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[Quantitative and functional characteristics of T-lymphocytes and monocytes in lymphosarcoma patients at various stages of the neoplastic process].

IKO monoclonal antibodies were used to study peripheral blood mononuclear types in 92 patients with various histomorphological types of diffuse lymphosarcoma at various stages of tumorous process. Absolute counts of CD7 and CD5 cells (T cells) were found reducing as was CD4 cell (T helpers) level as the disease progressed. CD8 cell (T suppressors) count reliably increased only in the phase of lymphoblastic lymphosarcoma leukemic degeneration. A group of patients with stage IV lymphoblastic lymphosarcoma was detected with drastically increased counts of mononuclears carrying mature T cell markers. Clinical course of the disease in these patients was characterized by the highest malignancy degree and metastatic involvement of the central nervous system. Examination of peripheral blood monocyte/macrophage ratio in the same patient population (n = 26) revealed reduced Fc receptor expression, EA phagocytosis, and increased levels of circulating immune complexes, these shifts augmenting with the tumor progress. The results may be valuable for prediction of lymphosarcoma course and for immunocorrection.

Adult↗

Preferential replication of murine xenotropic type-C virus in human lymphosarcoma-derived cell lines.

Murine xenotropic virus, designated 698/X, was recovered by implantation of human lymphosarcoma-derived cells U-698M into nude mice of Giovanella's colony. The budded and extracellular particles revealed typical type-C morphology, the latter possessing reverse transcriptase (RT) activity and exhibiting a buoyant density 1.17 g/ml in sucrose gradient. In competitive radioimmunoassay using iodinated p30 of Rauscher MuLV, the 698X viral concentrate and cell extracts of both implanted lymphosarcoma cells (U-698M-N-1 and U-715M-N-1) were as effective as Gross MuLV, thus indicating the murine origin of the virus. The propagation of the 698/X virus in five human, four mouse (permissive for N- and B-tropic MuLV), two rat and one bovine cell lines was followed by RT, XC syncytia assays and EM investigations. The replication of the 698/X virus seems to be restricted mainly to both human lymphosarcoma-derived cell lines U-698M and U-715M. The new recovery of the virus from the nude mouse by implantation of U-175M cells has asserted its high tropism to human lymphosarcoma cells and its murine origin. The comparative response of mouse, rabbit and rat cells exposed to both NZB and 698/X xenotropic murine viruses exhibited host range differences between these viruses. The rabbit SIRC and rat embryonic cells REC were fully permissive for the murine xenotropic NZB virus, while low viral production was detected by RT assay only in 698/X virus infected SIRC cells.

Animals↗

Leukocyte migration inhibition responses in canine lymphosarcoma.

The leukocyte migration inhibition (LMI) responses of 16 cases of canine lymphosarcoma were assessed at several stages of a combined chemotherapy immunotherapy regime. Pooled allogeneic lymphosarcoma cells used in treatment together with other allogeneic lymphosarcoma cells and autochthonous tumour cells were employed as antigens. Positive inhibitions were detected at all stages of treatment when medium controls were used but were not detected in five normal dogs with the same control. There was no association between relapse and remission and LMI response. When a normal lymph-node cell control was used only four dogs produced positive responses, all of which occurred after allogeneic cell administration. These positive responses could not be completely accounted for by sensitization to histocompatibility antigens but as they occurred both in remission and in relapse, including very advanced cases necessitating euthanasia, they were of no value in determining prognoses.

Animals↗

Reduced monocyte phagocytosis in patients with advanced Hodgkin's disease and lymphosarcoma.

The monocytes of 7 patients with advanced Hdgkin's disease (stages III and IV) and of two patients with generalized lymphosarcoma exhibited a highly significant impairment of the phagocytosis of IgG-coated red cells, regardless of receiving therapy or not. In contrast three patients with M. Hodgkin, stage II B, and one with lymphosarcoma in complete remission showed a rather elevated monocyte phagocytic acitivity. The nitroblue tetrazolium reduction by monocytes in the mean was significantly enhanced in all patients investigated, compared with normal persons, although only in one patient a bacterial infection was apparent at the time of the test. The possible implication of the findings in the well known immunodeficiency present in M. Hodgkin and lymphosarcoma is discussed.

Centrifugation, Density Gradient↗

Effects of thiol compounds on methotrexate uptake by murine lymphocytes from thymus and thymic lymphosarcoma.

The characteristics of methotrexate (MTX) uptake and the effects of exogenous sulfhydryl compounds (i.e. reduced glutathione and cysteine) on MTX accumulation in thymocytes and thymic lymphosarcoma cells has been studied. Significant differences in the rate and the extent of MTX uptake between normal and neoplastic cells were demonstrated. MTX accumulation was found to be more efficient in thymic lymphosarcoma cells as compared with parental cells. In the cells examined, MTX uptake was not affected by membrane impermeable GSH. In contrast, short-term exposure to cysteine revealed heterogeneity in MTX uptake systems between normal and neoplastic thymocytes. Thus, cysteine was demonstrated to enhance the rate and extent of MTX accumulation exclusively in thymic lymphosarcoma cells. The results obtained indicate that in neoplastic thymocytes biochemical changes had developed in the membrane redox state around the MTX uptake system. These alterations are chemically distinguishable by their characteristic response to cysteine. The findings suggest that the plasma membrane changes could be exploited for preferential enhancement of MTX uptake by neoplastic thymocytes.

Animals↗

Activity and concentration of cathepsin B as prognostic criteria for the development of mouse LS lymphosarcoma and Lewis lung adenocarcinoma.

We measured activity and content of cathepsin B in tumor tissues, liver, and spleen in mice with Lewis adenocarcinoma and LS-lymphosarcoma. Cathepsin B activity in Lewis adenocarcinoma cells was lower than in LS-lymphosarcoma cells, which was probably related to differences in their metastatic properties. Antitumor therapy increased activity and content of cathepsin B in tumor tissues. Changes in the content and activity of cathepsin B in tumor tissues can serve as a prognostic criterion for tumor regression during therapy. Cathepsin B is probably involved in apoptosis of tumor cells during chemotherapy of lymphosarcoma-LS with cyclophosphamide.

Animals↗

Reverse transcriptase activity and particles of retroviral density in cultured canine lymphosarcoma supernatants.

Lymphoid tissue from 43 cases of canine lymphosarcoma and from 40 clinically normal dogs have been examined for markers of retrovirus infection. From 69-76% of culture supernatants from lymphosarcomas were shown to contain particles of retroviral density and to possess poly rC-oligo dG templated polymerase (reverse transcriptase) activity compared with 17-24% of culture supernatants from normal canine lymphoid cells. In 6 culture supernatants from cases of lymphosarcoma, high molecular weight 60-70S RNA was detected and shown to be found in association with this particulate reverse transcriptase activity. No such RNA was detected in 6 culture supernatants from normal canine lymphoid cells.

Animals↗

Silencing of metallothionein-I gene in mouse lymphosarcoma cells by methylation.

Metallothionein-I (MT-I) gene is silenced by methylation of CpG islands in mouse lymphosarcoma P1798 cells but not in the thymus, the cell type from which the tumor was derived. Bisulfite genomic sequencing revealed that all 21 CpG dinucleotides present within -216 bp to +1 bp with respect to transcription start site are methylated in the tumor cell line, but none is methylated in the thymus. The lymphosarcoma cells induced MT-I in response to heavy metals only after demethylation with 5-azacytidine (5-AsaC). The electrophoretic mobility shift assay using specific oligonucleotide probes showed that the key transcription factors regulating MT-I gene (e.g., MTF-1, Sp 1 and MLTF/USF) are active in P1798 cells. In vivo footprinting of the proximal promoter region showed that none of the metal regulatory elements (MREs) or MLTF/USF are occupied in response to heavy metals. Demethylation of the lymphosarcoma cells with 5-AzaC resulted in constitutive footprinting at MLTF/ARE, and zinc-inducible footprinting at MRE-c, MRE-d and MRE-e sites. Demethylation of just 10-20% of the CpG islands was sufficient to render the gene inducible by cadmium or zinc. The MT-I induction persisted in the cancer cells for several generations even after withdrawal of 5-AzaC from the culture medium.

Animals↗

Central nervous system metastasis of a cutaneous epitheliotropic lymphosarcoma in a dog.

This report describes an uncommon case of a cutaneous epitheliotropic T-cell lymphosarcoma with central nervous system (CNS) manifestations in a 9-year-old mixed breed German shepherd dog. The animal had a history of sudden blindness, pyrexia and multifocal areas of hyperaemia in the oral mucosa. A biopsy from the muco-cutaneous junction of the lips led to the diagnosis of an epitheliotropic lymphosarcoma and the animal was humanely destroyed. At necropsy, hyperaemia in the oral mucosa was no longer detectable. In the brain, a mass effacing the optic chiasm and invading the hypothalamic area was found; histological examination revealed lymphoid tumour cell infiltration. In the epithelium of the oral mucosa, intra-epithelial lymphoid tumour cells, sometimes arranged in small clusters (Pautrier's microabscesses), in combination with a mild inflammation in the superficial dermis were observed. Skin and brain tumour cells expressed CD3 antigen, indicating their T-cell origin. This is, to our knowledge, the first report of a cutaneous epitheliotropic lymphosarcoma with CNS metastasis in a dog.

Animals↗

[Results of the synchronization therapy with vincristine and cyclophosphamide in lymphogranulomatosis, reticulum cell sarcoma and lymphosarcoma. A phase II study (author's transl)].

The effectiveness of synchronization therapy was tested on 88 patients who had already undergone some form of treatment for lymphogranulomatosis (stage III B and IV), generalized reticulum cell sarcoma or lymphosarcoma. This therapeutical concept is based on a partial synchronic increase in tumor cells induced by noncytocidal doses of vincristine, followed by cytostatic or cytocidal treatment with cyclophosphamide during DNA synthesis of the partially synchronized tumor cells. The therapeutic plan is similar to a single-agent therapy. In lymphogranulomatosis, complete remission could be achieved in 14 out of 19 cases (stage III B) and in 9 out of 24 cases (stage IV). The mean remission period during an orally administered cytostatic maintenance therapy was 15 1/2 months. The highest rate of remission was found in the mixed cell type of granulomas (23 out of 24 patients). In the non-Hodgkin's lymphomas, complete remission was achieved in 13 out of 30 cases (lymphosarcoma) and in 19 out of 15 cases (reticulum cell sarcoma). The mean remission period for orally administered cytostatic maintenance therapy was 16 months for lymphosarcoma and 11 1/2 months for reticulum cell sarcoma. These therapeutic results are comparable to those achieved by very effective schemes of combination chemotherapy but the toxic side-effects of synchronization therapy are considerably lower.

Adolescent↗

Clinical hematological progression of hereditary lymphosarcoma in rabbits.

Considerable diversity exists in the clinical progression data for lymphosarcoma both between and within species. Thirty-four rabbits with hereditary lymphosarcoma were used to define the clinical progression of this condition under controlled genetic conditions. Changes in the erythropoietic cells of the rabbit hemogram in cases of hereditary lymphosarcoma (ha/ha) follow a fairly well defined clinical course of about one-and-one-half months duration. Data are presented showing that these changes are subsequent to schanges in the granulocytic cells of the leukocyte series both peripherally and in the bone marrow.

Animals↗

Comparison of filtration leukapheresis and centrifugation leukapheresis in treatment of lymphosarcoma cell leukemia.

A patient with lymphosarcoma cell leukemia resistant to chemotherapy was treated with filtration leukapheresis and centrifugation leukapheresis. Filtration leukapheresis removed only 10(11) leukemia cells per 8.5 liters of blood processed, while centrifugation leukapheresis removed approximately six times as many leukemia cells from the same amount of blood. Lymph nodes and spleen diminished in size and the WBC count decreased after nine treatments. However, the patient remained markedly thrombocytopenic, and his bone marrow remained infiltrated with lymphosarcoma cells on repeat biopsy. This study shows that centrifugation leukapheresis is superior to filtration leukapheresis in removing significant numbers of circulating lymphosarcoma cells, though the clinical benefit of leukapheresis in this situation remains to be determined.

Blood↗

Bilateral lymphosarcoma of the breast.

A case is presented of bilateral lymphosarcoma of the breast in a 77-year-old woman. The pre-admission surgical history recorded a mastectomy in July 1972, for lymphosarcoma of the right breast. She had been well until shortly before admission in March 1974 because of a tumor in her left breast. This proved to be lymphosarcoma. Treatment consisted of a left mastectomy. At that time there were no signs of axillary or systemic involvement. Later, evidence of systemic lymphosarcomatosis necessitated starting chemotherapy.

Aged↗

Thymic lymphosarcoma of T cell lineage in a koala (Phascolarctos cinereus).

OBJECTIVE: To diagnose and characterise thymic lymphosarcoma in a koala. DESIGN: A pathological case. ANIMAL: Seven-year-old female koala. PROCEDURE: The neoplastic process was investigated macroscopically, haematologically, histologically and immunohistologically. RESULTS: The koala had difficulty swallowing because of a medial swelling in the lower neck. Biopsy of this mass and blood examination revealed lymphosarcoma with a leukaemic manifestation; necropsy and histopathological examination showed the mass to be thymus. Palatine tonsils, cervical, axillary and mesenteric lymph nodes, spleen, liver, gut, bronchi, genitalia and bone marrow were infiltrated by neoplastic cells. Immunohistological staining of the thymic mass, cervical and mesenteric lymph nodes, bone marrow, spleen and gut revealed the neoplastic cells to be of T lymphocyte origin (positive for both anti-human CD3 and CD5). CONCLUSIONS: It is speculated that the neoplastic process originated in the thymus and was disseminated by bloodborne neoplastic cells. This first report of thymic lymphosarcoma in a marsupial confirms that antibodies raised originally to investigate human lymphoid neoplasia can cross-react with neoplastic lymphocytes in koalas.

Animal Diseases↗

Cutaneous lymphosarcoma in a stallion.

Multiple cutaneous lymphosarcomas were diagnosed in an 8-year-old Thoroughbred stallion presented for evaluation of lumps on its scrotum. Histological examination of skin biopsy samples showed a homogenous pattern of lymphoid tissue suggestive of a T-cell lymphosarcoma. Immuno-histochemical tests showed a positive reaction to Rabbit/Anti-Human T-Cell, CD3 antibodies confirming T-cell lymphosarcoma. The animal was not treated and was subsequently euthanased.

Animals↗

Lymphosarcoma in 10 New World Camelids.

We evaluated the medical information from 10 New World Camelids with lymphosarcoma. Additionally, tumor tissue from 5 animals was examined by electron microscopy for evidence of retroviral particles. Lymphosarcoma was the most common neoplasm of New World Camelids in our hospital. Both llamas and alpacas, from 4 months to 15 years of age, were affected. Emaciation (7 of 8) and palpable masses (9 of 10) were the most common physical examination abnormalities, and a left-shifted leukogram (7 of 7) and hypoalbuminemia (6 of 7) were the most characteristic clinicopathologic findings. Lymphosarcoma was diagnosed by lymph node aspirate (n = 2), biopsy (n = 2), peritoneal fluid analysis (n = 2), or necropsy (n = 4). The clinical course after recognition of the disease was usually short, with a median survival of 1 month (1 week to 3 months). Organs with neoplastic infiltrates commonly included lymph nodes (n = 8), liver (n = 8), kidneys (n = 6), and lungs (n = 5). No retroviral particles were detected ultrastructurally.

Animals↗

Primary lymphosarcoma of the lung with unusual features.

Two unusual cases of primary lymphocytic lymphosarcoma of the lung are presented. The first patient is a 5-year-old girl who showed a massive involvement of the entire right lung by tumour. She was treated by radiotherapy followed by cyclophosphamide and was alive and well one year later. The second patient was an adult man who presented clinically with a tumour of the chest wall. Necropsy revealed an extensive direct spread of pulmonary lymphosarcoma with infiltration of the chest wall but without metastatic dissemination or lymph node involvement. Neither primary lymphocytic lymphosarcoma of the lung in a girl of 5 years nor presentation of such a tumour as a chest wall mass in an adult seems to have been described previously.

Adult↗

Histologic classification and immunophenotype of lymphosarcomas in cats with naturally and experimentally acquired feline immunodeficiency virus infections.

Lymphosarcoma (malignant lymphoma) is the commonest hematopoietic tumor in the cat. Many cases are associated with feline leukemia virus (FeLV) infection, but epidemiologic and experimental data suggest that feline immunodeficiency virus (FIV) may also have a role in lymphomagenesis. In this paper, we describe the clinical presentation, histologic classification, and immunophenotype of lymphosarcoma in eight domestic cats with natural or experimental FIV infections. The tumors were often of unusual distribution, with the majority of cases conforming to the least common anatomic classification of "miscellaneous." Histopathologic and immunophenotypic analysis using a panel of anti-cat and cross-reactive anti-human monoclonal and polyclonal antibodies identified seven of these tumors as high-grade B cell lymphomas of the centroblastic or immunoblastic subtypes. The remaining case was a T-cell tumor associated with a concurrent FeLV infection. Our findings, together with the results of an analysis of FIV proviral DNA in these tumors, indicate that the B-cell lymphosarcomas were comparable to those observed in human and simian immunodeficiency virus infections and that the role of FIV in lymphomagenesis is indirect and related to the potential for malignant transformation during polyclonal B cell activation.

Animals↗