Yong-Yang Yu

RNA Interference Against Peroxisome Proliferator-Activated Receptor δ Gene Promotes Proliferation of Human Colorectal Cancer Cells

PurposeThis study was designed to investigate the effects of peroxisome proliferator-activated receptor δ (PPAR δ) on the proliferation and apoptosis of human colorectal cancer cells.MethodsFor RNA interfering (RNAi), HCT-116 cells were transfected with short hairpin RNA (shRNA)-expressing plasmids against PPAR δ or negative control vectors, and the stably transfected cells were selected with G418. The efficacy of RNAi was assessed by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting analysis. The proliferation, cell cycle, and apoptosis of HCT-116 cells treated by RNAi, compared with those containing control vectors or untreated, were analyzed respectively by using MTT (methyl thiazolyl tetrazolium), flow cytometry, and TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick end-labeling (TUNEL) assay.ResultsRNAi targeting PPAR δ resulted in substantial suppression of PPAR δ expression and significantly promoted the proliferation of HCT-116 cells relative to those with control vectors or untreated, obviously decreasing the frequency of G1-phase cells but had no effect on cell apoptosis.ConclusionsPPAR δ may inhibit the proliferation of CRC cells and increase the number of cells in G1 phase, without any function in cell apoptosis.

Knockdown of PPAR δ Gene Promotes the Growth of Colon Cancer and Reduces the Sensitivity to Bevacizumab in Nude Mice Model

The role of peroxisome proliferator – activated receptor- δ (PPAR δ) gene in colon carcinogenesis remains highly controversial. Here, we established nude mice xenograft model using a human colon cancer cell line KM12C either with PPAR δ silenced or normal. The xenografts in PPAR δ-silenced group grew significantly larger and heavier with less differentiation, promoted cell proliferation, increased expression of vascular endothelial growth factor (VEGF) and similar apoptosis index compared with those of PPAR δ-normal group. After treated with the specific VEGF inhibitor bevacizumab, the capacities of growth and proliferation of xenografts were decreased in both groups while still significantly higher in PPAR δ-silenced group than in PPAR δ-normal group. Administration of PPAR δ agonist significantly decreased VEGF expression in PPAR δ-normal KM12C cells but not in PPAR δ-silenced cells. These findings demonstrate that, knockdown of PPAR δ promotes the growth of colon cancer by inducing less differentiation, accelerating the proliferation and VEGF expression of tumor cells in vivo, and reduces tumor sensitivity to bevacizumab. This study indicates that PPAR δ attenuates colon carcinogenesis.

The prognostic factors and multiple biomarkers in young patients with colorectal cancer.

The incidence of colorectal cancer (CRC) in young patients (≤50 years of age) appears to be increasing. However, their clinicopathological characteristics and survival are controversial. Likewise, the biomarkers are unclear. We used the West China (2008-2013, China), Surveillance, Epidemiology, and End Results program (1973-2011, United States) and Linköping Cancer (1972-2009, Sweden) databases to analyse clinicopathological characteristics, survival and multiple biomarkers of young CRC patients. A total of 509,934 CRC patients were included from the three databases. The young CRC patients tended to have more distal location tumours, fewer tumour numbers, later stage, more mucinous carcinoma and poorer differentiation. The cancer-specific survival (CSS) of young patients was significantly better. The PRL (HR = 12.341, 95% CI = 1.615-94.276, P = 0.010), RBM3 (HR = 0.093, 95% CI = 0.012-0.712, P = 0.018), Wrap53 (HR = 1.952, 95% CI = 0.452-6.342, P = 0.031), p53 (HR = 5.549, 95% CI = 1.176-26.178, P = 0.045) and DNA status (HR = 17.602, 95% CI = 2.551-121.448, P = 0.001) were associated with CSS of the young patients. In conclusion, this study suggests that young CRC patients present advanced tumours and more malignant pathological features, while they have a better prognosis. The PRL, RBM3, Wrap53, p53 and DNA status are potential prognostic biomarkers for the young CRC patients.

Occurrence and prognostic value of circumferential resection margin involvement for patients with rectal cancer

Background and aimTotal mesorectal excision (TME) was advocated owning to the reduction in local failure, while deficiency in pathologic details limited monitoring of surgical quality assurance. Here, we aimed to examine circumferential resection margin (CRM) by large tissue slice, discussing its rule in occurrence and relationship with prognosis, thus providing proof for the adoption of TME principles and the application of adjuvant therapy.Materials and methodsSpecimens of 106 patients with rectal cancer, who underwent potentially curative resection from December 2001 to September 2002, were examined. Follow-up data were collected.ResultsAltogether, 2,068 mesorectal nodes were examined with 272 involved by tumor. CRM involvement (CRMI) was examined in 20 specimens. In these 20 cases, seven, nine, and four were caused by tumor infiltration, lymph node metastasis, and both, respectively. Occurrence of CRMI was more common for lower-located cancers while also statistically related to tumor differentiation, infiltration, and lymph node metastasis. The difference in local recurrence rate, general recurrence rate, disease-free survival rate, and overall survival rate between the group with CRMI and the group without were all proven to be significant.ConclusionsDetailed pathologic examination, including status of CRM, is advocated since it provides accurate prognostic information. Surgeons could maximize the probability of cure by following the principle of TME. Preoperative adjuvant therapy was essential for advanced staged and lower-located lesions, which implied likelihood of CRMI.

Microsatellite Instability Did Not Predict Individual Survival in Sporadic Stage II and III Rectal Cancer Patients

Objectives: Tumors with high-frequency microsatellite instability (MSI-H) have unique biological behavior and the predictive role of microsatellite instability (MSI) status on survival of colorectal cancer is still debated. The prognostic significance of MSI status in sporadic stage II and III rectal cancer patients needs to be more precisely defined. So we investigated the relationship between MSI status and clinicopathological features and prognosis in these patients. Methods: DNAs from fresh-frozen paired samples of tumors and corresponding normal tissue from 128 stage II and III rectal cancer patients were analyzed for MSI by PCR amplification using markers recommended by a National Cancer Institute workshop on MSI. To assess prognostic significance, Cox proportional hazards modeling was used. Results: Twelve (9.3%) tumors in our study were MSI-H, 28 (21.9%) were low-frequency MSI (MSI-L) and 88 (68.8%) were microsatellite stable (MSS). Most of the MSI-H tumors compared with MSI-L and MSS tumors were found in female patients (p = 0.031), had mucinous histology (p = 0.023), high grade of differentiation (p = 0.002) and high level of preoperative serum carcinoembryonic antigen (p = 0.005). Rectal cancer patients with MSI-H did not show a better clinical outcome than those with MSI-L/MSS, neither in all cases (p = 0.986) nor in stage II and stage III disease analyzed separately (p = 0.705 and p = 0.664, respectively). Conclusions: Data provided here demonstrated there was high incidence of MSI-H and MSI was not a prognostic factor in sporadic stage II and III rectal cancers from the Chinese Han population included in this study. Tumor stage is more suitable than MSI status for prediction of individual survival in sporadic stage II and III rectal cancer patients.

Duodenal intussusception due to a giant neuroendocrine carcinoma in a patient with Peutz-Jeghers syndrome: case report and systematic review.

Duodenal intussusception is a rare entity. To date, only a few cases have been reported in the literature. In this report, a case of duodenal intussusception due to an unusual tumor was presented and the clinical features of this entity were discussed. A 42-year-old man with Peutz-Jeghers syndrome presented with epigastric pain, vomiting, and severe anemia. Computed tomography scan revealed synchronous duodenojejunal and jejunojejunal intussusceptions. An emergency laparotomy revealed a polypoid mass originating from the lateral wall of the descending duodenum with intussusception of the distal duodenum. Histological examination demonstrated a poorly differentiated neuroendocrine carcinoma with muscularis infiltration, vascular invasion, and a Ki-67 index of 20%. A comprehensive literature search revealed 44 English reports that provided adequate descriptions of an additional 47 such cases. Clinical presentation was usually chronic and nonspecific. Diagnostic modalities included ultrasonography, upper gastrointestinal series, computed tomography, and endoscopy. Five patients were due to a non-neoplastic lesion; however, the other 43 patients were secondary to a tumor, benign in 35 cases and malignant in eight cases. Only one patient was treated by endoscopic polypectomy, whereas the remaining underwent open surgeries. Duodenal intussusception is a challenging condition due to its rarity and nonspecific presentation. It should be considered in the differential diagnosis of gastric outlet obstruction, upper gastrointestinal bleeding, pancreatitis, and obstructive jaundice.

Efficacy of Surgery and Adjuvant Therapy in Older Patients With Colorectal Cancer: A STROBE-compliant article

AbstractThe present study aimed to assess the efficacy of surgery and adjuvant therapy in older patients (age ≥70 years) with colorectal cancer (CRC). Older CRC patients are under-represented in available clinical trials, and therefore their outcomes after receiving surgery and adjuvant therapy are unclear. From two prospective Swedish databases, we assessed a cohort of 1021 patients who underwent curative surgery for stage I, II, or III primary CRC, with or without adjuvant chemotherapy/radiotherapy. Of the patients with colon cancer (n = 467), 182 (39%) were aged <70 years, 162 (35%) aged 70 to 80 years, and 123 (26%) were aged ≥80 years. Of rectal cancer patients (n = 554), 264 (48%) were aged <70 years, 234 (42%) aged 70 to 80 years, and 56 (10%) aged ≥80 years. Older patients with either colon or rectal cancer had higher comorbidity than did younger patients. Older patients with colon cancer had equivalent postoperative morbidity and 30-day mortality to younger patients. Rectal cancer patients aged ≥80 years had a higher 30-day mortality than younger patients (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.6–4.55; P = 0.03). For either colon or rectal cancer, adjuvant chemotherapy compromised the 5-year overall survival (OS) of older patients with stage II disease and had no effect on those with stage III disease. Receiving adjuvant chemotherapy was a poor factor of OS for older patients with either colon (HR 1.88, 95% CI: 1.20–4.35, P = 0.03) or rectal cancer (HR 1.72, 95% CI: 1.05–2.26, P = 0.004). Preoperative short-course radiotherapy improved both OS and local control for older patients with stage III rectal cancer and had no effect on those with stage II disease. Radiotherapy was a favorable factor for the OS of the older patients with rectal cancer (HR 0.42, 95% CI: 0.21–3.57, P = 0.01). In conclusion, Older CRC patients had equal safety of surgery as younger patients, except rectal cancer patients aged ≥80 years that had a higher mortality. Adjuvant 5FU-based chemotherapy did not benefit older CRC patient, while neoadjuvant radiotherapy improved the prognosis of older patients with stage III rectal cancer.

The Ile646Val (2073A>G) Polymorphism in the Kinase-Binding Domain of A-Kinase Anchoring Protein 10 and the Risk of Colorectal Cancer

Objective: The purpose of this study is to investigate whether the Ile646Val (2073A>G) polymorphism in the kinase-binding domain of A-kinase anchoring protein 10 (AKAP10) is related to the risk of colorectal cancer (CRC), clinicopathological variables and the environmental factors for the development of CRC. Methods: Applying TaqMan allelic discrimination, we investigated AKAP10 Ile646Val (2073A>G) polymorphism in 288 Chinese CRC patients and 281 healthy controls. Results: Logistic regression analysis revealed a significant association of AKAP10 Ile646Val (2073A>G) polymorphism with increased CRC risk (adjusted OR = 1.44, 95% CI 1.01–2.07, p = 0.02). Stratification analysis showed that the increased risk associated with the variant genotypes (GG+AG) was more evident in male subjects (adjusted OR = 1.48, 95% CI 0.94–2.34, p = 0.03). Compared with the AA genotype, the adjusted OR for the variant genotypes was 1.81 (95% CI 1.08–3.05, p = 0.01) among young subjects (age <57 years). Among individuals who did not smoke or who smoked lightly, there was a significantly increased risk with the variant genotypes (adjusted OR = 1.66, 95% CI 1.08–2.56, p = 0.02). We did not observe a relationship between the AKAP10 polymorphism and other clinicopathological and environmental factors. Conclusions: Our data suggested that the AKAP10 2073A>G variation is associated with an increased risk of CRC in the Chinese population.

CD133 + CD54 + CD44 + circulating tumor cells as a biomarker of treatment selection and liver metastasis in patients with colorectal cancer

Introduction Liver is the most common site of distant metastasis in colorectal cancer (CRC). Early diagnosis and appropriate treatment selection decides overall prognosis of patients. However, current diagnostic measures were basically imaging but not functional. Circulating tumor cells (CTCs) known as hold the key to understand the biology of metastatic mechanism provide a novel and auxiliary diagnostic strategy for CRC with liver metastasis (CRC-LM). Results The expression of CD133+ and CD133+CD54+CD44+ cellular subpopulations were higher in the peripheral blood of CRC-LM patients when compared with those without metastasis (P<0.001). Multivariate analysis proved the association between the expression of CD133+CD44+CD54+ cellular subpopulation and the existence of CRC-LM (P<0.001). The combination of abdominal CT/MRI, CEA and the CD133+CD44+CD54+ cellular subpopulation showed increased detection and discrimination rate for liver metastasis, with a sensitivity of 88.2% and a specificity of 92.4%. Meanwhile, it also show accurate predictive value for liver metastasis (OR=2.898, 95% C.I.1.374–6.110). Materials and Method Flow cytometry and multivariate analysis was performed to detect the expression of cancer initiating cells the correlation between cellular subpopulations and liver metastasis in patients with CRC. The receiver operating characteristic curves combined with the area under the curve were generated to compare the predictive ability of the cellular subpopulation for liver metastasis with current CT and MRI images. Conclusions The identification, expression and application of CTC subpopulations will provide an ideal cellular predictive marker for CRC liver metastasis and a potential marker for further investigation.

Laparoscopic splenectomy with or without devascularization of the stomach for liver cirrhosis and portal hypertension: a systematic review

Open splenectomy and devascularization are effective treatments for cirrhotic patients with severe thrombocytopenia and variceal bleeding. However, it remains controversial whether laparoscopic splenectomy (LS) and devascularization (LSD) can be indicated and beneficial in these patients.