Epigallocatechin gallate inhibits dimethylhydrazine-induced colorectal cancer in rats.

BACKGROUND: Epigallocatechin gallate (EGCG) is a polyhydroxy phenolic compound extracted from tea and its antitumor effect has received widespread attention. We explored the inhibitory effect of EGCG on dimethylhydrazine (DMH)-induced colorectal cancer (CRC) using a rat model, predicted the interaction between EGCG and CRC target genes using a database, and explained the EGCG associated target pathways and mechanisms in CRC. AIM: To understand the inhibitory mechanisms of EGCG on CRC cell proliferation and identify its pharmacological targets by network pharmacology analysis. METHODS: DMH (40 mg/kg, s.c., twice weekly for eight weeks) was used to induce CRC in rats. After model establishment, the rats were administered with EGCG (50, 100, or 200 mg/kg, p.o., once daily for eight weeks) and killed 12 and 20 wk after the start of the experiment. Formation of aberrant crypt foci and tumor was studied by histological analysis. Using network pharmacology analysis, candidate and collective targets of EGCG and CRC were identified, and Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were used to predict the pathways altered by EGCG. RESULTS: At week 12, high-dose EGCG treatment significantly reduced the tumor formation rate, total number of tumors, cancerous and non-cancerous tumors, tumor volume, ascites formation, and aberrant crypt foci count. At week 20, all three doses of EGCG were effective. Seventy-eight collective targets of EGCG and CRC were identified, of which 28 genes were dysregulated in CRC. Kyoto Encyclopedia of Genes and Genomes and GO analyses showed that the dysregulated genes were enriched in hsa05210 (CRC), hsa04115 (p53 signaling pathway), and hsa04151 (PI3K-Akt signaling pathway), GO:0043124 (negative regulation of I-kappaB kinase/NF-kappaB signaling pathway), GO:0043409 (negative regulation of mitogen-activated protein kinase cascade), and GO:2001244 (positive regulation of intrinsic apoptotic signaling pathway) respectively. CONCLUSION: EGCG inhibits the formation of DMH-induced CRC by regulating key pathways involved in tumorigenesis.

Clinical significance of MLH1/MSH2 for stage II/III sporadic colorectal cancer.

BACKGROUND: The development of colorectal cancer (CRC) is a complicated multistep process that involves an accumulation of mutations in tumor suppressor genes and oncogenes. In the process of DNA replication, base mismatch often occurs due to various factors leading to abnormal expression of mismatch repair genes (MMR), among which MLH1 and MSH2 are the most important. Recently, numerous studies indicated that MLH1/MSH2 phenotype is associated with CRC. We wanted to elucidate the role of MLH1/MSH2 in the prediction and prognosis of CRC through long-term clinical observation. AIM: To evaluate the prognostic and predictive significance of MLH1/MSH2 in patients with stage II-III CRC using immunohistochemical analysis and GeneScan. METHODS: Specimens from 681 patients with CRC (395 stage II and 286 stage III, 387 males and 294 females) who underwent curative surgical resection from 2013 to 2016 were tested. Immunohistochemistry was used to analyze MMR status and the microsatellite status of 133 patients was determined by GeneScan analysis. RESULTS: Five hundred and fifty (80.76%) patients were MLH1/MSH2 positive and 131 (19.24%) were negative by immunohistochemistry. MLH1/MSH2-positive tumors were significantly more frequent in the colon than in the rectum, and had poor differentiation and less mucin production (P < 0.05). Patients of different groups did not differ in terms of age, gender, tumor size, tumor stage, lymphocytic infiltration, or circumscribed margin. MLH1/MSH2-negative patients had a more favorable OS than MLH1/MSH2-positive patients (P < 0.001). Univariate and multivariate analyses demonstrated MLH1/MSH2 expression as an independent prognostic and predictive factor for stage II/III CRC. MLH1/MSH2 expression was a strong prognostic factor in all patients [P < 0.001, hazard ratio (HR) = 4.064, 95%CI: 2.241-7.369]. Adjuvant chemotherapy had a greater correlation with survival advantage in MLH1/MSH2-negative patients with stage III disease (P < 0.001, HR = 7.660, 95%CI: 2.974-15.883). However, patients with stage II disease or MLH1/MSH2-positive patients with stage III disease did not benefit from adjuvant chemotherapy. GeneScan analysis demonstrated that among 133 patients, 105 (78.95%) were microsatellite stable, and 28 (21.05%) had microsatellite instability (MSI), including 18 (13.53%) with high MSI and 10 (7.52%) with low MSI. This is consistent with the immunohistochemical results. CONCLUSION: MLH1/MSH2 phenotype constitutes a pathologically and clinically distinct subtype of sporadic CRC. MLH1/MSH2 is an independent prognostic and predictive factor for outcome of stage II-III CRC.

Primary neuroendocrine tumor in the presacral region: A case report.

BACKGROUND: Primary neuroendocrine tumors (NETs) in the presacral region are extremely rare, some of which are caused by other primary tumors or metastatic rectal carcinoids. Nevertheless, cases of NETs have been increasing in recent years. This report describes the first primary neuroendocrine tumor in the presacral region that was found at our hospital within the last five years. CASE SUMMARY: The patient was identified as a 36-year-old woman with a presacral mass and pelvic floor pain. A digital rectal examination revealed a presacral mass with unclear margins and obvious tenderness. Magnetic resonance imaging (MRI) demonstrated a 57 mm × 29 mm presacral lump. An ultrasound-guided needle biopsy confirmed a well-differentiated neuroendocrine tumor. No other primary or metastatic tumors were found. CONCLUSION: Comprehensive consideration of our case report and literature reported by others suggests that a conclusive diagnosis of NETs should be based on computed tomography/MRI and pathological examinations. The treatment of primary NETs in the presacral region mainly relies on surgical procedures with follow-up.

Extranodal natural killer/T-cell lymphoma (nasal type) presenting as a perianal abscess: A case report.

BACKGROUND: Extranodal natural killer (NK) T-cell lymphoma (ENKTL), nasal type is a rare subtype of extranodal non-Hodgkin lymphoma characterized by vascular damage and necrosis. The lesions usually present in the nasal cavity and adjacent tissues, however, the disease originates from the gastrointestinal or genitourinary tract in 25% of cases. Since rectal involvement in ENKTL is rare, rectal symptoms in the course of ENKTL are often misdiagnosed and considered to be related to benign diseases such as rectal fistula or perianal abscess. CASE SUMMARY: We report the case of a 24-year-old Han Chinese female who initially presented with a perianal abscess that was subsequently diagnosed as nasal type ENKTL. Due to typical perianal pain, perianal abscess was diagnosed and surgical incision and drainage were performed. After recurrent, severe anal hemorrhages leading to hypovolemic shock and multiple surgeries, a diagnosis of ENKTL was made. The patient's condition gradually deteriorated, and she died shortly after initiation of chemotherapy. CONCLUSION: Systemic and neoplastic diseases should be included in the differential diagnosis of any potentially benign perianal abscess complicated with recurrent hemorrhages.

[Analysis on human papillomavirus 16 and 18 types infection among 805 patients with common anorectal lesions].

OBJECTIVE: To analyze the infection condition of human papillomavirus (HPV) type 16 and 18 in the squamous cells and columnar cells of patients with common anorecatal lesions. METHODS: Infections of HPV type 16 and 18 were determined with real-time fluorescent quantitative PCR in the wax-embedded surgical specimen of 805 patients with common anorectal diseases. RESULTS: The overall infection rate among 805 patients with anorecatal lesions was 66.1% (532/805). The infection rate was 82.6% (95/115) in patients with mixed hemorrhoids, 76.5% (88/115) in anal papillary fibromas, 74.8% (86/115) in internal hemorrhoids, 72.2% (83/115) in fistulas, 69.6% (80/115) in external hemorrhoids, 47.8% (55/115) in anal perianal abscesses, and 39.1% (45/115) in anal fissures. CONCLUSION: Infection rate of HPV type 16, 18 in common anorectal lesions is high.

[Study the value of screening hereditary nonpolyposis colorectal cancer kindreds by detecting the expression of hMLH1/hMSH2 with tissue microarray].

OBJECTIVE: To study the value of screening hereditary nonpolyposis colorectal cancer (HNPCC) kindreds by detecting the expressions of hMLH1/hMSH2 with tissue microarray. METHODS: A tissue microarray with 22 colorectal cancers from HNPCC families and 15 sporadic colorectal cancers was established, and the expressions of hMLH1/hMSH2 were detected by immunohistochemistry (IHC). RESULTS: The expressions of hMLH1 or hMSH2 were negative in 15 of 22 HNPCC and 1 of 15 sporadic colorectal cancers in routine IHC. The expressions of hMLH1 or hMSH2 were negative in 17 of 22 HNPCC and 2 of 15 sporadic colorectal cancers in tissue microarray. The examination of hMSH2 expression yielded same results between routine IHC and tissue microarray. There were no difference on the hMLH1 expressions between routine IHC and tissue microarray. CONCLUSION: Tissue microarray is a high-throughput way to detect the expressions of hMLH1/hMSH2 and is applicable to screen HNPCC kindreds.