PubMed Health⌕ Search

Biomedical subjects

H Fritsche

Publications and source records attributed to H Fritsche.

At least 19 recordsLinked to original sources
PubMed2001

2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology.

OBJECTIVE: To update the 1997 clinical practice guidelines for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of breast and colorectal cancers. These guidelines are intended for use in the care of patients outside of clinical trials. OPTIONS: Six tumor markers for colorectal cancer and eight for breast cancer were considered. They could be recommended or not for routine use or for special circumstances. In addition to carcinoembryonic antigen (CEA) and CA 15-3, CA 27.29 was also considered among the serum tumor markers for breast cancer. OUTCOMES: In general, the significant health outcomes identified for use in making clinical practice guidelines (overall survival, disease-free survival, quality of life, lesser toxicity, and cost-effectiveness) were used. EVIDENCE: A computerized literature search from 1994 to March 1999 was performed. VALUES: The same values for use, utility, and levels of evidence were used by the committee. BENEFITS, HARMS, AND COSTS: The same benefit, harms, and costs were used. RECOMMENDATION: Changes were recommended (see Appendix). VALIDATION: The updated recommendations were validated by external review by the American Society of Clinical Oncology's (ASCO's) Health Services Research Committee and by ASCO's Board of Directors. SPONSOR: American Society of Clinical Oncology.

Adult↗
PubMed2001

Changes in circulating carcinoma cells in patients with metastatic prostate cancer correlate with disease status.

OBJECTIVES: To investigate the diurnal variations in circulating tumor cells (CTCs) in metastatic carcinoma of the prostate (CAP) and to determine whether the change in CTCs correlated with disease progression. METHODS: Samples were prepared by immunomagnetic selection of cells from 7 mL of blood targeting the epithelial cell adhesion molecule and differential fluorescent labeling of the collected cells using a nucleic acid dye, antibodies directed against the common leukocyte (CD45), and cytokeratin antigens. Events that stained with the nucleic acid dye and expressed cytokeratin but lacked CD45 were defined as CTCs by multiparameter flow cytometry. RESULTS: Male controls (n = 22) exhibited 0.8 +/- 1.2 events per 7 mL blood compared with 5.9 +/- 4.7 in 10 samples from patients with localized CAP and 46.6 +/- 65.6 events in 10 samples from patients with metastatic CAP. Diurnal testing of 8 cases demonstrated stable levels of CTCs. Ten patients were serially analyzed during a 6-month period for serum prostate-specific antigen and CTCs. The correlation between the prostate-specific antigen level and CTC number was fair. Slow disease progression was found in 4 patients with low CTC numbers (3.0 +/- 3) but it was significantly higher than the control group (P <0.002). Rapid disease progression occurred in 6 patients who demonstrated high CTC numbers (68.5 +/- 71.9). Two patients received chemotherapy that caused substantial fluctuations in the CTCs with less pronounced changes in the prostate-specific antigen level. CONCLUSIONS: We conclude that the level of CTCs can be quantified in the circulation of patients with metastatic CAP and that the change in CTCs correlates with disease progression with no diurnal variations.

Aged↗
PubMed2001

Serum lactate dehydrogenase isoenzyme 1 and prediction of death in patients with metastatic testicular germ cell tumors.

The International Germ Cell Cancer Collaborative Group study of patients with metastatic testicular germ cell tumors showed that catalytic concentration of serum lactate dehydrogenase (S-LD), serum alpha-fetoprotein concentration (S-AFP), and serum human chorionic gonadotropin concentration (S-hCG) predicted death from tumor. The recent international TNM classification (T primary tumor, N lymph node metastasis, M distant metastasis) is based on these results. The aim of our study was to evaluate whether catalytic concentration of S-LD isoenzyme 1 (S-LD-1) was a better predictor than the criteria used for the international classification. In an evaluation series of 44 patients from Odense University Hospital, Denmark, a raised S-LD-1 (>1.0 x upper limit of reference values) had a predictive value for death from tumor in 5-years observation of 46%. The predictive value was 46% for S-LD, 25% for S-AFP, and 40% for S-hCG. A normal SLD-1 had a predictive value for survival over 5-years observation of 100%. It was 81% for S-LD, 75% for SAFP, and 77% for S-hCG. The fraction of the patients who died of tumor and had a raised tumor marker value was 100% for S-LD-1, 46% for S-LD, 9% for S-AFP, and 18% for S-hCG. The fraction of patients with a normal serum tumor marker value among those who survived was 61% for S-LD-1, 81% for S-LD, 94% for SAFP, and 94% for S-hCG. A validation series of 37 patients treated at the University of Texas MD Anderson Cancer Center showed similar findings. Combining the patients in the two series, a raised value of SLD-1 classified more patients into a subgroup with an impaired survival (53%) than S-LD (35%), S-AFP (6%), or S-hCG (11%), and the high risk subgroups based on the international classification (40%). The findings have implications for the staging and treatment of patients with metastatic testicular germ cell tumors.

Biomarkers, Tumor↗
PubMed2000

Performance of a neural network in detecting prostate cancer in the prostate-specific antigen reflex range of 2.5 to 4.0 ng/mL.

OBJECTIVES: To explore the potential role of a neural network-derived algorithm in enhancing the specificity of prostate cancer detection compared with the determination of prostate-specific antigen (PSA) and free PSA (fPSA) while maintaining a 90% detection rate. Recent information suggests that the incidence of detectable prostate cancer is similar in men whose PSA values range from 2.5 to 4.0 ng/mL and from 4.0 to 10.0 ng/mL. If the PSA threshold triggering a prostate biopsy is lowered to 2.5 ng/mL, approximately 13% of men older than 50 would be added to the patient biopsy pool. METHODS: One hundred fifty-one men were enrolled in a prospective, Institutional Review Board-approved protocol to evaluate the incidence of cancer in a population of men who participated in an early-detection program and whose PSA level was between 2.5 and 4.0 ng/mL. All the men underwent biopsy using an 11-core multisite-directed biopsy scheme, and all biopsy specimens were examined by one pathologist. All men had a second blood specimen drawn before the biopsy for a determination of serum PSA, creatinine kinase, prostatic acid phosphatase, and fPSA. A new neural network algorithm was developed with PSA, creatinine kinase, prostatic acid phosphatase, fPSA, and age as input variables to produce a single-valued prostate cancer detection index (PCD-I). This new algorithm was then prospectively tested in the 151 men. Performance parameters (including sensitivity, specificity, positive and negative predictive values, and biopsies saved) were calculated, and a comparative analysis was performed to evaluate the differences among the new algorithm, percent fPSA, PSA density, and PSA density-transition zone. RESULTS: Cancer was histologically confirmed in 24.5% (37 of 151) of the men. The median age of the men was 62 years (range 43 to 74). At a sensitivity of 92%, the specificity for percent fPSA was 11%. The new algorithm (PCD-I) demonstrated an additional enhancement of specificity to 62% at 92% sensitivity. Clinically, the PCD-I would result in a savings of 49% (74 of 151) of all biopsies or 63.6% (71 of 114) of all unnecessary biopsies. CONCLUSIONS: A new generation algorithm, derived from a neural network (PCD-I) incorporating the parameters of age, creatinine kinase, PSA, prostatic acid phosphatase, and fPSA can significantly enhance the specificity and reduce the number of biopsies while maintaining a 92% sensitivity rate.

Acid Phosphatase↗
PubMed2000

Tacrolimus does not abrogate the increased risk of acute graft-versus-host disease after unrelated-donor marrow transplantation with allelic mismatching at HLA-DRB1 and HLA-DQB1.

One hundred patients of median age 34 years (range, 14-53) received bone marrow transplants from unrelated donors serologically matched for human leukocyte antigen HLA-A, HLA-B, and HLA-DR using tacrolimus and minimethotrexate for prevention of acute graft-versus-host disease (GVHD). Sixty-eight patient-donor pairs had allelic matches at HLA-DRB1 and HLA-DQB1, 20 pairs had a single mismatch at HLA-DRB1 or HLA-DQB1, and 12 were mismatched at both HLA-DRB1 and HLA-DQB1. Minimum follow-up time was 6 months. Grades 2 to 4 GVHD occurred in 43% of patients with matched donors, 69% with single allele-mismatched donors, and 71% with double allele-mismatched donors; grades 3 to 4 GVHD occurred in 22%, 43%, and 64%, respectively. On multivariate analysis, the relative risk of grades 2 to 4 GVHD was 2.2 (95% CI, 1.1-4.5; P = .03) with a single allele mismatch and 2.7 (95% CI, 1.2-6.0; P = .02) with a double allele mismatch. The relative risks of grades 3 to 4 GVHD were 3.0 (95% CI, 1.2-7.6; P = .02) and 5.0 (95% CI, 1.9-12.6; P = .001), respectively. Day 100 treatment-related mortality was also adversely affected by allelic mismatching, occurring in 21% of those with matched donors, 50% with single allele-mismatched donors, and 42% with double allele-mismatched donors (P = .02), but overall survival at day 180 did not differ significantly among the 3 groups. Tacrolimus does not abrogate the adverse impact of allele mismatching at HLA-DRB1 and HLA-DQB1 on the risk of moderate-to-severe acute GVHD.

Acute Disease↗
PubMed2000

Restoration of Th1 cytokine synthesis by T cells of patients with chronic myelogenous leukemia in cytogenetic and hematologic remission with interferon-alpha.

Chronic myelogenous leukemia (CML) is a disorder of the hematopoietic stem cell that results in malignant expansion of myeloid cells with a cytogenetic abnormality, the translocation between chromosomes 9 and 22 known as the Philadelphia chromosome. Treatment with IFN-alpha has proven to be an effective therapy, inducing cytogenetic remission in CML patients. However, it is unknown whether IFN-alpha can restore normal immune function for patients who achieve a complete cytogenetic remission. To address this question, we used a method of intracellular staining and flow cytometric analysis to ascribe the syntheses of Th1 or Th2 cytokines to T-cell subsets of patients in chronic, in accelerated, and in blast crisis phases as well as patients who had achieved a complete cytogenetic remission with IFN-alpha. We assessed the cytoplasmic synthesis of cytokine in phorbol ester (phorbol 12-myristate 13-acetate)-activated CD4+ and CD8+ T-cell subsets of 81 patients with various stages of CML and 21 normal controls. The percentages of CD4+ and CD8+ T cells from patients in chronic, in accelerated, and in blast crisis phases that synthesized Th1 cytokines interleukin (IL)-2, IFN-gamma, and tumor necrosis factor-alpha were significantly lower than those of remission patients and normal controls. Conversely, the percentages of CD4+ and CD8+ T cells of patients in chronic, in accelerated, and in blast crisis phases of CML preferentially synthesized the Th2 cytokine IL-10. Patients who achieved a durable complete cytogenetic remission for >2 years without maintenance IFN-alpha therapy restored their preference for a Th1 cytokine profile that is necessary for efficient cytotoxic T-cell function.

Antineoplastic Agents↗
PubMed2000

Novel translational model for breast cancer chemoprevention study: accrual to a presurgical intervention with tamoxifen and N-[4-hydroxyphenyl] retinamide.

Surrogate end point biomarkers for risk assessment and efficacy of potential chemopreventive agents are needed to improve the efficiency and reduce the cost of chemoprevention trials. It is imperative to develop the best clinical breast model for translational surrogate end point biomarker studies, especially with respect to accrual feasibility. We have initiated a prospective study to develop biomarkers for tamoxifen and N-[4-hydroxyphenyl] retinamide by administering either a placebo or both drugs for 2-4 weeks to women with ductal carcinoma in situ or early invasive cancers in the interval between the initial diagnostic core biopsy and definitive surgery. The principle end point is pretreatment versus posttreatment tumor levels of Ki-67; a number of other exploratory markers will also be examined. The planned target sample size is 100 patients. Between February 1997 and February 2000, 4514 women who had either an abnormal mammogram or a diagnosed breast cancer were screened for the study. Of these 4514 screened patients, 52 (1%) were registered on the study. Major factors of nonparticipation in the remaining 4462 women were as follows: (a) no evidence of malignancy (2081 patients; 46%); (b) ineligible per protocol criteria (575 patients; 13%); (c) preoperative chemotherapy/tamoxifen (520 patients; 11%); (d) surgery scheduling conflict (360 patients; 8%); (e) outside needle biopsy (221 patients; 5%); (f) no residual disease after excisional biopsy (345 patients; 8%); and (g) second opinion only (123 patients; 3%). Other nonparticipation factors included fine needle aspiration only, refusal, tumor size > 2 cm, and estrogen replacement therapy (35 patients each; 2% each). The protocol was amended in midstudy to allow outside needle biopsy, tumor > 2 cm, and estrogen replacement therapy. Accrual to biomarker (nontherapeutic) protocols with delay in definitive cancer surgery is challenging but feasible. Although some accrual problems remain, we have nonetheless succeeded in recruiting 50% of our target sample size in a 3-year period.

Adult↗
PubMed2000

Effect of 13-cis-retinoic acid on serum prostate-specific antigen levels in patients with recurrent prostate cancer after radical prostatectomy.

The objective of this study was to determine whether there is any beneficial effect of oral 13-cis-retinoic acid (isotretinoin) on prostate cancer, using serum prostate-specific antigen (PSA) levels as a surrogate end point in patients with a rising serum PSA after radical prostatectomy. In the first phase, the effect of the drug on the serum PSA level was tested in 14 control patients with normal prostates. Our goal was to exclude any effect of isotretinoin on PSA secretion and metabolism and thus to validate any observed effect on PSA as indicative of anticancer activity. In the second phase, patients with rising PSA levels after radical prostatectomy and no evidence of metastatic disease were treated with oral isotretinoin at a daily dose of 1.0 mg/kg. Serum PSA levels were checked monthly for the first 4 months after initiation of treatment and every 3 months thereafter. No significant changes in serum PSA levels after 3 months of isotretinoin treatment were recorded in the control group (P = 1.000). Three of 11 postprostatectomy patients (27%) had a PSA reduction of 28%, 15%, and 6.6% after initiation of treatment that lasted for a period of 2-3 months. In two of these three patients, the PSA levels subsequently rose exponentially. Another patient displayed a stabilization of the serum PSA curve for 3 months after an initial sharp rise. No grade 3 or 4 toxicity was recorded in this group of patients. Isotretinoin had a modest, transient effect on the serum PSA level in 4 of 11 (36%) patients with a rising serum PSA after radical prostatectomy. We conclude that this drug is unlikely to be of major therapeutic benefit in prostate cancer patients when used as a single agent. However, its modest effect argues for the exploration of other, more potent retinoids for prostate cancer therapy.

Adult↗
PubMed1999

Interleukin-10 levels are often elevated in serum of adults with Hodgkin's disease and are associated with inferior failure-free survival.

BACKGROUND: Interleukin-10 (IL-10) is a pleiotropic cytokine that protects B- or T-lymphocytes and hemopoietic progenitors from apoptosis induced by doxorubicin, glucocorticoids, or deprivation of growth factors. IL-10 is also immunosupressive, and tumor cells secreting IL-10 can grow in syngeneic or allogeneic hosts, and can inhibit the generation of tumor-specific cytotoxic T cells. Hodgkin-Reed-Sternberg cells are derived from follicular center B cells and they may be latently infected by EBV. When this occurs they often express IL-10. Based on these considerations we investigated the relationship between pretreatment serum IL-10 levels and failure-free survival (FFS) in Hodgkin's disease (HD). PATIENTS AND METHODS: Untreated patients, older than 16 years, with biopsy-proven HD, were included if treated with ABVD or equivalent regimens, and if pretreatment serum was available. IL-10 levels were determined with a capture enzyme-linked immunoassay specific for cellular IL-10. RESULTS: Among healthy adult volunteers serum IL-10 levels ranged from 4.8-9.8 pg/ml (mean 7.1, standard deviation 1.5 pg/ml). Therefore levels > or = 10 pg/ml were considered elevated. We identified 101 patients with available serum. Their median age was 32 years, and 60% had B-symptoms. Ann Arbor stage was I in 4, II in 21, III in 35, and IV in 41 patients. Histology was nodular sclerosis in 74, mixed cellularity in 12, lymphocyte predominance in six, lymphocyte depletion in one, and unclassified in eight patients. Pretreatment serum IL-10 levels were elevated in 51 patients, and were higher in those with serum albumin < 3.5 g/dl, B symptoms, serum beta 2-microglobulin > or = 2.5 mg/l, anemia, and AAS III or IV. After a median follow-up of 32 months for survivors, 20 patients have progressed, and the three-year FFS of those with high vs. normal serum IL-10 was 60% +/- 9 vs. 91 +/- 9% (50% vs. 50% of the population; P = 0.004 by log-rank). Among patients with Ann Arbor stage III or IV the three-year FFS for those with high vs. normal serum IL-10 (58 vs. 42% of the population) was 57 +/- 9% vs. 92 +/- 6% (P = 0.008 by log-rank). Multivariate analysis using Cox's proportional hazards model confirmed that IL-10 was an independent variable associated with inferior FFS in this population. CONCLUSIONS: Elevation of serum IL-10 levels is frequent and is associated with inferior FFS in adults with ABVD-treated HD. This observation should be verified in other patient populations. In addition, the source and the role of IL-10 in the biology of HD should be further investigated.

Adolescent↗
PubMed1997

Toxicities of tacrolimus and cyclosporin A after allogeneic blood stem cell transplantation.

To determine how well tacrolimus (FK506) and cyclosporin A (CsA) are tolerated after HLA-identical blood stem cell transplantation, we performed a retrospective review of 87 adults transplanted consecutively who received FK506 (n = 40) or CsA (n = 47) in a nonrandomized fashion in combination with methylprednisolone for graft-versus-host disease (GVHD) prophylaxis and compared the incidences of complications potentially related to the immunosuppressive agents. Pre-transplant demographic characteristics, drug compliance and rates of acute GVHD were comparable for the two groups. Following first discharge, fewer patients in the FK506 group required antihypertensive therapy (32 vs 59%, P = 0.022), but more required insulin (34 vs 10%, P = 0.014). There was also a trend for more hyperkalemia and less moderate-to-severe venoocclusive disease in the FK506 group. However, nephrotoxicity, neurotoxicity, hemolytic-uremic syndrome, and cytomegaloviral or fungal infections through the first 100 days post-transplant did not differ significantly between the two groups. We conclude that for allogeneic blood stem cell transplant recipients, the incidence of complications related to FK506 and CsA in equally effective dose schedules in combination with methylprednisolone are similar with the exception of the risks of hypertension and hyperglycemia.

Acute Kidney Injury↗
PubMed1996

Allogeneic transplantation for advanced leukemia: improved short-term outcome with blood stem cell grafts and tacrolimus.

We have evaluated the use of blood stem cell grafts for rapid hematopoietic recovery and tacrolimus (FK506) as GVHD prophylaxis to reduce early mortality after allogeneic transplantation. Eighty-five adults with advanced leukemia received high-dose thiotepa, busulfan, and cyclophosphamide as a preparative regimen in a prospective Phase II study. All donors were HLA-matched and related. Marrow (BMT) was used for 44 patients and filgrastim-mobilized blood stem cells (SCT) for 41 patients. GVHD prophylaxis consisted of cyclosporine (CsA) or FK506 with methotrexate (MTX) or methylprednisolone (MP). The median time to neutrophil recovery was earlier after SCT than after BMT (day 10 vs. 17, P<0.001), but this was due to the selective use of MTX only in the BMT patients. The risk of grades 2-4 GVHD was lower with FK506 than with CsA (16% vs. 45%, P=0.02) and was the same for SCT recipients as for BMT recipients (33% vs. 34%). Regimen-related toxicity was significantly lower after SCT than after BMT but did not differ between the FK506 and CsA patients. In comparison with those receiving the standard transplant (BMT with CsA and MTX), only the SCT recipients using FK506 and MP had a significantly higher survival at day 180 posttransplant (84% vs. 53%, P=0.014). In multivariate analyses, use of FK506 was associated with a lower risk of treatment-related mortality and a higher survival at day 180, while the diagnosis of acute lymphoblastic leukemia was associated with a higher risk of treatment-related mortality. These data suggest that the use of blood stem cell grafts and FK506 can reduce the early mortality after allogeneic transplantation for advanced leukemia.

Adolescent↗
PubMed1996

Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after matched unrelated donor marrow transplantation.

Thirty adults with leukemia or lymphoma undergoing marrow transplantation from HLA-compatible unrelated donors received tacrolimus (FK506), a new immunosuppressive macrolide lactone, and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 36 years (range 21 to 49 years). Twenty-four patients had advanced disease, and 11 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/d intravenously (i.v.) by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued through day 180 posttransplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6, and 11. All patients engrafted. Grades 2-4 GVHD occurred in 34% (95% CI, 17% to 52%), and grades 3-4 GVHD in 17% (95% CI, 3% to 31%). Mild renal toxicity was common before day 100; 63% of patients had a doubling of creatinine, and 52% had a peak creatinine greater than 2 mg/dL, but only one patient was dialyzed. The median last i.v. dose of tacrolimus was 53% of the scheduled dose, and the median oral dose on day 100 was 41% of that scheduled. Overall survival at 1 year was 47% (95% CI, 27% to 66%). We conclude that tacrolimus can be combined safely with minidose methotrexate, and the combination has substantial activity in preventing acute GVHD after unrelated donor marrow transplantation.

Actuarial Analysis↗
PubMed1996

Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers.

Introduction of tumor markers into routine clinical practice has been poorly controlled, with few criteria or guidelines as to how such markers should be used. We propose a Tumor Marker Utility Grading System (TMUGS) to evaluate the clinical utility of tumor markers and to establish an investigational agenda for evaluation of new tumor markers. A Tumor Marker Utility Grading Worksheet has been designed. The initial portion of this worksheet is used to clarify the precise characteristics of the marker in question. These characteristics include the marker designation, the molecule and/or substance and the relevant alteration from normalcy, the assay format and reagents, the specimen type, and the neoplastic disease for which the marker is being evaluated. To determine the clinical utility of each marker, one of several potential uses must be designated, including risk assessment, screening, differential diagnosis, prognosis, and monitoring clinical course. For each of these uses, associations between marker assay results and expected biologic process and end points must be determined. However, knowledge of tumor marker data should contribute to a decision in practice that results in a more favorable clinical outcome for the patient, including increased overall survival, increased disease-free survival, improvement in quality of life, or reduction in cost of care. Semiquantitative utility scales have been developed for each end point. The only markers recommended for use in routine clinical practice are those that are assigned utility scores of "++" or " " on a 6-point scale (ranging from 0 to ) in the categories relative to more favorable clinical outcomes. Each utility score assignment should be supported by documentation of the level of evidence used to evaluate the marker. TMUGS will establish a standardized analytic technique to evaluate clinical utility of known and future tumor markers. It should result in improved patient outcomes and more cost-efficient investigation and application of tumor markers.

Biomarkers, Tumor↗
PubMed1995

Phase I clinical and pharmacological study of suppression of human antimouse antibody response to monoclonal antibody L6 by deoxyspergualin.

Development of human antimouse antibody (HAMA) is a major limiting factor in the application of murine mAb for clinical use. A novel immunomodulatory drug, deoxyspergualin (DSG), has shown potential to suppress antimouse antibody response in preclinical model systems. We conducted a Phase I trial to determine the effect of DSG on HAMA response to murine mAb L6 administered to patients with advanced cancers (in previous trials, this antibody elicited HAMA in two-thirds of the treated patients). L6 mAb was administered at a fixed dose of 200 mg/m2 on days 1-5. DSG was administered at doses of 50 mg/m2 [dose level (dl) 1] or 150 mg/m2 (dls II and III) on days 1-7. Treatment courses were repeated every 6 weeks (dls I and II) or every 3 weeks (dl III). HAMAs were quantitated by a commercially available ELISA assay (ImmuSTRIP; anti-isotypic antibodies) and a radiometric assay (antiisotypic and anti-idiotypic antibodies). Pharmacokinetics of L6 and DSG was also studied in all consenting patients. Among 24 evaluable patients, 2 patients developed detectable HAMAs using the ELISA (one each at dls I and II) after a median follow-up of 122 days (P = 0.0001 as compared to historical controls). Even in the two patients who developed HAMA, the HAMA levels were quite low (160 and 181 ng/ml; historical experience, 70-38,744 ng/ml). The radiometric assay detected anti-L6 antibodies in 13 patients (4, 6, and 3 at dls I-III, respectively) after a median of 82 days. The median highest anti-L6 antibody level was 129 ng/ml (range, 21-2150). The highest anti-L6 antibody level at dl III was only 44 ng/ml. The results suggest suppression of anti-idiotypic response also. No clinical antitumor activity was observed, and no significant changes in T4/T8 subsets or immunoglobulins occurred (suggesting a lack of generalized immunosuppression). We conclude that DSG can suppress HAMA response to L6. A starting dose of 150 mg/m2/day is recommended for Phase II trials to confirm this observation.

Adult↗
PubMed1993

Characterization of the DiFi rectal carcinoma cell line derived from a familial adenomatous polyposis patient.

The DiFi human colorectal cancer cell line was recently established from a familial adenomatous polyposis patient with extracolonic features characteristic of the Gardner syndrome. These cells have now been propagated for 150 passages in standard culture media and vessels without feeder layers or collagen coatings. They retain features of colonic epithelial cells such as surface microvilli, secretory vesicles, and desmosomes. Cytosol of DiFi cells contains a high level (502 U/mg protein) of the mucin CA 19-9. In addition, DiFi cells produce carcinoembryonic antigen, and induce tumors in athymic mice. Cytoskeleton analysis of DiFi cells by fluorescence microscopy showed a pronounced disorganization of actin cable structure. The isozyme genetic signature of DiFi cells is unique (0.01 probability of finding the same genetic signature in a different cell line), differs from that of HeLa cells, and has expressional features seen in other colorectal cell lines. The DiFi cell karyotype is tetraploid, contains many marker chromosomes, and shows numerous episomal particles. Two copies of chromosome 18 were absent, and only a single normal chromosome 17 was found. This parallels detection of allelic losses from DiFi cell DNA at loci on chromosomes 17p and 18 using molecular (cDNA) probes. DiFi cells clearly express transcripts for the c-myc proto-oncogene, the c-myb proto-oncogene, and the p53 tumor suppressor gene. Transforming growth factor beta inhibits DiFi cell growth in soft agar and suppresses c-myc expression in these cells. The value of this cell line in the study of genetic alterations in colorectal cancer is discussed.

Actins↗
PubMed1993

Quantitation of immunocytochemical estrogen and progesterone receptor content in fine needle aspirates of breast carcinoma using the SAMBA 4000 image analysis system.

Evaluation of estrogen receptors (ER) and progesterone receptors (PR) in breast carcinoma using ER and PR immunocytochemical assays (ER-ICA and PR-ICA) has traditionally been semiquantitative at best. We investigated the use of the SAMBA 4000 image analysis system for quantitation of immunocytochemical ER content in 23 cases and PR content in 20 cases of breast carcinoma after obtaining cytology specimens by fine needle aspiration (FNA). We compared the quantitative assessment obtained by image analysis, the quick score (QS), to the biochemical assay as well as to the ER-ICA and PR-ICA semiquantitative visual histochemical score (H-score). Using Pearson's linear correlation coefficient, we demonstrated that for both ER and PR, the QS obtained by the "area" or "nuclear" programs correlated significantly with the H-scores. However, while the QS obtained on the area program for both ER and PR correlated significantly with the biochemical assay, the QS obtained on the nuclear program did not. The discrepancy might reflect the smaller number of cells evaluated with the nuclear program as compared to the area one. These results show that the SAMBA 4000 system provides an objective means of quantitating ER and PR content by immunocytochemical methods.

Biopsy, Needle↗