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Biomedical subjects

Kelly M McMasters

Publications and source records attributed to Kelly M McMasters.

At least 37 records · Page 2Linked to original sources
PubMed2005

SW-620 cells treated with topoisomerase I inhibitor SN-38: gene expression profiling.

BACKGROUND: The goal of this study was to evaluate changes in gene expression in SW-620 cells in response to SN-38 in order to further elucidate the mechanisms by which SN-38 causes apoptosis and cell cycle arrest. METHODS: We used a quantitative gene expression microarray assay to identify the genes regulated by SN-38 treatment in colon cancer cells and confirmed our results with RT-PCR. By gene expression profiling, we first screened a proprietary list of about 22,000 genes. RESULTS: Treatment with SN-38 cells resulted in two-fold or greater alteration in the level of expression of 192 genes compared to control treatment. Most of the affected genes were not known to be responsive to SN-38 prior to this study. SN-38 treatment of these cells was found to affect the expression of various genes involved in DNA replication, transcription, signal transduction, growth factors, cell cycle regulation, and apoptosis, as well as other genes with unknown function. Changes in expression of 14 genes were confirmed by quantitative real-time polymerase chain reaction (RT-PCR). CONCLUSION: This study leads to an increased understanding of the biochemical pathways involved in SN-38-induced apoptosis and possibly to the identification of new therapeutic targets.

Journal Article↗
PubMed2005

Adenoviral E1a expression levels affect virus-selective replication in human cancer cells.

One of the promising strategies for targeting replication of oncolytic adenovirus in tumor cells is to regulate the expression of essential viral genes such as E1a by using tumor- or tissue-specific promoters that are preferentially active in cancer cells. However, this approach may lead to some degree of viral replication in normal cells other than in cancer cells if the viral gene also expresses in normal cells. In this study, we investigated the effect of E1a expression levels on the virus replication ability in human cells. Three vectors, all with mutated E1B55K, were created, one without any promoter controlling the E1a gene and two vectors with the E1a gene being controlled by either its endogenous promoter or a strong CMV promoter. We observed that the CMV promoter-mediated high levels of E1A expression could increase virus replication, resulting in the titers of the E1B55K-mutated virus being even higher than the wild-type virus in some cancer cells. However, the strong CMV promoter could not always enhance virus replication, such as in cancer cells OE33 and OsACL. The results suggest that whether increased E1A levels would enhance E1B55K-mutated virus replication may be also depended on cellular factors or pathways in cancer cells. We also observed that the virus without any promoter for the E1a gene could still express leaky levels of E1A which can lead to viral replication in normal and cancer cells. Future efforts in the development of transcription-controlled oncolytic adenoviruses should focus on how to completely block E1a expression in normal cells.

Adenoviridae↗
PubMed2005

Evaluation of intraoperative autotransfusion filtration for hepatectomy and pancreatectomy.

BACKGROUND: Hepatectomy and pancreatectomy are often associated with significant intraoperative blood loss leading to postoperative anemia, which has been demonstrated to lead to increased perioperative morbidity, a prolonged hospital stay, and decreased overall survival. Cancer has remained an absolute contraindication to autotransfusion because of the unproven concern about reinfusion of malignant cells. Thus, the aim of this study was to test for the presence of malignant cells in autotransfused filtered blood in patients undergoing major pancreatic and liver resection. METHODS: A prospective study of 20 consecutive patients evaluated the presence of malignant cells from autotransfusion filtered blood after resection by flow cytometric and immunohistochemical methods. RESULTS: Ten patients underwent major hepatectomy for metastatic colorectal cancer, with a median blood loss of 500 mL (range, 200-700 mL). Three patients received a total of six units of packed red blood cells. Ten patients underwent pancreaticoduodenectomy for adenocarcinoma with a median blood loss of 400 mL (range, 200-1300 mL). Five patients received a total of nine units of packed red blood cells. Flow cytometry did not demonstrate the presence of any cytokeratin-positive carcinoma cells in filtered blood. CONCLUSIONS: Intraoperative autotransfusion for major hepatectomy in metastatic colorectal cancer and pancreatectomy for adenocarcinoma is safe and should begin to be evaluated in a phase II study for efficacy.

Adenocarcinoma↗
PubMed2005

A nomogram that predicts the presence of sentinel node metastasis in melanoma with better discrimination than the American Joint Committee on Cancer staging system.

BACKGROUND: The threshold and indications for sentinel lymph node (SLN) biopsy in patients with melanoma remain somewhat arbitrary. Many variables associated with SLN positivity have previously been identified, including a significant association between the American Joint Committee on Cancer (AJCC) staging system and SLN status. We developed a user-friendly nomogram that takes several characteristics into account simultaneously to more accurately predict the presence of SLN metastasis for an individual patient. METHODS: A total of 979 patients who underwent successful SLN biopsy for cutaneous melanoma at a single institution between February 1991 and November 2003 were included in the analysis. Predictors were used to develop a nomogram, based on logistic regression analysis, to predict the probability of SLN positivity. A large multi-institutional trial with 3108 patients was used to validate the predictive accuracy of the nomogram compared with the AJCC staging system. RESULTS: The nomogram was developed and found to be accurate and discriminating. The concordance index of the nomogram, a measure of predictive ability, was .694 when evaluated with the validation dataset. In contrast, the concordance index of the AJCC staging system was lower (.663; P < .001). CONCLUSIONS: Using commonly available clinicopathologic information, we developed a nomogram to accurately predict the probability of a positive SLN in patients with melanoma. This tool takes several characteristics into account simultaneously. This model should enable improved patient counseling and treatment selection.

Female↗
PubMed2005

Popliteal lymph node dissection.

Most sentinel nodes are located in the cervical, axillary, and inguinal nodal basins. Sometimes, however, sentinel nodes exist outside these traditional nodal basins. Popliteal nodal metastasis is relatively uncommon, and popliteal lymph node dissection is infrequently necessary. However, with lymphoscintigraphic identification of popliteal sentinel nodes, surgeons are more frequently called on to address the popliteal nodal basin. Therefore, knowledge of the anatomy and surgical technique for popliteal lymphadenectomy is essential. This case study illustrates the importance of considering the approach to the popliteal lymph node basin for patients with melanoma.

Female↗
PubMed2005

Preferences for different methods of communicating information regarding adjuvant chemotherapy for breast cancer.

Many patients play an active role in determining their cancer treatments, and the communication of medical information influences patient decision-making. This study examined participants' preferences between various methods of communicating quantitative risks and benefits of adjuvant chemotherapy. Using clinical vignettes, participants were first asked to decide whether or not to endorse chemotherapy and were subsequently asked about their preferences for the methods used to communicate the risks and benefits. Participants preferred the absolute survival benefit method over negatively framed methods, such as relative or absolute risk reduction. We also present analysis of qualitative data which supports the conclusions drawn from quantitative analyses. In summary, the absolute survival benefit was shown to be the superior method of communicating quantitative risks and benefits of chemotherapy. Failure to use clear and concise methods of communicating quantitative risk and benefit information may compromise efforts to obtain informed consent for treatment.

Adult↗
PubMed2005

Biopsy type does not influence sentinel lymph node status.

BACKGROUND: This study sought to determine whether the type of biopsy examination independently affects sentinel lymph node (SLN) status in breast cancer patients. METHODS: A prospective multicenter study of patients who had SLN biopsy examination followed by axillary node dissection was analyzed to determine whether the type of biopsy examination influenced SLN status. RESULTS: Of the 3853 patients studied, 32% had a positive SLN. Patients were diagnosed by fine-needle (N = 293), core-needle (N = 2154), excisional (N = 1386), or incisional (N = 20) biopsy procedures. The rates of SLN positivity for these groups were 45%, 32%, 29%, and 65%, respectively (P < .001). Other factors predictive of SLN status included: patient age (P < .001), tumor size (P < .001), tumor palpability (P < .001), number of SLN removed (P < .001), type of surgery (mastectomy vs. lumpectomy) (P < .001), histologic subtype (P = .048), and the use of immunohistochemistry (P < .001). All of these factors remained significant in the multivariate model except for histologic subtype and biopsy examination type. CONCLUSIONS: Biopsy examination type does not independently influence the risk for nodal metastasis.

Adult↗
PubMed2005

Effect of lymphoscintigraphy drainage patterns on sentinel lymph node biopsy in patients with breast cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy examination is an accepted method of staging breast cancer patients. SLN biopsy examination in patients with drainage to the internal mammary chain (IMC) nodes is controversial. METHODS: A prospective study of SLN biopsy examination followed by axillary dissection was analyzed to determine how surgeons manage patients with IMC drainage and the rates of axillary SLN identification and positivity in these cases. RESULTS: Lymphoscintigraphy was performed in 2196 (53.2%) of the 4131 patients in this study. IMC drainage was noted in 80 patients (3.6%). An axillary SLN was identified in 29 of the 40 patients with IMC drainage alone (72.5%). The rate of finding a positive axillary lymph node did not differ based on the lymphoscintigraphic pattern (P = .470). CONCLUSIONS: Most surgeons do not perform IMC SLN biopsy procedures. Even when lymphoscintigraphy shows isolated drainage to IMC nodes, axillary SLNs usually are identified. Lymphoscintigraphy therefore has limited usefulness.

Adult↗
PubMed2005

Surgeon and community factors affecting breast cancer sentinel lymph node biopsy.

BACKGROUND: We sought to determine whether the results of sentinel lymph node (SLN) biopsy are related to practice and community factors. METHODS: This prospective study included more than 300 surgeons from a variety of practice environments. Most surgeons had minimal experience with SLN biopsy prior to this study. Patients underwent attempted SLN biopsy, followed by completion axillary dissection. Univariate and multivariate analyses were performed to assess factors related to the SLN identification rate and the false negative rate. RESULTS: A total of 4131 patients were enrolled. SLN identification rate was 93%; the false negative (FN) rate was 7.9%. The only factor that was significantly associated with improved SLN identification rate (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.12 to 2.36, P = .0126) and FN rate (OR 2.39, 95% CI 1.32 to 4.79, P = .0073) was surgeon experience (>20 SLN cases). CONCLUSIONS: Surgeon experience is the major factor that contributes to improved SLN biopsy results. SLN biopsy can be performed equally well by community and academic surgeons.

Adult↗
PubMed2005

Is incisional biopsy of melanoma harmful?

BACKGROUND: In the era of sentinel lymph node (SLN) biopsy, there has been concern that manipulation, injection, and massage of intact primary melanomas (after incisional or shave biopsy) could lead to an artifactual increased rate of SLN micrometastases or an actual increased risk of recurrence. The aim of this study was to evaluate the difference in the incidence of SLN metastasis, locoregional recurrence (LRR), disease-free survival (DFS), distant disease-free survival (DDFS), or overall survival (OS) for patients who undergo excisional versus incisional versus shave biopsy. METHODS: Analysis of database from a multicenter prospective randomized study from centers across the United States and Canada. Eligible patients were 18 to 71 years old, with cutaneous melanoma > or = 1.0 mm Breslow thickness. All patients underwent SLN biopsy using blue dye and radioactive colloid injection. SLNd were evaluated by serial histological sections with S100 immunohistochemistry. Statistical analysis was performed using univariate and multivariate analyses with a significance level of P < .05; survival analysis was performed by the Kaplan-Meier method with the log-rank test. RESULTS: A total of 2,164 patients were evaluated; 382 patients were excluded for lack of biopsy information. Positive SLNs were found in 220 of 1,130 (19.5%), 58 of 281 (20.6%), and 67 of 354 (18.9%) of patients with excisional, incisional, or shave biopsy, respectively (no significant difference). There were significant differences among the 3 biopsy types in ulceration (P = .018, chi2) and regression (P = .022, chi2); there were no differences in age, gender, Breslow thickness, Clark level, lymphovascular invasion, tumor location, or histologic subtype. Biopsy type did not significantly affect LRR, DFS, DDFS, or OS. CONCLUSIONS: The concern that incomplete excision of primary melanomas may result in an increased incidence of SLN micrometastases, artifactual or real, is unfounded. Similarly, there is no evidence that biopsy type adversely affects locoregional or distant recurrence. Although shave biopsy is generally discouraged because it may lead to inaccurate tumor thickness measurements, it does not appear to affect overall patient outcome.

Adolescent↗
PubMed2005

Factors predicting failure to identify a sentinel lymph node in breast cancer.

BACKGROUND: Although sentinel lymph node (SLN) biopsy is widely accepted as a minimally invasive method of nodal staging, failure to identify an SLN mandates a level I/II axillary node dissection. The purpose of this study was to elucidate factors that independently predict failure to identify an SLN. METHODS: Using a large multicenter prospective study of SLN biopsy for patients with invasive breast cancer, we performed univariate and multivariate regression analyses to determine clinicopathologic factors predictive of failure to identify an SLN. RESULTS: Of the total 4131 patients in the study, an SLN was not identified in 249 (6.0%). Tumor location (P = .409), biopsy type (P = .079), surgery type (P = .380), and histologic subtype (P = .999) were not significant predictors of failure to identify an SLN. On multivariate analysis, age greater than 60 years (OR = 1.469; 95% CI, 1.116-1.934, P = .006), nonpalpable tumors (OR = 0.639; 95% CI, 0.479-0.852, P = .002), injection technique with blue dye alone (OR = 0.389, 95% CI, 0.259-5.86, P < .001), and surgical experience of less than 10 SLN biopsy cases (OR = 1.886; 1.428-2.492, P < .001) were significant independent predictors of failure to identify an SLN. Optimal SLN biopsy technique using an intradermal and/or subareolar injection of radioactive colloid and blue dye can improve SLN identification rates regardless of patient and tumor characteristics. CONCLUSIONS: Patient age and tumor palpability significantly affect the ability to identify an SLN in patients with breast cancer. Optimal injection technique can significantly improve sentinel node identification rate regardless of these factors.

Adult↗
PubMed2005

Should sentinel lymph-node biopsy be used routinely for staging melanoma and breast cancers?

The sentinel lymph node (SLN) is the lymph node that represents the 'gate-keeper' of the lymphatic basin; it is the first node to receive lymphatic drainage from the site of the primary tumor. SLN biopsy is a staging procedure and should be considered as such; it is not meant to be a therapeutic operation. The SLN can be mapped and biopsied using tracer agents (e.g. radiolabelled colloid and/or vital blue dye), which are injected around the primary tumor site. Pathologic analysis of the SLN using a combination of serial sectioning of the node, standard hematoxylin and eosin staining, and immunohistochemistry decreases the false-negative rate compared with traditional nodal processing. SLN biopsy is associated with lower morbidity than full lymphadenectomy. The SLN technique accurately reflects the metastatic status of the regional lymph-node basin; recurrent nodal disease in the mapped basin is rare following a tumor-free SLN biopsy result. The objectives of this review are to provide a current and concise overview of the current literature on SLN biopsy and describe its role in clinical oncology.

Breast Neoplasms↗
PubMed2005

Clinicopathologic factors associated with false-negative sentinel lymph-node biopsy in breast cancer.

SUMMARY BACKGROUND DATA: Previous studies have suggested a variety of factors that may affect the false negative (FN) rate for sentinel lymph node (SLN) biopsy in breast cancer. Because FN results are relatively rare, no prior studies have had sufficient sample size to allow detailed statistical analysis of factors predicting FN results. METHODS: Patients with clinical stage T1-2, N0 invasive breast cancer were enrolled in a prospective, multicenter study. All patients underwent SLN biopsy, followed by planned completion axillary dissection regardless of the SLN results, to assess the FN rate. SLN biopsy was performed using radioactive colloid injection in combination with isosulfan blue dye in 94% of cases. Dermal, subdermal, peritumoral, or subareolar radioactive colloid injection techniques were used at the discretion of each institution. Univariate and multivariate analyses were performed to identify factors associated with a FN result. RESULTS: SLNs were identified in 3870 of 4117 patients (94%). There were 1243 true positive, 2521 true negative, and 106 FN results. Age, histologic subtype, the number of non-SLN removed, tumor palpability, type of breast biopsy, and SLN injection technique were not significant factors. On multivariate analysis, tumor size <2.5 cm, upper outer quadrant tumor location, removal of only a single SLN, minimal surgeon experience, presence of a single positive axillary LN, and use of immunohistochemistry (IHC) for SLN analysis were independently associated with an increased risk of FN results. CONCLUSIONS: Surgeon experience, tumor size and location, and the number of SLN removed are preoperative and intraoperative factors that independently predict the risk of a FN result. In contrast to suggestions from other smaller studies, age does not affect the likelihood of a FN result; a lesser, rather than greater, number of positive axillary nodes was associated with an increased likelihood of a FN result; and IHC analysis of the SLN increases, rather than decreases, the risk of FN results.

Adult↗
PubMed2004

Gene expression profiling of E2F-1-induced apoptosis.

It has been shown that adenovirus-mediated overexpression of E2F-1 can efficiently induce apoptosis in cancer cells with little effect on normal cells. However, the mechanisms by which E2F-1 induces apoptosis remains poorly understood. The goal of this study was to evaluate changes in gene expression in response to E2F-1 in order to help elucidate the mechanisms by which E2F-1 causes apoptosis. Therefore, we used a quantitative microarray assay to identify the genes regulated by E2F-1 in melanoma cells. By gene expression profiling, we first screened a proprietary list of about 12,000 genes. Overexpression of E2F-1 in melanoma cells resulted in two-fold or greater alteration in the level of expression of 452 genes compared to vehicle-treated control cells. Most of the affected genes were not known to be responsive to E2F-1 prior to this study. E2F-1 adenoviral infection of these cells was found to affect the expression of a diverse range of genes, including oncogenes, transcription factors and genes involved in signal transduction, cell cycle regulation, cell proliferation and apoptosis, as well as other genes with unknown function. Changes in expression of 17 of these genes were confirmed by quantitative real-time polymerase chain reaction (PCR). This is first application of the microarray technique in the study of the global profile of genes regulated by E2F-1 in melanoma cells. This study leads to an increased understanding of the biochemical pathways involved in E2F-1-induced apoptosis and possibly to the identification of new therapeutic targets.

Adenoviridae↗