BACKGROUND: Previous work has demonstrated that smokers have higher white blood cell counts than ... more BACKGROUND: Previous work has demonstrated that smokers have higher white blood cell counts than nonsmokers, but the effect of biochemically-confirmed smoking cessation on peripheral leukocyte counts has not been demonstrated in a large prospective study. METHODS: Subjects were healthy smokers enrolled in a trial of sustained-release bupropion for relapse prevention after smoking cessation. White blood cell (WBC) counts and absolute neutrophil counts (ANC) were measured at baseline, week 7 and week 52. Smoking status was assessed at weeks 7 and 52 by self-report and biochemically confirmed with expired air carbon monoxide levels. Multivariate analyses compared changes in WBC count and ANC between smokers who did and did not stop smoking, adjusting for treatment group, age, sex, and body mass index. RESULTS: Of 784 smokers enrolled, 461 had biochemically-confirmed tobacco abstinence after 7 weeks of bupropion; 429 were randomly assigned to receive continued bupropion or placebo until...
American Journal of Clinical Oncology, Oct 1, 2007
To estimate the cumulative percentage of second primary tumors (SPTs) in head and neck (H&amp... more To estimate the cumulative percentage of second primary tumors (SPTs) in head and neck (H&N) cancer patients and primary cancers in general Nicotine Dependence Center (NDC) population controls following tobacco dependence consultation seen between 1988 and 2001. A 1:1 matched pair design and a stratified Cox proportional hazard model were used. General NDC population controls were matched on age, gender, and NDC consult (type and date) to the H&N cancer patients. The study population included 101 H&N cancer patients (66 male, 35 female) with mean (SD) age of 58.7 (10.1) years. Baseline demographics and length of follow-up were similar between groups. However, H&N cancer patients smoked more cigarettes per day than controls (P < 0.003). For H&N cancer patients, the median time from initial H&N cancer diagnosis to NDC consult was 7 months (range, 0-292 months). Following the NDC consult, 27 H&N cancer patients developed 32 SPTs; whereas among the controls, 12 patients developed 12 other cancers (P = 0.013). There was no difference in the development of non-tobacco-related cancers (P = 0.273). However, H&N cancer patients were more likely to develop tobacco-related cancers (P = 0.01). Furthermore, there was a trend where the H&N cancer patients who continued to use tobacco were more likely to develop tobacco-related cancers than those who remained abstinent (P = 0.10). These findings confirm that H&N cancer patients are more prone to the development of tobacco-related cancers. Further, these findings suggest that H&N cancer patients who stop using tobacco are able to decrease the development of tobacco-related SPTs.
To determine the extent of side effects during the initial use of nicotine nasal spray for smokin... more To determine the extent of side effects during the initial use of nicotine nasal spray for smoking cessation. We performed a one-sample, noncomparative, open-label evaluation of the pattern of use, side effects, relief of withdrawal symptoms, and cotinine levels with nicotine nasal spray. Adult smokers were recruited to use the nicotine nasal spray for smoking cessation at a dosage of 1 to 2 mg/h. Subjects completed daily diaries, which included an assessment of nicotine withdrawal symptoms, previously reported irritant effects of the nicotine nasal spray, and symptoms of nicotine toxicity. A plasma cotinine level was measured at baseline and at day 7 for calculation of percentage replacement. The mean age of the 50 study subjects was 43.7 years, 46% were women, and the mean baseline smoking rate was 28.5 cigarettes per day. We found an increase in five symptoms (runny nose, nasal irritation, throat irritation, watering eyes, and sneezing) that had been essentially absent before initiation of use of the nicotine nasal spray. All but throat irritation decreased significantly during days 0 through 7 of the study. The mean daily frequency of nicotine nasal spray use for the first week was 15.0 doses. Use of the nasal spray decreased significantly (P<0.001) during the initial 8 weeks of treatment. The mean percentage cotinine replacement for those subjects who were abstinent at day 7 was 38.6%. Although nicotine nasal spray causes substantial irritant side effects during the first few days of use, these adverse effects decrease significantly within the first week. Despite these side effects, subjects continued to use the nicotine nasal spray and experienced a high rate of initial abstinence from smoking.
A 46-year-old woman presented for a second opinion regarding a 3-4 cm mass of the uterine cervix.... more A 46-year-old woman presented for a second opinion regarding a 3-4 cm mass of the uterine cervix. A prior biopsy had been interpreted as a malignant melanoma of the cervix, resulting in a radical hysterectomy with bilateral salpingooophorectomy. This was to be followed by external beam irradiation and immunotherapy; however, given the rarity of this diagnosis, the patient sought a second opinion at our institution. Further review of the pathological material from the hysterectomy revealed a morphologically benign perivascular epithelioid cell neoplasm rather than a malignant melanoma. Close monitoring of the patient was recommended; she is currently diseasefree more than three years after her initial presentation.
Do colorectal cancer patients with hyperbilirubinemia and liver metastases benefit from chemother... more Do colorectal cancer patients with hyperbilirubinemia and liver metastases benefit from chemotherapy? This study entailed a review of 3,019 consecutive patients with colorectal cancer. Within this cohort, 20 met the study's a priori selection criteria, which included a new diagnosis of colorectal cancer, no prior therapy, and a total bilirubin of ≥3.0 mg/dL. All 20 patients had liver metastases, and as a whole the group had a median serum bilirubin of 6.4 mg/dL (range 3.1, 28 mg/dL). Six patients received chemotherapy with an oxaliplatin-containing regimen, and four subsequently sustained a drop in their bilirubin. In one instance, a drop from 27.2 to 2.5 mg/dL occurred. These six patients lived a median of 71 days (range 23+, 283 days), but one treatment-related death occurred. In contrast, patients who received only supportive care lived a median of 28 days. Chemotherapy appears to provide modest benefit to newly diagnosed colorectal cancer patients with severe hyperbilirubine...
Archives of pediatrics & adolescent medicine, 2000
To determine the efficacy of nicotine patch therapy in adolescents who want to stop smoking and t... more To determine the efficacy of nicotine patch therapy in adolescents who want to stop smoking and to assess biochemical markers of smoking and nicotine intake. Nonrandomized, open-label trial using a 15 mg/16 h patch. Two midwestern cities. One hundred one adolescents aged 13 through 17 years smoking at least 10 cigarettes per day (cpd). Six weeks of nicotine patch therapy and follow-up visits at 12 weeks and 6 months. Self-reported smoking abstinence verified by expired-air carbon monoxide (CO) level of no more than 8 ppm, nicotine withdrawal symptoms, and plasma cotinine level. Forty-one participants were female (mean [+/- SD] age, 16.5 [+/- 1.1] years). Median baseline smoking rate was 20.0 cpd (range, 10-40 cpd). Biochemically confirmed point prevalence smoking abstinence was 10.9% (11/101) at 6 weeks and 5.0% (5/101) at 6 months. The mean (+/- SD) plasma cotinine level at baseline was 1510.9 +/- 732.7 nmol/L; for nonsmoking subjects at weeks 3 and 6, 607.8 +/- 386.2 and 710.0 +/-...
Pathologic grade and stage, immunohistochemical analysis of eight cell and tumor markers, and DNA... more Pathologic grade and stage, immunohistochemical analysis of eight cell and tumor markers, and DNA ploidy were studied in 36 cases of bladder cancer to determine the features of value in assessment of patients' survival. Tumors of high grade and advanced stage correlated with DNA aneuploidy, whereas low grade and early stage correlated with DNA diploidy when simultaneously evaluated with survival. In addition, blood group isoantigen A correlated with DNA ploidy in deceased patients, whereas blood group isoantigen H and oncogene-related protein p21 correlated with DNA ploidy in surviving patients. Despite the relatively small number of cases studied, these results suggest that pathologic grade and stage and immunohistochemical analysis of blood group isoantigens A and H and oncogene-related protein p21 hold additional value in the prediction of bladder cancer survival when evaluated simultaneously with DNA ploidy.
Monoclonal antibody F36/22 recognizes high-molecular-weight glycoprotein components associated wi... more Monoclonal antibody F36/22 recognizes high-molecular-weight glycoprotein components associated with neoplastic development of the ovary. Indirect immunoperoxidase staining techniques were performed on a panel of nonmalignant ovarian tissues, primary ovarian tumors, exfoliated ascitic tumor cells, and metastatic lesions. Normal ovarian tissue components (n = 20) failed to exhibit detectable levels of antigen, whereas benign ovarian tissues show a low incidence of immunostaining (three of 26) restricted to some ductal elements. One hundred % (19 of 19) of the immunopositive primary malignant tumors were histologically classified as adenocarcinomas. Each of the predominant adenocarcinoma histotypes consistently showed expression of the antigen with 30 to 100% of the tumor cells scored as immunopositive. Ascitic tumor cells obtained from all of the ovarian adenocarcinoma patients examined (47 of 47) displayed immunopositive reactions, whereas normal mesothelial cells in these specimens ...
Murine monoclonal antibody F36/22 was derived by immunizing BALB/c mice with human breast cancer ... more Murine monoclonal antibody F36/22 was derived by immunizing BALB/c mice with human breast cancer cells. This antibody reacts with an antigen located both on differentiated mammary ductal epithelia and on breast carcinomas, as examined by indirect immunoperoxidase techniques. Although the expression of this antigen correlated with estrogen receptor levels of breast tumors, antibody F36/22 did not directly react with estrophilin. In contrast to the expression of classical differentiation antigens, this antigen was found in a high percentage of poorly differentiated carcinomas of the breast. Staining intensities were similar for well- and poorly differentiated tumors; thus, antigen expression was not related to tumor grade. Intratumoral heterogeneity of antigen expression was observed in the majority of tumors. Since a subset (64 of 80) of the breast carcinomas examined have expressed the antigen, McAb 36/22 was of use for the immunological subclassification of tumors which were indist...
Cloned hybridoma cell lines were obtained from fusions of murine myeloma cells with lymphocytes o... more Cloned hybridoma cell lines were obtained from fusions of murine myeloma cells with lymphocytes of mice immunized against human breast cancer cells. Hybridomas F36/22 and M7/105 produced antibodies whose binding to breast cancer cells could not be inhibited by prior absorptions with fibroblasts, lymphoblastoid cells, or erythrocytes. Results from cell surface binding assays using a panel of tumor cell lines indicated that antibodies F36/22 and M7/105 recognized determinants expressed maximally on breast cancer cells. Antibody F36/22 reacted with normal mammary epithelial membranes and milk fat globule membranes, whereas antibody M7/105 produced no detectable binding to these specimens. Antigens carrying these epitopes each showed reactivity with concanavalin A lectin. The determinant corresponding to antibody F36/22 was detectable in histological sections of a subset of breast tumors obtained at surgery.
A quantitative immunoassay procedure has been constructed to evaluate levels of ductal carcinoma ... more A quantitative immunoassay procedure has been constructed to evaluate levels of ductal carcinoma antigen recognized by murine McAb F36/22. Using this method, 3% of 64 apparently healthy individuals and 13% of 40 patients with benign breast disease expressed serum antigen levels above 70 units/ml. Greater than 50% of 116 patients with clinical evidence of breast cancer demonstrated circulating ductal carcinoma antigen levels above 70 units/ml. Patients with ductal carcinomas of other sites, including prostate and gastrointestinal tumors, also demonstrated elevated levels of antigen (11 and 27%, respectively). The incidence of elevated serum ductal carcinoma antigen levels correlated significantly with the incidence of intratumoral antigen expression. Lectin binding, molecular weight, and density measurements indicated that circulating antigen occurs as a high-molecular-weight glycoprotein with mucin-like characteristics.
With the use of five murine monoclonal antibodies (1A5, 2A4, 3F1, F5 and 3A12) and an antigen-aff... more With the use of five murine monoclonal antibodies (1A5, 2A4, 3F1, F5 and 3A12) and an antigen-affinity purified goat polyclonal IgG antibody, the presence of a prostate-specific antigenic domain in human prostate-specific antigen molecule was identified. The results were based upon a series of quantitative competitive inhibition assays of each 125I-labeled monoclonal antibody and polyclonal antibody binding to prostate-specific antigen by unlabeled monoclonal antibodies as inhibitors, and immunohistochemical examination of an extensive panel of human tissue specimens. A cluster of two epitopes that are spatially related or in close topographical proximity and represent a prostate-specific antigenic domain are defined by the monoclonal antibodies 1A5, 2A4, 3F1, and F5, 3A12, respectively.
Evidence suggests that immunological response in chronic inflammation is dynamic, oscillating bet... more Evidence suggests that immunological response in chronic inflammation is dynamic, oscillating between active immunity and tolerance. We hypothesized that a similar dynamic exists in melanoma and administration of therapy during a unique phase of such oscillation could impact clinical outcome. Patients with metastatic melanoma eligible to undergo temozolomide underwent serial measurements of C-reactive protein (CRP) and immune biomarkers every 2-3 days for 2 weeks before starting therapy. Treatment was initiated prior to the estimated next CRP peak, or on day 14 post-registration if a peak was not identified. Time profiles of measured biomarkers were analyzed by fitting serially measured data points to 9 mathematical functions and were correlated to time of therapy and outcome. Data suggested that metastatic melanoma patients exhibit a dynamic immune response. The fluctuation of several biomarkers fitted cosine functions with periods which were multiples of 3-4 days. Chemotherapy del...
The chimeric monoclonal antibody cG250 recognises the G250/CAIX/MN antigen found on 95% of clear ... more The chimeric monoclonal antibody cG250 recognises the G250/CAIX/MN antigen found on 95% of clear cell renal cell carcinomas (RCCs). We performed a phase I clinical trial to evaluate the safety, blood pharmacokinetics (PK), and biodistribution of repeated doses of cG250. The primary endpoint was toxicity. Secondary endpoints were cG250 biodistribution and PK; measurement of human anti-chimeric-antibodies (HACA); and tumour response rates. Eligible patients had unresectable or metastatic clear cell RCC. Doses of 5, 10, 25, or 50 mg/m(2) were given weekly by intravenous infusion for six weeks. Three patients were treated at each dose level. Trace (131)I-labelled cG250 was administered on weeks 1 and 5. Thirteen patients participated and were evaluable. One patient developed brain metastases and was replaced. No grade 3 or 4 toxicities and no dose-limiting toxicity occurred. One patient died due to progressive disease within 30 days of receiving the study drug. One patient developed HAC...
BACKGROUND: Previous work has demonstrated that smokers have higher white blood cell counts than ... more BACKGROUND: Previous work has demonstrated that smokers have higher white blood cell counts than nonsmokers, but the effect of biochemically-confirmed smoking cessation on peripheral leukocyte counts has not been demonstrated in a large prospective study. METHODS: Subjects were healthy smokers enrolled in a trial of sustained-release bupropion for relapse prevention after smoking cessation. White blood cell (WBC) counts and absolute neutrophil counts (ANC) were measured at baseline, week 7 and week 52. Smoking status was assessed at weeks 7 and 52 by self-report and biochemically confirmed with expired air carbon monoxide levels. Multivariate analyses compared changes in WBC count and ANC between smokers who did and did not stop smoking, adjusting for treatment group, age, sex, and body mass index. RESULTS: Of 784 smokers enrolled, 461 had biochemically-confirmed tobacco abstinence after 7 weeks of bupropion; 429 were randomly assigned to receive continued bupropion or placebo until...
American Journal of Clinical Oncology, Oct 1, 2007
To estimate the cumulative percentage of second primary tumors (SPTs) in head and neck (H&amp... more To estimate the cumulative percentage of second primary tumors (SPTs) in head and neck (H&N) cancer patients and primary cancers in general Nicotine Dependence Center (NDC) population controls following tobacco dependence consultation seen between 1988 and 2001. A 1:1 matched pair design and a stratified Cox proportional hazard model were used. General NDC population controls were matched on age, gender, and NDC consult (type and date) to the H&N cancer patients. The study population included 101 H&N cancer patients (66 male, 35 female) with mean (SD) age of 58.7 (10.1) years. Baseline demographics and length of follow-up were similar between groups. However, H&N cancer patients smoked more cigarettes per day than controls (P < 0.003). For H&N cancer patients, the median time from initial H&N cancer diagnosis to NDC consult was 7 months (range, 0-292 months). Following the NDC consult, 27 H&N cancer patients developed 32 SPTs; whereas among the controls, 12 patients developed 12 other cancers (P = 0.013). There was no difference in the development of non-tobacco-related cancers (P = 0.273). However, H&N cancer patients were more likely to develop tobacco-related cancers (P = 0.01). Furthermore, there was a trend where the H&N cancer patients who continued to use tobacco were more likely to develop tobacco-related cancers than those who remained abstinent (P = 0.10). These findings confirm that H&N cancer patients are more prone to the development of tobacco-related cancers. Further, these findings suggest that H&N cancer patients who stop using tobacco are able to decrease the development of tobacco-related SPTs.
To determine the extent of side effects during the initial use of nicotine nasal spray for smokin... more To determine the extent of side effects during the initial use of nicotine nasal spray for smoking cessation. We performed a one-sample, noncomparative, open-label evaluation of the pattern of use, side effects, relief of withdrawal symptoms, and cotinine levels with nicotine nasal spray. Adult smokers were recruited to use the nicotine nasal spray for smoking cessation at a dosage of 1 to 2 mg/h. Subjects completed daily diaries, which included an assessment of nicotine withdrawal symptoms, previously reported irritant effects of the nicotine nasal spray, and symptoms of nicotine toxicity. A plasma cotinine level was measured at baseline and at day 7 for calculation of percentage replacement. The mean age of the 50 study subjects was 43.7 years, 46% were women, and the mean baseline smoking rate was 28.5 cigarettes per day. We found an increase in five symptoms (runny nose, nasal irritation, throat irritation, watering eyes, and sneezing) that had been essentially absent before initiation of use of the nicotine nasal spray. All but throat irritation decreased significantly during days 0 through 7 of the study. The mean daily frequency of nicotine nasal spray use for the first week was 15.0 doses. Use of the nasal spray decreased significantly (P<0.001) during the initial 8 weeks of treatment. The mean percentage cotinine replacement for those subjects who were abstinent at day 7 was 38.6%. Although nicotine nasal spray causes substantial irritant side effects during the first few days of use, these adverse effects decrease significantly within the first week. Despite these side effects, subjects continued to use the nicotine nasal spray and experienced a high rate of initial abstinence from smoking.
A 46-year-old woman presented for a second opinion regarding a 3-4 cm mass of the uterine cervix.... more A 46-year-old woman presented for a second opinion regarding a 3-4 cm mass of the uterine cervix. A prior biopsy had been interpreted as a malignant melanoma of the cervix, resulting in a radical hysterectomy with bilateral salpingooophorectomy. This was to be followed by external beam irradiation and immunotherapy; however, given the rarity of this diagnosis, the patient sought a second opinion at our institution. Further review of the pathological material from the hysterectomy revealed a morphologically benign perivascular epithelioid cell neoplasm rather than a malignant melanoma. Close monitoring of the patient was recommended; she is currently diseasefree more than three years after her initial presentation.
Do colorectal cancer patients with hyperbilirubinemia and liver metastases benefit from chemother... more Do colorectal cancer patients with hyperbilirubinemia and liver metastases benefit from chemotherapy? This study entailed a review of 3,019 consecutive patients with colorectal cancer. Within this cohort, 20 met the study's a priori selection criteria, which included a new diagnosis of colorectal cancer, no prior therapy, and a total bilirubin of ≥3.0 mg/dL. All 20 patients had liver metastases, and as a whole the group had a median serum bilirubin of 6.4 mg/dL (range 3.1, 28 mg/dL). Six patients received chemotherapy with an oxaliplatin-containing regimen, and four subsequently sustained a drop in their bilirubin. In one instance, a drop from 27.2 to 2.5 mg/dL occurred. These six patients lived a median of 71 days (range 23+, 283 days), but one treatment-related death occurred. In contrast, patients who received only supportive care lived a median of 28 days. Chemotherapy appears to provide modest benefit to newly diagnosed colorectal cancer patients with severe hyperbilirubine...
Archives of pediatrics & adolescent medicine, 2000
To determine the efficacy of nicotine patch therapy in adolescents who want to stop smoking and t... more To determine the efficacy of nicotine patch therapy in adolescents who want to stop smoking and to assess biochemical markers of smoking and nicotine intake. Nonrandomized, open-label trial using a 15 mg/16 h patch. Two midwestern cities. One hundred one adolescents aged 13 through 17 years smoking at least 10 cigarettes per day (cpd). Six weeks of nicotine patch therapy and follow-up visits at 12 weeks and 6 months. Self-reported smoking abstinence verified by expired-air carbon monoxide (CO) level of no more than 8 ppm, nicotine withdrawal symptoms, and plasma cotinine level. Forty-one participants were female (mean [+/- SD] age, 16.5 [+/- 1.1] years). Median baseline smoking rate was 20.0 cpd (range, 10-40 cpd). Biochemically confirmed point prevalence smoking abstinence was 10.9% (11/101) at 6 weeks and 5.0% (5/101) at 6 months. The mean (+/- SD) plasma cotinine level at baseline was 1510.9 +/- 732.7 nmol/L; for nonsmoking subjects at weeks 3 and 6, 607.8 +/- 386.2 and 710.0 +/-...
Pathologic grade and stage, immunohistochemical analysis of eight cell and tumor markers, and DNA... more Pathologic grade and stage, immunohistochemical analysis of eight cell and tumor markers, and DNA ploidy were studied in 36 cases of bladder cancer to determine the features of value in assessment of patients' survival. Tumors of high grade and advanced stage correlated with DNA aneuploidy, whereas low grade and early stage correlated with DNA diploidy when simultaneously evaluated with survival. In addition, blood group isoantigen A correlated with DNA ploidy in deceased patients, whereas blood group isoantigen H and oncogene-related protein p21 correlated with DNA ploidy in surviving patients. Despite the relatively small number of cases studied, these results suggest that pathologic grade and stage and immunohistochemical analysis of blood group isoantigens A and H and oncogene-related protein p21 hold additional value in the prediction of bladder cancer survival when evaluated simultaneously with DNA ploidy.
Monoclonal antibody F36/22 recognizes high-molecular-weight glycoprotein components associated wi... more Monoclonal antibody F36/22 recognizes high-molecular-weight glycoprotein components associated with neoplastic development of the ovary. Indirect immunoperoxidase staining techniques were performed on a panel of nonmalignant ovarian tissues, primary ovarian tumors, exfoliated ascitic tumor cells, and metastatic lesions. Normal ovarian tissue components (n = 20) failed to exhibit detectable levels of antigen, whereas benign ovarian tissues show a low incidence of immunostaining (three of 26) restricted to some ductal elements. One hundred % (19 of 19) of the immunopositive primary malignant tumors were histologically classified as adenocarcinomas. Each of the predominant adenocarcinoma histotypes consistently showed expression of the antigen with 30 to 100% of the tumor cells scored as immunopositive. Ascitic tumor cells obtained from all of the ovarian adenocarcinoma patients examined (47 of 47) displayed immunopositive reactions, whereas normal mesothelial cells in these specimens ...
Murine monoclonal antibody F36/22 was derived by immunizing BALB/c mice with human breast cancer ... more Murine monoclonal antibody F36/22 was derived by immunizing BALB/c mice with human breast cancer cells. This antibody reacts with an antigen located both on differentiated mammary ductal epithelia and on breast carcinomas, as examined by indirect immunoperoxidase techniques. Although the expression of this antigen correlated with estrogen receptor levels of breast tumors, antibody F36/22 did not directly react with estrophilin. In contrast to the expression of classical differentiation antigens, this antigen was found in a high percentage of poorly differentiated carcinomas of the breast. Staining intensities were similar for well- and poorly differentiated tumors; thus, antigen expression was not related to tumor grade. Intratumoral heterogeneity of antigen expression was observed in the majority of tumors. Since a subset (64 of 80) of the breast carcinomas examined have expressed the antigen, McAb 36/22 was of use for the immunological subclassification of tumors which were indist...
Cloned hybridoma cell lines were obtained from fusions of murine myeloma cells with lymphocytes o... more Cloned hybridoma cell lines were obtained from fusions of murine myeloma cells with lymphocytes of mice immunized against human breast cancer cells. Hybridomas F36/22 and M7/105 produced antibodies whose binding to breast cancer cells could not be inhibited by prior absorptions with fibroblasts, lymphoblastoid cells, or erythrocytes. Results from cell surface binding assays using a panel of tumor cell lines indicated that antibodies F36/22 and M7/105 recognized determinants expressed maximally on breast cancer cells. Antibody F36/22 reacted with normal mammary epithelial membranes and milk fat globule membranes, whereas antibody M7/105 produced no detectable binding to these specimens. Antigens carrying these epitopes each showed reactivity with concanavalin A lectin. The determinant corresponding to antibody F36/22 was detectable in histological sections of a subset of breast tumors obtained at surgery.
A quantitative immunoassay procedure has been constructed to evaluate levels of ductal carcinoma ... more A quantitative immunoassay procedure has been constructed to evaluate levels of ductal carcinoma antigen recognized by murine McAb F36/22. Using this method, 3% of 64 apparently healthy individuals and 13% of 40 patients with benign breast disease expressed serum antigen levels above 70 units/ml. Greater than 50% of 116 patients with clinical evidence of breast cancer demonstrated circulating ductal carcinoma antigen levels above 70 units/ml. Patients with ductal carcinomas of other sites, including prostate and gastrointestinal tumors, also demonstrated elevated levels of antigen (11 and 27%, respectively). The incidence of elevated serum ductal carcinoma antigen levels correlated significantly with the incidence of intratumoral antigen expression. Lectin binding, molecular weight, and density measurements indicated that circulating antigen occurs as a high-molecular-weight glycoprotein with mucin-like characteristics.
With the use of five murine monoclonal antibodies (1A5, 2A4, 3F1, F5 and 3A12) and an antigen-aff... more With the use of five murine monoclonal antibodies (1A5, 2A4, 3F1, F5 and 3A12) and an antigen-affinity purified goat polyclonal IgG antibody, the presence of a prostate-specific antigenic domain in human prostate-specific antigen molecule was identified. The results were based upon a series of quantitative competitive inhibition assays of each 125I-labeled monoclonal antibody and polyclonal antibody binding to prostate-specific antigen by unlabeled monoclonal antibodies as inhibitors, and immunohistochemical examination of an extensive panel of human tissue specimens. A cluster of two epitopes that are spatially related or in close topographical proximity and represent a prostate-specific antigenic domain are defined by the monoclonal antibodies 1A5, 2A4, 3F1, and F5, 3A12, respectively.
Evidence suggests that immunological response in chronic inflammation is dynamic, oscillating bet... more Evidence suggests that immunological response in chronic inflammation is dynamic, oscillating between active immunity and tolerance. We hypothesized that a similar dynamic exists in melanoma and administration of therapy during a unique phase of such oscillation could impact clinical outcome. Patients with metastatic melanoma eligible to undergo temozolomide underwent serial measurements of C-reactive protein (CRP) and immune biomarkers every 2-3 days for 2 weeks before starting therapy. Treatment was initiated prior to the estimated next CRP peak, or on day 14 post-registration if a peak was not identified. Time profiles of measured biomarkers were analyzed by fitting serially measured data points to 9 mathematical functions and were correlated to time of therapy and outcome. Data suggested that metastatic melanoma patients exhibit a dynamic immune response. The fluctuation of several biomarkers fitted cosine functions with periods which were multiples of 3-4 days. Chemotherapy del...
The chimeric monoclonal antibody cG250 recognises the G250/CAIX/MN antigen found on 95% of clear ... more The chimeric monoclonal antibody cG250 recognises the G250/CAIX/MN antigen found on 95% of clear cell renal cell carcinomas (RCCs). We performed a phase I clinical trial to evaluate the safety, blood pharmacokinetics (PK), and biodistribution of repeated doses of cG250. The primary endpoint was toxicity. Secondary endpoints were cG250 biodistribution and PK; measurement of human anti-chimeric-antibodies (HACA); and tumour response rates. Eligible patients had unresectable or metastatic clear cell RCC. Doses of 5, 10, 25, or 50 mg/m(2) were given weekly by intravenous infusion for six weeks. Three patients were treated at each dose level. Trace (131)I-labelled cG250 was administered on weeks 1 and 5. Thirteen patients participated and were evaluable. One patient developed brain metastases and was replaced. No grade 3 or 4 toxicities and no dose-limiting toxicity occurred. One patient died due to progressive disease within 30 days of receiving the study drug. One patient developed HAC...
Uploads