Biomedical subjects

S L Wong

Publications and source records attributed to S L Wong.

At least 19 recordsLinked to original sources

PubMed2006

Epidemiology and strain characterization of rotavirus diarrhea in Malaysia.

OBJECTIVES: The objectives of the study were to describe the epidemiology and strain characterization of rotavirus (RV), to determine the proportion of hospitalizations for diarrhea attributable to RV among children under 5 years of age, and to estimate the disease burden of RV diarrhea in Malaysia. METHODS: All children 0-59 months of age admitted for acute gastroenteritis to Kuala Lumpur Hospital (KLH) or Hospital Umum Sarawak (HUS) were surveyed. The periods of surveillance were from February 1, 2001 to April 30, 2003 in KLH and April 1, 2001 to March 31, 2003 for HUS. RESULTS: The highest rate of RV-associated diarrhea was among children aged 6-17 months, accounting for 55% of RV-associated diarrhea. There was no seasonality observed in either hospital. P[8]G9 strains were predominant, accounting for 73% of all strains in both hospitals, 80% from KLH and 61% from HUS. There was no mortality. CONCLUSIONS: RV was responsible for 38% of hospitalizations for diarrhea. It was most common in the 6-17 months age group. There was no seasonality observed for RV-associated diarrhea. The most prevalent strain of RV was P[8]G9. The estimated incidence of RV-associated diarrhea was 27 per 10000 population under the age of 5 years per year.

Age Factors↗

PubMed2005

Deaths in children during an outbreak of hand, foot and mouth disease in Peninsular Malaysia--clinical and pathological characteristics.

From July through December 1997, 11 previously healthy children in Peninsular Malaysia succumbed to an illness clinically characterised by an acute severe refractory left-ventricular failure, following a brief prodromal illness, in the midst of an outbreak of hand, foot and mouth disease (HFMD), similar to the reported experience in Sarawak and Taiwan. Retrospective reviews of the clinical features and results of laboratory, pathological and virological investigations of cases were conducted. The median age of the 11 case-patients was 31 months (range, 13 to 49 months); 6 were males. A brief prodromal illness of 3 days (range, 2 to 5 days) was characterised by fever (axillary temperature > 38 degrees C) (100%), oral ulcers (72%), extremity rashes (45%) and significant vomiting (55%). Upon hospitalisation, 7 of 11 case-patients had features suggestive of cardiogenic shock, while 4 of 11 case-patients developed shock during hospitalisation as evidenced by marked sustained tachycardia (heart rate > or = 180 beats per minute), poor peripheral pulses and peripheral perfusion, mottled extremities, pulmonary oedema (haemorrhagic pulmonary secretions in 8 of 11 cases during tracheal intubation, often precipitated by conservative crystalloid boluses, and radiographic evidence of acute pulmonary oedema in 5 of 7 cases) and markedly impaired left ventricular function on echocardiographic examination (7 of 7 cases). Three of 4 case-patients had aseptic meningitis while one case-patient also had an acute flaccid paraparesis. Despite supportive therapy, death occurred within a median of 13.4 hours following hospitalization. Post-mortem findings (all 8 specimens examined) consistently demonstrated brain-stem encephalitis with foci of neuronal necrosis and micro-abscesses. None of the 11 specimens examined revealed histological evidence of myocarditis. Enterovirus 71 (EV71) was detected in 10 of 11 case-patients, many (7) from various sterile tissue sites (5 from central nervous tissues). No other viruses were isolated or identified. Clinical features and pathological studies closely paralleled the reported experience in Sarawak and Taiwan. The uniform necropsy findings of necrotizing brain-stem encephalitis coupled with essentially normal myocardial histology, in concert with the concurrent and consistent detection of EV71 points to a primary EV71 encephalitis; as yet unclear neurogenic mechanisms may account for the cardiovascular manifestations.

Child, Preschool↗

PubMed2004

Interaction of glass-ionomer cements with moist dentin.

Glass-ionomer cements (GICs) are regarded as aqueous gels made up of polyalkenoic acid salts containing ion-leachable glass fillers. The consequence of water permeation across the GIC-dentin interface is unknown. This study used SEM, field-emission/environmental SEM (FE-ESEM), and TEM to examine the ultrastructure of GIC-bonded moist dentin. Dentin surfaces bonded with 6 auto-cured GICs were examined along the fractured GIC-dentin interfaces. Additional specimens fractured 3 mm away from the interfaces were used as controls. SEM revealed spherical bodies along GIC-dentin interfaces that resembled hollow eggshells. FE-SEM depicted similar bodies with additional solid cores. Energy-dispersive x-ray analysis and TEM showed that the spherical bodies consisted of a silicon-rich GIC phase that was absent from the air-voids in the controls. The GIC inclusions near dentin surfaces result from a continuation of the GI reaction, within air-voids of the original polyalkenoate matrix, that occurred upon water diffusion from moist dentin.

Adhesiveness↗

PubMed2004

Small area variations of cancer mortality in Hong Kong--the roles of health care and socio-economic status.

Variations of cancer incidence and cancer mortality across small areas in Hong Kong were explored and attempt made to link them to socio-economic differences. The entire Hong Kong population during the period 1984-88 was divided into 65 small areas. The geographic distributions of incidence and mortality for ten most frequent sites of cancers (6 male and 4 female) were analyzed by separating the systematic variance from the random variance. A Poisson regression model was fitted for each cancer using the standardized incidence ratio (SIR) as a covariate for mortality. The geographic variations in SIR for the individual cancers were, in turn, analyzed similarly using a socio-economic score as the covariate. We found a statistically significant systematic variance in mortality for all six male cancers and three of the four female cancers studied. More than 50% of the systematic variance of mortality for nine cancers could be explained by the geographic variations in incidence, suggesting that other factors, like the provision and/or outcomes of health care services, played a minor role. There were statistically significant systematic variances in SIR for all male and female cancers. The socio-economic score accounted for over 50% of the systematic variance for three cancer sites. This study illustrated an approach to explore underlying explanations for the geographic variations of disease incidence and mortality. As more aggregate exposure data become available at the small area level, this type of ecological analysis would help in delineating the contributions of various factors and guide investigators in their search for the etiology background of diseases.

Female↗

PubMed2002

Modelling death rates for carriers of hepatitis B.

Hepatitis B carriers who acquired the infection perinatally die from hepatocellular carcinoma (HCC) and cirrhosis at high rates. Published cohort studies are largely limited to males and are too small to estimate the age-specific risk of death. We therefore used routinely collected Hong Kong data to estimate the risks. Deaths were partitioned between carriers and non-carriers, then current life table calculations determined life expectancy and probability of dying from HCC or cirrhosis. HCC is the dominant cause of death for male carriers in middle adulthood with a lifetime risk of 27% for HCC compared to 4% for females. Predicted life expectancy is 72 years for male carriers, compared to 79 years for non-carriers. Female carriers have a life expectancy of 81 years and non-carriers 83 years. This model probably applies to all southern Chinese populations and emigrants with similar life history, and other populations that acquired infection early in life.

Adolescent↗

PubMed2001

p53 gene transfer does not enhance E2F-1-mediated apoptosis in human colon cancer cells.

E2F-1 and p53 are sequence specific transcription factors that are intimately involved in the regulation of the cell cycle. In addition to their role in cell cycle control, both E2F-1 and p53 have been identified as tumor suppressors and mediators of apoptosis. We have shown previously that adenoviral-mediated E2F-1 overexpression induces efficient apoptosis in colon adenocarcinoma cells. Previous reports have suggested that E2F-1 and p53 cooperate to mediate apoptosis and therefore, in this study, we examined the efficacy of combination gene therapy using adenovirus vectors expressing E2F-1 and p53 in human colon adenocarcinoma cell lines, HT-29 and SW620 (both mutant p53). Cells were treated by mock infection or infection with adenoviral vectors expressing b-galactosidase (LacZ), E2F-1, p53 or a combination of E2F-1 and p53. IC25 concentrations of each virus were estimated and used for each treatment in order to detect any synergistic or cooperative effects on tumor cell death in the combination therapy. By 5 days post infection, E2F-1-overexpressing cells exhibited growth inhibition and approximately 40-50% cell death in both cell lines. Co-expression of p53 with E2F-1 abrogated E2F-1-mediated growth inhibition and cell death. Cell cycle analysis revealed that overexpression of E2F-1 resulted in an accumulation of cells in G2/M phase, while overexpression of p53 resulted in a G1 phase accumulation. However, co-expression of E2F-1 and p53 counteracted each other as fewer cells accumulated in G1 and G2/M when compared to either p53 or E2F-1 alone. Furthermore, co-expression of p53 with E2F-1 resulted in decreased levels of E2F-1 protein expression. Mechanistically, upregulation of the CDK inhibitory protein, p21(WAF1/CIP1), was demonstrated in HT-29 cells following overexpression of either E2F-1, p53 or the combination E2F-1/p53 therapy. However, in SW620 cells, only the cells infected with Ad-p53 alone or in combination resulted in upregulation of p21(WAF1/CIP1). These results suggest that p53 and p21(WAF1/CIP1) may cooperate to inhibit the expression and activity of E2F-1. In conclusion, combination adenoviral vector-mediated E2F-1 and p53 gene transfer was not therapeutically advantageous in this in vitro model of human colon adenocarcinoma.

Adenocarcinoma↗

PubMed2001

Development and characterization of a series of soluble tetrameric and monomeric streptavidin muteins with differential biotin binding affinities.

The strong biotin-streptavidin interaction limits the application of streptavidin as a reversible affinity matrix for purification of biotinylated biomolecules. To address this concern, a series of single, double, and triple streptavidin muteins with different affinities to biotin were designed. The strategy involves mutating one to three strategically positioned residues (Ser-45, Thr-90, and Asp-128) that interact with biotin and other framework structure-maintaining residues of streptavidin. The muteins were produced in soluble forms via secretion from Bacillus subtilis. The impact of individual residues on the overall structure of streptavidin is reflected by the formation of monomeric streptavidin to different extents. Of the three targeted residues, Asp-128 has the most dramatic effect (Asp-128 > Thr-90 > Ser-45). Conversion of all three targeted residues to alanine results in a soluble biotin binding mutein that exists 100% in the monomeric state. Both wild-type and mutated (monomeric and tetrameric) streptavidin proteins were purified, and their kinetic parameters (on- and off-rates) were determined using a BIAcore biosensor with biotin-conjugated bovine serum albumin immobilized to the sensor chip. This series of muteins shows a wide spectrum of affinity toward biotin (K(d) from 10(-6) to 10(-11) m). Some of them have the potential to serve as reversible biotin binding agents.

Amino Acid Sequence↗

PubMed2001

Roles of glucitol in the GutR-mediated transcription activation process in Bacillus subtilis: glucitol induces GutR to change its conformation and to bind ATP.

GutR is a 95-kDa glucitol-dependent transcription activator that mediates the expression of the Bacillus subtilis glucitol operon. Glucitol allows GutR to bind tightly to its binding site located upstream of the gut promoter. In this study, a second functional role of glucitol is identified. Glucitol induces GutR to change its conformation and triggers GutR to bind ATP efficiently. After sequential binding of glucitol and ATP to GutR, GutR adopts a new conformation by forming a compact structure that is resistant to trypsin digestion. Under this condition, the ATP.glucitiol.GutR complex can dissociate slowly from the gutR-binding site (t(12) = 274 min). Interestingly, if ATP in the ATP.glucitiol.GutR complex is replaced by ADP, GutR adopts another conformation and can dissociate from the gutR-binding site even faster (t(12) = 82 min). In all these GutR-DNA binding studies in the presence of different ligands (glucitol, ATP, or ADP), only the off-rate is affected. The vital role of ATP in the GutR-mediated transcription activation process is reflected by the poor transcription from the gut promoter with GutR(D285A) which has a mutation in the motif B of the putative ATP-binding site. A working model for this transcription activation process is presented.

Adenosine Triphosphate↗

PubMed2001

Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of nonsentinel nodes following completion lymphadenectomy for melanoma.

INTRODUCTION: Most melanoma patients with sentinel lymph nodes (SLN) that are histologically positive for metastasis have no additional positive lymph nodes found upon completion lymph node dissection (CLND). Therefore, it has been suggested that CLND may not be required for all patients with positive SLN. This study was undertaken to determine the frequency with which nonsentinel nodes contain melanoma cells detected by RT-PCR. METHODS: Negative control lymph nodes were obtained from patients with breast and colon cancer. Positive control lymph nodes contained histologic evidence of melanoma. Nonsentinel nodes were harvested from melanoma patients undergoing CLND for a positive SLN. RT-PCR analysis for melanoma markers tyrosinase, gp100, MART-1, and MAGE-3 was performed, with Southern blot detection. The RT-PCR test was considered positive for the presence of melanoma cells if tyrosinase and at least one other marker were detected above background levels. RESULTS: RT-PCR analysis detected the presence of melanoma cells in 0/100 (0%) of negative control lymph nodes and 28/29 (97%) of positive control lymph nodes. A total of 117 histologically negative nonsentinel nodes from 13 patients who underwent CLND for positive SLN were evaluated. RT-PCR analysis was positive in 18/117 histologically negative nonsentinel nodes (15%) from 7/13 patients (54%). CONCLUSION: RT-PCR analysis suggests that when the SLN contains histologic evidence of melanoma, the remaining nodes in that basin are at risk for metastatic disease, despite the fact that these nonsentinel nodes are infrequently histologically positive.

Breast Neoplasms↗

PubMed2001

Predicting the status of the nonsentinel axillary nodes: a multicenter study.

BACKGROUND: Sentinel lymph node (SLN) biopsy is a minimally invasive procedure that provides accurate nodal staging information. The need for completion axillary dissection after finding a positive SLN for breast cancer has been questioned. HYPOTHESIS: The presence of nonsentinel node (NSN) metastases in the axillary dissection specimen correlates with tumor size, the number of SLNs removed, and the number of positive SLNs. DESIGN: Prospective, multi-institutional study. PARTICIPANTS AND METHODS: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a nationwide study involving 148 surgeons. All patients underwent SLN biopsy, followed by level I/II axillary dissection. All SLNs were evaluated histologically at a minimum of 2-mm intervals. Immunohistochemical analysis using antibodies for cytokeratin was performed at the discretion of each participating institution. All NSNs were evaluated by routine histologic examination. RESULTS: An SLN was identified in 1268 (90%) of 1415 patients. Increasing tumor size was significantly correlated with increasing likelihood of positive NSNs: T1a, 14%; T1b, 22%; T1c, 30%; T2, 45%; and T3, 57% (P =.002, chi(2) test). The presence of positive NSNs was not significantly associated with the number of SLNs removed. Patients with more than 1 positive SLN were more likely to have positive NSNs than those with only 1 positive SLN (50% vs 32%; P<.001, chi(2) test). Increasing tumor size and the presence of multiple positive SLNs were also associated with the presence 4 or more positive axillary nodes. Multivariate analysis confirmed that tumor size and the number of positive SLNs were independent factors predicting the presence of positive NSNs. CONCLUSIONS: The likelihood of positive NSNs correlates with increasing tumor size and the presence of multiple positive SLNs. However, even patients with small primary tumors have a substantial risk of residual axillary nodal disease after SLN biopsy. These data will be helpful in counseling patients regarding the need for completion axillary dissection after a positive SLN is identified.

Axilla↗

PubMed2001

Sentinel lymph node biopsy for melanoma: how many radioactive nodes should be removed?

BACKGROUND: Sentinel lymph node (SLN) biopsy has become a standard method of staging patients with cutaneous melanoma. Sentinel lymph node biopsy usually is performed by intradermal injection of a vital blue dye (isosulfan blue) plus radioactive colloid (technetium sulfur colloid) around the site of the tumor. Intraoperative gamma probe detection has been shown to improve the rate of SLN identification compared to the use of blue dye alone. However, multiple sentinel nodes often are detected using the gamma probe. It is not clear whether these additional lymph nodes represent true sentinel nodes, or second-echelon lymph nodes that have received radiocolloid particles that have passed through the true sentinel node. This analysis was performed to determine the frequency with which these less radioactive lymph nodes contain metastatic disease when the most radioactive, or "hottest," node does not. MATERIALS AND METHODS: In the Sunbelt Melanoma Trial, 1184 patients with cutaneous melanoma of Breslow thickness 1.0 mm or more had sentinel lymph nodes identified. Sentinel lymph node biopsy was performed by injection of technetium sulfur colloid plus isosulfan blue dye in 99% of cases. Intraoperative determination of the degree of radioactivity of sentinel nodes (ex vivo) was measured, as well as the degree of blue dye staining. RESULTS: Sentinel nodes were identified in 1373 nodal basins in 1184 patients. A total of 288 of 1184 patients (24.3%) were found to have sentinel node metastases detected by histology or immunohistochemistry. Nodal metastases were detected in 306 nodal basins in these 288 patients. There were 175 nodal basins from 170 patients in which at least one positive sentinel node was found and more than one sentinel node was harvested. Blue dye staining was found in 86.3% of the histologically positive sentinel nodes and 66.4% of the negative sentinel nodes. In 40 of 306 positive nodal basins (13.1%), the most radioactive sentinel node was negative for tumor when another, less radioactive, sentinel node was positive for tumor. In 20 of 40 cases (50%), the less radioactive positive sentinel node contained 50% or less of the radioactive count of the hottest lymph node. The cervical lymph node basin was associated with an increased likelihood of finding a positive sentinel node other than the hottest node. CONCLUSIONS: If only the most radioactive sentinel node in each basin had been removed, 13.1% of the nodal basins with positive sentinel nodes would have been missed. It is recommended that all blue lymph nodes and all nodes that measure 10% or higher of the ex vivo radioactive count of the hottest sentinel node should be harvested for optimal detection of nodal metastases.

Chi-Square Distribution↗

PubMed2001

Reliable lymphatic drainage to axillary sentinel lymph nodes regardless of tumor location within the breast.

BACKGROUND: This analysis was performed in order to determine whether primary tumor location in breast cancer affects the axillary sentinel lymph node (SLN) identification (ID) rate, the false negative (FN) rate, incidence of axillary nodal metastases, or the number of SLN identified. METHODS: In this prospective multi-institutional study, SLN biopsy was performed on clinical stage T1-2, N0 breast cancer patients using blue dye alone or in combination with radioactive colloid, followed by completion axillary LN dissection. RESULTS: Central tumor location was associated with an improved FN rate, which may be related to reliable drainage from the subareolar lymphatic plexus. Tumor location did not significantly affect the SLN ID rate or the mean number of SLN identified. Medial tumor location was associated with a decreased rate of axillary nodal metastasis. CONCLUSIONS: Breast cancers drain reliably to the axillary lymph nodes regardless of tumor location within the breast.

Axilla↗

PubMed2001

The use of cytokeratin staining in sentinel lymph node biopsy for breast cancer.

BACKGROUND: Controversy exists regarding the routine use of cytokeratin immunohistochemistry (IHC) in the histopathologic examination of breast cancer sentinel lymph nodes (SLN) because the clinical significance of micrometastases detected by IHC is unclear. This analysis was performed to determine the frequency of IHC-detected micrometastases. METHODS: All patients underwent SLN biopsy, followed by completion axillary dissection. This analysis included patients who had SLN evaluated by IHC. SLN were examined by hematoxylin and eosin (H&E) stain at 2-mm intervals, with IHC in 2 sections. The axillary dissection specimen was evaluated by routine H&E staining. RESULTS: IHC was performed in SLNs from 973 patients. Of the 869 patients with negative nodes by H&E, 58 (6.7%) were "upstaged" by IHC. In 6 of 58 patients (10.3%) who had IHC-only positive SLN, nodal metastases were found in the axillary dissection specimen. CONCLUSIONS: IHC resulted in upstaging of 6.7% of patients who had negative SLN on H&E staining. These patients had a 10.3% risk of residual axillary nodal metastases. However, the clinical significance of IHC-only positive SLN requires further study.

Axilla↗

PubMed2001

Utility of intraoperative frozen section analysis of sentinel lymph nodes in breast cancer.

BACKGROUND: Intraoperative frozen section pathologic analysis of sentinel lymph node (SLN) may guide immediate (single-stage) completion axillary dissection for patients with nodal metastases. METHODS: The results of 203 consecutive patients undergoing SLN biopsy who had intraoperative pathology consultation between January 1998 and September 2000 were reviewed. SLN were analyzed by standard frozen section procedures. Final pathologic analysis included hematoxylin and eosin (H&E) staining of serial sections at 2-mm intervals. RESULTS: Frozen section analysis correctly identified a positive or negative result in 185 of 203 cases (overall accuracy 91%). In 17 of 53 cases, the SLNs were negative for tumor by frozen section, but positive on permanent section analysis (sensitivity 68%). The mean size of the nodal metastases was 6.2 mm and 1.5 mm in patients found to have true positive and false negative results, respectively (P <0.003). A single false positive SLN is reported. CONCLUSIONS: Two thirds of the patients were spared the need for reoperative axillary lymphadenectomy.

Aged↗

PubMed2001

Radiofrequency ablation for unresectable hepatic tumors.

BACKGROUND: Radiofrequency ablation (RFA) is a relatively new treatment for unresectable hepatic tumors. The purpose of this analysis was to examine the frequency of complications and local recurrence associated with RFA. METHODS: Patients who underwent RFA of hepatic tumors with curative intent were included in this study. At laparotomy, RFA was performed using intraoperative ultrasound guidance. Computed tomography scans were obtained in the immediate postoperative period and every 3 to 6 months thereafter. RESULTS: Forty patients underwent RFA for 122 hepatic tumors. Thirty-one patients had metastatic lesions from colorectal cancer; 9 had other liver tumors. Complications occurred in 8 patients. With 9.5 months median follow-up, 6 patients had local recurrence of their ablated tumors. CONCLUSIONS: Our initial experience shows that RFA can effectively eradicate unresectable hepatic tumors. The rate and severity of complications appear acceptable. However, further study is necessary to assess long-term recurrence rates and effect on overall survival.

Catheter Ablation↗

PubMed2001

Sentinel lymph node biopsy for breast cancer: impact of the number of sentinel nodes removed on the false-negative rate.

BACKGROUND: Numerous studies have demonstrated that sentinel lymph node (SLN) biopsy can accurately determine axillary nodal status for breast cancer, but unacceptably high false negative rates have also been reported. Attention has been focused on factors associated with improved accuracy. We have previously shown that injection of blue dye in combination with radioactive colloid reduces the false negative rate compared with injection of blue dye alone. We hypothesized that this may be from the increased ability to identify multiple sentinel nodes. The purpose of this analysis was to determine whether removal of multiple SLNs results in a lower false negative rate. STUDY DESIGN: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multiinstitutional study. Patients with clinical stage T1-2, N0 breast cancer were eligible for enrollment. All patients underwent SLN biopsy using blue dye alone, radioactive colloid alone, or both agents in combination, followed by completion level I and II axillary dissection. RESULTS: A total of 1,436 patients were enrolled in the study from August 1997 to February 2000. SLNs were identified in 1,287 patients (90%), with an overall false negative rate of 8.3%. A single SLN was removed in 537 patients. Multiple SLNs were removed in 750 patients. The false negative rates were 14.3% and 4.3% for patients with a single sentinel node versus multiple sentinel nodes removed, respectively (p = 0.0004, chi-square). Logistic regression analysis revealed that use of blue dye injection alone was the only factor independently associated with identification of a single SLN (p<0.0001), and patient age, tumor size, tumor location, surgeon's previous experience, and type of operation were not significant. CONCLUSIONS: The ability to identify multiple sentinel nodes, when they exist, improves the diagnostic accuracy of SLN biopsy. Injection of radioactive colloid in combination with blue dye improves the ability to identify multiple sentinel nodes compared with the use of blue dye alone.

Breast Neoplasms↗

PubMed2001

Additive effect of adenovirus-mediated E2F-1 gene transfer and topoisomerase II inhibitors on apoptosis in human osteosarcoma cells.

Recently, it has been demonstrated that Etoposide, a topoisomerase II inhibitor, can induce apoptosis in MDM2-overexpressing tumor cells by inhibition of MDM2 synthesis. We have previously shown that E2F-1 overexpression induces apoptosis of MDM2-overexpressing sarcoma cells, which is related to the inhibition of MDM2 expression. Therefore, the present study was designed to investigate the in vitro and in vivo effect of combined treatment of adenovirus-mediated E2F-1 and topoisomerase II inhibitors on the growth inhibition and apoptosis in human sarcoma cells. Two human sarcoma cell lines, OsACL and U2OS, were treated with topoisomerase II inhibitors (Etoposide and Adriamycin), alone or in combination with adenoviral vectors expressing beta-galactosidase (Ad-LacZ) or E2F-1 (Ad-E2F-1). E2F-1 expression was confirmed by Western blot analysis. Ad-E2F-1 gene transfer at a low dose (multiplicity of infection, 2) markedly increased the sensitivity of human sarcoma cells to topoisomerase II inhibitor treatment. This cooperative effect of E2F-1 and topoisomerase II inhibitors was less marked in SAOS-2 cells (p53 and pRb null). Topoisomerase II inhibitors also cooperated with E2F-1 overexpression to enhance tumor cell killing in an in vivo model using xenografts in nude mice. When combined with Adriamycin or Etoposide, E2F-1 adenovirus therapy resulted in approximately 95% and 85% decrease in tumor size, respectively, compared to controls (P<.05). These results suggest a new chemosensitization strategy that is effective in MDM2-overexpressing tumors and may have clinical utility.

Adenoviridae↗

PubMed2001

Factors that predict the presence of sentinel lymph node metastasis in patients with melanoma.

BACKGROUND: This analysis was performed to identify prognostic factors that are predictive of sentinel lymph node (SLN) metastasis in melanoma. METHODS: Analysis was performed of a multi-institutional, prospective, randomized trial of SLN biopsy for melanoma. Eligibility criteria included age 18 to 70 years, Breslow thickness of 1.0 mm or more, and clinically negative regional lymph nodes. SLNs were evaluated by serial sectioning and immunohistochemistry for S100. Univariate chi-square and multivariate logistic regression analyses were performed to assess factors predictive of the presence of a positive SLN. Probability values of less than.05 were considered significant. RESULTS: SLNs were identified in 99.7% of patients. A total of 1058 patients were evaluated; 961 patients had complete data and were included in the statistical analysis. SLNs were positive for tumor in 208 of 961 patients (22%). Breslow thickness, Clark level, ulceration, and patient age were factors that were found to be independently predictive of the presence of SLN metastasis. CONCLUSIONS: Increasing Breslow thickness, Clark level of more than III, the presence of ulceration, and patient age of 60 years or less are the most important independent prognostic factors associated with the finding of positive SLN in patients with melanoma.

Adolescent↗