Comparison of therapeutic effects of endoscopic assisted different surgical approaches in hypertensive intracerebral hemorrhage: A retrospective cohort study.

We aimed to explore the therapeutic effects of endoscopically assisted surgical approaches for HICH. In this retrospective cohort study, we retrospectively analyzed the treatment status of 118 patients with HICH who underwent surgery for hematoma removal. Among them, 61 patients underwent endoscopically assisted hematoma removal surgery through the frontal lobe approach (frontal lobe group); 57 patients underwent endoscopic hematoma assisted via the temporal lobe approach (temporal lobe group). Treatment effects, cerebral hemodynamic status before and after treatment, postoperative prognosis at one month, and incidence of complications were compared between the 2 groups. We found that the total effective treatment rate in the frontal lobe group was higher than that in the temporal lobe group (P < .05). After surgery, the R during the contraction period of the common cerebral artery in both groups decreased compared to that before surgery, and the frontal lobe group was significantly lower than the temporal lobe group; the V and Q were higher than those before surgery, and the frontal lobe group was significantly higher than the temporal lobe group (P < .05). The prognosis of the frontal lobe group was better than that of the temporal lobe group (P < .05). Compared to the endoscopic-assisted temporal approach, the endoscopic-assisted frontal lobe approach for the treatment of HICH can improve cerebral hemodynamic status, enhance treatment efficacy, and improve prognosis.

First-principles insights into the C6N7 monolayer as a highly efficient sensor and scavenger for the detection of selective volatile organic compounds.

The design of new gas sensors and scavengers of volatile organic compounds (VOCs) is desirable for VOC enriching, separation and utilization. Herein, first-principles methods were performed to investigate the potential of C6N7 monolayers as highly efficient sensors and scavengers for selective VOCs (toluene, benzene, vinyl chloride, ethane, methanal, acetone, ethanol, and acetaldehyde). The physisorption of toluene, benzene, acetone, ethanol, acetaldehyde, and methanal has relatively high adsorption strength and can significantly tune the electronic properties and work function (Φ) of the C6N7, indicating that the C6N7 monolayer is highly sensitive and selective to these VOC gases. In addition, the desorption time of benzene, acetone, ethanol, acetaldehyde, and methanal is about 3, 0.4, 2.0 × 10-2, 3.0 × 10-2, and 3.6 × 10-5 s at 300 K, respectively, indicating that the C6N7-based sensor has high reusability at room temperature. The recovery time of toluene was about 7.8 × 102 s at 300 K, showing disposable toluene gas sensing of the monolayer. Our work confirms that the C6N7 monolayer as a resistance-type and Φ-type gas sensor and scavenger is highly sensitive, selective and reusable for VOCs (benzene, acetone, ethanol, acetaldehyde, and methanol), but is a disposable toluene gas sensor and scavenger at room temperature.

MicroRNA-325 targets lipocalin 15 to suppress proliferation, migration and invasion of breast cancer cells.

Introduction: Recent studies have proved the diverse roles of miRs in different cancer-related processes. This study was undertaken to determine the therapeutic implications of miR-325-3p in breast cancer. Material and methods: Expression analysis was carried out by qRT-PCR. Transfections were performed by Lipofectamine 2000 reagent. MTT assay was used for cell viability. Transwell assays were used for cell migration and invasion. Western blot analysis was used for protein expression analysis. Results: Gene expression analysis revealed miR-325 to be significantly suppressed in breast cancer tissues and cell lines. Nonetheless, ectopic expression of miR-325 resulted in suppression of the growth and colony development potential of the SK-BR-3 and CAMA-1 cells. Transwell assays showed that miR-325 overexpression also resulted in the decline of the migration and invasion of the SK-BR-3 and CAMA-1 cells. Bioinformatic analysis showed that miR-325 targets lipocalin 15 (LNC15) in breast cancer cells. LNC15 was also overexpressed in the breast cancer tissues and cell lines. However, overexpression of miR-325 caused a significant decline in the LNC15 expression in SK-BR-3 cells. Additionally, silencing of LNC15 resulted in inhibition of the growth, migration and invasion of the SK-BR-3 cells. Rescue assay showed that overexpression of LNC15 could promote the growth, migration and invasion of the miR-325 overexpressing effects. Conclusions: Taken together, the evidence shows that miR-325 acts as a tumor suppressor in breast cancer and may be used in the treatment of breast cancer.

EZH2 inhibitors-mediated epigenetic reactivation of FOSB inhibits triple-negative breast cancer progress.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer that lacks expression of estrogen receptor (ER) and progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) gene. Chemotherapy remains the standard of care for TNBC treatment, but considerable patients are very resistant to chemotherapy. Mutations or aberrant upregulation of EZH2 occur frequently, and EZH2 inhibitor (EZH2i) showed some preclinic antitumor effects in TNBC. METHODS: RNA-seq data of 3 TNBC cell lines either treated with 2 µM GSK343, or stably transduced with shEHZ2, compared to untreated controls (GSE112378) were analyzed by Limma R package. The Kaplan-Meier plotter (KM plotter) database was used to assess the relevance of FOSB mRNA expression to relapse-free survival (RFS) in TNBC. Cell number counting and colony formation assays were used to detect the biological effect of FOSB on the growth of TNBC cells in vitro. The effect of FOSB on TNBC tumor growth in vivo was investigated in a mice tumor xenograft model. Luciferase reporter and chromatin immunoprecipitation (Chip) assays were used to determine the regulatory roles of C/EBPß on FOSB expression. RESULTS: We found that FOSB, a member of the activator protein-1 complex, was a direct downstream target of EZH2. FOSB was significantly decreased in TNBC samples and associated with better relapse-free survival (RFS). EZH2-mediated histone 3 trimethylated on lysine 27 (H3K27me3), a marker of silent chromatin conformation, at the FOSB promoter inhibited it expression. Depletion of FOSB in TNBC cells promoted cell proliferation in vitro and tumor growth in vitro by inactivating the p53 pathway and conferred resistant to EZH2 inhibitor (EZH2i). Mechanistically, EZH2i promotes the shift from H3K27me3 to H3K27ac at the FOSB promoter, and recruits the transcription factor C/EBPß to activate FOSB gene transcription. CONCLUSION: Together, our results suggest that EZH2-mediated epigenetic inactivation of FOSB promotes TNBC expression and demonstrate that reactivation of FOSB expression by C/EBPß underlies the anti-TNBC action of EZH2is.

Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer.

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.

Multicenter cross-sectional screening of the BRCA gene for Chinese high hereditary risk breast cancer populations.

Due to lack of systematic reviews, BRCA, DNA Repair Associated (BRCA) mutations in the Chinese population are not completely understood. The following study investigates the prevalence and type of BRCA mutations in Chinese patients with high hereditary risk of breast cancer (BC). Patients Drwere recruited from 14 cities between October 2015 and February 2016, and were selected based on family and personal medical history. BRCA mutations were analyzed by collecting blood samples from all participants. 437 BC patients were included. A total of seventy-six (17.4%) mutation carriers were identified with no geographic difference. The mutation rate in the early-onset BC patients was lower compared to family history of breast/ovarian cancer (OC), bilateral BC, male BC, BC&OC or meeting ≥2 criteria (9.2 vs. 21.7, 24.0, 22.2, 16.7 and 24.3%, respectively, P=0.007). A total of 61 mutation sites were identified (BRCA1 32, BRCA2 29) including 47.5% novel sites and extra 10 variants of uncertain significance. A total of five sites were repeated in more than one unrelated patient. A total of 11 sites were associated with hereditary breast and ovarian cancer syndrome, two of which were confirmed by family pedigrees. Compared with BRCA- patients, patients with BRCA1 mutation tended to be triple-negative BC (P<0.001), whereas patients with BRCA2 mutation were more likely to be hormone receptor positive BC (P=0.02). The present study provides a general BRCA mutation profile in the Chinese population. The prevalence of BRCA mutation in BC patients with high hereditary risk is lower compared with Western populations. Chinese mutation type is different with Western people, without obvious founder mutation.

The genetic variants in the PTEN/PI3K/AKT pathway predict susceptibility and CE(A)F chemotherapy response to breast cancer and clinical outcomes.

The PI3K/PTEN/AKT pathway play a critical role in balancing cell growth and death. Epidemiologic studies suggested that mutations of the PI3K/PTEN/AKT pathway genes are associated with cancer risk, yet no data are available for PTEN rs701848, PIK3CA rs2699887, and AKT1 rs2494752 polymorphism and breast cancer(BC) risk. A case-control study was performed in 920 BC patients and 908 healthy controls using the TaqMan assay method. Overall, individuals with PTEN rs701848 TC, CC and TC/CC genotypes showed significant increased BC risk (P=0.043, P=0.002, P=0.008, respectively), and the C allele carriers had a 1.224-fold significantly increased risk of developing BC (P= 0.003). Moreover, a higher frequency of AKT rs2494752 AG genotype was observed among cases (P=0.045). Individuals harboring rs2494752 AG/AA genotype had a vital increased susceptibility to BC in the dominant model (P=0.039). More importantly, AKT1 rs2494752 GG genotype showed significantly rates of response to NCT chemotherapy (P=0.048). Furthermore, AKT1 rs2494752 AG genotype carriers showed significantly shorter DFS time, and GG genotype as the independent prognostic factor (DFS: adjusted HR=1.523, 95% CI=1.012-2.293, P=0.044; OS: adjusted HR=2.321, 95% CI=1.281-4.204, P=0.005). Moreover, MDR analysis consistently revealed that the combination of 3 selected SNPs and 7 known risk factors represented the best model to predicting BC prognosis. The luciferase assay showed that the G allele of rs2494752 significantly increased AKT1 promoter activity. These results suggest that PTEN rs701848 and AKT1 rs2494752 polymorphisms might be a candidate pharmacogenomic factor to assess the susceptibility of BC and response and prognosis prediction for interindividualized CE(A)F chemotherapy in BC patients.

Co-expression of Oct-4 and Nestin in human breast cancers.

The aim is to investigate the clinical implications of the Oct-4 and Nestin protein in human breast cancers. A total of 346 cases including 26 fresh and 320 paraffin-embedded tumor tissues were selected for characterizing the frequency of CD44(+)CD24(-) tumor cells by flow cytometry and the differential expression of the stem cell-related genes between CD44(+)CD24(-) and non-CD44(+)CD24(-) tumor cells was analyzed by PCR Array and immunofluorescence. In comparison with the non-CD44(+)CD24(-) tumor cells, the CD44(+)CD24(-), particularly for those with high percentage of Oct-4(+) and Nestin(+), tumor cells had higher tumorigenicity by forming mammospheres in vitro. More importantly, 42 (13.125%) out of 320 tumor tissues were positive for Oct-4 and Nestin staining. Universal analysis and multivariate analysis revealed that the expression of Oct-4 and Nestin was associated significantly with younger age, pathogenic degrees, lymph node metastasis and triple-negative breast cancer independently (P < 0.05) as well as shorter survival (P = 0.001). Oct-4 and Nestin were important regulators of the development of breast cancer, and Oct-4 and Nestin may be used as predictors for the prognosis of breast cancers.

Girdin protein: a new potential distant metastasis predictor of breast cancer.

To investigate the expression status and the clinical implications of Girdin protein in breast cancer. The expression status of Girdin protein and clinicopathological parameters in 820 breast cancer specimens was analyzed using immunohistochemistry staining and the relationship between Girdin protein and clinicopathological parameters. The prognosis of breast cancer was subsequently determined. Girdin protein was expressed positively in 295 (35.98%) of the 820 cases examined. The expression of Girdin protein was related to histological type and CerbB2 (P = 0.001, 0.006, and 0.001, respectively). After analyzing survival rates, the cases with highly expressed Girdin protein were shown to attain a significantly more distant metastasis rate and poorer postoperative, disease-specific survival than those with none or low expressed Girdin protein (P = 0.001). In the Cox regression test, Girdin protein was detected as an independent prognostic factor (P = 0.031). Girdin protein may be a potential new distant metastasis biomarker of breast cancer.

Clinical implications of stem cell gene Oct-4 expression in breast cancer.

PURPOSE: To explore the expression of stem cell genes in breast cancer and the relationship between stem cell gene expression and clinical and pathological characteristics and prognosis of breast cancer. BACKGROUND: By now, stem cell differentiation-related genes and the relationship between the genes and clinic-pathological characteristics and prognosis of breast cancer are still unclear. MATERIALS AND METHODS: CD44+/CD24- tumor cells were selected by Flow cytometry. The differential expression of genes between CD44+/CD24- tumor cells and non-CD44+/CD24- tumor cells were detected by RT(2) Profiler™ PCR Array. The expression of stem cell gene Octamer-4 (Oct-4) was analyzed by immunohistochemistry staining and the relationship between Oct-4 and clinicopathological parameters of breast cancer was determined. RESULTS: Seven different genes including stem cell differentiation-related factors (CD44, Oct-4, and nestin), cell cycle regulators (APC and CDC2), and growth factors (HGF and TGF) were detected as significantly differently expressed between CD44+/CD24- tumor cells and non-CD44+/CD24- tumor cells. Oct-4 protein expressed significantly higher in cancerous tissues than adjacent-tumor tissues (P = 0.001). Moreover, we observed that the expression of Oct-4 protein was related to histological type, lymph node status and molecular type of breast cancer (P = 0.001, 0.006, and 0.001, respectively). After survival analysis, the cases with highly expressed Oct-4 protein attained a significantly poorer postoperative disease-specific survival than those with none/low expressed Oct-4 protein (P = 0.001). In the Cox regression test, tumor size, histological type, disease stage, lymph node metastasis, Her-2 and Oct-4 were detected as the independent prognostic factors (P = 0.031, 0.012, 0.001, 0.002, 0.030, and 0.003, respectively). CONCLUSIONS: Oct-4 was highly expressed in CD44+/CD24- tumor cells, and may be a potential biomarker for the initiation, progression, and differentiation of breast cancer.

Clinical implications for nestin protein expression in breast cancer.

Recently, it was observed that nestin is preferentially expressed in basal/myoepithelial cells of the mammary gland, and that this intermediate filament may be used as a myoepithelial marker. However, the clinical and prognostic implications of nestin as a marker for breast cancer are still unclear. We examined mastectomy specimens from 150 breast cancers and matching, adjacent non-cancerous tissues using immunohistochemistry and western blotting. Overall, triple-negative breast cancers - that is, breast cancers that do not express estrogen receptors (ER), progesterone receptors (PR), or human epidermal growth factor receptor 2 (HER2/neu) - had higher expression rates for nestin than the other breast cancers (57.14%vs 9.30%; P < 0.001). In triple-negative breast cancers, significantly increased nestin expression rates were observed in patients with lymph node metastasis compared with those without node metastasis (25.00%vs 76.92%; P = 0.032). A similar phenomenon was observed for invasive ductal carcinomas compared with ductal carcinoma in situ (16.67%vs 73.33%; P = 0.046). Nestin expression was also found to be significantly related to ER, PR, and P53 expression (P < 0.05). Nestin expression was associated with both shorter breast cancer-specific survival and poor relapse-free survival in the lymph node-positive group (P = 0.028 and P = 0.012 respectively). After Cox regression was carried out, nestin was not shown to be an independent prognostic factor for breast cancer. These findings substantiate the possibility of using nestin as a marker for triple-negative breast cancer. Triple-negative breast cancer progression is associated with nestin; however, the underlying mechanisms of this relationship require further investigation.

Prognostic role of lymphatic vessel invasion in early gastric cancer: a retrospective study of 188 cases.

BACKGROUND: Lymphatic vessel invasion is an important prognostic factor for the gastric cancer without lymph node metastasis. However, the studies on early gastric cancers is still sparse. Therefore, we carried out this study to determine clinicopathological and surgical prognostic factors, especially lymphatic vessel invasion, for early gastric cancers. METHODS: Clinicopathological characteristics and prognostic outcomes of 188 patients who received a gastrectomy for early gastric cancer between 1980 and 2000 were retrospectively evaluated based on the subclassification of pN category. A multivariate analysis was performed by using the Cox regression model, where lymphatic vessel invasion and other potential prognostic factors were included. RESULTS: Of the 188 patients, 158 had T1N0M0 and 30 T1N1M0 cancers. In patients with T1N0M0 cancers, the survival rate was significantly lower in those with lymphatic vessel invasion than in those without (chi(2)=4.025, P=0.045). However, in patients with T1N1M0 cancers, the survival rates were not significantly different between those with and those without lymphatic vessel invasion (chi(2)=0.253, P=0.615). The multivariate analysis identified that age (P=0.033) and lymph node metastasis (P=0.019) were independent prognostic factors for all early gastric cancers. However, age (P=0.042), tumor location (P=0.032), and lymphatic vessel invasion (P=0.010) were the independent prognostic factors for T1N0M0 cancers. CONCLUSIONS: Lymphatic vessel invasion was an independent prognostic factor for T1N0M0 early gastric cancers, and thus may be a potential prominent factor that should be considered to be included in the category of lymphoid metastasis (both lymph node metastasis and lymphatic vessel invasion) in patients with early gastric cancer.

Impact of total retrieved lymph nodes on staging and survival of patients with gastric cancer invading the subserosa.

PURPOSE: To investigate the impact of total retrieved lymph nodes (tLNs) on staging and survival in patients with pT2b gastric cancer according to the nodal status. METHODS: Clinicopathological characteristics and prognostic outcomes of 392 patients with pT2b gastric cancer between 1980 and 2005 were retrospectively investigated based on the nodal status. RESULTS: The number of metastatic lymph nodes (mLNs) was highly correlated with the number of tLNs (P<0.001). The overall 5-year and 10-year survival rates were 39.0% (153/392) and 17.9% (70/392), respectively. The survival rates in patients with pN0 cancers did not differ significantly from that in patients with pN1 cancer when the tLNs were 25 or less. However, the survival rate in patients with N0 cancers was significantly greater than that in patients with pN1 cancers when the tLNs were more than 25 (64.3% vs. 36.9%, chi(2)=4.339, P=0.037). Moreover, both 5- and 10-year survival rates differed significantly among patients with pN1, pN2 and pN3 gastric cancer regardless of tLNs. Multivariate analysis revealed that age, tumor focus number, tumor location, and mLN, but not tLNs, were independent prognostic predictors in patients with pT2b gastric cancer. CONCLUSIONS: To improve the accuracy of staging, no less than 15 tLNs should be pathologically examined in patients with pN1-3, and 25 tLNs for the patients with N0. More tLNs may not be associated with a better prognosis in pT2b disease because the extent of lymph node dissection is pre-defined for the operation.

Prognostic significance of subclassification of pT2 gastric cancer: a retrospective study of 847 patients.

PURPOSE: To investigate the prognostic significance of subclassification of pT2 gastric cancers according to the nodal status. METHODS: Clinicopathological characteristics and prognostic outcomes of 847 gastric cancer patients who received a gastrectomy between 1985 and 2003 were retrospectively evaluated based on the subclassification of pT2 stage (i.e. pT2a and pT2b). RESULTS: Of the patients, 244 and 603 had pT2a and pT2b stage cancers, respectively. Patients with pT2a cancers had a significantly longer disease-specific 5-year survival rate than those with pT2b cancers (P<0.001). The prognosis was significantly better in patients with pT2a cancers than in patients with pT2b cancers at pN0, pN1 and pN2 (P=0.036, 0.021, and 0.019 respectively), but not pN3 stages (P=0.775). Multivariate analysis identified age, tumor location, pT stages, pN stages, and adjuvant chemotherapy as independent prognostic factors for pT2 gastric cancers. The survival rates were similar between pT2aN1 (stage II) and pT2bN0 (stage IB) cancers (P=0.604), and between pT2aN2 (stage IIIA) and pT2bN1 (stage II) cancers (P=0.936). CONCLUSIONS: Subclassification of pT2 gastric cancers into pT2a or pT2b is of prominent prognostic significance, and thus it is recommended that the current stage grouping conventions include subclassification of pT2, in order to more accurately predict the prognosis of patients.