Khee Chee Soo

National Cancer Centre Singapore, Singapore

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Publications (171)550.71 Total impact

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    ABSTRACT: An increasing number of patients are presenting with peritoneal carcinomatosis and more centers are performing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). While morbidity and mortality are shown to be acceptable, quality of life after surgery should be assessed. 63 patients who had CRS and HIPEC from 2001 to 2012 and who were still alive and on follow up were included. The EORTC-QLQ-C30 was administered to the patients. Median age was 53 years (14-71). 44% had ovarian primaries, 21% had appendicael primaries and 19% had colorectal primaries. Median follow-up was 1.08 years (0.06-9.8). The median time from surgery to the questionnaire was 1.3 years (0.24-10.18). There was no statistical difference in scores when comparing by age, gender, recurrence, gender, PCI score, presence of a complication and type of primary cancer. Scores were highest less than 6 months after surgery, dropped subsequently but rose again after 2 years. Our patients had better scores compared to a control group of outpatient cancer patients at our institution as well as the reference EORTC group. In keeping with previous quality of life studies done for CRS and HIPEC patients, we have shown that our patients can achieve a good quality of life after CRS and HIPEC even with recurrent disease.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 04/2014; · 2.56 Impact Factor
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    ABSTRACT: Data on quality of life (QOL) after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is scarce in the Asian population. This study assesses QOL outcomes after CRS and HIPEC in an Asian cancer center. Patients who completed CRS + HIPEC 6-18 months ago (27 patients) were enrolled in the study. QOL was measured via the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaires. The scores were compared with a group of 393 disease-free cancer patients, not on active treatment, who had ECOG scores of either 0 or 1. The 1-sample t test was used to compare differences in QOL scores between the 2 groups. A total of 27 patients were analyzed, of which 22 (81 %) were females. Median age was 51 years (15-59 years). CRS + HIPEC were performed for ovarian cancer in 15 patients (55 %), appendiceal carcinoma in 5 patients (19 %), and colorectal carcinoma in 4 patients (15 %). The median intraoperative peritoneal carcinomatosis index (PCI) score was 15 (2-31) while the completeness of CC score was 0 and 1 in 25 and 2 patients, respectively. The median duration after CRS + HIPEC was 10 months (6-16 months). Global health status and functional and symptom scores were largely similar between patients after CRS + HIPEC and the control group. Cognitive functioning scores and fatigue scores were significantly better in the group after CRS + HIPEC (p = 0.014 and 0.04). QOL after CRS and HIPEC can be equivalent to that of well-functioning, disease-free cancer patients.
    Annals of Surgical Oncology 09/2013; · 4.12 Impact Factor
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    ABSTRACT: Introduction: Peritoneal mesothelioma is a rare neoplasm. Due to the limited understanding of its biology and behaviour, peritoneal mesothelioma poses a diagnostic and management challenge. The management of peritoneal mesothelioma has been controversial; systemic chemotherapy, palliative surgery and cytoreductive surgery (CRS) with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) have been described. Materials and Methods: This study shares our experience with cytoreductive surgery and HIPEC for 5 out of the 6 cases of peritoneal mesotheliomas treated surgically, at a single institution in Singapore over the past 2 years. Computed tomography (CT) scans, positron emission tomography (PET)-CT scans and tumour markers were performed preoperatively but were not conclusive for the disease. All 6 cases presented to the Department of Surgical Oncology at National Cancer Centre Singapore, were diagnosed by histology of intraoperative biopsies. The combination of aggressive cytoreductive surgery and HIPEC was performed in 5 patients, with abandonment of procedure in 1 with extensive disease, who was treated with systemic chemotherapy instead. Results: Median duration of surgery, median length of hospital stay, and median follow-up duration were 7.04 hours, 11 days, and 15 months respectively. One postoperative morbidity relating to chemical peritonitis required exploratory laparotomy with good outcome. There were no mortality. All patients are alive at the last follow-up with no evidence of recurrences at 4 to 31 months from the time of their surgery. Conclusion: Peritoneal mesothelioma is a rare disease that requires early diagnosis and can be effectively treated by CRS and HIPEC in selected group of patients.
    Annals of the Academy of Medicine, Singapore 06/2013; 42(6):291-296. · 1.36 Impact Factor
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    ABSTRACT: BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival in selected patients with peritoneal carcinomatosis. We review our institutional experience with the procedure and evaluate the overall survival (OS) and disease-free survival (DFS) rates in 100 consecutive patients. METHODS: Data were prospectively collected from 100 consecutive patients with peritoneal carcinomatosis treated by CRS and HIPEC at the National Cancer Centre Singapore between April 2001 and May 2012. Our primary end points were OS and DFS. RESULTS: Of the 100 patients, 84 were of Chinese ethnicity, 3 were Malay, 6 were Indian, and 7 were of other ethnicities. Primary tumors were ovarian cancer (n = 39), colorectal cancer (n = 28), primary peritoneal (n = 6), appendiceal cancer (n = 20), and mesothelioma (n = 7). Median follow-up duration was 21 months. At 5 years, the DFS was 26.3 % and OS was 50.9 %. Factors influencing OS and DFS were cytoreductive score, primary cancer, and disease-free interval of more than 12 months on univariate analysis. The only factors that remained significant for prognosis after multivariate analysis were primary cancer and cytoreductive score. Thirty-day morbidity was 56 %, and there were no 30-day mortalities. CONCLUSIONS: CRS and HIPEC can be safely carried out in Asian patients with peritoneal carcinomatosis from ovarian, colorectal, appendiceal, mesothelioma, and primary peritoneal origins. Overall, the ovarian, appendiceal, mesothelioma, and primary peritoneal cancer patients tended to do better than the colorectal patients, but careful patient selection ensuring that optimal cytoreduction can be achieved is essential for the success of this procedure.
    Annals of Surgical Oncology 03/2013; · 4.12 Impact Factor
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    ABSTRACT: BACKGROUND: The purpose of the present study was to determine whether intrahepatic injection of 131I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular carcinoma (HCC). METHODS: From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4-6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan-Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong. RESULTS: The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval [95 % CI] 0.46-1.23; p = 0.25) and OS (HR = 0.88; 95 % CI 0.51-1.51; p = 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by 131I-lipiodol and hepatic artery dissection during angiography. CONCLUSIONS: The randomized trial provides insufficient evidence to recommend the routine use of 131I-lipiodol in these patients.
    World Journal of Surgery 03/2013; · 2.23 Impact Factor
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    ABSTRACT: INTRODUCTION: In recent years, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has gained increasing acceptance as a treatment modality for peritoneal carcinomatosis. In female patients, this procedure involves a total hysterectomy and bilateral saphingo-oophorectomy to remove the pelvic peritoneum. We present a case of an unfortunate female adolescent with peritoneal carcinomatosis who underwent cytoreductive surgery and HIPEC. In view of the compelling circumstance, an innovative surgical technique was used to attempt ovarian preservation. PRESENTATION OF CASE: A 14 year old girl with carcinoma of the sigmoid colon and peritoneal metastases was offered cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy. In view of her age, ovarian preservation with subcutaneous transposition was performed during cytoreductive surgery. She is currently well 6 months post surgery and has resumed normal menstruation. We review the literature regarding ovarian preservation with subcutaneous transposition and discuss its benefit in pre-menopausal women undergoing peritonectomy and cytoreductive surgery for peritoneal carcinomatosis. DISCUSSION: Subcutaneous transposition of the ovary in pre-menopasual patients requiring cytoreductive surgery spares them the sequelae of surgical castration. The subcutaneous location of the transposed ovary conveys advantages such as the ease of ultrasound surveillance and removal in event of disease recurrence. It also retains the possibility of future conception as the transposed ovary can easily be accessed for ovum extraction with assisted reproductive techniques. CONCLUSION: Ovarian preservation with subcutaneous transposition is a technique worth considering in the treatment of pre-menopausal women who require cytoreductive surgery for peritoneal carcinomatosis.
    International journal of surgery case reports. 01/2013; 4(3):305-307.
  • Melissa C C Teo, Khee Chee Soo
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    ABSTRACT: Cancer is the leading cause of mortality in Singapore. The age-standardized incidence rates continue to increase as the population grows and ages, and the influence of environmental and lifestyle choices bear their consequences. The increase is most marked in colorectal, breast and prostate cancers, mirroring the most common cancers seen in other developed countries. The eradication of infectious disease such as hepatitis B, through the implementation of the hepatitis B immunization programme in 1985, has led to the decline in liver cancer. The Singapore Cancer Registry collates detailed information on newly diagnosed and existing cancer cases, enabling the study and understanding of cancer trends in the population and across the different ethnic groups. A coordinated approach to address cancer prevention and treatment through public education and increased awareness, screening and early detection, and the institution of appropriate multidisciplinary care, on a background of continued basic and clinical research is required to deliver quality cancer care.
    Japanese Journal of Clinical Oncology 01/2013; · 1.90 Impact Factor
  • Yirong Sim, Fabian Yap, Khee Chee Soo, Yee Low
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    ABSTRACT: Medullary Thyroid Carcinoma (MTC) is the most common cause of death in MEN patients. It is curative by prophylactic total thyroidectomy, but controversies remain as to the optimal timing for prophylactic thyroidectomy. The current recommendation is for prophylactic total thyroidectomy before age 5, but a recent study suggested that in the ethnic Chinese, even "high risk" mutations did not result in early malignant change, and it was suggested that prophylactic thyroidectomy may be performed at a later age. We report a case of an ethnic Chinese girl with MEN2A codon 634 (C634R) mutation, whose operative specimen at prophylactic thyroidectomy at 4years 8months showed MTC. We advocate that management of MEN2A patients should be codon-directed, regardless of ethnicity.
    Journal of Pediatric Surgery 01/2013; 48(1):e43-e46. · 1.38 Impact Factor
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    ABSTRACT: PURPOSE: The liver and peritoneum are common sites of colorectal metastases. Hepatectomy for colorectal liver metastases (CLM) is considered gold standard treatment. We attempt to compare the survival outcomes for CLM patients after hepatectomy to that of patients with colorectal peritoneal metastases (CPM) who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A retrospective review of patients with CPM and CLM who underwent surgery between January 2003 and May 2011 was performed. The overall (OS) and disease-free survivals (DFS) were compared. RESULTS: There were 22 patients with CPM who underwent CRS and HIPEC and 186 patients who underwent hepatectomy for CLM. Patients with CPM had a 3-year OS of 39 % and DFS of 27.7 %. CLM patients showed a 3-year OS of 58.5 % and a DFS of 28.8 %. Most recurrences for CPM occurred within 2 years, while CLM patients continue to develop systemic recurrences over 3 years, showing a gradual decline in DFS and OS during this period of time. CONCLUSION: Our results show that CRS and HIPEC for CPM confer good OS and DFS rates and that the DFS after CRS and HIPEC is comparable to that after hepatectomy for CLM.
    Journal of Gastrointestinal Cancer 11/2012;
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    ABSTRACT: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death. Although sorafenib has been shown to improve survival of patients with advanced HCC, this improvement is modest and patients eventually have refractory disease. This study aims at investigating the antitumor, antiangiogenesis and antimetastatic activities of dovitinib in preclinical models of HCC. 21-0208 and SK-HEP1 cells as well as patient-derived HCC models were employed to study the antitumor effect of dovitinib. Changes of biomarkers relevant to FGFR/VEGFR/PDGFR pathways were determined by Western blotting. Microvessel density, apoptosis and cell proliferation were analyzed by immunohistochemistry. Treatment of SK-HEP1 cells with dovitinib resulted in G2/M cell cycle arrest, inhibition of colony formation in soft agar and blockade of bFGF-induced cell migration. Dovitinib inhibited basal expression and FGF-induced phosphorylation of FGFR-1, FRS2-α and ERK1/2. In vivo, dovitinib potently inhibited tumor growth of six HCC lines. Inhibition of angiogenesis correlated with inactivation of FGFR/PDGFR-β/VEGFR-2 signaling pathways. Dovitinib also caused dephosphorylation of retinoblastoma, upregulation of p-histone H2A-X and p27, and downregulation of p-cdk-2 and cyclin B1, which resulted in a reduction in cellular proliferation and the induction of tumor cell apoptosis. In an orthotopic model, dovitinib potently inhibited primary tumor growth and lung metastasis and significantly prolonged mouse survival. Dovitinib demonstrated significant antitumor and antimetastatic activities in HCC xenograft models. This study provides a compelling rationale for clinical investigation in patients with advanced HCC.
    Journal of Hepatology 03/2012; 56(3):595-601. · 9.86 Impact Factor
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    ABSTRACT: The extent of lymph nodes (LNs) metastasis is a major determinant for the staging and the most reliable adverse prognostic factor. Primary tumours can induce lymphatics and vasculature reorganisations within sentinel LN before the arrival of cancer cells and these key blood vessels are identified as high endothelial venules (HEV). The alterations of HEV in the presence of cancer, coupled with the increased proliferation rate of the endothelial cells, results in a functional shift of HEV from immune response mediator to blood flow carrier. We aim to evaluate tumour-induced vascularisation in regional LN of cancer patients by studying the morphological and functional alterations of HEV and its correlation to clinico-pathological features. This multi-centre study with a prospective database identified 65 consecutive patients with tongue squamous cell carcinoma (SCC) who underwent primary surgical treatment from 2001 to 2005. Immunohistochemical staining for HEV and image analysis were performed and analysed with correlation to the patients' clinico-pathological features. The total number of HEV is significantly associated to disease-free interval when controlling for the group (P = 0.022) as well as combining both groups as one cohort (P = 0.023). There is also a similar association comparing the HEV parameters to overall survival. Our results suggest that HEV possibly plays a key role in the pathogenesis of lymphatic and subsequent distant metastases and may provide the missing link in cancer metastasis. Confirmation of this hypothesis would offer a novel therapeutic approach to preventing metastasis by blocking the remodeling processes of HEV in LN.
    Annals of the Academy of Medicine, Singapore 01/2012; 41(1):21-8. · 1.36 Impact Factor
  • Hung Huynh, Richard Ong, Khee Chee Soo
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    ABSTRACT: PURPOSE OF STUDY: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death. Although sorafenib has been shown to improve survival of patients with advanced HCC, this improvement is modest and patients eventually have refractory disease. The purpose of this study is to assess the anti-tumor and anti-angiogenic activities of foretinib, a vascular endothelial growth factor receptor 2 (VEGFR-2) and c-Met inhibitor using mouse models of human HCC. EXPERIMENTAL TECHNIQUES: SK-HEP1 and 21-0208 HCC cells as well as patient-derived HCC models were employed to study the anti-tumor and antiangiogenic activities of foretinib. Changes of biomarkers relevant to hepatocyte growth factor (HGF) signaling pathways were determined by Western blotting. Microvessel density, apoptosis and cell proliferation were analyzed by immunohistochemistry. RESULTS: Treatment of SK-HEP1 cells with foretinib resulted in growth inhibition, G2/M cell cycle arrest, reduced colony formation and blockade of HGF-induced cell migration. In both orthotopic and ectopic models of HCC, foretinib potently inhibited tumor growth in a dose-dependent manner. Inhibition of angiogenesis correlated with inactivation of VEGFR-2/c-Met signaling pathways. Foretinib also caused elevation of p27 and Bim but reduced cyclin B1 expression and p-c-Myc, which resulted in a reduction in cellular proliferation and the induction of tumor cell apoptosis. In an orthotopic model, foretinib potently inhibited primary tumor growth and significantly prolonged mouse survival. DATA INTERPRETATIONS: Foretinib demonstrated significant antitumor activities in patient-derived HCC xenograft models. This study provides a compelling rationale for clinical investigation in patients with advanced HCC.
    Angiogenesis 12/2011; 15(1):59-70. · 3.97 Impact Factor
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    ABSTRACT: Malignancies of the oral cavity are conventionally diagnosed by white light endoscopy, biopsy and histopathology. However, it is often difficult to distinguish between benign lesions and premalignant or early lesions. There is a need for a more definitive, non-invasive technique for diagnosis of oral cavity lesions. A laser confocal endomicroscope offers non-invasive surface and subsurface imaging of tissue. We investigated its potential for fluorescence imaging of the oral cavity using hypericin, fluorescein and aminolevulinic acid. Fluorescence imaging was carried out both in vivo and on resected tissue samples of the oral cavity in both humans and animal models. Good structural images of the oral cavity were obtained. Morphological differences between normal and lesion tissue can be distinguished. The use of Pharmasolve® enhanced the subsurface depth from which images can be obtained. Our results show that laser confocal fluorescence endomicroscopy has great potential for the diagnosis of oral cavity malignancies.
    Journal of Mechanics in Medicine and Biology 11/2011; 07(01). · 0.76 Impact Factor
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    ABSTRACT: Well differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare variant of epithelial mesothelioma of low malignancy potential, usually found in women with no history of asbestos exposure. In this study, we perform the first exome sequencing of WDPMP. WDPMP exome sequencing reveals the first somatic mutation of E2F1, R166H, to be identified in human cancer. The location is in the evolutionarily conserved DNA binding domain and computationally predicted to be mutated in the critical contact point between E2F1 and its DNA target. We show that the R166H mutation abrogates E2F1's DNA binding ability and is associated with reduced activation of E2F1 downstream target genes. Mutant E2F1 proteins are also observed in higher quantities when compared with wild-type E2F1 protein levels and the mutant protein's resistance to degradation was found to be the cause of its accumulation within mutant over-expressing cells. Cells over-expressing wild-type E2F1 show decreased proliferation compared to mutant over-expressing cells, but cell proliferation rates of mutant over-expressing cells were comparable to cells over-expressing the empty vector. The R166H mutation in E2F1 is shown to have a deleterious effect on its DNA binding ability as well as increasing its stability and subsequent accumulation in R166H mutant cells. Based on the results, two compatible theories can be formed: R166H mutation appears to allow for protein over-expression while minimizing the apoptotic consequence and the R166H mutation may behave similarly to SV40 large T antigen, inhibiting tumor suppressive functions of retinoblastoma protein 1.
    Genome biology 09/2011; 12(9):R96. · 10.30 Impact Factor
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    Journal of Gynecologic Oncology 09/2011; 22(3):214-7. · 1.73 Impact Factor
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    ABSTRACT: While histopathology of excised tissue remains the gold standard for diagnosis, several new, non-invasive diagnostic techniques are being developed. They rely on physical and biochemical changes that precede and mirror malignant change within tissue. The basic principle involves simple optical techniques of tissue interrogation. Their accuracy, expressed as sensitivity and specificity, are reported in a number of studies suggests that they have a potential for cost effective, real-time, in situ diagnosis.We review the Third Scientific Meeting of the Head and Neck Optical Diagnostics Society held in Congress Innsbruck, Innsbruck, Austria on the 11th May 2011. For the first time the HNODS Annual Scientific Meeting was held in association with the International Photodynamic Association (IPA) and the European Platform for Photodynamic Medicine (EPPM). The aim was to enhance the interdisciplinary aspects of optical diagnostics and other photodynamic applications. The meeting included 2 sections: oral communication sessions running in parallel to the IPA programme and poster presentation sessions combined with the IPA and EPPM posters sessions.
    Head & Neck Oncology 08/2011; 3:38. · 3.13 Impact Factor
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    ABSTRACT: Hepatocellular carcinoma (HCC) is the fifth most common and third deadliest malignancy. Sorafenib has demonstrated 44% survival advantage over placebo and has emerged as a standard of care in advanced HCC. The therapeutic effects of sorafenib are however transient and hence additional treatment options are warranted. In this study, we aimed to compare the efficacy of sunitinib relative to sorafenib, two potent inhibitors of protein tyrosine kinases involved in tumor growth, metastasis, or angiogenesis. We reported that sorafenib and sunitinib suppressed tumor growth, angiogenesis, cell proliferation, and induced apoptosis in both orthotopic and ectopic models of HCC. However, the antitumor effect of 50 mg/kg sorafenib was greater than that of 40 mg/kg sunitinib. Sorafenib inhibited p-eIF4E Ser209, p-p38 Thr180/Tyr182 and reduced survivin expression. This was not seen with sunitinib. In addition, the antitumor and apoptotic effects of sorafenib, which are associated with upregulation of fast migrating Bim and ASK1 and downregulation of survivin, were greater than that of sunitinib. These observations explained in part the apparent superior anti-tumor activity of sorafenib compared to sunitinib. In conclusion, sunitinib demonstrated an inferior anti-tumor activity compared to sorafenib in ectopic and orthotopic models of human HCC. It remains to be seen whether such observations would be recapitulated in humans.
    Current cancer drug targets 08/2011; 11(8):944-53. · 5.13 Impact Factor
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    ABSTRACT: The localization of photosensitizers in the subcellular compartments during photodynamic therapy (PDT) plays a major role in the cell destruction; therefore, the aim of this study was to investigate the intracellular localization of Chlorin e6-PVP (Photolon™) in malignant and normal cells. Our study involves the characterization of the structural determinants of subcellular localization of Photolon, and how subcellular localization affects the selective toxicity of Photolon towards tumor cells. Using confocal laser scanning microscopy (CLSM) and fluorescent organelle probes; we examined the subcellular localization of Photolon™ in the murine colon carcinoma CT-26 and normal fibroblast (NHLC) cells. Our results demonstrated that after 30 min of incubation, the distribution of Photolon was localized mainly in the cytoplasmic organelles including the mitochondria, lysosomes, Golgi apparatus, around the nuclear envelope and also in the nucleus but not in the endo-plasmic reticulum whereas in NHLC cells, Photolon was found to be localized minimally only in the nucleus not in other organelles studied. The relationship between subcellular localization of Photolon and PDT-induced apoptosis was investigated. Apoptotic cell death was judged by the formation of known apoptotic hallmarks including, the phosphatidylserine externalization (PS), PARP cleavage, a substrate for caspase-3 and the formation of apoptotic nuclei. At the irradiation dose of 1 J/cm2, the percentage of apoptotic cells was 80%, respectively. This study provided substantial evidence that Photolon preferentially localized in the subcellular organelles in the following order: nucleus, mitochondria, lysosomes and the Golgi apparatus and subsequent photodamage of the mitochondria and lyso-somes played an important role in PDT-mediated apoptosis CT-26 cells. Our results based on the cytoplasmic organelles and the intranuclear localization extensively enhance the efficacy of PDT with appropriate photosensitizer and light dose and support the idea that PDT can contribute to elimination of malignant cells by inducing apoptosis, which is of physiological significance.
    International Journal of Oncology 07/2011; 39(4):821-31. · 2.66 Impact Factor
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    ABSTRACT: Nasopharyngeal carcinoma (NPC) is known for its high-metastatic potential. Here we report the identification of the proteoglycan serglycin as a functionally significant regulator of metastasis in this setting. Comparative genomic expression profiling of NPC cell line clones with high- and low-metastatic potential revealed the serglycin gene (SRGN) as one of the most upregulated genes in highly metastatic cells. RNAi-mediated inhibition of serglycin expression blocked serglycin secretion and the invasive motility of highly metastatic cells, reducing metastatic capacity in vivo. Conversely, serglycin overexpression in poorly metastatic cells increased their motile behavior and metastatic capacity in vivo. Growth rate was not influenced by serglycin in either highly or poorly metastatic cells. Secreted but not bacterial recombinant serglycin promoted motile behavior, suggesting a critical role for glycosylation in serglycin activity. Serglycin inhibition was associated with reduced expression of vimentin but not other epithelial-mesenchymal transition proteins. In clinical specimens, serglycin expression was elevated significantly in liver metastases from NPC relative to primary NPC tumors. We evaluated the prognostic value of serglycin by immunohistochemical staining of tissue microarrays from 263 NPC patients followed by multivariate analyses. High serglycin expression in primary NPC was found to be an unfavorable independent indicator of distant metastasis-free and disease-free survival. Our findings establish that glycosylated serglycin regulates NPC metastasis via autocrine and paracrine routes, and that it serves as an independent prognostic indicator of metastasis-free survival and disease-free survival in NPC patients.
    Cancer Research 02/2011; 71(8):3162-72. · 8.65 Impact Factor
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    ABSTRACT: The complete surgical removal of disease is a desirable outcome particularly in oncology. Unfortunately much disease is microscopic and difficult to detect causing a liability to recurrence and worsened overall prognosis with attendant costs in terms of morbidity and mortality. It is hoped that by advances in optical diagnostic technology we could better define our surgical margin and so increase the rate of truly negative margins on the one hand and on the other hand to take out only the necessary amount of tissue and leave more unaffected non-diseased areas so preserving function of vital structures. The task has not been easy but progress is being made as exemplified by the presentations at the 2nd Scientific Meeting of the Head and Neck Optical Diagnostics Society (HNODS) in San Francisco in January 2010. We review the salient advances in the field and propose further directions of investigation.
    Head & Neck Oncology 02/2011; 3(1):7. · 3.13 Impact Factor

Publication Stats

2k Citations
550.71 Total Impact Points

Institutions

  • 2002–2013
    • National Cancer Centre Singapore
      • • Department of Surgical Oncology
      • • Department of Medical Sciences
      • • Division of Cellular and Molecular Research
      Singapore
  • 1991–2013
    • Singapore General Hospital
      • • Department of General Surgery
      • • Department of Surgery
      Tumasik, Singapore
  • 2011
    • University College London
      Londinium, England, United Kingdom
  • 2009
    • Duke-NUS Graduate Medical School Singapore
      • PhD Program in Cancer and Stem Cell Biology
      Tumasik, Singapore
  • 2005–2006
    • National University of Singapore
      • Department of Pharmacy
      Singapore, Singapore
  • 1988–1993
    • Memorial Sloan-Kettering Cancer Center
      • • Head and Neck Service
      • • Department of Surgery
      New York City, New York, United States