Browsing by Author "ADELUSI, B."
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Item CIRCULATING TUMOUR ASSOCIATED ANTIGENS AS AID TO EARLY DIAGNQSIS OF CARCINOMA OF CERVIX(1982-10) ADELUSI, B.Earlier studies by this author in 1976 provided evidence of an association between an infective, sexually transmitted agent, the Herpes Simplex Virus Type-2 (HSV—2) and human carcinoma of the cervix, irrespective of geographic location or ethnic origin of the individuals. Similarly, HSV-2 related antigens were demonstrated by the indirect immuno-fluorescent technique in desquamated cells of carcinoma of the cervix tissues from tumour bearing patients. To highlight the Potentials of the detection of tumour antigens in tumour-faearing patients as aid to early diagnosis of the cancer, Isolation and purification of the Tumour Associated Antigens (TAA) of human cancer of the cervix were attempted by immunological and physicochemical procedures in this study. Two antigen preparations, one the Soluble Antigens (SA), and the other, the Membrane Bound Antigens (MBA) were prepared from a pool of cancer of the cervix (CaCx) tissues. The soluble antigens were extracted by homogenization in Earle’s Balanced Salt Solution (EBSS) containing antibiotics, and the membrane-bound antigens were solublised by 3-molar potassiurn Chloride (3 Molar KCl). For isolation and purification of TAA, procedures for the purification of proteins were explored. These include physicochemical stepwise ammonium sulphate fractionation, sephadex ion exchange chromatography, sephacryl S-200 gel filtration, and affinity chromatography to eliminate the normal tissue components of the antigen fractions. Hyperimmune rabbit sera were then prepared against the partially purified TAA. Immunodiffusion studies, employing hyperimmune rabbit sera prepared against the partially purified TAA were used to demonstrate tumour associated antigens in the various cancer antigen preparations, and Circulating Tumour Associated Antigens (C-TAA) in the sera of tumour- bearing patients. The TAA in the cancer tissues showed lines of identity with the C-TAA in patients sera. Techniques involving adsorption by immuno-precipitation-in-gel with Normal Cervix (NCx) tissue antigen preparations, and pooled Normal Human Sera (NHuS) were utilized for the removal of antibodies to NCx and NHuS in the rabbit sera, after which there were no reactions with NCx indicating the specificity of TAA for CaCx. A comparison of the soluble and 3 Molar KCl extracts of the cancer antigens by immuno-precipitation reaction, using adsorbed hyperimmune rabbit sera prepared against the partially purified CaCx TAA, demonstrated three TAA (TAA-1, close to the central antisera well, TAA-2, intermediate and TAA-3, close to and curving towards the peripheral antigen well) in the soluble antigen preparation. Only one TAA (probably identical to the TAA-3 of the soluble antigen) was demonstrated in the 3 Molar KCl extract. Using the rabbit antisera against the partially purified CaCx TAA, adsorbed with NCx and NHuS, results of coded sera showed that immunodiffusion reaction was able to detect circulating TAA in 75.0 per cent of patients with cancer as compared with 5.6% in women with benign gynecological diseases, 1.4% in pregnant women and 0.0% in healthy control women. The result indicates that the test has great potential for immunodiagnosis of cancer of cervix. Although the sensitivity of the test method was low, the specificity was high, and could provide a means of early diagnosis of neoplastic changes in the cervix. The detection of Circulating-TAA as tumour markers in sera of patients, may someday become routine, and thus make earlier diagnosis of cancer possible. Indications are that immuno-diagnostic procedures can be designed in ways that are reproducible, simple and reliable. Such serological tests would extend our present ability for detection and monitoring of malignancies.Item HERPES TYPE-2 VIRUS AND CARCINOMA OF THE CERVIX UTERI IN NIGERIANS: IMMUNOVIROLOGICAL STUDIES(1976-03) ADELUSI, B.In the search for the etiology of carcinoma of the cervix uteri, various factors have been implicated by various workers. The disease has been shown to have a venereal origin, following on its significant association with coital characteristics. These include early Initiation into hetero-sexual acts and frequency of coitus, multiplicity of coital Partners, multiparity, low socio-economic standards, venereal diseases and circumcision. Extensive epidemiologic studies have indicated that a "venoreally transmitted factor" might be responsible for the introduction of the squamous cell variety of the malignant disease. Recently, a strain of Herpes Simplex virus, antigenically distinct from the strain commonly associated with oral lesions, and designated Genital Herpes or Herpes Type-2 (HT-2) virus, was shown to be venereally transmitted, and might have oncogenic potentialities on the cervix. At the time the present studies were contemplated, little was documented about the clinical and histopathologic presentation of Carcinoma of the cervix in Ibadan. There was also no knowlege of the prevalence of Herpes Type-2 virus antibodies in the population, nor of the precise relationship, if any, of the virus to carcinoma of the cervix uteri in Ibadan. It was clear however, as a result of the work Edington and Maclean (1965) that carcinoma of the cervix uteri is very common in Ibadan, where it was shown to form the commonest female malignancy. Clinical, cytologic, histopathologic and immuno-virologic studies were undertaken to see if indeed carcinoma of the cervix uteri has a venereal origin, and to ascertain whether or not there is any association between the malignancy and HT-2 virus infection in Ibadan. In addition, sero-epidemiologic studies were also undertaken to determine the prevalence of HT-2 virus antibodies in various sectors of the Population. Evidence was provided to show that coital practice was a significant correlate of carcinoma of the cervix in Ibadan. Furthermore, Imuno- fluorescence and complement fixation tests were two Parameters used to provide evidence that Herpes Type-2 virus is associated with the disease, in that carcinoma of the cervix patients possessed significantly levels of antibodies against HT-2 virus as compared with patients having extra-cervical pelvic, and extra-pelvic malignancies and healthy Controls. In addition, HT-2 virus antigens were detected by immunofluorescence tests in the exfoliative cervical cells from all patients with carcinoma of the cervix, whereas no such virus antigens were found in exfoliated cervical cells from healthy Controls. In was concluded, that the observed association between HT-2 virus and carcinoma of the cervix in agreement with other studies, and the fact that the virus was not associated with other extra-cervical malignancies in this environment, indicate a significant relationship. Even though this may not necessarily be an etiologic one, the precise relationship of the virus and the malignancy would have to await further investigation.