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Journal Issue: Vol.2, No.2 - January 2003

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Editorial

Cervical Cancer: One Disease Worlds Apart

Neville F Hacker. MD Gynaecological Cancer Centre, Royal Hospital for Women, University of New South Wales, Sydney Australia. No Cancer epitomises the stark contrast between the developing world as well as cancer of the cervix. Cervical cancer is the second most common cancer in women world wide, and represents 12% of all female malignancies. It is estimated that there are 500,000 new cases diagnosed each year, of which 79% occur in developing countries?. It is the leading cause of cancer related death among women in developing countries, whereas in the developed world, its incidence and mortality have progressively decreased. In the United States, it no longer ranks in the top 10 cancers in women2. Invasive cervical cancer develops from cervical intrepithelial neoplasia (CIN), and the progression normally takes may years. Preinvasive disease is asymptomatic, but can be diagnosed by use of the Papanicolaou smear, and readily treated in an outpatient setting. Hence, most cases of invasive cervical cancer are preventable through regular screening. The major reason for the great disparity in incidence of the disease world-wide relates to screening practices in different countries. It has been estimated that only 5% of women in developing countries have been screened in the past 5 years, compared with 40% to 50% of women in developed countries3. Pap smear screening is costly and labour intensive, and requires a well educated population of women to attend regularly. In the developed world, National Cervical Screening programs exist in many countries, including Australia, and more sophisticated, automated Pap smear screening instruments are avaliable. In developing countries, mass screening by cytology is an unternable proposition, so alternative, less cosntly strategies have had to be developed4. Direct visualization, of the cervix after the application of 5% acetic acid (DVI) appears to be a feasible alternative in such countries5. This technique is aimed at diagnosing pre-invasive disease, and ?down staging? invasive cancer. In the developed world, vast sums of money are spent investigating very minor cytological abnormalities. For example, it is estimated there are 3 million women in the United States each year with pap smears showing low grade squamous intraepithelial lesions (LSIL?s) or atypical squamous cells of undetermined significance (ASCUS). Management options include immediate colposcopy and biopsy, follow-up with repeat smears every 4 ? 6 months and colposcopy if the abnormality persists, or triage using DNA testing for cancer associated HPV types 6. In developing countries, a ? see and treat? policy with relatively cheap modalities such as cryotherapy or LEEP (Loop Electrodiathermy Excision Procedure) for presumed pre-invasive lesions may be reasonable. Once invasive cancer develops, treatment is much more expensive and expertise unevenly distributed. Early cervical cancer may be treated by radical developing countries, which have yet to benefit significantly from the sub-specialization in Obstetrics and Gynaecology which has occurred in most western countries in the last 10-20 years. The developed world is now treating advanced cervical cancer with sophisticated techniques of chemoradiation7, but radiation equipment is scare in developing countries, and so is expertise in the management of advanced carvical cancer. In addition, compliance with treatment is a problem, many women failing to complete therapy once symptoms such as bleeding have been controlled. The great hope for cervical cancer is for some method of primary prevention. It is now believed that cervical cancer is caused by infection with high risk types of the sexually transmitted human papilloma virus (HPV), particularly types 16,18,31 and 45. Primary prevention should be possible through preventing HPV infection, and programs promoting delayed child bearing and sexual monogamy may be appropriate interventions for the developing world8. Several centers in the developed world are working on the development of prophylactic HPV vaccines and these should be a cost effective approach 9. We can only hope their introduction into the developing world is not delayed by low immunization rates in these countries and a shortage of health care workers4. REFERENCE 1. Shanta V, Krishnamurthi S, Gajalakshmi CK, Swaminathan R, Ravichandran K. Epidermilogy of Cancer of the Cervix: global and national perspective. J Indian Med Asso 2000;98 (2): 49-52 2. Jemal A, Thomas A, Murray T, Thun M. Cancer Statistic 2002. CA Cancer J Alin 2002;52:23-47. 3. Sherris J, Herdman C, Eliz C. Cervical Cancer in the developing world. West J Med 2001;175:231-233. 4. Soler ME, Gaffikin L, Blumenthal PD. Cervical cancer screening in deveolping contries. Prim Care Update Ob Gyn 2000;7:118-123. 5. Denny L, Kuhn L, Pollack A, Wright TC, Direct Visual Inspection for cervical cancer screening. Cancer 2002; 94:1699-1707. 6. Soloman D, Schiffman M, Tarone R. for the ALTS Group. Comparison of three management strategies for patients with atypical squamous cell of undetermined significance. Baseline results from a randomized trial. J Nat Cancer Inst 2001; 93:293-299 7. Rose PG, Bundy B, Watkins EB, Thigpen T, Deppe G, Maiman MA et al. Concurrent cisplatin ? based radiotherapy and chemotherapy for locally advabced cervical cancer.N. Engl J Med 1999;340: 1144-1153 8. Drain PK, Holmes KK, Hughes JP, Koustsky LA. Determinantof cervical cancer rates in developing countries. Int J Cancer;2002:100(2):199-205. 9. Harro CD, Pang Y-YS, Roden RBS,Hildesheim A, Wang Z, Reynolds MJ et al. Safety and immunogenicity trial in adult volunteers of a human papillomavirus 16 L1 virus ? like particle vaccine. J Nat Cancer Inst 2001,93:284-292


Profile

Profile .......... Demitrios A Spandidos

Demetrios A. Spandidos is Professor of Virology (since 1989) at the Medical School, University of Crete, Director of Clinical Virology Laboratory (since 1990) at the University Hospital in Heraklion, Crete and he was Research Professor and Director of the Laboratory of Molecular Oncology and Biotechnology (1988 ? 1998) at the Institute of Biological Research and Biotechnology at the National Hellenic Research Foundation in Athens, Greece. He is the founder and Editor of the International Journal of Oncology, Oncology Reports and Intenational Journal of Molecular Medicine. Dr. Spandidos was born in Agios Constantions, Sparta, Greece and obtained his B.S.C. in chemistry from the University of Thessaloniki, Greece in 1971, a Ph.D. in Biochemistry from McGill University in Montreal, Canada in 1976 and a D.Sc. in Genetics from the University of Glasgow, UK in 1989. He is Fellow of the Royal Society of Health (1994) London, UK, Fellow of the Royal College of Pathology (1997) London, UK and corresponding Member of the Academic National de Medicine de Buenos Aires, Argentina (1999). He was an MRC of Canada post-doctoral Fellow at the Department of Medical Genetics at the University of Toronto in 1976-1978, an Assistant Professor (Epimelitics) at the Hellenic Anticancer Institute in Athens in 1978-1979, an MRC of Canada Centennial Fellow at the Beatson Institute for Cancer Research from 1981-1989 when he took up his present appointments in Greece. The identification of cellular oncogenes has probably been the most important discovery in modern cancer research. Prior to their isolation and indentification as cellular homologues of retroviral transforming retroviruses and their oncogenes were experimental artifacts irrelevant to human cancer. Since then an explosion of work has demonstrated the direct relevance of cellular oncogenes and analysis of their role in multistage carcinogenesis. Dr. Spandidos has made extremely important and perhaps unique contributions in these fields. Dr. Spandidos was the first scientist in the field of oncology to develop and apply the gene transfer technique, which has become a most potent tool to investigate oncogenes (D.A.Spandidos and L.Siminovitch, Cell 12: 675-682, 1977; D.A. Spandidos and L. Siminovitch, Nature 271: 259-261, 1978). Thus, his work assisted in development of the gene transfer technology that has been of paramount importance in revealing new oncogenes, as well as implementing the molecular understanding of oncogenes and how the normal proto-oncogenes become activated into their malignant transforming cognates. This field has expanded tremendously over the past twenty years and Dr. Spandidos has continued to contribute actively, playing a major role in his scientific investigations on the ras oncogene. While at the Beatson Institute for Cancer Research in Glasgow he performed notable and important investigations on the nature of transformation of normal cells by introduction of single ras gene using retroviral LTRs and other strong promoters (D.A.Spandidos and N.M.Wilkie, Nature 310: 469-475, 1984; cited over 500 times). Some other ideas of his were very provocative at the time like the dual function of ras genes as oncogenes and onco-suppressors (D.A.Spandidos and N.M.Wilkie, Br J Cancer 58: 67, 1988 and D.A.Spandidos, et al, Anticancer Res 10:1543, 1990) which have now proven to be correct (Z.Zhang, et al, Nature Genet 28: 25, 2001). His most significant work includes the discovery of avian retrovirus (D.A Spandidos and A.E.Graham, J Virol 19: 977, 1976- more than 60 citations), the involvement of ras genes in colon tumours (D.A.Spandidos and I.B.Kerr, Br J Cancer 49:681, 1984 more than 210 citations), the role of ras and myc genes in apoptosis (A.H.Wyllie, K.A.Rose, R.G.Morris, C.M.Steel, E.Foster and D.A.Spandidos, Br J Cancer 56: 251, 1987-more than 185 citations), the involvement of c-myc (J.K Field, D.A Spandidos, et al, Oncogene 4: 1463, 1989- more than 105 citations) and p53 (J.K.Field, D.A.Spandidos, et al, Br J Cancer 64: 573, 1991-more than 240 citations) in head and neck carcinomas. Dr. Spandidos is the most highly cited scientist of the 20th century in all sciences for work performed in the Balkan countries. Dr. Spandidos has organized a number of international meetings on a variety of areas of oncology and molecular medicine and he ha served on the Editorial Boards of a number of journals and he is an Honorary Member of several societies. Dr. Spandidos has authored more than 380 publications, 600 communications and invited talks at international conferences and his work has received over 6000 citations. Although actively occupied in fundamental studies in cell and molecular oncology he has always been ready to explore the medical implications of his work with colleagues in the pathological and clinical sciences and has stimulated work in many different laboratories throughout the world. Part of his efforts has been to establish a scientific tradition in biomedical sciences in Greece, including the successful creation of a school of talented scientists with international recognition. As a result of the efforts of Dr. Spandidos, Greece has been put on the map of biomedical and cancer research at an international level.


Manuscript

Comparison of Whole Body Scintigraphy with Tc-99m-Methoxyisobutylisonitrile and Iodine-131 Na in Patients with Differentiated Thyroid Cancer

Dr Khalid Al-Saleh, Al-Shammeri Iman, Abdul Naseer Mohammed, H S Hooda, Reham Safwat, Al-Mohannadi Shihab

  1. Dr Khalid Al-Saleh
    Department of Radiation Oncology, Kuwait Cancer Control Center, Ministry of Public Health,
  2. Al-Shammeri Iman
  3. Abdul Naseer Mohammed
  4. H S Hooda
  5. Reham Safwat
  6. Al-Mohannadi Shihab

In this study we compared whole body scintigraphy Tc-99M-methoxyisobutylisonitrile (MIBI) and Iodine-131 NA(131I) for detection of residual and/or metastatic disease in well differentiated thyroid carcinoma. Methods: MIBI and I-131 scans were obtained in 60 patients. TSH measurements were done in all the patients prior to scintigraphy. Results: Out of 60 patients, for whom both I-131 and MIBI scans were positive in 59 (98.3%) patients, whereas MIBI scans were positive in only 17 (27%) patients. There was only one patient in which I-131 scan was negative and MIBI scan was positive. Conclusion: I-131 scintigraphy still remains the best way to successfully detect residual/metastatic disease in differentiated thyroid carcinoma.


P53 and Bcl 2 Expression in Breast Cancer. Prospective Study in Tunisia

Mrs Fourati- Kharrat, S Bouraoui, K Rahal, A Gamoudi , M V El May, N Mokni, A El May, M Ben Abdallah

  1. Mrs Fourati- Kharrat
    Service Immuno-Histo-Cytologie, Place Bad Saadoun, 1006 Tunis, Tunisia
  2. S Bouraoui
  3. K Rahal
  4. A Gamoudi
  5. M V El May
  6. N Mokni
  7. A El May
  8. M Ben Abdallah

Aim: Bc12 and P53 genes products continue to be extensively studied in breast cancer in order to identify factors and to optimise therapeutic approaches. We evaluated p53 and bc12 immuno-reactivity in 72 Tunisian breast cancers. Methods and results: a total of 72 paraffin-embedded tumors were evaluated for nuclear p53 and cytoplasmic bc12 immuno-reactivity. The results were semi-quantitated. The P53 over expression was seen in 65% of cases, and was significantly associated with high histological grade (p < 0.001), and correlated inversely to bcl2 (p = 0.02). Bcl2 expression was observed in 54% of cases. No correlation was seen between bcl2 expression and classic prognostic factors. Conclusion: in breast cancer P53 over-expression appears to be indicative of biologic aggressiveness and p53 accumulation reduces expression of bcl2 in tumors.


Post-Mastectomy Breast Restoration Alternatives: Do they have an Impact on Quality of Life Perceptions

Dr Linda. L Reaby

  1. Dr Linda. L Reaby
    RN, PhD
    Associate Professor, School of Nursing, Division of Science and Design, University of Canberra

Quality of life (QOL) perceptions were compared in three groups: 64 women who after post-mastectomy wore the external breast prosthesis, 31 women who after post-mastectomy had undergone breast reconstruction, and 65 women who had not experienced any major health alterations. The mastectomy groups had early breast cancer and were at least two years post diagnosis. The mastectomy groups had early breast cancer and were at least two years post diagnosis. The Ferrans and Powers Quality of Life Index (QLI) was used to measure the groups? QOL perceptions in the domains of health/functioning, socioeconomic, psychological/spiritual, family and overall QOL. The results showed that the prosthesis and reconstruction groups assigned lower satisfaction to long life and health than the control group. The reconstruction group assigned higher satisfaction to personal appearance than the other two groups. The prosthesis and reconstruction groups assigned access to health care as highly important, whereas, the control group assigned a lower satisfaction rating to this item. The study?s findings suggest that QOL perceptions are not greatly influenced by any particular method of breast restoration. This information should be given to women when they are making decisions regarding restoration alternatives. In addition, the findings indicate that women, in the long-term, are capable of adjusting to the impact of breast cancer and the stresses of mastectomy. Health professionals should encourage women newly diagnosed with breast cancer, opportunities to meet with women who have successfully coped with the disease and treatment. Such contact may facilitate rehabilitation, especially in the initial phase. The findings also highlight the need for health professionals to be vigilant about identifying and assisting women who are experience uncertainty related to fear of illness recurrence of illness.


The Majority of Gastric Cancer Metastases from Breast Cancer Lack E-cadherin Expression

Dr Babs Taal, Hans Peterse, Henk Boot

  1. Dr Babs Taal
    Netherlands Cancer Institute/Antoni van Leeuwenhoekhuis,
  2. Hans Peterse
  3. Henk Boot

Gastrointestinal metastases from breast cancer are uncommon, and usually associated with the infrequent lobular type of breast cancer: E-cadherin is important in maintaining the tissue architecture; loss of e-cadherin is generally considered am unfavourable sign, but findings are conflicting. To evaluate the prognostic role of e-cadherin we studied 32 patients with gastric metastases: 22 lobular, 7 ductal and 3 undifferentiated carcinoma. Gastric metastases developed late in the course of the disease (median interval from the primary 58 months). The skeleton was the first manifestation of metastatic disease in 47%. The estrogen receptor was positive in 34% and the progesteron in 28%. In 25 patients (78%) e-cadherin was absent. This finding was not correlated with hormone receptor sttus or the subtype of breast cancer. Response to systemic therapy was 9/20 (45%); median survival from the detection of gastric metastases 10 months with a 2 year survival of 27%. Contrary to expectations, loss of e-cadherin seemed to be a rather favourable, but not statistically significant factor.


Interaction of Bicalutamide and Radiation in Androgen-Dependent and Androgen-Independent Prostate Carcinoma Cells

Dr James A. Bonner, Michael Vander Kooy, Teresa Christianson, A Ahmed, Donald Tindall

  1. Dr James A. Bonner
    MD
    University of Alabama at Birmingham, Department of Radiation Oncology,
  2. Michael Vander Kooy
  3. Teresa Christianson
  4. A Ahmed
  5. Donald Tindall

Purpose: This project was undertaken to determine whether the known bicalutamide-induced growth arrest properties are associated with entry of prostate carcinoma cells into a cell cycle phase that may impact radio-sensitivity. Materials and Methods: An androgen-independent (PC3 Neo) cell line and its counterpart transfected with the androgen receptor (PC3AR) were used for these studies. Cell survival was assessed by colony formation, and cell cycle distributions were assessed by flow cytometry. Results and Conclusions: Exposure to bicalutamide (100 g/ml) produced a progressive accumulation of PC3AR cells in G1, with the maximum increase after 10 hours of exposure (140% of controls). Various pre-radiation exposures (2-24 hours) to bicalutamide did not result in any significant change in baseline radio-sensitivity of the PC3 Neo or PC3AR cells.


Treatment of Women with Metastatic Breast Cancer Forty Years Experience as a Medical Oncologist

Dr Geoffrey Falkson

  1. Dr Geoffrey Falkson
    Department Medical Oncology, University of Pretoria

"The three fates (clotho-birth; lachesis-life; atropos-death) are called cruel because they pay no regard to the wishes of anyone."


Relocation for Specialist Treatment for Pediatric Acute Lymphoblastic Leukemia

Dr Pam McGrath

  1. Dr Pam McGrath
    B.Soc.Wk, MA, Ph.D

Background: Children and young people diagnosed with Acute Lymphoblastic Leukemia (ALL) required the specialised care of a Pediatric Oncologist and of a tertiary pediatric oncology unit. As such, specialised care is only available in the major metropolitan centres, many families must relocate for long periods to access available treatments. Objective: The preliminary research available on relocation is restricted to adult haematological patients, and to date, there is no work exploring the impact of relocation on young families where the child is the patient. In order to address this gap in our knowledge, this article presents the findings on the experience of relocation for families coping with a patient diagnosed with pediatric ALL. Methodology: The findings are from an ongoing longitudinal study following up families referred for specialist treatment for childhood ALL to the Royal Children's Hospital (RCH), Brisbane, Queensland. Phenomenologcial, qualitative research methods have been used at time one (T1) of the three year study. Results: This study clearly demonstrates that relocation for specialist treatment for childhood ALL is highly stressful for families, disrupts their sense of normalcy and challenges their capacity to cope. Recommendations: There is a need for increasing support and assistance to families who have to relocate. Suggestions by participants in this study include improved information prior to transfer to the tertiary hospital, community nursing support and a "mentor or liaison person" to care for the parents during the initial stages of their relocation.


Social Support and Self-Esteem in Patients Afflicted with Cancer in the Reproductive Organs, Including Breasts

Dr Carina Bertero, Inez Johansson

  1. Dr Carina Bertero
    Assistant Professor, University College of Health Science, Department of Nursing Science
  2. Inez Johansson

Social support is generally considered as having positive effects on cancer patients' health and well being by supporting the patient to manage the crisis. But, a cancer diagnosis and its treatment do often have negative effects on self esteem and the cancer patients' life-concepts. The relationship between perceived social support and self-esteem among cancer patients were identified and explored in present study. Two hundred and sixteen respondents, living in the south of Sweden, completed the Norbeck Social Support Questionnaire and the Rosenberg Self-Esteem Scale. The sample consisted of 116 females and 100 males, ranged in the age from 26 to 82. The majority of the sample was married, had children and grandchildren. The average duration of illness was 5 years. The average number of people in each network was 8.0, and relative and friends were most frequently listed. The majority of the sample scored high self-esteem and statistical significance was shown in relation to age. No statistical significance was shown with respect to self-esteem and social support, but moderate correlations were found. Strongest correlations were found between emotional support and self-esteem. Increased knowledge about cancer patients' long term experience is needed in order to perceive them as patients with a chronic disease.


Lung Segmentation: Applications in Chest Radiology

Dr Samuel G Armato III

  1. Dr Samuel G Armato III
    PhD
    Assistant Professor of Radiology, Department of Radiology, The University of Chicago,

Computer-aided diagnostic schemes are being developed to assist radiologists in their medical decision-making tasks. Researchers at The University of Chicago are developing computerized techniques to evaluate chest radiographs and mammograms for potential abnormalities, including cancer. Automated segmentation of the lung fields usually initiates advanced schemes designed to detect pathology in chest radiographs. Details of one such segmentation scheme and its direct application to quantitative image analysis are discussed along with measures of the accuracy of the resulting lung segmentation contours. Lung segmentation in computed tomography (CT) scans is addressed as an initial step towards the automated three-dimensional detection of lung nodules.


Aspects of Diagnostic X-ray Imaging: Improvements in Image Quality and Implications for Radiation Dose

Dr Donald McLean

  1. Dr Donald McLean
    Senior Lecturer, School of Medical Radiation Sciences, University of Sydney

Radiographic image has been a valuable tool in medical diagnosis and has been at the forefront of technological change during the 105 years of its existence. Currently we are experiencing a rapid development in the technology of image receptors and the transfer of subsequent digital images using information technology. History has shown that unbridled technological advance can lead to an unfortunate record in terms of image quality and patient safety1. Recognition this has lead to development of quality assurance practices in radiology, particularly seen in the sub-specialty of mammography. The development of reference standards and levels for image quality and patient dose has allowed the use of uniformly high standard in these areas. Of current concern is the impact of digital image techniques, primarily CT and interventional procedures, which now contribute over 50% of the dose to the population in developed countries. These concerns need to be addressed with the implementation of quality assurance programs that include the measurement and monitoring of such techniques, as well as image quality measures, as new technical developments become available.



Molecular Basis of Cancer, General Considerations: Dual Effects of Adenovirus E1A Gene as Tumor Suppressor Gene and as Oncogene

Dr Santiago Ramon y Cajal Agueras

  1. Dr Santiago Ramon y Cajal Agueras
    Clinica Puerta de Hierro, C/Scan Martin de Porres

In this article, same important points regarding human carcinogenesis are discussed. Oncogenes, tumor heterogeneity and the adenovirus E1A gene as a tumor suppressor gene and as an oncogene are also summarized. Our previous studies dealt with the tumor variability induced by the activation of different oncogenes at the morphological and biological levels, as well as in response to anti-tumor, chemo-therapeutic and radio-therapeutic agents. Using a model of non-tumorigenic keratinocytes, we demonstrated that the adenovirus E1A gene induces a marked sensitivity to chemotherapeutic agents and gamma radiation. We also demonstrated, that in murine and human malignant tumor cell lines with multiple genetic alternations, including a mutated p53 gene or H-ras or E6 from HPVm were very sensitive to DNA-damaging agents after expression of the adenovirus E1A gene. We have studied the vivo effect of the expression on the malignant cells and after the infection with retrovirus ?E1A or with adenoviruses defective of both E1B genes, which can counteract the effects the effects of both E1B genes, which can counteract the effects of the E1A. In summary, we have shown that: a) The constitutive expression of the E1A gene in carcinoma cells and the injection of retrovirus E1A gene in producer cells in tumors is associated with a decrease in the tumorigenicity in vivo. b) Infection by E1B-defective adenoviruses increase the cellular cytotoxic response to treatment with cisplatin and radiotherapy. c) On the basis of these results, which demonstrate the in vivo anti-tumor effect of adenovirus E1A gene and a marked sensitization to DNA-damaging anti-tumor agents, we propose that adenovirus E1A gene can be considered as a new approach in anti-tumor gene therapy.

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