Actins ; metabolism ; Aged ; Aged, 80 and over ; Carcinoma, Renal Cell ; metabolism ; pathology ; Cell Differentiation ; Female ; Humans ; Immunohistochemistry ; Keratin-7 ; metabolism ; Keratin-8 ; metabolism ; Kidney Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Sarcoma ; metabolism ; pathology ; Vimentin ; metabolism

Carcinoma ; metabolism ; Cell Differentiation ; genetics ; Gallbladder Neoplasms ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Kangai-1 Protein ; genetics ; metabolism ; NM23 Nucleoside Diphosphate Kinases ; genetics ; metabolism

BACKGROUNDOsteosarcoma is characterized by high neovascularization and a high propensity for metastasis through bloodstream. This study was to examine whether there is evidence for vasculogenic mimicry in osteosarcoma and to illustrate mechanism of tumor blood vessels formation in osteosarcoma.

METHODSOsteosarcoma cell lines (U-2OS) were tested for their ability to form tubular networks in three-dimensional culture containing type I collagen. The structures of the tubular networks were observed with phase contrast microscope and transmission electron microscope (TEM). Morphometric studies using hematoxylin and eosin (HE) stain and CD31 immunohistochemical stain to show tumor-lined channels in human osteosarcoma were also performed.

RESULTSObservation with light microscope and TEM showed that highly aggressive osteosarcoma cell lines (U-2OS) formed networks containing channels when grown in three-dimensional culture containing type I collagen, in the absence of endothelial cells or fibroblasts. Morphometric observation using HE stain and CD31 immunohistochemical stain showed that tumor cell-lined channels were also detected in vivo in osteosarcoma; by comparison, all vascular areas in the pedicle of osteochondroma or outside osteochondroma were endothelial-lined.

CONCLUSIONThese observations strongly suggest that aggressive osteosarcoma cells may generate vascular channels that facilitate tumor perfusion independent of tumor angiogenesis and have the ability of vasculogenic mimicry.

Bone Neoplasms ; pathology ; ultrastructure ; Cell Line, Tumor ; Collagen ; biosynthesis ; Humans ; Immunohistochemistry ; Neovascularization, Pathologic ; pathology ; Osteosarcoma ; pathology

OBJECTIVETo investigate the expression of two tumor metastasis suppressor genes nm23 and KAI1 in gallbladder adenocarcinoma, and their clinicopathological significance.

METHODSSpecimens and clinical data from 31 gallbladder adenocarcinoma patients were collected. Histopathological grading and the expression of nm23 and KAI1 were detected by HE and immunohistochemical staining, respectively. All cases were followed up for at least three years.

RESULTSImmunohistochemical staining showed that the positive rate of nm23 and KAI1 proteins was 71.0% (22/31) and 61.3% (19/31), respectively. The positive expression rates of nm23 and KAI1 proteins in the early stage carcinomas were significantly higher than those in the moderate and advanced stage ones (P exact = 0.0051 and P exact = 0.0084), and both had an negative correlation with clinicopathologic stage (P trend = 0.0047 and P trend = 0.0058). There was a significant difference in the expression of nm23 and KAI1 proteins among well, moderately and poorly differentiated carcinomas (P exact = 0.0328 and P exact = 0.0020). The expression of nm23 and KAI1 was positively correlated with histopathological grade (P trend = 0.0086 and P trend = 0.0006). There was also a significant difference in the expression of nm23 and KAI1 proteins between 17 survival and 14 dead patients (P exact = 0.0038 and P exact = 0.0001 ). A synergistic effect of nm23 and KAI1 protein on the survival was observed , and seemed to be more important than any individual gene alone (P exact = 0.0005).

CONCLUSIONThe expressions of nm23 and KAI1 proteins are negatively correlated with clinical stage, but positively with histopathological grade in gallbladder adenocarcinoma. These two tumor metastasis suppressor genes may act synergistically to inhibit the tumor metastasis.

Adenocarcinoma ; metabolism ; pathology ; surgery ; Adult ; Aged ; Aged, 80 and over ; Cell Membrane ; metabolism ; Cholecystectomy ; Cytoplasm ; metabolism ; Female ; Follow-Up Studies ; Gallbladder Neoplasms ; metabolism ; pathology ; surgery ; Gene Expression Regulation, Neoplastic ; Humans ; Kangai-1 Protein ; metabolism ; Male ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases ; metabolism ; Neoplasm Metastasis ; Neoplasm Staging ; Survival Rate

OBJECTIVETo investigate the expressions of vascular endothelial growth factors (VEGF)-A, -C and -D and their prognostic significance and relation to angio- and lymphangiogenesis in gastric cancer.

METHODSThe expression of VEGF-A, -C and -D in 123 primary gastric cancers was detected by immunohistochemical staining. The lymphatic vessel density (LVD) and microvessel density (MVD) were assessed after immunohistochemical double-staining with D2-40 and CD34, respectively. The correlation between the expression of those VEGF factors and clinicopathological parameters were analyzed by univariate method. The overall survival was evaluated by Kaplan-Meier method and log-rank test. Multivariate analysis was carried out using Cox proportion hazard model.

RESULTSThe positive expression rate of VEGF-A, -C and -D in primary gastric cancer samples were 64.2%, 65.9% and 41.5%, respectively. High expression of VEGF-A, or -C or -D, or any two of them was correlated with high LVD (P < 0.05). High expression of both VEGF-A and -C was associated with high MVD, lymph node metastasis, LVI and MVI (P < 0.05). Both VEGF-C and -D high expression was correlated with LVI and lymph node metastasis (P < 0.05). The patients with high expression of these factors had a statistically shorter overall survival (P < 0.05). The patients with both VEGF-A and -C expression had the shortest survival (56 months). Multivariate analysis showed that VEGF-A high expression, MVD, lymph node metastasis and depth of tumor invasion were independent survival predictors (P = 0.033, 0.002, 0.019 and P < 0.001, respectively).

CONCLUSIONHigh expression of both VEGF-A and -C imply high potential of lymphangiogenesis, metastasis and poorer survival in gastric cancer patients. High expression of VEGF-C and -D may induce lymphangiogenesis and promote lymph node metastasis, but only VEGF-A is an independent predictor of survival.

Adult ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; Lymphangiogenesis ; Lymphatic Metastasis ; Lymphatic Vessels ; pathology ; Male ; Microvessels ; pathology ; Middle Aged ; Neovascularization, Pathologic ; Proportional Hazards Models ; Stomach Neoplasms ; metabolism ; pathology ; Survival Rate ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor C ; metabolism ; Vascular Endothelial Growth Factor D ; metabolism

Nowadays, the 5-year survival rate of childhood cancer patients can be more than 80%, but some patients with relapse and refractory cancers have shown no good response to traditional strategies. Chimeric antigen receptor engineered T (CAR-T) cell therapy is promising for these patients. CAR-T cells recognize the tumor-associated antigens in a non-major histocompatibility complex-restricted manner, so their anti-tumor ability is enhanced. There are four generations of CAR-T cells now. The complete remission rate of pediatric patients with relapse and refractory acute lymphoblastic leukemia can be as high as 90% when treated with CD19-targeting CAR-T cells. Furthermore, CAR-T cell therapy can also be used to bridge to transplantation and donor CAR-T cell infusion can be a strategy to prevent relapse after hematopoietic stem cell transplantation. As to solid tumors, only patients with neuroblastoma present good response to the GD2-targeting CAR-T cell therapy. The toxic or side effects of CAR-T cell therapy include cytokine release syndrome, off-tumor effect, tumor lysis syndrome, and insertion mutation. Although the CD19-targeting CAR-T cell therapy for childhood cancer can result in a high remission rate, the relapse rate is high, including CD19and CD19relapse. The mechanisms for relapse merit further investigatio.
Antigens, CD19 ; immunology ; Child ; Humans ; Immunotherapy, Adoptive ; adverse effects ; methods ; Neoplasms ; therapy ; Receptors, Antigen, T-Cell ; genetics ; T-Lymphocytes ; transplantation

Aim To investigate the effect of TaorenHonghua drug pair on intervertebral disc degeneration (IVDD) in rats.Methods Fifty healthy Wistar rats were randomly divided into control group,model group,sham group,meloxicam group and Taoren-Honghua drug pair group,with 10 rats in each group.We established dynamic and static forces imbalance of cervical disc degeneration model or sham surgery in rats.12 weeks later,rats were intragastrically administered with meloxicam,Taoren-Honghua drug pair or saline for 30 days.C4/5 and C6/7 discs were harvested from rats.ABOG staining was used for observation of intervertebral disc morphology,real time PCR for mRNA expressions of type Ⅱ collagen (Col Ⅱ) and type Ⅹ collagen (Col Ⅹ),and immunohistochemical staining for Col Ⅱ and Col Ⅹ.Results Compared with model group,Col Ⅱ expression increased,while Col X expression decreased in chondrocyte of intervertebral disc in Taoren-Honghua-treated group(P ＜ 0.01).Conclusion Taoren-Honghua drug pair could delay the degeneration of cartilage endplate in rat intervertebral disc.

Objective To evaluate the association between total fluid intake and the time of urination per day and the risk of bladder cancer. Methods A population-based case-control study was conducted in urban Shanghai, China, during January 1996 to December 1998. The study included 608 incident cases of bladder cancer and 607 age- and sex-matched controls. Unconditional logistic regression models were used to estimate the odds ratios(ORs)and their corresponding 95%confidence intervals(95%CIs)for bladder cancer associated with frequency of urination, after adjusted for age, gender, smoking status, history of occupation with high risk, history of bladder infections, body mass index and other confounding factors. The level of statistical significance was set at 0.05(two-sided). Results No significant trend was observed for the association between total fluid intake, time of nighttime urination and the risk of bladder cancer. Increasing time of urination during daytime was associated with decreased risk of bladder cancer(P for trend=0.014). ORs(95%CIs)for subjects who voided 4 times, 5 times and 6 or more times per day[0.72(0.49-1.05),0.60(0.41-0.87)and 0.62(0.43-0.90), respectively], when compared with those with less than 4times per day after adjustment of confounding factors. Data showed that smokers and nonsmokers who voided at least 6 times per day had the ORs of 0.72(95%CI: 0.45-1.15)and 0.46(95%CI:0.25-0.87)when compared to their counterparts who voided 3 times or less per day during the daytime. Subjects who urinated at least 6 times per day and consumed more than 1500 ml of total fluid per day experienced a significant 57% reduction in risk compared to subjects who urinated 3 times or less and consumed less than 750 ml of total daily fluid intake. Conclusion Increased urination frequency and total fluid intake, especially among those who never smoked might be associated with a reduced risk of bladder cancer.

Adult ; Aged ; China ; epidemiology ; ethnology ; Female ; Humans ; Hypertension ; epidemiology ; prevention & control ; Male ; Middle Aged ; Prevalence

Objective To investigate the feasibility of Catwalk-assisted system in analyzing the behavioral features of rat models of middle cerebral artery occlusion(MCAO).Methods Thirty male SD rats were randomly assigned to experimental group and control group.Suture-occluded method was used to establish the focal cerebral ischemia/reperfusion models in the experimental group.Traditional modified neurological severity scale(mNSS),vibrissae-evoked forelimb placing test and cylinder test were employed to analyze the behavioral characteristics of the SD rats 1,3,7,14 and 28 dafter establishment of rat models.Besides that,Catwalk-assisted gait analysis system was employed at the same time points.Results Catwalk-assisted gait analysis results suggest rats from experimental group had smaller intensity,print area and slower walk speed than rats from control group.Besides that,interlimb coordination also changed on the 3rd d of operation and existed until the 28th d of operation.Rotate step patterns like Ra(1.5％)and Rb(2.3％)were detected in experimental group but never seen in control group.Parameters as cadence,stance,swing and other regularity index had no significant changes between the 2 groups.Conclusion Catwalk analysis system,by analyzing such movement parameters of MCAO rats as intensity,speed,print area,step pattern and interlimb coordination,can commendably reflect the damage of brain ischemia and its changes crossing time,which can comprehensively analyze many behavioral features of the models.