Morphine and ketamine inhibit immune function of gastric cancer patients by increasing percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells in vitro.

BACKGROUND: There is conflicting evidence regarding effects of anesthetic and analgesic drugs on immune function of cancer patients. This study was designed to observe changes of T cell subpopulations in the gastric cancer (GC) patients and to assess effects of morphine and ketamine on the CD4(+) T cells, CD8(+) T cells, and regulatory T cells (Tregs) populations obtained from the GC patients in vitro. METHODS: The peripheral blood samples from 20 GC patients and 20 healthy volunteers were obtained. The peripheral blood mononuclear cells were isolated and incubated in a solution containing phorbol-myristate-acetate and ionomycin (2 µL/mL) in the presence or absence of morphine (50 ng/mL) or different-concentration ketamine (25, 50, and 100 µM). The CD4(+) T cells, CD8(+) T cells, and Tregs were determined using the flow cytometric assay. RESULTS: The percentages of CD8(+) T cells were significantly decreased, but the ratio of CD4(+)/CD8(+) T cells and Tregs populations was significantly increased in the GC control group compared with the normal control group (P < 0.05). The ratio of CD4(+)/CD8(+) T cells was significantly increased in the groups M and K3 compared with the control group (P < 0.05) but was significantly decreased in the group K1 compared with the group K3. The percentage of Tregs was significantly increased in the groups M, K1, K2, and K3 compared with the control group. With the increased concentrations, ketamine increased the number of Tregs. CONCLUSIONS: GC shifts the balance of CD4(+)/CD8(+) T cells toward CD4(+) T cells and increases the Tregs populations by inducing immune responses. Morphine increases the ratio of CD4(+)/CD8(+) T cells and Tregs populations. Ketamine affects the ratio of CD4(+)/CD8(+) T cells and Tregs populations in a dose-dependent model.

[Influence of artificial insemination with donor sperm on the pregnancy outcomes and safety of the offspring].

OBJECTIVE: To investigate the factors influencing the pregnancy outcomes of artificial insemination with donor sperm (AID), improve the pregnancy rate, and evaluate the safety of the offspring. METHODS: We retrospectively analyzed 7,761 cycles of AID for 5,109 infertile couples performed between July 1, 2005 and June 30, 2013 in the Center of Reproductive Medicine of Shenyang No 204 Hospital, the outcomes of pregnancy, and the incidence of birth defects. RESULTS: Totally, 2 252 clinical pregnancies were achieved by AID, in which the pregnancy rate per cycle was 29. 02% and the cumulative pregnancy rate was 44. 08%. The clinical pregnancy rate was remarkably higher in the females of ≤ 35 years than in those of > 35 years old (30.31% vs 20.18%, P < 0.01), in the women with < 5-year infertility than in those with > 5-year infertility (30.83% vs 28.16%, P < 0.01), and in the patients of the ovarian stimulation group than in those of the natural cycle group (33.22% vs 28.68%, P < 0.01) The clinical pregnancy rate was the highest in the first treatment cycle (29.87%), with statistically significant difference from the fourth cycle (23.61%) (P < 0.05), but not between the other cycles (P > 0.05). There were 28 cases of birth defects in the offspring (1.40%), including 6 cases (21.43%) involving the cardiovascular system, 4 (14.29%) involving the musculoskeletal system, 3 (10.71%) involving the urogenital system, 3 (10.71%) involving the central nervous system, 2 cases (7.14%) of cleft lip and palate, 2 (7.14%) involving the respiratory system, 2 (7.14%) involving the gastrointestinal digestive system, and other anomalies. CONCLUSION: Female age, infertility duration, and ovarian stimulation treatment are important factors influencing the clinical pregnancy rate of AID. Artificial insemination with cryopreserved donor sperm does not increase the incidence of birth defects, which is considered as a relatively safe technique of assisted reproduction.

Expression of stromal cell-derived factor 1 and CXCR7 ligand receptor system in pancreatic adenocarcinoma.

BACKGROUND: Stromal cell-derived factor 1 (SDF-1) is a chemokine that is expressed in some cancer cells and is involved in tumor cell migration and metastasis. CXCR7, a novel receptor for SDF-1, has been identified recently. Research has demonstrated that SDF-1/CXCR7 interaction could play an important role in cancer progression. In this study, we aimed to investigate the expression of the SDF-1/CXCR7 ligand receptor system and the relationship between this expressions and clinicopathological characteristics in pancreatic adenocarcinoma. METHODS: Expressions of SDF-1 and CXCR7 in 64 cases of pancreatic adenocarcinoma tissue and 24 cases of normal pancreatic tissue were detected immunohistochemically. RESULTS: Expressions of SDF-1 and CXCR7 were negative in normal pancreatic tissues. Respectively, positive expression rates of SDF-1 and CXCR7 in pancreatic adenocarcinoma were 45.3% and 51.6%. The expression of SDF-1 correlated with histological grades; the expression rate in moderate to low differentiation was higher than in high differentiation (P<0.05). The expression of CXCR7 positively correlated with lymph node metastasis (P<0.05). A log-rank test showed that the expression of SDF-1+/CXCR7+ correlated with poor prognosis (P<0.05). CONCLUSIONS: The SDF-1/CXCR7 receptor ligand system may take part in invasive progression and metastasis of pancreatic adenocarcinoma, and might be useful as an index for evaluating invasiveness and prognosis.

Isolated pancreatic tuberculosis in non-immunocompromised patient treated by Whipple's procedure: a case report.

PANCREATIC tuberculosis (TB) is a rare disease and its diagnosis is difficult because of the lack of specific clinical manifestations. Computed tomography (CT) and magnetic resonance imaging (MRI) have some diagnostic values in this disease, but it is easy to misdiagnose pancreatic TB as a pancreatic tumor.1 In this article, we present a case of non-immunocompromised patient developing an isolated pancreatic TB, report the CT and MRI findings, and the surgical procedure for it.

Identification of genes and candidate agents associated with pancreatic cancer.

Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas. A major challenge in current cancer research is biological interpretation of complexity of cancer somatic mutation profiles. It has been suggested that several molecular alterations may play important roles in pancreatic carcinogenesis. In this study, by using the GSE28735 affymetrix microarray data accessible from Gene Expression Omnibus (GEO) database, we identified differentially expressed genes (DEGs) between paired pancreatic cancer tissues and adjacent nontumor tissues, followed the protein-protein interaction of the DEGs. Our study identified thousands of DEGs involved in regulation of cell cycle and apoptosis in progression of pancreatic cancer. Sp1 was predicted to be the major regulator by transcription factors analysis. From the protein-protein interaction networks, we found that Tk1 might play an important role in the progression of pancreatic cancer. Finally, we predicted candidate agents, including tomatidine and nialamide, which may be used as drugs to treat pancreatic cancer. In conclusion, our data provide a comprehensive bioinformatics analysis of genes and pathways which may be involved in the progression of pancreatic cancer.

A comparative proteomic study identified calreticulin and prohibitin up-regulated in adrenocortical carcinomas.

BACKGROUND: Identifying novel tumor biomarkers to develop more effective diagnostic and therapeutic strategies for patients with ACC is urgently needed. The aim of the study was to compare the proteomic profiles between adrenocortical carcinomas (ACC) and normal adrenocortical tissues in order to identify novel potential biomarkers for ACC. METHODS: The protein samples from 12 ACC tissues and their paired adjacent normal adrenocortical tissues were profiled with two-dimensional electrophoresis; and differentially expressed proteins were identified by mass spectrometry. Expression patterns of three differently expressed proteins calreticulin, prohibitin and HSP60 in ACC, adrenocortical adenomas (ACA) and normal adrenocortical tissues were further validated by immunohistochemistry. RESULTS: In our proteomic study, we identified 20 up-regulated and 9 down-regulated proteins in ACC tissues compared with paired normal controls. Most of the up-regulated proteins were focused in protein binding and oxidoreductase activity in Gene Ontology (GO) molecular function classification. By immunohistochemistry, two biomarkers calreticulin and prohibitin were validated to be overexpressed in ACC compared with adrenocortical adenomas (ACA) and normal tissues, but also calreticulin overexpression was significantly associated with tumor stages of ACC. CONCLUSION: For the first time, calreticulin and prohibitin were identified to be novel candidate biomarkers for ACC, and their roles during ACC carcinogenesis and clinical significance deserves further investigation. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1897372598927465.

CYP3A5*3 polymorphism and cancer risk: a meta-analysis and meta-regression.

CYP3A5 is a cytochrome P450 superfamily member which is involved in the metabolism of drugs, steroid hormones, and other xenobiotics. Emerging evidences suggest that CYP3A5*3 (rs776746 A>G) polymorphism may play a role in the etiology of carcinogenesis and affect an individual's susceptibility to cancer in humans, but individually published studies showed inconclusive results. This meta-analysis aimed to derive a more accurate estimation of the correlation between CYP3A5*3 polymorphism and cancer risk. A literature search of PubMed, Embase, Web of Science, and China BioMedicine databases was conducted on articles published before January 1, 2013. Seventeen case-control studies were included with a total of 7,458 cancer patients and 7,166 healthy controls. The meta-analysis results showed that CYP3A5*3 polymorphism may increase the risk of cancer, especially in acute leukemia, chronic leukemia, and colorectal cancer. However, no statistically significant associations were found in prostate cancer, liver cancer, and other cancers. Further subgroup analysis by ethnicity indicated that CYP3A5*3 polymorphism was associated with an increased risk of cancer among Asian and Caucasian populations, but not among African populations. In conclusion, the current meta-analysis suggests that CYP3A5*3 polymorphism may play an important role in the development of acute and chronic leukemia and colorectal cancer, especially among Asian and Caucasian populations.

Expression of stromal cell-derived factor 1 and CXCR7 in papillary thyroid carcinoma.

Stromal cell-derived factor 1 (SDF-1) is a chemokine that is expressed in some cancer cells and is involved in tumor cell migration and metastasis. CXCR7, a novel receptor for SDF-1, has been identified recently. Researches demonstrated that interaction between SDF-1 and CXCR7 could play an important role in cancer progression. In this study, we aimed to investigate the expressions of SDF-1 and CXCR7 and the relationship between their expressions and clinicopathological characteristics in papillary thyroid carcinoma (PTC). Expressions of SDF-1 and CXCR7 in 33 cases of thyroid benign lesion tissue and 79 cases of PTC tissue and peritumoral non-malignant tissue were detected by immunohistochemical staining. Expressions of SDF-1 and CXCR7 were negative in peritumoral non-malignant tissues. Respectively, positive expression rates of SDF-1 and CXCR7 were 69.6 and 65.8 % in PTC, 12.1 and 30.3 % in thyroid benign tissue. The expression of SDF-1 and CXCR7 were positively correlated with lymph node metastasis. SDF-1 and CXCR7 expressions were related with the lymph nodes metastasis of PTC.

Nanoparticle-mediated local delivery of an antisense TGF-ß1 construct inhibits intimal hyperplasia in autogenous vein grafts in rats.

BACKGROUND: Intimal hyperplasia is one of the most important causes of vascular graft failure. Numerous studies have correlated transforming growth factor-ß1 (TGF-ß1) with extracellular matrix (ECM) deposition, a hallmark of intimal thickening. PRINCIPAL FINDINGS: In the present study, we performed immunohistochemistry, RT-PCR, and Western blot to examine the dynamic expression of TGF-ß1, TGF-ß1 receptor type I (TGF-ß RI), matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) during intimal hyperplasia in grafted veins of a rat model generated by grafting a portion of the right internal jugular vein to the ipisiliary carotid artery. Additionally, we determined whether nanoparticle-mediated delivery of a TGF-ß1 antisense-expressing construct prevented TGF-ß1 expression and intimal hyperplasia in grafted veins. In grafted veins, the expression of TGF-ß1 significantly increased on day 3 after transplantation, peaked on day 7, slightly decreased on day 14, and returned to baseline levels on day 28. The positive expression of TGF-ß RI in grafted veins remarkably increased on day 7, peaked on day 14, and decreased thereafter. MMP-1 expression decreased significantly, while TIMP-1 expression increased, significantly on days 14 and 28. Nanoparticle-mediated delivery of a TGF-ß1 antisense-expressing construct down-regulated TGF-ß1 expression and inhibited intimal hyperplasia in grafted veins. CONCLUSIONS: Our findings provide further evidence that TGF-ß1 plays an integral role in the development of intimal hyperplasia after vascular injury. Nanoparticle-mediated delivery of a TGF-ß1 antisense-expressing construct is a feasible strategy to target TGF-ß1-induced intimal thickening.

Prevention of pancreaticojejunal anastomotic leakage after pancreaticoduodenectomy with separate internal drainage of bile and pancreatic fluid.

OBJECTIVE: To introduce a new reconstructional procedure to decrease the complications after pancreaticoduodenectomy. METHODS: Separate internal drainage of bile and pancreatic fluid in pancreaticoduodenectomy was performed in 256 patients. The digestive tract was reconstructed with Child method, with invaginated pancreaticojejunostomy using a long silastic tube to drain pancreatic fluid internally, an end-to-side choledochojejunostomy and an end-to-side duodenojejunostomy or gastrojejunostomy. Gastrostomy drainage was also performed. RESULTS: No complications of pancreatic leakage were found. CONCLUSION: The separate internal drainage of bile and pancreatic fluid plays an important role in preventing pancreaticojejunal anastomotic leakage.