Biomedical subjects

K M McMasters

Publications and source records attributed to K M McMasters.

At least 19 recordsLinked to original sources

PubMed2006

Intraoperative magnetic resonance imaging for ablation of hepatic tumors.

BACKGROUND: The most significant rise in the use of hepatic ablation has come from image-guided techniques with both computed tomography (CT) and ultrasound (US). The recent development of open-configuration magnetic resonance scanners has opened up an entire new area of image-guided surgical and interventional procedures. Thus the aim of this study was to evaluate the use of intraoperative MRI (iMRI) ablation of hepatic tumors performed by surgeons. METHOD: Percutaneous iMRI hepatic ablation was performed from January 2003 to February 2005 for control of either primary or secondary hepatic disease. RESULTS: Eighteen hepatic ablations were performed on 11 patients with a median age of 71 (range: 51-81) years for metastatic colorectal cancer (n = 6), hepatocellular cancer (n = 2), cholangiocarcinoma (n = 2), and metastatic neuroendocrine (n = 1). Median hospital stay was 1 day, with complications occurring in 2 patients. After a median follow up of 18 months, there have been no local ablation recurrences, 5 patients are free of disease, 4 are alive with disease, 1 has died of disease, and 1 has died of other causes. CONCLUSIONS: Image-guided hepatic ablations represent a useful technique in managing hepatic tumors. Intraoperative MRI represents a new technique with initial success that has been limited to European centers. Further evaluation in U.S. centers has demonstrated iMRI to be useful for certain hepatic tumors that cannot be adequately visualized by US or CT.

Aged↗

PubMed2006

Selective replication of E1B55K-deleted adenoviruses depends on enhanced E1A expression in cancer cells.

E1B55K-deleted dl1520 could selectively replicate in cancer cells and has been used in clinical trials as an antitumor agent. The mechanism of virus selective replication in cancer cells, including a possible role of p53, is unclear. Studies with established cancer cell lines have demonstrated that some cancer cells are resistant to dl1520 replication, regardless of the p53 status. Hep3B cells supported the E1b-deleted adenoviruses to replicate, whereas Saos2 cells were resistant to viral replication. We applied p53-null Hep3B and Saos2 cells as models to clarify the replication ability of E1B55K-deleted adenoviruses with different expression levels of E1a. We show that lower E1A expression in Saos2 may be the reason for the poor replication in some cancer cells due to the fact that E1a promoter was less activated in Saos2 than in Hep3B. We also demonstrate that the E1B55K protein can increase E1A expression in Saos2 cells for efficient virus replication. In addition, the upstream regions of the E1a promoter have transcriptional activity in Hep3B cells but not in Saos2 cells. The viral E1B55K protein may activate cancer cellular factor(s) that targets the upstream regions of the E1a gene to increase its expression. This is the first study demonstrating that E1B55K protein affects the E1A production levels that is related to cancer selective replication. Our studies have suggested that increase of E1A expression from E1b-deleted adenoviruses may enhance killing cancer cells that otherwise are resistant to viral replication.

Adenoviridae↗

PubMed2002

Cost comparison of endoscopic stenting vs surgical treatment for unresectable cholangiocarcinoma.

BACKGROUND: Total lifetime costs of endoscopic vs surgical treatment for obstructive jaundice due to cholangiocarcinoma are difficult to assess. The purpose of this study was to compare total costs in these two groups, including all treatment and retreatments. METHODS: This retrospective study identified patients with biopsy-proven cholangiocarcinoma treated this decade with either endoscopic biliary stenting or surgical biliary-enteric bypass with or without resection. Outcomes and hospital charges were recorded. Ten matched control patients were compared from each group. Costs included those for cost of repeat endoscopy in the endoscopic group and for the management of recurrent obstructive jaundice in the surgical group. RESULTS: The groups were similar in age and gender ratio. The surgical approach was frequently for cure; therefore, surgical patients were by and large at an earlier stage of their disease than those in the endoscopic group. Mean survival for the endoscopic group was 19 months vs 16.5 months for the surgical group. The median total lifetime cost for surgical therapy was $60,986 vs $24,251 for endoscopic therapy. CONCLUSION: Endoscopic therapy is an effective palliative therapy for unresectable cholangiocarcinoma. Endoscopic therapy for this entity costs significantly less than surgical treatment. The cost benefit of endoscopic stenting over standard surgical bypass in the management of patients with unresectable cholangiocarcinoma, when considered along with its minimally invasive approach, makes this the procedure of choice for palliative therapy.

Aged↗

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

Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system.

PURPOSE: The American Joint Committee on Cancer (AJCC) recently proposed major revisions of the tumor-node-metastases (TNM) categories and stage groupings for cutaneous melanoma. Thirteen cancer centers and cancer cooperative groups contributed staging and survival data from a total of 30,450 melanoma patients from their databases in order to validate this staging proposal. PATIENTS AND METHODS: There were 17,600 melanoma patients with complete clinical, pathologic, and follow-up information. Factors predicting melanoma-specific survival rates were analyzed using the Cox proportional hazards regression model. Follow-up survival data for 5 years or longer were available for 73% of the patients. RESULTS: This analysis demonstrated that (1) in the T category, tumor thickness and ulceration were the most powerful predictors of survival, and the level of invasion had a significant impact only within the subgroup of thin (< or = 1 mm) melanomas; (2) in the N category, the following three independent factors were identified: the number of metastatic nodes, whether nodal metastases were clinically occult or clinically apparent, and the presence or absence of primary tumor ulceration; and (3) in the M category, nonvisceral metastases was associated with a better survival compared with visceral metastases. A marked diversity in the natural history of pathologic stage III melanoma was demonstrated by five-fold differences in 5-year survival rates for defined subgroups. This analysis also demonstrated that large and complex data sets could be used effectively to examine prognosis and survival outcome in melanoma patients. CONCLUSION: The results of this evidence-based methodology were incorporated into the AJCC melanoma staging as described in the companion publication.

Adolescent↗

PubMed2001

Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma.

PURPOSE: To revise the staging system for cutaneous melanoma under the auspices of the American Joint Committee on Cancer (AJCC). MATERIALS AND METHODS: The prognostic factors analysis described in the companion publication (this issue), as well as evidence from the published literature, was used to assemble the tumor-node-metastasis criteria and stage grouping for the melanoma staging system. RESULTS: Major changes include (1) melanoma thickness and ulceration but not level of invasion to be used in the T category (except for T1 melanomas); (2) the number of metastatic lymph nodes rather than their gross dimensions and the delineation of clinically occult (ie, microscopic) versus clinically apparent (ie, macroscopic) nodal metastases to be used in the N category; (3) the site of distant metastases and the presence of elevated serum lactic dehydrogenase to be used in the M category; (4) an upstaging of all patients with stage I, II, and III disease when a primary melanoma is ulcerated; (5) a merging of satellite metastases around a primary melanoma and in-transit metastases into a single staging entity that is grouped into stage III disease; and (6) a new convention for defining clinical and pathologic staging so as to take into account the staging information gained from intraoperative lymphatic mapping and sentinel node biopsy. CONCLUSION: This revision will become official with publication of the sixth edition of the AJCC Cancer Staging Manual in the year 2002.

Humans↗

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

Sentinel lymph node biopsy for melanoma: controversy despite widespread agreement.

Although sentinel lymph node (SLN) biopsy for melanoma has been adopted throughout the United States and abroad as a standard method of determining the pathologic status of the regional lymph nodes, some controversy still exists regarding the validity and utility of this procedure. SLN biopsy is a minimally invasive procedure, performed on an outpatient basis at the time of wide local excision of the melanoma, with little morbidity. Numerous studies have documented the accuracy of this procedure for identifying nodal metastases. There are four major reasons to perform SLN biopsy. First, SLN biopsy improves the accuracy of staging and provides valuable prognostic information for patients and physicians to guide subsequent treatment decisions. Second, SLN biopsy facilitates early therapeutic lymph node dissection for those patients with nodal metastases. Third, SLN biopsy identifies patients who are candidates for adjuvant therapy with interferon alfa-2b. Fourth, SLN biopsy identifies homogeneous patient populations for entry onto clinical trials of novel adjuvant therapy agents. Overall, the benefit of accurate nodal staging obtained by SLN biopsy far outweighs the risks and has important implications for patient management.

Chemotherapy, Adjuvant↗

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

Improved staging of node-negative patients with intermediate to thick melanomas (>1 mm) with the use of lymphatic mapping and sentinel lymph node biopsy.

BACKGROUND: Elective lymph node dissection (ELND) may contribute to a survival benefit in certain stratified subsets of melanoma patients. We hypothesized that lymphatic mapping and sentinel lymph node (SLN) biopsy (with complete node dissection if metastases are present) may improve both staging and survival of patients with clinically negative nodes, without subjecting all patients to the morbidity associated with complete ELND. METHODS: We reviewed the data for all 14,914 N0 patients of the AJCC Melanoma Staging Database to determine the effect of SLN biopsy and ELND on staging and survival. RESULTS: Retrospective analysis revealed that there was an apparent statistically significant survival advantage to SLN biopsy in patients with melanomas > 1 mm (n = 9024; 68.5% and 26.2% reduction in mortality compared with patients staged to be N0 by clinical exam and ELND, respectively; P < .0001). Five-year survivals were 90.5%, 77.7%, and 69.8%, respectfully, for patients staged by SLN biopsy (n = 2552), ELND (n = 2014), and clinical examination alone (n = 5192). The survival advantage of SLN biopsy was statistically significant for each T-stage category (T2, T3, and T4) and ulceration status. There was no advantage to SLN biopsy in patients with melanomas <1 mm (n = 5890). CONCLUSIONS: SLN biopsy provides more accurate staging and may contribute to a survival benefit in populations of patients with melanoma.

Adult↗

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↗