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At least 127 records · Page 7Linked to original sources
PubMed1991

Elimination of clonogenic breast cancer cells from human bone marrow. A comparison of immunotoxin treatment with chemoimmunoseparation using 4-hydroperoxycyclophosphamide, monoclonal antibodies, and magnetic microspheres.

Autologous bone marrow transplantation (ABMT) may aid in the management of breast cancer, but is currently limited to patients without bone marrow metastases. In earlier studies, 5 logs of malignant clonogenic breast cancer cells could be eliminated from human bone marrow using a combination of chemoseparation with 4-hydroperoxycyclophosphamide (4-HC) and immunoseparation with monoclonal antibodies and magnetic microspheres. In this report the authors compare chemoimmunoseparation to treatment with immunotoxins for elimination of tumor cells from human bone marrow and for the preservation of normal precursors. Breast cancer cells from each of five cell lines were mixed with a tenfold excess of irradiated human bone marrow cells. Treatment with a combination of five immunotoxins reduced clonogenic tumor cell growth by 1.8 to 5.5 logs depending upon the cell line. With two of the five cell lines, clonogenic tumor cells were eliminated quantitatively. Using the CAMA-1 breast cancer cell line, treatment with multiple immunotoxins was compared with chemoimmunoseparation with 4-HC, a panel of five unconjugated monoclonal antibodies and magnetic microspheres. Chemoimmunoseparation eliminated 3.5 to 5.4 logs of malignant cells, while preserving 21% of Colony-forming unit-granulocyte-macrophage (CFU-GM) and 37% of burst-forming unit-erythrocyte (BFU-E). No clonogenic breast cancer cells could be detected. Immunotoxin treatment eliminated 2.2 to 5.4 logs of clonogenic breast cancer cells, but had no effect on the bone marrow precursors. In seven of ten experiments, however, clonogenic breast cancer cells remained after immunotoxin treatment. Consequently, treatment with 4-HC, multiple murine monoclonal antibodies and magnetic microspheres provided more consistent elimination of tumor cells than separation with immunotoxins, but was significantly more toxic for marrow precursors.

Antibodies, Monoclonal↗
PubMed1991

Coordinate elevation of serum markers in ovarian cancer but not in benign disease.

Effective screening for occult ovarian cancer will require a strategy that is both sensitive and specific. Preliminary data suggest that CA 125 is elevated at diagnosis in a majority of patients with ovarian cancer. Although CA 125 is sufficiently specific to prompt its evaluation as one component of a strategy to detect ovarian cancer in postmenopausal women, a further improvement in specificity would facilitate cost-effective screening. In an attempt to develop a more specific screening strategy, multiple markers were assayed in a panel of sera from 47 patients with ovarian cancer and in a separate panel of sera from 50 individuals with benign disease whose serum CA 125 levels exceeded 35 U/ml. Among the patients with ovarian cancer, elevations of CA 125 (greater than 35 U/ml) were observed in 91%, CA 15-3 (greater than 30 U/ml) in 57%, TAG 72 (greater than 10 U/ml) in 49%, placental alkaline phosphatase (PLAP) in 25%, human milk fat globule protein (HMFG) 1 in 77%, HMFG2 in 62%, and NB/70K in 57%. Among the 50 sera selected from patients with benign disease, CA 125 was more than 35 U/ml in 100% and more than 65 U/ml in 42%. Among those patients with benign disease and elevated CA 125, NB/70K was elevated in 62%, HMFG1 in 26%, and HMFG2 in 12%, whereas TAG 72 and CA 15-3 were elevated in only 6% and 2%, respectively. In addition PLAP appeared promising; elevated enzyme levels were not found in the benign disease group. Among patients with ovarian cancer with CA 125 levels more than 35 U/ml, either TAG 72 or CA 15-3 was elevated in 77%. In the false-positive group, only 6% had elevations of one or the other marker. The CA 125 levels in cancer patients were, however, substantially greater than in patients with benign disease. If sera from patients with ovarian cancer were diluted to a range comparable to that found in benign disease, at least one of the two confirmatory tests was elevated in 63% of the samples from the malignant cases. Consequently, use of CA 15-3 and TAG 72 in combination with CA 125 can increase the apparent specificity of the CA 125 assay for distinguishing malignant from benign disease. Prospective studies will be required to test critically whether the use of additional serum markers in combination with the CA 125 assay would contribute to the specificity of a cost-effective screening strategy for ovarian cancer.

Alkaline Phosphatase↗
PubMed1992

Histologic grade does not predict prognosis in optimally treated, advanced-stage nodular sclerosing Hodgkin's disease.

Forty-two patients with advanced-stage nodular sclerosing Hodgkin's disease (NSHD) were treated uniformly with combination chemotherapy and radiation therapy at the University of Nebraska Medical Center between 1982 and 1987. The cases were subclassified into low-grade (13 cases) and high-grade (29 cases) categories using the British National Lymphoma Investigation (BNLI) histologic criteria. After a median follow-up interval of 48 months, no significant differences with regard to the complete remission rate (100% versus 90%), remission durability (85% versus 96%), or predicted 4-year actuarial survival (92% versus 86%) were observed between the two groups, respectively. It was concluded that the BNLI grading scheme for NSHD does not predict the clinical outcome of patients with advanced-stage NSHD who receive optimal therapy.

Adolescent↗
PubMed1992

Detection of a novel marker in the bronchial secretions of patients with non-small cell lung cancer using the 4B5 monoclonal antibody.

A murine monoclonal antibody designated 4B5 was raised against the high molecular weight fraction of pooled sputum from patients with non-small cell lung cancer (NSCLC). Immunohistochemical staining indicated that 4B5 binds to histologically normal bronchial epithelium distant from tumor in 72% (39 of 54) of patients with NSCLC, but it binds to the primary cancer in only 13% (7 of 54) of the same patients. The antibody reacted less intensely with the bronchial epithelium in 16.6% (3 of 18) of autopsied patients without significant lung disease. The antigen recognized by 4B5 is a high molecular weight glycoprotein of more than 400 kilodaltons, judged by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot analysis. Antigenic activity persisted after heating and resisted treatment with neuraminidase, but it was destroyed using protease and periodate. Multiple epitopes were present on each molecule recognized by 4B5. The determinants recognized by this antibody deserve additional study as possible markers of premalignant change in patients with NSCLC.

Antibodies, Monoclonal↗
PubMed1992

Fibronectin is an immunosuppressive substance associated with epithelial ovarian cancer.

BACKGROUND: Although the ascites of patients with ovarian cancer has been reported to contain immunosuppressive factors, the identity and source of this activity has not been determined. Previously, the authors showed that conditioned media from two of four epithelial ovarian cancer cell lines inhibits proliferation of mitogen-stimulated human lymphocytes. The physical characteristics of the inhibitory substance are unlike those of peptide growth factors but closely resemble those of fibronectin. METHODS AND RESULTS: In the current study, it was found that the two ovarian cancer cell lines that produce the inhibitory substance have more fibronectin on the cell surface and secrete significantly more immunoreactive fibronectin into their culture media than the other two ovarian cancer cell lines. In addition, the immunosuppressive activity was bound to a gelatin-Sepharose affinity column, known to bind fibronectin. Finally, in ascites from 20 patients with advanced epithelial ovarian cancer, fibronectin levels correlated with the ability to inhibit proliferation of lectin-stimulated lymphocytes (P < 0.001). CONCLUSIONS: Fibronectin is produced by some ovarian cancer cell lines and acts to inhibit proliferation of mitogen-stimulated lymphocytes. Additional studies are needed to clarify the role of fibronectin in ovarian cancer.

Ascites↗
PubMed1993

Peripheral T-cell lymphoma in childhood and adolescence. A clinicopathologic study of 22 patients.

BACKGROUND: Peripheral T-cell lymphoma (PTCL), although the most common T-cell lymphoma in adults, is relatively rare in childhood, and only small series have been reported. METHODS/RESULTS: Twenty-two cases of PTCL were studied that occurred in patients 18 months to 20 years of age. Nine were seen when the condition was diagnosed, and the other 13 were referred after they had relapses. The stage at diagnosis was I or II (45%), III (41%), and IV (14%). Patients with Stage IV disease were younger than those with Stage I or II disease (2.5 versus 14.8 years, P = 0.04). Twelve patients had extranodal disease when the diagnosis was made; the skin was the most common site. Ten tumors were classified as diffuse large cell type; five, as diffuse anaplastic large cell type; and seven, as diffuse mixed cell type. Twenty of the 21 tumors tested were CD30 (Ki-1 or Ber-H2) antigen positive. Of the nine patients seen when the diagnosis was made and treated by the authors, three had a relapse (median, 12 months), a 2-year relapse-free survival (RFS) rate of 61%. For the total group, the RFS was longer for patients older than 12 years of age compared with those who were younger (20 versus 12 months, P = 0.05). Overall, six patients remained in their first complete remission. Sixteen patients had a relapse, and 13 of these underwent bone marrow transplantation (BMT). Six of these remained in complete remission (median, 18 months after BMT). Overall, only 6 of 22 patients died (median survival, > 60 months). CONCLUSION: It was concluded that aggressive therapy, including BMT for relapses, can provide prolonged disease control in most children with PTCL.

Adolescent↗
PubMed1993

Prognostic significance of clinical and pathologic features in diffuse large B-cell lymphoma.

BACKGROUND AND METHODS: The diffuse large cell non-Hodgkin lymphomas are a heterogeneous group of neoplasms that are potentially curable. To identify important predictors of clinical outcome, the authors evaluated the clinical and pathologic features of 114 patients with newly diagnosed diffuse large B-cell lymphoma who were uniformly staged and treated with curative intent. The authors were particularly interested in determining whether any pathologic features added to the ability of the clinical features to predict patient survival. RESULTS: Several clinical and pathologic features were found to be associated with survival by univariate analysis. However, multivariate analysis disclosed that only the stage of disease and the symptom status were significantly associated with survival. Low stage and lack of B symptoms were favorable indicators of overall survival and failure-free survival. CONCLUSIONS: The authors suggest that the evaluation of pathologic features in diffuse large B-cell lymphoma has little prognostic utility and recommend that the pathology evaluation be limited to features that are useful for diagnostic purposes.

Aged↗
PubMed1993

Superior vena cava thrombosis related to catheter malposition in cancer chemotherapy given through implanted ports.

BACKGROUND: Thrombosis of the central veins is one of the most frequent complications of implanted venous access devices. Among the first cases occurring in our patients, most were associated with left-sided placement of the ports, with catheter tips lying against the external wall in the upper half of the superior vena cava. Some chest radiographs showed lateromediastinal opacities centered on the catheter tip, suggesting a vessel injury. This position allows a narrow contact between the catheter tip and the vessel wall, thus endothelial injuries might result from mechanical and chemical attack. METHODS: To assess the role of catheter position, we reviewed the routine chest radiographs of 379 patients who received chemotherapy through venous access devices and were followed up at our department between December 1985 and December 1990. Four groups (upper left, upper right, lower left, and lower right) were defined according to the level of the catheter tip (innominate veins or upper half of the vena cava versus lower half of the vena cava or auricula) and to the side of port implantation. RESULTS: Ten patients developed symptomatic venous thrombosis (superior vena cava in 9 patient, left subclavian vein in 1 patient). A strong correlation existed between catheter position and incidence of thrombosis: upper left, 8/28 (28.6%); upper right, 1/33 (3%); lower right, 1/68 (1.5%); and lower left, 0/250. Since 1988, we have insisted on replacement of malpositioned catheters, and we have observed fewer thromboses (2/191 versus 8/188). CONCLUSIONS: The current study suggests that patients with left-sided ports and catheter tips lying in the upper part of the vena cava are at high risk for severe thrombotic complications.

Antineoplastic Agents↗
PubMed1994

Multivariable analysis of DNA ploidy, p53, and HER-2/neu as prognostic factors in endometrial cancer.

BACKGROUND: Several molecular-genetic alterations in endometrial cancers, including aneuploidy and aberrant expression of p53 and HER-2/neu, have been associated with poor prognosis. To determine the importance of molecular-genetic factors relative to more traditional surgical-pathologic prognostic factors, a multivariable analysis was performed. METHODS: Immunohistochemical staining for p53, HER-2/neu, estrogen receptor, progesterone receptor, and epidermal growth factor receptor was performed on frozen sections from 100 primary endometrial cancers. DNA ploidy was determined using computerized image analysis of Feulgen-stained touch preparations. In addition, information regarding surgical-pathologic features of the cancers was obtained. Univariable analysis was performed followed by multivariable analysis using Cox's proportional hazards model to identify variables predictive of poor prognosis. RESULTS: With univariable analysis, race, histologic type, stage, grade, myometrial invasion, estrogen receptor, progesterone receptor, ploidy, p53 and HER-2/neu were predictive of the presence of persistent or recurrent disease. In the multivariable analysis, only International Federation of Gynecology and Obstetrics stage (P = 0.005), grade (P = 0.005), myometrial invasion (P = 0.024), and ploidy (P = 0.028) were significant. CONCLUSIONS: Among molecular-genetic prognostic factors, DNA ploidy was the most strongly predictive of persistent or recurrent disease.

Aged↗
PubMed1994

Transforming growth factor-beta inhibits proliferation of human ovarian cancer cells obtained from ascites.

BACKGROUND: Previously, the authors found that immortalized ovarian cancer cell lines generally were resistant to the growth inhibitory effect of transforming growth factor-beta and frequently had lost the ability to produce or activate this growth factor. In this study, the authors examined whether early passage epithelial ovarian cancer cells obtained from ascites are growth-inhibited by or produce transforming growth factor-beta. METHODS: Ovarian cancer cells were purified from ascites by percoll gradient density centrifugation, and inflammatory cells were removed using anti-CD45 antibody. The effect of transforming growth factor-beta on the proliferation of ovarian cancer cells was assessed using the thymidine incorporation assay. Immunohistochemical staining for transforming growth factor-beta 1 and beta 2 also was performed in these cells. RESULTS: Transforming growth factor-beta (10 ng/ml) significantly inhibited [3H]thymidine incorporation in 19 of 20 (95%) primary ovarian cancers (P < 0.05). In cases in which significant inhibition was seen, the mean thymidine incorporation was 33 plus or minus 28% of control values. In addition, there was no difference in dose-dependent inhibition of proliferation between ovarian cancer cells and normal ovarian epithelial cells. Eleven of 18 ovarian cancers (61%) were found to express immunohistochemically detectable transforming growth factor-beta, but immunostaining was not observed in 39% of cases. CONCLUSIONS: Although most primary ovarian cancer cells remain sensitive to the growth-inhibitory effect of transforming growth factor-beta, loss of production may interrupt the transforming growth factor-beta autocrine inhibitory loop and play a role in the development of some ovarian cancers.

Ascites↗
PubMed1995

Soluble interleukin-2 receptor alpha is elevated in sera of patients with benign ovarian neoplasms and epithelial ovarian cancer.

BACKGROUND: Previous studies have established that soluble interleukin-2 receptor alpha (sIL-2R alpha) levels are elevated in ascites and sera from individuals with advanced ovarian cancer (International Federation of Gynecology and Obstetrics [FIGO] Stage III/IV). This study was undertaken to evaluate sIL-2R alpha levels in individuals with benign ovarian neoplasms and early stage ovarian cancer (FIGO Stage I/II). Comparison with CA 125 levels was performed to assess screening potential. METHODS: Sera from 92 healthy individuals, 61 with benign adnexal masses, 12 patients with FIGO Stage I/II ovarian cancers, and 27 patients with FIGO Stage III/IV ovarian cancers were assayed for sIL-2R alpha by enzyme-linked immunosorbent assay and CA 125 by radioimmunoassay. RESULTS: The mean serum sIL-2R alpha levels for benign pelvic masses, and Stage I/II and Stage III/IV epithelial ovarian cancer were 1507 +/- 82, 1631 +/- 274, and 2596 +/- 384 U/ml, respectively. The difference between mean serum sIL-2R alpha levels in individuals with benign adnexal masses and Stage III/IV epithelial ovarian cancer was statistically significant (P < 0.05). In addition, of the four individuals with FIGO Stage I/II ovarian cancer who had CA125 levels below 35 U/ml, the accepted upper limit of normal, three patients had elevated serum sIL-2R alpha levels. Eleven of 12 patients (92%) with potentially curable Stage I/II disease had elevated serum levels of either sIL-2R alpha or CA125 and 8 of 12 (67%) had elevations of both sIL-2R alpha and CA125. Sensitivity and specificity of a combination of CA 125 and soluble IL-2R alpha were 88.5% and 27.1%, respectively. CONCLUSION: Soluble interleukin-2 receptor alpha levels do not appear to differentiate between benign adnexal lesions and early malignancy; however, measurement of sIL-2R alpha levels in combination with CA125 warrants further evaluation to determine if together they will identify individuals with Stages I and II ovarian cancer.

Biomarkers, Tumor↗
PubMed1995

Toward an optimal algorithm for ovarian cancer screening with longitudinal tumor markers.

Stored samples from women in the Stockholm screening study were reassayed for CA125II (Centocor, Malvern, PA) and OVX1. The postmenopausal women older than age 50 without ovarian cancer were randomly split into a training set to develop a screening test based on longitudinal marker levels and a second set to validate the test. The CA125II data from each woman is summarized by the slope and intercept from a linear regression of log(CA125II) on time since first sample. The slope versus the intercept for the training set and the ovarian cancer cases formed a bivariate scatter plot. A curve was drawn on the scatter plot that separated most of the women with ovarian cancer from all other women; it delineated a screening test. The specificity of this test was examined on the validation set with a specificity of 99.8%. Bayes' theorem was used to calculate the risk of ovarian cancer (ROC) based on the intercept, slope, and assay variability. It is important to account for assay variability because it can produce large slopes over short periods of time. The maximum risk, which identified 83% (5 of 6) of the ovarian cancers detected within a year of last assay, was applied as a test to the training set and confirmed a high specificity of 99.7%. With this specificity and sensitivity, the ROC algorithm using the CA125II assay has an estimated positive predictive value of 16%, substantially greater than the positive predictive value based on a single assay. Further study is planned to confirm the sensitivity of this approach.

Aged↗
PubMed1995

Ovarian cancer screening. The use of serial complementary tumor markers to improve sensitivity and specificity for early detection.

BACKGROUND: The use of serum tumor markers for the early detection of ovarian cancer has been limited because of their low sensitivity and low positive predictive value. CA 125 levels are elevated in only about one half of women with Stage I ovarian cancer, thus researchers have focused on using the serial measurement of complementary markers to improve the sensitivity, specificity, and positive predictive value of this approach for screening. METHODS: Multiple serum markers have been analyzed in women with early stage epithelial ovarian cancer. CA 125, CA 15-3, C19-9, CA 54-61, CA 72-4, CEA, HMFG2, IL-6, IL-10, LSA, M-CSF, NB70K, OVX1, PLAP, TAG72, TNF, TPA, and UGTF have been studied alone and in combination in this setting. Complementarity and logistic regression analyses have been performed to assess those markers with the highest likelihood of improving sensitivity and specificity for early detection. Serial analysis of a second-generation CA 125 measuring the intercept (initial level) and slope (change of levels over time) can be used to discriminate malignant cases from benign and normal cases. RESULTS: Analyses have shown that the serial measurement of the new, more sensitive CA 125 has a high sensitivity (83%), specificity (99.7%), and positive predictive value (16%) for the early detection of ovarian cancer. OVX1 used in combination with CA 125 provides the best complementarity. Serial measurements of the two markers have sensitivities in the range of that for transvaginal ultrasonography. CONCLUSION: The serial measurement of complementary serum markers can improve the use of marker screening for epithelial ovarian cancer. With the use of several different methods of analysis, it has been shown that this approach improves the sensitivity, specificity, and positive predictive value of serum markers CA 125 and OVX1. A procedure that measures complementary serum markers over time can be used as a primary screening technique followed by transvaginal ultrasonography. This could provide a cost-effective means of early detection and could significantly decrease the probability of surgical intervention for false-positive test results.

Biomarkers, Tumor↗
PubMed2001

OVX1, macrophage-colony stimulating factor, and CA-125-II as tumor markers for epithelial ovarian carcinoma: a critical appraisal.

BACKGROUND: Ovarian carcinoma remains the leading cause of death from gynecologic malignancy in Australia, the Netherlands, and the United States. CA-125-II, the most widely used serum marker, has limited sensitivity and specificity for detecting small-volume, early-stage disease. Therefore, a panel of three serum tumor markers-OVX1, CA-125-II, and macrophage-colony stimulating factor (M-CSF)-has been used to evaluate the sensitivity and specificity of multiple markers for the detection of early-stage ovarian carcinoma. METHODS: Preoperative serum levels of OVX1, CA-125-II, and M-CSF were measured in 281 patients with primary ovarian epithelial tumors of different histotypes. Among these tumors, 175 were malignant, 29 were of borderline malignancy, and 77 were benign. The three markers also were measured in sera from 117 apparently healthy women. Marker levels were considered abnormal at CA-125-II > 35 U/mL, OVX1 > 7.2 U/mL, and M-CSF > 3.5 ng/mL. RESULTS: Among 175 women with malignant ovarian tumors, at least one of the three serum markers was elevated in 85%, whereas CA-125-II was elevated in 80% (P = 0.008). In 58 patients with Stage I ovarian carcinoma, at least one of the three serum markers was elevated in 76%, whereas CA-125 levels were elevated in 66% (P = 0.04). For patients with borderline and benign tumors, a combination of the three antigens had slightly higher sensitivity compared with CA-125-II, but the differences were not statistically significant. Among 117 apparently healthy women, CA-125-II was elevated in 4%, and one of the three markers was positive in 17%. CONCLUSIONS: The sensitivity of a combination of three serum markers was significantly greater than the sensitivity of the CA-125-II assay alone in patients with primary ovarian epithelial tumors of different histotypes. This was true for all stages, including early-stage, potentially curable disease. When used as single markers, however, only the CA-125-II assay could distinguish invasive Stage I tumors from apparently healthy women.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed2001

Synthesis of 5-substituted pyrrolo[1,2-b]pyridazines with antioxidant properties.

5-Substituted pyrrolo[1,2-b]pyridazines have been prepared by cyclisation of pyridazine with diphenylcyclopropenone followed by further functionalisations in the pyrrolo[1,2-b]pyridazine 5-position. Several compound exhibit profound inhibition of lipid peroxidation in vitro. Lipid peroxidation of boiled rat liver microsomes was induced by ascorbic acid/FeSO4 and the peroxidation was determined by measuring the thiobarbituric acid reactive material.

Animals↗
PubMed2004

Prognostic factors influencing survival in patients with B-cell small lymphocytic lymphoma.

The term "B-cell small lymphocytic lymphoma" (B-SLL) is generally reserved for patients with lymph node masses that show the histology and immunophenotype of B-cell chronic lymphocytic leukemia (B-CLL) but who are not leukemic. The aim of our study was to define clinical factors that predict for survival in B-SLL. Thirty-nine patients with B-SLL and with less than 5,000 mature-appearing lymphocytes/microL in the peripheral blood were studied. The median follow-up of survivors was 6.6 years (range, 1.6-12.3 years). The estimated 5-year overall survival (OS) and failure-free survival (FFS) were 66% and 23%, respectively. In the univariate analysis, significant adverse predictors for OS were age > or =60 years, B symptoms, elevated serum LDH, low hemoglobin (<11 g/dL), and high International Prognostic Index (IPI) score (3-5). In multivariate analysis, the IPI score was the only significant predictor of OS. Anemia and B symptoms were additionally predictive of poor OS in patients with low IPI scores.

Adult↗
PubMed1994

Neuropsychological deficit among elderly workers in aluminum production.

A cross-sectional study was conducted at a Norwegian primary aluminum plant. All workers aged 61-66 years were offered early retirement benefits. Among the workers, 47 met the study criteria and 38 (81%), comprising 14 potroom workers, 8 foundry workers, and 16 controls, volunteered to participate. They were tested with a neuropsychological test battery. Workers in potrooms with Søderberg electrolytic cells were found to show signs of impairment of the nervous system. A test for tremor discriminated significantly between the potroom group and the controls. There was a suggestion of increased risk of impaired visuospatial organization and a tendency to a decline in psychomotor tempo in the potroom workers. We suggest that the above findings may be related to long-term occupational exposure in the potroom, and further to chronic low-dose exposure to aluminum.

Aged↗