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<p><b>OBJECTIVE</b>To establish three orthotopically transplanted model of human primary malignant spleen lymphoma in the nude mice.</p><p><b>METHODS</b>Orthotopic transplantation of histologically intact human primary malignant splenic lymphoma tissue obtained from patients was introduced into the splenic parenchyma of nude mice. Tumorigenicity, invasion, metastasis and morphological characteristics of the transplanted tumor were studied by light microscopy, electron microscopy and immunohistochemical methods.</p><p><b>RESULTS</b>The first kind, a strain of human primary malignant spleen lymphoma (non-Hodgkin's, cleaved B cell, BFNHL-HMN-1) screened from 11 patients which had been passaged in vivo for 41 generations, a second kind, a liver metastasis model of human primary malignant spleen lymphoma (non-Hodgkin's, cleaved B cell, LM-BFNHL-HMN-2) which had been passaged for 47 generations and a third kind of human primary malignant spleen lymphoma (non-Hodgkin's, T-immunoblastic cell, TINHL-HMN-3) having passaged for 37 generations were all successfully transplanted in 611 nude mice. Models of BFNHL-HMN-1 and TINHL-HMN-3 tumor gave nodular growth and lymph node metastasis in the spleen hilum but without any metastasis in the abdominal lymph nodes or organs. In the LM-BFNHL-HMN-2 model, not only did the tumor cells grow in the spleen, but in spleen hilum, lymph nodes and liver also. The orthotopically transplanted tumor cells were similar to the original human tumor in light histopathology, ultrastructure features, DNA content and chromosomal karyotype.</p><p><b>CONCLUSION</b>These three models are able to serve as useful tools for the study of biologic characteristics and experimental treatment of human primary malignant lymphoma.</p>
Subject(s)
Animals , Humans , Mice , Disease Models, Animal , Lymphoma , Pathology , Mice, Nude , Neoplasm Metastasis , Neoplasm Transplantation , Splenic Neoplasms , Pathology , Xenograft Model Antitumor AssaysABSTRACT
Objective Liver metastasis model of human primary gastric lymphoma in nude mice was reproduced for an experiment to evaluate the inhibitory effect of cytokine-induced killer (CIK) cells on the growth and liver metastasis of primary gastric lymphoma. Methods Surgical orthotopic implantation of a histologically intact liver metastasis fragment derived from a surgical specimen of a patient with metastatic gastric lymphoma was initally implanted, in order to reprodueing a liver metastasis model of human primary gastric lymphoma. Peripheral blood mononuclear cells (PBMC), isolated by blood cell separator from healthy donors and patients with primary gastric lymphoma, were incubated in vitro. rhIFN-?, rhIL-2 and anti-CD3 McAb were added to PBMC in order to prepare CIK cells as well as lymphokine-activated killer (LAK) cells. CIK and LAK cells from different donors were used in treating gastric malignant lymphoma, so as to investigate the inhibitory effect of 2 kinds of effector cells on the growth of the tumor and liver metastasis. Results The liver metastasis model of human primary gastric malignant lymphoma in nude mice was successfully reproduced. After administration of different agents continuously for 20 days (0.3ml/d), the inhibitory rates of the following 4 groups, healthy donors LAK group (2?1010/ml), healthy donors CIK group (2?1010/ml), patients CIK group (1?1010/ml) and patient CIK group (2?1010/ml), were 39.28%, 53.57%, 40.38% and 56.42%, respectively. The liver metastasis rates in control group, healthy donors LAK group, healthy donors CIK group, patients CIK group (1?1010/ml) and patient CIK group (2?1010/ml), were 100.0%, 62.5%, 50.0%, 62.5% and 37.5%, respectively. Tumor weights of all treatment groups were lighter than that of saline group (P
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Objective A liver metastasis model of human primary malignant lymphoma of small intestine was reproduced in nude mice in an attempt to provide an ideal animal model for elucidating the mechanism of liver metastasis of primary small intestinal lymphoma.Methods A piece of surgically obtained liver metastatic tissue of small intestinal lymphoma was implanted into the mucous membrane of small intestine in nude mice to reproduce the model.After metastasis of this tumor to the liver occurred,a portion of the metastais was transplanted into the mucous membrane of small intestine of another nude mouse.This process was repeated 4 times in order to obtain a cell line with the characteristics of high malignant lymphoma metastasis to liver.The survival rate of the experimental animals,regional invasion rate and metastasis rate were observed,and the morphological characteristics(light microscopy,electron microscopy and immunohistochemistry),karyotype analysis and DNA content of the neoplastic cells were also determined.Results A liver metastasis model of human primary malignant lymphoma of small intestine in nude mice(termed HSIL-0402)was successfully reconstructed,by repeated implantation of liver metastatic tumor in vivo.Histopathology showed HSIL-0402 tumor was a high grade non-Hodgkin's lymphoma.Immunohistology showed the cells were CD19,CD20,CD45 and CD79a positive,but negative for CD3 and CD7.The modal number of chromosome was between 56-69.DNA index(DI)was 1.61?0.37,which showed heteroploid.So far,HSIL-0402 had been maintained for 27 passages in nude mice,exhibiting 100% of transplantability,liver metastatic rate,and resuscitation rate after liquid nitrogen cryopreservation.Lymph node metastasis and celiac seeding occurred in 67.4% and 61.7% of a total of 156 observed animals.The HSIL-0402 model displayed various manifestations reminiscent of highly metastatic invasive behavior in nude mice,including invasive growth,hematogenous metastasis,lymph node metastasis and celiac seeding.Conclusion The present study successfully re-established a spontaneous liver metastasis model of human primary malignant lymphoma of small intestine in nude mice,HSIL-0402,which provides an ideal animal model for the researches on biological mechanism of liver metastasis and anti-metastasis therapy of human primary small intestinal lymphoma.
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Objective To reproduce high metastasis models of human primary colorectal lymphoma in nude mice by orthotopic transplantation, and to investigate their biologic features. Methods Histologically fresh lymphoma tissues from primary and liver metastatic lesions of human primary colorectal lymphoma obtained during operations were transplanted into colorectal mucosa of nude mice. Tumorgenecity, invasion, metastasis, morphology (light microscopy, electron microscopy and immunohistochemistry), karyotype analysis and DNA content of the orthotopically transplanted tumors were studied. Results According to the new WHO classification of malignant lymphoma, a strain of liver metastasis model of human primary colonic lymphoma (non-Hodgkin's, B cell) in nude mice by orthotopic transplantation (HCBL-0301), and a strain of high metastasis model of human primary rectal lymphoma (non-Hodgkin's, B cell) in nude mice by orthotopic transplantation (HRBL-0302) were successfully screened from four cases of human primary colorectal lymphoma. Histopathology of transplanted tumors showed high grade non-Hodgkin's large B cell lymphoma. The cells were positive for CD19, CD20, CD22 and CD45, but negative for CD3 and CD7. The number of chromosome was between 55 and 69. DNA index (DI) was 1.59~1.71 (i.e. heteroploid). So far, HCBL-0301 and HRBL-0302 had been passaged for 31 and 27 generations in nude mice, respectively, and transplantation was successful in 326 nude mice. Since the third generation, both the growth rate of transplantation and rate of resuscitation after being thawed from liquid nitrogen cryopreservation were 100%. In HCBL-0301, metastasis to the right lobe of liver was most common and metastatic rate was 100%; additionally, rates metastasis to of lymph node and peritoneal seeding were 67.4%. In HRBL-0302, metastasis to the left and right lobes of liver was most common with metastasis rate of 63.7%, and rates of metastasis to lymph node and peritoneal seeding were 56.4%. Transplanted human primary colorectal lymphoma could autonomously and invasively grow in the colorectum of nude mice, with occurrence of hematogenic, lymph node and implantation metastases. Conclusions The study successfully replicated high metastasis models of human primary colorectal lymphoma in nude mice by orthotopic transplantation. HCBL-0301 and HRBL-0302 models can be used in the research on pathogenesis, mechanism of invasion and metastasis and experimental therapy of human primary colorectal lymphoma.
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Objective To provide an experimental tool for explo ri ng pathogenesis and experimental treatment strategies for primary lymphoma of th e liver. Methods Histologically intact lymphoma tissues from pa tients with primary lymphoma of the liver were transplanted into hepatic parench yma of nude mice. Tumorgenecity, invasion, metastasis, morphological characteris tics(light microscopy, electron microscopy and immunohistochemistry), serologica l test(AFP, HBsAg and LDH), karyotype analysis and DNA content of orthotopically transplanted tumors were studied. Results Orthotopically trans planted model of human primary malignant lymphoma of the liver in nude mice(desi gnated as HLBL-0102) was successfully reproduced. Histopathology of transplante d tumors showed primary lymphoma of the liver(non-Hodgkin's, B cell). The cells were positive for CD19,CD20,CD45RO and CD79a, but negative for CD3 and CD7. Ser ological tests showed that the serum was AFP negative and HBsAg positive, and t he concentration of LDH was 1267.5U/L. The number of chromosome was between 55 and 59. DNA index(DI) was 1.57~1.61(i.e. heteroploid). So far, the strain HLB L-0102 has grown for 3 years and been passaged for 37 generations in nude mice. Altogether 283 nude mice were used for transplantation. The growth rate and res uscitation rate of liquid nitrogen cryopreservation of transplanted tumors were both 100%. The transplanted tumors autonomoasly and invasively grew in the live r of nude mice, damaging adjacent liver tissues, bile ducts, and veins in the po rtal area. There was no involvement of other tissues and organs or distal lymph nodes. Orthotopically transplanted tumors were consistent in histopathological a nd ultrastructural features, DNA content and chromosomal karyotype with the orig inal human tumor. Conclusions The study is the first attempt to successfully reproduce orthotopically transplantation model of human primary ma lignant lymphoma of the liver in nude mice. HLBL-0102 completely replicates th e natural clinical process of primary lymphoma of the liver, and provides an ide al animal model for further research on the biology and experimental therapeutic strategies of primary lymphoma of the liver.
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To probe course and mechanism of cellular immune respone in early syphilitic lesion, the expression levels of CD3, CD20, CD68 were determined by immunohistochemistry and a computer image analysis system. The results showed that the expressions of CD3, CD20, and CD 68 were positive in 43 cases of primary and secondary syphilis. The expression level of CD68 was higher thanthat of CD3, CD20, especially around blood vessels. The expression level of CD 20 was very low. This study indicates that T cells, B cells, and in particular macrophages play an important cellular immunologic regulating role in clearance of Treponema pallidum from the infected tissue, but the efficacy is not high enough.
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Two cell strains from human pancreatic cancer taken surgically were transplanted to the pancreas of pureline BALB/C-nu/nu nude mice and 9 generations of PTNMP-1 and 6 generations of PTNMP-2 were obtained. Biological properties were studied. It yielded a transplant success rate of 95% - 100% and large amount of CEA. Analysis of the karyotype confermed that they retained the karyotype of human cancer cells. Some lymphatic and blood stream metastasis and invasion could be found in the nude mice orthotopically transplanted with tumour, showing that the transplanted tumour had characteristics identical with the donor tumour.
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to establish the human malignant lymphoma model in nude mice, orthotopic transplantation of histologically intact gastric lymphoma tissue from 11 patients was implanted into gastric submucosa of nude mice. Tumorgenicity, invasion, metastasis and morphological characteristics of the transplanted tumors were studied by light microscopy, electronic microscopy, and immunohistochemistry. Two strains screened from 11 cases of human gastric lymphoma were the high metastasis model (HGL HMN 1)and the in situ model of human gastric lymphoma (HGL HMN 2) passaged in vivo for the 36th and 27th generations respectively. 329 nude mice were transplanted. Since the 3rd generation, the tumor transplantation growth rate and the resuscitation rate from liquid nitrogen were 100% .Lymph node metastasis, blood metastasis, and seeding metastasis were present. The transplanted tumors were similar to the original human malignant lymphoma in histopathological, ultrastructure features, DNA content and chromosomal karyatype. Its spontaneous growth occurred in the stomach of the nude mice,accompanied by destructive infiltration of every tissue layer of the stomach wall. Its invasion and metastasis simulated integrally the clinic process of human malignant lymphoma. These models can be used to study the etiology, invasion, metastasis and experimental treatment of human malignant lymphoma.