Osteonecrosis of the jaw induced by bisphosphonates therapy in bone metastases patient: Case report and literature review.

Medication-related osteonecrosis of the jaw (MRONJ) is an increasingly common bone-related adverse event in recent years. We reported 3 bone metastases of patients who developed MRONJ after receiving bisphosphonates therapy. All patients underwent surgical necrotic bone resection combined with leukocyte and platelet-rich fibrin concentrate (L-PRF) therapy. After 6 months of follow-up, no recurrence and adverse event has been observed. This report shows that treatment with necrotic bone resection and L-PRF is an effective therapy and should be considered as an alternative treatment for the management of advanced cases of MRONJ.

Marsdenia tenacissima Extract Induces Autophagy and Apoptosis of Hepatocellular Cells via MIF/mToR Signaling.

Hepatocellular carcinoma (HCC) seriously endangers humans. In traditional Chinese medicine, Marsdenia tenacissima (MTE) has anti-inflammatory, antiasthmatic, antihypertensive, and anticancer effects. This study reveals the antiproliferative effect of MTE on the HCC cells in vitro and provides a theoretical basis for the development and clinical application of anti-HCC agents. Methods. MHCC-97H and HepG2 cells were cultured in vitro and exposed to various concentrations and durations of MTE, and an MTT assay was used to detect the effects of MTE on cell proliferation. Transmission electron microscopy revealed the morphological changes in the two cell lines after MTE stimulation. The MTE effects on the apoptosis and cell cycle distribution of the cell lines were detected by flow cytometry. Western blotting and qRT-PCR were used to detect target gene expression at the protein and mRNA levels, respectively. Results. MTE reduced the viability of the MHCC-97H and HepG2 cells in a dose- and time-dependent manners (P < 0.05). Autophagic vesicles and apoptotic bodies were found in the MHCC-97H and HepG2 cells after MTE incubation, and the Annexin V-PI assay showed that the apoptotic rates of the cell lines increased with increasing MTE concentration (P < 0.05). Autophagy inducer rapamycin promoted the MTE-induced apoptotic rates of the cell lines, whereas autophagy inhibitor chloroquine inhibited the apoptotic rates. More cells in the S phase were found in the two cell lines after MTE treatment (P < 0.05). After MTE incubation, MIF, CD47, and beclin-1 protein levels significantly increased. Furthermore, in the MTE group, Akt, mTOR, and caspase3 expressions decreased; however, LC 3 expression increased, which was significantly different from the control group (P < 0.05). Conclusions. MTE inhibited proliferation and induced autophagy, apoptosis, and S phase cell cycle arrest in the MHCC-97H and HepG2 cells. These effects might be related to the activation of MIF and mTOR signaling inhibition.

GSTM1 and GSTT1 null genotype increase the risk of hepatocellular carcinoma: evidence based on 46 studies.

BACKGROUND: It is well known that hepatocellular carcinoma (HCC) has been one of the most life-threatening diseases all over the world. Plenty of internal and extrinsic factors have been proven to be related to HCC, such as gene mutation, viral hepatitis, and Nitrosamines. Though previous studies demonstrated that glutathione S-transferase (GST) genotypes are associated with HCC, the conclusions are inconsistent. Therefore, we carried on a renewed meta-analysis to expound the connection between the null GSTM1, GSTT1 polymorphisms and the risk of HCC. METHODS: We searched PubMed, Web of Science, Embase, and CNKI databases to select qualified researches which satisfied the inclusion criteria up to July 31, 2018. Finally, we selected 41 articles with 6124 cases and 9781 controls in this meta-analysis. We use ORs and 95% confidence interval (CI) to evaluate the correlation intension between the GSTM1 and GSTT1 null genes and the risk of HCC. All the statistical processes were executed by Stata (version 12.0). RESULTS: The pooled analysis showed that both GSTM1 null genotypes (OR = 1.37, 95% CI = 1.18-1.59) and GSTT1 null genotypes (OR = 1.43, 95% CI = 1.23-1.66) increased the risk of HCC. And GSTM1-GSTT1 dual-null genotypes also increased the risk of HCC (OR = 1.58, 95% CI = 1.22-2.05). In the subgroup analysis, we obtained significant results among Asians when stratified by race, and the results are GSTM1 null OR = 1.44, 95% CI = (1.22-1.71), GSTT1 null OR = 1.48, 95% CI = (1.25-1.77), GSTM1-GSTT1 null OR = 1.58, 95% CI = (1.19-2.09), while we didn't obtain significant results among Caucasians or Africans. Stratified analyses on the type of control indicated a higher risk of HCC associated with GSTM1, GSTT1 single null genotypes and GSTM1-GSTT1 dual-null genotypes in healthy people. No evidence of significant connection was discovered in chronic liver disease (CLD) except in GSTT1 single null. CONCLUSIONS: Our study indicated that an individual who carries the GSTM1, GSTT1 single null genotypes and GSTT1-GSTM1 dual-null genotypes is more likely to develop HCC.

Pooling-analysis on hMLH1 polymorphisms and cancer risk: evidence based on 31,484 cancer cases and 45,494 cancer-free controls.

To elucidate the veritable relationship between three hMLH1 polymorphisms (rs1800734, rs1799977, rs63750447) and cancer risk, we performed this meta-analysis based on overall published data up to May 2017, from PubMed, Web of knowledge, VIP, WanFang and CNKI database, and the references of the original studies or review articles. 57 publications including 31,484 cancer cases and 45,494 cancer-free controls were obtained. The quality assessment of six articles obtained a summarized score less than 6 in terms of the Newcastle-Ottawa Scale (NOS). All statistical analyses were calculated with the software STATA (Version 14.0; Stata Corp, College Station, TX). We found all the three polymorphisms can enhance overall cancer risk, especially in Asians, under different genetic comparisons. In the subgroup analysis by cancer type, we found a moderate association between rs1800734 and the risk of gastric cancer (allele model: OR = 1.14, P = 0.017; homozygote model: OR = 1.33, P = 0.019; dominant model: OR = 1.27, P = 0.024) and lung cancer in recessive model (OR = 1.27, P = 0.024). The G allele of rs1799977 polymorphism was proved to connect with susceptibility of colorectal cancer (allele model: OR = 1.21, P = 0.023; dominate model: OR = 1.32, P <0.0001) and prostate cancer (dominate model: OR = 1.36, P <0.0001). Rs63750447 showed an increased risk of colorectal cancer, endometrial cancer and gastric cancer under all genetic models. These findings provide evidence that hMLH1 polymorphisms may associate with cancer risk, especially in Asians.

Pooling-analysis for diagnostic and prognostic value of MiRNA-100 in various cancers.

Many studies manifested miRNA-100 was deregulated in various cancers, which indicated that miRNA-100 might be a potential biomarker of cancer diagnosis and prognosis. However, the role of miRNA-100 was still uncertain. We searched for qualified studies using PubMed, EMBASE, Web of Science, Cochrane library and CNKI databases. The diagnostic effect was evaluated by the pooled sensitivity, specificity, and other indexes. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) were calculated to assess the prognostic value. This meta-analysis included 7 and 19 studies about diagnosis and prognosis, respectively. The results of pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were 0.75 (95%CI: 0.71-0.78), 0.74 (95%CI: 0.69-0.78), 2.61 (95%CI: 1.81-3.76), 0.33 (95%CI: 0.24-0.45), 8.46 (95%CI: 4.85-14.77), respectively. And, the area under SROC curve (AUC) was 0.8141. We also found that lower expression of miRNA-100 in cancer tissues could significantly predict poorer prognosis in overall cancer (HR = 0.59, 95%CI: 0.39-0.90), especially in genital system tumors (HR = 0.42, 95%CI: 0.27-0.66, P = 0.431), bladder cancer (HR = 0.21, 95%CI: 0.06-0.73, P = 0.143) and esophageal squamous cell carcinoma (HR = 0.26, 95%CI: 0.13-0.52, P = 0.164). Our studies concluded that miRNA-100 has a certain value in diagnosis and it may indicate a poor prognosis of cancers.

Meta-analysis of programmed cell death 1 polymorphisms with systemic lupus erythematosus risk.

The association of polymorphisms in programmed cell death 1 (PDCD1) gene with systemic lupus erythematosus (SLE) risk is inconsistent across different studies. This meta-analysis is aimed to provide reliable evidence to the association of five common PDCD1 polymorphisms (PD1.1, PD1.2, PD1.3, PD1.5 and PD1.6) with SLE risk. A total of 28 studies with 4,344 SLE cases and 5,474 healthy controls were included in this meta-analysis. PD1.3 polymorphism was significantly associated with SLE in the overall population (A vs. G: OR = 1.35, 95% CI = 1.12-1.63; GA vs.GG: OR = 1.41, 95% CI = 1.12-1.76; AA+GA vs. GG: OR = 1.41, 95% CI = 1.13-1.7). In the stratified analyses based on ethnicity, we found a significant association in Caucasians and in Mexicans. In the subgroup analyses by gender, a significant association was found between PD1.3 polymorphism and SLE risk in males. The results also suggested an association between the PD1.6 polymorphism and decreased SLE risk (A vs. G: OR = 0.84, 95% CI = 0.73-0.96). Our meta-analysis revealed that PD1.3 polymorphism may increase the susceptibility to SLE, particularly in Caucasians, while PD1.6 may be a protective factor to SLE.

Role of interleukin-12 gene polymorphisms in the onset risk of cancer: a meta-analysis.

Many molecular epidemiologic studies have explored the possible links between interleukin-12 (IL-12) polymorphisms and various cancers. However, results from these studies remain inconsistent. This meta-analysis is aimed to shed light on the associations between three common loci (rs568408, rs2243115, rs3212227) of IL-12 gene and overall cancer risk. Our meta-analysis finally included 33 studies comprising 10,587 cancer cases and 12,040 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the cancer risk. We observed a significant association between IL-12B rs3212227 and overall cancer risk, especially in hepatocellular carcinoma, nasopharyngeal cancer, and among Asians. IL-12A polymorphisms (rs2243115 and rs568408) were found no influence on overall cancer risk. Nevertheless, stratification analyses demonstrated that rs568408 polymorphism contributed to increasing cancer risk of Caucasians and cervical cancer. And, rs2243115 may enhance the risk of brain tumor. These findings provided evidence that IL-12 polymorphisms may play a potential role in cancer risk.

FEN1 gene variants confer reduced risk of breast cancer in chinese women: A case-control study.

This study aimed to assess the associations of two common Flap endonuclease 1 (FEN1) polymorphisms (rs4246215 and rs174538) with breast cancer risk in northwest Chinese women. We conducted a case-control study with 560 breast cancer patients and 583 age-matched healthy controls from Northwest China. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to estimate the associations. We found a significantly reduced risk of breast cancer associated with T allele of rs4246215 (allele model: OR 0.81, 95% CI 0.68-0.96; homozygote model: OR = 0.59, 95% CI = 0.40-0.87; recessive model: OR = 0.61, 95% CI = 0.42-0.89), especially in postmenopausal women (OR = 0.58, 95% CI = 0.35-0.97). Furthermore, the polymorphism showed a decreased association with larger tumor size (heterozygote model: OR = 0.63, 95% CI = 0.44-0.92; dominant model: OR = 0.63, 95% CI = 0.44-0.90). For rs174538, we did not find any difference in all genetic models. However, rs174538 was associated with lymph node metastasis (heterozygote model: OR = 0.57, 95% CI = 0.39-0.81; dominant model: OR = 0.61, 95% CI = 0.43-0.86) and estrogen receptor status (heterozygote model: OR = 1.50, 95% CI = 1.05-2.15; dominant model: OR = 1.42, 95% CI = 1.01-1.98). Haplotype analysis showed that Trs4246215Grs174538 haplotype was a protective factor of breast cancer (OR = 0.34, 95% CI = 0.14-0.81). Our results suggest that FEN1 polymorphisms may reduce the risk of breast cancer in Chinese women.

Association of transcription factor 7-like 2 gene polymorphisms with breast cancer risk in northwest Chinese women.

Genetic variations in transcription factor 7-like 2 (TCF7L2) are associated with cancer risk. This study was conducted to establish the relationship between TCF7L2 polymorphisms (rs1225404, rs7003146, and rs7903146) and clinical features and risk of breast cancer in Northwest Chinese Han women. In this study, three polymorphisms of TCF7L2 (rs1225404, rs7003146, and rs7903146) were genotyped in 458 patients with breast cancer and 500 healthy controls using the Sequenom MassARRAY-iPLEX system. We evaluated the associations between the polymorphisms and breast cancer using odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs). The C allele of rs1225404 was associated with increased breast cancer risk (OR = 1.58, P = 0.0004, PC= 0.0012), whereas the G allele of rs7003146 was associated with decreased breast cancer risk (OR = 0.71, P = 0.01, PC= 0.03). Furthermore, the rs1225404 polymorphism positively correlated with negative progesterone receptor status. A positive correlation with positive estrogen receptor (ER) status was observed for the rs7003146 polymorphism. Our results suggest that TCF7L2 polymorphisms rs1225404 and rs7003146, but not rs7903146, may affect breast cancer risk in Northwest Chinese women. Additionally, the tag polymorphisms in TCF7L2 are associated with the clinical features of breast cancer, which may provide us novel insight into the pathogenesis of breast cancer.

Impacts of the mTOR gene polymorphisms rs2536 and rs2295080 on breast cancer risk in the Chinese population.

Mammalian target of rapamycin (mTOR) gene polymorphisms exert the major effects on the regulation of transcriptional activity and miRNA binding or splicing, which may be associated with cancer risk by affecting mTOR gene expression. However, inconsistent results have been previously reported. The present study evaluated the correlation between mTOR rs2536/rs2295080 polymorphisms and breast cancer risk. This case-control study was performed with 560 breast cancer patients and 583 healthy controls from the northwest of China. mTOR polymorphisms (rs2536 and rs2295080) were genotyped by Sequenom MassARRAY. We assessed the associations with odds ratios (ORs) and 95% confidence intervals (95% CIs). The association between mTOR rs2536 polymorphism and breast cancer risk was undetectable in our study (P > 0.05). In parallel, the significant effects were observed between mTOR rs2295080 polymorphism and breast cancer risk in the allele, codominant, and recessive models (P < 0.05). We detected no significant correlations between rs2536 polymorphism and the clinical parameters of breast cancer patients, while rs2295080 polymorphism was associated with lymph node (LN) metastasis. The Crs2536Grs2295080 haplotype was correlated with a significantly decreased risk of breast cancer (P < 0.05). In sum, the findings suggested that mTOR rs2295080 had a protective role on breast cancer susceptibility among Chinese population, while rs2536 polymorphism had no association with breast cancer risk.

Clinicopathological and prognostic significance of metastasis-associated in colon cancer-1 (MACC1) overexpression in colorectal cancer: a meta-analysis.

Metastasis-associated in colon cancer-1 (MACC1) has been reported to be overexpressed in diverse human malignancies, and the increasing amount of evidences suggest that its overexpression is associated with the development and progression of many human tumors. However, the prognostic and clinicopathological value of MACC1 in colorectal cancer remains inconclusive. Therefore, we conducted this meta-analysis to investigate the effect of MACC1 overexpression on clinicopathological features and survival outcomes in colorectal cancer. PubMed, CNKI, and Wanfang databases were searched for relevant articles published update to December 2015. Correlation of MACC1 expression level with overall survival (OS), disease-free survival (DFS), and clinicopathological features were analyzed. In this meta-analysis, fifteen studies with a total of 2,161 colorectal cancer patients were included. Our results showed that MACC1 overexpression was significantly associated with poorer OS and DFS. Moreover, MACC1 overexpression was significantly associated with gender, localization, TNM stage, T stage, and N stage. Together, our meta-analysis showed that MACC1 overexpression was significantly associated with poor survival rates, regional invasion and lymph-node metastasis. MACC1 expression level can serve as a novel prognostic factor in colorectal cancer patients.

Two common functional catalase gene polymorphisms (rs1001179 and rs794316) and cancer susceptibility: evidence from 14,942 cancer cases and 43,285 controls.

Recent studies have focused on the associations of catalase polymorphisms with various types of cancer, including cervical and prostate cancers. However, the results were inconsistent. To obtain a more reliable conclusion, we evaluated the relationship between the two common catalase gene polymorphisms (rs1001179 and rs794316) and cancer risk by a meta-analysis. Our meta-analysis included 37 published studies involving 14,942 cancer patients and 43,285 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the cancer risk. The results demonstrated that the rs1001179 polymorphism was associated with an increased cancer risk in the recessive and homozygote models (TT vs. CC: OR = 1.19, P = 0.01; TT vs. CT+CC: OR = 1.19, P <0.001). Furthermore, stratified analyses revealed a significant association between the rs1001179 polymorphism and prostate cancer in all models except the homozygote comparison. An association of the rs794316 polymorphism with cancer risk was detected in two genetic models (TT vs. AA: OR = 1.34, 95% CI = 1.03-1.74, P <0.001; TT vs. AT+AA: OR = 1.39, 95% CI = 1.09-1.77, P = 0.01). Additional well-designed studies with large samples should be performed to validate our results.

Role of IL-17A rs2275913 and IL-17F rs763780 polymorphisms in risk of cancer development: an updated meta-analysis.

Single nucleotide polymorphisms (SNPs) in the interleukin-17 (IL-17) gene have been shown to be correlated with susceptibility to cancer. However, various studies report different results of this association. The aim of the present work was to clarify the effects of IL-17A G197A (rs2275913) and IL-17F T7488C (rs763780) polymorphisms on cancer risk. We performed systematic searches of the PubMed and CNKI databases to obtain relevant publications. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association of rs2275913 and rs763780 polymorphisms with cancer risk. Data were extracted from the selected studies, and statistical analysis was conducted using the STATA software. Our results indicated that rs2275913 and rs763780 polymorphisms significantly increase cancer risk, especially in gastric cancers. Subgroup analysis suggested the existence of a significant correlation between rs763780 polymorphism and cancer susceptibility in Caucasian populations. This updated meta-analysis confirms that rs2275913 and rs763780 polymorphisms are highly associated with increased risk for multiple forms of cancer.