Comparison between Arm Port and Chest Port for Optimal Vascular Access Port in Patients with Breast Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: This meta-analysis was conducted to compare the complication rates between arm and chest ports in patients with breast cancer. Design and Data Sources. PubMed, Embase, Cochrane library, Chinese National Knowledge Infrastructure (CNKI), and Wanfang database were used to perform a systematic review and meta-analysis of publications published from the inception of the database to 11, October 2019. Our search generated a total of 22 articles published from 2011 to 2019, including 6 comparative studies and 16 single-arm articles, involving 4131 cases and 5272 controls. Single-arm studies combined with comparative studies were also pooled and analyzed. Finally, subgroup analysis was performed to compare the rates of infection and thrombosis between these two ports. Eligibility Criteria. Included articles were research studies comparing complication rates of arm ports with chest ports in patients with breast cancer. Any review or meta-analysis article would be removed. Data Extraction and Synthesis. Demographic data and information for the following analysis were extracted. DerSimonian and Laird random effect meta-analysis was conducted to analyze comparative studies while Begg's and Egger's tests were used for assessment of publication bias. Meta-regression analysis was performed to explain the sources of heterogeneity. RESULTS: There was no difference in the risk of overall complications between arm and chest ports for comparative studies (P=0.083). While results of pooled comparative and single-arm studies indicated that arm port would increase the overall complication risks with RR of 2.64, results of the subgroup analysis showed that there was no difference in the risk of catheter-related infection between these two ports. However, arm port might be associated with the higher thrombosis rates compared with chest port according to the results of the analysis for only comparative studies (RR of 2.64, results of the subgroup analysis showed that there was no difference in the risk of catheter-related infection between these two ports. However, arm port might be associated with the higher thrombosis rates compared with chest port according to the results of the analysis for only comparative studies (P=0.083). While results of pooled comparative and single-arm studies indicated that arm port would increase the overall complication risks with RR of 2.64, results of the subgroup analysis showed that there was no difference in the risk of catheter-related infection between these two ports. However, arm port might be associated with the higher thrombosis rates compared with chest port according to the results of the analysis for only comparative studies (P=0.083). While results of pooled comparative and single-arm studies indicated that arm port would increase the overall complication risks with. CONCLUSIONS: This study indicated that the arm port might increase the risk of overall complication risks as well as the risk of catheter-related thrombosis compared with the chest port. However, these reported findings still need to be verified by large randomized clinical trials.

Silencing of SOCS-1 and SOCS-3 suppresses renal interstitial fibrosis by alleviating renal tubular damage in a rat model of hydronephrosis.

Our study was performed to elucidate how SOCS-1/3 silencing suppresses renal interstitial fibrosis (RIF) by alleviating renal tubular damage in rat models affected by hydronephrosis. Male Wistar rats were randomly selected to establish hydronephrosis rat model, after which all rats were classified into normal, model, negative control (NC), siRNA-SOCS-1, siRNA-SOCS-3, and siRNA-SOCS-1 + siRNA-SOCS-3 groups. The levels of urine protein, serum creatinine (Scr), and blood urea nitrogen (BUN) were detected. ELISA was performed to determine levels of cystatin (CysC), ß2-microglobulin (ß2-MG), interleukin (IL)-6, and tumor necrosis factor (TNF)-α. RT-qPCR and Western blotting were used for mRNA and protein expressions of SOCS-1, SOCS-3, α-smooth muscle actin (α-SMA), and transforming Growth Factor (TGF)-ß1. Compared with the normal group, the levels of Scr, BUN, urine protein, NAG, CysC, ß2-MG, IL-6, and TNF-α were increased in other groups, as well as elevated mRNA and protein expressions of SOCS-1, SOCS-3, α-SMA, and TGF-ß1. The siRNA-SOCS-1, siRNA-SOCS-3, and siRNA-SOCS-1 + siRNA-SOCS-3 groups were found with decreased levels of Scr, BUN, urine protein, NAG, CysC, ß2-MG, IL-6, and TNF-α, as well as mRNA and protein expressions of SOCS-1, SOCS-3, α-SMA, and TGF-ß1, including positive rates of SOCS-1 and SOCS-3 proteins in comparison with the model and NC groups. In comparison with the siRNA-SOCS-1 and siRNA-SOCS-3 groups, the siRNA-SOCS-1 + siRNA-SOCS-3 group exhibited decreased levels of Scr, BUN, urine protein, NAG, CysC, ß2-MG, IL-6, and TNF-α. Our study demonstrated that silencing of SOCS-1/3 may suppress RIF by alleviating the renal tubular damage in rat models affected by hydronephrosis.

Impact of LPL gene rs283 polymorphism on exercise-induced changes in metabolism of obese adolescents and the regulatory mechanisms behind it.

NEW FINDINGS: What is the central question of this study? We investigated whether the LPL gene rs283 polymorphism affects exercise-induced changes in body composition and lipid and glucose metabolism in obese adolescents and whether it is functional. What is the main finding and its importance? Chinese obese adolescents of Han nationality with the GG genotype of the rs283 polymorphism were more sensitive to exercise-induced reduction of the body fat percentage, insulin resistance and plasma triglyceride levels. The G allele can significantly increase reporter gene expression level, which may be the molecular reason for the difference in exercise-induced parameter changes among obese adolescents. The aim of this investigation was to explore the association between the rs283 polymorphism located in the lipoprotein lipase (LPL) gene and exercise-induced changes in body composition and lipid and glucose metabolism in obese adolescents and to probe into the molecular regulatory mechanisms. Fifty-five obese adolescents of Han nationality underwent aerobic training for 4 weeks. Body composition and lipid and glucose metabolic parameters were tested before and after the training. The rs283 polymorphism was genotyped by PCR-restriction fragment length polymorphism, and association analysis with the weight-reducing effect was performed. The regulatory mechanisms of the rs283 polymorphism were explored through the dual-luciferase reporter assay. Exercise-induced change rates were as follows: the change in body fat percentage of GG genotype groups was 3.37 ± 1.60, significantly higher than that of GA genotype groups (2.09 ± 1.53, P < 0.01); the change in the homeostasis model assessment of insulin resistance was 0.52 ± 0.13, obviously higher than that of GA genotype groups (0.44 ± 0.10, P < 0.05); and the change in triglyceride was 51.91 ± 6.56, much higher than that of GA genotype groups (47.06 ± 5.36, P < 0.01). The relative luciferase activity of the reporter gene in recombinant vector carrying the G allele was 2.67 ± 0.22, markedly higher than that in recombinant vector carrying the A allele (1.63 ± 0.03, P < 0.01). Chinese obese adolescents of Han nationality with GG genotype of the rs283 polymorphism were more sensitive to exercise-induced parameter changes. The G allele can improve reporter gene expression level, indicating the effects of rs283 on gene expression.

Beclin 1 expression is closely linked to colorectal carcinogenesis and distant metastasis of colorectal carcinoma.

Beclin 1 participates in development, autophagy, differentiation, anti- apoptosis, neurodegeneration, tumorigenesis and cancer progression. The roles of Beclin 1 in colorectal carcinogenesis and its subsequent progression are still unclear. Here, the mRNA and protein expression of Beclin 1 were determined in colorectal carcinoma and matched mucosa by Reverse transcriptase-polymerase chain reaction and Western blot. Immunohistochemistry and in situ hybridization (ISH) were performed on tissue microarryer with colorectal carcinoma, adenoma and mucosa. The expression of Beclin 1 mRNA and protein was found to be higher in colorectal carcinoma than matched mucosa by real-time PCR and Western blot (p < 0.05). According to the ISH data, Beclin 1 expression was lower in colorectal non-neoplastic mucosa (NNM) than adenoma and carcinoma (p < 0.05). Immunohistochemically, primary carcinoma showed stronger Beclin 1 expression than NNM and metastatic carcinoma in the liver (p < 0.05). Beclin 1 protein expression was negatively related to liver and distant metastasis (p < 0.05), but not correlated with age, sex, depth of invasion, lymphatic or venous invasion, lymph node metastasis, tumor-node-metastasis (TNM) staging, differentiation or serum carcinoembryonic antigen (CEA) concentration (p > 0.05). Survival analysis indicated that Beclin 1 expression was not linked to favorable prognosis of the patients with colorectal carcinoma (p > 0.05). Cox's model indicated that depth of invasion and distant metastasis were independent prognostic factors for colorectal carcinomas (p < 0.05). It was suggested that Beclin 1 expression is closely linked to colorectal carcinogenesis and distant metastasis of colorectal carcinoma.

Downregulated inhibitor of growth 3 (ING3) expression during colorectal carcinogenesis.

BACKGROUND & OBJECTIVES: ING3 (inhibitor of growth protein 3) overexpression decreased S-phase cell population and colony-forming efficiency, and induced apoptosis at a p53-mediated manner. The aim of this study was to investigate the clinicopathological and prognostic significance of ING3 expression in colorectal carcinogenesis and subsequent progression. METHODS: ING3 expression was examined by immunohistochemistry on tissue microarray containing colorectal non-neoplastic mucosa (NNM), adenoma and adenocarcinoma. Colorectal carcinoma tissue and cell lines were studied for ING3 expression by Western blot or RT-PCR. RESULTS: ING3 mRNA was differentially expressed in Colo201, Colo205, DLD-1, HCT-15, HCT-116, HT-29, KM-12, SW480, SW620 and WiDr cells. Carcinomas showed significantly lower ING3 expression than matched NNM at mRNA level (P< 0.05), but not at protein level. Immunohistochemically, ING3 expression was significantly decreased from NNM, adenoma to adenocarcinoma (P< 0.05). ING3 expression was not correlated with age, sex, tumour size, depth of invasion, lymphatic or venous invasion, lymph node metastasis, tumour- node- metastasis staging or differentiation. Kaplan-Meier analysis indicated that ING3 protein expression was not associated the prognosis of the patients with colorectal carcinoma (P< 0.05). INTERPRETATION & CONCLUSIONS: Our study showed that downregulated ING3 expression might play an important role in colorectal adenoma-adenocarcinoma sequence. Further studies are required to understand the mechanism.

Influence of different hypoxia models on metastatic potential of SGC-7901 gastric cancer cells.

Gastric cancers are one of the most common gastrointestinal tumors with proclivity to metastasis. Hypoxia is an important feature in solid tumor microenvironment; accumulating evidence suggests that chronic and repetitive exposure to hypoxia and reoxygenation seems to provide an advantage to tumor growth. However, mechanisms of intermittent hypoxia regulating gastric cancer metastatic potential remain to be elucidated. In the present study, we established the continuous and intermittent gastric cancer hypoxia models, and we compared the effects of these models on gastric cancer cell metastatic potential. Hypoxia-inducible factor-1α (HIF-1α) and hypoxia target protein/genes expression in response to different hypoxia models were analyzed by Western blot, immunofluorescence, and real-time PCR assays. Gastric cancer cell migration and invasion ability were analyzed by wound healing and Boyden chamber assay. Colony formation and tumor spheroid formation assays were used to assess the ability of self-renewal. Stem-related protein OCT4 and HIF-1α expression were also analyzed by confocal immunofluorescence in single tertiary generation spheroid. We demonstrated that the intermittent hypoxia model upregulated expression of both HIF-1α and hypoxia target protein/genes in a time-dependent manner compared with that of SGC-7901 cells cultured under normoxia. Remarkably, HIF-1α protein was more prone to being located in the nucleus of SGC-7901 cells under conditions of intermittent hypoxia. Gastric cancer cells' migration and invasion ability were significantly enhanced after hypoxic culture; moreover, intermittent hypoxia-conditioned SGC-7901 cells exhibited higher invasiveness than the continuous hypoxia-conditioned SGC-7901 cells. Gastric cancer stem/progenitor cell subpopulation was also enlarged which indicated an enhanced self-renewal ability in hypoxic cultured SGC-7901 cells. Our study emphasizes the significance of hypoxia in regulating gastric cancer cell metastasis potential. Compared with continuous hypoxia, intermittent hypoxia is a more effective and potent hypoxic stimulus. These results provide a new insight to investigate the hypoxic microenvironment within solid tumors.

Tumor-associated mesothelial cells are negative prognostic factors in gastric cancer and promote peritoneal dissemination of adherent gastric cancer cells by chemotaxis.

Peritoneal dissemination is highly frequent in gastric cancer. Damage to human peritoneal mesothelial cell (HPMC) barriers provokes gastric cancer peritoneal dissemination (GCPD), the key events during GCPD, is characterized by fibroblastic development. In this study, we have studied the association between fibroblast activation protein (FAP) expression in peritoneum and the pathological features of the primary tumor. The clinical prognosis of gastric cancer patients was evaluated according to FAP expression. In a gastric cancer cell-HPMC co-culture system, expression of E-cadherin, α-smooth muscle actin, and FAP were evaluated by Western blotting. Gastric cancer cell migration and adhesion to HPMC were also assayed. Our results showed positive peritoneal staining of FAP in 36/86 cases (41.9 %), which was associated with a higher TNM stage in primary gastric cancer and higher incidence of GCPD (both p<0.05). Survival analysis showed FAP expression was an independent prognostic factor of poor survival (p=0.02). Peritoneum of FAP-positive expression exhibited a distinct fibrotic development and expressed higher level of the mesenchymal marker α-SMA, which was confirmed by the in vitro Western blot assay. In HPMC and gastric cancer cell adherence assay, SGC-7901 cells preferentially adhered to TA-HPMC at different cell densities (both p<0.05). Additionally, SGC-7901 cells were more prone to chemotaxis by FAP-expressed tumor-associated-human peritoneal mesothelial cells (TA-HPMC) compared with HPMC co-cultured with normal gastric glandular epithelial cells in a time-dependent manner (both p<0.05). Our study indicated a positive correlation between peritoneum FAP expression and GCPD. FAP-expressed TA-HPMC might be an important cellular component and instigator of GCPD.

The mannose-sensitive hemagglutination pilus strain of Pseudomonas aeruginosa shift peritoneal milky spot macrophages towards an M1 phenotype to dampen peritoneal dissemination.

Peritoneal dissemination (PD) of tumor cells is the most frequent pattern of gastric cancer recurrence and the leading cause of death. Peritoneal milky spots are deemed as the site of origin of gastric cancer PD wherein the main cellular components are macrophages. A vaccine derived from the mannose-sensitive hemagglutination pilus strain of Pseudomonas aeruginosa (PA-MSHA) has exhibit strong immune modulatory properties. In the present study, we tested the hypothesis whether the PA-MSHA vaccine activated peritoneal milky spot macrophages (PMSM) in a manner that would attenuate PD. It was observed that PA-MSHA activated PMSM towards a classical activation phenotype via a toll-like receptor4/9-dependent mechanism, which increased interleukin-12 levels and promoted the expression of co-stimulatory and antigen-presenting molecules like CD80, CD86, and MHC-II (P < 0.05). In addition, PA-MSHA-treated PMSM exhibited strong nonspecific antitumor effects in both contact-dependent and contact-independent modes of action (P < 0.05). In mice treated with PA-MSHA before inoculating gastric cancer cells, we noted alleviated PD toward the untreated mice. In conclusion, our findings demonstrated that PA-MSHA can stimulate PMSM towards an M1 phenotype and that activated PMSM inhibit gastric cancer growth and PD both in vitro and in vivo. The results of the current study provide a mechanistic insight that is relevant to the potential application of PA-MSHA in the treatment of gastric cancer-mediated PD.

Transforming growth factor-beta1 signaling blockade attenuates gastric cancer cell-induced peritoneal mesothelial cell fibrosis and alleviates peritoneal dissemination both in vitro and in vivo.

Peritoneal dissemination is the most frequent metastatic pattern of advanced gastric cancer and the main cause of death in gastric cancer patients. Transforming growth factor-beta1 (TGF- ß1), one of the most potent fibrotic stimuli for human peritoneal mesothelial cells, has been shown to play an important role in this process. In this study, we investigated the effect of TGF- ß1 signaling blockade in gastric cancer cell (GCC)-induced human peritoneal mesothelial cell (HPMC) fibrosis. HPMCs were cocultured with the high TGF- ß1 expressing GCC line SGC-7901 and various TGF- ß1 signaling inhibitors or SGC-7901 transfected with TGF-ß1-specific siRNA. HPMC fibrosis was monitored on the basis of morphology. Expression of the epithelial cell marker, E-cadherin, and the mesenchymal marker, α-smooth muscle actin (α-SMA), was evaluated by Western blotting and immunofluorescence confocal imaging. GCC adhesion to HPMC was also assayed. In nude mouse tumor model, the peritoneal fibrotic status was monitored by immunofluorescent confocal imaging and Masson's trichrome staining; formation of metastatic nodular and ascites fluid was also evaluated. Our study demonstrated that GCC expressing high levels of TGF-ß1 induced HMPC fibrosis, which is characterized by both upregulation of E-cadherin and downregulation of α-SMA. Furthermore, HPMC monolayers fibrosis was reversed by TGF- ß1 signaling blockade. In vivo, the TGF- ß1 receptor inhibitor SB-431542 partially attenuated early-stage gastric cancer peritoneal dissemination (GCPD). In conclusion, our study confirms the significance of TGFß1 signaling blockade in attenuating GCPD and may provide a therapeutic target for clinical therapy.

[Preventive administration of antibiotics to patients with benign prostatic hyperplasia before urodynamic examination].

OBJECTIVE: To discuss the effect and safety of preventive administration of antibiotics to patients with benign prostatic hyperplasia (BPH) before urodynamic examination. METHODS: A total of 256 BPH patients to undergo urodynamic examination were randomly divided into a control group (n = 118) and a trial group (n = 138). The former received no pre-treatment while the latter were given cefoxitin sodium iv at 1.0 g 30 minutes before complete urodynamic examination. Then we compared the incidence rates of urinary tract infection between the two groups. RESULTS: Statistically significant differences were found in the incidence rate of urinary tract infection between the control and trial groups (20.3% [24/118] vs 7.3% [10/138], P < 0.01), as well as in those with diabetes mellitus (6.7% [3/45] vs 23.5% [8/34], P < 0.05), those with residual urine > 50 ml (5.4% [3/56] vs 18.5% [10/54], P < 0.05), and those with both diabetes mellitus and residual urine (9.5% [2/21] vs 44.4% [8/18], P < 0.05). Only 3 patients (2.2%) in the trial group had mild adverse drug reactions. CONCLUSION: For BPH patients, particularly those with diabetes mellitus and residual urine, preventive administration of antibiotics before urodynamic examination is safe and can effectively protect the patients against urinary tract infection.

Starch derivative-based superabsorbent with integration of water-retaining and controlled-release fertilizers.

Phosphate rock (PHR), a traditional fertilizer, is abundant, but is hard to be utilized by plants. To improve the utilization of PHR, and to integrate water-retaining and controlled-release fertilizers, an agricultural superabsorbent polymer based on sulfonated corn starch/poly (acrylic acid) embedding phosphate rock (SCS/PAA/PHR) was prepared. PHR can be suspended and well-dispersed in SCS/PAA by sulfonated corn starch (SCS). PHR and KOH were mixed in acrylic acid solution to provide phosphorus (P) and potassium (K) nutrients, respectively. Impacts on water absorption capacity of the superabsorbent were investigated. The maximum swelling capacity in distilled water or 0.9 wt.% (weight percent) NaCl solution reached 498 g g(-1) and 65 g g(-1) (water/prepared dry superabsorbent) respectively. Moreover, release behaviours of P and K in SCS/PAA/PHR were also investigated. The results showed that SCS/PAA/PHR possessed excellent sustained-release property of plant nutrient, and the SCS/PAA could improve the P release greatly. Besides, the XPS analysis was employed to study the relationship between PHR and superabsorbent polymer.

Beclin 1 expression is an independent prognostic factor for gastric carcinomas.

Beclin 1, an important autophagy-related protein in human cells, is involved in autophagy, differentiation, anti-apoptosis, and cancer progression, which is increased during periods of cell stress and extinguished during the cell cycle. In order to clarify the role of Beclin 1 in gastric carcinogenesis and subsequent progression, its expression was examined by immunohistochemistry and in situ hybridization (ISH) on tissue microarrays containing gastric carcinomas, adjacent non-neoplastic mucosa, and metastatic lymph node. Gastric carcinoma tissue and cell lines were studied for Beclin 1 expression by Western blot or RT-PCR, respectively. The results demonstrated that Beclin 1 was distinctively expressed in GES-1, AGS, BGC-823, GT-3 TKB, HGC-27, KATO-III, MGC-803, MKN28, MKN45, SCH, SGC-7901, or STKM-2 at both mRNA and protein levels. However, Beclin 1 mRNA was highly expressed in gastric carcinoma than matched mucosa by real-time PCR and ISH (P < 0.05). Beclin 1 expression was negatively related to distant metastasis and poor prognosis of gastric carcinoma (P < 0.05). Beclin 1 was highly expressed in male than female patients with gastric carcinoma (P < 0.05). The 65-year-elder patients with gastric carcinoma had higher Beclin 1 expression than the younger ones (P < 0.05). The diffuse-type carcinomas showed less Beclin 1 expression than intestinal- and mixed-type ones (P < 0.05). In intestinal-type gastric carcinoma, Beclin 1 expression was inversely associated with venous invasion, lymph node metastasis, and tumor-node-metastasis (TNM) staging (P < 0.05). Kaplan-Meier analysis indicated that Beclin 1 expression was positively linked to favorable prognosis of the patients with overall and intestinal-type carcinoma (P < 0.05). Cox's proportional hazard model indicated that venous invasion, lymph node metastasis, distant metastasis, TNM staging, and Beclin 1 expression were independent prognostic factors for gastric carcinomas (P < 0.05). It was suggested that aberrant Beclin 1 expression is closely linked to pathogenesis, metastasis, and differentiation of gastric carcinoma. Beclin 1 expression might be employed to indicate the favorable prognosis of gastric carcinomas as an independent factor.

Aberrant SERCA3 expression is closely linked to pathogenesis, invasion, metastasis, and prognosis of gastric carcinomas.

Sarco (endo)plasmic reticulum Ca(2+)-ATPase (SERCAs) 3 is involved in calcium mobilization from endoplasmic reticulum into cytosol and closely links to metabolism, neuronal plasticity, gene transcription, cell growth, differentiation, apoptosis, protein folding, and carcinogenesis. To clarify the role of SERCA3 in gastric carcinogenesis and subsequent progression, its expression was examined by immunohistochemistry and in situ hybridization (ISH) on tissue microarrays containing gastric carcinomas, adjacent non-neoplastic mucosa (NNM), and metastatic lymph node. SERCA3 expression was studied in gastric carcinoma tissue and cell lines by Western blot, reverse transcriptase-polymerase chain reaction, or immunofluorescence. The results demonstrated that SERCA3 was distinctively expressed in GES-1, AGS, BGC-823, GT-3TKB, HGC-27, KATO-III, MGC-803, MKN28, MKN45, SCH, SGC-7901, and STKM-2 at both mRNA and protein levels. The carcinomas showed higher SERCA3 mRNA expression than the matched NNM by real-time PCR and ISH (P > 0.05). Immunohistochemically, SERCA3 expression was decreased from gastric NNM, primary to metastatic carcinoma (P > 0.05). SERCA3 expression was negatively related to depth of invasion, distant metastasis, and tumor node metastasis (TNM) staging (P > 0.05), but not to age, sex, lymphatic or venous invasion, or lymph node metastasis (P > 0.05). Kaplan-Meier analysis indicated that SERCA3 expression was positively associated with favorable prognosis of the patients with gastric carcinoma (P > 0.05). Cox's proportional hazard model indicated that venous invasion, distant metastasis and TNM staging (P > 0.05) were independent prognostic factors for gastric carcinomas. It was suggested that downregulated SERCA3 expression is closely linked to pathogenesis, invasion, metastasis, and prognosis of gastric carcinomas. It might be employed to indicate the pathobiological behaviors and prognosis of gastric carcinomas.

Sugarcane bagasse derivative-based superabsorbent containing phosphate rock with water-fertilizer integration.

To improve the water-fertilizer utilization ratio and mitigate the environmental contamination, an eco-friendly superabsorbent polymer (SPA), modified sugarcane bagasse/poly (acrylic acid) embedding phosphate rock (MSB/PAA/PHR), was prepared. Ammonia, phosphate rock (PHR) and KOH were admixed in the presence of acrylic acid to provide nitrogen (N), phosphorus (P) and potassium (K) nutrients, respectively. Impacts on water absorption capacity of the superabsorbent polymer (SAP) were investigated. The maximum swelling capacity in distilled water and 0.9 wt.% (weight percent) NaCl solution reached 414 gg(-1) and 55 gg(-1) (water/prepared SAP), respectively. The available NPK contents of the combination system were 15.13 mgg(-1), 6.93 mgg(-1) and 52.05 mgg(-1), respectively. Moreover, the release behaviors of NPK in the MSB/PAA/PHR were also studied. The results showed that the MSB/PAA/PHR has outstanding sustained-release plant nutrients property.

Study on the skip metastasis of axillary lymph nodes in breast cancer and their relation with Gli1 expression.

The skip metastasis (SM) of axillary lymph nodes (ALN) in breast cancer is an important phenomenon which is crucial to determine the correct choice of surgical resection. The mechanism of SM of ALN is unclear. Gli1 protein is a core epithelial-to-mesenchymal transition (EMT) regulatory factor that plays essential roles in both development and disease processes and has been associated with metastasis in carcinomas. The aim of this study was to investigate the clinicopathological characteristics of SM and evaluate the significance of Gli1 expression in breast cancer patients with metastasis of ALN. Clinicopathological data from 1,037 female breast cancer patients who underwent radical mastectomy were retrospectively reviewed. In this study, an SM was defined as level I absence but level II and/or level III involvement. The expression of Gli1 was evaluated by immunohistochemistry in 102 non-SM cases with positive nodes and 33 SM cases. In univariate analysis, we found that pN category, TNM stage, intrinsic subtypes and Gli1 expression was significant risk factor of SM. Further logistic regression analysis revealed that luminal A cases had a lower risk of SM relative to luminal B 1 (HER2 negative) cases. Further multivariate analysis revealed that Gli1 expression and numbers of positive lymph nodes were the independent factors which associated with SM. Collectively, Breast cancer with SM of ALN associated with the intrinsic subtype of the luminal B1. Gli1 expression related with the procession of breast cancer with SM, which can be used as a predictor of SM of ALN in breast cancer.

MTA1 expression correlates significantly with ER-alpha methylation in breast cancer.

Metastasis tumor antigen 1 (MTA1), a novel candidate metastasis-associated gene, is known to increase the migration and invasion of various tumor cells in vitro. It also plays an important role in tumorigenesis and tumor aggressiveness of breast cancer. Estrogen receptor alpha (ERα) plays an important role in the etiology of breast cancer and has been widely accepted as a prognostic marker for breast cancer and a response predictor for endocrine therapy. The ERα gene methylation has been linked to the lack of ERα expression in breast cancer. The aim of the study is to assess the correlation between the ERα methylation and MTA1 expression in breast cancer and further to investigate whether the repressed ERα methylation can downregulate the expression of MTA1 in vitro. In general, we found ERα methylation had significant correlation with the MTA1 expression (p < 0.05) in female patients of breast cancer (n = 102) by methylation-specific polymerase chain reaction and immunohistochemistry. To gain a deeper insight into the molecular mechanism underlying the relation between MTA1 and ERα methylation, we treated the invasive breast cancer cell lines with the demethylating agent, found the downregulation of MTA1 protein expression, and mRNA with the unmethylation of ERα (p < 0.05). And the invasive ability of breast cancer cells was significantly positively associated with MTA1 expression. These unique findings have greatly extended our current knowledge about the relation between ERα methylation and MTA1 expression. These data strongly support the hypothesis that methylation is involved in the relation between MTA1 and ERα in breast cancer.

Midkine confers Adriamycin resistance in human gastric cancer cells.

Midkine (MDK) is a heparin-binding molecule involved in the regulation of growth and differentiation during embryogenesis, which is overexpressed in most of human malignant tumors and may act as an oncoprotein. The aim of the current study was to investigate the mechanism of MDK involved in the Adriamycin (ADR) resistance in human gastric cancer cells in vitro. We found that Adriamycin-resistant SGC7901 (SGC7901/ADR) exhibited 58.6-fold greater resistance to ADR compared with Adriamycin-sensitive SGC7901 cell line. MDK mRNA and protein expression levels were significantly higher in SGC7901/ADR than in SGC7901. To gain a deeper insight into the role of MDK in SGC7901/ADR, we stably transfected Adriamycin-sensitive SGC7901 with viral vector expressing MDK. Our result showed that multidrug resistance type I (MDR1) was found in SGC7901/ADR, not in SGC7901 by RT-PCR regardless of MDK transfection. P-Glycoprotein, which is the MDR1-coded protein, was found in SGC7901/ADR, not in SGC7901 by Western blot regardless of MDK transfection. We investigated whether an activation of the tyrosine kinase pathway would change the drug resistance phenotype with MDK transfection. Western blot results showed the upregulation of phosphorylated protein kinase B (AKT) and phosphorylated extracellular signal-regulated protein kinase (ERK) in Adriamycin-sensitive SGC7901 cell by MDK transfection accompanied with drug resistance to ADR, although the level of AKT and ERK protein expression did not change, so our results suggested that MDK, which can activate AKT and ERK by phosphorylation, induced the Adriamycin resistance in gastric cancer cells. Understanding the molecular mechanisms, driving MDK-induced ADR resistance, will provide benefits in developing new therapies for gastric cancer.

Promoter methylation status and expression of estrogen receptor alpha in familial breast cancer patients.

The hypermethylation of estrogen receptor alpha (ERα) promoter is a common molecular alteration in sporadic breast cancer (BC), but its involvement in familial BC remains largely unknown. In the present study, we analyzed the methylation statuses of four regions (ER1, ER3, ER4, and ER5) of the ERα promoter and the ERα expression levels of 113 familial BC patients in a Han Chinese Population from northeastern China and evaluated the association between major clinicopathological features and the hypermethylation statuses of the ERα gene. Tumor samples were analyzed for ERα methylation status by the methylation-specific polymerase chain reaction for ERα, PR, p53, BRCA-1, and BRCA-2 by immunohistochemical (IHC) staining and for Her-2 status by IHC and fluorescence in situ hybridization (FISH). ERα methylation was observed in tumor tissues in 47/113 (41.6%) familial BC patients. There were no significant differences in the methylation statuses among ER1 (20.4%), ER3 (18.6%), ER4 (17.7%), and ER5 (19.5%; χ (2) = 3.89, p > 0.05). An association between ERα expression level and its promoter methylation level was found. In addition, ERα methylation was significantly correlated with tumor size, PR expression, p53 nuclear accumulation, and BRCA-1 and BRCA-2 statuses. In conclusion, in familial BC patients, the level of ERα gene promoter methylation correlates with ERα expression, PR, p53 nuclear accumulation, and BRCA-1 and BRCA-2 statuses. Epigenetic alteration of ERα gene may play an important role in the pathogenesis of familial BC.

Elevated p-CREB-2 (ser 245) expression is potentially associated with carcinogenesis and development of breast carcinoma.

CREB-2, also known as ATF-4, belongs to the CREB proteins, a family of transcription factors phosphorylated at serine residues by protein kinase A (PKA). This family is known to stimulate the transcription of genes containing CRE elements. Recently, some studies have demonstrated elevated CREB-2 expression in certain tumor types, including breast carcinoma, compared to their corresponding non-tumor tissues. However, the expression and clinical significance in malignant tumors, including breast carcinoma, of p-CREB-2 (ser 245), a phosphorylated form of the CREB-2 protein at serine 245 site, which is believed to be an active type of this protein, have not been clearly documented. In the present study, we investigated the expression of p-CREB-2 (ser 245) in a group of tumor and non-tumor breast tissues, including normal breast epithelia, hyperplasia, dysplasia, carcinoma in situ and infiltrating carcinoma of the breast using tissue microarray and immunohistochemistry (IHC). p-CREB-2 (ser 245) immunostaining was detected in the nucleus and cytoplasm of these tissues. Compared to normal breast epithelia and breast hyperplasia (total positive rate 13.3%), there was increased expression of p-CREB-2 (ser 245) in dysplasia, carcinoma in situ (total positive rate 35.7%) and infiltrating carcinoma of the breast (total positive rate 60.0%) (p<0.05). The highest expression of p-CREB-2 (ser 245) was found in infiltrating breast carcinoma (total positive rate 60%) compared to normal breast epithelia and all types of non-infiltrating lesions (total positive rate 27.6%) (p<0.05). In addition, increased expression of p-CREB-2 (ser 245) was found to be associated with lymph node metastasis in infiltrating breast carcinoma (p<0.05). Immunofluorescent staining confirmed stronger staining of p-CREB-2 (ser 245) in breast cancer MCF 7 and MDA-MB-231 cells compared with normal breast epithelial MCF 10A cells. Western blotting revealed elevated expression levels of p-CREB-2 (ser 245) in 17 cases of breast carcinoma compared with corresponding normal breast tissues (p<0.05). These results indicate that elevated expression of p-CREB-2 (ser 245) may potentially contribute to carcinogenesis and cancer development of breast carcinoma.

MTA1 expression correlates significantly with cigarette smoke in non-small cell lung cancer.

Metastasis tumor antigen 1 (MTA1), a novel candidate metastasis-associated gene, is known to increase the migration and invasion of various tumor cells in vitro. Expression of MTA1 has been shown to be closely correlated with aggressiveness in a variety of human cancers including non-small cell lung cancer (NSCLC). Cigarette smoke is the most established risk for lung carcinogenesis; however, its effects on the progression of NSCLC are still unclear. In this study, we investigated MTA1 expression and analyzed its association with cigarette smoke in NSCLC by immunohistochemistry. To gain a deeper insight into the molecular mechanism underlying the relation between MTA1 and cigarette smoke, we treated the NSCLC cell lines with cigarette smoke extract (CSE). MTA1 mRNA levels and proteins were detected in NSCLC cell lines via reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis. Matrigel invasion assay was performed to evaluate cell invasive ability with the treatment of CSE. Immunohistochemical analysis showed MTA1 expression in NSCLC (61/96, 63.5%) was higher than that in adjacent normal lung tissues (15/96, 15.6%; p < 0.05). Moreover, it was significantly associated with smoking history (p < 0.05). The results of RT-PCR and western blotting showed the upregulation of MTA1 after the treatment of CSE in NSCLC cell lines. Matrigel invasion assays showed that MTA1 upregulation and cell invasion was accompanied with the treatment of CSE in the NSCLC cell lines. MTA1 expression correlated with cigarette smoke in NSCLC and suggested that it may play an important role in the smoked-related progress of NSCLC.