Biomedical subjects

P H Tan

Publications and source records attributed to P H Tan.

At least 19 recordsLinked to original sources

PubMed2007

The Transplantation Society--new key opinion leaders of tomorrow 2006.

One of the new initiatives taken by the immediate past president of The Transplantation Society, KJ Wood, is to introduce a new series of meetings named 'New Key Opinion Leaders of Tomorrow'. The Transplantation Society invites the leading young investigators in the field of transplantation to participate in this meeting together with the present leaders of the field. The key objective of this meeting is to identify the potential key opinion leaders of tomorrow. Each presentation during the meeting was jointly given by the senior and junior investigators. The meeting in Buenos Aires covered six main topics on clinical, translational and basic transplantation. These included: innate immunity and inflammation; transplant infectious diseases; tumour and transplantation; medical and ethical aspects of transplantation; dendritic cells (stimulating and manipulating the immune response to a transplant); and ABO incompatible donor recipient pairs. This report focuses on the emerging biological therapeutics and their ramifications on clinical transplantation.

Animals↗

PubMed2006

The role of 5' untranslated region in translational suppression of OKL38 mRNA in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide. OKL38 is a pregnancy-induced growth inhibitory gene and its expression is lost in various breast cancer cell lines and kidney tumor. To determine the role of OKL38 expression in HCC, we investigated its expression in various HCC samples and liver cancer cell lines. Western blot analysis revealed that OKL38 protein was absent or reduced in 64.2% (18 of 28) of the HCCs examined and four liver cancer cell lines. Immunohistochemistry study demonstrated that OKL38 protein was undetectable in 41.3% (38 of 92) of HCC, whereas 39.1% (36 of 92) of HCC showed low expression of the protein. Lost or reduced expression level of OKL38 protein was significantly correlated to high tumor stages in HCC (P=0.0042). Overexpression of the OKL38 caused cell death in Chang liver cells. 5' Untranslated region (5'UTR) deletion studies demonstrated that OKL38 was downregulated via translation suppression associated with the 5'UTR of its mRNA. Taken together, the 5'UTRs of OKL38 might play an important role in downregulation of its protein and the absence of OKL38 could lead to the development or progression of HCC.

5' Untranslated Regions↗

PubMed2006

Aspirin-treated human DCs up-regulate ILT-3 and induce hyporesponsiveness and regulatory activity in responder T cells.

Mature dendritic cells (mDCs) are potent antigen presenting cells, but immature DCs (iDCs) have been shown to have reduced antigen stimulatory capacity. Different strategies have been investigated to augment the tolerogenic capacity of dendritic cells (DCs). We demonstrate that in aspirin-treated human DCs, there is reduced expression of CD1a, HLA-DR and CD86, up-regulation of ILT-3 expression and marginal increases in PDL-1. Aspirin-treated DCs are partially resistant to phenotypic changes following maturational stimuli, such as lipopolysaccharide (LPS) or TNFalpha, IL-1alpha and PGE2. Aspirin-treated DCs demonstrate normal endocytic function, but have a reduced ability to stimulate allogeneic T cells, which is comparable to iDCs. Furthermore, they induce hyporesponsiveness and regulatory activity in responder naïve and memory T cells; for naïve T cells this is achieved more quickly and efficiently than with iDCs. We investigated the mechanism of this regulatory activity and found that both cell-cell contact and inhibitory cytokine activity are involved, although no one cytokine predominates in importance. Blocking ILT-3 or IL-12 does not diminish the capacity of these DCs to induce regulation or Foxp3 expression on the regulatory T cells. Results demonstrate that aspirin-treated DCs display tolerogenic potential, which is of interest in their therapeutic potential in reducing chronic allograft rejection.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

Nuclear morphometry in columnar cell lesions of the breast: is it useful?

AIMS: To evaluate the nuclear morphometric features of breast columnar cell lesions (CCLs) observed on mammotome core biopsies, to determine if there are significant measurable differences between those with atypia and those without. Correlation with follow-up open excision specimens was made. METHODS: Mammotome core biopsies performed on patients that contained CCLs were derived from the departmental case files. Histological material was reviewed and foci of CCLs demarcated for nuclear morphometric assessment, which was accomplished using an imaging system. Nuclear parameters studied were nuclear area and perimeter, circularity factor and feret's diameter. Statistical analysis used the GraphPad Prism software, with p<0.05 indicating significance. RESULTS: On examination of core biopsies of 40 patients with CCLs, 8 lesions were benign, 4 showed atypical lobular hyperplasia, 8 showed CCLs with nuclear atypia, 19 disclosed atypical ductal hyperplasia (ADH) and 1 showed ductal carcinoma in situ (DCIS). The nuclear area, perimeter and feret's diameter of CCLs with atypia were significantly greater than those without (p = 0.04, 0.03 and 0.019, respectively), whereas no difference was observed in the circularity factor. Follow-up open excision biopsy specimens in 24 patients showed upgrading to DCIS in 40% of cases diagnosed initially with ADH on core biopsy compared with 20% of CCLs with atypia. CONCLUSIONS: Nuclear morphometry in CCLs confirms nuclear size as the key parameter in the assessment of nuclear atypia. Whether it can be potentially used as an adjunctive tool depends on the establishment of appropriate cut-offs.

Adult↗

PubMed2006

Metaplastic carcinoma of the breast: a clinicopathological review.

BACKGROUND: Mammary metaplastic carcinoma encompasses epithelial-only carcinoma (high-grade adenosquamous carcinoma or pure squamous cell carcinoma), biphasic epithelial and sarcomatoid carcinoma and monophasic spindle cell carcinoma. AIM: To evaluate the clinicopathological features of a large series of 34 metaplastic carcinomas. METHODS: 10 epithelial-only, 14 biphasic and 10 monophasic metaplastic carcinomas were assessed for nuclear grade, hormone receptor status, HER2/neu (cerbB2) oncogene expression, Ki-67 and p53, lymph node status and recurrence on follow-up. RESULTS: Intermediate to high nuclear grade were assessed in most (33/34) tumours. Oestrogen and progesterone receptors were negative in 8 of 10 epithelial-only, all 14 biphasic, and 9 of 10 monophasic tumours, cerbB2 was negative in 7 of 10 epithelial-only, all 14 biphasic and 8 of 10 monophasic tumours. Ki-67 was found to be positive in 6 of 10 epithelial-only, 6 of 14 biphasic, and 7 of 10 monophasic tumours, whereas p53 was positive in 6 of 10 epithelial-only, 7 of 14 biphasic, and 8 of 10 monophasic tumours. Lymph node metastases were seen in 7 of 7 epithelial-only, 7 of 11 biphasic, and 3 of 7 monophasic tumours. Recurrences were seen in 4 of 7 epithelial-only, 8 of 9 biphasic, and 4 of 9 monophasic tumours. CONCLUSIONS: All three subtypes of metaplastic carcinoma are known to behave aggressively, and should be differentiated from the low-grade fibromatosis-like metaplastic carcinoma, which does not metastasize. Oncological treatment options may be limited by the frequently negative status of hormonal receptor and cerbB2.

Adenocarcinoma↗

PubMed2006

Inverted papilloma of urinary bladder: is long-term cystoscopic surveillance needed? A single center's experience.

OBJECTIVES: To review all cases of urinary bladder inverted papilloma (IP) in our institution and determine the need for cystoscopic surveillance. IP is an uncommon benign tumor of the urinary tract. Its multiplicity, recurrence, and association with transitional cell carcinoma (TCC) suggest possible malignant potential, leading to conflicting clinical conclusions regarding the need for surveillance. METHODS: All consecutive patients from January 1991 to December 2004 with IP were included in this study. A single pathologist performed the histologic review. The patients had undergone cystoscopy and ultrasound evaluation of the kidneys every 6 months. RESULTS: Of the 52 patients, 45 were men and 7 were women. The average age at presentation was 58.9 +/- 11.8 years (range 30 to 79). No patient had a synchronous or previous bladder tumor. The most common complaint was macroscopic hematuria. Ten cases were incidental findings during bladder ultrasonography or cystoscopy. All were solitary tumors, most commonly found at the bladder neck. The average follow-up period was 62 +/- 23 months, with no recurrence. One case of subsequent noninvasive papillary TCC developed 15 months later. The initial histologic findings had revealed cytologic atypia, with suspicious urine cytology findings. On review, it was more compatible with TCC with an inverted pattern. CONCLUSIONS: Although our cases exhibited benign biologic behavior, the presence of cytologic atypia and suspicious urine cytology require exclusion of TCC with an inverted pattern. Thus, in histologically proven solitary bladder IP with no associated TCC, cystoscopic surveillance may not be necessary.

Adult↗

PubMed2006

Cytology is useful in breast screening: results and long-term follow-up of the Singapore Breast Screening Pilot Project.

OBJECTIVE: The Singapore Breast Screening Pilot Project (SBSPP) was embarked upon (1994-1997) to determine if mammography was useful in early breast cancer detection among Asian women. PATIENTS AND MEASUREMENTS: Of 28 231 women screened, fine needle aspiration cytology (FNAC) was performed in 232 individuals as part of the triple assessment. RESULTS: Absolute and complete sensitivities for the diagnosis of carcinoma were 46.7% and 82.2%, respectively, based on the results of FNAC. Specificity was 63.3%. The inadequate rate was 31%. Five women who were considered cancer-free on triple assessment and, in two cases open diagnostic biopsy during the SBSPP, subsequently developed breast cancer after a median follow-up of 6 years. CONCLUSION: Although our FNAC results compared relatively well with international standards, they reflect a small cohort, and may face additional difficulties in a larger programme.

Biopsy, Fine-Needle↗

PubMed2006

Preoperative and intraoperative diagnosis of low-grade adenosquamous carcinoma of the breast: potential diagnostic pitfalls.

AIMS: Low-grade adenosquamous carcinoma (LGAC), a rare variant of metaplastic breast cancer, may mimic benign or other low-grade malignant lesions histologically. Diagnostic difficulty may be encountered when evaluating breast cytology, core needle biopsy or intraoperative frozen section specimens. METHODS AND RESULTS: Pathology reports, cytology aspirates and histological slides of LGAC diagnosed at the Department of Pathology, Singapore General Hospital, were reviewed. Four cases of LGAC were analysed. Cytology from the first case showed atypical cells and the subsequent surgical excision specimen showed a complex sclerosing lesion with LGAC. The second and third cases were investigated by core needle biopsies: the preoperative histological features were suggestive of but not diagnostic of LGAC, until further excision biopsies were performed. The fourth case entailed a frozen section specimen, for which definitive diagnosis was deferred to paraffins. The patients remained well with no evidence of recurrent disease to date. CONCLUSIONS: When limited material, in the form of needle aspirates, core biopsy specimens or frozen sections, is submitted for histology, making a diagnosis of LGAC is not only challenging, but may be impossible. In difficult cases, careful pathological assessment, clinicopathological correlation and follow-up or complete excision biopsy may prove invaluable in establishing a definitive diagnosis.

Biomarkers, Tumor↗

PubMed2006

Expression of indoleamine 2,3-dioxygenase (IDO) by endothelial cells: implications for the control of alloresponses.

Indoleamine 2,3-dioxygenase (IDO) is an important enzyme in the regulation of immune responses; cells that express IDO can suppress T-cell responses and promote tolerance. Because of the critical role of endothelial cells in graft rejection, we have investigated the role of IDO expression by vascular endothelial cells and its consequence on immunoregulation. We compared the expression of IDO by primary human umbilical vein endothelial cells (HUVECs), human saphenous vein endothelial cells (HSVECs) and arterially derived endothelial cells using reverse transcriptase PCR, Western blotting and assays for enzymatic activity. In HUVECs IDO is upregulated by incubation with cytokines or in mycoplasma-infected cells. On the other hand HSVECs and arterially derived endothelial cells express little IDO, which is poorly upregulated upon activation (except by mycoplasma). Inhibition of IDO activity improved the ability of HUVECs to stimulate allogeneic T-cell responses. If either HUVECs or HSVECs are transfected with the gene encoding IDO, then they are incapable of stimulating allogeneic T-cell responses and induce anergy in allospecific T cells (which can also act as regulatory cells). The variable expression of IDO in different endothelial cells is important not only in understanding the role of endothelial cells in the regulation of graft rejection, but also as a potential therapeutic strategy.

Arteries↗

PubMed2006

Rosai-Dorfman disease of the testis: an unusual entity that mimics testicular malignancy.

A 47 year old Chinese man with diabetes mellitus and previously treated pulmonary tuberculosis presented with painless right testicular enlargement of 1 month's duration. He underwent an orchidectomy for presumed testicular neoplasm corroborated clinicoradiologically. Histological examination of the testicular mass revealed an inflammatory lesion comprising lymphocytes, plasma cells and sheets of pale staining histiocytes, some containing lymphocytes within their ample cytoplasm, suggestive of emperipolesis. S100 immunohistochemistry stained the histiocytes, while ultrastructural examination confirmed emperipolesis. A diagnosis of Rosai-Dorfman disease was made, an exceedingly rare testicular lesion. Clinicoradiological findings mimicked a neoplasm, while the inflammatory histological appearances with occasionally discerned multinucleated cells raised the possibility of xanthogranulomatous orchitis. Tuberculous orchitis was excluded through negative Ziehl-Neelsen stains and PCR for mycobacterium, while seminoma, which sometimes features a predominant inflammatory component obscuring neoplastic cells, was excluded by absent immunostaining for placental alkaline phosphatase and CD117.

Diabetes Complications↗

PubMed2006

An unusual cause of granulomatous inflammation: eosinophilic abscess in Langerhans cell histiocytosis.

Eosinophilic abscess inciting a granulomatous response has rarely been reported and appears not to have been described in the setting of a neoplasm. In this report, a case is described where a granulomatous response occurred around eosinophilic abscesses in a patient with Langerhans cell histiocytosis, an association which has not previously been documented. On histology, the excised lymph node showed the presence of eosinophilic abscess and necrosis surrounded by granulomas, which in turn were surrounded by Langerhans cells, a feature confirmed on immunohistochemistry. Although rare, this case highlights the importance of careful examination of eosinophilic abscess with granulomatous inflammation in order to exclude an underlying neoplasm.

Abscess↗

PubMed2006

World Transplant Congress. Boston, Massachusetts, USA, 22-27 July 2006.

The World Transplant Congress (WTC) is the first joint international transplant meeting co-organised by the Transplantation Society, the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS). It was the first meeting of this calibre that was being held by three world-renowned authorities in the field of transplantation. Under the direction of the congress president, AB Cosimi, the attendance of this meeting is a 'must' for all working in the field of transplantation. The congress had provided an important forum for the exchange of new scientific and clinical information that is relevant to solid organ and tissue transplantation. In addition, it also created an arena for the interchange of ideas regarding the care and management of transplant recipients. There were many sessions that were engineered in order to facilitate the discussion of socioeconomic, ethical and regulatory issues related transplantation. On the whole, the meeting has set a very high standard for any future transplant congresses to match-providing the delegates with updates on transplantation with the new scientific prospectives in T cell costimulation, innate immunity (dendritic cells), anatomy of immune response and regulatory T cell biology. More importantly, it has highlighted the potentials of harnessing these new findings for future biological therapies in preventing rejection and inducing tolerance.

Animals↗

PubMed2006

Strategies to improve non-viral vectors--potential applications in clinical transplantation.

Prevention of acute rejection has been well controlled with immunosuppressive drugs. However, the long-term control of rejection is less satisfactory and the side effects of chronic usage of these drugs are far from acceptable. Thus, more imaginative options for therapy need to be explored. Gene therapy has potential promise in preserving allografts, preventing rejection and inducing tolerance. Despite this initial promise in many animal models, the translation of gene therapy to the clinical arena has been slow. This may be related in part to the deficiencies in vector development. Existing viral vectors are efficient at transducing allografts, but they induce inflammatory and pathogenic effects. Although the alternative non-viral systems are relatively innocuous, they are less efficient at gene delivery. This review systematically analyses the limitations of non-viral vector technology and the strategies that have been developed to overcome these limitations. Future development of non-viral vectors may have potential application in clinical transplantation.

Animals↗

PubMed2006

9th American Society of Gene Therapy annual meeting.

The American Society of Gene Therapy, under the presidency of Mark Kay, held its annual meeting in Baltimore, MD, USA this year. This meeting was well received by academics and industry alike in order to promote research, development and application of gene therapy. Exchange of information, promotion of education and development of clinical translation have been the main aims of this society. On face value, the meeting seems to highlight that gene-based treatment is coming of age. Many drawbacks of gene-based treatments were discussed at this meeting with an intense vigour. Immunology has been the major hurdle in restricting the full realisation of gene therapy in the clinical arena. In summary, the field of gene therapy has progressed from its infancy stage of trying to get it to work, to another stage where attempts are being made to overcome the problems associated with its application, in particular, in relation to human immune responses to the vector and the transgene. This progress should be celebrated and not treated as a failure of this form of therapy, as to make this progress is indeed an achievement for any form of therapy.

Genetic Therapy↗

PubMed2005

Fat necrosis of the breast--a review.

Fat necrosis of the breast is a benign condition that most frequently affects peri-menopausal women. It can mimic breast cancer clinically or radiologically. In other cases it can obscure malignant lesions. The core of this review is derived from a MEDLINE database literature search from 1966-2004. Further references were from lateral search. In this paper, we review the pathogenesis and pathology clinical and radiological features of fat necrosis of the breast. The implication of fat necrosis in the management of patients with breast lump is also discussed. Fat necrosis of breast is a complex process. Therefore, a systematic review of this condition will enable surgeons, radiologists and oncologists working in the field of breast disease to understand it better and improve its management.

Biopsy, Fine-Needle↗

PubMed2005

The evolving role of gene-based treatment in surgery.

BACKGROUND: The completion of the sequencing of the human genome in 2003 marked the dawn of a new era of human biology and medicine. Although these remarkable scientific advances improve the understanding of human biology, the question remains how this rapidly expanding knowledge of functional genomics affects the role of surgeons. This article reviews the potential therapeutic application of gene therapy for various surgical conditions. METHODS: The core of this review was derived from a Medline database literature search. RESULTS AND CONCLUSION: The currently available vectors in the field of gene therapy and their limitations for clinical applications were analysed. The achievements of gene therapy in clinical trials and the future ramifications for surgery were also explored. Whether gene therapy takes a major role in surgical practice will depend greatly on the success of future vector development. Advances in viral vector technology to reduce the inflammatory effect, and improvements in the efficiency of gene delivery using non-viral vector technology, would allow this form of therapy to become more clinically applicable.

Drug Resistance↗

PubMed2005

Systemic administration of naked DNA with targeting specificity to mammalian kidneys.

A major challenge for gene therapy is to be able to deliver efficiently the gene of interest to specific cell types. Here we describe a safe and simple effective naked DNA gene delivery method, via inferior vena cava (IVC) injection, to the recipient's kidneys. It was further demonstrated that gene expression was concentrated in the proximal tubular epithelial cells of the cortico-medullary region of the kidney. Confocal microscopy analyses demonstrated the presence of the exogenous DNA in the renal cell membrane 10 min postgene delivery. However, it was only by 30 min that the presence of the exogenous DNA could be detected in the cell cytoplasm and in the nuclei of the renal cells. Stable expression of the beta-galactosidase gene could be detected for up to 35 days and no toxicity or any adverse pathological effect associated with the delivery method could be observed. Importantly, this IVC gene delivery method could promote the targeting of genes to carcinoma established in the kidney of SCID mice. These results provide the first evidence to support that stable gene expression could be achieved in the renal cells of kidney and the established carcinoma in the kidneys following in vivo gene delivery with naked DNA and could therefore provide the potential to design protocols for the gene therapy of the kidney diseases.

Animals↗

PubMed2005

Pathological diagnosis of columnar cell lesions of the breast: are there issues of reproducibility?

AIMS: To assess inter/intraobserver variability in the interpretation of a series of digitised images of columnar cell lesions (CCLs) of the breast. METHODS: After a tutorial on breast CCL, 39 images were presented to seven staff pathologists, who were instructed to categorize the lesions as follows: 0, no columnar cell change (CCC) or ductal carcinoma in situ (DCIS); 1, CCC; 2, columnar cell hyperplasia; 3, CCC with architectural atypia; 4, CCC with cytological atypia; 5, DCIS. Concordance with the tutor's diagnosis and degree of agreement among pathologists for each image were determined. The same set of images was re-presented to the pathologists one week later, their diagnoses collated, and inter/intraobservor reproducibility and level of agreement for individual images analysed. RESULTS: Diagnostic reproducibility with the tutor ranged from moderate to substantial (kappa values, 0.439-0.697) in the first exercise. At repeat evaluation, intraobserver agreement was fair to perfect (kappa values, 0.271-0.832), whereas concordance with the tutor varied from fair to substantial (kappa values, 0.334-0.669). There was unanimous agreement on more images during the second exercise, mainly because of agreement on the diagnosis of DCIS. The lowest agreement was seen for CCC with cytological atypia. CONCLUSIONS: Interobserver and intraobserver agreement is good for DCIS, but more effort is needed to improve diagnostic consistency in the category of CCC with cytological atypia. Continued awareness and study of these lesions are necessary to enhance recognition and understanding.

Biopsy↗