Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer.

Colorectal cancer (CRC) is the most common digestive malignancy across the world. Its first-line treatments applied in the routine clinical setting include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, resistance to therapy has been identified as the major clinical challenge that fails the treatment method, leading to recurrence and distant metastasis. An increasing number of studies have been attempting to explore the underlying mechanisms of the resistance of CRC cells to different therapies, which can be summarized into two aspects: (1) The intrinsic characters and adapted alterations of CRC cells before and during treatment that regulate the drug metabolism, drug transport, drug target, and the activation of signaling pathways; and (2) the suppressive features of the tumor microenvironment (TME). To combat the issue of therapeutic resistance, effective strategies are warranted with a focus on the restoration of CRC cells' sensitivity to specific treatments as well as reprogramming impressive TME into stimulatory conditions. To date, nanotechnology seems promising with scope for improvement of drug mobility, treatment efficacy, and reduction of systemic toxicity. The instinctive advantages offered by nanomaterials enable the diversity of loading cargoes to increase drug concentration and targeting specificity, as well as offer a platform for trying the combination of different treatments to eventually prevent tumor recurrence, metastasis, and reversion of therapy resistance. The present review intends to summarize the known mechanisms of CRC resistance to chemotherapy, radiotherapy, immunotherapy, and targeted therapy, as well as the process of metastasis. We have also emphasized the recent application of nanomaterials in combating therapeutic resistance and preventing metastasis either by combining with other treatment approaches or alone. In summary, nanomedicine is an emerging technology with potential for CRC treatment; hence, efforts should be devoted to targeting cancer cells for the restoration of therapeutic sensitivity as well as reprogramming the TME. It is believed that the combined strategy will be beneficial to achieve synergistic outcomes contributing to control and management of CRC in the future.

Serum albumin guided plasmonic nanoassemblies with opposite chiralities.

Chiral assemblies by combining natural biomolecules with plasmonic nanostructures hold great promise for plasmonic enhanced sensing, imaging, and catalytic applications. Herein, we demonstrate that human serum albumin (HSA) and porcine serum albumin (PSA) can guide the chiral assembly of gold nanorods (GNRs) with left-handed chiroptical responses opposite to those by a series of other homologous animal serum albumins (SAs) due to the difference of their surface charge distributions. Under physiological pH conditions, the assembly of HSA or PSA with GNRs yielded left-handed twisted aggregates, while bovine serum albumin (BSA), sheep serum albumin, and equine serum albumin behaved on the contrary. The driving force for the chiral assembly is mainly attributed to electrostatic interaction. The opposite chiroptical signals acquired are correlated with the chiral surface charge distributions of the tertiary structures of SAs. Moreover, the chirality of the assembly induced by both HSA and BSA can be enhanced or reversed by adjusting the pH values. This work provides new insights into the modulation of protein-induced chiral assemblies and promotes their applications.

Identification of an MiRNA-mRNA Regulatory Network in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is the fourth most prevalent cancer in the world. However, the molecular mechanism underlying CRC is largely unknown. OBJECTIVE: To explore the pathogenic mechanism of CRC and to facilitate better diagnosis and treatment of this disease. METHODS: Differentially expressed miRNAs (DEMs) and genes (DEGs) in CRC vs. Control samples from the miRNA expression data in GSE115513 and the miRNA and mRNA expression data in the TCGA-COAD dataset were screened, followed by the construction of the miRNAmRNA regulatory network. Functional and pathway enrichment analysis, protein-protein interaction (PPI) analysis, and survival analysis were then performed for these DEGs and DEMs. RESULTS: We identified 64 DEMs from the GSE115513 dataset and 265 DEMs and 2218 DEGs from the TCGA-COAD dataset. miR-27a-3p was a hub DEM with the highest degree in the miRNA-mRNA network, while GRIN2B and PCDH10 were hub DEGs targeted by multiple miRNAs, including miR-27a-3p. SNAP25 and GRIN2B were also hub DEGs with the highest degree of interactions in the PPI network. These DEMs and DEGs were significantly enriched in multiple KEGG pathways, including proteoglycans expression and cAMP signaling pathway in cancer. Finally, seven DEGs, including FJX1 Dsc2, and hsa-miR-375, were revealed to be correlated with CRC prognosis. CONCLUSION: Aberrant expressions of genes and miRNAs were involved in the pathogenesis of CRC, probably by regulating proteoglycans expression and cAMP signaling. miR-27a-3p, PCDH10, GRIN2B, FJX1, Dsc2, and hsa-miR-375 were identified as potential targets for understanding the pathogenic mechanism of CRC. In addition, FJX1, Dsc2 and hsa-miR-375 were identified as potential predictive markers for CRC prognosis.

EIF4E regulates STEAP1 expression in peritoneal metastasis.

Gastric cancer is the most prominent form of malignancy in China, and the high mortality associated with it is mostly due to peritoneal metastasis. We have previously elucidated that the RNA-binding protein poly r(C) binding protein 1 (PCBP1) and miR-3978 function as repressors of peritoneal metastasis, partially by downregulation of six-transmembrane epithelial antigen of the prostate 1 (STEAP1). We now show that STEAP1 is regulated at the level of cap-dependent translation initiation by phosphorylated eIF4E. Chemically inhibiting phosphorylation of eIF4E or genetic ablation of phosphorylated eIF4E inhibit translational upregulation of STEAP1 in the peritoneal metastasis mimicking cell line MKN45 in comparison to the normal mesothelial cell line HMrSV5. Thus phosphorylation of eIF4E is required for peritoneal metastasis of gastric cancer via translational control of STEAP1. Chemical inhibitors targeting phosphorylation of eIF4E or its interaction with the translation initiation complex thus might prove effective in treating patients with peritoneal metastasis.

MicroRNA (miR)-597-5p Inhibits Colon Cancer Cell Migration and Invasion by Targeting FOS-Like Antigen 2 (FOSL2).

Our previous work had shown that FOS-like antigen 2 (FOSL2) is regulated by miR-143-5p in colorectal cancer (CRC). Given that it has been shown by others that FOSL2 is also a target of miR-597-5p in breast adenocarcinoma, the objective of the current work was to determine whether FOSL2 is regulated by miR-597-5p in CRC and the role of miR-597-5p in CRC. MiR-597-5p expression was determined in RNA obtained from 30 paired samples of colon cancer and tumor adjacent normal tissue, as well as in the LoVo (CRC cell line) and FHC (normal colonic epithelial cells) by quantitative real time polymerase chain reaction (qRT-PCR). MiR-597-5p expression was significantly downregulated in both CRC tissue and LoVo cells. Reporter assays using wild-type and miR-597-5p seed mutant FOSL2 confirmed that FOSL2 is a bona fide target of miR-597-5p. Modulating miR-597-5p expression levels in FHC and LoVo cells using antagomir and mimic, respectively, impacted expression of epithelial and mesenchymal cell markers as well as in vitro migration and invasion, without any effect on cell proliferation, showing that miR-597-5p functions as a suppressor of epithelial to mesenchymal transition. Restoration of FOSL2 expression rescued pro-metastatic functional properties of LoVo cells conforming that effect of miR-597-5p was being mediated by targeting FOSL2. Xenograft assays in athymic nude mice showed that miR-597-5p mimic did not reduce tumor incidence or growth in LoVo cells. However, using a hepatic metastasis model showed that miR-597-5p mimic can significantly prevent hepatic metastatic nodule formation as well as FOSL2 expression in these metastatic nodules. Importantly, FOSL2 mRNA and miR-597-5p expression was found to be inversely correlated in an independent cohort of 21 CRC patients Cumulatively our results show that miR-597-5p functions as a suppressor of metastatic progression in CRC by targeting FOSL2. Replenishment of miR-597-5p can be a potential therapeutic target where its expression along with FOSL2 can serve as potential diagnostic markers in CRC.

STEAP1 Regulates Tumorigenesis and Chemoresistance During Peritoneal Metastasis of Gastric Cancer.

In China, majority of the mortality in gastric cancer are associated with peritoneal metastasis. Since most gastric tumors are metastatic at initial diagnosis, the treatment of gastric cancer is limited to radical resection. Therefore, it is imperative to identify diagnostic and prognostic biomarkers. From 2014 to 2015, 20 patients were enrolled in the study. To search translationally upregulated genes in the context of epithelial to mesenchymal transition (EMT), polysome profiling was performed. The MTT, migration, and invasion assay were conducted to determine cell proliferation, migration, and invasion ability respectively. Experiments of gain and loss of function were performed using the overexpression plasmid, siRNA, and shRNA. Xenograft assay was established using nude mice to explore the role of targets translationally upregulated gene in vivo. Polysome profiling defined the landscape of translationally regulated gene products with differential expression between non-metastatic and metastatic cohorts. Six-transmembrane epithelial antigen of the prostate 1 (STEAP1) was found to be the most translationally upregulated gene product in either experimental groups. STEAP1 was found to be required for cell proliferation, in vitro migration and invasion, and in vivo tumorigenesis. RNAi-mediated silencing of STEAP1 potentiated chemosensitivity of the MKN45 cells to docetaxel treatment, highlighting the importance of STEAP1 as a novel biomarker in gastric cancer patients with peritoneal metastasis. STEAP1 is thus induced translationally and its expression promotes proliferation, migration, invasiveness, and tumorigenicity of gastric cancer. STEAP1 can be a potent candidate for designing of targeted therapy.

Fos-like antigen 2 (FOSL2) promotes metastasis in colon cancer.

Among different cancers, incidence and mortality of colorectal cancer (CRC) is one of the highest. KRAS mutation is one of the underlying features in the pathogenesis of CRC with CRC tumors harboring mutant KRAS exhibiting a more aggressive behavior compared to CRC tumors with wild type KRAS. We had earlier shown that the microRNA-143 (miR-143) replenishment not only chemosensitizers CRC cell line with mutant KRAS instead of wild-type KRAS gene, to paclitaxel-mediated cytotoxicity, but also inhibits cell migration and invasion ability. Hence, the study aimed to determine how miR-143 replenishment is inhibiting pre-metastatic behavior in CRC cells with mutant KRAS. Top ten mRNA targets of miR-143 as predicted by TargetScan were evaluated by qRT-PCR in LoVo cells which were performed mock transfection or miR-143 mimic transfection. Evaluation of the changes in cognate mRNA target(s) was done in 30 paired CRC tissue and tumor adjacent normal tissue specimens and in LoVo cells by western blot. Effect of the mRNA target on pro-metastatic behavior was assayed by gain- and loss-of-function studies using a combination of western blotting and in vitro cell proliferation and transwell migration/invasion assay in LoVo cells and in the normal colonic epithelium cell line FHC. In vivo effect of the cognate mRNA target on CRC metastasis was assayed by xenograft assay. Of the 10 predicted mRNA targets, FOSL2 (P < 0.05) and IGFBP5 (P > 0.05) was down regulated in LoVo cells transfected with the miR-143 mimic. FOSL2 mRNA levels were significantly downregulated in CRC tissue specimens compared with adjacent normal tissue (P < 0.05). Immunoblot analysis showed that FOSL2, but not IGFBP5, protein expression is down regulated in LoVo cells after the miR-143 mimic transfection. FOSL2 overexpression in the normal colonic epithelial cell line FHC or siRNA-mediated silencing in LoVo cells induced and repressed, respectively, pro-mesenchymal cell features. Whereas manipulation of FOSL2 expression did not have any effect on cell proliferation rates, silencing its expression inhibited cell migration and invasion ability in vitro. In addition, silencing of FOSL2 expression in the LoVo cells can significantly inhibited invasion of hepatic, while no effect was found for tumorigenic potential. Our results suggest that FOSL2 is a critical regulator of CRC metastasis and might be an important marker for prognostic in CRC patients.

Author Correction: Expression of both poly r(C) binding protein 1 (PCBP1) and miRNA-3978 is suppressed in peritoneal gastric cancer metastasis.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Expression of both poly r(C) binding protein 1 (PCBP1) and miRNA-3978 is suppressed in peritoneal gastric cancer metastasis.

The expression of legumain which has been shown overexpressed in patients with metastatic gastric cancer is positively correlated to both disease progression and outcome, and negatively correlated to microRNA (miR)-3978 expression. The RNA-binding protein, poly r(C) binding protein 1 (PCBP1) was the most downregulated protein in the metastatic tissue specimens. Quantitative real-time PCR showed that PCBP1 expression is transcriptionally downregulated in peritoneal metastasis tissues. RNA immunoprecipitation experiments showed that PCBP1 and miR-3978 are sequestered in normal peritoneal tissue, but the complex is disrupted following metastatic progression. PCBP1 expression mimicked miR-3978 expression across gastric cancer patients. Finally, replenishment of PCBP1 or miR-3978 expression in the peritoneal metastasis cell line MKN45 decreased legumain protein expression and chemosensitized the cells to treatment with docetaxel. However, replenishment of one and concomitant depletion of the other failed to induce chemosensitivity to docetaxel. Replenishment of miR-3978 also resulted in induction of PCBP1 protein expression, potentially indicating that miR-3978 expression might downregulate a negative regulator targeting PCBP1. Our current study reveals PCBP1 as an additional biomarker in peritoneal metastasis. PCBP1 and miR-3978 expression were correlated and suggests a potential interplay of differential miRNA biogenesis and RNA binding protein during metastatic progression.

MiRNA-3978 regulates peritoneal gastric cancer metastasis by targeting legumain.

Gastric cancer incidence and mortality are among the highest in China, with majority of the mortality related to peritoneal metastasis of gastric cancer. Treatment is limited to radical resection, which is impeded by incidence of metastasis at time of initial diagnosis, thus making it imperative to identify diagnostic and prognostic biomarkers. Legumain, a lysosomal cysteine endopeptidase of the asparaginyl endopeptidase family, has been shown to be overexpressed in patients with metastatic gastric cancer disease and its expression was positively correlated to both disease progression and outcome. However, the mechanism of legumain expression is currently unknown. Legumain overexpression was found to occur at the level of post transcriptional gene regulation. In situ prediction algorithms identified legumain as a putative target of miR-3978. MiR-3978 was significantly decreased in peritoneal metastatic tissue specimens and in MKN45 cells that mimic peritoneal metastasis features. Reporter assays using LGMN (encoding legumain) 3' untranslated region (UTR) showed that miR-3978 interacted with the wild-type but not miR-3978-seed mutant. Ectopic expression of miR-3978 mimic in the MKN45 cell line significantly decreased proliferation and suppressed in vitro migration and invasion. The miR-3978 mimic inhibited gastric carcinoma and metastatic progression in a mice model by regulating legumain protein expression. Inverse correlation of LGMN mRNA and miR-3978 levels in 20 gastric patients at different stages of metastatic disease confirmed the same. Cumulatively, our results indicate that loss of miR-3978 leads to increased expression of legumain, which indicates that miR-3978might be a biomarker for peritoneal metastasis in patients with gastric cancer.

Waterborne exposure to bisphenol F causes thyroid endocrine disruption in zebrafish larvae.

While bisphenol F (BPF) has been frequently detected in various environmental compartments, limited information is available on its effect on thyroid endocrine system. In the present study, zebrafish (Danio rerio) embryos were exposed to 0.2, 2, 20, and 200 µg/L of BPF from 2 h post-fertilization (hpf) to 144 hpf. The whole-body content of thyroid hormones, thyroid-stimulating hormone (TSH), and transcription of genes belonging to the hypothalamic-pituitary-thyroid (HPT) axis were investigated. BPF exposure resulted in alterations of both T3 and T4 contents, increased the ratios of T3/T4, demonstrating thyroid endocrine disruption. Moreover, TSH content was significantly induced in a concentration-dependent manner after exposure to BPF. The increased gene transcription of dio2 might assist to degrade increased T3 contents. Treatment with BPF also significantly increased transcription of genes involved in thyroid hormone regulation (crh) and synthesis (nis and tg) as a compensatory mechanism for the decrease of T4 contents. However, the gene encoding protein involved in TH transport (ttr) was transcriptionally significantly down-regulated after exposure to BPF. Taken together, these results suggest that BPF alters the transcription of genes involved in the HPT axis as well as changes whole-body contents of thyroid hormones and TSH in zebrafish embryos/larvae, thus causing an endocrine disruption of the thyroid system.

MicroRNA-143 replenishment re-sensitizes colorectal cancer cells harboring mutant, but not wild-type, KRAS to paclitaxel treatment.

Colorectal cancer (CRC) global incidence is one of the highest among cancers. The KRAS gene has been shown as a robust biomarker for poor prognosis and drug resistance. MicroRNA-143 (miR-143) and let-7 are families of tumor suppressor microRNAs that are often downregulated in CRC, especially with coexistent KRAS mutations. In order to evaluate if miR-143 and/or let-7b replenishment would re-sensitize CRC cells to paclitaxel treatment, we investigated in effect of miR-143 and let-7b replenishments on sensitivity to paclitaxel treatment in KRAS mutant LoVo and wild-type SW48 CRC cell lines. Our results showed that miR-143, but not let-7b, increased sensitization of KRAS mutant tumor cells to paclitaxel. Furthermore, transfection of miR-143, but not let-7b, mimic negatively regulated the expression of mutant but not wild-type KRAS. Combination of miR-143 mimic and paclitaxel induced the onset of apoptosis, and reverted in vitro metastatic properties (migration and invasion) in KRAS mutant tumor cells. MiR-143 thus can be used as a chemosensitizer for the treatment of KRAS mutant tumors and warrants further investigations in in vitro and pre-clinical in vivo models.

A case of annular pancreas accompanied with intraductal papillary mucinous neoplasm-case report.

OBJECTIVES: Annular pancreas is a rare congenital anomaly characterized by pancreatic tissues wrapping completely or incompletely around the descending duodenum. In most patients with annular pancreas, onset occurs in early childhood. Adults with annular pancreas are prone to duodenal ulcers and pancreatitis. Intraductal papillary mucinous neoplasm (IPMN) is a type of papillary mucinous secretory epithelial tumor, which originates in the main pancreatic duct and/or branch duct. We report a case of annular pancreas accompanied with intraductal papillary mucinous neoplasm. METHODS: A 52-year-old male patient hospitalized due to recurrent upper abdominal pain for one and a half years was enrolled in this study. RESULTS: One case of annular pancreas accompanied with intraductal papillary mucinous neoplasm which manifested as recurrent chronic pancreatitis was found. After pancreaticoduodenectomy, the patient died from uncontrollable gastrointestinal bleeding. CONCLUSIONS: To the best of our knowledge, this is the first case in China and the second case worldwide of annular pancreas accompanied with IPMN in English literature.

Expression of eag1 channel associated with the aggressive clinicopathological features and subtype of breast cancer.

BACKGROUNDS: Expression of eag1 channel (Eag1) is associated with cell malignant transformation, tumor cell metastasis and poor prognosis of the patient. This study aimed at examining whether expression of the Eag1 associated with aggressive clinicopathological feature and the molecular subtype of breast cancer. MATERIALS AND METHODS: 109 patients who received breast cancer operation during January 2009 to December 2010 in Chinese-Japanese Friendship Hospital of Jilin University were recruited. We investigated the association of the Eag1 with clinicopathological features and molecular subtype of in triple negative breast cancer (TNBC) by univariate or multivariate analysis in a cross-section study. RESULTS: The positive rate of Eag1 was 18.5% higher in TNBC compared with non-triple negative breast cancer (Non-TNBC) (P = 0.012, OR = 2.83, 95% CI = 2.16-3.47). Compared with the Eag1 negative group, the expression of Eag1 was linked to the larger tumor size (P = 0.002), advanced TNM stage (P = 0.029), high proportion of positive lymph node (87.6% vs. 65%, P = 0.014) and invasive ductal carcinoma (91% vs. 75%, P = 0.046). CONCLUSIONS: The expression of Eag1 may be partially explained the aggressive behavior of TNBC in the breast cancer tissue.

MicroRNA-103 promotes colorectal cancer by targeting tumor suppressor DICER and PTEN.

MicroRNAs (miRNAs) are a class of small, noncoding RNAs that act as key regulators in various physiological and pathological processes. However, the regulatory mechanisms for miRNAs in colorectal cancer remain largely unknown. Here, we found that miR-103 is up-regulated in colorectal cancer and its overexpression is closely associated with tumor proliferation and migration. In addition, repressing the expression of miR-103 apparently inhibits colorectal cancer cell proliferation and migration in vitro and HCT-116 xenograft tumor growth in vivo. Subsequent software analysis and dual-luciferase reporter assay identified two tumor suppressor genes DICER and PTEN as direct targets of miR-103, and up-regulation of DICER and PTEN obtained similar results to that occurred in the silencing of miR-103. In addition, restoration of DICER and PTEN can inhibit miR-103-induced colorectal cancer cell proliferation and migration. Our data collectively demonstrate that miR-103 is an oncogene miRNA that promotes colorectal cancer proliferation and migration through down-regulation of the tumor suppressor genes DICER and PTEN. Thus, miR-103 may represent a new potential diagnostic and therapeutic target for colorectal cancer treatment.

Expression, purification and characterization of human interferon-γ in Pichia pastoris.

Human interferon-γ (hIFN-γ) is a multifunctional protein known to possess immunoregulatory, antiviral and anticancer functions. In the present study, in order to explore the biological roles of hIFN-γ and its mechanisms of action, IFN-γ was cloned and expressed in Pichia pastoris (P. pastoris) under the control of alcohol oxidase promoter 1 (AOX1). The protein was secreted by two different signal peptides, the native secretion signal peptide of hIFN-γ and the Saccharomyces cerevisiae α signal peptide. Following 96 h of methanol induction, Tricine-SDS-PAGE Coomassie staining, western blot analysis and N-terminal protein sequencing revealed that the level of recombinant hIFN-γ (rhIFN-γ) secreted by the native secretion signal was barely detectable, while the α signal peptide secreted ~300 mg/l. rhIFN-γ was purified by Vivaflow 200, SP Sepharose Fast Flow and Vivaspin 2 ml, yielding >96% of a highly purified rhIFN-γ preparation, with a specific activity of 1 x 10(7)-1.4 x 10(7) IU/mg protein as determined by an antiviral assay. The results demonstrated that the experimental procedures developed are capable of producing a large quantity of active rhIFN-γ from P. pastoris.

[Application of totally laparoscopic anastomosis in laparoscopic gastrectomy].

OBJECTIVE: To explore the safety and feasibility of the total laparoscopic anastomosis in laparoscopic gastrectomy. METHODS: Clinical data of 36 patients who received totally laparoscopic anastomosis and another 47 patients who received anastomosis through small incision in our department from July 2012 to July 2013 were retrospectively analyzed. Clinical outcomes were compared between the two groups. RESULTS: The operation was successfully carried out in all the 83 patients. The mean incision length was (7.1±0.9) cm in small incision group and (2.6±0.4) cm in totally laparoscopic group, while the mean time of anastomosis was (70.9±9.0) min and (29.1±4.9) min respectively. Six patients felt moderate pain and 41 felt severe pain in small incision group, while 29 patients felt moderate pain and 7 felt severe pain in totally laparoscopic group. Anastomotic leakage occurred in 1 case after operation in small incision group and there was no related anastomosis complication in totally laparoscopic group. CONCLUSIONS: Total laparoscopic anastomosis is safe and feasible in laparoscopic gastrectomy for gastric cancer. Compared with small incision-assisted anastomosis, totally laparoscopic anastomosis is associated with shorter time and less pain.

Measurement and analysis of facial nerve on fully displayed multislice computed tomographic multiplanar reconstruction image.

The objectives of this study were to measure the length of horizontal segment of facial nerve (HFN), the length of vertical segment of facial nerve (VFN), and the angle between these 2 segments on a fully displayed multislice computed tomographic multiplanar reconstruction (MPR) images of HFN and VFN and to analyze the data with respects to side, sex, and age. Parameters of 234 patients (468 observations, 118 men and 116 women, aged 4-70 years) with intact temporal bone were measured on multislice computed tomographic multiplanar reconstruction images. The data gained were analyzed by statistical method. The left and right lengths of VFN were significantly different (P < 0.05). And the length of HFN, the length of VFN, and the angle between males and females were significantly different (P < 0.05). We divided the data into 3 groups to study correlations between measurements and age. In underaged group, there was a strong positive correlation between the length of VFN and age; the value of Pearson correlation was 0.645. And there was a weak correlation between the angle and the age; the value of Pearson correlation was 0.270. In older-aged group, there was a moderate negative correlation between the length of VFN and age; the value of Pearson correlation was -0.408. Our results are of high potential to expand the visual field to facial nerve and may provide more detailed information to surgeries of facial nerve, middle ear, and temporal bone.

Association between MDM2 SNP309 T>G and risk of gastric cancer: a meta-analysis.

BACKGROUND: As a negative regulator of P53, MDM2 plays an important role in carcinogenesis; a polymorphism in its promoter region. SNP309 T>G, is known to increase the expression of MDM2, thus being considered related to higher susceptibility to neoplasia. However, no agreement has been achieved regarding its effects on gastric cancer. METHODS: The present systematic meta-analysis was performed based on comprehensive literature search from Pubmed, Web of science and CBM databases. RESULTS: It was suggested from 6 independent studies that the GG genotype is associated with a significantly increased risk of gastric cancer (Recessive: OR = 1.43, 95% CI = 1.08-1.91, P = 0.013), and subgroup analysis also confirmed the relationship (English publications-recessive model: OR = 1.45, 95% CI = 1.10-1.91, P = 0.009; Studies in China-recessive model: OR = 1.58, 95% CI = 1.08-2.30, P = 0.017). No publication bias was detected. CONCLUSION: The meta-analysis indicated a significant inverse association between GG genotype carriage and elevated risk of gastric cancer. However, more studies and detailed information are needed to fully address the topic.

[Interpretation of D2 radical operation and en bloc mesogastric excision in gastric cancer].

As a surgical oncology concept, complete mesenteric excision has been widely accepted. As to different organs, in addition to the rectum and the colon, the range or the criteria of the so-called complete mesenterium is not yet entirely clear. For the stomach, the mesogastric structure is so complicated, and the embryology and anatomy of the mesogastrium or the perigastric ligaments differed significantly. Even to perform a resection in accordance with the anatomy plane of mesogatrium, the mesogastric plane is still extended as compared to the current standard D2 radical resection. We therefore propose the concept of surgical mesogastrium, which means that the essence of en bloc mesogastric excision (EME) should be surgical mesogastric resection. In clinical practice, we found that a lot of symmetric similarity exists in stomach and colon, the morphological transformation from stomach to the colon can be accomplished to some extent by extension and folding of the stomach, and striking match exists in the morphology, distribution of the blood vessels, lymphatic drainage and mesenterium (mesogastrium or mesocolon). On this basis, we propose the plane of the surgical mesogastrium, which includes the gastrohepatic ligament, hepatoduodenal ligament, hepatopancreatic folds, splenicpancreatic folds, gastrophrenic ligament, gastrosplenic ligament, gastrocolic ligament (supracolic omentum) and omentum. This surgical mesogastric plane coincides with the current plane of D2 radical resection. This paper further discussed the N staging of gastric cancer. By comparative study of the stomach and the colon, we could re-classify the stomach-associated lymph nodes into three groups, the perigastric, the middle and the roots, which may resolve the long-standing controversy between the Eastern and Western regarding this issue. In addition, we also agree with the presence of lymph node metastasis in the plane outside of the surgical mesogastrium, the so-called lateral lymph node metastasis. As for the N staging of gastrointestinal cancer, we must firstly define the lymph node metastasis as mesenteric (mesogastric or mesocolic lymph node) and extra-mesenteric (later lymph node). In case of lateral lymph node metastasis, which should be considered as M1 stage (distant metastasis) unless there is evidence to suggest lateral lymph node metastasis, otherwise extended lateral lymph node dissection should be avoided. In case of mesenteric (mesogastric or mesocolic) lymph node metastasis, classification should be in accordance with the current NCCN guideline, which was divided by the number of lymph node metastasis (N1-N3).