Robotic versus laparoscopic liver resection in posterosuperior region: a retrospective study of consecutive cases.

BACKGROUND: Minimally invasive liver resection of the posterosuperior region is considered a challenging procedure due to poor exposure and difficult bleeding control. A robotic approach is supposed to be advantageous in posterosuperior segmentectomy. Its benefits over laparoscopic liver resection (LLR) remain undetermined. This study compared robotic liver resection (RLR) and LLR in the posterosuperior region performed by a single surgeon. MATERIALS AND METHODS: We retrospectively analyzed consecutive RLR and LLR performed by a single surgeon between December 2020 and March 2022. Patient characteristics and perioperative variables were compared. A 1:1 propensity score matched (PSM) analysis was performed between both groups. RESULTS: The analysis included 48 RLR and 57 LLR procedures in the posterosuperior region. After PSM analysis, 41 cases of both groups were retained. In pre-PSM cohort, the operative time in the RLR group was significantly shorter than in the LLR group (160 vs. 208 min, P = 0.001), especially in radical resection of malignant tumors (176 vs. 231 min, P = 0.004). The total Pringle maneuver duration was also markedly shorter (40 vs. 51 min, P = 0.047), and the estimated blood loss in the RLR group was lower (92 vs. 150 mL, P = 0.005). The postoperative hospital stay (POHS) in the RLR group was significantly shorter (5.4 vs. 7.5 days, P = 0.048). In PSM cohort, operative time in the RLR group was also significantly shorter (163 vs. 193 min, P = 0.036), and the estimated blood loss was lower (92 vs. 144 mL, P = 0.024). However, the total Pringle maneuver duration and POHS showed no significant difference. The complications were similar between two groups in both pre-PSM and PSM cohorts. CONCLUSION: RLR in the posterosuperior region was as safe and feasible as LLR. RLR was associated with reduced operative time and blood loss than LLR.

Utilization of hepatitis B virus surface antigen positive grafts in liver transplantation: A matched study based on a national registry cohort.

BACKGROUND AND AIM: Donor shortage has become worldwide limitation in liver transplantation (LT). Use of hepatitis B virus surface antigen positive (HBsAg+) donors could be an alternative source of donor organs. This study aims to investigate the safety and efficacy of LT using HBsAg+ liver grafts and associated long-term outcome. METHODS: This was a retrospective study of adults LT registered in the database of the China Liver Transplant Registry between January 2015 and September 2018. By propensity score matching (1:1), 503 eligible patients who received HBsAg+ liver grafts were compared with 503 matched patients who received HBsAg- liver grafts. RESULTS: The 1-, 3-, and 5-year patient survival rates were 81.52%, 72.04%, and 66.65% in HBsAg+ donor group, which were comparable with 83.93%, 77.27%, and 65.73% in HBsAg- donor group (P = 0.222). The 1-, 3-, and 5-year graft survival rates were also comparable between the two groups (81.49%, 71.45%, and 67.26% vs 83.62%, 77.11%, and 65.81%, respectively, P = 0.243). Most main complications were not increased in HBsAg+ donor group except for the retaining of HBsAg positivity after LT. Furthermore, transplanting HBsAg+ liver grafts did not result in inferior outcomes either in HBsAg+ or HBsAg- recipients. The risk of tumor recurrence after LT was not increased in hepatocellular carcinoma patients. CONCLUSIONS: The outcomes of using HBsAg+ liver grafts were comparable with those of HBsAg- liver grafts. Our study provided strong evidence for the safe use of HBsAg+ grafts in LT to expand the donor liver pool.

A comparison of robotic versus laparoscopic distal pancreatectomy: a single surgeon's robotic experience in a high-volume center.

BACKGROUND: Robotic surgery is the most recent advanced minimally invasive approach for distal pancreatectomy. However, its benefits over laparoscopic distal pancreatectomy (LDP) remain undetermined. Previous studies were limited by their small sample size or variations in surgeon skills. This study aimed to compare robotic distal pancreatectomy (RDP) performed by a single surgeon with LDP performed by skilled laparoscopic surgeons in a high-volume center. METHODS: We retrospectively analyzed consecutive RDP performed by a single surgeon between December 2020 and November 2021 with LDP performed by experienced surgeons during the same period in a high-volume center. Patient characteristics and perioperative variables were compared. RESULTS: The analysis included 55 RDP and 146 LDP procedures. The operative time in the RDP group was significantly shorter than the LDP group (171 vs. 222 min, P < 0.001), both in spleen-preserved (154 vs. 212 min, P < 0.001) and spleen-removed (192 vs. 230 min, P = 0.005) procedures. The RDP group made more frequent use of the stapler technique for pancreas transection (87.3 vs. 68.5%, P = 0.007), and its estimated blood loss was lower (79 vs. 155 mL, P < 0.001) than the LDP group. The postoperative hospital stay in the RDP group was significantly shorter than the LDP group (8 vs. 12 days, P < 0.001). The groups were similar in their complication distributions. CONCLUSION: RDP is as safe and feasible a minimally invasive approach as LDP. The advanced manipulation and visualization capabilities of the robotic approach in distal pancreatectomy could help reduce operative time and blood loss, and is related to shorter postoperative hospital stay.

Selection of treatment for hepatic epithelioid hemangioendothelioma: a single-center experience.

BACKGROUND: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare angiogenic tumor with no recognized effective treatment. Treatment options used worldwide include liver transplantation (LT), liver resection (LR), radiofrequency ablation (RFA), chemotherapy, and observation. The aim of this study was to describe the efficacy of different treatment options used for HEHE at our center. METHODS: The medical charts of 12 patients with HEHE (9 women and 3 men) who were diagnosed and treated at the First Affiliated Hospital of Zhejiang University, China, between January 2011 and December 2017 were retrospectively reviewed. RESULTS: The patients were diagnosed by postoperative histopathology or fine needle aspiration biopsy. Two patients with diffuse lesions received LT and were alive without recurrence at the last follow-up. Three patients received LR as the initial treatment, and all of them developed recurrence during the follow-up period. One patient received RFA and remained free of disease, while the remaining six patients opted for simple observation rather than treatment. One of the patients who received LR passed away because of tumor recurrence within 32 months after surgery; the other patients showed no significant disease activity after treatments for their recurrent lesions. As of April 2018, the mean follow-up duration was 39.6 ± 20.1 months (15-82 months). CONCLUSIONS: There are multiple strategies for HEHE. Considering its indolent course, initial observation for assessment of the lesion behavior may aid in the selection of appropriate treatment. Surgery or LT is suitable for patients with disease progression during the observation period. However, our sample size was small, and further studies are required to gather more information that can aid in optimal treatment selection.

Lower tacrolimus trough levels in the late period after living donor liver transplantation contribute to improvements in long-term clinical outcomes.

BACKGROUND: Previous studies have emphasized the need to reduce tacrolimus (TAC) trough levels in the early post-liver transplantation (LT) period. However, whether late-period TAC trough levels influence the long-term outcomes of liver recipients is not clear. METHODS: We enrolled 155 adult liver recipients survived more than 3 years after living donor liver transplantation because of non-malignant liver diseases. The maintenance immunosuppressive regimens were TAC monotherapy and combined therapy with mycophenolate mofetil. Patients were divided into three groups according to their late-period TAC trough levels: < 3 ng/mL group, 3-5 ng/mL group, and  >5 ng/mL group. The complications and adverse effects of TAC were analyzed. RESULTS: Each group showed similar rejection, graft loss and mortality. Patients achieved the < 5 ng/mL state in less than 4 years had fewer new-onset diabetes, hyperlipidemia, de novo malignancies, and hepatitis B virus recurrence; the complications of renal dysfunction and hypertension rates were the same among these 3 groups. CONCLUSIONS: Collectively, our findings indicated that lower TAC trough levels in the late period of liver transplantation are safe, improve the long-term outcomes.

Role of [18F] fludeoxyglucose positron emission tomography in the selection of liver transplantation candidates in patients with hepatocellular carcinoma.

BACKGROUND: The Milan criteria are widely accepted among many centers. However, patients with hepatocellular carcinoma beyond the Milan criteria might still benefit from liver transplantation (LT) when tumor itself is not aggressive. [18F] fluorodeoxyglucose positron emission tomography/computed tomography imaging could provide useful information of tumor behaviors, which is helpful to predict the prognosis for many tumors. METHOD: In order to determine its role in candidate selection for LT, we therefore retrospectively analyzed 103 recipients with preoperative positron emission tomography (PET) findings. RESULTS: Positive PET findings (PET+) were significantly associated with tumor nodule numbers (P=0.013), tumor grade (P=0.025), macro- (P=0.002) and micro-vascular invasion (P=0.002), as well as the Milan criteria (P=0.018). PET+ patients had significantly increased risk of tumor recurrence post-LT compared to PET negative (PET-) patients (P=0.007). The 1-, 3-, and 5-year overall survival rate of PET- patients were 96.0%, 87.2% and 76.2%, compared to 74.7%, 55.4% and 49.9% in PET+ patients, respectively (P<0.05). The 1-, 3-, and 5-year recurrence-free survival rate of PET- patients were 91.8%, 81.9% and 76.0%, compared to 70.1%, 39.3% and 21.9% in PET+ patients, respectively (P<0.05). Recipients within the Milan criteria showed comparable 1-, 3-, and 5-year survival rates in comparison with those beyond the Milan criteria with a PET- findings (1-, 3-, and 5-year overall survival rates, 97.5%, 83.3%, and 83.3% vs 90.0%, 80.0%, and 66.7%, P= 0.123; 1-, 3-, and 5-year recurrence-free survival rates, 95.1%, 73.1%, and 73.1% vs 90.0%, 78.8%, and 65.6%, P=0.148). CONCLUSIONS: Certain patients with hepatocellular carcinoma and negative PET findings, who have exceeded the Milan criteria, are also eligible candidates for LT. Preoperative PET/CT imaging is an important marker, which should be incorporated in extended candidate selection criteria for LT.

Prognostic prediction of male recipients selected for liver transplantation: With special attention to neutrophil to lymphocyte ratio.

AIM: Neutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker that has a close relationship with tumor progression and metastasis. In this study, we aimed to investigate the role of NLR in the prognosis of male candidates with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). METHODS: We analyzed the clinical data of 248 male HCC candidates who underwent LT in our Liver Transplantation Center between 2002 and 2012. All risk factors were analyzed by univariate and multivariate Cox analysis and survival rates were calculated by Kaplan-Meier log-rank test. RESULTS: NLR was proved to be an independent risk factor affecting overall survival (OS) (P < 0.001) and tumor-free survival (TFS) (P = 0.003) of male candidates with HCC following LT. Additionally, our study showed that elevated NLR (>4) was associated with early tumor recurrence by Kaplan-Meier analysis. Furthermore, we established Model_OS and Model_TFS to predict prognosis based on multivariate Cox analysis. Our study showed that male candidates with HCC who exceeded the Milan criteria but within Model_OS could achieve similar OS as those within the Milan criteria (P = 0.220). Similarly, male patients who exceeded the Milan criteria but within Model_TFS could achieve similar TFS as those within the Milan criteria (P = 0.197). CONCLUSION: Proper inflammatory response may effectively reduce tumor recurrence after LT. Elevated NLR (>4) within a certain range is associated with early tumor recurrence. NLR-based models are efficient and safe for prognostic prediction among male candidates with HCC for LT.

Anti-virus prophylaxis withdrawal may be feasible in liver transplant recipients whose serum HBeAg and HBV DNA are negative.

Anti-virus prophylactic therapy may be not necessary for the prevention of hepatitis B virus (HBV) recurrence after HBV-related liver transplantation (LT). However, studies on completely stopping the hepatitis B immune globulin (HBIG) and nucleos(t)ide analogs (NUC) after LT are few. The aim of the current study was to evaluate the safety of anti-virus prophylaxis withdrawal in liver recipients whose serum hepatitis B e antigen (HBeAg) and HBV DNA are negative. We analyzed 190 patients undergone LT for HBV-related liver disease from 2006 to 2012 and found that 10 patients completely stopped the HBIG and NUC due to poor compliance. These patients were liver biopsied and checked monthly with serum HBV markers, HBV DNA and liver function. Among the 10 patients, 9 did not show the signs of HBV recurrence after a mean follow-up of 51.6 months (range 20-73) after withdrawal of the HBIG and NUC. The average time from LT to the withdrawal of the anti-virus drug was 23.8 (13-42) months; one patient showed hepatitis B surface antigen-positive and detectable HBV DNA after stopping anti-virus drugs and this patient was successfully treated with entecavir. Our data suggested that complete withdrawal of anti-virus prophylaxis was safe and feasible for patients whose serum HBeAg and HBV DNA were negative at the time of LT.

Safe use of liver grafts from hepatitis B surface antigen positive donors in liver transplantation.

BACKGROUND & AIMS: Liver grafts from hepatitis B surface antigen (HBsAg) positive donors could have potential to increase the donor pool. However, knowledge is extremely limited in this setting because currently available data are mostly from case reports. We aimed to assess the outcomes and experiences of liver transplantation from HBsAg positive donors in a single centre study. METHODS: From January 2010 to February 2013, 42 adult patients underwent liver transplantation from HBsAg positive donors and 327 patients from HBsAg negative ones. The outcomes including complications and survival of two groups were compared and antiviral therapy retrospectively reviewed. RESULTS: HBsAg positive liver grafts were more likely to be allocated to patients with hepatitis B (HBV)-related diseases. Post-transplant evaluation showed similar graft function regaining pace and no differences in complications such as primary non-function, acute rejection and biliary complications. Patient and graft survivals were comparable to that of HBsAg negative grafts. Furthermore, HBsAg persisted after transplant in all patients that received positive grafts. The donor HBV serum status determined the one of the recipient after transplantation. No HBV flare-ups were observed under antiviral therapy of oral nucleotide analogues, regardless of using hepatitis B immunoglobulin combination. CONCLUSIONS: Utilization of HBsAg positive liver grafts seems not to increase postoperative morbidity and mortality. Therefore it is a safe way to expand the donor pool when no suitable donor is available. Our experience also suggests that hepatitis B immunoglobulin should be abandoned in recipients of HBsAg positive liver grafts, in whom HBV prophylaxis could be the only oral antiviral therapy.

Drug-Loaded Biomimetic Carriers for Non-Hodgkin's Lymphoma Therapy: Advances and Perspective.

Chemotherapy remains the mainstay of treatment for the lymphoma patient population, despite its relatively poor therapeutic results, high toxicity, and low specificity. With the advancement of biotechnology, the significance of drug-loading biomimetic materials in the medical field has become increasingly evident, attracting extensive attention from the scientific community and the pharmaceutical industry. Given that they can cater to the particular requirements of lymphoma patients, drug-loading biomimetic materials have recently become a potent and promising delivery approach for various applications. This review mainly reviews the recent advancements in the treatment of tumors with biological drug carrier-loaded drugs, outlines the mechanisms of lymphoma development and the diverse treatment modalities currently available, and discusses the merits and limitations of biological drug carriers. What is more, the practical application of biocarriers in tumors is explored by providing examples, and the possibility of loading such organisms with antilymphoma drugs for the treatment of lymphoma is conceived.

Splenectomy for treating hepatosplenic candidiasis: Two cases and literature review suggesting its feasibility.

Background: Hepatosplenic candidiasis is a rare but severe complication in immunocompromised patients undergoing chemotherapy. Antifungal agents are widely accepted as the first choices for therapy. However, resistance to or side-effect of antifungal agents may comxpromise its efficiency. Splenectomy has also been rarely performed as treatment for this disease. Methods: We present two cases of splenectomy for treating hepatosplenic candidiasis after failure of the initial drug therapy. Literatures on splenectomy as treatment for hepatosplenic candidiasis were searched in Pubmed and summarized. Results: Two leukemia patients developed hepatosplenic candidiasis after received chemotherapy for their primary diseases. Various antifungal agents including amphotericin B were all demonstrated failure to cure fever and the Candida abscesses due to resistance or intractable side-effect. Laparoscopic splenectomy were finally performed and resolved the candidiasis successfully. A total of 12 splenectomy cases for treating hepatosplenic candidiasis had been previously reported in literature. All the cases showed either resistance or unimproved to initial antifungal therapies. Splenectomy provided salvage therapeutic value in all cases. Conclusion: Splenectomy has therapeutic effect and may change the traditional concept in most surgeons. The present study may expand an alternative strategy in clinical practice guideline for the management of hepatosplenic candidiasis.

Galectin Family Members: Emerging Novel Targets for Lymphoma Therapy?

The galectin family of proteins has high affinity with ß-galactoside-containing glycans. These proteins participate in cell growth and differentiation, cell adhesion, cell signal transduction, cell apoptosis, and other cellular activities. In recent years, a large number of studies have described the expression and correlation of galectins in different tumors. Each member of the family plays a vital role in tumor growth, progression, angiogenesis, adhesion, and tumor immune escape. Studies on the roles of galectins in lymphoma have mainly involved galectin-1, -3, -7, and -9. The results suggest that galectins may become novel targets for precise tumor treatment. This article reviews current research progress regarding galectins in lymphoma and provides new ideas for exploring them as novel targets for treating lymphoma and other important medical issues.

A Nomogram Estimation for the Risk of Microvascular Invasion in Hepatocellular Carcinoma Patients Meeting the Milan Criteria.

OBJECTIVE: We aimed to develop and validate a nomogram for preoperatively estimating the risk of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) within the Milan criteria. METHODS: The clinical data of 312 HCC patients who underwent liver surgery at the xxx from Jan 2017 to Dec 2019 were retrospectively collected. Then, the study population was categorized into the training and validation group based on the date of surgery. To identify risk factors related to MVI, we conducted a series of logistic regression analyses. By combining these risk factors, a nomogram was then established. We further clarified the usability of our model through the area under the ROC curve (AUC), decision curve analysis (DCA), and calibration curve. RESULTS: Pathological examination revealed MVI in 108 patients with HCC (34.6%). Three independent predictors were identified: level of alpha-fetoprotein (AFP) exceeds 194 ng/mL (OR = 2.20, 95% CI: 1.13-4.31, p = 0.021), size of tumor (OR = 1.59; 95% CI: 1.18-2.12; P < 0.001) and number of tumors (OR = 3.37, 95% CI: 1.64-7.28, p < 0.001). A nomogram was subsequently built with an AUC of 0.73 and 0.74 respectively in the training cohort and validation cohort. The calibration curve showed a relatively high consistency between predicted probability and observed outcomes. Besides, the DCA revealed that the model was clinically beneficial for preoperatively predicting MVI in HCC. CONCLUSIONS: A model for evaluating the risk of MVI HCC patients was developed and validated. The model could provide clinicians with a relatively reliable basis for optimizing treatment decisions.

Kupffer cells contribute to concanavalin A-induced hepatic injury through a Th1 but not Th17 type response-dependent pathway in mice.

BACKGROUND: Increasing evidence suggests that a close interaction of Kupffer cells with T cells plays a central role in concanavalin A-induced hepatic injury in mice, but the underlying mechanisms remain obscure. The present study aimed to determine the relative roles of Th1 and Th17 type responses in concanavalin A-induced hepatic injury in mice, and to investigate whether or not Kupffer cells contribute to hepatic injury via a Th1 or Th17 type response-dependent pathway. METHODS: Immune-mediated hepatic injury was induced in C57BL/6 mice by intravenous injection of concanavalin A. Kupffer cells were inactivated by pretreatment with gadolinium chloride 24 hours before the concanavalin A injection. The interferon-gamma (IFN-gamma) and interleukin-17 (IL-17) pathways were blocked by specific neutralizing antibodies. Hepatic injury was assessed using serum transferase activity and pathological analysis. Expression of inflammatory cytokines within the liver was detected by real-time polymerase chain reaction and immunohistochemistry. RESULTS: Neutralization of IFN-gamma significantly attenuated concanavalin A-induced hepatic injury. However, neutralization of IL-17 failed to suppress the injury. Inactivation of Kupffer cells by gadolinium chloride pretreatment protected against concanavalin A-induced injury and significantly reduced hepatic cytokine levels including TNF-alpha, IL-6 and IFN-gamma but not IL-17. CONCLUSION: Our findings suggest that Kupffer cells contribute to concanavalin A-induced hepatic injury via a Th1 type response-dependent pathway and production of inflammatory cytokines including TNF-alpha, IL-6 and IFN-gamma.

Involvement of Th17 and Th1 effector responses in patients with Hepatitis B.

BACKGROUND: Local production of cytokines within the liver may play a pivotal role in the regulation of pathophysiological processes during inflammation. CD4+ T cells are regarded as the most prolific cytokine producers. The purpose of this study was to quantify intrahepatic expression of Th1, Th2, Th17, and Treg-associated cytokines or transcription factors in patients with acute hepatitis B or chronic hepatitis B (CHB) and to analyze their relative roles in the promotion and regulation of hepatitis B virus (HBV)-associated liver diseases. METHODS: Distribution and expression of IL-17, IFN-gamma, IL-4, Foxp3, and other cytokines in liver tissues were detected by immunohistochemistry and real-time quantitative PCR. Patients with hepatitis B were compared with patients with chronic hepatitis C, primary biliary cirrhosis, alcoholic liver cirrhosis, and healthy controls. RESULTS: The frequencies of intrahepatic IL-17 and IFN-gamma-producing cells in patients with HBV-associated liver dysfunction were much higher than that of IL-4 and Foxp3-positive cells. The level of the IL-17/IFN-gamma-positive cell ratio of patients with Child-Pugh class C (1.57+/-0.09) was much higher than that of patients with Child-Pugh class B (1.00+/-.02) or A (0.93+/-0.05). There are more IL-17-producing cells than IFN-gamma-producing cells accumulating in the liver with severe hepatocellular damage. Liver IL-17-producing cell infiltration was positively associated with the grade of liver inflammation in CHB and positively correlated to intrahepatic IL-8 expression (r=0.801, p<0.01) or neutrophil infiltration (r=0.917, p<0.01). CONCLUSIONS: These results suggest that the balance of effector CD4+ Th responses (Th17 and Th1 responses) and regulatory response is an important element of immune regulation. Inappropriate, excessive, and non-specific Th17 and Th1 effector responses may be involved in the pathogenesis of HBV-associated liver inflammation and hepatocellular damage. Th17 response, especially, may exacerbate the inflammatory processes leading to liver failure. IL-17-mediating liver neutrophil recruitment via induction of IL-8 may be one potential mechanism of liver injury in patients with hepatitis B. An improved understanding of the factors that influence the differentiation and function of these cell types in vivo will be of great importance to the future development of immune therapies in HBV-associated liver disease.

Metastatic renal cell carcinoma to the pancreas and subcutaneous tissue 10 years after radical nephrectomy: a case report.

BACKGROUND: Synchronous renal cell carcinoma metastasizing to the pancreas and subcutaneous tissue is very rare. Unusual metastatic sites require attention during follow-up of renal cell carcinoma. It is extremely rare for renal cell carcinoma to metastasize to the pancreas; it is also very rare for it to metastasize to the subcutaneous tissue and extremely rare for it to synchronously metastasize to the pancreas and subcutaneous tissue almost a decade after radical nephrectomy. It is well known that most pancreatic tumors are primary pancreatic adenocarcinoma. However, the pancreas can also be an uncommon site for metastasis. We present a rare case of synchronous metastasis of renal cell carcinoma to the pancreas and subcutaneous tissue; we believe it to be only the second such case reported to date. CASE PRESENTATION: We describe a case of a 74-year-old Chinese man who was diagnosed with metastatic renal cell carcinoma to the pancreas and subcutaneous tissue at the same time, 10 years after left radical nephrectomy. He received distal pancreatectomy with spleen preservation plus resection of the subcutaneous tissue lesions on the left side of the anterior abdominal wall and right waist. Pathology showed that all resected metastatic tumors were of the clear cell type. The patient was seen in regular follow-up afterward. CONCLUSION: Synchronous metastatic renal cell carcinoma to the pancreas and subcutaneous tissue is very rare, and it might occur after primary tumor resection. Patients must undergo lifelong monitoring and follow-up with regular examination so that any possible metastasis can be detected early. The optimal resection strategy should involve adequate resection margins and maximal tissue preservation of the pancreas, because renal cell carcinoma metastasizing to the pancreas and subcutaneous tissue has a good prognosis with long-term survival.

LncRNA HOTAIR Contributes to Sorafenib Resistance through Suppressing miR-217 in Hepatic Carcinoma.

BACKGROUND: Sorafenib is a multi-target kinase inhibitor that has been approved as a unique target drug for the treatment of advanced hepatocellular carcinoma (HCC). However, due to the frequent occurrence of drug resistance, its treatment efficacy is often limited. The aim of this study was to explore the function of HOX transcript antisense intergenic RNA (HOTAIR) for the treatment of HCC with sorafenib, and its underlying mechanism. METHODS: A cell counting kit-8 (CCK-8) assay and Edu assay were used to examine the viability and proliferation of HCC cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of HOTAIR and miR-217 in HCC cells. Small interfering (si) RNA was transfected to knockdown HOTAIR to explore its biological function. A Western blot and immunofluorescence were performed to detect the level of E-cadherin and Vimentin expression. RESULTS: Sorafenib resistance was increased in HCC cells with high HOTAIR expression. Moreover, a knockdown of HOTAIR could improve the therapeutic effect of sorafenib on HCC via increasing E-cadherin and decreasing Vimentin expression. Additionally, a HOTAIR knockdown could increase the sensitivity of sorafenib for HCC treatment by up-regulating miR-217. CONCLUSIONS: Lnc HOTAIR could increase sorafenib resistance in HCC by inhibiting miR-217. Our research attempts to elucidate a more effective treatment and provides novel insight into potential clinical treatment for HCC.

AntagomiR-199a Enhances the Liver Protective Effect of Hypoxia-Preconditioned BM-MSCs in a Rat Model of Reduced-Size Liver Transplantation.

BACKGROUND: Reduced-size liver transplantation (LT) was invented to overcome the shortage of donor livers; however, it has proven to be more susceptible to ischemia-reperfusion injury. Bone marrow-derived mesenchymal stem cell infusion has been shown to be protective following LT. Optimization of MSC infusion has been performed, among which hypoxia preconditioning and miRNA modulation have shown promise. MiR-199a inhibition was reported to induce angioneogenesis; however, whether mir-199a inhibition enhances the protective effect of Bone marrow-derived mesenchymal stem cells in LT remains unknown. In this study, we combined antagomiR-199a with hypoxia-preconditioned MSC (H-MSC) infusion to discuss their effect and mechanism in a rat model of reduced-size LT. METHODS: A reduced-size LT model was constructed and H-MSCs were intraportally injected during operation. AgomiR-199a and antagomir-199a were injected through the caudal vein once a day after LT. The level of apoptosis and proinflammatory cytokines were measured. An anti-vascular endothelial growth factor (VEGF) antibody was injected to further explore the underlying mechanism. RESULTS: AntagomiR-199a plus H-MSC not only significantly decreased ALT and AST 72 h after LT but also ameliorated the level of apoptosis and inhibited inflammatory reactions. On the contrary, agomir-199a reduced the protective effect of the H-MSC infusion. In terms of mechanism, the liver protective effect of miR-199a inhibition was abolished by treatment with a VEGF-neutralizing antibody. CONCLUSIONS: AntagomiR-199a enhanced the protective effect of H-MSCs infusion via activation of the hypoxia induction factor 1α/VEGF axis.

Interaction of B7-H1 on intrahepatic cholangiocarcinoma cells with PD-1 on tumor-infiltrating T cells as a mechanism of immune evasion.

BACKGROUND AND OBJECTIVES: The B7-H1/PD-1 pathway has recently been found to contribute to immune evasion of cancer cells from host immune system. This study aimed to investigate the expression of B7-H1 and its receptor PD-1 and to explore their significance in the progression of intraheptic cholangiocarcinoma (ICC). METHODS: Thirty-one surgically resected ICC tissues and the corresponding cancer adjacent tissues were enrolled from 2006 to 2007. Immunohistochemical studies were performed with antibody of B7-H1, PD-1, CD8, and CD4. Apoptosis status of tumor-infiltrating lymphocytes (TILs) was detected by TUNEL assay. RESULTS: Expression of B7-H1 and PD-1 was found to be up-regulated in ICC tissues compared with the cancer adjacent tissues. Tumor-related B7-H1 expression was significantly correlated with both tumor differentiation and pTNM stage and was inversely correlated with CD8+ TILs but not CD4+ TILs. TILs in primary carcinoma showed a high level of apoptosis. CONCLUSION: B7-H1/PD-1 pathway may be linked to malignant potential of ICC and contribute to tumor immune evasion by promoting CD8+ TILs apoptosis. Thus, this pathway may indeed be a potential therapeutic target in the treatment of this disease.

BCL11A: a potential diagnostic biomarker and therapeutic target in human diseases.

Transcription factor B-cell lymphoma/leukemia 11A (BCL11A) gene encodes a zinc-finger protein that is predominantly expressed in brain and hematopoietic tissue. BCL11A functions mainly as a transcriptional repressor that is crucial in brain, hematopoietic system development, as well as fetal-to-adult hemoglobin switching. The expression of this gene is regulated by microRNAs, transcription factors and genetic variations. A number of studies have recently shown that BCL11A is involved in ß-hemoglobinopathies, hematological malignancies, malignant solid tumors, 2p15-p16.1 microdeletion syndrome, and Type II diabetes. It has been suggested that BCL11A may be a potential prognostic biomarker and therapeutic target for some diseases. In this review, we summarize the current research state of BCL11A, including its biochemistry, expression, regulation, function, and its possible clinical application in human diseases.