Plumbagin,a medicinal plant (Plumbago zeylanica)-derived 1,4-naphthoquinone,inhibits growth and metastasis of human prostate cancer PC-3M-luciferase cells in an orthotopic xenograft mouse model

We present here first time that Plumbagin (PL), a medicinal plant-derived 1,4-naphthoquinone, inhibits the growth and metastasis of human prostate cancer (PCa) cells in an orthotopic xenograft mouse model. In this study, human PCa PC-3M-luciferase cells (2 × 10⁶) were injected into the prostate of athymic nude mice. Three days post cell implantation, mice were treated with PL (2 mg/kg body wt. i.p. five days in a week) for 8 weeks. Growth and metastasis of PC-3M-luciferase cells was examined weekly by bioluminescence imaging of live mice. PL-treatment significantly (p = 0.0008) inhibited the growth of orthotopic xenograft tumors. Results demonstrated a significant inhibition of metastasis into liver (p = 0.037), but inhibition of metastasis into the lungs (p = 0.60) and lymph nodes (p = 0.27) was not observed to be significant. These results were further confirmed by histopathology of these organs. Results of histopathology demonstrated a significant inhibition of metastasis into lymph nodes (p = 0.034) and lungs (p = 0.028), and a trend to significance in liver (p = 0.075). None of the mice in the PL-treatment group showed PCa metastasis into the liver, but these mice had small metastasis foci into the lymph nodes and lungs. However, control mice had large metastatic foci into the lymph nodes, lungs, and liver. PL-caused inhibition of the growth and metastasis of PC-3M cells accompanies inhibition of the expression of: 1) PKCε, pStat3Tyr705, and pStat3Ser727, 2) Stat3 downstream target genes (survivin and Bcl_xL), 3) proliferative markers Ki-67 and PCNA, 4) metastatic marker MMP9, MMP2, and uPA, and 5) angiogenesis markers CD31 and VEGF. Taken together, these results suggest that PL inhibits tumor growth and metastasis of human PCa PC3-M-luciferase cells, which could be used as a therapeutic agent for the prevention and treatment of human PCa.     

Positron emission tomography/computed tomography in patients with hepatocellular carcinoma undergoing liver transplantation. Useful,necessary or irrelevant?

Hepatocellular Carcinoma (HCC) is an aggressive tumor entity, with the only curative options being surgical resection or orthotopic liver transplantation (OLT). The presence of one single tumor nodule of less than 5 centimeters diameter or a maximum of 3 nodules, with the largest of these not exceeding 3 centimeters (Milan criteria) constitute the clinical situation in which the best results for OLT in patients with HCC have been achieved. The survival of patients fulfilling the Milan criteria after transplantation is comparable to patients with similar tumor stages without cirrhosis, undergoing hepatic resection. The application of PET in oncology has become increasingly common in the last decade as it is a non-invasive tool that also gathers information about the degree of the biological aggressiveness of the tumor. The objective of this study was to perform a review of the literature, identifying the strengths and weaknesses of the PET as a prognostic tool in patients with HCC after OLT.     

原位肝移植前后胆道及血管的磁共振成像评估*

背景：磁共振成像扫描技术的完善，实现了“一站式”磁共振综合检查，即1次检查过程中运用多种序列，同时对肝脏血管、胰胆管系统及上腹部器官进行影像评估，方便、快速、简捷。 目的：评价磁共振成像检查在肝移植前后的应用价值。 方法：选择中南大学湘雅三医院移植中心收治的肝硬化及肝癌患者38例，男27例，女11例，年龄23~68岁。原位肝移植前后进行磁共振成像检查，同时行双排螺旋CT检查，比较两种方法的优劣，最后以手术、病理检查结果确认。 结果与结论：所有终末期肝脏疾病患者原位肝移植前后经磁共振成像检查，能较准确地描述出肝癌病灶的情况，血管及胆道系统的异常解剖形态及其内栓子和结石的情况，其结果明显优于双排螺旋CT检查。说明磁共振成像在肝移植前评估和移植后并发症早期发现中有非常重要的作用。     

In vivo serial selection of human pancreatic cancer cells in orthotopic mouse models produces high metastatic variants irrespective of Kras status

Introduction

Kras mutations have been thought to play an important role in pancreatic cancer progression. In this study, we evaluated how serially passaging primary pancreatic tumors with and without Kras mutations, in nude mice, can generate more aggressive variants of human pancreatic cancer.

Materials & methods

Orthotopic mouse models of human pancreatic cancer were established by injecting 1 × 10⁶ cells of the Kras wildtype BxPC-3 cell line, expressing red fluorescent protein or the Kras mutant Panc-1 cell line expressing green fluorescent protein, into the pancreas. Pancreatic tumors were harvested from premorbid mice to establish cell lines. One million passaged cells were then orthotopically injected into another set of mice. Serial passaging continued until decreasing lifespan of the implanted mice stabilized, which occurred by six passages. Mice harboring serially-passaged cell lines were followed with weekly imaging.

Results

Serially passaging generated more aggressive variants of both human pancreatic cancer cell lines, one of which was Kras wild-type (BXPC-3) and the other Kras mutant, Panc-1, which displayed faster tumor growth and shortened survival time. Overall survival decreased from 18 wk in mice with the parental cell line (passage 0) tumor to ∼6 wk in mice by passage 6. Average time to metastasis was shortened from 14 wk to ∼3 wk or less. At termination, mice with the passaged tumor demonstrated a greater extent of distant metastasis.

Conclusions

Serial passaging of tumor creates more aggressive variants of human pancreatic cancer cell lines regardless of Kras mutation. The aggressive variants can be used to study the molecular basis of highly malignant pancreatic cancer and to screen for effective agents against this disease.     

超声对引起原位肝移植术后黄疸相关因素的分析

目的探讨超声对于提示引起原位肝移植术后黄疸相关因素的价值。方法28例实施肝移植术后临床拟诊黄疸的患者，以二维超声检查移植肝内外胆管及肝周情况，以彩色多普勒超声（CDI）评估移植肝动、静脉血流情况，并结合临床资料、肝穿刺活检病理诊断结果和内镜逆行胰胆管造影（ERCP）综合分析。结果22例患者术后出现胆道并发症，其中5例CDI提示有肝动脉并发症，超声检出胆漏者4例，胆道梗阻者18例；其余6例肝穿刺活检证实有排斥反应。结论多普勒超声显像可以较好地提示引起原位肝移植术后黄疸的相关因素，有利于临床医师作出正确的病情判断及确定相应的治疗方案。     

Intraoperative management and early post-operative outcomes of patients with coronary artery disease who underwent orthotopic liver transplantation

Background: Coronary artery disease (CAD) is frequently observed in aging end-stage liver disease (ESLD) patients who require orthotopic liver transplantation (OLT). This situation is challenging for both the pa- tients and the medical staff. Methods: We retrospectively studied the case records of 26 ESLD patients with CAD who underwent OLT with total clamping of the inferior vena cava between 2014 and 2018. We analyzed the details of the pre-operative evaluation, intraoperative anesthetic management and post-operative prognosis of these patients. Results: All patients tolerated the anhepatic stage well. Post-reperfusion syndrome (PRS) was observed in 13 patients (50%) and 2 of them were severe but corrected well. ST-segment depression was frequently observed during the anhepatic stage and reperfusion stage. No mortality due to cardiac-related events occurred among the patients during hospitalization. OLT with the modi ed piggyback technique could successfully be performed in ESLD patients with mild and moderate CAD. Conclusions: A thorough evaluation and optimization of recipients, strict monitoring and optimized man-agement of circulation, knowledge of the complicated changes during OLT procedures, and strategies to ameliorate post-reperfusion syndrome favorite the outcomes.     

Management of hepatitis C infection before and after liver transplantation

Chronic hepatitis C (CHC) is the most common indication for liver transplantation (LT). Aggressive treatment of hepatitis C virus (HCV) infection before cirrhosis development or decompensation may reduce LT need and risk of HCV recurrence post-LT. Factors associated with increased HCV risk or severity of recurrence include older age, immunosuppression, HCV genotype 1 and high viral load at LT. HCV recurrence post-LT leads to accelerated liver disease and cirrhosis development with reduced graft and patient survival. Currently, interferon (IFN)-based regimens can be used in dual-agent regimens with ribavirin, in triple-agent antiviral strategies with direct-acting antivirals (e.g., protease inhibitors telaprevir or boceprevir), or before transplant in compensated patients to reduce HCV viral load to prevent or reduce the risk of post-LT recurrence and complications; they cannot be used in patients with decompensated cirrhosis. IFN-based regimens are used in less than half of HCV-infected patients waiting for LT due to extremely low efficacy and poor tolerability. However, antiviral therapy is indicated after LT in patients with histologically confirmed CHC despite tolerability issues. Improvements in side effect management have increased survival in patients achieving therapeutic targets. HCV treatment pre- and post-LT results in significant health care costs especially when lack of efficacy leads to disease worsening, although studies have shown sofosbuvir treatment before LT vs conventional post-LT dual antiviral is cost effective. The suboptimal efficacy and tolerability of IFN-based therapies, plus the significant economic burden, means the need for effective and well tolerated IFN-free anti-HCV therapy for pre- and post-LT remains high.     

肝移植术时凝血功能障碍的处理

目的:探索同种原位肝移植术(OLT)时凝血功能障碍的诊断与治疗.方法:回顾性分析我院23例次OLT术前和术中凝血功能、术中出血量与输注凝血因子、血小板和红细胞悬液的关系.结果:术前69.6%、56.5%、30.4%肝病患者分别有凝血酶原时间(PT)、活化部分凝血活酶时间(aPTT)、凝血酶时间(TT)延长·中位延长时间分别为6.3、21.8、6.8 s;纤维蛋白原(Fg)和血小板计数(BPC)中位值分别为1.38g/L和47×109/L.术中100%、91.3%、65.2%患者PT、aPTT、TT分别较对照延长,中位延长时间分别为10.3、55.2、18.8 s;Fg和BPC的中位值分别为1.26 g/L和27×109/L.术前凝血功能正常或纠正充分者16例次,术中血制品用量明显减少,红细胞悬液中位用量4600 ml;而术前凝血功能纠正不充分者7例,术中出血量增多,血制品用量也明显增加,红细胞悬液中位用量9000 ml.结论:肝移植术加重术中凝血功能障碍;充分的术前准备和动态监测凝血功能并酌情补充血液成分可减少术中出血和输血,以保障手术顺利进行.     

Knockdown of liver-intestine cadherin decreases BGC823 cell invasiveness and metastasis in vivo

AIM: To assess BGC823 gastric cancer (GC) cell metastasis after knockdown of liver-intestine cadherin (CDH17) and the therapeutic value of CDH17-RNAi-lentivirus in vivo.METHODS: We evaluated primary tumor growth and assessed local infiltration and systemic tumor dissemination using an orthotopic implantation technique. The therapeutic value of CDH17 knockdown was examined by intratumoral administration of CDH17-RNA interference (RNAi)-lentivirus in an established GC tumor xenograft mouse model. Furthermore, a comparative proteomic approach was utilized to identify differentially expressed proteins in BGC823 and lenti-CDH17-miR-neg cells following CDH17 knockdown.RESULTS: Metastases in the liver and lung appeared earlier and more frequently in animals with tumors derived from BGC823 or lenti-CDH17-miR-neg cells than in tumors derived from lenti-CDH17-miR-B cells. Average tumor weight and volume in the CDH17-RNAi-lentivirus-treated group were significantly lower than those in the control group (tumor volume: 0.89 ± 0.04 cm³ vs 1.16 ± 0.06 cm³, P < 0.05; tumor weight: 1.15 ± 0.58 g vs 2.09 ± 0.08 g, P < 0.05). Fifteen differentially expressed proteins were identified after CDH17 silencing in BGC823 cells, including a variety of cytoskeletal and chaperone proteins as well as proteins involved in metabolism, immunity/defense, cell proliferation and differentiation, cell cycle, and signal transduction.CONCLUSION: Our data establish a foundation for future studies of the comprehensive protein expression patterns and effects of CDH17 in GC.