Objective To provide an ideal animal model for exploring the pathogenesis and experimental treatment of malignant melanoma in the small intestine.Methods Fresh tissue of lung metastatic lesions from patients with malignant melanoma of the smallintestine were transplanted into mucosa of the small intestine in nude mice.After 4 times of screening.the tissue of the lung metastatic lesions from the nude mice were transplanted into the small intestine of additionat nude mice.Tumorgenecity and metastasis of transplanted tumors were observed,and were analyzed by morphology,karyotype and flow cytometry.Results A lung metastatic model of human primary malignant melanoma of the small intestine in nude mice was successfully constructed and named HSIM-0601.Massive melanin granules and melanin complex were seen in cytoplasm of tumor cells.Immunohistochemical straining of S-100 and HMB-45 were positive.The number of chromosome was between 57 and 59.DNA index was 1.49.HSIM-0601 was passed for 26 generations.A total of 173 nude mice were used for tumor transplantation.The growth rate of the transplanted tumors and resuscitation rate of liquid nitrogen cryopreservation were both 100%.In HSIM-0601.lung metastasis rate was 100%(173/173)and lymph node metastasis rate was 61.3%(106/173).Conclusions The HSIM-0601 successfully mimics the natural clinicopathologic course of patients with primary small intestinal melanoma,and provides an ideal animal model for research on pathogenesis,metastasis and experimentM therapy of malignant lymphoma in the small intestine.

ObjectiveTo investigate the anatomical changes and dose variation of rectum during radiotherapy in patients with cervical cancer.Methods Ten patients with cervical cancer underwent intensity-modulated radiotherapy using online cone beam computed tomography (CBCT) before each fraction.Rectum was contoured on each CBCT and projected onto the planning CT to analyze the changes of the rectal volume and position.The rectal volume receiving ≥ 45 Gy ( V45 ) was evaluated accordingly.Results227 CBCT images in 10 patients were collected.The rectal volume changed from ( 35.0 ± 7.3)cm3 to (97.7±14.7) cm3.The shift of rectal center was (0.14 ±0.06) cm in left and right direction,(0.24±0.10) cm in anterior and posterior direction,and (0.55±0.28) cm in superior and inferior direction.The V45 of rectum varied from (9.19±2.46)％ to (60.54 ±11.67)％.In7 of the 10 patients,rectal volume and V45 of the rectum had significant positive correlation (r =0.582 - 0.743,all P ＜ 0.01 ).Among the 227 images,the V45 of rectum was ≤50％ in 68 images (30.0％ ).ConclusionsSignificant changes in rectal volume and position occurred during fractionated radiotherapy in patients with cervical cancer,which resuhs in variations in the dose rectum received.For most patients,rectal volume and the V45of rectum had significant positive correlation.

Objective To investigate bladder anatomical changes and dose variation in patients with cervical cancer.Methods We analyzed 20 patients,undergoing external beam radiotherapy scanning cone beam CT(CBCT)before each fraction.Bladder was contoured on each CBCT,was projected onto the planning CT and assesses anatomical changes and dose variation.Results A total 451 CBCT images,for 20 patients were collected for analysis,show more change in bladder volume and position.In 15 cases bladder volume and V45 had no significant correlation(r=0.225 -0.473,all P>0.05),4 cases shows negative correlation(r=-0.564,P<0.05;r=-0.597,P<0.01;r=-0.942,P<0.01;r=-0.816,P<0.01),1 case shows positive correlation(r=0.662,P<0.01).Have more than the criteria(V45≤50%)number is 64/451(14.2%)in whole treatment.Conclusions For most patients by filling adequacy bladder,bladder dose variation is acceptable:CTV lager for individual patients should be closely observed its regression,implementation of the offline or online calibration.

OBJECTIVETo construct a mouse model of highly metastatic gastric lymphoma with orthotopic transplantation of human primary gastric lymphoma specimen.

METHODSA fresh surgical specimen of primary gastric lymphoma was obtained intraoperatively and implanted into the submucosa of stomach in nude mice. Tumor formation, invasion, metastasis, morphological characteristics under light microscopy and electron microscopy, immunohistochemistry,and the karyotype of orthotopically transplanted tumor cells were studied.

RESULTSAn orthotopic highly metastatic model of human primary gastric lymphoma in nude mice(HGBL-0305) was successfully established. Histopathology of transplanted tumors showed primary gastric diffuse large B cell lymphoma. CD19, CD20, CD22 and CD79alpha were positive, while CD3 and CD7 were negative. The number of chromosome ranged from 56 to 69. DNA index(DI) was 1.47+/-0.12(i.e. heteroploid). Until now, HGBL-0305 model has been maintained for 45 generations by orthotopic passage for almost 4 years in nude mice. A total of 156 nude mice were used for transplantation. The growth rate and resuscitation rate of liquid nitrogen cryopreservation of transplanted tumor cells were both 100%. The autonomic growth of the transplanted tumor cells invaded and destructed all the layers of the nude mice stomach. The metastasis rates of liver, spleen, lymph node, and peritoneal seeding were 69.5%, 55.6%, 45.7%, and 30.5%, respectively.

CONCLUSIONSAn orthotopic highly metastatic model of human primary gastric lymphoma in nude mice is successfully established. HGBL-0305 model may simulate the natural course of primary gastric lymphoma in human and provides an ideal animal model for studies on pathogenesis, metastasis biology and anti-metastatic therapies of primary gastric lymphoma.

Animals ; Antigens, CD ; metabolism ; Disease Models, Animal ; Female ; Humans ; Lymphoma ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Metastasis ; Stomach Neoplasms ; pathology ; Xenograft Model Antitumor Assays

Platinum-based anticancer drugs have been becoming one of the most effective drugs for clinical treatment of malignant tumors for its unique mechanism of action and broad range of anticancer spectrum. But, there are still several problems such as side effects, drug resistance/cross resistance and no-specific targeting, becoming obstacles to restrict its expanding of clinical application. In recent years, supramolecular chemistry drug delivery systems have been gradually concerned for their favorable safety and low toxicity. Supramolecular macrocycles-platinum complexes increased the water solubility, stability and safety of traditional platinum drugs, and have become hot focus of developing novel platinum-based anticancer drugs because of its potential targeting of tumor tissues/organs. This article concentrates in the research progress of the new drug delivery system between platinum-based anticancer drugs with three generations of macrocycles: crown ether, cyclodextrin, cucurbituril and calixarene.
Antineoplastic Agents ; pharmacology ; Calixarenes ; Crown Compounds ; Cyclodextrins ; Drug Delivery Systems ; Humans ; Macrocyclic Compounds ; pharmacology ; Neoplasms ; drug therapy ; Platinum Compounds ; pharmacology

Objective To study the asymmetry of the soft tissue thickness of upper eyelids in Shanghai female undergraduates undergoing double eyelid surgery.Methods Data were collected in 565 female students from Shanghai universities.Before surgery,oblique sagittal view images of the upper eyelids by 3.0T MRI were obtained and the following parameters were measured: soft tissue thickness at upper tarsal plate margin and upper central tarsal plate,sub-eyebrow and intra-orbital septum fat pad areas,and whole upper eyelid soft tissue areas.The resected orbicularis and intra-orbital septum fat were weighed by a highly accurated electronic balance.The eyelid asymmetry index (EAI) was calculated.Results The MRI (U/U2) central tarsal plate soft tissue thickness were:4.46±0.90 in the right side and 3.78±1.01 in the left; the intra orbital septum fat areas were:172.33±49.29 in the right and 136.34±37.42 in the left; the whole tissue areas were: 697.13±146.99 in the right and 500.66±158.87 in the left (P＜0.01 for all).The weight of the resected orbicularis oculi muscle and intra orbital septum fat pad were (0.18±0.05) g and (0.17±0.06) g for the right side,and (0.15±0.04) g and (0.06±0.05) g for the left side (P＜0.01 for all),respec tively.The orbicularis EAI was 0.17±0.06,and the intra orbital septum fat EAI was 0.41 ±0.08.Conclusions The asymmetric phenomenon of the upper eyelids' soft tissue thickness is commonly found in the Shanghai female undergraduates,and the main manifestation is that orbicularis and intra orbital septum fat in right side are thicker than that in the left.

Gastrectomy ; Humans ; Laparoscopy ; Stomach Neoplasms/surgery*

Objective To investigate the inhibitory effect of a disintegrin and metalloprotease 12 silenced by shR?NA on self-renewal capacity of CD133 positive giloma cells. Methods The shRNA recombinant lentivirus aimed at si?lencing ADAM12 was prepared. Human glioma cells U87 were employed in this study and assigned into three groups:shRNA-ADAM12, shRNA-NCandshRNA-C. ADAM12 expression was detected at mRNA and protein level using Re?al-time quantitative-PCR and western bloting, respectively. U87 cells were cultured with stem cell culture medium, to obtain cell sphere formation in which CD133 positive glioma cells were enriched. Immunofluorescence was employed to detect the expression of ADAM12 and CD133 in cell spheres and U87 cells; Self-renewal was tested by using tumor sphere formation assay. Molecular markers for differentiated or undifferentiated cells (CD133,GFAP and Tuj1) were de?tected at protein using western blotting. Western blotting was employed to test protein expression of HES1. Results AD?AM12 shRNA significantly down-regulated the mRNA and protein expression levels of ADAM12. Compared with shRNA–C group, the relative expression levels of mRNA in shRNA-ADAM12 group and shRNA-NC group were 0.22 ± 0.03 and 0.98 ± 0.06 (F=425.37,P<0.01). The relative expression levels of protein in shRNA-ADAM12 group, shRNA-NC group and shRNA-C group were 28.72%±2.36%, 69.21%±3.92%and 69.04%±3.57%, respectively (F=145.42,P<0.01). Immunofluorescence staining showed that expression levels of ADAM12 and CD133 in cell spheres were significantly higher than those in normal cells. The number of spheres in three groups were 45.5±2.3、104.2±5.8 and 109.6±6.2, tumor sphere formation ability of shRNA-ADAM12 group was lower than that of shRNA-NC group and shRNA-C group (F=147.03,P<0.01). Compared with the shRNA-NC group and shRNA-C group, the protain expression of GFAP and Tuj1 were increased up to 166% and 146% (P<0.01) whereas the protein expression levels of CD133 and HES1 were down-regulated by 54% and 50% (P<0.01). Conclusion Knockdown of ADAM12 may suppress self-renewal ability of CD133 positive glioma cells by inhibiting the Notch pathway activity.

BACKGROUND AND OBJECTIVEIn recent years, incidence and mortality of lymphoma are markedly increasing worldwide. However, the pathogenesis and mechanism of invasion and metastasis for lymphoma are not yet fully clarified. It is mainly due to the lack of ideal animal models, which can precisely simulate the invasion and metastasis of lymphoma in the human body. So, it is very necessary to establish a highly metastatic nude mouse model of human lymphoma. This study developed a liver-metastatic model of primary gastric lymphoma in nude mice by using orthotopic surgical implantation of histologically intact patient specimens into the corresponding organs of the recipient small animals.

METHODSA histologically intact fragment of liver metastasis derived from a surgical specimen of a patient with primary gastric lymphoma was implanted into the submucosa of the stomach in nude mice. Tumorigenicity, invasion, metastasis, morphologic characteristics (via light microscopy, electron microscopy, and immunohistochemistry), karyotype analysis, and DNA content of the orthotopically transplanted tumors were studied.

RESULTSAn orthotopic liver metastatic model of human primary gastric lymphoma in nude mice (termed HGBL-0304) was successfully established. The histopathology of the transplanted tumors showed primary gastric diffuse large B-cell lymphoma. CD19, CD20, CD22, and CD79alpha were positive, but CD3 and CD7 were negative. The serum level of lactate dehydrogenase (LDH) was elevated [(1010.56+/-200.85) U/L]. The number of chromosomes ranged from 75 to 89. The DNA index (DI) was 1.45+/-0.25 (that is, heteroploid). So far, the HGBL-0304 model has been passed on for 45 generations of nude mice. A total of 263 nude mice were used for the transplantation. Both the growth and resuscitation rates of liquid nitrogen cryopreservation of the transplanted tumors were 100%. The transplanted tumors autonomically invasively grew and damaged a whole layer in the stomach of nude mice. The metastasis rates of liver, spleen, lymph node, and peritoneal seeding were 100%, 94.3%, 62.6%, and 43.5%, respectively.

CONCLUSIONSThe study successfully establishes an orthotopic liver metastatic model of human primary gastric lymphoma in nude mice. The HGBL-0304 model can completely simulate the natural clinical process of primary gastric lymphoma and provides an ideal animal model for the research on the biology of metastasis and antimetastatic experimental therapies of primary gastric lymphoma.

Aged ; Aneuploidy ; Animals ; Antigens, CD ; metabolism ; CD79 Antigens ; metabolism ; Disease Models, Animal ; Humans ; L-Lactate Dehydrogenase ; blood ; Liver ; pathology ; Liver Neoplasms ; genetics ; metabolism ; secondary ; ultrastructure ; Lymphatic Metastasis ; Lymphoma, Large B-Cell, Diffuse ; genetics ; metabolism ; pathology ; ultrastructure ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Splenic Neoplasms ; secondary ; Stomach Neoplasms ; genetics ; metabolism ; pathology

Objective To investigate the effects of siRNA-mediated knockdown of S100A4 expression on the inva?sion and migration of SNB19 glioma cells. Methods The S100A4 expression was knockdowned using S100A4 siRNA in SNB19 glioma cells. Glioma cells were assigned into control group,siRNA-negative control treated group (siRNA-NC) and siRNA-S100A4 group. RT-PCR and western blot were used to detect the mRNA and protein expression of S100A4, respectively. The wound-healing assay and transwell invasion assay were used to determine the ability of migration and invasion of SNB19 glioma cells, respectively. The expression of matrix metalloproteinase 9 (MMP-9), matrix metallopro?teinase 2 (MMP-2) and E-cadherin proteins were evaluated by using western blot. Moreover, the morphology of lamellipo?dia of glioma cells were examined by using inverted phase-contrast microscopy. Results The mRNA and protein expres?sion levels of S100A4 was obviously down-regulated after transfection of S100A4 siRNA. Compared with control group, the mRNA expression levels of S100A4 in siRNA-NC group and siRNA-S100A4 group were 0.97±0.07 and 0.21±0.04,respectively(P<0.01). The protein expression levels of S100A4 in control, siRNA-NC and siRNA-S100A4 groups were 78.12%±2.63%, 77.16%±3.00%and 37.95%±2.71%, respectively(P<0.01). The migration and invasiveness capability were decreased up to 46% and 55% in the siRNA-S100A4 group compared with the control group(P<0.01). The pro?tein expression levels of MMP-9 and MMP-2 were inhibited up to 62% and 68%(P<0.01)whereas the expression of E-cadherin was increased up to 154%(P<0.01)in the siRNA-S100A4 group. The lamellipodia became smaller or unex?tended in siRNA-S100A4-treated SNB19 glioma cells. Conclusion S100A4 plays an important role in the invasion and migration of glioma cells, suggesting that S100A4 might be a potential candidate for anti-glioma strategy to prevent the invasion and migration of glioma cells.