Objective To elucidate the immunologic mechanism and clinical effect of high intensity focused ultrasound (HIFU) combined with dendritic cell and cytokine induced killer cell (DC-CIK) immunotherapy on patients with pancreatic cancer.Methods Seventy-two pancreatic cancer patients were divided randomly into 2 equal groups,one treated with HIFU only the other treated with HIFU and DC-CIK immunotherapy.Ultrasound imaging and a variety of immunological indexes were recorded before and after treatment and the clinical effects in the two groups were compared.Moreover,autogenous tumor cells were isolated from the combination therapy group and the killing activity of DC-CIK which loaded tumor antigen processed by HIFU on autogenous tumor cells was observed.Results Tumor antigen processed by HIFU can improve the killing activity of DC-CIK on autogenous tumor cells.After treatment,the immunological indexes,of all patients were better than before treatment.(58.26 ± 17.97 versus 52.15 ± 14.22 pg/ml with IL-12 22.14 ± 6.39 versus 17.36 ± 5.73 ng/ml with HSP70 and 0.94 ± O.34 versus 1.32 ± O.61 ng/ml with TGF-β,P ＜ 0.05 ) ; The combination group was significantly better than the HIFU group with regard to the average scores of quality of life (75.89 ± 19.65 versus 67.22 ± 16.34,P＜0.05),pain (3.15 ±0.82 versus 3.59 ± 1.04,P ＜0.05),tumor markers (107.55 ±27.58 versus 123.63 ±34.12 U/ml) and survival time (18.92±6.47 versus 13.36 ±5.78 mos).Conclusion HIFU can improve the immunologic status and anti-tumor response in patients with pancreatic cancer.HIFU combined with DC-CIK has good synergistic therapeutic effect for treating pancreatic cancer.

Objective To investigate the effects of high spermatic vessel dissection on testicular morphological alteration of SD rats in prepuberty,puberty and sexual maturity phases.Methods Thirty-day-old SD rats were divided into 2 groups underwent sham operation and left high spermatic vessel dissection as a simulation of Palomo′s maneuver.Detailed morphological investigations were made at 3 different postoperative intervals among the 3rd day,30th day and 56th day.Results High spermatic vessel dissection in prepubertal rats induced acute testicular ischemia in the operated testes on the 3rd day.Most of the operated testes on the 30th day showed testicular atrophy.And all the operated testes showed testicular atrophy and sperm disappearance in epididymis on the 56th day.Conclusion High dissection of spermatic vessel in prepubertal rats induced testicular ischemia in prepuberty and testicular growth failure in puberty,testicular atrophy completely and sperm production losing in sexual maturity phase.

Carcinoma, Hepatocellular ; etiology ; DNA, Viral ; metabolism ; Hepatitis B ; complications ; Hepatitis C ; complications ; Humans ; Liver Neoplasms ; etiology ; Trans-Activators ; physiology ; Viral Core Proteins ; physiology ; Viral Nonstructural Proteins ; physiology

At present, cancer is still one of the most serious threats to human health. Despite the wide application of multiple cancer therapies in clinical practice, the therapeutic effects of most cancers are still far from satisfactory. In recent years, the discovery of regulated cell death may be a good first step on the road to treat cancer. Ferroptosis is triggered by lipid peroxidation of unsaturated fatty acids in cell membrane catalyzed by iron ion. It has been widely concerned as an emerging target for cancer therapy. With the booming of biomedical nanotechnology, ferroptosis as an emerging therapeutic target has attracted extensive attention. Here, we review the advance on the intersection of ferroptosis and biomedical nanotechnology. First, the research background of ferroptosis and nano-preparation as well as the feasibility of ferroptosis-based nano-drug delivery systems (nano-DDS) for cancer treatment are presented and analyzed. Then, the strategies for inducing ferroptosis based on nano-DDS are summarized, mainly including: the promotion of Fenton reaction, the inhibition of glutathione peroxidase 4 (GPX-4) and the restriction of the cysteine-glutamate exchange transporter (system Xc^-). Furthermore, the combination therapy strategies based on biomedical nanotechnology induced ferroptosis are also discussed. Finally, we shine the spotlight on the prospects and challenges of ferroptosis-based nanotherapeutics in clinical application.

OBJECTIVETo investigate the possible association between the single nucleotide polymorphisms (SNPs) (C-8343G, C-1863T and R72P) in TP53 gene and susceptibility to liver metastases of colorectal cancer (CRC) in a Chinese population.

METHODSThe genotypes of each SNP in TP53 gene were determined by either TaqMan assays or PCR-based restriction fragment length polymorphism (RFLP) method in 121 colorectal cancer patients with liver metastases and sex-, age-matched 280 cases with nonmetastatic CRC as a control. Immunohistochemical staining for P53 was performed on paraffin-embedded sections. Odds ratios (ORs) for colorectal liver metastases and 95% confidence intervals (CIs) from unconditional logistic regression models were used to evaluate relative risks.

RESULTSNo significant association of C-8343G or C-1863T with colorectal liver metastases risk was observed. However, the R allele of the TP53 R72P polymorphism was more frequently found in metastatic cases than in nonmetastatic cases (P= 0.037). When compared with PP homozygotes, the ORs of metastases for RP heterozygotes was 2.21 (95% CI: 1.13-4.33), for RR homozygotes was 2.26 (95% CI: 1.03-4.94), and for carriers of the 72R allele (RP or RR genotype) was 2.22 (95% CI: 1.16-4.26). Stratified analysis indicated that carrying the 72R allele had a more pronounced increase in colorectal liver metastases risk among patients with positive P53 expression tumors (OR= 3.28, 95% CI: 1.21-8.88), whereas no significantly increased metastases risk was found in patients with negative P53 expression tumors (OR= 1.37, 95% CI: 0.52-3.62).

CONCLUSIONThe R allele of the TP53 R72P polymorphism may contribute to the etiology of liver metastases in CRC patients, particularly among those with positive P53 expression tumors. Both TP53 C-8343G and C-1863T may be not associated with colorectal liver metastases risk.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; complications ; genetics ; Female ; Genes, p53 ; genetics ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Liver Neoplasms ; genetics ; secondary ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length ; genetics

Copy number aberrations (CNAs) in chromosome arm 8q have been associated with unfavorable clinical outcomes of several cancers and progressive tumor characteristics of hepatocellular carcinoma (HCC).This study was to identify correlation of CNAs in 8q with clinical outcomes of HCC patients,and further screen for differentially expressed genes in outcome-related CNAs.Array comparative genomic hybridization and expression arrays were performed to detect CNAs and expression levels,respectively.The correlations between CNAs in 8q and outcomes were analyzed in 66 patients,with a median follow-up time of 45.0 months (range,2.6-108.6 months).One hundred and nine cases were further evaluated to identify differentially expressed genes in the potential outcome-related CNAs.Copy number gain in 8q was observed in 22 (33.3 ％) of the 66 HCC cases.The most recurrent gains (with frequencies ＞20％) were 8q13.3-21.3,8q21.3-23.3,8q23.3-24.13,8q24.13-24.3,and 8q24.3.Survival analysis showed that 8q24.13-24.3 gain was significantly associated with reduced overall survival (P=0.010).Multivariate Cox analysis identified 8q24.13-24.3 gain as an independent prognostic factor for poor overall survival (HR=2.47;95％CI=1.16-5.26;P=0.019).A panel of 17 genes within the 8q24.13-24.3 region,including ATAD2,SQLE,PVT1,ASAP1,and NDRG1 were significantly upregulated in HCCs with 8q24.13-24.3 gain compared to those without.These results suggest that copy number gain at 8q24.13-24.3 is an unfavorable prognostic marker for HCC patients,and the potential oncogenes ATAD2,SQLE,PVT1,ASAP1,and NDRG1 within the regional gain,may contribute coordinately to the 8q24.13-24.3 gain-related poor prognosis.

OBJECTIVETo evaluate the possible association of the MTHFR C677T polymorphism with genetic susceptibility to hepatocellular carcinoma (HCC) in a Chinese population.

METHODSFive hundred and eight HCC cases and 543 controls were studied. The MTHFR genotypes were determined using a PCR-based restriction fragment length polymorphism (RFLP) method. Odds ratios (ORs) for HCC and 95% confidence intervals (CIs) from unconditional logistic regression models were used to evaluate relative risks. Potential HCC risk factors were included in the logistic regression models as covariates in the multivariate analyses on genotypes and HCC risks.

RESULTSNo overall significant difference in genotype distribution was found when comparing all HCC cases to controls (P = 0.258). However, a significantly increased risk of HCC was observed among T/T homozygotes (adjusted OR = 1.66, 95% CI = 1.08-2.54, P<0.05) compared to C-allele carriers (CC or CT). When stratified with sex, this trend was more prominent in females, but not in males. Females who were homozygous (T/T) for the C677T polymorphism were at a 2.64-fold (95% CI = 1.19-5.88, P<0.05) increased risk of developing HCC when compared to C-allele carriers. However in males, T/T homozygotes had a similar risk with C-allele carriers.

CONCLUSIONThe MTHFR C677T polymorphism may be associated with a higher HCC risk in females, but not in males in this population.

Aged ; Carcinoma, Hepatocellular ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Liver Neoplasms ; genetics ; Logistic Models ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Middle Aged ; Polymorphism, Genetic

OBJECTIVETo evaluate the significance of a panel of immunohistochemical markers for distinguishing hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (ICC).

METHODSTen markers including hepatocyte paraffin 1 (Hep Par 1), polyclonal carcinoembryonic antigen (pCEA), CD34, CD10, CD105, multidrug resistance-associated protein-3 (MRP-3), cyclooxygenase-2 (COX-2), mucinous glycoprotein-1 (MUC-1), aquaporin-1 (AQP-1) and CK19 were immunohistochemically stained in the samples from 90 surgically resected HCC and 80 ICC, respectively,and the positive rate of their expression were compared statistically.

RESULTSThe positive expression rates of Hep Par 1, pCEA, CD34, CD10, CD105, MRP-3, COX-2 were 85.6%, 82.2%, 87.8%, 18.9%, 8.9%, 11.1% and 48.9%, respectively, in HCC. While the positive expression rates of MUC-1, AQP-1 and CK19 were 73.8%, 65% and 92.5%, respectively, in ICC.

CONCLUSIONBased on our results, Hep Par 1 and CD34 can be used as the first line markers, and pCEA and COX-2 as the second line makers, for differential diagnosis of hepatocellular carcinoma from intrahepatic cholangiocarcinoma. While MUC-1 and CK19 can be used as the first line markers and AQP-1 as the second one for the differential diagnosis of intrahepatic cholangiocarcinoma from hepatocellular carcinoma.

Bile Duct Neoplasms ; chemistry ; diagnosis ; Bile Ducts, Intrahepatic ; chemistry ; Biomarkers, Tumor ; analysis ; Carcinoma, Hepatocellular ; chemistry ; diagnosis ; Cholangiocarcinoma ; chemistry ; diagnosis ; Diagnosis, Differential ; Female ; Hepatocytes ; chemistry ; pathology ; Humans ; Immunohistochemistry ; Liver Neoplasms ; chemistry ; diagnosis ; Male ; Middle Aged

This meta-analysis was carried out to evaluate the relationship between NM23 expression and the prognosis of patients with colorectal cancer.We searched PubMed,EMBASE and Web of Science for relevant articles.The pooled odd ratios (ORs) and corresponding 95％CI were calculated to evaluate the prognostic value of NM23 expression in patients with colorectal cancer,and the association between NM23 expression and clinicopathological factors.In total,2289 patients were pooled from 24 available studies.The incorporative OR combined by 16 studies with overall survival showed that high NM23 expression was associated with better overall survival (OR=0.67,95％CI:0.49-0.93,P=0.02,I2=56％,Ph=0.004).And a new estimate without heterogeneity was produced when only combining high-quality studies (OR=0.70,95％CI:0.56-0.86,P=0.0007,I2=46％).In disease free survival (DFS),we also obtained a good prognosis (OR=0.30,95％CI:0.14-0.68,P=0.004).Although we failed to find any significance in N status (P=0.10),elevated NM23 expression was related to well tumor differentiation (OR=0.60,95％CI:0.44-0.820,P=0.001) and Dukes' A&B (OR=0.55,95％CI:0.32-0.95,P=0.03).These results indicated that over-expressed NM23 might be an indicator of good prognosis,well tumor differentiation and Dukes' A&B of patients with colorectal cancer,but no significance was found in N status.

BACKGROUND/AIMS: To reveal possible factors predicting the effect of adefovir dipivoxil (ADV) treatment on chronic hepatitis B (CHB) and optimize the utilization of ADV. METHODS: In total, 168 treatment-naive CHB patients were enrolled, including 117 hepatitis B e antigen (HBeAg)-positive patients and 51 HBeAg-negative patients who met the inclusion criteria. All patients were treated with ADV 10 mg per day for 48 weeks. Multiple logistic regression analyses were used to investigate baseline factors, and responses at weeks 12 and 24 were analyzed as predictive values. RESULTS: Multiple regression analyses showed that baseline HBeAg status and HBV DNA levels significantly affected the virological response (VR) (p<0.05), baseline ALT levels were an independent predictor of serological response (SR) (p<0.05) and the body mass index (BMI) may affect the biochemical response (BR) (p<0.05). There was a statistically significant difference in the VR and SR between patients with a primary nonresponse (PNR) at week 12 and those with a VR at week 12 (p<0.01). Additionally, the VR was significantly different between patients with HBV DNA lower than 103 copies/mL at week 24 and those with greater than 103 copies/mL (p<0.01). CONCLUSIONS: Patients with negative HBeAg, lower HBV DNA levels and higher ALT values at baseline are more suitable for ADV treatment, whereas patients with lower BMIs may be more amenable to ALT normalization. Adjustments for treatment strategy should be considered if PNR at week 12 or HBV DNA > or =10(3) copies/mL at week 24 is observed.
Adenine ; Body Mass Index ; DNA ; Hepatitis B ; Hepatitis B e Antigens ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Logistic Models ; Organophosphonates