Monoclonal antibodies to an ectopically expressed alkaline phosphatase in a human malignant cell line

The D98/AH-2 cell line (a subline of HeLa) expresses a form of alkaline phosphatase (ALP) which closely resembles the adult and fetal intestinal forms of ALP. To characterize this ectopic form of ALP, four monoclonal antibodies were raised against D98/AH-2 ALP, and their binding with ALPs from D98/AH-2 cells, placenta, fetal intestine (meconium), adult intestine, and liver was compared using an electrophoretic titration procedure. The ALPs were either untreated or treated with neuraminidase. All four monoclonal antibodies bound desialated D98/AH-2 ALP most strongly. Adult intestinal ALP, which does not contain sialic acid residues, reacted much more strongly than either sialated or desialated fetal intestinal ALP. Two of the four monoclonal antibodies reacted very weakly or not at all with placental ALP, but two others reacted more strongly with placental ALP than with fetal intestinal ALP. None of the antibodies reacted with liver ALP. From these results, it appears that D98/AH-2 ALP may be a modified form of adult intestinal ALP.     

Alkaline phosphatase isozymes in human testicular germ cell tumors, their precancerous stage, and three related cell lines

The four known isozymes of the human alkaline phosphatase (ALP) were detected by isoelectric focusing in extracts of various types of germ cell tumors, three related cell lines, and their precancerous elements (atypical germ cells). In seminoma, placental alkaline phosphatase (PLAP) and germ cell alkaline phosphatase (PLAP-like) could be separated by isoelectric focusing following isolation by immunoaffinity. The occurrence of both isozymes in seminoma could explain partial heat sensitivity and variation in electrophoretic patterns of the seminoma isozyme frequently observed upon starch gels, in comparison to the normal placental phenotype. The four ALP isozymes are produced not only in germ cell tumors, but already in precancerous tissues. Quantitative analysis showed that the amount of the four isozymes varies in parallel in the tumors tested. Maximal expression was found in seminoma. The relation between ALP gene overexpression and gene amplification by polyploidy of chromosomes 1 and 2 in these lesions is discussed. On the other hand, the ectopic expression of intestinal alkaline phosphatase and PLAP associated with overexpression of PLAP-like in tumor cells as well as in their precancerous stage indicates gene activation by some unknown mechanisms, probably a regulatory process affecting the three tissue-specific ALP genes simultaneously.     

Tumour and cellular localization by use of monoclonal and polyclonal antibodies to placental alkaline phosphatase

Monoclonal and polyclonal antibodies against placental alkaline phosphatase (PLAP) were evaluated for tumour immunolocalization of human PLAP-producing Hep 2 tumours in nude mice. The antibodies were labelled with 125I and injected i.p. in mice with developing Hep 2 tumours. The distribution of 125I-anti PLAP in various tissues showed that the labelled antibody was enriched in the tumour, the mean concentration ratio being 7.1 and 6.8 for polyclonal and monoclonal antibodies, respectively. A PLAP negative tumour (RD) showed a mean ratio of 1.2. There was a positive correlation between PLAP content and uptake of labelled antibody in the tumours. Hep 2 tumour cells in tissue culture showed 100% positivity for PLAP, while imprints of the tumour after passage in nude mice showed 40-50% positivity. PLAP offers potential as a useful marker for localizing tumours in humans.     

Changes in the ganglioside composition of human neuroblastoma cells under different growth conditions

The ganglioside composition of human neuroblastoma cells (LA-N-1 and LA-N-5) was studied in samples obtained from (1) original cells in tissue cultures, (2) tumors grown in nude mice inoculated with original cells and (3) cells in tissue cultures re-established from the mouse tumors. The amounts of "a" pathway gangliosides (GM2, GM1 and GD1a) and those of the "b" pathway (GD3, GD2, GD1b and GT1b) differed according to the culture conditions. The "b" pathway gangliosides were markedly increased in the tumors grown in nude mice. In contrast, the "a" pathway gangliosides were abundant in cultures of both original and re-established cells. We also measured the enzymatic activities of UDP-N-acetylgalactosamine: GM3, N-acetylgalactosaminyl transferase (EC 2.4.1.92) and of CMP-N-acetylneuraminic acid: GM3 sialyl transferase (EC 2.4.99.8) in neuroblastoma cells cultured under these conditions. These enzymes are thought to be the key enzymes involved in the synthesis of the "a" and "b" pathway gangliosides. Though there was no significant difference in the activity of N-acetylgalactosaminyl transferase between original cells and tumors in nude mice, re-established cells showed a definitely higher activity (3.5 times higher than in the original cells). On the other hand, tumors grown in nude mice had a markedly higher activity of sialyl transferase than that of original cells or re-established cells. These findings suggest that the culture conditions and/or the type of cell growth play some role in the synthesis and expression of gangliosides in neuroblastoma cells.     

Placental-type alkaline phosphatase in cervical neoplasia

Monoclonal antibodies reactive with placental-type alkaline phosphatase have formed the basis of methods for detection of this oncodevelopmental antigen in patients with pre-invasive and invasive cervical neoplasia, with or without evidence of papilloma virus infection. Disease-related elevations of placental-type alkaline phosphatase were not observed in patients' sera. Solubilised cervical smears or biopsy material, and cervical mucus swabs, often contained substantial amounts of this isoenzyme; however, there was no significant difference between any of the patient and control groups. Thus, serological and smear test assays for placental-type alkaline phosphatase were not useful in differential diagnosis of cervical lesions. However, its presence in most biopsy specimens, often at high levels, indicated possible application for in vivo radioimmunoimaging studies of invasive or metastatic cervical cancer.     

Human osteosarcoma cells, tumorigenic in nude-mice, express beta(1)-integrins and low-levels of alkaline-phosphatase activity

The interactions between cells and the extracellular matrix (EM) have important effects on tumor invasion and metastasis. Osteosarcoma (OS) is a highly metastatic tumor, secondary lesions occurring early in the natural history of the disease. Despite the clinical relevance of disseminated disease in this neoplasia, the metastatic ability and other features related to the metastatic phenotype have not been extensively investigated in human OS cells. In this study the expression of bone matrix proteins, of their receptors, and the ability to adhere to and grow on some EM components in vitro were examined in human OS cell lines and related to their tumorigenic and metastatic potential in vivo. A significantly higher expression of integrin subunits alpha2, alpha5 and alpha6, a better-organized surface expression of fibronectin and laminin, and a lower alkaline phosphatase (ALP) activity was accompanied by a higher ability to grow in vitro on EM components and to produce tumors in nude mice. On the other hand, no relationship was found between these features and the metastatic ability. Therefore, tumorigenicity of human OS cells might be related to an overexpression of some integrins and to a peculiar expression of some bone matrix proteins, possibly associated with distinct differentiative levels. Further investigations on clinical material will possibly help defining the actual prognostic value of these parameters.     

蟾酥脂质微球注射液对四种荷瘤裸鼠肿瘤生长的抑制作用

目的:观察蟾酥脂质微球注射液对荷人肝癌Hep G2、人食管癌EC9706、人结肠癌HCT-8和人胃癌BGC 803瘤株裸鼠肿瘤生长的抑制作用.方法:在BALB/c-nu裸鼠右前肢腋下接种4种人癌细胞株建立荷瘤动物模型,移植10 d后采用均衡法随机分为5组,即蟾酥脂质微球注射液高剂量组(2.50 mg/kg)、中剂量组(1.25 mg/kg)、低剂量组(0.63 mg/kg)以及阳性药组(氟尿嘧啶注射液,1.25 mg/kg)和阴性对照组(等体积脂质微球空白注射液),每组7只裸鼠,给药体积0.2 ml.采用尾静脉注射方法给药,各组动物于分组后每周给药2次,连续给药6次.于给药后动态检测并计算各组肿瘤体积(Vt)、肿瘤相对体积(VRT)、肿瘤增殖率(T/C),末次给药后3 d检测并计算各组肿瘤质量和抑瘤率.结果:各组裸鼠给药前肿瘤体积均无显著性差异.荷人肝癌Hep G2细胞瘤裸鼠给药7 d后,各剂量组肿瘤体积和相对肿瘤体积均较阴性对照组明显降低(P<0.05),末次给药后中、高剂量组T/C值<40%,各剂量组的平均肿瘤质量均较阴性对照组明显降低(P<0.05),高剂量组的抑瘤率为74.07%.荷人食管癌EC9706瘤裸鼠末次给药后,各剂量组肿瘤体积和相对肿瘤体积均较阴性对照组明显降低(P<0.05),中、高剂量组T/C值<40%,各剂量组的平均肿瘤质量均较阴性对照组明显降低(P<0.05),高剂量组的抑瘤率为70.38%.荷人结肠癌HCT-8细胞瘤裸鼠末次给药后,各剂量组肿瘤体积和相对肿瘤体积均较阴性对照组明显降低(P<0.05),高剂量组T/C值<40%,各剂量组的平均肿瘤质量均较阴性对照组明显降低(P<0.05),高剂量组的抑瘤率为52.42%.荷人胃癌BGC 803细胞瘤裸鼠末次给药后,中、高剂量组的肿瘤体积和相对肿瘤体积均较阴性对照组明显降低(P<0.05),各剂量组T/C值>40%,各剂量组的平均肿瘤质量均较阴性对照组明显降低(P<0.05),高剂量组的抑瘤率为47.42%.结论:蟾酥脂质微球注射液具有确切的抑制人肝癌Hep G2、食管癌EC9706、结肠癌HCT-8和胃癌BGC 803瘤株增殖的作用,作用效果以抑制人肝癌Hep G2和人食管癌EC9706瘤株生长作用为最佳.     

Isozyme phenotypes of polyoma virus tumors in mice

Isozyme profiles for 32 enzyme systems were studied in tumors induced by two strains of polyoma virus (2PTA and LID1), in two conventional mouse strains (C3H/BiDa and NIH), and in athymic (nude) mice of two genetic backgrounds (C3H/Hes nu/nu and NIH nu/nu). Tumors studied were: primary and transplant passages of salivary gland tumors (127); primary thymic epithelial tumors (12); primary subcutaneous sarcomas (6); primary hair follicle tumors (5); primary and transplant passages of mammary tumors (18); primary ameloblastomas (3); and primary renal medullary sarcomas (3). Regardless of mouse strain or virus strain, the isozyme arrays were highly constant and unique for each tumor histotype with the exception of salivary and mammary tumors, which shared a single profile differing from that of each of the other histotype-associated profiles. Other tumor types could be distinguished from each other and from the salivary-mammary tumor pair by as few as five isozymes: glycerol-3-phosphate dehydrogenase; glyceraldehydephosphate dehydrogenase; lactate dehydrogenase; sorbitol dehydrogenase; and alkaline phosphatase. Twelve nonpolyoma mammary tumors and their passages from mouse mammary tumor virus-expressed C3H/Hes nu/+ mice were analyzed for the same enzymes; variations in activity and isozyme profiles were found for ten enzyme systems. Three spontaneous salivary myoepitheliomas in BALB/c mice were also analyzed; two different lactate dehydrogenase profiles were observed, and all three tumors lacked the placental alkaline phosphatase present in polyoma virus-induced salivary tumors. Uniformity of isozyme phenotype may be characteristic of DNA virus transformation of cells in a particular differentiative state. This uniformity does not appear to occur in mouse mammary tumor virus-associated tumors, spontaneous tumors, and, according to the literature, chemically induced tumors.     

Flow cytometric analysis of human uterine sarcomas and cell lines

Flow cytometric techniques were used to characterize multiple human uterine sarcomas and cell lines derived from some of these tumors. Analysis of DNA content showed that 9 of the 11 uterine sarcomas investigated were composed of at least one aneuploid population as well as a distinct diploid population. These data indicate that aneuploidy, as measured by flow cytometry, is a characteristic more common to uterine sarcomas than that previously reported for uterine adenocarcinomas. Unlike the original tumors, the cell lines established from three of the sarcomas contained predominantly diploid populations with only minor aneuploid populations. Treatment of one of the sarcoma cultures with tumor promoters did not result in an increase in the aneuploid populations. Tumors which arose in nude mice upon transplantation of two of the sarcomas did not contain the same distribution of tumor subpopulations as found in the original sarcomas. Apparently, the in vitro culture and and in vivo nude mouse conditions were not appropriate for maintaining the original equilibrium between the aneuploid and diploid subpopulations but instead provided a selective environment that resulted in the preferential growth of only certain tumor populations. Dual-parameter analysis of DNA content and alkaline phosphatase levels of one of the sarcomas were useful for distinguishing the aneuploid from the diploid population coexisting in this tumor. Our data suggest that flow cytometry is a valuable tool to analyze the characteristics of the tumor populations residing in primary uterine sarcomas as well as to determine which of these tumor subpopulations survive in culture and transplantation to nude mice.     

Effect of Ascorbic Acid, Lysine, Proline, and Green Tea Extract on Human Osteosarcoma Cell Line MNNG-HOS Xenografts in Nude Mice: Evaluation of Tumor Growth and Immunohistochemistry.

Structural changes in the extracellular matrix (ECM) are necessary for cell migration during tissue remodeling. MMPs, VEGF, Ki-67 (proliferative protein), and constituents of ECM play a critical role in angiogenesis and underlie neoplastic invasion and metastasis. This prompted us to investigate the effect of a diet containing lysine, proline, arginine, ascorbic acid, and green tea extract (NM) on the growth of tumors induced by implanting human osteosarcoma MNNG in athymic nude mice and the expression of MMPs, VEGF, Ki- 67 and fibronectin in these tumors, as well as the production of mucin (by PAS staining). We also investigated the effect of the supplemented diet on serum ascorbic acid, total protein content, alkaline phosphatase activity, and liver enzymes. Athymic male nude mice (n = 12) were inoculated with 3x106 osteosarcoma cells MNNG-HOS and randomly divided into group A (fed a regular diet) and group B (fed a regular diet supplemented with 0.5% NM). Four weeks later, the mice were sacrificed. Results showed that NM inhibited the growth and reduced the size of tumors in nude mice. Histological evaluation revealed increased mitotic index, MMP-9, and VEGF secretion in the control group tissues. Results demonstrate that the nutrient mixture of lysine, proline, arginine, ascorbic acid, and green tea extract tested strongly suppressed the growth of tumors without adverse effects in nude mice, suggesting potential as an anticancer agent.     

Effect of ascorbic acid, lysine, proline and green tea extract on human osteosarcoma cell line MNNG-HOS xenografts in nude mice

Structural changes in the extracellular matrix (ECM) are necessary for cell migration during tissue remodeling MMPs, VEGF, Ki-67 (proliferative protein), and constitutents of ECM play a critical role in angiogenecontaining lysine, proline, arginine, ascorbic acid, and green tea extract (NM) on the growth of tumors induced by implanting human osteosarcoma MNNG in athymic nude mice and the expression of MMPs, VEGF, Ki-67 and fibroenectin in these tumors, as well as the production of mucin (by PAS staining). We also investigated the effect of the supplemented diet on serum ascorbic acid, total protein content, alkaline phosphatase activity, and liver enzymes Athymic male nude mice (n=12) were inoculated with 3×10⁶ osteosarcoma cells MNNG-HOS and randomy divided into group A (fed a regular diet) and group B (fed a regular diet supplemented with 0.5% NM). Four weeks later, the mice were sacrificed. Results showed that NM inhibited the growth and reduced the size of tumors in nude mice. Histological evaluation revealed increased mitotic index, MMP-9, and VEGF secretion in the control group tissues. Results demonstrate that the nutrient mixture of lysine, proline, arginine, ascorbic acid, and green tea extract tested strongly suppressed the growth of tumors without adverse effects in nude mice, suggesting potential as an anticancer agent.     

Induction of sarcomas in nude mice by implantation of Syrian hamster fetal cells exposed in vitro to nickel subsulfide.

In vitro exposure of Syrian hamster fetal cells to nickel subsulfide (alpha Ni3S2) yielded positive colony assays for morphological transformation. A dose-response relationship was found between the concentration of alpha Ni3S2 and the incidence of morphological transformation. Exposures of alpha Ni3S2 induced morphological transformation at concentrations (0.1 or 1.0 microgram/ml of culture medium) which did not impair cell plating efficiency. Nickel monosulfide (NiS) did not induce morphological transformation of Syrian hamster fetal cells under the same conditions. Clones of alpha Ni3S2-transformed cells were able to grow in soft agar medium and demonstrated increased basal and induced activities of ornithine decarboxylase. Undifferentiated sarcomas developed in 26 of 27 nude mice at the site of s.c. injection of clones of alpha Ni3S2-transformed cells. No tumors developed in 19 control nude mice which were given s.c. injections of nontransformed Syrian hamster fetal cells which had not been exposed to alpha Ni3S2. This study demonstrates that fetal cells which undergo transformation following exposure to alpha Ni3S2 are capable of producing malignant tumors in nude mice.     

Establishment and Characterization of a Simian Virus 40-Immortalized Osteoblastic Cell Line from Normal Human Bone

We established a human osteoblastic cell line immortalized by simian virus 40 (SV40) in vitro , and designated it SV-HFO. Immunocytochemically, the cells were positive for SV40 large T-antigen, vimentin and osteocalcin, but negative for keratin and epithelial membrane antigen. The cells had characteristic morphologic and ultrastructural features of osteoblasts, produced alkaline phosphatase, and synthesized osteocalcin, the levels of which were elevated by treatment of the cells with 1α,25-dihydroxyvitamin D₃. The cells proliferated and showed such osteoblastic properties even under serum-free conditions. The cells grew in soft agar, but did not form tumors when transplanted into athymic nude mice. Karyotypic analysis by the Q-banding technique showed that these cells were of human origin. The SV-HFO cell line is expected to serve as a suitable model for studying metabolism and carcinogenesis in human bone.     

Macrophages Promote Coal Tar Pitch Extract-induced Tumorigenesis of BEAS-2B Cells and Tumor Metastasis in Nude Mice Mediated by AP-1

Background: We sought to evaluate the role of tumor associated macrophages (TAMs) on the promotion of coal tar pitch extract (CTPE)-induced tumorigenesis of human bronchial epithelial cells (BEAS-2B) and tumor metastasis in nude mice, and related mechanisms. Materials and Methods: BEAS-2B cells were first treated with 2.4 mg/mL CTPE for 72 hours. After removal of CTPE, the cells were continuously cultured and passaged using trypsin-EDTA. THP-1 cells were used as macrophage-like cells. BEAS-2B cells under different conditions (n=6/group) were injected into the back necks of nude mice, and alterations of tumor xenograft growth, indicative of tumorigenicity, and tumor metastasis were determined. Pathological changes (tumor nests and microvascular lesions) of HE-stained tumor tissues were also evaluated. The expression of AP-1(c-Jun) in xenografts and metastatic tumors was determined using immunohistochemistry. Results: Tumor size and weight in nude mice transplanted with the mixture of CTPE-induced passage 30 BEAS-2B and THP-1 cells (2:1) were increased compared to those from the CTPE-treated BEAS-2B cells at passage 30 alone at different observation time points. Tumor metastasis to lymph nodes and liver was only detected after transplantation of a mixture the two kinds of cells. The numbers of tumor nests and microvascular lesions, and the expression levels of AP-1 (c-Jun) in tumors from the mixture of two kinds of cells were increased apparently in contrast to those in tumor from the CTPE-treated BEAS-2B cells of passage 30 alone. In addition, there was positive correlation between AP-1 (c-Jun) expression level and the number of microvascular lesions, or between AP-1 (c-Jun) expression level and tumor metastasis in these two groups. Conclusions: TAMs not only facilitate tumorigenesis transformation of CTPE-induced BEAS-2B cells, but also promote tumor growth, angiogenesis and metastasis in nude mice in vivo, which may be mediated by AP-1.     

Intestinal alkaline phosphatase isoenzyme in patients with primary liver cancer during treatment with N10-propargyl 5, 8-dideazafolic acid (CB 3717)

Serum aspartate transaminase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (gamma GT) activities and the serum ALP isoenzyme pattern have been measured in eleven patients undergoing treatment with CB3717. There were increases in the activity of all three enzymes. The ALP isoenzyme pattern showed an increased contribution of the intestinal isoenzyme to the serum ALP activity. This may be due to increased intestinal mucosal leakage or impaired uptake and breakdown of the intestinal isoenzyme by the liver.     

Characterization of a human osteosarcoma cell line (Saos-2) with osteoblastic properties

This study examines the osteoblastic properties of the established human osteosarcoma cell line Saos-2. Saos-2 cells inoculated into diffusion chambers, which were implanted i.p. into nude mice, produced mineralized matrix in 4 of 6 chambers at 8 weeks. In 5 of 6 chambers there was a strong positive alkaline phosphatase reaction. In culture the alkaline phosphatase levels increased with time and cell density, reaching very high levels at confluence: 4-7 mumol/mg protein/min. The cells show a sensitive adenylate cyclase response to parathyroid hormone, 50% effective dose = 2.8 nM, which increases with cell density and is further raised by dexamethasone treatment. They also exhibit typical binding of 1-25-dihydroxyvitamin D3 to 3.2S receptor protein with an apparent Kd of 0.21 nM; the numbers of sites per cell were 3,300 at 50,000 cells/cm2 and 1,800 at 280,000 cells/cm2. The presence of osteonectin was visualized with a monoclonal antibody which revealed a reticular pattern on the cell surface. Osteonectin was also detected in the medium by Western blots, migrating at around Mr 40,000 in nonreduced gels and Mr 44,000 in reduced gels. The Saos-2 cells thus possess several osteoblastic features and could be useful as a permanent line of human osteoblast-like cells and as a source of bone-related molecules.     

Functional and morphological characteristics of transplantable rat pituitary tumors established in nude mice

Two strains of transplantable rat pituitary tumors, MtT SA5 and MtT SA6, have been established in female nude mice from a single original pituitary tumor which had spontaneously occurred in a female Wistar rat at 759 days of age. MtT SA5 tumor produces prolactin (PRL), growth hormone, and adrenocorticotropic hormone, and MtT SA6 tumor secretes PRL and growth hormone. Additionally, both tumors induce severe nephropathy and promote pathogenicity of murine hepatitis virus, resulting in hepatic necrosis. Electron micrographs of MtT SA5 and MtT SA6 tumors revealed three and two types of cells, respectively, in reference to secretory granules. The tumors seem to consist of mixed population, each cell secreting each hormone. Since marked adrenal enlargement and relatively low serum corticosterone levels were found in MtT SA5-bearing rats, it is suggested that MtT SA5 tumor secretes adrenocorticotropic hormone and/or its related peptides which induce adrenal hyperplasia with little or no stimulation of corticoid production. In nude mice bearing MtT SA5 tumor, concentrations of growth hormone in serum and tumor tissue were exceedingly higher than those of PRL, while they were in the same magnitude in MtT SA6-bearing nude mice. We also found that PRL levels in serum and tumor tissue of MtT SA5-bearing nude mice were much higher in males than females, although those of MtT SA5-bearing rats were not significantly different in both sexes.     

人小肠原发性恶性淋巴瘤裸鼠原位移植模型的建立

目的 建立人小肠原发性恶性淋巴瘤裸鼠原位移植模型,为探讨其发病机制和实验治疗提供工具。方法 将5例人小肠恶性淋巴瘤新鲜组织植入裸鼠小肠黏膜层内,观察原位移植成瘤率和移植瘤的侵袭、转移,并进行形态学(光镜、电镜、免疫组织化学)、染色体核型和流式细胞分析。结果 有3例原位移植获得成功。依据新的WHO恶性淋巴瘤分类标准,建成1株人小肠原发性(非霍奇金B细胞)恶性淋巴瘤裸小鼠原位移植模型(HSIL-1)、1株人小肠原发性(非霍奇金B细胞)恶性淋巴瘤裸小鼠原位移植高转移模型(HSIL-2)和1株人小肠原发性(非霍奇金T细胞)恶性淋巴瘤裸小鼠原位移植模型(HSIL-3)。免疫组织化学显示,HSIL-1和HSIL-2的CD19、CD20、CD22、CD40、CD45、CD72阳性,HSIL-3的CD3、CD7、CD45RO阳性。染色体众数范围55～69条,为亚三倍体核型。移植瘤细胞的DNA指数为1.46～1.71,均为异倍体。HSIL-1、HSIL-2和HSIL-3分别传至32代、27代和21代,共移植裸鼠443只,其肿瘤移植生长率、液氮冻存复苏成活率和自发转移率均为100％。移植瘤在裸鼠小肠内呈侵袭性生长,破坏肠壁各层组织结构,出现血道、淋巴道及种植性转移。原位移植瘤与来源人小肠恶性淋巴瘤细胞一致。结论 3株人小肠原发性恶性淋巴瘤裸鼠原位移植模型完整地模拟了人小肠原发性恶性淋巴瘤患者的临床过程,为研究小肠恶性淋巴瘤的发病机制和实验治疗提供了理想的动物模型。     

Human endometrial carcinomas serially transplanted in nude mice and established in continuous cell lines.

Three out of five human endometrial carcinomas were successfully grafted into nude mice (BALB/c/nu/nu). Two of these tumors could be maintained by serial transplantation. The morphological characteristics displayed by the grafted tumors were comparable to those of the original carcinomas. Permanent cell lines were established from these two tumors. Reinjection of cells grown in vitro into nude mice produced nodules of identical histology as compared to original solid transplants. The influence of medroxyprogesterone acetate on tumor growth in vivo and cell proliferation in vitro was studied. This hormonal treatment did not produce any significant effect on tumor cells, either in vitro or in vivo, for the two endometrial carcinomas. After medroxyprogesterone administration, a slight but non-significant growth inhibition of the tumor cells in vitro was observed and the tumor transplants in vivo did not appear to be influenced. The experiments illustrate the possible use of this model for testing potential anti-cancer agents.     

Increase in alkaline phosphatase activity in the liver of mice bearing Ehrlich ascites tumor.

In mice bearing Ehrilich ascites tumors, alkaline phosphatase activity was increased fivefold in the liver and by 50% in the kidney. In mice bearing solid tumors caused by inoculation of tumor cells into the axillary region, the activity of this enzyme in the liver was increased 11-fold, whereas the activity in the kidney did not change. Alkaline phosphatase activities in the liver and kidney were not altered by administration of adrenal steroids. Adrenalectomy, fasting, and pregnancy did not affect the activity of alkaline phosphatase in the liver and kidney. Treatment with tumor extracts or ascites fluid of normal mice increased liver alkaline phosphatase activity. These findings suggested that the elevation of liver alkaline phosphatase activity was cuased primarily by the tumor itself, and not by hormonal imbalance provoked secondarily by the presence of the tumor.