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Journal Issue: Vol.3, No.4 - October 2004

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Editorial

Dr M Krishnan Nair

Dr. M .Krishnan Nair MD, FRCR The Austral-Asian Journal of Cancer (AJC) is the brainchild of the doctors of Regional Cancer Centre, Trivandrum and doctors from Kuwait and Australia. The publication of this International Journal on cancer is continuing successfully under the leadership of Dr Mohammed A.Al-Jarallah, Minister of Health, Kuwait and Dr Thomas Koilparampil, a Senior Staff member in the Department of Radiotherapy and Clinical Oncology in the Regional Cancer Centre, Trivandrum, who are Editors-in-Chiefs of the AJC. The activities for the publication of this journal started 6 years ago when I was the Director of Regional Cancer. As Chairman of Advisory Committee, I had the privilege of deciding the direction of this journal from its infancy. The main editorial office of AJC was started in Regional Cancer Centre, Trivandrum in 1998. Austral Asian Region includes major countries like India, China, Japan, Australia and Indonesia, which have a complex ethno-geographic composition. The cancers in this region are mostly preventable such as cancer of the liver, lung, cervix, mouth, breast and stomach. As this region accommodates 2/3rd population of the world in sheer numbers, cancer problem in this region is quite formidable. This region has countries which are economically most backward but some can even match the richest countries of the world. We have emerging economic giants like China and India. While the scarce health service provision in the poor developing countries is justifiable, it is sad to note that even these which have gained economically during the last few years have not correspondingly improved their health budgets. Certain features make cancer conducive for health action in their region, such as the largest number of preventable cancer, mainly due to smoking and other forms of tobacco use. It is predicted that in China, 1 out of 4 deaths by 2010 will be due to lung cancer. Control of tobacco use as such should be one of the priorities in this region. Due to Hepatitis B Vaccination, the cancer of the liver in China is fast coming down. That experience should be duplicated by countries in the region to safeguard their populations, so also in lung cancer by anti-tobacco measures. Oral cancer is a problem mostly of South Asia. It is well known that there are two forms of this cancer, one is tobacco related and the other occurring in non-habitual youngsters. The latter is highly aggressive and rapidly fatal. The etiology of such cancer needs extensive research. The ingenuity of commercial firms make sure that when one socially unacceptable habit gets discouraged,it gets replaced with something else even more harmful. A classical example is the replacement of betel nut chewing with pan masala. Similarly, South African region accommodates more than 250,000 cervical cancer patients. This would certainly justify a major program for HPV vaccine and cancer screening. But with the kind of infrastructure of the health service of the South Asia, a cancer screening program cannot be even thought of. Hence, the IARC's attempt to use visual inspection methods in early cancer detection is laudable. While in this region, we have got countries with highly developed treatment facilities; there are countries where treatment facilities are almost non-existent or where people have to travel thousand of miles to reach a cancer treatment facility. In India itself, there are certain states like Bihar, Orissa, Uttaranchal etc where the treatment facilities are extremely poor. In the absence of treatment facilities, early detection becomes irrelevant. Now that at least some of the therapy equipments are manufactured locally, governments should attempt to install them in a geographically balanced fashion and provide treatment nearer to their homes. It should be remembered that in the absence of appropriate treatment facilities, the patients will be forced to seek inappropriate therapies with wastage of money and lives. More than 70% of cancer patients in this region are diagnosed late except in Japan. This emphasizes the need for extensive palliative care facilities. One of the main constraints in delivering palliative care is the non-availability of human resource and drugs. Though, this region produces most of the morphine in the world, because of regulations, Morphine is not available for pain relief of cancer patients. None of the countries in this region seem to take up this issue seriously. Research in cancer is a very important area to be addressed immediately. If one looks at cancer journals coming out from U.K. and USA, one would find that there are very few references on cancer in Asia. This is because of two things (i) medical scientists in Asia do not care to publish their research, (ii) this may be because these journals do not have much interest in the publication of material on cancers which are less frequent in the West. It is high time that professional organizations in Asia Pacific region lay more stress on cancers of this region. I congratulate AJC and its editors on the significant success it has so far achieved in projecting the cancer problem of the Austral Asian Region. Dr.M. Krishnan Nair, Founder Director (Retd.), Regional Cancer Centre, Trivandrum


Profile

Profile - Dr. James R. Hebert, Sc. D

Dr.James R. Hebert, Sc.D Dr. James R. Hebert is one of the leading epidemiologists in the world. Much of his work over the past two decades has focused on either cancer or nutrition or both. As a nutritional epidemiologist, most of Dr.Hebert's career has been devoted to studies aimed at investigating the role of diet in cancer and cardiovascular disease (CVD). This work has been based in a number of different settings (including in the U.S and India) and has employed a variety of epidemiological and bio-statistical techniques designed specifically to overcome existing, often serious, methodologic problems. A major theme of his methodological research over the past 15 years has been on improving ways to assess diet so as to obviate errors in self-report that can cause major problems with interpreting results of statistical analyses and drawing inferences from epidemiological studies. Because the patho-physiology of CVD is understood better than that of cancer, some of his teams' work in the area of assessment has focused on the relationship between diet and known disease-related intermediate endpoints, such as serum lipids. Knowledge of these physiological relationships has enabled Dr. Hebert's research team to employ methods of construct validity to improve methods of assessing diet. Construct validation makes use of well-known physical and biological relationships [constructs] in identifying errors patterns in self-report data. This work has led to identifying biases in self-reports, mainly due to social approval and social desirability1-5. The error coefficients have been used to refine estimates of the effect of the diet on health-related outcomes and to improve methods of intervening on diet (and other health-related behaviours) in primary and secondary prevention trials. Work conducted with colleagues in India has produced breakthroughs in dietary self-assessment methods for use in India (6-10) and has helped to identify areas where more methodologic work will be needed (11). After working overseas on the epidemiology of child growth and in humanitarian aid (for the UN and centered primarily on nutrition) on and off for about 7 years, Dr. Hebert returned to the US to work in cancer research. His first job in this arena, in 1985, was with the American Health Foundation, now known as the Institute for Cancer Prevention, in New York City. He convinced its Director, Ernst Wynder, that he could be the Head of the Section of Nutritional Epidemiology, as the world in which he had worked earlier was at least as ?messy? as was (and is) this field. Dr. Wynder wrote one of the first papers on smoking and lung cancer12, and was the founder of the American Health Foundation. Dr. Hebert is greateful for the opportunity to have worked with Dr. Wynder and other wounderful colleagues around the world and over the years. Cancer epidemiology affords him a fantastic opportunity to make a difference in people?s lives because it calls for an ability to analyze, write and persuade. It also requires a willingness to learn about a variety of topics ? ranging from molecular genetics to public policy. Like most disciplines in public health, it also requires an appreciation of the social dimensions of health-related problems. Dr. Hebert came to South Carolina, in 1999, because of the superb fit between the needs of the people and his career trajectory. Cancer rate disparities in this state are the largest in the U.S., and for some cancers proportionally much larger than for any other disease. Even with the encumbrance of being Chair of the Department of Epidemiology and Biostatistics he managed to get numerous studies funded in this arena. Currently, Dr. Hebert is Principal Investigator on nine federally funded cancer-related grants, including Cancer Research Network (CRN), which is the first initiative ever co-funded by the U.S. Centres for Disease Control and Prevention and the National Cancer Institute. Over the past year, Dr. Hebert has worked with leaders from the University of South Carolina, the Medical University of South Carolina, and the Hollings Cancer Centre to develop a Statewide Cancer Prevention and Control Program. The develop a Statewide Cancer Prevention and Control Program. The Memorandum of Understanding that created this program and naming him as the Founding Chair was signed in July 2003. It is the first such agreement between these universities in South Carolina?s history. It also is the first such collaborative program in the US. In addition to being the P.I. on the Cancer Research Network, Dr. Hebert is the Chair of the Research Task Force of the South Carolina Cancer Alliance (SCCA). The SCCA is an organization unlike any other in the United States. Collaborators represent every constituency in the state: every university with a research presence, every medical system that treats cancer patients, virtually all grass roots organizations focusing on cancer or important cancer-related risk factors (e.g.tobacco), all state agencies that house geocoded data, major NGOs (e.g.,the American Cancer Society), and a wide variety of consumer advocates. It is Dr. Hebert?s intention to lead this effort in such a way that the SCCA can plan and advocate for things that really matter in people?s lives. Over the next five years, Dr. Hebert?s intension is to make the cancer research and treatment efforts in South Carolina coalesce into an NCI-designated Comprehensive Cancer Center. This will require a lot of cooperation between the major universities, healthcare facilities, and community groups in the state. He wants to devote himself to this, as it provides excellent opportunities to address on of its most pressing public health needs in one of the US? poorest states. Since the late 1980s, Dr. Hebert has been a strong proponent of conducting epidemiologic studies13 of diet and cancer in places with potentially high information, as opposed to purely outcome, yield. Consistent with this view, since the early 1990s he has worked with Dr. Prakash C.Gupta and colleagues at the Tata Institute for Fundamental Research in Mumbai and their various field operations on a multi-site study on the role of dietary factors in oral precancerous lesions11, 14,15. Currently Dr. Hebert works with Dr.Gupta on the Mumbai Cohort Study16. Dr. Hebert?s article in this isssue of the journal addresses philosophical and methodologic issues as they relate to the epidemiologic study of cancer from an international prespective. Through his career Dr. Hebert has advocated for a very expansive view that very much includes an international perspective on local, regional, and national problem. His work in India and Africa will continue to be central to the overall research mission. Dr. Hebert is quoted as sayin ?As long as I am here (or anywhere for that matter), I will not just talk the talk. This will require being mindful of both the social and scientific imperative of the work to which I am called.? REFERENCES 1. Hebert JR, Clemow L, Pbert L, Ockene IS, Ockene JK, Social desirability blas in dietary self-report may compromises the validity of dietary intake measures. Int J Epidemiol 1995;24-389-98. 2. Hebert JR, Ma Y, Clemow L, Ockene IS, Saperia G, Stanek EJ, Merriam PA, Ockene JK, Gender differences in social desirability and social approval bias in dietary self report. Am J Epidemiol 1997;146:1046-55. 3. Hebert JR, Peterson KE, Hurley TG, Stoddard AM, Cohen N, Field AE, Sorensen G. The effect of social desirability trait on self reported dietary measures among multi-ethnic female health center employees. Ann Epidemiol 2001;11:417-27. 4. Hebert JR, Patterson RE, Gorfine M, Ebbeling CB, St. Jeor ST, Chlebowski RT. Differences between estimated caloric requirements and self-reported caloric intake in the Women?s Health Initiative. Ann Epidemiol 2003;13:629-37. 5. Hebert JR, Ma Y, Ebbeling CB, Matthews CE, Ockene IS. Self. Report data. In: Ockene IS, Burke LE, eds. Compliance in Healthcare and Research. Armonk, NY: Futura; 2001:163-79. 6. Hebert JR, Gupta PC, Bhonsle R, Verghese F, Ebbeling C, Barrow R, Ellis S, Ma Y. Determinants of acciracy in estimating the weight and volume of commonly used foods: A cross-cultural comparison. Ecol Food Nutr 1999;37:475-502. 7. Hebert JR, Gupta PC, Bhonsle RB, Murti PR, Mehta H, Verghese F, et al. Development and testing of a quantitative food frequency questionnaire for use in Kerala, India. Public Health Nutr 1998;123-30. 8. Hebert JR, Gupta PC, Bhonsle RB, Sinor PN, Mehta H, Mehta FS. Development and testing of a quantitative foood frequency questionnaire for use in Gujarat, India. Public Health Nurt 1999;2:39-50. 9. Hebert JR, Gupta PC, Mehta H, Ebbeling CB, Bhonsle RR, Varghese F. Sources of variability in dietary intake in two distinct regions of rural India: implications for nutrition study design and interpretation. Eur J Clin Nutr 2000;54:479-86. 10. Gupta PC, Hebert JR. Quantitative food frequency questionnaires-applicability in India [letter;comment]. Natl Med J India 1999;12:138-9. 11. Hebert JR, Gupta PC, Bhonsle RB, Mehta H, Zheng W, Sanderson M, Teas J. Dietary exposures and oral precancerous lesions in Srikakulum District, Andhra Pradesh, India, Public Health Nutr 2002;5:303-12. 12. Wynder EL, Graham EA. Tobacco smoking as a possible etiologic factor in bronchiogenic carcinoma: A study of six hundred and eogjty-four proved cases. JAMA 1950;143:329-36. 13. Hebert JR, Miller Dr. Methodologic considerations for investigating the diet-cancer link. Amt J Clin Nutr 1988;47:1068-77. 14. Gupta PC, Hebert JR, Bhonsle RB, Murti PR, Mehta H, Mehta FS. Influence of dietary factors on oral precancerious lesions in a population-based case-control study in Kerala, India. Cancer 1999;85;1885-93. 15. Gupta PC, Hebert JR, Bhonsle RB, Sinor PN, Mehta H, Mehta FS. Dietary factors in oral leukoplakia and submucous fibrosis in a population-based case-control study in Gujarat, India. Oral Dis 1998;4:200-6. 16. Shukla HC, Gupta PC, Mehta HC, Hebert JR, Descriptive epidemiology of body mass index of an urban adult population in Western India. J Epidemiol Comm Health 2002;56:876-80. Expression of P53, Ki-67 and bcl-2 Oncoproteins in Human Breast Cancer and Their Clinicopathologic Significance Wang Qiangxiu1, Ephata E. Kaaya2, Chen Lihua1 and Wang Jiayao 1 Department of Pathology, Shandon Provincial Hospital, Jinan, China. 2 Department of Pathology, Muhimbili University College of Health Science, University of Dar es Salaam, Tanzania.


Manuscript

Expression of p53, Ki-67 and bcl-2 Oncoproteins in Human Breast Cancer and their Clinicopathologic

Prof Ephata E. Kaaya, Qiangxiu Wang, Lihua Chen, Jiayao Wang

  1. Prof Ephata E. Kaaya
    Department of Pathology, Muhimbili University College of Health Sciences,
  2. Qiangxiu Wang
  3. Lihua Chen
  4. Jiayao Wang

Breast cancer is the leading cancer site in women, both in the developed and the developing world. The incidence of breast cancer has been increasing in recent years in China. In order to study the interrelation between mutant p53, Ki-67 and bcl2 proteins, and their clinicopathologic significance in breast cancer, 69 cases of breast carcinoma were investigated using LSAB immunohistochemical method. Nuclear staining of mutant p53 and Ki?67 were observed in 26% and 39% of specimens, respectively. Cell cytoplasm staining of bcl-2 protein was observed in 36% of specimens. Expression of mutant p53 was associated with older patients (P=0.011). The observed strong relationship between the expression of p53, Ki-67 and bcl-2 proteins with disease duration suggests that patients who present late to hospital tend to have tumors with high proliferating rate which are also more aggressive. Statistically significant correlation was detected between the frequency of expression of p53, Ki-67, or bcl-2 protein and tumor grading. These results suggest that p53, Ki-67 and bcl-2 proteins are involved in tumorigenesis and development of breast cancer with different biological behavior. Therefore assessment for expression of p53, Ki-67 and bcl-2 oncoproteins can be used as prognostic markers in breast cancer and are of significance in determining and planning management of patients.


Radiology of Intrathoracic Neoplasms in AIDS

Dr Linda B Haramati, Dr Elizabeth R Jenny-Avital

  1. Dr Linda B Haramati
    M.D
    Department of Radiology, Albert Einstein College of Medicine, Montefiore Medical Center
  2. Dr Elizabeth R Jenny-Avital
    MD
    Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, Jacobi Medical Center,

AIDS-related neoplasms constitute and important group of diseases that continue to cause significant morbidity and mortality in HIV-infected patients. The following article will concentrate on a state-of-the-art review of a group of AIDS-related neoplasms which have intrathoracic manifestations. We aim to discuss current understanding of the etiology and usual thoracic radiograph manifestations of Kaposi sarcoma, lymphoma, bronchogenic carcinoma, and cervical and anal carcinoma. Familiarity with the epidemiology and typical radiographic findings for these AIDS-related neoplasms is essential in establishing correct diagnosis.


Angiogenseis in Breast Cancer: Association with P53 Status

Fourati Asma, Khomsi Fathi, Michele El May, Rahal Khaled, Ben Abdallah Mansour, Ahmed El May

  1. Fourati Asma
    Service Immuno-Histo Cytologie Place Bab Saadoun
  2. Khomsi Fathi
  3. Michele El May
  4. Rahal Khaled
  5. Ben Abdallah Mansour
  6. Ahmed El May

Aim: Angiogenesis is significant prognostic factor in breast cancer, but the factors that control angiogenesis invivo are not well defined. The purpose of this study was to investigate P53 expression in breast cancer and to examine the relationship between P53 over expression and the degree of angiogenesis. Methods: A total of 52 paraffin-embedded tumors were evaluated immunohistochemically for the expression of P53 and CD34 angiogenesis factor. Results: Majority of P53 positive cases (82%) demonstrated high level of micro-vessel density (MVD); 118% demonstrated no CD 34 expression. In contrast there was no variation in the CD34 expression among P53 negative tumors. Conclusion: This data suggests that micro-vessel density is promoted by P53 over-expression in breast cancer, and is correlated with high histologic grade.



Pathogenesis of Doxorubicin-Induced Cardiomyopathy

Dr Marcel Horky, Dr J Umlauf

  1. Dr Marcel Horky
    MD
    Department of Pathological Physiology, Faculty of Medicine, Masaryk University
  2. Dr J Umlauf
    Masaryk University,

A severe, cumulative, dose-dependent chronic cardiac toxicity is the major limitation of anthracycline therapy. Chronic cardio-toxicity occurs in patients after prolonged administration of Dox; a similar cardio-toxicity can be elicited in many animal species, including the mouse, the rat, the rabbit, the dog, and the monkey, after treatment with Dox. The cardio-toxicity consists of a chronic, progressive cardio-myopathy with myocyte vacuolation and degeneration, interstitial edema, and fibroplasia leading to congestive heart failure. Despite considerable work on the subject, the pathogenesis of the doxorubicin-induced cardio-myopathy is not well understood. However, Dox has been shown to exert a multiplicity of complex biochemical effects on the myocardium, including the following: binding to DNA and alteration of nucleic acids and protein synthesis, lipid peroxidation subsequent to free radical generation, release of histamine and catecholamines, damage to mitochondria, an effect on various cellular membranes, and excess calcium influx, and an effect on collagen matrix. A combination of these effects probably triggers the myocardial lesion.


Pre-operative Chemo-Radiation of Pancreatic Cancer

Dr Fahad Al-Enezi, Dr Sadeq Abuzollouf, Dr Shafica Al-Awadi

  1. Dr Fahad Al-Enezi
    Medical Oncology Department, Kuwait Cancer Control Centre
  2. Dr Sadeq Abuzollouf
    Radiation Oncology Department, Kuwait Cancer Control Centre
  3. Dr Shafica Al-Awadi
    Medical Oncology Department, Kuwait Cancer Control Centre

The management of pancreatic tumors poses a therapeutic challenge to practicing oncologists. The content of this article has been presented in a combined medical and surgical oncology conference held at Kuwait in December 2003. Three papers were presented about the treatment of pancreatic tumors. This paper dealt with the neo-adjuvant chemo-radiotherapy for locally advanced pancreatic cancer. We identified through literature review tow subsets in this regard. The rationale of this approach was presented based on literature reviews. The other two papers discussed the management of metastatic tumors and the role of targeted therapy in pancreatic tumors.


The Role of CCAAT/Enhancer Binding Proteins in Human Disease

Dr Adrian F. Gombart

  1. Dr Adrian F. Gombart
    Ph.D
    Cedars-Sinai Medical Center, Burns & Allen Research Institute,

Numerous invitro and invivo models implicate the CCAAT/enhancer binding protein (C/EBP) family as important regulators of cellular growth, differentiation and function. Conversely, the loss of their normal activity plays a role in the development of human disease. The first member of this family implicated in human diseases. The first member of this family implicated in human disease was C/EBP (CHOP/GADD153). Translocations involving this gene were described in myxoid liposarcomas. Recently, mutations in the C/EBPE gene were described in a human condition known as neutrophil specific granule deficiency (SGD). Most recently, 7-10% of acute myeloid leukemias possess mutations in the C/EBPA gene. This review will focus on the involvement of C/EBP family members in human disease.


Genetic Markers of Cancer Susceptibility

Dr Ravindran Ankathil

  1. Dr Ravindran Ankathil
    Additional Professor, Division of Cancer Research, Regional Cancer Centre

The basic principles of multistage carcinogenesis predict that a number of factors, in addition to exposure to specific causative agents, influence the probability that tumours will develop in an important factor in the genesis of common cancers. Human populations display a wide range of inherent sensitivities to carcinogenesis. Only a fraction of the individuals exposed to carcinogen, even a potent one, will develop neoplasia. Individual susceptibility to cancer may result from several factor, including inherited or acquired alterations in proto- oncogenes and tumour suppressor genes, differences in the metabolism of carcinogenic chemicals (uptake, activation and detoxification), genes controlling the repair of DNA or cellular damage, hormonal factors etc. Epigenetic changes in expression of these genes can also affect host susceptibility. Over the next decade, cancer researchers will be increasingly preoccupied with genetically susceptible subgroups and genetic markers of cancer susceptibility may emerge as a major focus for the next era of cancer research.


Alteration of Brain Tissue Metabolism Assessed by 1H-MRS in Patterns Treated for NSCLC

Dr T Rutkowski, A Cichon, M Sokol, A Zajusz, R Tarnawski

  1. Dr T Rutkowski
    Radiotherapy Department, Centre of Oncology, Maria Sklodowska-Curie Memorial Institute,
  2. A Cichon
  3. M Sokol
  4. A Zajusz
  5. R Tarnawski

Aim: To assess the brain tissue metabolism using 1 H-MRS, in patients treated for NSCLC. Material and Methods: The studied group consisted of 34 patients with NSCLC treated with radical intention in the Center of Oncology Maria Sktodowska-Curia Memorial Institute in Gliwice. 1H-MRS single voxel spectra were acquired from frontal (FL) and occipital lobes (OL). The control group consisted of 30 healthy volunteers (CG). Results: NAA/Cr was significantly lower, Cho/Cr and Cho/NAA were significantly elevated particularly in FL. Considerable elevated Lac/NAA and Lip/NAA were observed in FL and OL. Conclusion: Brain metabolism is significantly changed in patients with NSCLC. At the time being is difficult to predict the practical value of proposed diagnostic approach. Thus, further study is needed to establish mechanism underlying observed alteration. This is crucial particularly for long survivors for proper prevention and treatment.


Overview of Cervical Cancer (Cervix Uteri) in Kuwait: Retrospective Study

Dr Saroj Vasishta, Ahmed Ragheb, Abraham Varghese, Omar El Hattab, Medhat Oteifa, Adel Al-Asfour

  1. Dr Saroj Vasishta
    MD
    P.O. Box 3128, Salmiyah Central: 22032
  2. Ahmed Ragheb
  3. Abraham Varghese
  4. Omar El Hattab
  5. Medhat Oteifa
  6. Adel Al-Asfour

Cervical cancer is the fifth most common cancer in Kuwait females living in Kuwait. In 2002, cancer cervix represented 4.6% of all cancer cases among Kuwait females and 4.7% of all cancer cases among non-Kuwaiti females, while the crude incidence rate was 3.5 per 100,000 among Kuwaiti females and 3.1 per 100,000 among non-Kuwaiti females (1). The aim of this study is to review the clinico-pathological pattern of this disease in Kuwait, the various treatment modalities used in their management and their results. Case records of one hundred and six women with cervical cancer treated between 1995 and 1999 at Kuwait Cancer Control Centre available, were retrospectively studied and analysed. In our study population, 37% females were Kuwaitis, median age was 45 years and 75.5% presented with stage IB & stage II tumors. The commonest presenting symptom was vaginal bleeding. Almost half of the patients were treated with radical radiotherapy and half with surgery with or without post-operative radiotherapy. Few patients treated abroad received neo-adjuvant chemotherapy. Thirty two patients (31%) relapsed during follow-up. The overall 5 years survival was 79% in Stage 1, 86% in Stage II, 47% in stage III and 0% in Stage IV (1 year survival in Stage IV being 50%). The commonest late radiation sequelae was grade 2 vaginal atrophy and telangiectasia occurring in 22% of the irradiated patients followed by proctitis & rectal bleeding.


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