Intracerebroventricular analgesia enhanced by intrathecal (IT) dynorphin A(1-17) antibody.
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
Biomedical subjects
J Fujimoto
Publications and source records attributed to J Fujimoto.
Molecular analysis of 5' J region of immunoglobulin heavy chain gene in human acute leukemias.
Ig heavy chain (IgH) J (JH) region organization in 83 human acute leukemias was studied. In 31 of the 35 precursor B acute lymphocytic leukemia (ALL) the rearrangements of the IgH gene involved sites between D regions 5' to DQ52 and JH. The study of the IgH gene organization in 43 T lineage ALL showed nine cases with the rearrangement at the IgJH region, one of which involved the D region 5' to DQ52. When analyzed with another restriction enzyme (BglII), three of the remaining eight showed rearrangement between DQ52 and JH. In the remaining five samples rearrangement of the IgJH region was not shown, but the restriction fragment length polymorphism (RFLP) between MspI sites in 5'DQ52 loci was observed. Thus the RFLP in 5'DQ52 locus was identified and was distinguished from the recombination between DQ52 and JH in non-B lineage leukemias.
Blotting, Southern↗
Molecular diversity of precursor B acute lymphoblastic leukemias identified by the immunoglobulin heavy chain gene organization.
Acute leukemias with morphological, cytochemical, and immunological characteristics correlating to precursor B lymphocyte and with germ line configuration of immunoglobulin heavy (IgH) chain loci were studied for the organization of antigen receptor genes including C mu, Ig light (IgL) chain, T cell receptor (TCR) beta and gamma. Three of the five lymphoblast samples retained the germ line configuration of both Ig JH and C mu region. The other two samples showed deletion of the entire JH region resulting in the rearrangement of the C mu region. None of these five cases had a Ig L chain gene rearrangement. The three cases with germ line IgJH and C mu loci were revealed to belong to stage I (HLA DR+), stage II (HLADR+, CD19+), and stage III (HLADR+, CD19+, CD10+) B precursor ALLs, respectively. The two cases with deletion of IgJH region also belonged to stage II and III B precursor ALL. Thus immunologically classified stage II and III B precursor ALLs include those with germ line IgH region, representing ALLs at a very early stage of B cell development. A subgroup of B precursor ALL with deleted IgJH region, which is abortive at the molecular genetic level, was also identified. Karyotype abnormalities involving chromosomal region 11q23 in the leukemias with germ line IgH region are also discussed.
B-Lymphocytes↗
Human yolk-sac tumor antigen 2G10: biochemical characterization and significance as a serum antigen.
The biochemical characterization of human yolk-sac tumor (YST) antigen 2G10, detected by monoclonal antibody (MAb) M912-2G10, was studied. Previous results indicated that glycolipids having a non-reducing terminal N-acetyllactosamine structure were the epitope of 2G10 on human erythrocytes. In this study, the glycoprotein nature of 2G10 on the infantile embryonal carcinoma line, MTE, was investigated. 2G10 activity, measured by a new enzyme-linked immunosorbent assay (2G10-ELISA), was recovered in residual fractions of MTE from which glycolipids were removed. Chromatographically, 3H-galactose-labelled 2G10 on MTE had a molecular weight (mw) of about 580 kDa, which decreased after pronase or alkaline-borohydride treatment. Our results indicate the glycoprotein nature of 2G10 on MTE. Furthermore, 2G10, both on erythrocytes and on MTE, was sensitive to galactosidase but not to neuraminidase and fucosidase, suggesting that terminal galactose is involved in the antigenic structure. It was also found by 2G10-ELISA that 2G10 sheds from tumor cells. Shedding occurs in nude mice transplanted with MTE as well as in patients with germ-cell tumors (GCTs). The serum level of 2G10 in non-tumor patients was low, but high levels were detected in patients with YSTs and with GCTs having YST components. Immunohistochemically, the presence of 2G10-positive YST components was shown in patients who had high serum levels of 2G10. Sera from other urogenital and childhood solid tumors did not have elevated 2G10. The mw of shed 2G10 was lower than that of 2G10 on the cell surfaces. Our results clearly indicate the usefulness of serum 2G10 as a tumor marker for GCTs having YST components.
Animals↗
Human sarcomatous Wilms' tumor lines: evidence for epithelial differentiation in clear cell sarcoma of the kidney.
The biological nature of human sarcomatous Wilms' tumor (SWT) was studied by analyzing newly established SWT lines, both heterotransplantable in nude mice and cultured in vitro. Five lines in nude mice include two from clear cell sarcoma of the kidney (CCSK), two from malignant rhabdoid tumor of the kidney (MRTK), and one from unclassified sarcoma. Five in vitro lines include three from CCSK, one from MRTK, and one from unclassified sarcoma. All of these in vitro cell lines produced tumors when innoculated in nude mice. Most of lines, especially of MRTK and unclassified sarcoma, well maintained their original morphological characteristics. However, CCSK lines, both heterotransplantable and in vitro, often showed unique morphological changes such as the increase of cells with eosinophilic cytoplasms and the production of mucin. Ultrastructurally, clusters of intermediate filaments, twisted sheaves of filaments resembling tonofilaments, intermediate junctions, and intracellular canaliculi were found in these cells. These findings suggested that CCSK had the latent epithelial nature which became obvious in the cell lines. This was confirmed by immunohistochemical and immunoblotting analyses with anticytokeratin antibodies. The result proved that CCSK expressed cytokeratin 8 (Mr 52,000) and 19 (Mr 40,000) as well as nephroblastic Wilms' tumor and strongly indicated that there was a close relationship between CCSK and nephroblastic Wilms' tumor.
Animals↗
[Criteria of curability in the resection therapy for hepatocellular carcinoma].
The present study was aimed at determining a criteria for curability of hepatic resection in the treatment of hepatocellular carcinomas. The 239 patients hepatectomized from 1973 through 1987 were included for analysis. The patients with the tumor thrombi(V) or intrahepatic metastasis(IM) scattered over the unilateral lobe(IM2) showed very poor prognosis in spite of macroscopically complete resections. Consequently, these conditions were categorized into non-curative group(NC). The 5-year survival rate of the tumors less than 2 cm was 42%, which was much better than that of 5 cm or more group but no better than that of 2 to 5 cm group. When the prognosis was compared by an extent of resection among the patients with the tumors of less than 5 cm in size and V(-), the patients with lobectomy showed a 5-year survival rate of 84%, much better than 45% of those with segmentectomy or less range. The surgical margin (SM) negative patients showed a better prognosis than the SM positive patients with a slight difference. The tumor backgrounds of the 39 patients who survived three years with disease free condition were as follows: V(-) in all, no intrahepatic metastasis(IM0) in 79%, no IM2, massive resection for all IM1 in whom IM was confined to the area close to the main tumors, a tumor size of 5 cm or less in 82%, SM(-) in 62%. From the findings described above, we defined a complete resection for V(-) and IM0-1 as a curative condition, of which absolute curative resections(AC) corresponded to the patients with the tumors of 5 cm or less and SM(-), and relative curative ones(RC) to the remainders.(ABSTRACT TRUNCATED AT 250 WORDS)
Carcinoma, Hepatocellular↗
Prognosis of cervical cancers with reference to steroid receptors.
The relationship among the prognosis of a patient with cancer of the cervix and endocrine background [production of estrogen receptor (ER), progestogen receptor (PR), and androgen receptor (AR)], clinical stage, histological type, lymph node metastasis, age, and treatment was studied. ERs were detected in almost all cases, regardless of the histological type of cancer. The detection rate and level of PR were in the decreasing order of large-cell non-keratinizing (LNK) carcinoma, keratinizing (K) carcinoma, and small-cell non-keratinizing (SNK) carcinoma of the cervix. Thus, the presence and level of PR in squamous cell carcinoma of the cervix were considered to be an indicator of the degree of differentiation. PR was not detected in cases of adenocarcinoma of the cervix. This may explain the poor responsiveness to progestogen treatment in adenocarcinoma of the cervix. There was no relationship between the patient's prognosis and the presence of PR or AR, but the prognosis of patients with lesions rich in ER (greater than or equal to 5 fmol/micrograms DNA) tended to be better than that of patients with lesions poor in ER (less than 5 fmol/micrograms DNA). The prognosis of patients before menopause tended to be better than that postmenopause. These findings indicate a relationship between cancer of the cervix and endocrine background.
Adenocarcinoma↗
Giant lymph node hyperplasia (Castleman's disease) with spontaneous production of high levels of B-cell differentiation factor activity.
A 13-year-old girl presented with general fatigue, back pain, anemia, hyperimmunoglobulinemia, and a mediastinal mass on chest radiograph. A mass was surgically removed, and its histologic examination determined the diagnosis of giant lymph node hyperplasia (Castleman's disease). With removal of the hyperplastic lymph node, the clinical symptoms soon disappeared and the abnormal laboratory findings were markedly improved within 1 month: serum IgG levels decreased from 4350 mg/dl to 1829 mg/dl. Immunostaining on the lymph node sections revealed polyclonal B-lymphocyte and T-lymphocyte populations. The patient's lymph node cells were cultured without any mitogenic stimulation, and the culture supernatants were assayed for their B-cell differentiation factor (BCDF) activity to induce IgG production by our Epstein-Barr virus-transformed cell line. The patient's lymph node cells produced high levels of BCDF activity: the supernatants could increase the IgG production from 140 ng/ml to 410 ng/ml when the values became from 140 ng/ml to 142 ng/ml or 148 ng/ml with those of the control lymph node cells. These results suggest that the hyperimmunoglobulinemia and its prompt improvement with removal of the hyperplastic lymph node may have been related to the spontaneous production of high levels of BCDF activity by the lymph node cells in the patient.
Adolescent↗
Diversity of molecular phenotypes in acute leukemias.
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Acute Disease↗
A monoclonal antibody (MSN-1) against a newly established uterine endometrial cancer cell line (SNG-II) and its application to immunohistochemistry and flow cytometry.
To determine a phenotypic difference between normal endometrium and endometrial adenocarcinoma, a new monoclonal antibody (MSN-1) was produced by immunizing a new endometrial cancer cell line (SNG-II), which was established in 1981 from a 43-year-old Japanese woman with stage II uterine endometrial cancer. MSN-1 recognized the Lewis-b carbohydrate moiety on the cell surface glycolipid and seldom reacted immunohistochemically with normal endometrium but with about 90% of endometrial cancer cases. By application of MSN-1 to flow cytometry, the possibility of differentiating endometrial normal cells from cancer cells was demonstrated.
Adenocarcinoma↗
A monoclonal antibody specifically reactive with Ewing's sarcoma.
We have developed a mouse monoclonal antibody 5C11 (IgG2a) against cell surface antigen of Ewing's sarcoma (ES). 5C11 specifically reacted with ESs but not with other small round cell tumours in childhood, i.e. neuroblastomas, primitive neuroectodermal tumours (PNETs), rhabdomyosarcomas and malignant lymphomas. 5C11 did not react with any other tumours in children except for hepatoblastomas. No reactivity has been identified in normal tissues with the exception of fetal hepatocytes. Immunoelectron microscopically, 5C11 reactive antigen was located on cell membrane of ES cells. Biochemically, 5C11 immunoprecipitated a cell surface protein having molecular weight of 81,000 Da. 5C11 is the first antibody which can clearly distinguish ES from neurogenic tumours, especially from PNETs which were recently reported to have common features to ESs regarding chromosal abnormality and proto-oncogene expression but show evident differentiation into neurogenic direction. The results strongly indicate the usefulness of 5C11 not only for diagnostic purpose when no specific marker is available but also for studying the histogenesis of ES. In addition, no reactivity in normal tissue implies its potential application as a therapeutic reagent when the management of ES patients is still a great problem in clinical field.
Adolescent↗
Inhibition of tumor angiogenesis activity in C3H mouse mammary tumor by medroxyprogesterone acetate.
The growth of the C3H mouse mammary tumor (MMT) is considered to be hormone independent. Medroxyprogesterone acetate (MPA) had no effect on the growth of transplanted autochthonous MMT or the colony-formation of MMT cells. The tumor angiogenesis factor (TAF) activity of tumor-extract prepared from C3H mouse with transplanted autochthonous MMT and injected with 0.67 mg of MPA (in vivo MPA group) and that prepared from the colony of MMT cells treated with 10(-6) M MPA (in vitro MPA group) was lower (100.0% and 9.8%) than those of the in vivo and in vitro cortisol groups (325.5% and 44.3%), and the in vivo and in vitro groups without treatment (393.5% and 46.8%), respectively. The fibroblast growth factor (FGF) activity of the in vivo and in vitro MPA groups was lower (23.7% and 2.7%) than those of the in vivo and in vitro cortisol groups (54.7% and 11.3%), and the in vivo and in vitro groups without treatment (49.6% and 11.3%), respectively. Therefore, MPA may reduce neovascularization induced by TAF and FGF, although it had no effect on the growth of this MMT, and it had a glucocorticoid action similar to that of cortisol.
Angiogenesis Inducing Agents↗
Inhibition of tumor angiogenesis activity by medroxyprogesterone acetate in gynecologic malignant tumors.
More than 30% of the colony formation of dispersed tumor cells was inhibited by medroxyprogesterone acetate (MPA) in 2 out of 6 cases of endometrial cancer, in 1 out of 6 cases of cervical cancer, and in 3 out of 12 cases of ovarian cancer. The colony formation inhibited by MPA was not related to clinical stage or histological type. There was no significant difference in the tumor angiogenesis factor (TAF) activity of any case of endometrial, cervical and ovarian cancer between the cortisol-treated group and the controls. TAF activity was inhibited by MPA in 4 out of 6 cases of endometrial cancer, in 5 out of 6 cases of cervical cancer, and in 9 out of 12 cases of ovarian cancer. There was no significant difference in the fibroblast growth factor (FGF) activity of any case of endometrial, cervical and ovarian cancer between the cortisol-treated group and the controls. FGF activity was inhibited by MPA in 3 out of 6 cases of endometrial cancer, in 5 out of 6 cases of cervical cancer, and in 10 out of 12 cases of ovarian cancer. The cases in which the colony formation was inhibited by MPA were not related to the cases in which TAF or FGF activity was inhibited by MPA. Therefore, MPA may reduce neovascularization induced by TAF and FGF, and can depress secondary spreading of some endometrial, cervical and ovarian cancer via the mechanism of terminal process of secondary spreading, regardless of the presence of glucocorticoid actions similar to that of cortisol, and the reduction of cell proliferation.
Adenocarcinoma↗
Effect of medroxyprogesterone acetate on secondary spreading of endometrial cancer.
We examined the effect of medroxyprogesterone acetate (MPA) on secondary spreading of endometrial cancer. There was no significant difference in the adhering capacity of dispersed Ishikawa cells (derived from well-differentiated endometrial cancer) to a cell basement membrane matrix, fibronectin or laminin between cells treated with MPA, with cortisol, and without treatment. The adhering capacity of cells treated with cortisol to collagen type IV was higher than that without treatment. However, the adhering capacity was little affected by treatment with MPA. These results indicate that although cortisol may induce the initial process of metastasis by inducing the attachment of tumor cells to the basement membrane of vascular endothelium, MPA has no influence on the attachment, although it has a glucocorticoid action similar to that of cortisol. There was no significant difference in tumor angiogenesis factor (TAF) or fibroblast growth factor (FGF) activity of the tumor extract from Ishikawa cell colonies between cortisol-treated and control group. TAF or FGF activity of the MPA-treated group was lower than that of the control group. MPA may reduce the neovascularization in the terminal process of metastasis via the reduction of TAF and FGF produced by tumor cells, in spite of its glucocorticoid action.
Angiogenesis Inducing Agents↗
Mechanism of antitumoral activity of medroxyprogesterone acetate for endometrial cancer.
The colony-formation of Ishikawa cells, which originate from well differentiated endometrial cancer, and produce progestogen receptors (PR), was inhibited by high concentrations of medroxyprogesterone acetate (MPA). However, the colony-formation was not inhibited by norethindrone (ENT), as a luteohormone or 17 beta-hydroxy-11 beta-(4-dimethylaminophenyl-1)-17 alpha(prop-1-ynyl)-estra-4, 9-dien-3-one (RU-486), as an antiprogestogen. Colony-formation in cells treated with MPA alone was not significantly different from that in those treated with MPA combined with either ENT or RU-486. ENT and RU-486 have high affinity with PR as does MPA. If the suppressive effect by MPA on colony-formation is mediated via PR, then this suppression should be competitively inhibited by ENT or RU-486. Our findings indicate that the effect of MPA is not mediated via PR.
Antineoplastic Agents↗
[Nuclear DNA analysis of hepatocellular carcinoma].
Retrospective DNA ploidy studies of paraffin-embedded blocks were performed by flow cytometry on 212 surgically resected hepatocellular carcinoma. One hundred and sixty-four of 212 specimens yielded evaluable DNA histograms. Eighty-three cases showed a DNA diploid pattern and 81 a DNA non-diploid pattern. The incidence of non-diploid pattern increased with the tumor size. (2cm; 15.4%, 2-5; 42.3%, 5-10; 70.8% greater than 10; 73.3%). The DNA pattern correlated with the backgrounds, the degree of vascular invasion, intrahepatic metastasis and serum AFP levels. Survival of patients with non-diploid pattern was significantly less than those with diploid patients in any different stage. Of thirty who survived three years with disease free condition, 20 patients showed diploid patterns. Though remaining 10 patients were non-diploid patterns, 9 were high DNA index more than 1.5. It is concluded that flow cytometric DNA ploidy study had prognostic value for patients with surgically resected hepatocellular carcinoma.
Carcinoma, Hepatocellular↗
Human sarcomatous Wilms' tumor. Characterization with 5H10, a newly established monoclonal antibody.
Immunophenotypic features of human sarcomatous Wilms' tumor (SWT) were studied using a newly established mouse monoclonal antibody (5H10, IgG1). 5H10 was produced against CR-SW2, one of several transplanted SWT lines in nude mice, and defines a 200-kDa cell surface protein. The antibody was found to react equally with all subtypes of SWT; clear cell sarcoma of the kidney, malignant rhabdoid tumor of the kidney, and unclassified sarcoma. Furthermore, it reacted equivalently with surgically resected tumors, transplanted tumors in nude mice, and cell lines in vitro. On the other hand, 5H10 was entirely negative for any of the components of nephroblastic Wilms' tumor (NBW). Considering these results, 5H10 appears to recognize the antigen expressed preferentially on SWT, and therefore the subtypes of SWT may be closely related to one another immunophenotypically. In normal human tissues, however, 5H10 only reacted with fetal kidneys, its reactivity being restricted to the lower limbs of S-bodies in both the metanephros and mesonephros. No reactivity was identified in any other tissues including adult kidney. These results indicate that 5H10 detects an oncofetal antigen expressed preferentially in both SWTs and fetal kidney and that the histogenesis of SWT should be considered in connection with nephrogenesis.
Animals↗
[Differentiation of human germ cell tumor cells].
Human germ cell tumors are an excellent model for investigating the mechanism of human early embryogenesis as well as cellular differentiation. Three human EC cell lines, NCR-G 2, 3 and 4 were newly established from testicular mixed embryonal carcinomas in vitro, G3 and G4 cells were capable of somatic cell differentiation. The G3 cells demonstrated the most noticeable antigenetical changes with the administration of retinoic acid. SSEA-1 appeared on some cells whereas expression of HLA-A, B, C as well as 2H2, 2D7 and 5D4 antigens tended to be reduced in G3 cell line. 2H2, 2D7 and 5D4 antigens which we recently produced were immature human EC specific cell surface antigens, defined by mouse monoclonal antibodies, obtained immunization with G2 cells. The production of hCG, high molecular weight cytokeratin and intercellular matrices such as type IV collagen and laminin were inducible in G3 cells. Thus, G3 cells are thought to be one of the most pluripotent human EC cells. These findings clearly indicate that the EC cell lines we established provide an opportunity to study differentiation mechanism of human germ cell tumors and also human somatic cells.
Animals↗