Screening of flavonoids in Litchi Semen and its targets of intervention in colonic adenocarcinoma by weighted gene co-expression network analysis and molecular docking / 中草药

Objective: To screen the flavonoid constituents and targets of Litchi Semen in the intervention of progression and metastasis of colon adenocarcinoma (COAD). Methods: Through DRAR-CPI and SWISS database, potential targets of 19 flavonoids in Litchi Semen were searched. COAD gene expression data and clinical characteristic data from TCGA database were downloaded. Weighted gene co-expression network analysis (WGCNA) was used to establish the gene co-expression network and identify the co-expression module of COAD. The common targets of co-expression module and potential targets were used as the compound to interfere with the drug target of COAD. Protein interaction network analysis, KEGG and GO analysis were performed by String database. The Hub gene was extracted as potential biomarkers of COAD by the cytoHubba, and the interaction network of components, targets and pathways was established by the Cytoscape. The expressions of potential biomarkers were verified by HPA database, and the compounds were docked with the potential biomarkers. Results: A total of 18 co-expression modules were identified with seven of them were correlated with clinical features, such as survival time and tumor stage. Turquoise module was related to the development and transfer of COAD. 19 flavonoids in Litchi Semen acted on 380 potential targets. 34 targets repeated with turquoise module were selected as targets. GO analysis showed that the target points were enriched in 304 GO items, including 229 biological processes, 31 cell composition and 44 molecular functions; KEGG analysis showed that target points were enriched in cancer pathways, cell cycle, and progesterone-mediated 40 pathways including oocyte cancer pathway, cell senescence, and p53 signaling pathway. The genes of CDC25A, CDC25C, CCNB2 and AURKB were screened by cytoHubba as potential biomarkers which related to the progress and transfer of COAD. Compared with para-cancerous tissues, immunohistochemistry results obtained from HPA database showed that the protein expressions of CDC25C, AURKB and CCNB2 in COAD were increased significantly (P < 0.05), which were consistent with gene expression in TCGA data set. Narirutin, procyanidin A2, phloridzin and ent-epicatechin which were well combined to CDC25A, CDC25C and AURKB through hydrogen bond were screened. Conclusion CDC25A, CDC25C, CCNB2 and AURKB were the potential biomarkers closely related to the progression and metastasis of COAD. The mechanism of intervention of flavonoids in Litchi Semen on the progression and metastasis of COAD may be related to the regulation of biological processes, such as cell division, G2/M phase transformation of cell cycle, and the regulation of cancer pathway, p53 signaling pathway and other signaling pathways. Narirutin, procyanidin A2, phloridzin, ent-epicatechin and rutin could be treated as potential inhibitors of CDC25A, CDC25C and AURKB.

Expression and significance of COX-2 ,MMP-9 and PTEN in colonic adenocarcinoma tissues / 重庆医学

Objective To explore the expression and significance of COX-2 ,MMP-9 and PTEN in colonic adenocarcinoma tissues .Methods Seventy-two cases of pathologically archived paraffin specimens after colonic adenocarcinoma radical operation in the hospital from March 2014 to May 2016 were collected ,30 cases of colonic adenoma tissues and 30 cases of normal mucosal mem-brane tissues served as the controls .The expressions of COX-2 ,MMP-9 and PTEN were detected by adopting the immunohisto-chemical SP method .Then the correlation between COX-2 ,MMP-9 and PTEN with clinicopathological features of colonic adenocar-cinoma was analyzed .Results The positive expression rate of COX-2 and MMP-9 in colonic adenocarcinoma tissues was significant-ly higher than that in colonic adenoma tissues and normal colon mucosal membrane tissues (P<0 .05);the positive expression rate of PTEN was significantly lower than that in colonic adenoma tissues and normal colon mucosal membrane tissues (P<0 .05) .The expression of COX-2 ,MMP-9 and PTEN in colonic adenocarcinoma was correlated with the tumor invasive depth ,lymph node me-tastasis and TNM staging(P<0 .05) ,while had no correlation with sex ,age ,tumor morphology ,tumor size and differentiation de-gree(P>0 .05) .COX-2 ,MMP-9 and PTEN expressions showed negative correlation (r= -0 .260 ,-0 .282 ,P<0 .05) ,COX-2 and MMP-9 expression showed a positive correlation (r=0 .335 ,P=0 .004) .Conclusion The abnormal expression and interaction of COX-2 ,MMP-9 and PTEN are closely correlated with the occurrence ,invasion and metastasis of colonic adenocarcinoma .Their combined detection has an important significance for early diagnosis and prognosis assessment of colonic adenocarcinoma .

A Case of Metastatic Colonic Adenocarcinoma of the Eyelid

PURPOSE: To report a metastatic colonic adenocarcinoma in the left upper eyelid. CASE SUMMARY: A 73-year-old male presented to our clinic with a palpable mass in his left upper eyelid that had appeared 10 days prior. The patient had a history of colon cancer that was diagnosed 2 years previously with liver and lung metastases, and he had underwent colon resection followed by chemotherapy. A 10.7 x 14.7 x 9.0 mm mass was observed on orbital computed tomography and a biopsy confirmed that the mass was a metastatic colonic adenocarcinoma. Because radical resection of the mass could not be performed, a debulking surgery was performed instead. The patient was followed up while receiving conservative treatment, but he died 3 weeks after surgery. CONCLUSIONS: Metastatic tumors in the eyelids are very rare and colonic adenocarcinoma metastases in the eyelids are even less common. Thus, a biopsy examination and appropriate treatment should be administered to patients with a history of malignancy who present with an eyelid mass.

Reseccionea hepáticas en el servicio de cirugía general del Hospital Privado: 13 años de experiencia resecciones hepátidas / Liver resection in hospital privado's general surgery department: 13- year experience liver resections

Las resecciones hepáticas constituyen el tratamiento de elección en las neoplasias hepáticas primárias y en algunos casos de tumores metastáticos, pero conllevan tasas significativas de morbilidad y mortalidad. Objetivo: Presentar nuestra experiencia en cirurgías hepáticas. Material y método: Se incluyeron 40 paciente sometidos a hepatectomías en nuestra Institución desde diciembre de 1991 a diciembre de 2004. Los datos fueron recolectados en forma retrospectiva y analizados mediante método estadístico descriptivo. Resultados: Los diagnósticos incluyeron enfermedades hepáticas primarias benignas (n=9, 22.5%) y malígnas (n=7, 17.5%) y enfermedades hepáticas metastásicas (n=24, 60%). Dentro de las metástasis, la más frecuente fue el adenocarcinoma de colon (n=7, 17.42%). El índice de complicaciones quirúrgicas inmediatas fue del 55% (n=22). Hubo 4 muertees peri-operatorias (10%) y la tasa promedio de estadía hospitalaria fue de 10,8 días. Conclusiones: Nuestros hallazgos demostraron que la indicación más frecuentes de resección hepática en nuestra experiencia es las metástasis de adenocarcinoma de colon y que los resultados observado en nuestra serie son comparables a los obtenidos por otras Instituciones a nivel mundial con similar flujo de pacientes.

Liver resection constitutes the treatment of choice in the liver primary neoplasms and some cases of metastatic tumors, but entail significant morbidity and mortality rates. OBJECTIVE: To present our experience in hepatic surgery. MATERIAL AND METHODS: We included 40 patients who underwent hepatectomies in our Institution from December 1991 through December 2004. The information was collected retrospectively and was analized descriptive and statistically. RESULTS: 40 patients underwent 40 hepatectomies. The diagnosis included primary benign hepatic disease (n= 9, 22.5%), primary hepatic malignancy (n= 7, 17.5%) and metastatic hepatic disease (n= 24, 60%). In the metastatic group, the most frecuent pathology was colonic adenocarcinoma (n= 17, 42%). There were 4 perioperatory deaths (10%) and the average hospitaly stay was 10.8 days. CONCLUSIONS: our data shows that the most frequent indication of hepatic resection in our experience was metastatic colonic adenocarcinoma as compared to the other Institutions with similar experience.

Immunohistochemical Study of Metallothionein Expression in Colonic Adenocarcinoma: Correlation with p53, Topoisomerase II-alpha Expression and Apoptosis

PURPOSE: Although immunohistochemically detectable metallothionein (MT) overexpression has been described in proliferation epithelial tumor cells, the clinical significance of the expression remains to be elucidated. Therefore, the present article is focused on evaluating the possible significance of MT expression in colonic adenocarcinoma and its relationship with p53 overexpression, Topoisomerase II-alpha as new cell proliferating marker and apoptosis. METHODS: The following formalin-fixed paraffin embedded surgical or biopsied samples were immunohistochemically stained for MT, p53 and topoisomerase II-alpha, and performed in situ TUNEL method for evaluation of apoptotic cell ; normal control mucosa (78 cases), tubular adenomas (20 cases) and adenocarcinomas with various degree of differentiation (78 cases). RESULTS: The MT immunohistochmical reactivity was decreased in colonic adenocarcinoma than that of normal glandular epithelial and tubular adenoma, with the frequency of MT expression in colonic adenocarcinoma depending upon tumor differentiation only. But the frequency of p53 expression was correlated with T-stage, lymph node metastasis and clinical staging, while topoisomerase II-alpha expression and apoptosis in colonic adenocarcinoma were correlated with lymph node metastasis and clinical staging. The immunohistochemical expression of MT and p53 expression in colonic adenocarcinoma was inversely correlated. Also, the inverse correlation between MT expression and expression of toposiomerase II-alpha indices and apoptotic indices were noted. CONCLUSION: These data suggest that MT expression may play a role in proliferative activity and apoptosis in colonic adenocarcinoma. Although MT expression is correlated to tumor differentiation, further studies of a possibility of prognostic factor, such as p53, are required for the determination of significant relationships in other clinicinopathologic indices.

Expression of Cytokeratins 7 and 20 in Cholangiocarcinoma and Metastatic Colonic Adenocarcinoma of the Liver

The distinction between cholangiocarcinoma (CC) and metastatic colonic adenocarcinoma of the liver (MCA) is often difficult, particularly in needle biopsy and fine-needle aspiration specimens, if histologic features alone are used. To examine the differences in the expressions of the cytokeratin (CK) 7 and 20 in the CCs and MCAs, we performed immunohistochemical studies on surgically resected 19 CCs and 23 MCAs. We used monoclonal antibodies against CK 7 and CK 20, and applied microwave antigen retrieval technique on formalin-fixed, paraffin-embedded tissue. We interpreted diffuse cytoplasmic reactivity found in > or =5% of tumor cells as positive. CCs showed CK 7+/CK 20- immunophenotype in 63%, CK 7+/CK 20+ in 32%, CK 7-/CK 20+ in 5%, and CK 7-/CK 20- in 0%. MCAs exhibited CK 7-/CK 20+ immunophenotype in 87%, CK 7+/CK 20+ in 9%, CK 7-/CK 20- in 4%, and CK 7+/CK 20- in 0%. CK 20-reactive cells in CCs were frequently columnar in shape (p<0.05). In conclusion, the CK 7/CK 20 immunophenotype was useful in the differentiation of CCs from MCAs: the CK 7+/CK 20- immunophenotype strongly suggested CCs, whereas the CK 7-/CK 20+ immunophenotype strongly suggested MCAs.

The Usefulness of Cytokeratin 7 and Colon Ovarian Tumor Antigen in the Differential Diagnosis of Primary and Metastatic Ovarian Tumors

Cytokeratin 7 has been known to be present in various types of human epithelial cells including the ovarian neoplasms, but not in colon cancers. The antibody to colon ovarian tumor antigen (COTA) has been introduced as a marker of colon and ovarian tumors. The aim of this study was to evaluate the usefulness of cytokeratin 7 and COTA in the differential diagnosis between ovarian primary and metastatic tumors. Nineteen primary ovarian epithelial tumors, seven metastatic carcinomas of the ovary from the stomach, three metastatic carcinomas of the ovary from the colon, one mucinous tumor of the ovary associated with a mucinous tumor of the appendix and pseudomyxoma peritonei, and nineteen colonic and twenty gastric adenocarcinomas were stained with monoclonal antibodies to cytokeratin 7 and COTA. The results are summerized as follows; In the primary ovarian tumors, 94.4% were positive for cytokeratin 7 and 50% were positive for COTA. In the primary colonic adenocarcinomas, 94.7% were negative for cytokeratin 7 and 68% were positive for COTA. In the metastatic ovarian tumor from the colonic adenocarcinomas, 100% were negative for cytokeratin 7 and positive for COTA. In the primary gastric adenocarcinomas, 40% were negative for cytokeratin 7 and 85% were negative for COTA. In the metastatic ovarian tumor from the gastric adenocarcinomas, 43% were negative for cytokeratin 7 and 14% were negative for COTA. From the results of this study, it could be concluded that in the differential diagnosis of primary ovarian tumors from metastatic colonic carcinomas, positive reaction for cytokeratin 7 suggests a primary ovarian tumor but a negative reaction for cytokeratin 7 and positive reaction for COTA suggest metastatic colonic carcinomas. The results of this study also reveal that cytokeratin 7 and COTA are not useful in the differential diagnosis of primary ovarian tumors from metastatic gastric carcinomas.