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Biomedical subjects

I Kubonishi

Publications and source records attributed to I Kubonishi.

At least 37 records · Page 2Linked to original sources

High serum levels of CA125 and interleukin-6 in a patient with Ki-1 lymphoma.

We report a 53-year-old-man with an aggressive Ki-1 lymphoma who had high serum CA125, a marker protein of the epithelial ovarian cancer, and interleukin-6 (IL-6) concentrations. Both CA125 and IL-6 levels decreased after chemotherapy and elevated with disease progression. The patient's lymphoma cells obtained before chemotherapy grew continuously in vitro, were IL-6 dependent and were found to secrete CA125 in culture medium. These results indicate that CA125 can be secreted by Ki-1 lymphoma cells and IL-6 may promote the growth of Ki-1 lymphoma cells.

Aged↗

PTHrP-mediated hypercalcaemia in a case of CML blast crisis.

We report a 52-year-old man with chronic myelogenous leukaemia (CML) who developed hypercalcaemia in blast crisis. There was a high serum level of parathyroid hormone-related protein (PTHrP). The leukaemia cells secreted PTHrP into culture medium when cultured in vitro and were shown to express PTHrP mRNA by reverse transcription-polymerase chain reaction. Transplantation of the leukaemia cells into nude mice resulted in the production of Ph1 chromosome-positive tumours which caused increased levels of calcium and PTHrP in the blood. These results indicated that the hypercalcaemic event in the patient was induced by PTHrP of CML cell origin.

Blast Crisis↗

Establishment of a new myeloid cell line with i(17q) as the sole chromosomal anomaly from the bone marrow of a patient with myelodysplastic syndrome.

A new myeloid cell line, MTO-94, was established from the bone marrow of a patient with myelodysplastic syndrome (MDS). MTO-94 cells matured in culture medium without the addition of growth factors, and yielded neutrophils with pseudo-Pelger Huët anomaly or hypersegmentation until 6 months. Ten months after the start of cell cultivation, MTO-94 consisted of myeloblasts. Surface phenotypes were as follows: CD7 90.3%, CD13 99.6%, CD33 75.6%, HLA-DR 96.3% and CD34 0.9%. The karyotype was 46, XY i(17q). The proliferation of MTO-94 cells was enhanced by rhIL-3, G-CSF, rhGM-CSF and rhSCF but not by rhIL-6 and erythropoietin. MTO-94 cells with i(17q) might be useful in the study of biological aspects of not only MDS, but also hematological malignancies with i(17q) as the sole chromosomal anomaly.

Aged↗

Biphenotypic leukemia with a new translocation, t(2;6)(q31;q23).

A t(2;6)(q31;q23) was found in a patient with acute biphenotypic leukemia. This cytogenetic change has not been reported previously in acute lymphocytic leukemia (ALL) or biphenotypic leukemia, although deletion of 6q has been frequently found in ALL.

Cell Lineage↗

Establishment of a clonal cell line producing granulocyte colony-stimulating factor and parathyroid hormone-related protein from a lung cancer patient with leukocytosis and hypercalcemia.

Squamous cell lung carcinoma cells obtained from a patient who presented with leukocytosis and hypercalcemia were transplanted into nude mice and a serially transplantable cell line, OKa-N-1, was established. The nude mice transplanted with OKa-N-1 cells displayed leukocytosis and hypercalcemia. Serum levels of granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP) were both elevated in these mice. In vitro cultivation of this tumor cell line gave rise to a clonal cell line, OKa-C-1. Nude mice transplanted with the OKa-C-1 cell line also showed leukocytosis and hypercalcemia with high serum G-CSF and PTHrP levels. The culture supernatant of OKa-C-1 contained high levels of G-CSF and PTHrP. Immunohistochemical studies showed the expression of PTHrP in OKa-C-1 cells. Reverse transcription polymerase chain reaction revealed the presence of G-CSF and PTHrP mRNA in this cell line. Dexamethasone treatment inhibited the transcription of G-CSF and PTHrP genes. This new human squamous carcinoma cell line, OKa-C-1, would be useful for studying the mechanism of simultaneous production of G-CSF and PTHrP and their control in cancer patients with leukocytosis and hypercalcemia.

Animals↗

Lung squamous cell carcinoma producing both parathyroid hormone-related peptide and granulocyte colony stimulating factor.

An autopsy case of a 61 year old male with primary squamous cell carcinoma of the lung with associated marked leukocytosis and hypercalcemia is reported. High levels of serum parathyroid hormone-related peptide (PTHrP) and granulocyte colony stimulating factor (GCSF) were detected. The tumor cells distinctly showed positive cytoplasmic immunoreactions with anti-PTHrP and anti-GCSF antibodies. Marked granulocytosis and thin bony trabeculae lacking osteoblasts were observed in the vertebral bone. Calcium deposits were found in the proximal tubules of the kidneys. Infarcts were seen as a result of fibrin thrombosis of the splenic artery. The tumor was successfully transplanted into nude mice in which the high levels of serum PTHrP and GCSF were reproduced. These results indicate that the tumor simultaneously produced both PTHrP and GCSF causing the paraneoplastic syndromes of hypercalcemia and leukocytosis.

Animals↗

Differential tumorigenicity between Epstein-Barr virus genome-positive and genome-negative cell lines with t(11;14)(q13;q32) derived from mantle cell lymphoma.

Epstein-Barr virus (EBV) genome has been detected in several human lymphoproliferative diseases, but the oncogenic function of EBV is not fully understood. We previously established EBV-positive (SP-50B) and EBV-negative (SP-53) cell lines with the t(11;14)(q13;q32) chromosome abnormality from a single patient with mantle cell lymphoma. Monoclonal EBV DNA in a circular episomal form was demonstrated in the SP-50B cells by Southern blot hybridization with the EBV-terminal fragment probe. SP-50B cells were positive for not only EBV-encoded nuclear antigen-1 (EBNA1) but also latent membrane protein-1 and EBNA2. None of the EBV-encoded proteins was expressed in SP-53 cells. The isogenic EBV-infected and EBV-free cell lines of neoplastic clones made it possible to examine a tumorigenic role of EBV. Only EBV-positive SP-50B cells possessed malignant phenotypes, such as growth ability in low serum, colony formation in soft agarose, and tumorigenicity in nude mice. On the other hand, a lymphoblastoid B-cell line established by infecting the patient's normal B lymphocytes in vitro with exogenous EBV had no tumorigenicity. These results suggested that EBV infection, if it occurred in neoplastic lymphoma cells, could play a role in acquisition of malignant phenotypes.

Animals↗

A unique chromosome translocation, t(11;12;18)(q21;q13;q21) [correction of t(11;12;18)(q13;q13;q12)], in primary lung lymphoma.

A 54-year old man with a primary lung lymphoma of mucosa-associated lymphoid tissue (MALT) origin whose tumor cells had a t(11;12;18)(q13;q13;q12) chromosome abnormality is described. The morphologic, immunologic, and molecular biologic investigations showed that the patient's lung tumor consisted of small lymphoid cells that expressed monoclonal IgM, kappa-type immunoglobulin, and immunoglobulin gene (JH and C kappa) rearrangements. Cytogenetic study revealed that the tumor cells contained a unique chromosome translocation, t(11;12;18)(q13;q13;q12), that has not been reported previously in lymphoma.

Chromosome Aberrations↗

Direct transplantation of chronic myelogenous leukemia cells into nude mice and establishment of a leukemic stem cell (Ph1+, CD34+) line dependent on mouse bone marrow stromal cells in vitro.

Peripheral blood cells from a female patient with Ph1-positive chronic myelogenous leukemia (CML) in blast crisis were serially transplanted in BALB/c nude mice for 16 passages. This in vivo cell line, designated CML-N-1, had Ph1 chromosome abnormality and BCR gene rearrangement. The cells expressed CD11b, CD13, CD33, CD34, CD38, and HLA-DR antigens until the 11th passage and subcutaneous tumors produced by these passages were composed of admixtures of immature and maturing cells that differentiated to basophils when cultured in vitro. From the 12th passage on, the tumors became composed mainly of immature cells expressing CD13, CD34, and HLA-DR, and no longer differentiated to basophils even upon in vitro culture. In contrast to the vigorous proliferation in vivo, CML-N-1 cells from any passage failed to proliferate in vitro under standard liquid culture conditions with or without growth factors, such as granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, monocyte colony-stimulating factor, interleukin 3, interleukin 6 and stem cell factor. However, a continuously growing cell line, designated CML-C-1, was established by culturing CML-N-1 cells on feeder layers of mouse bone marrow stromal cells. This mouse bone marrow stromal cell-dependent cell line showed immature cell morphology and expressed early myeloid phenotype positive for CD13, CD34, and HLA-DR. These results indicate that mouse bone marrow stromal cells provide a certain growth factor(s) active on human leukemia cells.

Adult↗

12-0-Tetradecanoylphorbol 13-acetate (TPA)-induced enzymatic change of human non-T, non-B lymphoid leukemia cell lines.

Culture of two lymphoid leukemia cell lines with 5 x 10(-9) to 10(-7) M 12-0-tetradecanoyl-phorbol 13-acetate (TPA) induced the significant increase in sialyltransferase, acid phosphatase and butyrate esterase activities, the decrease in poly(A) polymerase and terminal deoxynucleotidyl transferase (TdT) activities. B4-, J5-, TdT- or PNA-positive cells were decreased in TPA-treated cells, while B1-positive cells were increased. These results suggest enzymatic changes as an aspect of TPA-induced differentiation in lymphoid leukemia cell lines. These enzymatic activities may be useful markers for the differentiation of lymphoid leukemia cells.

Cell Differentiation↗

Expression of the candidate Wilm's tumor gene, WT1, in human leukemia cells.

Wilms' tumor (WT) is a pediatric malignancy that occurs in embryonic kidney. Recently, a putative Wilms' tumor gene (WT1), located on chromosome 11p13, was isolated and characterized. We found constitutive expression of WT1 mRNA in eight out of 22 hematopoietic cell lines and seven out of 26 clinical samples which were derived from patients with various types of hematologic malignancies. WT1 mRNA was detected in four out of six myeloid cell lines, four out of 10 cases of acute myelocytic leukemia, three out of 15 lymphoid cell lines, one out of nine cases of lymphoid malignancies, and one out of six cases of chronic myelocytic leukemia in accelerated phase and blast crisis. One unclassified hematopoietic cell line and a case of myelodysplastic syndrome also expressed WT1 mRNA. No mutations were detectable in the cell lines by Southern blot analysis and a polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis in the four zinc finger domains of the WT1 gene. These results suggest that WT1 gene is expressed in several types of immature lymphoid or myeloid leukemia cells possibly without alterations of the WT1 gene.

Adult↗

[A case of Jordans' anomaly].

A 71 year-old female with jordans' anomaly was described. Fat-containing vacuoles were observed in neutrophils, eosinophils, basophils, monocytes and lymphocytes of the peripheral blood, but not in erythrocytes and platelets. In the bone marrow they were also observed in myeloid cells including myeloblasts, erythroblasts and megakaryocytes. In the granulocyte series, numbers of vacuole-containing cells and numbers of vacuoles increased as leukocytes matured. Histochemically, vacuoles were thought to contain neutral fat based on staining with Sudan III. However serum lipids showed no abnormalities. Both the reduction rate of NBT and the phagocytic activities for Candida albicans were normal.

Aged↗

The establishment of an interleukin-6-dependent myeloma cell line (FLAM-76) carrying t(11;14)(q13;q32) chromosome abnormality from an aggressive nonsecretory plasma cell leukemia.

A new myeloma cell line designated FLAM-76 was established from a patient with an aggressive nonsecretory plasma cell leukemia. The cell line exhibited morphologic features of flaming cells and contained an abundant eosinophilic cytoplasm with many dilated cisternae of rough endoplasmic reticulum. FLAM-76 cells were positive for cytoplasmic kappa (kapp)-type immunoglobulin but did not secrete it into the culture medium. The cells proliferated in the presence of exogenous interleukin-6 (IL-6) and more than 800 pg/ml of IL-6 was necessary for their continuous growth. The cells did not grow without IL-6, and they did not produce IL-6. Thus, the growth of FLAM-76 appeared to be regulated by the paracrine mechanism of IL-6. Alpha-interferon (alpha-IFN) inhibited the IL-6-dependent growth of FLAM-76 in doses greater than 1000 U/ml. FLAM-76 cells expressed CD38 (OKT10) and cell adhesion-associated antigens such as CD44 and CD54 (ICAM-1). Chromosome analysis revealed FLAM-76 to have a hypodiploid chromosome constitution with t(11;14)(q13;q32) abnormality, which frequently is seen in neoplasms of B-cell origin. Immunoglobulin (JH and Ck) gene rearrangement (but no BCL-1 gene rearrangement) was found in this cell line.

Aged↗

Establishment of a new Hodgkin's cell line (HD-70) of B-cell origin.

A new Hodgkin's cell line, designated HD-70, was established from the peripheral blood of a 69-year-old man with Hodgkin's disease of nodular sclerosing type. The cell line grows in a single cell suspension and has a doubling time of 28 hours. The cells have a round or irregular nucleus or multiple nuclei in relatively abundant cytoplasm that is positive for acid phosphatase, alpha-naphthyl butyrate esterase, and periodic acid-Schiff stains. HD-70 cells are positive for CD30 (Ki-1/Ber-H2), CD15 (Leu-M1), and CD71 (OKT9) antigens and contain cytoplasmic immunoglobulin (Ig) (A, kappa). Southern blot analysis showed that the cells have Ig heavy and kappa light chain gene rearrangement and lack T-cell receptor gene rearrangement. Chromosome analysis disclosed that the cells have a human karyotype with complicated abnormalities, including a 14q+. Heterotransplantation of the HD-70 cell line into newborn hamsters treated with antilymphocyte serum produced massive tumors with remarkable fibrosis and collagen band formation. These tumors displayed histologic features similar to those of the nodular sclerosing type tumor of the patient. Such fibrosis production and collagen band formation in heterotransplanted tumors suggest that a certain cytokine that induces fibrosis might be produced by HD-70 cells. This cell line may be useful for understanding the biology and pathogenesis of Hodgkin's disease.

Aged↗