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PubMed1990

Lymphocyte subpopulations in sheep with lymphosarcoma resulting from experimental infection with bovine leukaemia virus.

Sheep were experimentally infected with bovine leukaemia virus (BLV) and developed leukaemia and lymphosarcoma 30-88 weeks later. Ten sheep with lymphosarcoma were necropsied and lymphocyte subpopulations were evaluated in peripheral blood lymphocytes (PBL) and lymphocyte suspensions prepared from a range of lymph nodes, tumours and spleen. The leukaemic phase of BLV infection was characterized by an increase in the number of circulating B lymphocytes. The number of T lymphocytes was also increased with the CD8+ subpopulation proliferating at a much greater rate than the CD4+ subpopulation. In PBL the CD4:CD8 ratio fell rapidly as leukaemia developed, being 1.15 (+/- 0.18) 5-8 weeks before necropsy and 0.38 (+/- 0.09) at necropsy. During this period the number of B lymphocytes increased from 11.2 (+/- 0.7) to 379.4 (+/- 85.8) x 10(9)/L. CD4:CD8 ratios were also low in all lymph nodes and spleens of leukaemic sheep at necropsy. Most of the cells in solid tumours were B lymphocytes but a small population of T lymphocytes with a low CD4:CD8 ratio was identified.

Animals↗
PubMed1995

Targeted disruption of CD44 in MDAY-D2 lymphosarcoma cells has no effect on subcutaneous growth or metastatic capacity.

CD44 splice variants have been shown to be involved in metastasis of carcinomas. In addition, the standard form of CD44 has been implicated in metastasis, particularly of melanomas and lymphomas. To investigate this, we have generated a CD44-negative mutant of the highly metastatic murine MDAY-D2 lymphosarcoma. The two CD44 alleles of this diploid cell line were sequentially disrupted by homologous recombination, using isogenic CD44 genomic constructs interrupted by a neomycin or hygromycin resistance-conferring gene. The resulting double knockout (DKO) cells had completely lost the capacity to bind to immobilized hyaluronic acid, but did not differ from MDAY-D2 cells in integrin expression or in vitro growth. Subcutaneous (s.c.) growth potential and metastatic capacity of MDAY-D2 and DKO cells were assessed by s.c. and i.v. injection of the lowest cell dose (10(3) or 10(4), respectively) that gave rise to tumor formation by MDAY-D2 cells in approximately 100% of the mice. Quite unexpectedly, we observed no difference at all in either s.c. growth rate or local invasion into surrounding tissues between MDAY-D2 cells and the CD44-negative DKO cells. Also hematogenous metastasis formation upon i.v. injection was similar: both parental and DKO cells metastasized extensively to the spleen, liver, and bone marrow. We conclude that, at least for these MDAY-D2 lymphosarcoma cells, the standard form of CD44 is dispensable for tumor growth and metastasis. Our results show that targeted disruption of genes in tumor cells is a feasible approach to study their role in tumorigenesis and metastasis.

Animals↗
PubMed1975

Distribution of anticancer agents in spontaneous animal tumors. II. Distribution of gallium in canine lymphosarcoma.

The physiologic disposition of pharmacologic doses of gallium was studied in control dogs and dogs with spontaneous lymphosarcoma. Gallium 67 (67Ga) was administered iv with carrier gallium added at a dose of 8 mg/kg. About 50% of the injected dose was excreted in the urine by 48 hours (mostly in the first 12 hr), whereas negligible amounts were excreted in bile. The distribution of 67Ga in normal tissues was similar in control and tumor-bearing dogs. The tissue-to-plasma concentrations of gallium were considerably greater than 1 in the kidney cortex, bone marrow, bone, small intestine, and liver 6-72 hours after administration of the drug. At comparable time periods, tissue-to-plasma ratios of gallium were less than 1 in skeletal muscle and brain. In dogs with lymphosarcoma there was neither selective uptake nor selective retention of gallium in comparison to most normal tissues. In fact, several normal tissues, particularly kidney cortex and bone marrow, concentrated gallium greatly in excess of tumors. Qualitatively similar findings were obtained in a dog with malignant melanoma. These findings were contrary to what one would predict from reports showing that carrier-free 67Ga is selectively concentrated in various human and animal tumors. This indicates the need for more extensive studies of the physiologic disposition of pharmacologic (antitumor) doses of gallium in humans and appropriate animal models.

Animals↗
PubMed1977

Invasion of lymphosarcoma cells into the perfused mouse liver.

Liver of (C57BL X DBA)F1 mice were perfused in situ with a synthetic hemoglobin-free medium, to which murine lymphosarcoma cells were added. All cells were arrested. They were only found in the sinusoids, predominantly in periportal areas. Many lymphosarcoma cells penetrated the walls of the sinusoids with protrusions that extended into and through the endothelial cells. The protrusions often also invaded hepatocytes, and some cells migrated out of the sinusoids. The percentage of the cells that penetrated endothelium was constant and reproducible (68 +/- 4%) in experiments lasting longer than 90 minutes, but the percentage of these cells that also invaded hepatocytes varied greatly. Parellel experiments in vivo yielded similar results, except that the number of cells that invaded hepatocytes was generally much lower. The advantages of the perfused liver as a model for experimental study of the invasion mechanism were evaluated.

Animals↗
PubMed1980

Characterization of X-tropic endogenous retrovirus-specific RNA uninfected tissues and lymphosarcoma of BALB/c mice.

Analysis of endogenous X-tropic BALB/c retrovirus-specific RNAs in a BALB/c mouse tissue containing mostly non-driving cells (liver), in two normal tissues having significant proportions of dividing cells (20-h regenerating liver and 12-day embryo) and in cells of a lymphosarcoma of BALB/c mice were carried out by determining the extent to which the RNAs from these tissues hybridized to the virus 3H-cDNA probe and by their relative sedimentation values in a sucrose gradient. RNAs from 20-h regenerating liver, 12-day embryo and lymphosarcoma, each containing a significant proportion of proliferating cells, showed 8 to 21 % higher hybridization values than normal liver RNA. Differences in the exact size classes of virus-specific RNAs and, in their relative proportions were found to exist in the four different tissue types examined and no correlation between a specific RNA size-profile and the proliferating activity of a tissue could be detected.

Animals↗
PubMed1998

Cutaneous, multilocular T-cell lymphosarcoma in a horse--clinical, ultrasonographic and pathological findings.

Clinical, ultrasonographic and pathological findings of a cutaneous, multilocular T-cell lymphosarcoma (malignant lymphoma) in a 13-year-old, brown Austrian warmblood mare are reported. The horse was under clinical observation, and the tumours were sonographically monitored over an 8 month period, revealing worsening of body condition, weight loss, lameness of the left hindlimb and a slight increase in the tumours size. Most of the tumours were covered by normal skin, one showed ulceration. Ultrasonography of the tumours allowed accurate anatomical localization in relation to the adjoining tissue, assessment of their internal structure, of involvement of adjacent muscles and of a regional lymph node, and it facilitated the percutaneous fine-needle aspiration. Necropsy confirmed muscular infiltration in three locations. Light microscopy and immunohistology led to the diagnosis of a T-cell lymphosarcoma.

Animals↗
PubMed1975

Mediastinal lymphosarcoma simulating pericarditis.

A case of lymphosarcoma of the heart in a 10-year-old boy is presented. The clinical picture simulated a pericarditis. Prednisolone had a remarkably good temporary effect. Post-mortem examination showed a highly differentiated lymphosarcoma invading the pericardium and myocardium from a primary mediastinal localisation. Cytologic examination for malignant cells in the pericardial fluid must not be forgotten in a case of unexplained pericardial effusion.

Child↗
PubMed1998

Cranial vena caval thrombosis secondary to invasive mediastinal lymphosarcoma in a cat.

A 12-year-old female cat was diagnosed with a cranial vena caval thrombosis in association with a mediastinal lymphosarcoma. The cause of the cranial vena caval thrombosis was thought to be invasion of the venous wall by neoplastic lymphoid cells. Clinical signs of cranial vena caval thrombosis, such as swelling and oedema of the submandibular area, the ventral part of the neck and the forelimbs, were related to a space-occupying mediastinal lymphosarcoma, which also induced respiratory distress and cyanosis. Non-selective angiocardiography demonstrated the occlusion of the cranial vena cava and abnormal venous collateral vessels feeding the heart which are accepted as the venographic hallmark of clinically overt cranial vena caval syndrome. At postmortem examination, an intracaval thrombus, 5 cm in length, was seen extending from the costocervical vein to the sulcus terminalis of the right atrium.

Animals↗
PubMed2002

Hypereosinophilic paraneoplastic syndrome in a cat with intestinal T cell lymphosarcoma.

A 10-year-old, neutered female, domestic shorthair cat was presented with a recent history of weight loss, polydipsia, diarrhoea and vomiting. On physical examination, intestinal thickening and mesenteric lymph node enlargement were apparent. Clinical investigations revealed peripheral blood eosinophilia, eosinophilic abdominal effusion and eosinophilic mesenteric lymphadenitis. There was a temporary response to treatment with glucocorticoids but signs progressed and the cat was euthanased. On histology, there was eosinophilic infiltration and fibroplasia of intestine and mesenteric lymph nodes. Large aggregates of neoplastic round cells in the intestine and lymph nodes were identified as T lymphocytes using immunohistochemistry. A diagnosis of intestinal T cell lymphosarcoma was made. This case demonstrates that hypereosinophilic paraneoplastic syndrome may occur in cats with lymphosarcoma. Eosinophil chemotaxis may be a response to the production of interleukin-5 by neoplastic lymphocytes.

Animals↗
PubMed1987

Ataxia due to lymphosarcoma in a young horse.

A 20-month-old, Standard-bred colt was presented with an acute onset of hindlimb ataxia. Clinical and radiographic examination identified a compressive lesion affecting the spinal cord at the level of the 17th to 18th thoracic vertebrae. After euthanasia, post-mortem examination revealed a tumour in the epidural space, diagnosed histologically as a lymphosarcoma. Neoplastic lymphoid cells were also present in the abdominal lymph nodes and brain. Because of the disseminated nature of lymphosarcoma in the horse, involvement of the central nervous system is likely to be more common than is presently recognised.

Animals↗
PubMed2000

Haematological and biochemical findings in cats in Australia with lymphosarcoma.

OBJECTIVE: To describe, for the first time, haematological and serum biochemical findings in cases of lymphosarcoma in Australian cats. DESIGN: A prospective multi-institutional study. PROCEDURE: Of 118 affected cats presented to the authors over a 18-month period, 97 were evaluated haematologically and 87 biochemically. Haematological analysis usually included determination of packed cell volume, haemoglobin concentration, red blood cell and leukocyte counts, differential leukcocyte count, reticulocyte count and examination of buffycoat smears for neoplastic cells. Serum biochemical analysis was done primarily with a discrete analyser and included a panel of commonly used analytes. RESULTS: Nonregenerative anaemia was present in 54% (52/97) of cats. Neutrophilia, present in 65% (59/91) of cats, was commonly associated with lymphocytopaenia, eosinopaenia and monocytosis. Of the 13 cats with a secondary leukaemic manifestation, only five had distinct lymphocytosis. Serum biochemical abnormalities either were nonspecific, such as hypoglycaemia in 37% (32/87) of cats, or related to specific tissue involvement, such as hypoalbuminaemia in 76% (31/41) of cats with alimentary involvement and azotaemia in 60% (15/25) of cats with renal involvement. CONCLUSION: It was shown for the first time that haematological and serum biochemical findings are of limited value in diagnosing lymphosarcoma in Australian cats, except if they are leukaemic. Although clinical pathological changes were common, they were nonspecific or related to specific tissue involvement. Their value in assessing response to therapy needs to be examined further. Patient characteristics such as age, breed and sex also had limited effect on laboratory findings and those observed were of little consequence. Additionally, histological and immunophenotypical variations in tumour type had little effect on laboratory findings.

Animals↗
PubMedDate not supplied

Efficacy and toxicity of doxorubicin/cyclophosphamide maintenance therapy in dogs with multicentric lymphosarcoma.

Doxorubicin/cyclophosphamide were evaluated as maintenance drugs for dogs with multicentric lymphosarcoma (n = 28). Median remission time of all dogs was 173 days. Remission duration was shorter, however, in dogs with stage IV/V disease, in dogs with pretreatment hypoalbuminemia, and in dogs that had received glucocorticoids before initiation of chemotherapy (P less than 0.04). Nineteen dogs were evaluable for toxicity. Dose-limiting gastrointestinal toxicosis was observed in three dogs, neutropenia was observed in three dogs, and cardiomyopathy was observed in three dogs. The doxorubicin/cyclophosphamide protocol described in this report is safe and effective in treating canine multicentric lymphosarcoma. Clinical stage, pretreatment steroid therapy, and hypoalbuminemia are prognostic factors for response to this protocol.

Animals↗
PubMedDate not supplied

Feline spinal lymphosarcoma: a retrospective evaluation of 23 cats.

A retrospective study of pathologically confirmed cases of feline spinal lymphosarcoma (FSL) admitted to the Colleges of Veterinary Medicine at the University of Georgia and North Carolina State University from 1973 to 1988 was conducted. Two hundred fourteen cases of feline lymphosarcoma were diagnosed histopathologically; involvement of the central nervous system (CNS) was identified in 26 (12.1%). Twenty-three of these tumors involved the spinal cord, and 22 of the 23 were solitary. A predilection for the thoracic and lumbar vertebral canal was noted. Most cats with spinal disease were young, with mean and median ages of 43 and 24 months, respectively; 67 cats were 36 months of age or younger. In most cases, affected cats had acute neurological deterioration after an initial insidious course. Extraneural abnormalities were not consistently present. Neoplastic lymphocytes diagnostic of FSL were identified on cerebrospinal fluid (CSF) analysis in 6 of 17 cats evaluated. Sixteen of 17 cats evaluated had serologically positive test results for feline leukemia virus (FeLV) p27 antigen, and all cats tested for feline immunodeficiency virus (FIV) antibodies had negative test results.

Animals↗
PubMed1983

DNA rearrangement and altered RNA expression of the c-myb oncogene in mouse plasmacytoid lymphosarcomas.

Three types of tumors termed plasmacytomas (ABPC's), lymphosarcomas (ABLS's), and plasmacytoid lymphosarcomas (ABPL's) arise in BALB/c mice treated with pristane and Abelson murine leukemia virus (A-MuLV). While most ABPC's and BLS's contain integrated A-MuLV proviral genome and synthesize the v-abl RNA, most ABPL's do not. The ABPL tumors were examined for the expression of other oncogenes that may be associated with their transformed state, in the absence of transforming virus. These tumors expressed abundant c-myb RNA of unusually large size and showed DNA rearrangements of the c-myb locus.

Abelson murine leukemia virus↗
PubMed2000

A novel truncated env gene isolated from a feline leukemia virus-induced thymic lymphosarcoma.

We PCR amplified the exogenous feline leukemia virus (FeLV)-related env gene species from lymphosarcomas induced by intradermally administered plasmid DNA of either the prototype FeLV, subgroup A molecular clone, F6A, or a new molecular clone, FeLV-A, Rickard strain (FRA). Of the nine tumors examined, six showed the presence of deleted env species of variable sizes in the tumor DNA. One env mutant, which was detected in a FRA-induced thymic lymphosarcoma, had a large internal deletion beginning from almost the N-terminal surface glycoprotein (SU) up to the middle region of the transmembrane (TM) protein of the env gene. The deduced polypeptide of this truncated env (tenv) retained the complete signal peptide and seven amino acids of the N-terminal mature SU of FRA env gene, followed by eight amino acids from the frameshift in the TM region. To study the biological function of tenv, we used a murine retrovirus vector to produce amphotropic virions. Infection of feline fibroblasts (H927), human fibrosarcoma cells (HT1080), or human B-lymphoma cells (Raji) led to pronounced cytotoxicity, while the tenv virus did not induce significant cytotoxicity to feline T-lymphoma cells (3201B) or human T-lymphoma cells (CEM). Together, these results convincingly demonstrated that the genetic events that led to truncation in the env gene occurred de novo in FeLV lymphomagenesis and that such a product, tenv could induce cytotoxicity to fibroblastic and B-lymphoid cells but not to T-lymphoid tumor cells. This type of selective toxicity might be potentially important in the development of the neoplastic disease.

Amino Acid Sequence↗
PubMed1969

Preliminary clinical assessment of I.C.R.F. 159 in acute leukaemia and lymphosarcoma.

I.C.R.F. 159, a new antitumour agent, has been assessed in six patients with acute leukaemia and three with lymphosarcoma. In all but two there was a considerable fall in circulating primitive cells, and in one there was bone-marrow evidence of a partial remission. Severe toxic effects were seen in only one case; they consisted of alopecia and gastroenteritis. It is suggested that I.C.R.F. 159 is worth further examination in all forms of acute leukaemia and lymphosarcoma.

Aged↗
PubMed1970

L-asparaginase in treatment of acute leukaemia and lymphosarcoma.

L-Asparaginase was used to treat 40 patients with acute leukaemia or lymphosarcoma. Fifteen with acute lymphoblastic leukaemia either untreated or in relapse after previous therapy were given "Squibb," "Bayer," or "Porton" L-asparaginase. Five of these patients had complete remission of their disease, and four had good partial remission. Eleven patients with acute myeloid leukaemia were treated for a short period with L-asparaginase alone. None of them went into remission though a pronounced fall in the numbers of circulating white cells was seen. Six patients with lymphosarcoma received L-asparaginase, two of them having good partial remissions.The toxic side-effects of the L-asparaginase from the three sources seemed to vary, and L-asparaginase from Erwinia carotovora appeared to be antigenically different from the enzyme produced by Escherichia coli.The way in which leukaemic cells become resistant to the action of the enzyme requires further investigation. To overcome this resistance asparaginase should be used in combination with other drugs in the treatment of acute leukaemia.

Acute Disease↗