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Biomedical subjects

M Teh

Publications and source records attributed to M Teh.

At least 19 recordsLinked to original sources

Lymphocytic gastritis-like T cell lymphoma: molecular evidence of an unusual recurrence.

This report describes a patient with a gastric biopsy specimen showing histomorphological and immunohistochemical appearances indistinguishable from those usually present in lymphocytic gastritis, a rare condition of unknown aetiology with a distinctive phenotype. The patient had a history of a biopsy confirmed T cell non-Hodgkin lymphoma at two anatomical sites (bladder and stomach), which was subsequently treated. Molecular analysis of the T cell receptor (TCR) gamma chain gene rearrangements showed a distinct monoclonal T cell population in the bladder and gastric biopsies. The same analysis in the lymphocytic gastritis-like biopsy sample showed a monoclonal population with identical base pair size to that identified in the other specimens. This report highlights the importance of TCR gene rearrangement analysis in the diagnosis of unusual gastric inflammation, and the use of capillary electrophoresis based polymerase chain reaction in the follow up of lymphoproliferative disorders.

Antigens, CD↗

Inhibition of angiopoietin-1 expression in tumor cells by an antisense RNA approach inhibited xenograft tumor growth in immunodeficient mice.

Angiopoietin-1 (Ang1) is an angiogenic growth factor that functions through activation of its endothelium-specific tyrosine kinase receptor Tie2; it mediates the interaction between endothelial and surrounding cells to promote the remodeling, maturation and stabilization of blood vessels. Although Ang1 is expressed constitutively in many adult tissues, its role in tumor growth and metastasis is not clear. Here we describe experiments in which Ang1 expression was inhibited in HeLa cells by an antisense RNA approach. The modified HeLa cells produced significantly less Ang1 protein both in cultured cells and in tumors formed when these cells were injected into immunodeficient mice. The Ang1 antisense tumors grew much more slowly, with significantly reduced tumor angiogenesis compared with control tumors. Furthermore, they also had substantially increased tumor cell apoptosis and decreased tumor necrosis. Our results indicate that the perturbation of Ang1 expression in tumors could be an effective method to control tumor growth by inhibiting tumor angiogenesis and that antisense RNA is an efficient way to inhibit Ang1 protein production in tumor cells.

Angiopoietin-2↗

Cytochrome P4501A2 (CYP1A2) activity and lung cancer risk: a preliminary study among Chinese women in Singapore.

There is increasing evidence for the role of heterocyclic and other arylamines in carcinogenesis, including lung carcinogenesis. Chinese women have a high rate of lung cancer despite a low smoking prevalence, and studies in this population may provide useful information on risk factors other than smoking. Hepatic CYP1A2 and NAT2 are involved in the metabolism of carcinogenic arylamines, and NAT2 also catalyzes the detoxification pathway for these compounds. In this study, we examined the effect of CYP1A2 activity using a urinary caffeine metabolic ratio assay for 54 Chinese women with newly diagnosed lung cancer (including 28 adenocarcinomas) and 174 hospital controls. Among them, NAT2 genotype was available for 47 cases and 98 controls. There was no effect of CYP1A2 activity on overall risk of lung cancer in the study population [odds ratio (OR) 0.8, 95% confidence interval (CI) 0.4-1.6, adjusted for age at diagnosis, smoking and cruciferous vegetable intake]. For adenocarcinomas, the OR was 1.5, 95% CI 0.6-3.4. After further adjustment for NAT2 acetylator genotype, the OR for adenocarcinoma was 1.8 (95% CI 0.7-4.8). When the combined NAT2/CYP1A2 status was examined, women with slow NAT2 and rapid CYP1A2 activity were at highest risk (adjusted OR 6.9, 95% CI 1.3-37.6) relative to women with rapid NAT2 and slow CYP1A2 activity, for lung adenocarcinoma. While larger studies are needed to confirm or refute these results, they are consistent with a role for heterocyclic arylamines in lung carcinogenesis in this primarily non-smoking population.

Adenocarcinoma↗

Dietary isothiocyanates, glutathione S-transferase -M1, -T1 polymorphisms and lung cancer risk among Chinese women in Singapore.

Chinese populations consume a diet relatively high in isothiocyanates (ITCs), a derivative of cruciferous vegetables known to have cancer-protective effects. This class of compounds is metabolized by the glutathione S-transferase family of enzymes, which are also involved in the detoxification of tobacco-related carcinogens such as polycyclic aromatic hydrocarbons and alkyl halides. We evaluated the association between dietary isothiocyanate intake, GSTM1 and GSTT1 polymorphisms, and lung cancer risk in 420 Chinese women: 233 histologically confirmed lung cancer patients and 187 hospital controls. Among these, 58.8% of cases and 90.3% of controls were lifetime nonsmokers. An allele-specific PCR method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in DNA isolated from peripheral blood. Higher weekly intake of ITCs (above the control median value of 53.0 micromol) reduced the risk of lung cancer to a greater extent in smokers [adjusted odds ratio (OR), 0.31; 95% confidence interval (CI), 0.10-0.98] than nonsmokers (OR, 0.70; 95% CI, 0.45-1.11). The inverse association was stronger among subjects with homozygous deletion of GSTM1 and/or GSTT1. Among nonsmokers with GSTM1-null genotype, higher intake of ITCs significantly reduced the risk of lung cancer (OR, 0.54; 95% CI, 0.30-0.95), an effect not seen among those with detectable GSTM1 (OR, 1.07; 95% CI, 0.50-2.29). Our results, in a Chinese female population, are consistent with the hypothesis that ITC is inversely related to the risk of lung cancer, and we show that among nonsmokers this effect may be primarily confined to GST-null individuals. Conjugation and elimination of ITCs is enhanced in GST-non-null relative to -null individuals, such that the GST metabolic genotype modifies the protective effect of ITCs on lung cancer development.

Adult↗

Fumes from meat cooking and lung cancer risk in Chinese women.

Chinese women are recognized to have a high incidence of lung cancer despite a low smoking prevalence. Several studies have implicated domestic exposure to cooking fumes as a possible risk factor, although the exact carcinogens have yet to be identified. Heterocyclic amines are known carcinogens, which have been identified in cooked meat, and also in fumes generated during frying or grilling of meats. We conducted a case-control study of 303 Chinese women with pathologically confirmed, primary carcinomas of the lung and 765 controls to examine the association between exposure to meat cooking and lung cancer risk. Data on demographic background, smoking status, and domestic cooking exposure, including stir-frying of meat, were obtained by in-person interview while in hospital. The response rates among eligible cases and controls were 95.0 and 96.9%, respectively. The proportion of smokers (current or ex-smokers) among cases and controls was 41.7 and 13.1%, respectively. Adenocarcinomas comprised 31.5% of cancers among smokers and 71.6% among nonsmokers. When cases were compared with controls, the odds ratio (OR) for lung cancer (all subtypes) among ex-smokers was 4.3 [95% confidence interval (CI) 2.7-6.8] and that among current smokers was 5.0 (95% CI, 3.4-7.3). Among smokers, women who reported that they stir-fried daily in the past had a significantly increased risk of lung cancer (adjusted OR, 2.0; 95% CI, 1.0-3.8) and among these women, risk was enhanced for those who stir-fried meat daily (OR, 2.7; 95% CI, 1.3-5.5). Women who stir-fried daily but cooked meat less often than daily did not show an elevated risk (OR, 1.0. 95% CI, 0.5-2.4). Risk was further increased among women stir-frying meat daily who reported that their kitchen was filled with oily fumes during cooking (OR, 3.7; 95% CI, 1.8-7.5). These cooking practices on their own did not increase risk among nonsmokers in our study population. Our results suggest that inhalation of carcinogens, such as heterocyclic amines generated during frying of meat, may increase the risk of lung cancer among smokers. Further studies in different settings are warranted to examine this possibility, which may also help to explain the higher risk observed among women smokers compared with men.

Adenocarcinoma↗

An unusual case of multiple recurrence of a glomangioma.

Glomus tumour is a benign lesion arising from the glomus apparatus of the skin and subcutaneous tissue. Glomangioma is the angiomatous variant, which is uncommon. We report a very rare presentation of a glomangioma with multiple recurrences. We advocate preoperative angiography to delineate the extent of the lesion to facilitate complete excision.

Adult↗

NAT2 slow acetylator genotype is associated with increased risk of lung cancer among non-smoking Chinese women in Singapore.

Among non-smokers, the factors resulting in lung carcinogenesis are poorly understood. We conducted a hospital-based case-control analysis of 294 Chinese women, of whom 217 were non-smokers, to evaluate the role of polymorphic N-acetyltransferase (NAT2) as a susceptibility factor for the disease. The proportion of slow acetylator genotypes among non-smoking cases (n = 92) and controls (n = 125) was 38.0 and 24.0%, respectively [odds ratio (OR) 2.0, 95% confidence interval (CI) 1.1-3.7]. No effect of NAT2 genotype was seen among smokers. Among non-smokers, the effect was marked for adenocarcinomas (OR 2.1, 95% CI 1.1-4.0). As NAT2 activity is known to modify risk of arylamine-induced carcinogenesis, our results suggest that exposure to arylamines in the environment may play a role in risk of lung cancer among non-smokers.

Acetylation↗

Effects of physical barriers in prevention of adhesions: an incisional hernia model in rats.

BACKGROUND: Adhesion formation between viscera and mesh is almost inevitable following incisional hernia repair with prosthetic mesh. Such adhesions may lead to intestinal obstruction and enterocutaneous fistulae formation and make further laparotomies extremely difficult. Sodium carboxymethylcellulose (SCMC) and Interceed TC7 (oxidized regenerated cellulose) as physical barriers have been shown to be effective in reducing postoperative adhesions. MATERIALS AND METHODS: To evaluate the effects of SCMC and Interceed TC7, we used an incisional hernia model in rats. A ventral abdominal defect (15 x 25 mm) was created in each of 36 male rats which were then divided into three equal groups. In Group I (control) the defect was repaired with polypropylene mesh (PPM) only; in Group II the defect was repaired after a layer of Interceed TC7 was laid over the viscera with Interceed TC7-covered PPM; in Group III the defect was repaired after a layer of SCMC was laid over the viscera with SCMC-coated PPM. Six of the animals from each group were sacrificed at Postoperative Day 7 and the adhesions were scored. The remaining 6 were sacrificed at Day 30 and histological evaluation was made in addition to the adhesion score. RESULTS: Animals in the SCMC-treated group developed significantly less adhesions (P = 0.0002) compared with control and Interceed TC7-treated groups. However, histological analysis revealed poor fibroblast proliferation with impaired wound healing in the SCMC group. CONCLUSION: SCMC prevented adhesion formation but seriously impaired wound healing, and Interceed TC7 was ineffective in preventing adhesion in this model.

Animals↗

Haemangioendothelioma in an infant's wrist.

A rare case of an epitheloid haemangioendothelioma presenting as an aggressive soft tissue mass in the wrist of an infant is presented. The management of the lesion presents particular difficulties because of its diffuse involvement of surrounding muscles, tendons and neurovascular bundle and the importance of preserving hand function. The epitheloid haemangioendothelioma rarely occurs extravascularly with less than 15 such cases reported in the literature.

Angiography↗

Effect of cisapride on functional dyspepsia in patients with and without histological gastritis: a double-blind placebo-controlled trial.

In the present double-blind placebo-controlled study the effect of cisapride on functional dyspepsia was evaluated in patients with and without histological gastritis. Patients with functional dyspepsia and whose symptoms persisted after a 2 week run-in period with antacid treatment were randomized to receive cisapride (10 mg) or matching placebo three times daily for 4 weeks. Symptoms of epigastric pain, bloating, nausea, belching, early satiety and heartburn were graded on a four-point scale based on patients' feedback and diary card recording. A global response was also formulated by the investigators. One hundred and four patients entered the study and 76 completed the trial, comprising 36 patients with histological gastritis and 40 patients without gastritis. Symptom scores in both gastritis and non-gastritis groups were significantly improved by both cisapride and placebo; however, the improvement was not statistically different between the two treatment groups. Cisapride produced a good or better global response in 58% of subjects with histological gastritis and in 53% of subjects without gastritis compared with 47% and 52%, respectively, of patients on placebo; this difference was not statistically significant. Gastric histology did not influence the effect of cisapride on the symptoms of functional dyspepsia.

Adult↗

An immunohistochemical study of p53 protein in ovarian mucinous neoplasms.

p53 gene mutations are among the most common genetic lesions in human cancers. While previous studies have established the presence of p53 protein in ovarian carcinomas some have not shown the alteration of the p53 gene to be a feature in benign or borderline ovarian epithelial neoplasms. In this study we examined both benign and borderline malignant/malignant mucinous neoplasms for p53 protein accumulation by the means of an anti-human p53 protein monoclonal antibody on paraffin sections. Our results show that p53 protein accumulation is associated to a similar degree with both malignant mucinous cystadenocarcinomas and mucinous cystademonas of borderline malignancy. This suggests that p53 mutations may play an important and early role in the malignant transformations of one-third or more of mucinous ovarian neoplasms. Furthermore, among the mucinous cystadenomas of borderline malignancy where p53 staining was present, staining could be found in the morphologically benign areas thus indicating that, despite their innocuous appearance, such epithelial cells might have already taken a very important step in their evolution to frank malignancy.

Cystadenoma↗

An immunohistochemical study of p53 protein in cervical intraepithelial neoplasia and squamous cell carcinoma.

p53 mutations are known to occur frequently in human cancers where they are considered to be an important event in the stepwise progression towards malignant transformation. It is therefore interesting to compare p53 expression in the uterine cervix for non-neoplastic/metaplastic squamous epithelium, cervical intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma. One hundred and nineteen biopsied and resected specimens of the uterine cervix were stained with an anti-human p53 protein monoclonal antibody by the streptavidin-biotin immunoperoxidase method. Histologically these could be categorized into non-neoplastic/dysplastic conditions, including condyloma (34 cases), CIN 1-3 (66 cases) and invasive squamous cell carcinoma (19 cases). Fifty eight per cent (11/19) of the invasive squamous cell carcinomas and 11% (7/66) of the CIN stained positively for p53. Except for 3 cases of invasive squamous cell carcinoma, there was only sporadic intranuclear staining of less than 5% of the cells. No staining was observed in all non-neoplastic/metaplastic squamous epithelial cells. The pattern of p53 staining is significantly different for all 3 categories. However it is undetermined as to whether the positive immunoperoxidase staining is a direct consequence of p53 gene mutation or otherwise.

Antibodies, Monoclonal↗

Extraskeletal Ewing's sarcoma presenting with pulmonary embolism.

Small round cell tumours with the morphologic characteristics of Ewing's sarcoma arise rarely in soft tissues of the extremities, retroperitoneum, chest and orbit. Patients usually present with symptoms arising from the swelling at the primary site. We report on a patient with a retroperitoneal extraskeletal Ewing's sarcoma who presented with massive tumour embolism to the pulmonary vasculature. To our knowledge, this is the first report of extraskeletal Ewing's sarcoma presenting with pulmonary tumour embolism.

Adult↗

p53 expression in hepatocellular carcinoma in a population in Singapore with endemic hepatitis B virus infection.

AIMS: To study the expression and clinical significance (if any) of p53 protein in hepatocellular carcinomas (HCC) arising in a population with endemic hepatitis B virus (HBV) infection. METHODS: Immunohistochemical staining was performed on formalin fixed, paraffin was embedded histological sections of 46 HCC cases using an antihuman p53 monoclonal antibody; serial sections were also stained for hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) and alpha fetoprotein (AFP). Nuclear p53 staining was assessed according to intensity (absent, weak or strong) and extent (< 5%, 6-25%, 26-50%, and > 50%) of positive cells. Tissue HBsAg, HBcAg and AFP were recorded as absent or present. RESULTS: The p53 protein was expressed in 35% (16 of 46) of HCCs; the positive rate in grade III/IV tumours (13 of 31; 42%) was higher than in grade I/II tumours (three of 15; 20%) but this was not statistically significant. HBsAg positive tumours showed almost the same proportion of p53 staining (11 of 29; 38%) as HBsAg negative ones (five of 17; 29%). CONCLUSIONS: The p53 protein was expressed in 35% of HCC cases. There was no statistically significant correlation between HBV infection and p53 protein expression. Similarly, there was no definite correlation between p53 positivity and tumour size, histological grade or vascular invasion.

Adult↗

An immunohistochemical study of p53 protein in gallbladder and extrahepatic bile duct/ampullary carcinomas.

BACKGROUND: p53 mutations are known to occur frequently in human cancers, including gallbladder carcinoma. However, there has been no study of p53 expression in extrahepatic bile duct/ampullary carcinoma. Furthermore, gallbladder carcinoma is associated with cholelithiasis, whereas no such association is known for extrahepatic bile duct carcinoma, suggesting that they could arise from different pathogenetic mechanisms. METHODS: Twenty-four gallbladder carcinomas and 35 extrahepatic bile duct/ampullary carcinomas were stained with an anti-human p53 protein monoclonal antibody by the streptavidin-biotin immunoperoxidase method. Both the extent and intensity of p53 protein staining were noted. RESULTS: Ninety-two percent of the gallbladder carcinomas stained for p53 protein compared with only 66% of the extrahepatic bile duct/ampullary carcinomas. The statistical significance was maintained even when the comparison was restricted to strong p53 staining in moderately to poorly differentiated adenocarcinomas (P < 0.05). Of the gallbladder carcinomas, poorly differentiated adenocarcinomas stained more strongly than well to moderately differentiated adenocarcinomas; the converse was true for extrahepatic bile duct/ampullary adenocarcinomas. CONCLUSION: The majority of gallbladder and extrahepatic bile duct/ampullary carcinomas stain for p53 protein. The incidence and pattern of staining is different, however, and supports the contention that these could be different tumors with differing etiologies and pathogenetic mechanisms.

Adenocarcinoma↗

p53 expression in pseudoepitheliomatous hyperplasia, keratoacanthoma, and squamous cell carcinoma of skin.

BACKGROUND: Expression of p53 protein has been described in a variety of human malignant tumors. Recent reports have also demonstrated its presence in benign and reactive lesions. The significance of p53 expression is unclear. METHODS: This study examines the p53 expression in proliferative lesions of skin, including 6 pseudoepitheliomatous hyperplasia, 33 keratoacanthoma, and 45 squamous cell carcinoma, and to evaluate its significance. RESULTS: p53 expression was observed in all of the six cases of pseudoepitheliomatous hyperplasia, 78.8% of keratoacanthoma, and 75.5% of squamous cell carcinoma. The staining pattern of pseudoepitheliomatous hyperplasia and keratoacanthoma was generally less intense and extensive compared with that of squamous cell carcinoma. A keratoacanthoma with nuclear atypia that showed strong and extensive p53 staining was also encountered. The perilesional skin in sun-exposed sites often showed the presence of p53-positive keratinocytes. Control skin taken from the buttock was negative for p53 protein. Conversely, p53 was often expressed in carcinomas arising from sun-exposed as well as sun-protected sites. p53 positivity involved mainly the undifferentiated cells at the base of the epidermis or periphery of tumor cords. Differentiated keratinized cells were not stained. p53-positive fibroblasts were also noted in the inflammatory and granulation tissues of pseudoepitheliomatous hyperplasia. CONCLUSIONS: p53 expression in skin is common and appears to be an early event in a series of genetic alterations reflecting underlying actinic damage, which may lead to but does not necessarily indicate neoplastic or malignant transformation. Because p53 staining is seen in proliferative and undifferentiated cells and ceases to be expressed when the cells differentiate, it appears that the expression of p53 protein, mutant or wild-type, is an indicator of immaturity and proliferative capacity of the cell rather than one of neoplasia or malignancy.

Carcinoma, Squamous Cell↗

An immunohistochemical study of p53 protein in the different histological subtypes of gastric carcinoma.

p53 mutations are known to occur frequently in human cancers, including gastric carcinomas. Previous studies of its incidence in gastric carcinomas had shown a varying incidence ranging from a low of 4% to as high as 57%. In this study, 42 cases of gastric carcinomas were analyzed for p53 using a commercially available mouse monoclonal antibody in routinely formalin-fixed paraffin-embedded tissue sections. These included 22 intestinal-type (7 well/moderately differentiated and 15 poorly differentiated), 16 diffuse-type and 4 mixed. Altogether, 60% of our cases stained positively for p53. Overall, well/moderately differentiated intestinal-type carcinomas stained more frequently for p53 than poorly differentiated intestinal-type carcinomas (p < 0.075). A comparison between the incidence in diffuse-type (69%) and intestinal type (55%) was unremarkable. p53 staining was also present in 3 of the 4 early cases studied. The results suggest that p53 mutations play an important role in carcinogenesis in gastric carcinoma and further implies that p53 mutation may be an early occurrence during tumor transformation.

Carcinoma↗