Tiantao Kuang

Induction of protective and therapeutic anti-pancreatic cancer immunity using a reconstructed MUC1 DNA vaccine

BackgroundPancreatic cancer is a common, highly lethal disease with a rising incidence. MUC1 is a tumor-associated antigen that is over-expressed in pancreatic adenocarcinoma. Active immunotherapy that targets MUC1 could have great treatment value. Here we investigated the preventive and therapeutic effect of a MUC1 DNA vaccine on the pancreatic cancer.MethodsMUC1-various tandem repeat units(VNTR) DNA vaccine was produced by cloning one repeat of VNTR and inserting the cloned gene into the pcDNA3.1. In the preventive group, female C57BL/6 mice were immunized with the vaccine, pcDNA3.1 or PBS; and challenged with panc02-MUC1 or panc02 cell. In the therapeutic group the mice were challenged with panc02-MUC1 or panc02 cell, and then immunized with the vaccine, pcDNA3.1 or PBS. The tumor size and the survival time of the animals were compared between these groups.ResultsThe DNA vaccine pcDNA3.1-VNTR could raise cytotoxic T lymphocyte (CTL) activity specific for MUC1. In the preventive experiment, the mice survival time was significantly longer in the vaccine group than in the control groups (P < 0.05). In the therapeutic experiment, the DNA vaccine prolonged the survival time of the panc02-MUC1-bearing mice (P < 0.05). In both the preventive and therapeutic experiments, the tumor size was significantly less in the vaccine group than in the control groups (P < 0.05). This pcDNA3.1-VNTR vaccine, however, could not prevent the mice attacked by panc02 cells and had no therapeutic effect on the mice attacked by panc02 cells.ConclusionThe MUC1 DNA vaccine pcDNA3.1-VNTR could induce a significant MUC1-specific CTL response; and had both prophylactic and therapeutic effect on panc02-MUC1 tumors. This vaccine might be used as a new adjuvant strategy against pancreatic cancer.

Granulocytic sarcoma of the pancreas: A case report and review of the literatures

BackgroundGranulocytic sarcoma (GS) is a form of acute myeloid leukemia (AML), also known as extramedullary myeloid tumor or chloroma. It forms a solid malignant tumor consisting of myelocytes or granulocytes and is typically located in bone while occurrence in other parts of the body is rare.Case presentationWe reported a 40-year-old male patient who had jaundice, highly elevated bilirubin, and a mass highly suspicious of pancreatic head carcinoma. We performed surgery and the pathology and immunohistochemistry suggested GS; however the blood test and the bone marrow infiltration showed no evidence of AML. In our review of the published reports of GS, we only found six reports of the GS in the pancreas, and we suggested that immunohistochemical staining should be used to accurately differentiate GS from other pancreatic cancer and other types of leukemia.ConclusionsThe accurate diagnosis of GS is necessary for determining prognosis and deciding appropriate therapy.

Laparoscopic versus open distal pancreatectomy for benign or premalignant pancreatic neoplasms: a two-center comparative study.

ObjectiveTo compare the peri-operative outcomes for laparoscopic distal pancreatectomy (LDP) and open distal pancreatectomy (ODP) for benign or premalignant pancreatic neoplasms in two institutions.MethodsThis prospective comparative study included 91 consecutive patients who underwent LDP (n=45) or ODP (n=46) from Jan. 2010 to Dec. 2012. Demographics, intra-operative characteristics, and post-operative outcomes were compared.ResultsThe median operating time in the LDP group was (158.7±38.3) min compared with (92.2±24.1) min in the ODP group (P<0.001). Patients had lower blood loss in LDP than in the ODP ((122.6±61.1) ml vs. (203.1±84.8) ml, P<0.001). The rates of splenic conservation between the LDP and ODP groups were similar (53.3% vs. 47.8%, P=0.35). All spleen-preserving distal pancreatectomies were conducted with vessel preservation. LDP also demonstrated better post-operative outcomes. The time to oral intake and normal daily activities was faster in the LDP group than in the ODP group ((1.6±0.5) d vs. (3.2±0.7) d, P<0.01; (1.8±0.4) d vs. (2.1±0.6) d, P=0.02, respectively), and the postoperative length of hospital stay in LDP was shorter than that in ODP ((7.9±3.8) d vs. (11.9±5.8) d, P=0.006). No difference in tumor size ((4.7±3.2) cm vs. (4.5±1.8) cm, P=0.77) or overall pancreatic fistula rate (15.6% vs. 19.6%, P=0.62) was found between the groups, while the overall post-operative complication rate was lower in the LDP group (26.7% vs. 47.8%, P=0.04).ConclusionsLDP is safe and effective for benign or premalignant pancreatic neoplasms, featuring lower blood loss and substantially faster recovery.總結目 的评估腹腔镜胰体尾切除术安全有效性,对比腹腔镜胰体尾切除术与开腹胰体尾切除术治疗胰腺体尾部良性或低度恶性病变临床疗效。创新点本研究为回顾性对照研究,相较于过往腹腔镜胰体尾切除术与开腹胰体尾切除术的对照研究,其创新点一为本组91 例病例均为良性或低度恶性病例,剔除了恶性病变病例;二为本研究中腹腔镜胰体尾切除术组及开腹胰体尾切除术组分别由两家大型综合医院胰腺疾病诊治中心的两组医生分别施行手术,这样避免了病人及手术方式选择等造成的影响,结果更为客观。方法回顾分析自2010 年1 月至2012 年12 月浙江大学医学院附属邵逸夫医院45 例施行腹腔镜胰体尾切除术治疗胰腺体尾部良性或低度恶性病变病例(LDP 组),以及同期上海复旦大学附属中山医院46 例施行开腹胰体尾切除术胰腺体尾部良性或低度恶性病变病例(ODP 组)的相关临床资料,进行对照研究。结论本研究包括胰腺体尾部良性或低度恶性病例91 例,其中LDP 组45 例(无中转开腹)和ODP 组 46 例。手术时间分别为(158.7±38.3) min(LDP 组)和(92.2±24.1) min(ODP 组);术中出血LDP 组明显少于ODP 组( (122.6±61.1) ml vs. (203.1±84.8) ml,P<0.001)。两组保脾率相似(53.3% vs. 47.8%,P=0.35),其中LDP 组中保脾病例均保留脾血管。在术后恢复指标方面,LDP 组优于ODP 组,恢复进食流质时间((1.6±0.5) d vs. (3.2±0.7) d,P<0.01)及恢复活动时间((1.8±0.4) d vs. (2.1±0.6) d,P=0.02)较短,且LDP 组术后住院时间也少于ODP 组((7.9±3.8) d vs. (11.9±5.8) d, P=0.006)。术后胰瘘率两组无明显差异(15.6% vs. 19.6%,P=0.62),但术中总并发症率LDP 组低于ODP 组(26.7% vs. 47.8%,P=0.04)。研究结果显示腹腔镜胰体尾切除术治疗胰腺体尾部良性或低度恶性肿瘤安全可行,与开腹胰体尾切除术术相比术中出血更少、术后恢复更快,具有明显微创优势。

TRAF6 is over-expressed in pancreatic cancer and promotes the tumorigenicity of pancreatic cancer cells.

Pancreatic cancer is one of the most lethal malignancies, with a poor response to chemotherapy and therefore it is important to identify novel therapeutic targets. TNF receptor-associated factor 6 (TRAF6) , a regulator of NF-κB signaling, has been found recently to be involved in tumorigenesis. However, its function in pancreatic cancer remains poorly understood. Here, we found that the expression of TRAF6 was up-regulated in pancreatic cancer tissues. Moreover, over-expression of TRAF6 in pancreatic cancer cells promoted cell proliferation and migration, whereas down-regulation of TRAF6 impaired the tumorigenicity of pancreatic cancer cells in vitro and in vivo. Mechanistically, TRAF6 regulated the expression of multiple genes involved in cell growth, apoptosis and migration. Our results suggested several important roles of TRAF6 in the pathogenesis of pancreatic cancer. TRAF6 might therefore represent a potential therapeutic target.

Post-splenectomy intrapancreatic accessory spleen mimicking endocrine tumor of the pancreas

Highlights • The first case of IPAS arising after splenectomy.• The IPAS has similar features of pancreatic neuroendocrine tumor on images.• Typical pathologic data and characteristics of IPAS were presented and described.• A brief review of IPAS was included.

DNA-PKcs deficiency sensitizes the human hepatoma HepG2 cells to cisplatin and 5-fluorouracil through suppression of the PI3K/Akt/NF-κB pathway

The aim of the present study was to investigate the effects of DNA-PKcs deficiency on the chemosensitivity of human hepatoma HepG2 cells to cisplatin (CDDP) and 5-fluorouracil (5-Fu), and to explore the underlying molecular mechanism. After transfection with DNA-PKcs siRNA or control siRNA, HepG2 cells were exposed to combination treatment of CDDP and 5-Fu. The cell viability, DNA damage, cell apoptosis, intracellular reactive oxygen species and glutathione (GSH) level, expression of apoptosis related proteins, activity of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway, and nuclear factor-κB (NF-κB) pathways were assessed. The combination of CDDP and 5-Fu had a synergistic cytotoxic effect in HepG2 cells in terms of the cell viability, DNA damage, apoptosis, and oxidative stress level. DNA-PKcs siRNA could sensitize the HepG2 cells to the combined treatment. DNA-PKcs suppression further reduced the Akt phosphorylation level and Bcl-2 expression in HepG2 cells exposed to CDDP and 5-Fu, but enhanced the expression of pro-apoptotic proteins p53 and caspase-3. Moreover, CDDP could inhibit the transcriptional activity of NF-κB through degradation of IkB-α, while 5-Fu alone seemed in some extent increases the NF-κB activity. The combined treatment with CDDP and 5-Fu resulted in significantly decrease of the transcriptional activity of NF-κB, which was further aggravated by DNA-PKcs siRNA treatment. In conclusion, DNA-PKcs suppression had complementary effects in combination with CDDP and 5-Fu treatment in HepG2 cells, which was associated with suppression of NF-κB signaling pathway cascade, activation of caspase-3 and p53, as well as down-regulation of Bcl-2 and GSH.

Survival prediction in pancreatic cancer patients with no distant metastasis: a large-scale population-based estimate

AIM To identify the risk factors for overall survival (OS) of pancreatic ductal adenocarcinoma patients with no distant metastasis, and formulate a novel nomogram for prognostic prediction. PATIENTS & METHODS Data were obtained from Surveillance, Epidemiology, and End Results database of pancreatic ductal adenocarcinoma patients with no distant metastasis as the primary cohort, and 127 patients at our institution were enrolled as the validation cohort. The prognostic nomogram integrating all independent risk factors for predicting OS was established to achieve superior discriminatory ability. RESULTS The constructed nomogram showed excellent performance and superior predictive accuracy for OS according to the concordance index and calibration curve. CONCLUSION One more advanced and accurate predictive model will be obtained to assist in risk stratification via the constructed nomogram.

SF3B4 is decreased in pancreatic cancer and inhibits the growth and migration of cancer cells

Splicing factor 3b subunit 4, a critical component of pre-message RNA splicing complex, has been reported to play an important part in the tumorigenesis. However, the expression pattern and biological role of splicing factor 3b subunit 4 in pancreatic cancer have never been investigated. In this study, we found that both the messenger RNA (p < 0.001) and protein level of splicing factor 3b subunit 4 were decreased significantly in pancreatic cancer specimens compared with their adjacent normal tissues. Overexpression of splicing factor 3b subunit 4 in pancreatic cancer cells inhibited cell growth and motility in vitro, while suppressing splicing factor 3b subunit 4 expression promoted the proliferation and migration of pancreatic cancer cells. In addition, splicing factor 3b subunit 4 was found to inhibit the activity of signal transducer and activator of transcription 3 signaling via downregulating the phosphorylation of signal transducer and activator of transcription 3 on a tyrosine residue at position 705. Taken together, these findings demonstrated that splicing factor 3b subunit 4 acted as a suppressive role in pancreatic cancer and indicated that restoring the function of splicing factor 3b subunit 4 might be a strategy for cancer therapy.

One Hundred Twenty-One Resected Solid Pseudopapillary Tumors of the Pancreas: An 8-Year Single-Institution Experience at Zhongshan Hospital, Shanghai, China.

Objectives The aims of this study were to introduce our experience with treating patients with pancreatic solid pseudopapillary tumors (SPTs) and to investigate the clinical risk factors for recurrence of SPTs because no consensus has been established to date. Methods One hundred twenty-one patients underwent surgical resection from January 2008 to December 2015 in our institution. Clinical data were collected from the standardized reports. Results Of the 121 patients, 93 (76.9%) were women, 28 (23.1%) were men, and the mean age at diagnosis was 33.7 years (range, 11–68 years). Sixty patients were subjected to short-term complications, and 8 patients experienced long-term complications, some of whom may require surgery. The tumor located in the distal pancreas (P = 0.02), and a Ki-67 index value > 1.5 (P = 0.01) indicated malignancy according to the World Health Organization 2000 classification. One hundred three patients responded to follow-up, and 3 cases (2.9%) were subject to liver metastases. Recurrence was more frequently observed in tumors classified as high-grade malignancies according to the World Health Organization 2010 classification (P = 0.013), synchronous metastases (P < 0.001), peripancreatic fat infiltration (P = 0.018), and lymphovascular invasion (P < 0.001). Conclusions Evaluating the risk of the recurrence of SPTs still requires systematic and multicenter trials in the future, even some pathological features showed statistical differences.

The value of systemic inflammatory markers in identifying malignancy in mucinous pancreatic cystic neoplasms

The treatment decision-making of mucinous pancreatic cystic neoplasm (PCN) has become a common clinical problem since the diagnostic accuracy of current tests in identifying malignancies in pancreatic cysts is limited. In this study, we aimed to validate the predictive value of systemic inflammatory factors in detecting malignant PCNs. Two hundred and forty-five patients with pathologically confirmed mucinous PCNs in a single Chinese institution were retrospectively analyzed. Receiver operating characteristic (ROC) curves were calculated to determine the optimal cut-off values and measure the diagnostic value. The results showed that neutrophil count (P = 0.009), lymphocyte count (P = 0.002), neutrophil-to-lymphocyte ratio (NLR, P < 0.001), platelet-to-lymphocyte ratio (PLR, P < 0.001) and lymphocyte-to-monocyte ratio (LMR, P < 0.001) were distributed differently among the various differentiation groups of PCN. The univariate analyses indicated that a neutrophil count ≥ 2.8 × 109/L (P = 0.024), lymphocyte count ≤ 1.9 × 109/L (P < 0.001), PLR ≥ 125 (P < 0.001), NLR ≥ 1.96 (P < 0.001), and LMR ≤ 4.29 (P < 0.001) were significantly associated with invasive carcinomas in PCN patients. In addition, the multivariate analyses demonstrated that PLR ≥ 125 and LMR ≤ 4.29 were independent predictors of invasive malignancies. The ROC curves exhibited the malignant detection utility of the independent factor-based predictive model with an area under the curve (AUC) of 0.858 (P < 0.001). In conclusion, systemic inflammatory markers provide a supportive and easily accessible tool for the preoperative diagnoses of malignant PCNs.