As a distinct T cell subset with acknowledged specific function and marker, CD4+CD25+FOXP3+ regulatory T cells are thought to dampen T-cell immunity and to be the main obstacle tempering antitumor immunotherapy. Accumulating evidence has confirmed an increased pool of regulatory T cells both in the peripheral blood and the tumor microenvironment of cancer patients, which are indicative of disease progression, response to therapy, invasive phenotype and prognosis. Therefore, manipulation of regulatory T cells—including depletion, blocking trafficking into tumors, or reducing their differentiation and suppressive mechanisms—and concomitant stimulation of effector T cells, systemically or locally in tumors, represent new strategies for cancer treatment.

The biological characteristic of carcinomas is determined both by the stromal microenvironment and the oncogene or anti-oncogene.The tumor stroma is also known as the reactive stroma which is composed of base member,immunocell,capillary,fibroblasts and ECM.Fibroblasts are the majority of tumor stromal cells.The relationship between fibroblasts and the initiation,progression of carcinoma has being in the spot light.In this review,we summarized the advance in the study of carcinoma-associated fibroblasts.

Smad3 is a major transporter in the transforming growth factor β (TGF-β) signaling pathway.It is in charge of the transfer of TGF-β signal from the surface of the cell membrane into the nucleus.The TGF-β signal can be bound to the target gene in the nucleus and regulate its expression.Abnormalities in Smad3 expression level and functional status will lead to abnormal signal transduction,involving cell growth,proliferation,development,differentiation,migration,apoptosis and other basic life activities.This review focused on the differential expression of Smad3 in hepatocellular carcinoma (HCC)and the adjacent tissue.The character of Smad3 in HCC is outlined in three parts:Smad3 upstream signaling source,Smad3 self-assembly maturation and Smad3 downstream effects,which may provide a summary and reference for the follow-up study on Smad3.

Objective To investigate the diagnosis and treatment of hepatic metastasis from gastrointestinal stromal turnor(GIST).Methods The clinical data of 16 patients with GIST who had been admitted to our hospitalfrom December 1993 to May 2007 were retrospectively analyzed.Results Of all patients,14 underwent radical resection and 2 underwent palliative operation.Two patients with palliative operation and 3 with radical resection were administered with imatinib postoperatively. All patients were followed up for 3-161 months,and GIST metastasis and invasion was observed in 8 of the 14 patients who received radical resection.Of the 7 patients with hepatic metastasis.3 were treated with hepatic artery chemoembolization,1 was administered with imatinib,2 received reoperation and 1 did not receive any treatment. Reoperation was carried out on 1 patient who had abdominal wall metastasis.The 1-and 3-year survival rates of the 16 patients were 92%and 74%,respectively.Conclusions The recurrence rate of GIST after hepatectomy is high.Complete surgical resection is the best curative treatment for hepatic metastasis from GIST and GIST recurrence.The combination of surgical resection and imatinib administration may help to improve the prognosis of patients with hepatic metastasis from GIST.

Objective To investigate the effects of preventive chemotherapy for hepatocellular carcinoma (HCC) exceeding Milan criteria after liver transplantation. Methods The clinical data of 243 patients who had undergone orthotopic liver transplantation for HCC exceeding Milan criteria from April 2001 to July 2007 were retrospectively analyzed. Of all patients, 162 received preventive chemotherapy after transplantation. Results The 1- and 3-year survival rates and disease-free survival rates were not statistically different between patients who had received chemotherapy (78.5%, 63.7% ; 76.8%, 52.5% ) and those without chemotherapy (56.6%, 39.1%; 69.3%, 64.7% ) (X2 = 3.084, 0.444, P > 0.05). Cox regression analysis demonstrated that postoperative chemotherapy was not an independent factor affecting the survival rates of HCC patients without vascular invasion, but an independent factor affecting the survival rates of HCC patients with vascular invasion. Conclusions Early preventive chemotherapy could obviously increase the survival rate and delay the tumor recurrence of patients with HCC exceeding Milan criteria, especially for HCC patients with vascular invasion.

Objective To evaluate salvage liver transplantation(LT)for postoperative tumor recurrence or liver dysfunction in patients of hepatocellular carcinoma(HCC).Methods From April 2001 to March 2006,97 HCC patients with the tumor within Milan Criteria underwent LT as the primary treatment(71 cases)and salvage LT because of after resection tumor recurrence(n=20)or postoperative liver dysfunction(n=6).Perioperative and postoperative parameters and long-term survival were compared between the groups of primary LT and salvage LT.Results The mean age(50.0 years vs.49.7 years),gender,and etiology of liver disease(hepatitis B/C/nonviral)were comparable between the two groups.In the salvage LT group.the mean time between liver resection and LT was 2.50 years.Clinical characteristics such as tumor number(1.37 vs.1.50),operative time(7.92 hours vs.8.56 hours),blood loss (1981.69 ml vs.2626.92 ml)and transfusion(1981.69 ml vs.2626.92 ml)were not statistically different (P＞0.05)between the two groups.The size of largest tumor was significantly different between salvage LT group and the primary LT group(2.81 cm vs.2.05 cm)(t=2.298,P=0.028).By a median follow up of 14.63 months,overall survival after liver transplantation was not different between the 2 groups(X2=0.003.P=0.959).Conclusion In selected patients,liver resection prior to transplantation does not increase the morbidity or impair long.term survival following LT.Therefore.1iver resection prior to transplantation can be integrated with the treatment strategy for HCC.

Objective To investigate the efficacy and safety of radical nephrectomy associated with venous thrombectomy and the role of preoperative angioembolization.Methods From Sep 2006 to Dec 2014,the data from 15 cases with renal cell carcinoma and venous tumor thrombus were collected and analyzed retrospectively.The 15 patients included 8 men and 7 women,whose age ranged from 16 to 75 years.Before operation,all patients underwent imaging examinations which demonstrated the renal tumor and venous thrombus.The tumors size ranged from 5.4 to 14.5 cm.The levels of venous thrombus included 0 grade in 4 cases,Ⅰ grade in 2 cases,Ⅱ grade in 6 cases and Ⅲ grade in 3 cases.The 15 patients were divided into angioembolization group (n =5) and non-angioembolization group (n =10) according to the conduction of preoperative angioembolization.Results All cases successful accepted the nephrectomy.The venous thrombectomy were undergone in 14 cases except for one case due to the severe adhesion between renal vein and aorta.The average operative time was 243.3 ± 77.0 min.The mean blood loss was 1 373.3 ± 1 440.9 ml and the volume of blood transfusion was 533.3 ± 521.9 ml.The average time of postoperative hospital stay was 12.7 ± 5.2 days.Symptomatic tumor thrombus embolism didn't occur in all cases,perioperatively.There were no significant difference between these two groups in operative time,blood loss,blood transfusion volume and postoperative hospital stay (P ＞ 0.05).Eight cases were followed up with a period of 6 to 69 months.Four cases had disease-free survival during follow up.Two cases died at 30 and 55 months after surgery,respectively.One had tumor recurrence at 6 months after surgery.One patient accepted a 6-months target therapy (sunitinib) before surgery.However,his thrombus could not be removed during the operation.After the operation,he continued to choose the target drug therapy for 18 months.No progression for thrombosis or metastasis has been found.Conclusions Nephrectomy and venous thrombectomy could be safe and effective for renal cell carcinoma associated with venous thrombosis.Preoperative angioembolization could not reduce the perioperative risk such as blood loss.

Objective To investigate the role and mechanism of TMPRSS4 in radiation induced metastasis of hepatocellular carcinoma (HCC).Methods Metastatic model of human HCC was established by orthotopic implantation of histologically intact human HCC tissue into the liver of nude mice.Mice bearing xenografts in liver were killed after radiation and the residual tumors were resected and reimplanted into the liver of normal nude mice.At the end of sixth week,the mice were killed and the histopathological features,tumor volume,intrahepatic and lung metastasis were evaluated.Expression of epithelial-mesenchymal transition (EMT) related genes including N-cadherin,Vimentin,SIP1 and TMPRSS4 were measured by Western blotting and RT-PCR.Results The tumor volume and frequency of lung metastasis of control group was 2.25±0.52 cm3 and 66.7％,respectively.Compared to control group,tumor diameter (1.61±0.51 cm3,P＜0.05) and lung metastasis (12.5％,P＜0.05) were significantly inhibited 2 days after radiation.Whereas,30 days after radiation,tumor growth recovered (2.60±0.61 cm3,P＞0.05) and lung metastasis was enhanced (100％,P＜0.05).There were no intrahepatic metastasis in the control group and in the group of reimplantation of HCC 2 days after radiation,while the tumors from those 30 days after radiation showed enhanced intrahepatic metastasis (18 ± 8.05,P＜ 0.01 ),with overexpression of SIP1,N-cadherin,Vimentin and TMPRSS4,and reduced expression of E-cadherin.Conclusion The metastasis potential of residual HCC after radiation was first inhibited and then promoted.Overexpression of TMPRSS4 plays a critical role in radiation induced long-term metastasis of HCC by facilitating EMT.

Objective To appraise and compare protein expression profiles in sera of patients without or with recurrence following liver transplantation for hepatocellular carcinoma (HCC) using SELDI-TOF-MS technique,and establish the diagnostic and predictive model. Methods A total of 76 sera (41 from disease free survival patients and 35 from recurrence individuals) were collected pretransplantation and differentially expressed proteins were identified by SELDI-TOF-MS. The intensity values for each peak were analyzed by Biomarker Wizard Software to screen serum proteome biomarkers related to the recurrence post-transplantation. By using Biomarker Patterns Software, the classification trees were generate. from randomly selected samples (30 fingerprints obtained from each group). The sensitivity and specificity of best decision tree were then chosen for blind test with 16 samples (5 from recurrence individuals and 11 from recurrence-free survival patients). Results There were significant differences only in tumor size and the presence of vascular invasion between recurrence group and recurrence-free survival group (P＜0.05). According to serum protein fingerprints, a total of 368 protein peaks were identified at the mass-to-charge ratio (M/Z) value ranging from 2000 to 300 00. There were 22 significant differential proteins between two groups. Among them, 9 proteins were up-regulated and 13 proteins were down-regulated -espectively in recurrence group. The intensity values of differential proteins were input into BPS for classification tree analysis and the best performing tree could distinguish two groups successfully. As a result of blind assessment for this model,a sensitivity of 80.0 % (4/5) and specificity of 72.7 % (8/11) were obtained. Conclusion Some of differential proteins screened by SELDI-TOF-MS technique in the serum may be correlated with the prognoses of liver transplantation patients with HCC. The decision tree may be useful for the clinical application of formulating the indication for liver transplantation, detecting extrahepatic micrometastasis and setting up the diagnostic and treatment strategies.

Objective To investigate the risk factors influencing early and late recurrences after resection of primary clear cell carcinoma of the liver (PCCCL).Methods 214 PCCCL patients treated by curative resection from January 1996 to March 2006 were retrospectively analyzed.Recurrences were classified into early (≤1 year) and late (＞1 year) recurrences.Results 99 patients developed recurrences,with early recurrence in 28 patients and late recurrence in 71 patients.The 3-and 5-year overall survival (OS) rates for recurrent PCCCL were significantly worse than those with no recurrence (68.7％ and 46.2％ vs 72.2％ and 64.3％,P=0.003).The 1-,3-and 5-year OS rates for late recurrence were 100％,80.3％ and 54.6％,which were significantly better than those with early recurrence (85.7％,39.3％ and 25.0％,P=0.001).On multivariate analysis,aminoleucine transferase (ALT) level and vascular invasion were independent risk factors for early recurrence,while age was the only significant risk factor for late recurrence.Conclusions The time to recurrence was the main determinant for prognosis of recurrent PCCCL,Clarifying the different risk factors for early and late recurrences will help postoperative follow-up,early detection of recurrence,and hopefully will improve survival.