Biomedical subjects

Nicole Kelbick

Publications and source records attributed to Nicole Kelbick.

6 recordsLinked to original sources

PubMed2006

Vacuum-assisted apical suction devices induce passive electrical changes consistent with myocardial ischemia during off-pump coronary artery bypass graft surgery.

OBJECTIVE: Off-pump coronary artery bypass graft surgery is common therapy to completely revascularize diseased hearts. In order to graft posterior arteries in this procedure, the heart must be lifted from the chest cavity and manipulated to expose the surgical field using an apical suction device. This suction device may cause unwanted myocardial ischemia. METHODS: In this observational study, we measured myocardial electrical impedance, a parameter that responds to myocardial ischemia, as well as ST-segment changes during off-pump coronary artery bypass graft surgery in 12 patients with two-vessel coronary artery disease undergoing revascularisation of the left anterior descending and the posterior descending coronary arteries. During the posterior descending artery revascularisation phase of the procedure the apical suction device was oriented over the electrodes used to measure myocardial electrical impedance, thus allowing us the opportunity to assess myocardial ischemia in this region of the heart. RESULTS: In these 12 patients, myocardial electrical impedance progressively increased under the suction device during posterior coronary artery revascularisation, suggesting that myocardial ischemia developed in this region of the myocardium. ST-segment changes were negligible while the heart was vertically displaced (and the suction device attached), but increased immediately when the heart was returned to the neutral anatomical position. CONCLUSION: Our data suggest that the apical suction device may cause ischemia while the heart is vertically displaced and electrically disconnected from the body. Under these conditions, ST-segment changes may not detect myocardial ischemia. Myocardial electrical impedance has the potential to reliably detect intraoperative myocardial ischemia under these circumstances.

Coronary Artery Bypass, Off-Pump↗

PubMed2006

HER-2 is an independent prognostic factor in endometrial cancer: association with outcome in a large cohort of surgically staged patients.

PURPOSE: To evaluate HER-2 expression and amplification in a large cohort of endometrial cancer with complete surgical staging and outcome data. PATIENTS AND METHODS: A tissue microarray was constructed of 483 patients with endometrial cancer of diverse histologic type and stage and tested for HER-2 expression and amplification using current standards of practice. There was outcome data for 83% of all patients and 81% with complete surgical staging. RESULTS: Both expression and amplification of HER-2 was associated with high-grade (P = .0001) and high stage (P = .0001) endometrial cancer. The highest rate of HER-2 expression and amplification was seen in serous carcinoma (43% and 29%), while grade 1 endometrioid adenocarcinoma showed the lowest levels (3% and 1%). For all histologic types, the rate of HER-2 expression and amplification was remarkably different (P < .0001) for grade 3 cancers (31% and 15%) versus grade 2 (7% and 3%) and grade 1 cancers (3% and 1%), with similar results for endometrioid type (P < .0001). Both HER-2 expression and amplification correlated with disease-specific survival and progression-free survival in univariate analyses. By multivariate analysis HER-2 expression in the presence of amplification (P = .012) correlated with overall survival, but not expression in the absence of amplification. Overall survival was significantly shorter (P = .0001) in patients who overexpressed (median, 5.2 years) and/or showed amplification of HER-2 (median, 3.5 years) versus those that did not (median of all cases, 13 years). CONCLUSION: Our results would suggest that HER-2 is an important oncogene in high grade and stage endometrial cancer, but plays only a minor role in the much more common low grade and stage tumors that encompass the majority of clinical practice.

Adolescent↗

PubMed2006

Improved survival with an intact DNA mismatch repair system in endometrial cancer.

OBJECTIVE: To correlate survival and surgical-pathologic factors with DNA mismatch repair status in patients with endometrial cancer. METHODS: Specimens from 336 patients with endometrial cancer were used to create a tissue microarray. Immunohistochemistry with antibodies against the mismatch repair genes MLH1, MSH2, MSH6, and PMS2 were used to stain the tissue microarray. Clinical, pathologic, and survival data were collected and correlated with the immunohistochemistry results. RESULTS: Mismatch repair deficiency was seen in 29% (84 of 294) of cases. Correlation was noted between lack of expression of MLH1 and an increased risk for lymphvascular space involvement (32% versus 21%, P=.05) and cervical involvement (26% versus 14%, P=.02). Lack of expression of either MLH1 or MSH2 was associated with thinner patients (85% had a body mass index less than 40 versus 73% of patients with normal expression, P=.02), as well as with the absence of a history of previous primary malignancy (0 verus 13 cases [4%], P=.023). The estimated disease-free survival is 88%; despite a small number of recurrences, there was a nonsignificant improvement in disease-free survival in tumors with an intact mismatch repair system (P=.1). Significantly improved disease-free survival was seen in patients with normal MLH1 and MSH2 expression compared with those with abnormal expression (92% versus 81%, P=.035). CONCLUSION: Defects in DNA mismatch repair in endometrial cancer is correlated with negative prognostic factors and worse progression-free survival (without a difference in overall survival) compared with tumors with an intact mismatch repair system. LEVEL OF EVIDENCE: II-3.

Adaptor Proteins, Signal Transducing↗

PubMed2005

MYC amplification and polysomy 8 in chondrosarcoma: array comparative genomic hybridization, fluorescent in situ hybridization, and association with outcome.

PURPOSE: To identify recurrent regions of genomic gain or loss in chondrosarcoma in a clinically relevant and statistically valid fashion. MATERIALS AND METHODS: Array comparative genomic hybridization (CGH) results of 15 frozen tumor samples of high-grade chondrosarcoma for chromosome 8 are presented. A separate subset of 116 cartilaginous tumors with outcome data was used for validation. RESULTS: Array CGH identified gain at 8q24.12-q24.13, the region of the MYC (c-Myc) oncogene, as a frequent change in high-grade chondrosarcoma. In the validation arm of 116 cartilaginous tumors, MYC was frequently amplified in G2 (15%), G3 (20%), and dedifferentiated (21%) chondrosarcomas. No amplification was identified in samples of enchondroma and grade 1 chondrosarcoma. In samples without MYC amplification, polysomy 8 was a frequent finding in grade 1 (18%), grade 2 (31%), grade 3 (80%), and dedifferentiated (29%) chondrosarcomas, but was not found in any samples of enchondroma. MYC protein expression was identified in all samples with amplification, but was also frequent in the remaining samples without amplification or polysomy 8. Kaplan-Meier survival curves for overall survival showed a statistically significant difference for patients with MYC amplification or polysomy 8 (P = .034). Univariate analysis involving Cox proportional hazards models showed that grade (P = .003), polysomy 8 (P = .045), and MYC amplification (P = .053) correlated with shorter overall survival. By multivariate analysis, grade of chondrosarcoma (P = .026) was the only factor to reach statistical significance. CONCLUSION: MYC amplification and polysomy 8 can be used as markers of prognostic importance in chondrosarcoma. Molecular targeting of MYC expression may have therapeutic potential in the future for subsets of chondrosarcoma.

Aneuploidy↗

PubMed2005

Correlation of cyclooxygenase-2 (COX-2) and aromatase expression in human endometrial cancer: tissue microarray analysis.

OBJECTIVE: The objective of this study was to compare the prevalence of cyclooxygenase-2 (COX-2), aromatase, and hormone receptor immunohistochemical (IHC) expression to well defined clinical-pathologic prognostic factors in a large group of surgically staged endometrial cancer patients. STUDY DESIGN: A tissue microarray (TMA) was constructed from 336 separate specimens of endometrial cancer. IHC was performed for estrogen (ER) and progesterone (PR) receptor, COX-2, COX-1, and aromatase. RESULTS: The majority of tumors expressed COX-2 (59%) and aromatase (65%). COX-2 staining significantly correlated with aromatase expression ( P < .014) but did not correlate with ER and PR. COX-2 expression was correlated with worsening histologic grade ( P < .026) and approached statistical significance for deep myometrial invasion ( P < .055). After applying multivariate analysis, no single IHC or combination of IHCs correlated with intrauterine poor prognostic factors or advanced stage. Only myometrial invasion >50% (OR 6.98, P < .001) and nonendometrioid histology (OR 4.933, P < .001) were predictive of advanced stage after multivariate analysis. CONCLUSION: COX-2 and aromatase are expressed in the majority of endometrial cancer patients. COX-2 expression was not associated with the great majority of surgical-pathologic prognostic factors. COX-2 expression did significantly correlate with aromatase expression, suggesting that intratumoral production of estrogen in endometrial cancer may be an important mechanism in tumorigenesis.

Adolescent↗

PubMed2004

Combination immunotherapy of B-cell non-Hodgkin's lymphoma with rituximab and interleukin-2: a preclinical and phase I study.

PURPOSE: Cytokine-induced modulation of innate immunity is being explored to enhance the activity of monoclonal antibodies. Severe combined immunodeficient (SCID) mice engrafted with peripheral blood leukocytes (PBLs) from Epstein Barr virus-seropositive donors develop human B-cell non-Hodgkin's lymphomas [B-NHLs (hu-PBL-SCID mouse model)]. We used this hu-PBL-SCID mouse model to study the synergism between interleukin (IL)-2 and rituximab. We also conducted a phase I trial of IL-2 and rituximab in relapsed B-NHL to study whether expansion of natural killer (NK) cells and enhanced cellular cytotoxicity could be safely accomplished in vivo. EXPERIMENTAL DESIGN: Hu-PBL-SCID mice were treated with various schedules of rituximab and IL-2, with survival as the end point. Patients with relapsed B-NHL received rituximab (375 mg/m2 weekly x 4) followed by daily low-dose IL-2 (1 MIU/m2/day x 4 weeks) with pulses of intermediate-dose IL-2 (3-15 MIU/m2). Toxicity, NK cell numbers, and cellular cytotoxicity were measured. RESULTS: In the hu-PBL-SCID mouse, the combination of rituximab and IL-2 showed greater activity against B-NHL than either agent alone. Treatment was most effective when IL-2 was given before rituximab. Twelve patients with heavily pretreated B-NHL entered the phase I trial. Toxicity was manageable, and responses were observed. NK cell expansion and enhanced cellular cytotoxicity against a B-cell lymphoma target were observed but did not correlate with response. CONCLUSIONS: The combination of IL-2 and rituximab is synergistic against B-NHL in the hu-PBL-SCID model. In the phase I trial, a sequential combination of rituximab and IL-2 was well tolerated and achieved biological end points. Responses were observed.

Adult↗