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PubMed1979

Lymphoma development in mice and humans: diversity of initiation is followed by convergent cytogenetic evolution.

Human B cell lymphoma and murine T cell leukemia can be initiated by several agents. The present paper formulates some thoughts on the role of cytogenetic changes in the subsequent neoplastic process. Initiation creates long-lived preneoplastic cells. In some respects, they are comparable to in vitro-transformed ("immortalized") cell lines that maintain a diploid karyotype and are not tumorigenic in vivo. The development of a tumorigenic ("autonomous") clone is dependent on additional changes at the genetic level. In human B and murine T cell lymphoma, there are characteristic nonrandom chromosomal changes. The 14q+ marker appears to play a key role in human B cell lymphomas. The reciprocal 8;14 translocation in Burkitt lymphoma is a specialized subclass within this category. In murine T cell leukemia, trisomy 15 is the predominant change. The clustering of these nonrandom changes to tumors derived from a certain cell type rather than to tumors induced by a given etiological agent has important implications for the understanding of the genetic control of cellular responsiveness to growth-regulating forces in vivo.

AKR murine leukemia virus↗
PubMed1977

Persistently abnormal brain scintigraphy after cerebral infarction.

The current literature indicates nuclear brain images typically return to normal within two to three months following an episode of cerebral infarction. In this report, two patients are described who demonstrated no significant change in their brain scan abnormalities 11 and 17 months following their strokes. Computed tomography confirmed the clinical impression that the persistent brain scan abnormalities were due to cerebral infarction rather than to neoplastic process.

Aged↗
PubMed1979

Giant cell tumor of bone. Variations in patterns of appearance of different cell types.

Eleven benign giant cell tumors of bone were studied in the electron microscope, and the fine structural localization of acid phosphatase was elucidated. Three distinct cell types are always present in these tumors: stromal cells type 1; stromal cells type 2; and multinucleated giant cells. Small mononuclear cells may also occur, but are not likely to be actively participating in the neoplastic process. The range of variability in the fine structure of the different cell types constituting this tumor has been established. Variations in appearances include: a) presence of nuclear pseudoinclusions in stromal cells type 1 and multinucleated giant cells; b) aberrations in the structure of the rough surfaced endoplasmic reticulum in the same cell types; c) occurrence of ruffled borders, ectoplasmic layers and cytoplasmic labyrinths containing acid phosphatase in the giant cells. Some giant cells show evidence of marked phagocytic activity and contain large and numerous residual bodies carrying acid phosphatase. The significance of the interrelations between the different cell types are discussed and the possible role of stromal cells type 2 in immunological mechanisms directed against the tumor cells are mentioned.

Acid Phosphatase↗
PubMedDate not supplied

Persistence of nucleolar RNA-rich structures and Ph1 duplication in the blastic crisis of chronic myeloid leukaemia.

Nucleolar persistence in metaphase plates is a feature observed in most of the cells in neoplastic processes. Pathological persistence or fragmentation of the nucleoli is thought to be the cause of some numerical chromosomal aberrations due to non-disjunction of the chromatids, with particular involvement of the satellite chromosomes. Thus, a combined selective staining of both the nucleoli (amido black 10B according to Mundkur and Brauer's cytochemical technique) and the chromosomes (neutral red) was applied to the metaphase plates of patients with chronic myeloid leukaemia in the blastic crisis. Duplicated Ph1 was associated with amido black-stained areas at a very high rate in some cases. Since the blastic crisis in chronic myeloid leukaemia is characterized by the appearance of an increased number of immature, highly nucleolated cells, these findings lend support to the hypothesis that the duplication of the Ph1 represents a feature possibly favoured by the pathological persistence of nucleolar RNA-rich structures in the metaphase.

Adult↗
PubMed1979

Microenvironmental influences on the in vivo behavior of neoplastic lymphocytes.

A transplantable hamster lymphocytic neoplasma of probable monoclonal derivation, induced by the oncogenic DNA simian virus 40, has been adapted to grow in the allogeneic host either as leukemia (characterized by dissemination and poor prognosis) or as lymphoma (characterized by localization and favorable prognosis) [Diamandopoulos, G. Th. (1978) Proc. Natl. Acad. Sci. USA 75, 2011-2015]. In the present experiments the circumstances under which neoplastic lymphocytes that are transplanted in allogeneic animals retain, lose, or regain the capacity for dissemination or localization are assessed. Results indicate that the in vivo behavior of neoplastic lymphocytes is not a stable, irreversible characteristic that is transmitted to the cell progeny. On the contrary, it can be altered by the origin/tissue microenvironment in which the cells proliferate. It is suggested that, whereas neoplastic cell mutation followed by host selection could be responsible for changes in cell behavior, a more likely explanation is that the proliferating neoplastic lymphocytes acquire reversible nonmutational phenotypic characteristics during their interaction with the host microenvironment, which modify their behavior and, as a result, the prognosis of the neoplastic process.

Animals↗
PubMed1979

Suppression of in vitro antibody response by spleen cells of mice infected with Friend-associated lymphatic leukemia virus.

The ability of spleen cells of mice infected with oncornaviruses to depress the in vitro antibody responsiveness of normal lymphoid cells was exploited in an attempt to clarify the role played by the lymphatic leukemia virus (LLV) component in the immunodepressive properties of the Friend leukemia complex. Spleen cells of mice infected with LLV or, for comparison, with the entire complex were added to cultures of sheep erythrocyte-primed uninfected spleen cells, and the antibody-forming cells produced by the latter, after antigen restimulation, were assayed. The addition within 2 days from culture initiation of low numbers of cells infected with either virus preparation suppressed all stages of the response affecting the production of both immunoglobulin M and immunoglobulin G antibody. The activity of infected cells resisted doses of ultraviolet radiation which inhibit cell multiplication but was abolished by disrupting the cells and was prevented by the presence of anti-LLV antibodies. The LLV-infected spleen cells responsible for suppression were not removed by treatments which selectively remove or kill macrophages and exhibited surface properties of B lymphocytes. These results were interpreted as indicating that the effect is due to virus (or viral products) released by B cells. The suppressing cells in the spleens of mice in the early days of Friend leukemia complex infection presented superimposable properties, supporting the concept that their activity is also due to the LLV they release in large quantities. However, in later stages of infection, the spleens of Friend leukemia complex-infected mice also contained non-B-suppressing cells possibly derived from the proliferation of nonlymphoid LLV-producing cells caused by the neoplastic process.

Animals↗
PubMed1977

Treatment of Paget's disease of bone with mithramycin.

The hypothesis that Paget's disease of bone is a low grade neoplastic process led us to use the cytotoxic antibiotic mithramycin in its treatment. The dramatic effects observed on the serum calcium and alkaline phosphatase, and urinary hydroxyproline are compatible with the concept that mithramycin is primarily toxic to osteoclasts. Subjective and objective clinical effects establish this agent as useful in the treatment of Paget's disease despite its observed toxicity to other organ systems.

Chemical and Drug Induced Liver Injury↗
PubMed1975

Influence of carbon tetrachloride or riboflavin on liver carcinogenesis with a single dose of aflatoxin b1.

Liver carcinogenesis with a single dose of aflatoxin B1 (7 mg/kg body weight) has been investigated in a group of female Wistar strain rats by repeated biopsies and necropsies. Another group received a subsequent intoxication with carbon tetrachloride by inhalation (approximately 200 doses) and another one was overloaded with riboflavin (25 parts/10(6) in drinking water). The frequency of hepatomata was almost equal in the aflatoxin and aflatoxin-carbon tetrachloride group. It was lowere in the riboflavin-aflatoxin group. In these 3 groups cirrhosis was never present in neoplastic livers. Megalocytosis was the first lesion observed. All tumoral livers had previous or concomitant megalocytosis. This modification was about as frequent, intense and widespread in aflatoxin-CCl4 and aflatoxin groups but appeared much earlier, as did the first hepatoma, in the aflatoxin-CCl4 group. It was less frequent, less intense and less widespread in the riboflavin-aflatoxin group than in the aflatoxin group. There was also a lower frequency of hepatomata in the riboflavin-aflatoxin group, but the difference was not significant due to the too small number of animals involved. The facts are not a proof of the existence of an obligatory link between megalocytosis and carcinogenesis since a slight megalocytosis was observed in the riboflavin group not affected by the neoplastic process. However, the simplest explanation of our results would be to consider that the potential tumour cells are located among the megalocytic cells, without admitting that every megalocyte is obligatorily a precancerous cell. CCl4 seems to act in shortening the time of appearance of megalocytosis. The protective effect of riboflavine should be regarded with more caution.

Aflatoxins↗
PubMedDate not supplied

[Etiological role of the herpes simplex virus in causing cervical cancer].

The results of the composite virological and immunological examinations of 46 patients with cervical carcinoma (CC) attest to the association of herpes simplex virus (HSV) with neoplastic processes. HSV strains were isolated from the tumour tissue as well as from the cervical canal secretions and blood of 4 patients. A higher level of virus-neutralizing and complement-fixing antibodies to HSV was found in sera from CC patients as compared with the control group of normal women. Antibody to HSV type 2 was found in 38.8% of sera from the patients and 12.6% in the control group. Lymphocytes from CC patients induced blasttransformation reaction to HSV twice as frequently as those from healthy subjects. The virus-specific antigen was found in tumour cells of 36% CC patients in immunofluorescent examinations of smears from the cervix. The presented results are related to the determination of the etiological role of HSV in cervical carcinoma.

Adult↗
PubMed1977

Histological and histochemical studies of oral cancer.

Increasing attempts are now being made to measure and to assess the relative importance of histologic features in oral premalignant and malignant conditions in order to improve the accuracy of diagnosis and prognosis. Though certain individual features, such as DNA content of cell nuclei, or stereological parameters like nuclear : cytoplasmic ration or desmosome density can be very accurately quantified, no single feature can completely characterize the neoplastic process. Multifactorial studies are thus of great importance, even though it is not practicable to measure all the parameters included with the sam accuracy; in such studies retrospective computation of the relative importance of individual parameters is of greater value than arbitarily assigned weights. So far as early prediction of malignant transformation in oral premalignant lesions is concerned, great interest is now being shown in the reactivity of glucose-6-phosphate dehydrogenase in epithelial cells. For predicting the prognosis of patients with established squamous cell carcinoma of the mouth, it is now realized that thenature and intensity of the host immune inflammatory response seen in the connective tissue within the surrounding the tumour and in affected regional lymph nodes, is at least as important as are the features of the tumour cells themselves.

Cell Division↗
PubMed1977

Antineoplaston A in cancer therapy. (I).

Twenty-one patients with advanced cancer or leukemia were treated with antineoplaston A and followed for up to nine months. Dosage by intravenous, intramuscular, subcutaneous, rectal, intrapleural, intravesical and/or topical administration ranged from 0.6 to 33 U/m2/24 h. Treatment was well tolerated, although side effects included fever of short duration and elevation of platelet and white blood count. In 18 cases some degree of clinical improvement was observed. Complete remission occurred in 4 cases. More than 50% remission occurred in 4 other cases which, along with another 6 cases, are continuing the treatment with high doses of antineoplaston A and show a continuing regression of the tumors although not yet achieving the criteria for complete remission; 2 of these 6 cases seem unlikely to achieve remission. Two patients temporarily discontinued treatment. During treatment, 5 patients expired; in 2 of them, however, was seen significant regression of the neoplastic process. The deaths were not due to cancer or to any toxicity incurred by the treatment.

Administration, Topical↗
PubMed1979

Local reaction to gingival injections of MER/BCG in guinea pigs.

The local reaction to gingival injections of methanol extraction residue of BCG (MER/BCG) was investigated in guinea pigs to help determine the potential of this agent in treating oral carcinoma. The drug was used in a standard and diluted form. Both concentrations were well tolerated and caused no ulceration or necrosis. Histological examinations performed at predetermined intervals showed an inflammatory response to the standard and the diluted solution. This reaction was more pronounced when the higher concentration was used. No changes in the alveolar bone were found in either of the groups. Complete healing with scar formation was evident four to six weeks later. The absence of severe reactions after injections of MER should encourage further investigations of this agent in the local treatment of neoplastic processes in the oral cavity.

Animals↗
PubMed1977

["Primary" reticulum-cellsarcoma of the retina. I. Clinico-pathologic study of 5 patients (author's transl)].

Between 1964 and 1974 a primary reticulum-cellsarcoma of the retina was diagnosed histologically in 5 patients (between 44 and 71 years), in one already clinically. The initial diagnosis had been "uveitis" (2), "panuveitis" (1), "iridocyclitis with central retinal artery occlusion" (1), and "chorioretinitis" (1). The usual antiinflammatory therapy was without effect in every instance. All patients showed neurological symptoms with cerebral manifestations. Twice the cerebral biopsies had been misinterpreted initially as "atypical glioblastoma multiforme", once as Neuro-Behçet. The disease progressed over a course of 2--10 years from the initial ophthalmic symptoms to death. A review of the literature is given and the differential-diagnosis to necrotizing forms of retinitis, dissiminated chorioiditis neoplastic processes of retina and uvea and degenerative diseases are discussed. The primary reticulum-cellsarcoma of the retina must be considered in the differential-diagnosis of uveitis or panuveitis if 1. there is progression in spite of the usual antiinflammatory therapy, 2. the initial infiltrations are seen in the deep layers of the sensory retina.

Adult↗
PubMed1978

Islet cells as a component of pancreatic ductal neoplasms. I. Experimental study: ductular cells, including islet cell precursors, as primary progenitor cells of tumors.

The ductular complex of the Syrian hamster pancreas represents a system of conduit which encompasses intercalated (intralobular), periinsular, and intrainsular ductules. The intercalated (intralobular) ductules comprise centroacinar and intercalated cells. A meshwork of small ductules (invisible by usual histologic procedures) surrounds islets (periinsular ductules) and extends in the form of often ramified tiny channels within the islet (intrainsular ductules). Although the function of the latter ductules is obscure, their cells seem to make up one of the undifferentiated cellular units of the pancreas, and as such are also the progenitors of beta-cells of the islets (islet cell precursor = IP). Systematic histologic examination of the pancreas in this species treated with pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine indicated that ductular cells, especially those of periinsular and intrainsular origin, are the most responsive to this carcinogen. The neoplastic process was initiated with hyperplasia of intercalated (intralobular) ductular and interlobular ductal cells associated with newly formed islets (nesidioblastosis). This process was followed by excess formation of mature but especially of immature islet cells and their precursors (IP) in the islet periphery, as well as with the appearance, distention, and multiplication of periinsular and particularly of intrainsular ductules. The hyperplasia, metaplasia, and malignant alteration of these periinsular and intrainsular ductules (including IP) and, to a lesser degree, of intercalated ductules indicated their histogenetic relationship and their potency for reproducing embryonic tissue on carcinogenic stimulus. The similarity of some induced lesions to diabetes has been emphasized.

Animals↗
PubMed1979

Organ and tumor specificity of colon mucoprotein antigen in a rat model.

We purified a high-molecular-weight colon mucoprotein antigen (CMA) from normal F344 rat colon and from a transplantable dimethylhydrazine-induced colon carcinoma. Chemical analysis of the mucins showed similar amino acid and carbohydrate compositions. This finding was in contrast to the major differences that occurred in the composition of human CMA as a consequence of neoplasia. Immunohistochemical techniques were used in an examination of organ and tumor specificities. A New Zealand White rabbit antiserum against purified normal rat CMA, appropriately absorbed, detected a normal colon-specific determinant(s). The organ-specific determinant was lost as a consequence of neoplasia. However, a new tumor-specific determinant was then detected. CMA may have a potential role as an organ-specific marker of the neoplastic process.

Amino Acids↗
PubMed1975

[Progressive multifocal encephalitis (PML)].

In four cases of progressive multifocal leucoencephalitis the basic disease was always a malignant lymphogranuloma. Changes in the brain were multifocal, however the frontoparietal area of the white matter was affected most frequently and foci in this part were oldest. In these foci demyelination with atypical astrogliosis predominated, and there was a very small number of scavenger cells. At the periphery of foci always proliferation and enlargement of homogenous oligodendroglia nuclei were found sometimes with inclusions which in immunoassay sometimes had a common antigen with papovirus SV 40 and on electronoptic examination always contained many virions of the papovirus. No direct relationship was found between the duration of the neoplastic process, its type and changes in the CNS.

Adult↗
PubMed1976

Serological and epidemiological considerations of the role of herpes simplex virus type 2 in cervical cancer.

To assess the possible biological significance of the observations that women with cervical cancer tend to be younger at first intercourse than control women, data from 1823 women were analyzed for the relationship between age at 1st intercourse and number of sex partners. Women who were younger at first intercourse had more sex partners than did women who were older at first intercourse. The interdependence of age at first intercourse and number of sex partners does not exlude the possibility that intercourse at an early age represents a biologically significant event in which the neoplastic process is initiated. However, it is equally possible that younger women at first intercourse may have multiple sex partners and be at greater risk of coming in contact with a putative oncogenic agent later in life. In addition, sera from patients with herpesvirus infections were assayed for cross-reacting and type-specific antibodies. Approximately 80% of the total antibody activity was to the cross-reacting antigen and only 20% was to the type-specific antigens in the sera of patients infected with either type 1 or type 2 virus. Among patients infected with both types of virus, less antibody activity to the type-specific antigens and more antibody activity to the cross-reacting antigens were found. These observations are discussed with respect to case-control seroepidemiological studies.

Age Factors↗