Analysis of Peoxisome Proliferator-Induced Rat Tumour Cell Antigens Using Monoclonal Antibodies.

In this thesis a study of peroxisome proliferator-induced rat liver tumours was performed, and the antigenic characteristics of the tumour cells examined. Peroxisome proliferators are non-genotoxic, non-mutagenic carcinogens which produce tumours in rodents, notably hepatocellular carcinomas. These tumours are similar in histology to hepatocellular carcinomas of other etiology. 1. The ciprofibrate-induced rat liver tumour cells exhibited a significantly longer survival time in vitro as compared to their normal counterparts. They also exhibited a potential for cell proliferation in vitro. The tumour cells were clearly transformed showing characteristically higher agglutinibility with plant lectins (wheat germ agglutinin and concanavalin-A) and a potential for growth and colony formation in semisolid media such as soft agar and methylcellulose. 2. Monoclonal antibodies (MoAbs) were raised against the tumour cells using two different schedules of immunization. The schedule of prolonged and multiple immunization was found to be more efficient for the production of tumour-specific MoAbs. A number of clones were obtained showing reactivity with either tumour cells, normal cells or both. A total of 23 MoAbs were obtained showing preferential or selective reactivity with the tumour cells. On further characterization, five of these (M-19, M-23, M-28, M-54 and M-56) did not react with any other normal or fetal rat tissues. 3. Some of the MoAbs also reacted with pre-neoplastic and peri-neoplastic tissues from the ciprofibrate-treated rat livers, and most of the MoAbs were reactive with liver tumours induced by ciprofibrate in other rats. 4. The antigens identified by these MoAbs were mainly cytoplasmic, as observed by immunocytochemical methods. The MoAbs were also tested in a cross-species system, but showed no reactivity with normal human tissues and little reactivity with non-hepatic human tumours. Two of the MoAbs (M-23 and M-28) reacted strongly with human hepatocellular carcinoma. 5. Immunoblotting was used to study further the antigens identified by the MoAbs. The antigens demonstrated a size range between 45 kd and 159 kd. While some of these molecular weights may correspond to cellular enzymes induced by peroxisome proliferators (e. g. cytochrome P-450), several of them appear to be new antigens not previously described. The elucidation of their structure and function, and their examination as specific tumour markers may help in the diagnosis or treatment of human hepatocellular carcinoma

Analysis of Peoxisome Proliferator-Induced Rat Tumour Cell Antigens Using Monoclonal Antibodies.

In this thesis a study of peroxisome proliferator-induced rat liver tumours was performed, and the antigenic characteristics of the tumour cells examined. Peroxisome proliferators are non-genotoxic, non-mutagenic carcinogens which produce tumours in rodents, notably hepatocellular carcinomas. These tumours are similar in histology to hepatocellular carcinomas of other etiology. 1. The ciprofibrate-induced rat liver tumour cells exhibited a significantly longer survival time in vitro as compared to their normal counterparts. They also exhibited a potential for cell proliferation in vitro. The tumour cells were clearly transformed showing characteristically higher agglutinibility with plant lectins (wheat germ agglutinin and concanavalin-A) and a potential for growth and colony formation in semisolid media such as soft agar and methylcellulose. 2. Monoclonal antibodies (MoAbs) were raised against the tumour cells using two different schedules of immunization. The schedule of prolonged and multiple immunization was found to be more efficient for the production of tumour-specific MoAbs. A number of clones were obtained showing reactivity with either tumour cells, normal cells or both. A total of 23 MoAbs were obtained showing preferential or selective reactivity with the tumour cells. On further characterization, five of these (M-19, M-23, M-28, M-54 and M-56) did not react with any other normal or fetal rat tissues. 3. Some of the MoAbs also reacted with pre-neoplastic and peri-neoplastic tissues from the ciprofibrate-treated rat livers, and most of the MoAbs were reactive with liver tumours induced by ciprofibrate in other rats. 4. The antigens identified by these MoAbs were mainly cytoplasmic, as observed by immunocytochemical methods. The MoAbs were also tested in a cross-species system, but showed no reactivity with normal human tissues and little reactivity with non-hepatic human tumours. Two of the MoAbs (M-23 and M-28) reacted strongly with human hepatocellular carcinoma. 5. Immunoblotting was used to study further the antigens identified by the MoAbs. The antigens demonstrated a size range between 45 kd and 159 kd. While some of these molecular weights may correspond to cellular enzymes induced by peroxisome proliferators (e. g. cytochrome P-450), several of them appear to be new antigens not previously described. The elucidation of their structure and function, and their examination as specific tumour markers may help in the diagnosis or treatment of human hepatocellular carcinoma

Be a true listener, rather than a good conversationalist

Oncology patient care is an ever evolving field both as a science and a clinical art. We evaluate, diagnose, and treat cancer patients daily. We break the bad and the good news to them. We are the hope on which their life and dreams hang on. We, as practitioners, have to assess each patient as an intelligent observer. We have to devise our strategy to break heartbreaking news to them in a tailored and personalized fashion according to the physical, psychological, emotional, and social status of the patient. The process has to be gentle, perceptive, pragmatic, yet truthful. These need to be reasonably good observational, listening, comprehending, and delivering potentials; which are sharpened by experience and skills

Cashmirins A and B, new antifungal and urease inhibitory prenylated coumarins from Sorbus cashmiriana

Cashmirins A (1) and B (2), new prenylated coumarins, have been isolated from the EtOAc- soluble fraction of the whole plant of Sorbus cashmiriana Hedlung, Monog. along with seselin (3), scopoletin (4), 3-hydroxyxanthyletin (5) and luteolin (6), reported for the first time from this species. Their structures were elucidated by spectroscopic techniques including MS, 1D and 2D NMR spectroscopy. Both new compounds 1 and 2 were investigated for biological activities and showed significant antifungal and urease inhibitory activities. Compounds 1 and 2 exhibited significant activity against Aspergillus flavus, Macrophomina phaseolina, Trichophyton simii, Trichophyton schoenleinii, and Pseudallescheria boydri. Both compounds also exhibited significant inhibitory activity against Jack bean urease with IC50 values of 28.2±0.12 µM and 30.3±0.18 µM, respectively compared to thiourea used as positive control

Cashmirins A and B, new antifungal and urease inhibitory prenylated coumarins from Sorbus cashmiriana

Abstract Cashmirins A (1) and B (2), new prenylated coumarins, have been isolated from the EtOAc- soluble fraction of the whole plant of Sorbus cashmiriana Hedlung, Monog. along with seselin (3), scopoletin (4), 3-hydroxyxanthyletin (5) and luteolin (6), reported for the first time from this species. Their structures were elucidated by spectroscopic techniques including MS, 1D and 2D NMR spectroscopy. Both new compounds 1 and 2 were investigated for biological activities and showed significant antifungal and urease inhibitory activities. Compounds 1 and 2 exhibited significant activity against Aspergillus flavus, Macrophomina phaseolina, Trichophyton simii, Trichophyton schoenleinii, and Pseudallescheria boydri. Both compounds also exhibited significant inhibitory activity against Jack bean urease with IC50 values of 28.2±0.12 µM and 30.3±0.18 µM, respectively compared to thiourea used as positive control

Age at diagnosis of female breast cancer in Oman: Issues and implications

Introduction: Female breast cancer (BC) is the most frequent malignancy diagnosed globally, about 23% of the diagnosed cancers. BC incidence varies geographically, highest in Western Europe and lowest in Africa. BC in females is strongly correlated to age, the highest incidence rate amongst older women reinforcing the importance of hormonal status. BC in young females has an aggressive phenotype. There is a shared observation amongst practicing oncologists that BC in Middle East and the developing world presents at an earlier age. Aim and Objective: The aims of this study are to evaluate the age at presentation of female BC in Oman, and to compare our data with international and regional published data. It discusses the impact of young age Breast Cancer. Materials and Methods: All diagnosed female BC cases registered from 1996-2010 all over the country, were retrieved from the National Cancer Registry, Ministry of Health. BC cases were analyzed with respect to age at presentation. The data were compared with regional and international data. Results: A total of 14,109 cancer cases were recorded during the period of study. BC was the leading malignancy as 1,294 cases (9.1%). Female BC patients were 1,230; denoting 19.2% of all female cancers. 53.5% of female BC presented below 50 years of age. Male BC constituted 5% of total, with 67% of male BC occurring over 50 years of age. Compared with data from Oman, the highest rates in UK and other Western countries are above 50 years of age. These rates are four to 10 times higher than local in different age groups. Interestingly, these rates increase with increasing age in UK from 40-45 to up to 85+, keep on increasing and go up to four times higher with higher age. This phenomenon, of increasing incidence rates with age, is not observed in our local population. Discussion: BC is significantly correlated to age as reported from Western population. BC is reported at a younger age from developing and Arab World, which need to be further studied and validated. This phenomenon of BC in younger age may have significant implications and effects ranging from screening, diagnosis, management, prognosis, and cost of treatment. Conclusion: The impact on young women diagnosed with BC is enormous, ranging from psychosocial to healthcare services and economics. There is a need to study it further in depth in developing World