Biomedical subjects

Marcella M Johnson

Publications and source records attributed to Marcella M Johnson.

33 records · Page 2Linked to original sources

PubMed2004

Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies.

BACKGROUND: The CD52 antigen is a glycoprotein anchored on the cell membrane of mature B and T lymphocytes, monocytes, and eosinophils. Alemtuzumab (CAMPATH-1H; anti-CD52) is currently approved for the treatment of patients with refractory chronic lymphocytic leukemia (CLL). The authors investigated the possibility that CD52 may be shed from cells and, once soluble, may bind to injected alemtuzumab, forming immune complexes. METHODS: The authors used Western blot analysis, immunoprecipitation, and enzyme-linked immunoadsorbent assay to investigate the presence of soluble CD52 (sCD52) in the plasma specimens of 117 patients with CLL. They also used in vitro mixing experiments to examine the ability of sCD52 to compete with cells and sequester therapeutic alemtuzumab. RESULTS: The authors detected high levels of sCD52 in the plasma specimens of patients with CLL. sCD52 can compete with cells in vitro for binding to alemtuzumab, and can form complexes in patients receiving alemtuzumab. Plasma levels of sCD52 were found to be correlated (r)with Rai stage (P = 0.0001), beta-2-microglobulin (beta-2M) levels (P = 0.00002), soluble CD23 levels (r = 0.42, P < 0.001), and immunoglobulin mutation status (P = 0.003). In the multivariate analysis adjusted for beta-2M level, patients with sCD52 levels > 2336 nM/L had a nearly 4-fold increase in risk of death. Higher levels of plasma alemtuzumab were achieved when levels of sCD52 were lower. CONCLUSIONS: These data not only demonstrated that sCD52 was detectable and useful in the staging and monitoring of patients with CLL, but also showed that sCD52 formed immune complexes with alemtuzumab and may influence the efficacy and toxicity of alemtuzumab therapy.

Adult↗

PubMed2004

Expression of thyrotropin-releasing hormone by human melanoma and nevi.

PURPOSE: Thyrotropin-releasing hormone (TRH) is a tripeptide hormone produced by the hypothalamus in response to hypothyroidism. RNA transcripts for the TRH prohormone have recently been described in melanoma cell lines. To expand these findings, we have examined cultured melanoma cells and melanocytes, human melanoma tumors, and nevi for the expression of TRH. EXPERIMENTAL DESIGN: Five melanoma cell lines were analyzed by reverse transcription-PCR/Southern blotting for preproTRH message. The same melanoma lines and two melanocyte lines were examined by immunocytochemistry for TRH protein expression and for growth response to exogenous TRH. Immunohistochemistry was used to test for TRH protein in sections of 19 melanomas, 33 dysplastic nevi, and 27 benign nevi. RESULTS: TRH message and protein were detected in all melanoma cell lines examined. Melanocytes were also found to express TRH protein. Four of the five melanoma cell lines but neither melanocyte line responded with a increase in proliferation to low concentrations of exogenous TRH. TRH immunoreactivity was observed in 12 of 19 melanomas (63%), 23 of 33 (69.7%) dysplastic nevi, and 14 of 27 (51.9%) benign nevi. Expression in dysplastic nevi was significantly greater than in benign nevi. Upon separate analysis of nevi from melanoma patients, the difference between dysplastic and benign nevi was even more significant. However, in healthy individuals, no difference between dysplastic and benign nevi was observed. Furthermore, dysplastic nevi from melanoma patients had a significantly higher percentage of TRH-positive cells when compared with healthy individuals. CONCLUSIONS: TRH is commonly expressed by melanomas and dysplastic nevi and may function as a melanoma autocrine growth factor. The presence of TRH in dysplastic nevi may be predictive for the development of melanoma. Our findings have significant clinical and biological implications for future research into the early stages of melanoma initiation and progression.

Cell Line, Tumor↗

PubMed2004

Serum levels of insulin growth factor (IGF-I) and IGF-binding protein predict risk of second primary tumors in patients with head and neck cancer.

PURPOSE: Second primary tumors (SPTs) are a hallmark of head and neck squamous cell carcinomas (HNSCCs). Serum levels of insulin growth factors (IGFs) and their binding proteins (IGFBPs) have been associated with subsequent development of several epithelial cancers in prospective studies. EXPERIMENTAL DESIGN: To examine the role of IGFs in SPT development, we conducted a nested case-control study within a randomized, placebo-controlled chemoprevention trial in patients with early-stage HNSCC. We compared prediagnostic serum IGF-I and IGFBP-3 levels in 80 patients who subsequently developed SPTs and 173 controls (patients without SPTs) matched to the cases on age (+/-5 years), sex, ethnicity, year of randomization, and length of follow-up. RESULTS: The cases exhibited significantly higher levels of IGF-I and IGFBP-3 than did the controls (P = 0.001 and 0.019, respectively). Elevated IGF-I levels were associated with a 3.66-fold significantly increased risk of SPT. Lower and higher IGFBP-3 levels were associated with a 2.22- and 7.12-fold significant increased risk, respectively. The median SPT-free time was significantly shorter in patients with higher IGF-I levels than in patients with lower IGF-I levels (P < 0.0001). A similar trend was observed for IGFBP-3 (P = 0.002). Moreover, in the Cox proportional hazards model, higher IGF-I levels were significantly associated with increased risk of SPT with a hazard ratio of 2.78. Patients with the lower and higher IGFBP-3 levels also exhibited significantly increased risks with hazard ratios of 1.65 and 2.17, respectively. CONCLUSIONS: This is the first study demonstrating that higher IGF-I levels, and lower and higher IGFBP-3 levels are risk factors for SPT development. Thus, measuring serum IGF-I and IGFBP-3 levels may be useful markers in assessing the risk of second tumors in patients successfully treated for their index cancer.

Adult↗

PubMed2004

Biochemotherapy in patients with metastatic anorectal mucosal melanoma.

BACKGROUND: Patients with metastatic anorectal melanoma generally have an unfavorable prognosis, but no effective systemic therapy has been reported. METHODS: The authors retrospectively evaluated the medical records of all patients with metastatic anorectal melanoma treated with biochemotherapy between January 1991 and December 2001 at the University of Texas M. D. Anderson Cancer Center (Houston, TX). RESULTS: The search yielded 18 patients. Of these patients, 14 had undergone treatment with cisplatin (CDDP), vinblastine (VB), dacarbazine (DTIC), interferon alpha-2b (IFN), and interleukin 2 (IL-2); 2 had undergone treatment with CDDP, VB, DTIC, and IFN; 1 had undergone treatment with CDDP, IFN, and IL-2; and 1 had undergone treatment with CDDP, VB, temozolomide, IFN, and IL-2. All IL-2 treatments were administered intravenously. The median follow-up time was 12.2 months (range, 3.5-43.7 months). Eight patients (44%) had major responses, including two (11%) complete responses (CRs). Three patients were lost to follow-up evaluation after the completion of treatment. The median time to progression among the 15 remaining patients was 6.2 months. Four patients, including 1 with a CR, were alive at their last documented follow-up visits (survival: 14.0, 20.7, 31.3, and 43.7 months, respectively). The median overall survival was 12.2 months. Among 13 patients who received biochemotherapy as first-line systemic therapy, 6 patients (46%) had major responses, including two (15%) CRs. The median time to progression for this group was 6.2 months, and the median overall survival was 12.9 months. CONCLUSIONS: Biochemotherapy had substantial activity against metastatic anorectal melanoma and should be considered for use in the treatment of metastatic disease from primary anorectal melanoma.

Adult↗

PubMed2004

Cyclooxygenase-2 is essential for HER2/neu to suppress N- (4-hydroxyphenyl)retinamide apoptotic effects in breast cancer cells.

We reported that HER2/neu reduces the sensitivity of breast cancer cells to N-(4-hydroxyphenyl)retinamide (4-HPR) by suppressing nitric oxide production. We show that HER2/neu uses Akt to induce cyclooxygenase-2 (COX-2) expression and that inhibition of Akt or COX-2 increases 4-HPR-induced apoptosis and nitric oxide production. Apoptosis induced by the 4-HPR and COX-2 inhibitor combination, although unaffected by an anti-HER2/neu antibody, was reversed by the COX-2 product prostaglandin E(2), indicating that COX-2 is a major mechanism by which HER2/neu suppresses 4-HPR apoptosis in breast cancer cells. Combining 4-HPR with COX-2 inhibitors may be a novel chemopreventive strategy against HER2/neu-overexpressing breast tumors.

Antineoplastic Agents↗

PubMed2004

Differential time to positivity: a useful method for diagnosing catheter-related bloodstream infections.

BACKGROUND: Catheter-related bloodstream infections are associated with recognized morbidity and mortality, especially in critically ill patients. Accurate diagnosis of such infections results in proper management of patients and in reducing unnecessary removal of catheters. OBJECTIVE: To evaluate differential time to positivity as a method for diagnosing catheter-related bacteremias caused by both short-term and long-term use of central venous catheters. DESIGN: Prospective study design. SETTING: M.D. Anderson Cancer Center, Houston, Texas, a tertiary care cancer center. PATIENTS: All patients, between September 1999 and November 2000, who had the same organism isolated from blood cultures drawn simultaneously through the central venous catheter and the peripheral vein. MEASUREMENTS: Time necessary for the blood cultures from the central venous catheter and the peripheral vein to become positive, as well as other relevant patient information. RESULTS: 191 bloodstream infections with positive simultaneous central venous catheter and peripheral vein blood cultures were included. One hundred eight patients had catheter-related bacteremias, and 83 had non-catheter-related bacteremias. Catheter-related bacteremias were more frequently caused by staphylococci and less likely to be associated with underlying hematologic malignant conditions, neutropenia, and longer duration of hospitalization. As a diagnostic tool for catheter-related bacteremia (using a composite definition reference standard according to the Infectious Diseases Society of America guidelines), differential time to positivity of 120 minutes or more was associated with 81% sensitivity and 92% specificity for short-term catheters and 93% sensitivity and 75% specificity for long-term catheters. CONCLUSION: Differential time to positivity of 120 minutes or more is highly sensitive and specific for catheter-related bacteremia in patients who have short- and long-term catheters.

Bacteremia↗

PubMed2004

Clinical relevance of circulating angiogenic factors in patients with non-Hodgkin's lymphoma or Hodgkin's lymphoma.

Vascular endothelial growth factor (VEGF), basic-fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and angiogenin are important angiogenic factors. In 65 patients with non-Hodgkin's lymphoma (NHL), pre-treatment VEGF, bFGF, and HGF levels were significantly elevated compared to normal individuals, while angiogenin levels were significantly subnormal. In 37 patients with Hodgkin's disease, pre-treatment levels of VEGF and HGF were significantly elevated, bFGF levels were normal, and angiogenin levels were significantly subnormal. In patients with NHL, post-therapy levels of angiogenin were independently predictive of survival. Both pre-therapy and post-therapy VEGF levels were independently predictive of survival in patients with HD.

Adolescent↗

PubMed2004

Needle localization for excisional biopsy of breast lesions: comparison of effect of use of full-field digital versus screen-film mammographic guidance on procedure time.

The time required to perform needle localization with full-field digital (FFD) mammography was compared with the time required to perform it with screen-film (SF) mammography in 158 women with breast lesions. The time needed to position the patient before the first image was acquired, needle placement time, and total procedure time were compared between techniques. Regression modeling was performed to assess the effect of mammographic guidance method while simultaneously adjusting for other significant covariates. By using the backward selection technique, statistically nonsignificant variables were removed one at a time to produce a final model for which all statistically significant effects were defined as those with P <.10. Total procedure time for all lesions was shorter with FFD than with SF mammography. The time needed to position the patient and needle placement time were also significantly shorter with FFD than with SF mammography. Procedure time for needle localization of breast lesions is significantly shorter with FFD than with SF mammographic guidance.

Adult↗

PubMed2004

CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment: a quantitative analysis correlated with FDG PET findings.

OBJECTIVE: We correlated changes in tumor density on CT with changes in glucose metabolism, or the maximum standardized uptake value (SUV(max)), on FDG PET and sought to develop CT imaging criteria that can be used to objectively evaluate tumor response in patients with metastatic gastrointestinal stromal tumors (GISTs) who undergo treatment with imatinib mesylate. MATERIALS AND METHODS: Using the criteria established by the Response Evaluation Criteria in Solid Tumors (RECIST) group, we selected 173 tumors (in 36 patients) for study. Tumor size and density were determined objectively, and overall tumor response (OTR) was evaluated subjectively on CT images. The changes in these parameters before and after treatment were correlated with changes in SUV(max). RESULTS: Significant decreases were seen in both tumor density (mean, 12.3 H [16.5%]; p < 0.0001) and SUV(max) (mean, 3.43 [64.9%]; p < 0.0001). OTR evaluated subjectively, correlated well with changes in SUV(max) (p < 0.0001). No statistically significant association was found between changes in tumor density and changes in SUV(max) (p = 0.3088), but 70% (14/20) of the patients with tumors that showed response on FDG PET exhibited at least a partial response by a change in tumor density. Tumor size was found to have decreased significantly 2 months after treatment (p = 0.0070). However, in 75% of the patients, the disease was stable according to the traditional tumor response criteria of RECIST. CONCLUSION: FDG PET is sensitive and specific for evaluating tumor response but cannot be used in patients whose baseline FDG PET results are negative for tumors. Although subjective evaluation was a better indicator of treatment response than was tumor density alone, the tumor density measurement is a good indicator and provides a reliable quantitative means of monitoring the tumor. RECIST, using only tumor size, was unreliable for monitoring GISTs during the early stage of imatinib mesylate treatment.

Adult↗

PubMed2003

Second primary tumors in patients with upper aerodigestive tract cancers: joint effects of smoking and alcohol (United States).

OBJECTIVE: This study evaluated the joint effects of tobacco smoking and alcohol consumption on the risk of second primary tumors (SPT) in patients with early-stage head and neck squamous cell carcinoma (HNSCC). METHODS: Data are presented for 1181 patients enrolled in a placebo-controlled chemoprevention trial of 13-cis-retinoic acid. Nearly 17% of patients presented with a SPT. The log rank test and Cox proportional hazards model were used to examine risk factors for SPT development. RESULTS: After adjusting for the time from the index diagnosis to randomization, age at diagnosis, stage, and site of the primary cancer, the factors that emerged as simultaneous predictors of SPT development were continued smoking and alcohol intake after the index diagnosis. Increased SPT risk was associated with older age (RR = 2.1; 95% CI 1.5-2.8); stage II diagnosis (RR = 1.5; 95% CI 1.1-2.1); index diagnosis of pharyngeal cancer (RR = 1.6; 95% CI 1.1-2.5); current smoking at registration (RR = 2.1; 95% CI 1.3-3.6) and continued alcohol consumption post-diagnosis (RR = 1.3; 95% CI 1.0-1.7). CONCLUSION: Important associations exist between SPT development and continued smoking and alcohol consumption after treatment for HNSCC.

Aged↗

PubMed2003

Plasma interleukin 8 level predicts for survival in chronic lymphocytic leukaemia.

The malignant B cells of patients with chronic lymphocytic leukaemia (CLL) constitutively express interleukin 8 (IL-8) and IL-8 receptors. Ex vivo culture with exogenous IL-8 enhances IL-8 expression and prolongs leukaemia cell survival, partly through increased bcl-2 expression. IL-8 may function as an autocrine growth and apoptosis resistance factor in CLL. Therefore, we evaluated the prognostic relevance of plasma IL-8 levels in 151 CLL patients [median age 61 years (range, 32-84 years), median plasma IL-8 level 18.9 pg/ml (9.1-89.1 pg/ml)]. All Rai stages were represented; advanced stage was associated with significantly higher plasma IL-8 levels (P < 0.0001, Kruskal-Wallis). Also, plasma IL-8 level was correlated with serum beta2-microglobulin (beta2-M) (R = 0.24, P = 0.0081), haemoglobin (R = -0.39, P < 0.0001) and platelet count (R = -0.23, P = 0.0049) by Spearman's rank correlation. Univariate analysis using Cox proportional hazards models identified elevated IL-8 and beta2-M as significant prognostic factors with relative risks of 7.43 (P = 9.1 x 10(-9)) and 16.40 (P = 5.9 x 10(-10)) respectively. High levels of IL-8 were associated with shorter survival independent of beta2-M level. Using recursive-partitioning procedures, an IL-8 cut-off point of 26.2 pg/ml segregated a group of CLL patients with significantly shorter survival (median 9.3 months) (P < 0.0001). In conclusion, plasma IL-8 level in CLL patients correlates with other prognostic factors, such as Rai stage and beta2-M, and is associated with increased risk of death in CLL patients. The role of IL-8 inhibitors in the treatment of patients with CLL should be explored.

Adult↗

PubMed2003

Circulating CD20 and CD52 in patients with non-Hodgkin's lymphoma or Hodgkin's disease.

The cell surface proteins CD20 and CD52 differ significantly in their structures and are expressed on the majority of B cells. Both circulating CD20 (cCD20) and circulating CD52 (cCD52) have been recently documented in patients with chronic lymphocytic leukaemia. A retrospective study to establish whether cCD20 and/or cCD52 were detectable in patients with lymphoma, and the clinical associations of these soluble antigens if detected, was conducted. cCD20 and cCD52 levels were analysed in a cohort of 65 patients with non-Hodgkin's lymphoma (NHL) and 37 with Hodgkin's disease (HD). Patients with NHL had elevated pretherapy levels of cCD20 and cCD52 compared with normal individuals. Patients with HD had significantly lower than normal pretherapy levels of both cCD20 and cCD52. cCD20 levels were marginally elevated post-therapy in NHL patients while in patients with HD, cCD20 levels remained significantly lower than normal after therapy. Serum cCD52 levels became significantly lower than normal post-therapy in NHL patients, and remained significantly lower than normal in HD patients. No predictive effects were found for pretherapy or post-therapy levels of cCD52 on survival for either cohort of patients. Post-therapy cCD20 levels independently highly correlated with survival in patients with NHL. Prospective evaluation will be required to establish if cCD20 and cCD52 may be used as biomarkers in the diagnosis, prognostic categorization, and monitoring of the clinical course in patients with lymphoma. The clinical significance of circulating antigen in patients receiving monoclonal antibody therapy directed against CD20 and/or CD52 warrants study.

Adolescent↗

PubMed2003

Revised American Joint Committee on Cancer staging criteria accurately predict sentinel lymph node positivity in clinically node-negative melanoma patients.

BACKGROUND: The American Joint Committee on Cancer (AJCC) has recently modified staging criteria for primary melanoma patients and recommends sentinel lymph node (SLN) biopsy in many because microscopic nodal metastasis represents the most important factor predicting survival. The purpose of this study was to correlate the incidence of SLN metastasis with revised AJCC staging. METHODS: The records of 1375 melanoma patients undergoing SLN biopsy were reviewed. Univariate and multivariate analyses were performed to identify predictors of a positive SLN. Patients were stratified by using revised AJCC criteria to determine whether such groups also predicted positive SLNs. RESULTS: A positive SLN was found in 16.9% of patients. By multivariate analysis, tumor thickness (relative risk [RR], 3.4) and ulceration (RR, 2.2) were dominant independent predictors of SLN metastases; age < or =50 years (RR, 1.8) and axial tumor location (RR, 1.5) were also significant. When patients were stratified by AJCC staging criteria, a significant increase in SLN metastases between successive stages was demonstrated. CONCLUSIONS: Stratification of patients by using AJCC classification reveals an increasing risk of SLN metastases with successive stage groups. Given the significant association of SLN status and survival, the ability of the revised AJCC staging system to predict survival is likely due to its ability to predict the risk of occult nodal disease.

Adolescent↗

PubMed2003

Are en face frozen sections accurate for diagnosing margin status in melanocytic lesions?

To assess the diagnostic accuracy of margin evaluation of melanocytic lesions using en face frozen sections compared with standard paraffin-embedded sections, we studied 2 sets of lesions in which en face frozen sections were used for analysis of surgical margins (13 from malignant melanomas [MMs] and 10 from nonmelanocytic lesions [NMLs]). Routine permanent sections were cut after routine processing. The slides were mixed and coded randomly. Fifteen dermatopathologists examined the cases separately. Margin status was categorized as positive, negative, or indeterminate. Kappa statistics were calculated per dermatopathologist and per case. One case from each group was excluded because epidermis was not available in the routine sections. Of 330 evaluations (22 cases, 15 dermatopathologists), there were 132 diagnostic discrepancies (40.0%): 66 each for MM and NML (mean per case for both diagnoses, 6). In 9 instances (6.8%), the change was from positive (frozen) to negative (permanent) and in 43 (32.6%), from negative (frozen) to positive (permanent). There was poor agreement between frozen and permanent sections (kappa range per dermatopathologist, -0.1282 to 0.6615). If permanent histology is considered the "gold standard" for histologic evaluation, en face frozen sections are not suitable for accurate surgical margin assessment of melanocytic lesions.

Aged↗

PubMedDate not supplied

High prevalence of hypothyroidism among patients with cutaneous melanoma.

We have previously reported a high prevalence of hypothyroidism among patients with uveal melanoma. The objectives of the present study were to determine if a similar pattern of thyroid pathology exists among patients with cutaneous melanoma as well. To address this question, the medical records of all patients registered at the University of Texas M.D. Anderson Cancer Center with a diagnosis of cutaneous melanoma during the years 1997 and 1998 were examined for a history of overt hypothyroidism, defined as a requirement for thyroid hormone replacement. Data regarding stage and site of the primary tumor were obtained for these patients and for age/gender matched euthyroid controls from the same melanoma study population. Among 1,580 cutaneous melanoma patients (948 M/632 F), 111 (7.0%) gave a history of hypothyroidism [23/948 M (2.4%) and 88/632 F (13.9%)]. The prevalences of hypothyroidism for both males and females were significantly higher than those reported for the general population. Characteristics of the primary tumor did not differ between cases and controls, although there was a trend for a lower rate of primary tumor ulceration among the hypothyroid case subjects. We conclude that hypothyroidism of varied etiologies is common among patients with cutaneous melanoma. These data suggest that melanoma may be responsive to hormones of the thyroid hormone control loop, raising many questions of clinical and biologic importance.

Adult↗