Haifeng Gong

Multidrug resistance-associated protein 3 confers resistance to chemoradiotherapy for rectal cancer by regulating reactive oxygen species and caspase-3-dependent apoptotic pathway

This study aimed to clarify the role of multidrug resistance-associated protein 3 (MRP3) in resistance to neoadjuvant chemoradiotherapy and long-term prognosis of advanced rectal cancer. Immunohistochemistry was used to measure MRP3 expression in biopsy specimens of 144 stage II-III rectal cancer patients who received preoperative chemoradiotherapy. The effect of MRP3 expression on short-term pathological response and postoperative long-term prognosis were assessed using the Cox proportional hazards model. Short interfering RNAs targeting MRP3 were synthesized and used to transfect human colorectal carcinoma cell lines. The effect of MRP3 down-regulation on cell proliferation and apoptosis in response to 5-fluorouracil and/or irradiation were examined in vitro and in xenograft mouse models, respectively. The content of intracellular reactive oxygen species and the activity of caspase-3-dependent apoptotic pathway in response to irradiation were further evaluated. High expression (immunoreactive score > 6) of MRP3 significantly predicted poor pathological response to chemoradiotherapy (tumor regression grade ≤ 2 vs. ≥3, p = 0.002) in univariate analysis and unfavorable long-term prognosis (5-year overall survival: HR = 1.612, 95% CI, 1.094-2.375, p = 0.016; 5-year disease-free survival: HR = 1.513, 95% CI, 1.041-2.200, p = 0.030) in multivariate Cox analysis. MRP3 down-regulation significantly increased 5-fluorouracil or irradiation-induced cell apoptosis and attenuated tumor growth following irradiation in animal models. MRP3 inhibition significantly reduced intracellular reactive oxygen species exporting from cells following irradiation, and increased expression of cleaved poly ADP-ribose polymerase and caspase-3. Aberrant expression of MRP3 in rectal cancer confers chemo-radioresistance. MRP3 might be a predictive factor and an attractive target in treating advanced rectal cancer.

Lentivirus-mediated silencing of USO1 inhibits cell proliferation and migration of human colon cancer cells.

Belonging to the tether factors family, USO1 (vesicle transport factor) plays a critical role in endoplasmic reticulum–Golgi trafficking and vesicular transport which is important to tumorigenesis. However, the mechanism of USO1 in colon cancer was still unknown. In our research, the expression of USO1 was knockdown in colon cancer cells (HCT116 and HT-29) by using a special lentivirus shRNA approach. A series of experiments were carried out to evaluate the effect of deregulation of USO1, including cell proliferation, apoptosis, cell migration and cell cycle. Knockdown of USO1 inhibits the ability of cell proliferation and migration. Furthermore, the deregulation of USO1 induces early apoptosis and decreased cells in G2-M phase. We demonstrate for the first time that USO1 gene has a critical role in human colon cancer. Our finding represents that USO1 gene may be a promising target for therapy and diagnosis in treatment of human colon cancer.

Hematogenous transverse colon metastasis from primary hepatocellular carcinoma

Dear Editor: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second-leading cause of cancer-related deaths. Despite the development of treatment modalities and surgical instruments over the past 2 decades, the long-term outcome of HCC is not satisfactory because of the high rates of recurrence and metastasis. Extrahepatic metastasis is common and the most frequent sites are the lungs, lymph nodes, bone, and adrenal gland. Metastasis to the gastrointestinal (GI) tract is rare. It is reported that the incidence is 0.5–2 % of clinical cases and 4 % in autopsy series. Here, we reported an HCC patient with hematogenous transverse colon metastasis. A 47-year-old man was admitted to our hospital because of hematemesis in 2009. A computed tomography (CT) scan revealed a 2.1×2.2 cm-sized mass in the hepatic segment V with enhancement on the arterial phase, and filling defect could be seen in the portal and splenic vein. Besides, the CT also showed cirrhosis and splenomegaly. Physical examination was unremarkable, and the laboratory findings showed a slight elevation of total bilirubin (22.2 μmol/L) and γglutamyl transpeptidase (53 U/L) and a decrease in platelet count (60×10/L). Hepatitis B surface antigen (HBsAg), hepatitis B e antibody (HBeAb), and hepatitis B core antibody (HBcAb) were positive. All other values such as white blood cell, hemoglobin, albumin, prothrombin time, alphafetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA12-5) were normal. He was diagnosed with primary HCC, cirrhosis, portal hypertension, and hypersplenism. Ultimately, he underwent resection of the hepatic tumor, spleen, cholecyst, and portal azygous disconnection on February 5th, 2009. Two months later, he received transcatheter arterial embolization (TAE) once to ensure a radical cure. Then, he was followed up by AFP, CEA, CA19-9 levels, and ultrasound every 3 months, and CT scan was performed every 6 months. A CT scan showed that a 1.8 cm-sized mass was located in the hepatic segment VIII with enhancement on the arterial phase, while with low attenuation on the delayed phase in 2012. He received re-resection for the recurrent HCCwhich was confirmed by histopathology and underwent transcatheter arterial angiography and chemoembolization (TACE). After TACE, the patient was followed up as he did before and there was no evidence of recurrence for 2 years. In 2014, he was occasionally found to be positive in fecal occult blood test (FOBT). A colonoscopy was performed which showed a mass in transverse colon. Positron emission tomography/computed tomography (PET/CT) was implemented to make sure that other sites were free from metastasis. Finally, he underwent transverse colectomy and a mass measuring 4.5×4×2.5 cm, infiltrating to the serous membrane was identified. Histopathologic examination showed that the large polygonal tumor cells arranging in nets were presented with eosinophilic cytoplasm, large basophilic nuclei with prominent nucleoli, which were similar to HCC. Meanwhile, the immunohistochemical results demonstrated the tumor cells were positive for hepatocyte antigen (HPC) and cytokeratin 8&18 (CK 8&18), while negative for caudal type homeoboxtranscription factor 2 (CDX2), supporting the diagnosis of metastatic HCC. Xiaoming Zhu and Zheng Lou contributed equally to this work.

Embolization of blood-supply artery followed by surgery for treatment of mesorectal Castleman's disease: case report and literature review.

Abstract A 23-year-old male patient was diagnosed as having a hypervascular pelvic mass by ultrasonography and magnetic resonance examination. A pathology puncture showed vitreous vascular Castleman’s disease. Because of concerns about tumor blood supply, embolization under digital subtraction angiography (DSA) was performed on the artery of the pelvic tumor before resection of the mass and surrounding rectum. Castleman’s disease of pelvic lymph node (mixed type, mainly hyaline vascular type) was confirmed pathologically from postoperative biopsy. Embolization of the blood-supply artery of a hypervascular mass should be considered before surgery is performed.

Pull-through and conformal resection for very low rectal cancer: a more satisfactory technique for anal function after sphincter preserving operation

Background: The aim of this study was to investigate oncologically whether pull-through and conformal resection technique (PTCR) could replace abdominoperineal resection (APR) in selected patients with very low rectal cancer. Methods: This was a retrospective review of prospectively collected data. The study was conducted at a tertiary teaching hospital, Shanghai, China from January 2010 to December 2013. All patients who underwent operations because of very low rectal cancer were enrolled in this study. The primary outcome measured was the development of recurrence including distant metastasis and local recurrence. Anal function was assessed with the Wexner incontinence score and digital examination. Results: A total of 228 patients with very low rectal cancer underwent surgical treatment [coloanal anastomosis (CAA) group 126 patients, APR group 73 patients, and PTCR group 29 patients]. There was no difference in surgical complication rate among the three groups. There were no significant differences in daily fecal frequency, Wexner incontinence score, and rate of satisfactory fecal continence between the CAA and PTCR group. There were no differences in local recurrence and distant metastasis among CAA group, APR group and PTCR group. Conclusions: PTCR is an anus-preserved procedure with clean distal margin and satisfied anal function without compromising short-term oncological outcomes in selected patients with very low rectal cancer.