Persistent immunologic stimulation as a factor in oncogenesis, with special reference to Burkitt's tumor
About: This article is published in The American Journal of Medicine.The article was published on 1970-03-01. It has received 132 citations till now.
Citations
More filters
TL;DR: Results from a prospective sero-epidemiological study initiated in Uganda in 1971 indicate that children with high antibody titres to Epstein-Barr virus structural antigens are at high risk of developing Burkitt's lymphoma.
Abstract: Results from a prospective sero-epidemiological study initiated in Uganda in 1971 indicate that children with high antibody titres to Epstein-Barr virus structural antigens are at high risk of developing Burkitt's lymphoma. These findings strongly support a causal relationship between the Epstein-Barr virus and Burkitt's lymphoma but suggest that the oncogenic potential of the virus is realised only in exceptional circumstances.
557 citations
530 citations
TL;DR: Though the knowledge of cancer in this region is improving, better surveillance of cancer incidence, mortality, and prevalence of risk factors is urgently needed to monitor the development of the cancer epidemic, formulate appropriate cancer-control strategies, and assess the outcomes of these strategies.
Abstract: Cancer is an under-emphasised issue in Africa, partly because of the overwhelming burden of communicable diseases. However cancer is a common disease in Africa with 650 000 people, of a population of 965 million, diagnosed annually. Furthermore, the lifetime risk in females (between 0 and 64 years) of cancer is about 10%, which is only about 30% lower than the risk in developed countries. In females, the lifetime risk of dying from cancer in Africa is almost double the risk in developed countries. This Review is the first of two papers and focuses on the current knowledge of the distribution and trends of the most common cancers in Africa. The cancers with the highest incidence are cervical, breast, and now HIV-associated Kaposi's sarcoma. The top five cancers in males--Kaposi's sarcoma (constituting 12.9% of all cancers in males) and cancer of the liver (14.8%), prostate (9.5%), bladder (6.1%), and non-Hodgkin lymphoma (5.7%)--and in females--cancer of the cervix (constituting 23.3% of all cancers in females) and breast (19.2%), Kaposi's sarcoma (5.1%), cancer of the liver (5.0%), and non-Hodgkin lymphoma (3.7%)--are discussed in detail. The second paper will focus on the causes and control of cancer in Africa. The cancer burden in Africa is likely to increase as a result of increases in HIV-associated cancers, changes in lifestyles associated with economic development, and the increasing age of the population (despite AIDS). Although the knowledge of cancer in this region is improving, better surveillance of cancer incidence, mortality, and prevalence of risk factors is urgently needed to monitor the development of the cancer epidemic, formulate appropriate cancer-control strategies, and assess the outcomes of these strategies.
414 citations
TL;DR: Non-Hodgkin's lymphoma is a second tumor that may occur late in the course of patients treated for Hodgkin's disease--particularly in patients who have received both radiation therapy and chemotherapy, and may be another cancer that represents a substantial late risk of combined-modality therapy.
Abstract: We studied the clinical and pathological features of six cases of non-Hodgkin's lymphoma (diffuse undifferentiated in four cases and diffuse histiocytic in two cases) occurring in patients treated for Hodgkin's disease. All six patients had received both radiation therapy and chemotherapy. Abdominal or gastrointestinal involvement was present in five of the six cases. None of the patients had evidence of Hodgkin's disease when the diagnosis of non-Hodgkin's lymphoma was made. Five of the six patients were among a study group of 579 patients with Hodgkin's disease, prospectively followed since diagnosis. At 10 years the actuarial risk of development of non-Hodgkin's lymphoma in this study group is 4.4 per cent (1.2 to 15.0) (per cent probability with 95 per cent confidence limits) and is similar to that of developing acute leukemia: 2.0 per cent (0.3 to 12.9). Non-Hodgkin's lymphoma is a second tumor that may occur late in the course of patients treated for Hodgkin's disease — particularly in pati...
344 citations
TL;DR: Both clinical and experimental evidence indicates that the diseases or procedures that lower the immune functions in mammals are associated with a higher incidence of malignancies.
Abstract: Publisher Summary This chapter reviews some of the experimental and clinical findings linking immunodepression with malignant development. This material has accumulated for the past two decades and sufficient information, whether contradictory or not, is now available to permit an appraisal of the role of immune functions as the regulators of tumor development in animals and man. The idea that immunodepression enhances malignant development has become an integral part of the experimental support of the immune surveillance theory. In its more formal presentations, the theory of immunological surveillance against neoplasia included some basic points, with variations in terminology, but which have appeared with regularity as an integral part of the theory. The degree of immunodepression obtained in many experiments is quite profound and is clearly of a different magnitude than the immune defects occasionally observed in tumor-bearing humans. If immune mechanisms are important in host resistance to antigenic malignancies, any interference with the normal expression of host immunity should facilitate malignant development. Thus, both clinical and experimental evidence indicates that the diseases or procedures that lower the immune functions in mammals are associated with a higher incidence of malignancies.
324 citations
References
More filters
2,457 citations
TL;DR: Indirect immunofluorescence tests led to the brilliant staining of a small proportion of the cells in five different cultures derived from Burkitt's (African) lymphomas, and several observations suggest that the stainable cells might be those which are seen to harbor virus particles under the electron microscope.
Abstract: Henle, Gertrude (Children's Hospital of Philadelphia, Philadelphia, Pa.), and Werner Henle. Immunofluorescence in cells derived from Burkitt's lymphoma. J. Bacteriol. 91:1248-1256. 1966.-Indirect immunofluorescence tests led to the brilliant staining of a small proportion of the cells in five different cultures derived from Burkitt's (African) lymphomas. The reaction was not restricted to the 17 sera from cases of this disease but extended to many sera from American individuals, whether healthy donors or patients suffering from a variety of illnesses. The incidence of positive sera increased with age from about 30% in childhood to > 90% in adults. Fluorescein-isothiocyanate-conjugated human gamma-globulins were suitable for direct staining of the same proportion of cells. The stained cells appeared to be in varying stages of degeneration, but cultural conditions leading to an increase in the cellular death rates failed to result in a rise in fluorescent cells. Several observations suggest that the stainable cells might be those which are seen to harbor virus particles under the electron microscope. Two cell lines derived from leukemic patients in this country also contained a small fraction of stainable cells but two others, and numerous primary human leukocyte cultures, gave consistently negative results. Attempts to relate the staining to known viral antigens have failed to implicate herpes simplex, varicella, cytomegalo, and reo viruses types 1, 2, and 3. The nature of the virus carried by the lymphoma cells as well as of the staining reactions remains to be determined.
1,363 citations
TL;DR: It is indicated that EBV is related to, and probably the cause of, infectious mononucleosis, and that the agent has a world-wide dissemination.
Abstract: A herpes-type virus has been detected with remarkable frequency in cell lines derived from Burkitt's lymphomas, leukemic tissues, or buffy coats of a variety of patients and healthy donors.'-8 This agent is being named EB virus (EBV), for convenience, after the cell lines in which it was first observed.' M\\ost of the virus particles seen by electron microscopy in a small proportion of the cells are judged noninfectious because they are defective.\" 9. 10 To date, EBV has been transmissible only to cultured human cells of the hematopoietic system.\"'12 Virus-producing cells are readily detectable by indirect immunofluorescence tests with various human sera or by direct staining with fluorescein isothiocyanate-conjugated human y-globulins.'3'-7 Attempts to identify the agent by appropriate virus-specific immunofluorescence tests have failed. Thus EBV appears to be a new member of the herpes group.'3-\"5 From human serum surveys it is evident that infections by EBV, or a close relative of it, are frequent, and that the agent has a world-wide dissemination.\"3 117, 18 The age distribution of antibodies to EBV among American children parallels that of antibodies to other common viruses, such as measles, mumps, or poliomyelitis in the prevaccination era. 18 Except for the fact that all Burkitt's tumor patients studied thus far'3 1' and a high percentage of patients with carcinomas of the postnasal spaces'9 were found to have high titers of antibodies to EBV antigens, no other suggestive relationship of the virus to known disease entities has been recorded. The present report indicates that EBV is related to, and probably the cause of, infectious mononucleosis. Materials and Methods.-The techniques for growth and maintenance of cell lines derived from Burkitt's tumors have been described, as well as the procedures for preparation of cell smears, detection of EB virus antigens, and corresponding antibodies by immunofluorescence.3, 16 Cells of the EB-3 line were routinely used, which had been kept for 4-7 days on arginine-deficient Eagle's basal medium with 25% fetal calf serum (BME25) obtained by preincubation at 370C for 7 days or merely by omission of the amino acid. The arginine deficiency inhibits cellular growth but increases the number of EBV antigen-producing cells by a factor of 5-10 (to be published). Results.-The indirect immunofluorescence test for antibodies to EB virus was used in a search for illnesses that might be caused by this agent. In one series of tests, paired acute stage and convalescent sera from pediatric patients with unidentifiable viral infections were examined with negative results.18 As another approach, serial sera were tested that had been collected from children in prospective studies of viral infections. Such sets of sera were kindly supplied by Dr. John P. Fox from the \"New York Virus Watch,\" and by Dr. John H. Dingle from the Cleveland Family Study. Of the first group, 33 sets were examined that had been collected over periods of from one to four
1,128 citations
TL;DR: Herpes-type viral antigen and C-group chromosomal marker previously described in cultured Burkitt cells were found in all of the female cell cultures that were obtained.
Abstract: Cultured cells derived from male patients with Burkitt's lymphoma and harboring herpes-type virus particles were lethally irradiated. These irradiated cells induced normal peripheral leukocytes of female infants to grow within 2 to 4 weeks after mixed cultivation. Cells of a line free of this agent failed to stimulate growth. If either type of cell was cultured separately, it did not survive under the experimental conditions. Herpes-type viral antigen and C-group chromosomal marker previously described in cultured Burkitt cells were found in all of the female cell cultures that were obtained.
570 citations
01 Mar 1969
TL;DR: Malignant lymphomas developed in 5 renal homograft recipients treated at 3 widely separated transplantation centers and appears to be an indirect complication of organ transplantation and/or the measures taken to prevent rejection.
Abstract: Malignant lymphomas developed in 5 renal homograft recipients treated at 3 widely separated transplantation centers. The development of these tumors appears to be an indirect complication of organ transplantation and/or the measures taken to prevent rejection.
497 citations