.64 - 2.83, p = 0.000, fixed-effects model). CONCLUSIONS: HOTTIP may serve as an independent biomarker for predicting the clinical outcome of cancer patients.

Association of the HOTAIR rs4759314 polymorphism with cancer risk: a meta-analysis.

PURPOSE: To explore the association between HOTAIR rs4759314 and cancer risk. METHODS: A comprehensive online search was conducted using PubMed, EMBASE, and CNKI databases to identify relevant studies. The case-control studies related to HOTAIR rs4759314 polymorphism and cancer risk were selected according to the inclusion and exclusion criteria. The retrieval time was until November 2015. After extracting the basic data information and performing an evaluation of the quality of the literature, the meta-analysis was performed using STATA 12.0 software, by calculating the odds ratio (OD) and 95% confidence interval (95% CI), and further subgroup analysis, literature publication bias testing, and sensitivity analysis. RESULTS: The studies included a total of 5025 patients with cancer and 5657 controls. The results found no significant association between the HOTAIR rs4759314 polymorphism and cancer risk in a Chinese population (G vs A, OR=1.06, 95% CI :0.87-1.30 ; GG/GA vs AA, OR=1.07, 95% CI: 0.87-1.32; GG vs GA/AA, OR=0.75, 95% CI:0.39-1.43; GA vs AA, OR=1.08, 95% CI: 0.88-1.33; GG vs AA, OR=0.76, 95% CI:0.39-1.45) (all p<0.05). However, A allelic gene was associated with lower risk of gastric cancer, while G allelic gene may act as a genetic susceptibility factor for gastric cancer in Chinese population. CONCLUSION: No significant association was noted between the HOTAIR rs4759314 polymorphism and cancer risk in a Chinese population.

Protein interactions of cortactin in relation to invadopodia formation in metastatic renal clear cell carcinoma.

In the present study, we wanted to examine the predominant factor/s in the initiation of metastasis. We used samples of advanced grades of renal clear cell carcinoma with documented clinical history of vena caval spread as the experimental group. The major rationale for this selection is the fact that renal cell carcinoma metastasize extensively through the inferior vena cava up to the pulmonary bed and often exist as a continuous mass of metastatic tissue. As cortactin plays a significant role in invadopodia formation during initiation of metastasis, in the present study, we tested expression of cortactin and phospho(tyr421)-cortactin in different grades of renal cell clear carcinoma and examined its property to bind to actin. The findings of the present study suggest that the variations of the local physiological milieu are the driving forces for metastasis by enhancing molecular mechanisms for lamellipodia formation. We conclude that localization of cortactin in cancer cells and interaction between actin and its nucleators are crucial for cancer progression.

Anti-Inflammatory Salicin Derivatives from the Barks of Salix tetrasperma.

The genus Salix L. is traditionally used in folk medicine to alleviate pain caused by various kinds of inflammation. In the present study, 10 undescribed salicin derivatives along with 5 known congeners were isolated from the barks of Salix tetrasperma, and their structures were elucidated by spectroscopic analyses, single-crystal X-ray diffraction, electronic circular dichroism (ECD) calculations, and chemical conversions. Compounds 4-6 significantly inhibited NO production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, and the most active 4 obviously suppressed the production of IL-1ß and IL-6 and decreased iNOS and COX-2 expression in a dose-dependent manner. Further Western blotting analysis revealed that the anti-inflammatory mechanism of 4 is possibly mediated through the MAPK and NF-κB signaling pathways.