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Higher Rates of Anatomical Insertion of Medial Hamstring Tendon Regeneration Post-Anterior Cruciate Ligament Reconstruction with Stump Preservation Graft Harvesting Technique: A Prospective, Randomized, Double-Blinded Clinical Trial with Magnetic Resonance Imaging Evaluation

Low CA, Teo SH

J ISAKOS, 2024 Apr 25.
PMID: 38677365 DOI: 10.1016/j.jisako.2024.04.013

OBJECTIVE: (s): The purpose of this study was to compare the regeneration of semitendinosus and gracilis tendons from two different graft harvesting techniques which are the stump preservation and conventional graft harvesting technique. We hypothesised that the stump preservation graft harvesting technique which preserved the distal attachment of tendons at their insertion would facilitate anatomical regeneration to the pes anserinus.
METHODS: This is a prospective, randomised double-blinded study whereby thirty consecutive patients who underwent single bundle anterior cruciate ligament reconstruction with ipsilateral semitendinosus and gracilis autografts were recruited. The patients were randomly assigned to the stump preservation group (14 patients) or conventional group (16 patients). magnetic resonance imaging (MRI) evaluation was performed preoperatively and at 6-months postoperatively.
RESULTS: At 6-months follow-up, MRI evaluations showed a higher percentage of insertion of regenerated semitendinosus and gracilis at the pes anserinus in the stump preservation group (75.0%) than that in the conventional group (68.8%). There was significantly higher proximal shift of musculotendinous junction of semitendinosus (5.70 cm versus 3.36 cm, p = 0.029) and gracilis (5.28 cm versus 3.16 cm, p = 0.045) in the conventional group postoperatively.
CONCLUSION: The stump preservation technique yields higher percentage of anatomical insertion of regenerated tendons and lesser amount of proximal shift of musculotendinous junction.
LEVEL OF EVIDENCE: III - Prospective study with up to two negative criteria.
Fulltext A review of breast cancer research in Malaysia

Yip CH, Bhoo Pathy N, Teo SH

Med J Malaysia, 2014 Aug;69 Suppl A:8-22.
PMID: 25417947 MyJurnal

Four hundred and nineteen articles related to breast cancer were found in a search through a database dedicated to indexing all original data relevant to medicine published in Malaysia between the years 2000-2013. One hundred and fifty four articles were selected and reviewed on the basis of clinical relevance and future research implications. Overall, Malaysian women have poor survival from breast cancer and it is estimated that half of the deaths due to breast cancer could be prevented. Five-year survival in Malaysia was low and varies among different institutions even within the same disease stage, suggesting an inequity of access to optimal treatment or a lack of compliance to optimal treatment. Malaysian women have poor knowledge of the risk factors, symptoms and methods for early detection of breast cancer, leading to late presentation. Moreover, Malaysian women experience cancer fatalism, belief in alternative medicine, and lack of autonomy in decision making resulting in delays in seeking or avoidance of evidence-based medicine. There are ethnic differences in estrogen receptor status, HER2 overexpression and incidence of triple negative breast cancer which warrant further investigation. Malay women present with larger tumours and at later stages, and even after adjustment for these and other prognostic factors (stage, pathology and treatment), Malay women have a poorer survival. Although the factors responsible for these ethnic differences have not been elucidated, it is thought that pharmacogenomics, lifestyle factors (such as weight-gain, diet and exercise), and psychosocial factors (such as acceptance of 2nd or 3rd line chemotherapy) may be responsible for the difference in survival. Notably, survivorship studies show self-management programmes and exercise improve quality of life, highlighting the need to evaluate the psychosocial impact of breast cancer on Malaysian women, and to design culturally-, religiously- and linguistically-appropriate psycho-education programmes to help women cope with the disease and improve their quality of life. Research done in the Caucasian populations may not necessarily apply to local settings and it is important to embark on local studies particularly prevention, screening, diagnostic, prognostic, therapeutic and psychosocial research.
Fulltext The great mimic again? A case of tuberculosis knee

Teo Sh, Teh K, Azura L, Ng Y

Malays Orthop J, 2011 Nov;5(3):32-4.
PMID: 25279034 MyJurnal DOI: 10.5704/MOJ.1111.005

Tuberculosis (TB), once a disease confined to undeveloped or developing nations is currently in resurgence due to pandemic human immunodeficiency virus infection and immigration from endemic areas. TB is also known as the 'great mimicker'. Extra-pulmonary tuberculosis affecting the knee is rare in all forms of TB (0.1-0.3%). Here, we report a case of isolated highly erosive TB knee in a previously fit Burmese migrant worker. He presented with after a history of fall into a drain. The patient also reported pain and swelling over his left knee for the previous three years. He had been treated for a bacterial infection of the knee in another hospital but defaulted due to financial constraints. Arthrotomy of the knee was performed including washout. Diagnosis of TB of the knee was made based on the synovial fluid and tissue culture. Treatment with antituberculosis drugs was then initiated.
Systematic review and meta-analysis of lifestyle and reproductive factors associated with risk of breast cancer in Asian women

Ang BH, Teo SH, Ho WK

Cancer Epidemiol Biomarkers Prev, 2024 Jul 17.
PMID: 39018331 DOI: 10.1158/1055-9965.EPI-24-0005

INTRODUCTION: Assessing breast cancer risks from lifestyle and reproductive factors is critical for developing population-specific risk prediction tools. However, limited studies have evaluated these risks in recent Asian birth cohorts.
METHODS: We systematically reviewed articles published from January 2010 to December 2023, examining breast cancer risk factors in Asian women. Data were described narratively, estimates pooled, and prevalence and attributable proportions compared across Asian populations.
RESULTS: Of the 128 studies reviewed, 103 reported adjusted effect sizes for meta-analysis. Lifestyle and reproductive factors were predictive of breast cancer risk in Asian women, with varying impacts on pre-menopausal and post-menopausal women. Relative risks were similar within Asian populations and in comparison to European populations, except for menarche, menopause, and hormone receptor therapy. However, risk factor distributions differed across populations. Whilst alcohol intake (21%) and oral contraceptive use (20%) emerged as the most attributable modifiable risk factors in Europeans, passive smoking (24%) and higher BMI (17%,≥24kg/m2 among post-menopausal women) were predominant in Asians.
CONCLUSION: Our study shows that whilst the effects of lifestyle and reproductive breast cancer risk factors are largely similar across different populations, their distributions vary.
IMPACT: Our analysis underscores the importance of considering population-specific risk factor distributions when developing risk prediction tools for Asian populations.
Zebrafish: predictive model for targeted cancer therapeutics from nature

Zulkhernain NS, Teo SH, Patel V, Tan PJ

Curr Cancer Drug Targets, 2014;14(8):764-73.
PMID: 25348017 DOI: 10.2174/1568009614666141028121347

Targeted therapy, the treatment of cancer based on an underlying genetic alteration, is rapidly gaining favor as the preferred therapeutic approach. To date, although natural products represent a rich resource of bio-diverse drug candidates, only a few have been identified to be effective as targeted cancer therapies largely due to the incompatibilities to current high-throughput screening methods. In this article, we review the utility of a zebrafish developmental screen for bioactive natural product-based compounds that target signaling pathways that are intimately shared with those in humans. Any bioactive compound perturbing signaling pathways identified from phenotypic developmental defects in zebrafish embryos provide an opportunity for developing targeted therapies for human cancers. This model provides a promising tool in the search for targeted cancer therapeutics from natural products.
Fulltext A cross sectional study on the motivators for Asian women to attend opportunistic mammography screening in a private hospital in Malaysia: the MyMammo study

Hassan N, Ho WK, Mariapun S, Teo SH

BMC Public Health, 2015;15:548.
PMID: 26065413 DOI: 10.1186/s12889-015-1892-1

To date, because of limited budgets and lower incidence of breast cancer, the majority of Asian countries do not have population-based screening programmes, but instead offer opportunistic screening. However, there have been few studies which have assessed the motivators for women attending such programmes and the appropriateness of the programmes in terms of targeting women at risk.
Fulltext The impact of COVID-19 pandemic on orthopaedic specialty in Malaysia: A cross-sectional survey

Teo SH, Abd Rahim MR, Nizlan NM

J Orthop Surg (Hong Kong), 2020 7 24;28(2):2309499020938877.
PMID: 32700619 DOI: 10.1177/2309499020938877

PURPOSE: This study aims to investigate further how the coronavirus disease 2019 (COVID-19) pandemic is affecting orthopaedic surgeon in Malaysia in terms of exposure, general perceptions of risk, and the impact on their current and future practice.
METHODS: Orthopaedic surgeons nationwide were invited through email and text messages to answer an online self-administered questionnaire collecting demographic information, COVID-19 exposure experience, perception of risk, and impact on orthopaedic practice.
RESULTS: Of the respondents, 4.7% and 14.0% were involved in frontline treatment for COVID-19 patients with non-orthopaedic and orthopaedic problem, respectively. Respondents working in Ministry of Health had highest percentage of involvement as frontliner, 7.8% (8/103) and 20.4% (21/103) for non-orthopaedic and orthopaedic related COVID-19 treatment, respectively (not significant). Their main concern was an infection of family members (125/235, 53.2%). Majority of respondents were still working (223/235, 94.9%), running outpatient clinics (168/223, 75.3%), and continued with their semi-emergency (190/223, 85.2%) and emergency surgeries (213/223, 95.5%). Of the surgeons, 11.2% (25/223) did not screen their patients for COVID-19 prior to elective surgeries, 30.9% (69/223) did not have any training on proper handling of personal protective equipment (PPE), 84.8% (189/223) make decision to manage more conservatively due to COVID-19 and 61.9% (138/223) had their income affected. Of the surgeons, 19.3% (43/223) started using telehealth facilities.
CONCLUSION: Direct exposure to treatment of COVID-19 patients among the respondent is low and the main concern was infecting their family member. There are still several surgeons who did not conduct preoperative COVID-19 screening and practice without proper PPE training.
CHEK2*1100delC does not contribute to risk to breast cancer among Malay, Chinese and Indians in Malaysia

Thirthagiri E, Cheong LS, Yip CH, Teo SH

Fam Cancer, 2009;8(4):355-8.
PMID: 19399639 DOI: 10.1007/s10689-009-9244-x

A truncating mutation (1100delC) in the cell cycle checkpoint kinase-2 gene, CHEK2, has been identified as a risk factor for familial and sporadic breast cancer in some Northern and Western European populations. However, the prevalence of CHEK2*1100delC in breast cancer appears to be population dependent. We analysed the prevalence of CHEK2*1100delC in 668 breast cancer cases, of which 542 were invasive breast cancers, from a hospital-based cohort of breast cancer patients from Kuala Lumpur, Malaysia. The variant was not found in any patients in this cohort, suggesting that CHEK2*1100delC is rare in our population, and unlikely to contribute significantly to risk to breast cancer among the Malay, Chinese and Indian ethnic groups in Malaysia. This suggests that screening for this allele should not be routinely conducted in Malaysia.
Fulltext Performance of a subsidised mammographic screening programme in Malaysia, a middle-income Asian country

Lee M, Mariapun S, Rajaram N, Teo SH, Yip CH

BMC Public Health, 2017 01 28;17(1):127.
PMID: 28129762 DOI: 10.1186/s12889-017-4015-3

BACKGROUND: The incidence of breast cancer in Asia is increasing because of urbanization and lifestyle changes. In the developing countries in Asia, women present at late stages, and mortality is high. Mammographic screening is the only evidence-based screening modality that reduces breast cancer mortality. To date, only opportunistic screening is offered in the majority of Asian countries because of the lack of justification and funding. Nevertheless, there have been few reports on the effectiveness of such programmes. In this study, we describe the cancer detection rate and challenges experienced in an opportunistic mammographic screening programme in Malaysia.
METHODS: From October 2011 to June 2015, 1,778 asymptomatic women, aged 40-74 years, underwent subsidised mammographic screening. All patients had a clinical breast examination before mammographic screening, and women with mammographic abnormalities were referred to a surgeon. The cancer detection rate and variables associated with a recommendation for adjunct ultrasonography were determined.
RESULTS: The mean age for screening was 50.8 years and seven cancers (0.39%) were detected. The detection rate was 0.64% in women aged 50 years and above, and 0.12% in women below 50 years old. Adjunct ultrasonography was recommended in 30.7% of women, and was significantly associated with age, menopausal status, mammographic density and radiologist's experience. The main reasons cited for recommendation of an adjunct ultrasound was dense breasts and mammographic abnormalities.
DISCUSSION: The cancer detection rate is similar to population-based screening mammography programmes in high-income Asian countries. Unlike population-based screening programmes in Caucasian populations where the adjunct ultrasonography rate is 2-4%, we report that 3 out of 10 women attending screening mammography were recommended for adjunct ultrasonography. This could be because Asian women attending screening are likely premenopausal and hence have denser breasts. Radiologists who reported more than 360 mammograms were more confident in reporting a mammogram as normal without adjunct ultrasonography compared to those who reported less than 180 mammograms.
CONCLUSION: Our subsidised opportunistic mammographic screening programme is able to provide equivalent cancer detection rates but the high recall for adjunct ultrasonography would make screening less cost-effective.
Change in gait after high tibial osteotomy: A systematic review and meta-analysis

Lee SH, Lee OS, Teo SH, Lee YS

Gait Posture, 2017 09;57:57-68.
PMID: 28577508 DOI: 10.1016/j.gaitpost.2017.05.023

We conducted a meta-analysis to analyze how high tibial osteotomy (HTO) changes gait and focused on the following questions: (1) How does HTO change basic gait variables? (2) How does HTO change the gait variables in the knee joint? Twelve articles were included in the final analysis. A total of 383 knees was evaluated. There were 237 open wedge (OW) and 143 closed wedge (CW) HTOs. There were 4 level II studies and 8 level III studies. All studies included gait analysis and compared pre- and postoperative values. One study compared CWHTO and unicompartmental knee arthroplasty (UKA), and another study compared CWHTO and OWHTO. Five studies compared gait variables with those of healthy controls. One study compared operated limb gait variables with those in the non-operated limb. Gait speed, stride length, knee adduction moment, and lateral thrust were major variables assessed in 2 or more studies. Walking speed increased and stride length was increased or similar after HTO compared to the preoperative value in basic gait variables. Knee adduction moment and lateral thrust were decreased after HTO compared to the preoperative knee joint gait variables. Change in co-contraction of the medial side muscle after surgery differed depending on the degree of frontal plane alignment. The relationship between change in knee adduction moment and change in mechanical axis angle was controversial. Based on our systematic review and meta-analysis, walking speed and stride length increased after HTO. Knee adduction moment and lateral thrust decreased after HTO compared to the preoperative values of gait variables in the knee joint.
Fulltext Surgery for BRCA, TP53 and PALB2: a literature review

Song CV, Teo SH, Taib NA, Yip CH

Ecancermedicalscience, 2018;12:863.
PMID: 30174725 DOI: 10.3332/ecancer.2018.863

Introduction: The presence of a deleterious mutation, most commonly a BRCA mutation, has a tremendous impact on the management of breast cancer. We review the surgical management of BRCA mutation carriers, and two other potentially high-risk mutations, TP53 and PALB2.
Methodology: A search was done on PubMed, limited to reviews and the English language only. The search terms used were 'BRCA' or 'PALB2' or 'TP53' and 'surgery'. Fifteen articles were identified by searching and one article was obtained from other sources.
Results: Breast-conserving surgery has equivalent survival, but may have an increased risk of local recurrence, compared to mastectomy among BRCA mutation carriers. Contralateral prophylactic mastectomy may not improve overall survival, despite reducing the risk of developing contralateral breast cancer. The use of preoperative genetic testing allows patients to have combined curative and prophylactic surgery. However, preoperative genetic testing may influence patients to make rash decisions. In healthy BRCA mutation carriers, bilateral prophylactic mastectomy is done to prevent breast cancer from occurring. Bilateral prophylactic mastectomy is highly effective in reducing the risk of breast cancer in healthy BRCA mutation-positive women and may have a survival benefit. Prophylactic oophorectomy reduces the risk of ovarian cancer, but may not have an effect on the risk of breast cancer. There is a lack of studies on surgery for non-BRCA mutations. TP53 and PALB2 are potentially high-risk mutations for breast cancer, which may justify the use of prophylactic surgery. Advice should be given on a case-by-case basis.
Conclusion: A comprehensive approach is needed to provide optimum treatment for breast cancer patients with deleterious mutations.
p53 Status does not affect photodynamic cell killing induced by hypericin

Lee HB, Ho AS, Teo SH

Cancer Chemother Pharmacol, 2006 Jul;58(1):91-8.
PMID: 16211395

Given that p53 is a tumor suppressor that plays a central role in the cellular response to DNA damage and that more than 50% of all cancers have mutated p53, the wider utility of photodynamic therapy (PDT) in the treatment of cancer will depend on an understanding of whether p53 status modulates response to PDT. In this study, we investigated the photosensitivity of isogenic cell lines that differ only in their p53 status to PDT using hypericin as the photosensitizer.
Fulltext Seeded Growth Route to Noble Calcium Carbonate Nanocrystal

Islam A, Teo SH, Rahman MA, Taufiq-Yap YH

PLoS One, 2015;10(12):e0144805.
PMID: 26700479 DOI: 10.1371/journal.pone.0144805

A solution-phase route has been considered as the most promising route to synthesize noble nanostructures. A majority of their synthesis approaches of calcium carbonate (CaCO3) are based on either using fungi or the CO2 bubbling methods. Here, we approached the preparation of nano-precipitated calcium carbonate single crystal from salmacis sphaeroides in the presence of zwitterionic or cationic biosurfactants without external source of CO2. The calcium carbonate crystals were rhombohedron structure and regularly shaped with side dimension ranging from 33-41 nm. The high degree of morphological control of CaCO3 nanocrystals suggested that surfactants are capable of strongly interacting with the CaCO3 surface and control the nucleation and growth direction of calcium carbonate nanocrystals. Finally, the mechanism of formation of nanocrystals in light of proposed routes was also discussed.
Fulltext Variants in 6q25.1 Are Associated with Mammographic Density in Malaysian Chinese Women

Mariapun S, Ho WK, Kang PC, Li J, Lindström S, Yip CH, et al.

Cancer Epidemiol Biomarkers Prev, 2016 Feb;25(2):327-33.
PMID: 26677210 DOI: 10.1158/1055-9965.EPI-15-0746

Mammographic density is an established risk factor for breast cancer and has a strong heritable component. Genome-wide association studies (GWAS) for mammographic density conducted in women of European descent have identified several genetic associations, but none of the studies have been tested in Asians. We sought to investigate whether these genetic loci, and loci associated with breast cancer risk and breast size, are associated with mammographic density in an Asian cohort.
Fulltext Ethnic differences in mammographic densities: an Asian cross-sectional study

Mariapun S, Li J, Yip CH, Taib NA, Teo SH

PLoS One, 2015;10(2):e0117568.
PMID: 25659139 DOI: 10.1371/journal.pone.0117568

BACKGROUND: Mammographic density is a strong risk factor for breast cancer and is highly variable, but, to date, few studies have examined density in Asian women, particularly those in low and middle-income Asian countries where genetic and lifestyle determinants may be significantly different.
METHODS: A total of 1,240 women who attended an opportunistic mammogram screening programme were eligible for analysis. Mammographic density was estimated using a fully-automated thresholding method and differences across ethnic groups were examined using linear regression in 205 randomly selected Chinese women, 138 Malay and 199 Indian women.
RESULTS: Percent density was significantly higher in Chinese women (28.5%; 95% CI 27.0%, 30.0%) compared to Malay (24.2%; 95% CI 22.5%, 26.0%) and Indian (24.3%; 95% CI 22.8%, 25.7%) women (p<0.001), after adjustment for age, BMI, menopausal status, parity and age at first full term pregnancy. Correspondingly, adjusted nondense area was significantly lower in Chinese (72.2cm2; 95% CI 67.9cm2, 76.5cm2) women compared to Malay (92.1cm2; 95% CI 86.9cm2, 97.2cm2) and Indian (97.7cm2; 95% CI 93.4cm2, 101.9cm2) women (p<0.001), but dense area did not differ across the three ethnic groups.
CONCLUSIONS: Our study shows that higher percent density and lower nondense area reflect the higher incidence of breast cancer in Chinese compared to Malay and Indian women in Malaysia. Known lifestyle determinants of mammographic density do not fully account for the ethnic variations observed in mammographic density in this Asian cohort.
Fulltext The decision-making journey of Malaysian women with early breast cancer: a qualitative study

Abdullah A, Abdullah KL, Yip CH, Teo SH, Taib NA, Ng CJ

Asian Pac J Cancer Prev, 2013;14(12):7143-7.
PMID: 24460266

BACKGROUND: The survival outcomes for women presenting with early breast cancer are influenced by treatment decisions. In Malaysia, survival outcome is generally poor due to late presentation. Of those who present early, many refuse treatment for complementary therapy.
OBJECTIVE: This study aimed to explore the decision making experiences of women with early breast cancer.
MATERIALS AND METHODS: A qualitative study using individual in-depth interviews was conducted to capture the decision making process of women with early breast cancer in Malaysia. We used purposive sampling to recruit women yet to undergo surgical treatment. A total of eight participants consented and were interviewed using a semi-structured interview guide. These women were recruited from a period of one week after they were informed of their diagnoses. A topic guide, based on the Ottawa decision support framework (ODSF), was used to facilitate the interviews, which were audio recorded, transcribed and analysed using a thematic approach.
RESULTS: We identified four phases in the decision-making process of women with early breast cancer: discovery (pre-diagnosis); confirmatory ('receiving bad news'); deliberation; and decision (making a decision). These phases ranged from when women first discovered abnormalities in their breasts to them making final surgical treatment decisions. Information was vital in guiding these women. Support from family members, friends, healthcare professionals as well as survivors also has an influencing role. However, the final say on treatment decision was from themselves.
CONCLUSIONS: The treatment decision for women with early breast cancer in Malaysia is a result of information they gather on their decision making journey. This journey starts with diagnosis. The women's spouses, friends, family members and healthcare professionals play different roles as information providers and supporters at different stages of treatment decisions. However, the final treatment decision is influenced mainly by women's own experiences, knowledge and understanding.
Study site: Breast surgical units, Klang Valley, Malaysia
Artomandin, a new xanthone from Artocarpus kemando (Moraceae)

Ee GC, Teo SH, Rahmani M, Lim CK, Lim YM, Go R

Nat Prod Res, 2011 Jun;25(10):995-1003.
PMID: 21644180 DOI: 10.1080/14786419.2010.534471

A new furanodihydrobenzoxanthone, artomandin (1), together with three other flavonoid derivatives, artoindonesianin C, artonol B, and artochamin A, as well as β-sitosterol were isolated from the stem bark of Artocarpus kemando. The structures of these compounds were determined on the basis of spectral evidence. All of these compounds displayed inhibition effects to a very susceptible degree in cancer cell line tests. Compound 1 also exhibited significant antioxidant capacity in the free radical 1,1-diphenyl-2-picrylhydrazyl tests.
Fulltext Clinical characteristics of triple-negative breast cancer: experience in an Asian developing country

Tan GH, Taib NA, Choo WY, Teo SH, Yip CH

Asian Pac J Cancer Prev, 2009 Jul-Sep;10(3):395-8.
PMID: 19640180

INTRODUCTION: Triple negative (TN) breast cancers are defined by a lack of expression of oestrogen, progesterone, and HER2 receptors. They tend to have a higher grade, with a poorer outcome compared to non-TN breast cancers.
OBJECTIVE: The aim of this study is to determine the incidence of TN breast cancer in an Asian country consisting of Malays, Chinese and Indians, and to determine the factors associated with this type of breast cancer.
RESULTS: The incidence of TN breast cancer in the University Malaya Medical Center is 17.6%. There is no significant difference amongst the Malays, Chinese and Indians. In bivariate analysis, TN breast cancer was significantly associated with younger age and Grade 3. However, in multivariate analysis using logistic regression, TN breast cancer was only associated with Grade 3.
CONCLUSION: The incidence of TN breast cancer in our study is similar to other studies, and associated with a higher grade.
Study site: University Malaya Medical Centre (UMMC)
Light-activated cytotoxic compounds from Malaysian microorganisms for photodynamic therapy of cancer

Kamal N, Sabaratnam V, Abdullah N, Ho AS, Teo SH, Lee HB

Antonie Van Leeuwenhoek, 2009 Feb;95(2):179-88.
PMID: 19125347 DOI: 10.1007/s10482-008-9301-8

Photodynamic therapy (PDT) is a promising cancer treatment which involves activation of a photosensitizing drug with light to produce reactive oxygen species that kill tumors without causing damage to unirradiated normal tissues. To date, only Photofrin, Foscan and Levulan have been approved for clinical treatment of cancer. Tropical habitats such as those found in Malaysia are attractive sources of new therapeutic compounds as tremendous chemical diversity is found in a large number of plants, animals, marine- and micro-organisms. In our screening program for novel photosensitizers from nature, colorful strains of fungi (from Aspergillus and Penicillium genus) and bacteria (including actinomycetes and photosynthetic bacteria) were collected from various habitats in Peninsular Malaysia, such as coastal soil, peat soil, marine sponges and wastewater ponds. Methanolic extracts from a total of 85 different species were evaluated with a short-term cell viability assay for photo-cytotoxicity, where a promyelocytic leukemia cell-line, HL60 incubated with 20 microg/ml of extracts was irradiated with 9.6 J/cm(2) of a broad spectrum light. Two of these extracts, one from Rhodobacter sphaeroides (PBUM003) and one from Rhodopseudomonas palustris (PBUM001) showed moderate to strong photo-cytotoxicity. Subsequent bioassay guided isolation of the PBUM001 extract yielded known photosensitisers that are based on bacteriochlorophyll-a by comparing their molecular weight data, HPLC profiles and UV-vis absorption spectra with literature values, thereby demonstrating the validity of our screening approach.
HPV infection and the alterations of the pRB pathway in oral carcinogenesis

Lim KP, Hamid S, Lau SH, Teo SH, Cheong SC

Oncol Rep, 2007 Jun;17(6):1321-6.
PMID: 17487385 DOI: 10.3892/or.17.6.1321

Inactivation of the retinoblastoma (pRB) pathway is a common event in oral squamous cell carcinoma particularly through the aberrant expression of the components within this pathway. This study examines the alterations of molecules within the pRB pathway by looking at the presence of homozygous deletions in p16(INK4A) and the expression patterns of pRB, cyclin D1 and CDK4, as well as the presence of human papillomavirus (HPV) in our samples. In our study, 5/20 samples demonstrated deletions of p16(INK4A) exon 1alpha. pRB overexpression was found in 20/20 samples, the expression was mainly observed in all layers of the epithelia, particularly in the basal layer where cells are actively dividing and aberrant pRB expression was found in 12/20 samples. Cyclin D1 and CDK4 overexpression was detected in 6/20 and 2/20 samples respectively in comparison to hyperplasias where both proteins were either not expressed or expressed at minimal levels (<10%). Strikingly, HPV was found to be present in all of our samples, suggesting that HPV plays a significant role in driving oral carcinogenesis. Notably, 17/20 of our samples showed more than one alteration in the pRB pathway, however, we did not find any significant relationship between the presence of HPV, homozygous deletion of p16(INK4A) and overexpression of pRB, cyclin D1 and CDK4. Collectively, this data demonstrates that alterations in the pRB pathway are a common event and involve the aberration of more than one molecule within the pathway. Furthermore, the involvement of HPV in all our samples suggests that HPV infection may play an important role in oral carcinogenesis.

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