Elevated homocysteine levels contribute to larger hematoma volume in patients with intracerebral hemorrhage.

BACKGROUND: We investigate whether plasma homocysteine (HCY) levels are associated with hematoma volume and outcome in patients with intracerebral hemorrhage (ICH). METHODS: A total of 69 patients admitted within 24 hours after ICH onset was divided into 2 groups based on admission plasma HCY levels (low homocysteinemia [LHCY] group, plasma HCY concentrations ≤14.62 µmol/L, versus high homocysteinemia [HHCY] group, >14.62 µmol/L). RESULTS: Mean hematoma volumes for 2 groups (LHCY and HHCY) were 13.18 and 23.09 mL (P = .012), respectively, in patients with thalamoganglionic ICH, but hematoma volumes between 2 groups had no significant difference among patients with lobar or infratentorial ICH. On multivariate linear regression analysis, elevated HCY levels significantly correlated with larger hematoma volume in patients with thalamoganglionic ICH (B = .604, P = .004) after adjustment for confounding factors. Poor outcomes (6-month modified Rankin Scale scores ≥3) were not significantly different between 2 groups (low homocysteinemia group, 31.4%, versus high homocysteinemia group, 41.2%, P = .400). CONCLUSIONS: Elevated plasma HCY levels were associated with larger hematoma volume only in patients with thalamoganglionic ICH. HCY levels might not be predictors of the 6-month clinical outcome in patients with ICH.

Alendronate-conjugated amphiphilic hyperbranched polymer based on Boltorn H40 and poly(ethylene glycol) for bone-targeted drug delivery.

A novel type of alendronate(ALE)-conjugated amphiphilic hyperbranched copolymer based on a hydrophobic hyperbranched Boltorn H40 (H40) core with ALE targeting moiety and many hydrophilic poly(ethylene glycol) (PEG) arms was synthesized as a carrier for bone-targeted drug delivery. The star copolymer H40-star-PEG/ALE was characterized using nuclear magnetic resonance (NMR), Fourier transformed infrared spectroscopy (FTIR), and gel permeation chromatography (GPC) analysis. Benefiting from its highly branched structure, H40-star-PEG/ALE could form micelles in aqueous solution, which was confirmed by transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques. The cytotoxicity and hemolysis of the H40-star-PEG/ALE micelles were evaluated via methylthiazoletetrazolium (MTT) assay against NIH/3T3 normal cells and red blood cell (RBC) lysis assay, respectively. As a model anticancer drug, doxorubicin (DOX) was encapsulated into the H40-star-PEG/ALE micelles. The anticancer activity of DOX-loaded micelles was evaluated by MTT assay against an HN-6 human head and neck carcinoma cell line. The strong affinity of H40-star-PEG/ALE micelles to bone was confirmed by the hydroxyapatite (HA) binding assay. These results indicate that the H40-star-PEG/ALE micelles are highly promising bone-targeted drug carriers for skeletal metastases.

Association between MMP-12-82A/G polymorphism and cancer risk: a meta-analysis.

BACKGROUND: Numerous studies have focused on the association between MMP-12-82A>G polymorphism and cancer risk, but produced inconsistent results. Therefore, we performed a meta-analysis of case-control study to evaluate the association of MMP-12-82A>G polymorphism and cancer risk. METHODS: A systematic literature search was conducted among PubMed, Web of Science, Science Direct, China National Knowledge Infrastructure (CNKI) and Wangfang databases updated on May 1st, 2015. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of association between this polymorphism and cancer risk. RESULTS: A total of seventeen case-control studies with 7,450 cases and 7,348 controls were identified and analyzed. Overall, there was no statistically significant association between MMP-12-82A>G polymorphism and increased risk of cancer under all genetic models. Subgroup analysis by ethnicity observed that there is no strong relationship between MMP-12-82A>G polymorphism and cancer risk among Asian and European populations. Furthermore, stratified analysis based on the source of control revealed no statistically significant association between MMP-12-82A>G polymorphism and cancer risk either in hospital-based or population-based studies. However, when we stratified analysis based on cancer type, significant association was found in ovarian cancer, but not in other types of cancer. CONCLUSION: This meta-analysis suggests that MMP-12-82A>G polymorphism is not significantly associated with overall cancer risk. However, MMP-12-82A>G polymorphism may increase the susceptibility to ovarian cancer.

Increased expression of USP22 is associated with disease progression and patient prognosis of salivary duct carcinoma.

OBJECTIVES: Ubiquitin-specific protease 22 (USP22) could exhibit a critical function in pathological processes, including oncogenesis and cell cycle progression. This study examines the protein expression of USP22 in salivary duct carcinoma (SDC) in association with patient survival and other clinicopathologic parameters. MATERIALS AND METHODS: Quantitative RT-PCR and immunohistochemistry (IHC) were used to determine the expression of USP22 protein in 44 SDCs in comparison with 20 non-cancerous salivary tissues. Furthermore, we analyzed the correlation between the expression of the USP22 protein and various clinicopathologic factors including survival status of patients with SDC. RESULTS: The incidence of positive USP22 expression was 63.7% in 44 SDC tissues. The mRNA level of USP22 expression in SDC samples was significantly higher than that in non-cancerous salivary tissues (P < 0.001), which was consistent with the IHC result (P < 0.001). Moreover, statistical analysis showed that positive USP22 expression was positively related to pT classification, pN classification and AJCC stage. Notably, high USP22 expression was significantly associated with shorter overall survival (P = 0.023) and disease-specific survival (P = 0.019). Multivariate Cox regression analysis revealed that USP22 expression level was an independent prognostic factor for both overall survival (P < 0.001) and disease-free survival (P < 0.001). CONCLUSION: Our results indicate that activation of USP22 correlates with SDC progression and therapy failure. Overexpression of USP22 may contribute to the progression of SDC and thus may serve as a new molecular marker to predict the prognosis of SDC patients.

USP22 is useful as a novel molecular marker for predicting disease progression and patient prognosis of oral squamous cell carcinoma.

BACKGROUND AND OBJECTIVE: The significance of ubiquitin-specific protease 22 (USP22) as a potential marker has been growing in the field of oncology. The aim of this study was to investigate the role of USP22 and the association with its potential targets in oral squamous cell carcinoma (OSCC). METHODS: Immunohistochemistry was used to determine the expression of USP22 protein in 319 OSCC patients in comparison with 42 healthy controls. The clinical correlations and prognostic significance of the aberrantly expressed protein was evaluated to identify novel biomarker of OSCC. RESULTS: The incidence of positive USP22 expression was 63.32% in 319 conventional OSCC tissues. The protein expression level of USP22 was concomitantly up-regulated from non-cancerous mucosa to primary carcinoma and from carcinomas to lymph node metastasis (P<0.001). Moreover, statistical analysis showed that positive USP22 expression was positively related to lymph node metastasis, Ki67, Cox-2 and recurrence. Furthermore, it was shown that patients with positive USP22 expression had significantly poorer outcome compared with patients with negative expression of USP22 for patients with positive lymph nodes. Multivariate Cox regression analysis revealed that USP22 expression level was an independent prognostic factor for both overall survival and disease-free survival (P<0.001 and P<0.001, respectively). Cancer cells with reduced USP22 expression exhibited reduced proliferation and colony formation evaluated by MTT and soft agar assays. CONCLUSION: To our knowledge, this is the first study that determines the relationship between USP22 expression and prognosis in OSCC. We found that increased expression of USP22 is associated with poor prognosis in OSCC. USP22 may represent a novel and useful prognostic marker for OSCC.

Increased expression of CD147 and MMP-9 is correlated with poor prognosis of salivary duct carcinoma.

PURPOSE: The aim of this study was to investigate expression of CD147 and MMP-9 in salivary duct carcinoma (SDC) so as to determine whether these two genes may be correlated with poor prognosis of SDC. METHODS: We examined the significance of the CD147 and MMP-9 expression in SDC (n = 35), non-cancerous salivary tissue (n = 20) in previously untreated patients using immunohistochemical staining. Furthermore, we analyzed the correlation between the expression of these two genes and various clinicopathologic factors including survival status of patients with SDC. RESULTS: Positive stain of CD147 and MMP-9 was seen in all 35 cases of tumor samples. A statistical correlation was observed between CD147 and MMP-9 expression in SDC tissues. The incidences of high expression were 45.71% for CD147 and 51.43% for MMP-9 in 35 SDC tissues, respectively. High expression of CD147 and MMP-9 was significantly correlated with clinical feature and shorter progression-free survival (PFS) (P (CD147) = 0.031; P (MMP-9) = 0.020) and overall survival (OS) (P (CD147) = 0.044; P (MMP-9) = 0.013). CONCLUSION: CD147 and MMP-9 expression is correlated with invasion, metastasis and shorter PFS/OS of SDC. Patients with high expression of CD147 and MMP-9 had poor prognosis than SDC patients with low expression.

New mutation of the patched homologue 1 gene in a Chinese family with naevoid basal cell carcinoma syndrome.

Naevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is inherited in an autosomal dominant mode characterised by a combination of developmental anomalies and a predisposition to form tumours. Our aim was to search for patched homologue 1 (PTHC1) mutations in a Chinese family with NBCCS. Mutation analysis of PTCH1 was done of all 10 members of this family by amplified polymerase chain reaction and direct sequencing. Two novel PTCH1 mutations (3146A-->T, 1686C-->T) were identified in all five affected members. The mutation, 3146A-->T in exon 17, is predicted to lead to different PTCH protein translations. 1686C-->T mutation in exon 11 is a nonsense mutation. These mutations were not found in any unaffected members of this family or in 100 unrelated healthy Chinese people. Our findings suggest that the 3146A-->T mutation in the PTCH gene may be the cause of NBCCS by affecting the conformation and function of the PTCH protein.