Research on cancer diagnosis in Malaysia: current status

Cancer is a major morbidity and mortality concern in Malaysia. Based on National Cancer Registry data, the Malaysian population is estimated to bear a cancer burden of about 40,000 new cases per year, and a cumulative lifetime risk of about 1:4. Cancer research in Malaysia has to consider needs relevant to our population, and resources constraints. Hence, funding bodies prioritise cancers of high prevalence, unique to our community and posing specific clinical problems. Cancer diagnosis is crucial to cancer management. While cancer diagnosis research largely aims at improvements in diagnostic information towards more appropriate therapy, it also impacts upon policy development and other areas of cancer management. The scope of cancer diagnosis upon which this paper is based, and their possible impact on other R&D areas, has been broadly categorized into: (1) identification of aetiological agents and their linkages to the development of precancer and cancer (impact on policy development, cancer prevention and treatment), (2) cancer biology and pathogenesis (impact on cancer prevention, treatment strategies and product development), (3) improvements in accuracy, sensitivity and specificity in cancer detection, monitoring and classification (impact on technology development) and (4) prognostic and predictive parameters (impact on treatment strategies). This paper is based on data collected by the Working Group on Cancer Diagnosis Research for the First National Conference on Cancer Research Coordination in April 2004. Data was collated from the databases of Institutions/Universities where the authors are employed, the Ministry of Science, Technology and Innovation (MOSTI) and targeted survey feedback from key cancer researchers. Under the 7th Malaysia Plan, 76 cancer projects were funded through the Intensified Research in Priority Areas (IRPA) scheme of MOSTI, amounting to almost RM15 million of grant money. 47(61.8%) of these projects were substantially in cancer diagnosis, accounting for 65.6% (RM 9.7 million) of cancer project funds. The 8th Malaysia Plan saw a change in research strategy. The IRPA agency fielded several top-down projects which encouraged a multicentre and multidisciplinary approach. This resulted in larger funding per project i.e. RM32 million for 49 projects. There was also a surge of interest in drug development and natural products. Because of this shift in direction, cancer diagnosis projects constituted only 51% of IRPA-funded cancer projects. Nonetheless funding for cancer diagnosis research has exceeded that of the 7th Malaysia Plan, being RM12.5 million by March 2004. The majority of such research is carried out at the Universities, engaging a large number of young scientists and postgraduate students (51 MSc and 21 PhD). A lot of research findings presented at scientific meetings have not yet been published and there is a glaring shortage of patents and commercialization of research findings (such as creation of test kits). Because diagnosis is very much a part of clinical practice, many researchers felt satisfied and confident that their work will be translated into practice and will significantly improve diagnostic services in Malaysia. National guidelines and consensus development on at least three malignancies i.e. breast cancer, oral cancer and lymphoma, have substantial basis in local R&D work. Problems encountered in research included (1) insufficient funding to realize research objectives, (2) lack of local expertise (most research assistants are inexperienced BSc graduates with no or minimal research experience), (3) inadequate technical support from vendors during equipment failure, (4) inexperienced Institutional development units to assist in product development, (5) lack of venture capital for commercialization of findings, and (6) inadequate incentives to undertake research. Researchers pointed out that plans to promote research should include the establishment of (1) regional and national cancer tissue banks, (2) a National Cancer Research Institute, (3) a dedicated cancer research fund, (4) a registry of cancer researchers, (5) national research coordinators, (6) improved coverage by the National Cancer Registry, (7) more international collaboration, (8) a better career structure for researchers, (9) improved Institutional support for product realization, and (10) better recognition for cancer researchers.     

Survival Rate and Prognostic Factors for Colorectal Cancer in Sabah,Borneo, Malaysia: A Retrospective Cohort of a Population-Based Study

Background: Colorectal cancer is a major public health problem with significant number of cases and death in the population. This study aimed to determine the 5-year overall survival rate and the prognostic factors for colorectal cancer patients in Sabah. Methods: This was a retrospective cohort study conducted using secondary data from Malaysian National Cancer Registry (MNCR) database. A 5-year overall survival and the median survival time were determined with Kaplan-Meier survival curve. Cox regression analysis was done to determine the prognostic factors on survival. Results: A total of 1,152 patients were included in this study. The majority of the patients had colon cancer and presented at late stage (stage III and IV) as compared to early stage (stage I and II). From the analysis, the 5-year overall survival for colorectal cancer was 23.2% (95% CI: 21.8, 24.6) and the median survival time was 16 months (95% CI: 14.3, 17.7).  Higher survivals are seen in males (23.6%, 95% CI: 20.4, 24.7), aged 50-74 years old (24.2%, 95% CI: 22.4, 26.0), Chinese (25.5%, 95% CI: 23.0, 28.0), lived in Keningau (25.6%, 95% CI: 20.8, 30.4), colon as primary tumor site (24.5%, 95% CI: 22.5, 26.4), diagnosed with stage I (55.6%, 95% CI: 48.7, 62.5) and received surgery with chemotherapy or radiotherapy (31.3%, 95% CI: 27.8, 34.8). The significant prognostic factor was the stage at diagnosis. Patients with stage IV colorectal cancer (HR: 11.18; 95% CI: 3.48, 35.93) had eleven times risk of dying as compared to stage I. Conclusion: The survival rate for colorectal cancer patients in Sabah was comparatively lower than other states in Malaysia and in some Asian countries. Those patients who presented at later stage had poorer survival. Health promotion and community-based screening program should be emphasized in addition to encouraging early diagnosis to improve survival.     

Two new sarpagine-type indole alkaloids and antimalarial activity of 16-demethoxycarbonylvoacamine from Tabernaemontana macrocarpa Jack

Journal of Natural Medicines - Two new sarpagine-type indole alkaloids (1 and 2), together with five known alkaloids; 12-methoxy-4-methylvoachalotine (3), 16-demethoxycarbonylvoacamine (4),...     

Primitive neuroectodermal tumor of the lung with pericardial extension: a case report

A 16-year-old student presented with a 4-week history of progressive shortness of breath, loss of appetite, and occasional blood-tinged sputum. The chest X-ray revealed massive right-sided pleural effusion with cardiomegaly. An echocardiogram revealed a large pericardial mass with massive pericardial effusion. Subsequent computed tomography of the thorax revealed a large heterogeneous mass in the right lung with extension into the pericardium. Lung biopsy revealed primitive neuroectodermal tumor (PNET) with small round blue cells, Homer–Wright rosettes, and CD99 positivity. We discuss pericardial metastases of PNET and its implication in this patient.     

Mass attenuation coefficient of tannin-added <Emphasis Type="Italic">Rhizophora</Emphasis> spp. particleboards at 16.59–25.56 keV photons,and <Superscript>137</Superscript>Cs and <Superscript>60</Superscript>Co gamma energies

The aim of this study was to determine the suitability of tannin-added Rhizophora spp. particleboards as phantom materials in the application of low- and high-energy photons. The tannin-added Rhizophora spp. particleboards and density plug phantoms were created with a target density of 1.0 g/cm³. The elemental composition and effective atomic number of the particleboards were measured using energy dispersive X-ray analysis. The mass attenuation coefficient of the particleboards for low-energy photons were measured using the attenuation of X-ray fluorescence. The mass attenuation coefficients of high-energy photons were measured using the attenuation of ¹³⁷Cs and ⁶⁰Co gamma energies. The results were compared to the calculated value of water using XCOM calculations. The results showed that the effective atomic number and mass attenuation coefficients of tannin-added Rhizophora spp. particleboards were similar to those of water, indicating the suitability of tannin-added Rhizophora spp. particleboards as phantom materials for low- and high-energy photons.     

Organ transplantation in Malaysia: a need for a comprehensive legal regime

Organ transplantation has become increasingly routine as a means of saving and improving the quality of lives of thousands of people each year. However, transplant activity is increasingly constrained by the shortage of organs. The major impediment in procuring organs for transplant in Malaysia is the lack of cadaveric donors. The lack of cadaveric donors has encouraged patients to go to countries like India and China to purchase organs especially kidneys for transplantation. The inadequacies of the existing Malaysian Human Tissues Act 1974 has also contributed to this problem. For instance, the word 'tissue" is not defined under the Act. This raises complex and ethical questions as to the scope of the definition for "tissue". There is also no definition of "the person lawfully in possession of the body." This is significant as he is the person who is empowered by the Act to authorise removal of tissue. Further, there is also no articulation of a hierarchy of relatives who are deemed the next of kin. In a situation involving a large number of relatives, asserting different opinions, this may pose a problem. The articulation of a priority list is particularly difficult in Malaysia as it is a multi-cultural society where the hierarchy of relatives with the right to claim decision-making powers may vary in different cultures. Furthermore, there is also a pressing need for a legislation to ensure that the rights of potential live donors are protected. At the moment, the Human Tissues Act 1974 only relates to cadaveric donors whereas live donors fall within the purview of the common law. The system of "opting out" should be considered in Malaysia whereby every individual is presumed to be a donor unless he or she registers an objection. But this system can only be fair if every person in the community is given notice of the law and understands its implications. For the system to work, there must also exist a simple and effective way of registering objections. There is a need for continuous intensive public education and counselling. A nationally co-ordinated mechanism must be in place to ensure effectiveness of identifying potential donors and recipients.     

PMEPA1/TMEPAI isoforms function via its PY and Smad‐interaction motifs for tumorigenic activities of breast cancer cells

PMEPA1 (prostate transmembrane protein, androgen‐induced 1)/TMEPAI (transmembrane prostate androgen‐induced protein) is highly expressed in diverse cancers, including breast, lung and prostate cancers. It consists of four isoforms with distinct extracellular regions (isoforms a‐d). The expression and function of these isoforms are still poorly understood. Hence, we aimed to identify the preferentially expressed isoforms in breast cancer cells and analyze possible differences in tumorigenic functions. In this study, we used 5′ Rapid Amplification of cDNA Ends (RACE) and Western blot analyses to identify the mRNA variants and protein isoforms of TMEPAI and found that TMEPAI isoform d as the major isoform expressed by TGF‐β stimulation in breast cancer cells. We then generated CRISPR/Cas9‐mediated TMEPAI knockout (KO) breast cancer cell lines and used a lentiviral expression system to complement each isoform individually. Although there were no clear functional differences between isoforms, double PPxY (PY) motifs and a Smad‐interaction motif (SIM) of TMEPAI were both essential for colony and sphere formation. Collectively, our results provide a novel insight into TMEPAI isoforms in breast cancer cells and showed that coordination between double PY motifs and a SIM of TMEPAI are essential for colony and sphere formation but not for monolayer cell proliferation.     

Withdrawing and withholding medical treatment: a comparative study between the Malaysian, English and Islamic law

The permissibility and lawfulness of withdrawing and withholding medical treatment has attracted considerable debates and criticisms, as the legal issues are drawn into entering the slippery slope of euthanasia. Proponents of "sanctity of life" views that withdrawing and withholding medical treatment with knowledge that death would result is still within the sphere of euthanasia, whereas proponents of "quality of life" argue that it is not, as death is not intended. Their arguments maintain that for patients who are totally dependant on machines to ensure the work of some bodily functions, living may amount to little more than survival as dying is prolonged. Furthermore, the prolonging of life of the dying patient has profound implications on patients themselves, their relatives, dependants and medical providers. Thus, withdrawing and withholding medical treatment would not only respect a patient's right to self-determination, by allowing them to die in their underlying condition, but will ensure that medical providers are able to concentrate on more worthwhile treatments. This paper discusses the intractable difficulties with the moral distinction between withholding and withdrawing treatment and euthanasia, as well as makes a comparative study between the present state of law in Malaysia and England on this issue. The paper further highlights the differences between civil law and Islamic law in this controversial area.