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Biomedical subjects

H F Sears

Publications and source records attributed to H F Sears.

At least 37 records · Page 2Linked to original sources
PubMed1985

Circulating tumor markers and assessment of response to intrahepatic chemotherapy of colon carcinoma.

To assess the change in concentrations of circulating gastrointestinal cancer-associated antigens in response to therapy, we analyzed the sera of patients with hepatic metastasis from colorectal carcinoma who were treated with intrahepatic arterial chemotherapy. Serial serum samples were assessed for the tumor-associated antigens, carcinoembryonic antigen (CEA) and the gastrointestinal cancer antigen CA 19-9. Computed axial tomographic (CAT) scans were made to assess the size of the hepatic metastasis. In 9/10 of these patients the CEA predicted tumor response within 2-6 weeks after initiation of treatment, and in 7/10 the information was supported or more dramatically demonstrated by the CA 19-9. Combining data from both tumor markers may provide a more accurate assessment of the clinical response than one antigen alone. Recurrence of hepatic metastatic growth or extrahepatic tumor also was identified by elevation of one or both circulating tumor-associated antigens prior to other laboratory or clinical evidence of tumor growth.

Adult↗
PubMed1985

Phase II clinical trial of a murine monoclonal antibody cytotoxic for gastrointestinal adenocarcinoma.

A murine monoclonal antibody (MAb) which binds to human metastatic gastrointestinal adenocarcinomas can be administered safely and has tumor effects in some patients. Its therapeutic effect was assessed in 20 patients with measurable advanced colorectal carcinoma that was refractory to prior surgical resection, chemotherapy, and/or radiotherapy. All patients had agreed to receive no other therapy at the time of MAb administration and follow-up evaluation. In one patient, tumor at all known sites responded after a single i.v. injection of antibody. One other patient had a marked reduction in a hepatic metastasis where binding of 131I-labeled F(ab')2 MAb fragments was demonstrated but not in his abdominal wall metastases where no MAb binding could be demonstrated. In a third patient, stabilization persisting for 12 mo of an aggressively growing tumor was observed. The antibody was well tolerated in all patients, although 10 patients mounted an anti-murine immunoglobulin antibody response.

Adenocarcinoma↗
PubMed1984

Increased sensitivity in detecting tumor-associated antigens in sera of patients with colorectal carcinoma.

A monoclonal antibody defining the Lewis blood group determinant was used to immobilize antigen in sera of patients with adenocarcinoma of the gastrointestinal tract, and a second radiolabeled antibody, which defines a gastrointestinal cancer-associated antigen (GICA), was used to detect the immobilized antigen. With this approach, elevated antigen levels were found in 34 of 49 (69%) of sera from patients with advanced colorectal carcinoma as compared with 9 of 292 (3%) of sera from patients with non-malignant gastrointestinal diseases and of healthy donors. For early primary colorectal carcinoma, the combination of anti-Lewis and anti-GICA monoclonal antibodies was more sensitive in detecting GICA than using anti-GICA antibody alone. Double determinant radioimmunoassay revealed the glycolipid determinant lacto-N-fucopentaose (LNF) III circulating in colorectal carcinoma patients' sera. 53% of patients older than 65 years had elevated levels of the LNF III determinant compared to none of age-matched, apparently healthy donors or patients with benign gastrointestinal tract lesions, and 18% of patients with inflammatory gastrointestinal tract diseases. In younger patients, the differences were less marked. Our results suggest the potential usefulness of Lewis and LNF III determinants as markers for the detection of gastrointestinal tract malignancies.

Adult↗
PubMed1984

Binding of murine immunoglobulin to human tissues after immunotherapy with anticolorectal carcinoma monoclonal antibody.

An anticolorectal carcinoma antibody, 17-IA, that is of gamma 2a isotype and has been used in previous immunotherapy trials, binds to an antigen on most human colon tumors. This antigen is destroyed by the fixative and embedding procedures employed for routine histologic evaluation of tissues. It can be demonstrated by the avidin/biotin-labelled peroxidase complex (ABC) immunoperoxidase technique on briefly fixed, frozen sections of fresh human tissues. With this assay technique, the antibody is found to bind in vitro to both human colonic carcinoma and normal gastrointestinal epithelia. Tissues removed from patients having received the 17-IA antibody intravenously in an immunotherapy trial show bound antibody 1-2 after administration. This is no longer evident 3 weeks later though the antigen is present on the cell surface and is still capable of binding antibody in vitro.

Animals↗
PubMed1984

Extraction of circulating gastrointestinal cancer antigen using solid-phase immunoadsorption system of monoclonal antibody-coupled membrane.

An immunoadsorption system of monoclonal antibody immobilized on a polyolefin alloy fiber is described for extraction of serum gastrointestinal cancer antigen (GICA). Continuous circulation or single passage of plasma from gastrointestinal cancer patients through this antibody-fiber matrix resulted in 90% depletion of circulating GICA in 2 h using 0.6 mg immobilized antibody, and 90% depletion in 5 min using 8 mg antibody. Continual circulation resulted in total GICA removal in both cases. Desorption of antibody or of antibody-containing complexes was minimal. This methodology provides a selective and convenient means of removing any targeted substance by monoclonal antibody from the serum, and thus overcomes many of the shortcomings associated with conventional plasmapheresis.

Animals↗
PubMed1984

Human anti-idiotype antibodies in cancer patients: Is the modulation of the immune response beneficial for the patient?

Inoculation of human subjects with mouse monoclonal antibody results in the production of anti-idiotype antibody that reacts with the binding site of the monoclonal antibody. This reaction is hapten-inhibited, suggesting that an internal image of the antigen is produced by the anti-idiotype response. The anti-idiotype antibody isolated from sera of three patients showed significant crossreactivity. Patients who developed the anti-idiotype antibody improved clinically and had long remission from their disease. The possible presence of the internal image of cancer antigen on the human immunoglobulin molecule may change the conditions under which the immune system reacts to the tumor antigen and may open new approaches to the control of tumor growth.

Adenocarcinoma↗
PubMed1984

Detection of a circulating gastrointestinal cancer antigen in sera of patients with gastrointestinal malignancies by a double determinant immunoassay with monoclonal antibodies against human blood group determinants.

Monoclonal antibodies (MoAbs) produced against determinants A and B of the human ABO blood group system and against the Lea and Leb determinants of the Lewis (Le) blood group system detected these determinants on molecules released by cultured cells of human colorectal, gastric and/or pancreatic carcinoma (Ca) but not by a variety of other cells maintained in culture. Circulating Le antigen could be demonstrated in sera of patients by inhibiting the binding of MoAbs to a target preparation. A double determinant radioimmunoassay (DDIA) was then developed to detect the association of blood group determinants with a previously defined gastrointestinal cancer antigen (GICA). The DDIA with the anti-blood group and anti-GICA antibody was in some cases more sensitive in detecting GICA in sera than using the anti-GICA MoAb alone. Of 55 sera from patients with primary and early recurrent colorectal carcinoma (CRC), 10 (18%) were scored positive in the DDIA using only anti-GICA MoAb. When MoAb binding to a determinant on Leb and on H, type I, was used as first antibody in DDIA followed by anti-GICA MoAb 11 additional sera were reactive, increasing the percentage of positive sera to 38. Using the same combinations of MoAbs, the sensitivity of detection of GICA was only slightly improved from 63 to 66% in sera of patients with advanced CRC. The number of false positive sera from patients with non-malignant gastrointestinal diseases or from healthy donors remained at low levels when anti-blood group determinant antibodies were used together with anti-GICA MoAb. The results indicate that DDIAs with MoAbs against different blood group determinants and tumour associated antigens can improve the detection of circulating antigens in patients with early stage cancer.

ABO Blood-Group System↗
PubMed1984

Effects of monoclonal antibody immunotherapy on patients with gastrointestinal adenocarcinoma.

Twenty patients with metastasis of gastrointestinal malignancies were treated with an anti-colorectal cancer mouse monoclonal antibody 1083-17-1A of the IgG2a class between December 1980 and January 1983. With two exceptions, all patients received a single injection of monoclonal antibody in a dose range of 15-1,000 mg/patient. No untoward immediate or delayed reaction to the initial injection was observed in any of the patients. Mouse immunoglobulin circulated in the patients' blood for 2-50 days, depending on the dose of monoclonal antibody injected, and was detected in tumor tissue within 1 week of its administration. Eight of nine patients who received doses of 366-1,000 mg monoclonal antibody did not develop anti-mouse antibodies, while eight of nine who received less than 200 mg developed anti-mouse immunoglobulin antibody. Three of this heterogeneous group of patients have no detectable disease now--10, 13, and 22 months since immunotherapy.

Adenocarcinoma↗
PubMed1983

Detection of carcinoembryonic antigen and related antigens in sera of patients with gastrointestinal tumors using monoclonal antibodies in double-determinant radioimmunoassays.

Of 14 monoclonal antibodies produced in six different laboratories, 13 bound to purified preparations of carcinoembryonic antigen (CEA). All antibodies reacted to spent medium of colorectal carcinoma cell lines. Competitive binding studies indicated that 12 different antigenic determinants representing six different groups were detected on the CEA molecule(s). Six antibodies were used in double determinant radioimmunoassays (RIA) to detect CEA and CEA-related antigens in sera of 311 patients with various gastrointestinal diseases and of normal donors. None of up to 115 sera of healthy donors had elevated antigen levels with four out of the six monoclonal antibodies tested, whereas up to 9% of sera showed elevated antigen levels when tested with two antibodies. Between 1.4% and 4.4% of sera from patients with inflammatory and benign neoplastic diseases of the gastrointestinal tract were positive. Antigen levels were elevated in 56 to 75% (depending on antibody used) of sera from patients with advanced gastrointestinal tumors. These preliminary results indicate that double-determinant immunoassays with a panel of monoclonal antibodies might improve conventional CEA assays by reducing the number of false positive sera detected by polyclonal sera in patients with benign inflammatory bowel diseases.

Antibodies, Monoclonal↗
PubMed1983

Metastatic colon carcinoma detected with radiolabeled F(ab')2 monoclonal antibody fragments.

Nine patients with colonic carcinoma were studied with I-131-labeled F(ab')2 fragments of an anti-colorectal carcinoma monoclonal antibody. A total of 69% of colon cancer sites were detected without background subtraction; metastases from a concurrent breast carcinoma in one patient were not seen. Lesions ranged from 1.5 to 8 cm. The mean thyroid uptake of I-131 at 24 hours was 0.25%. Half-lives of I-131 in the blood (protein-bound and total) fit a two-compartment model, with half-lives of 3.5 and 27.6 hours for the protein-bound fraction and 3.6 and 23.8 hours for total I-131. Using quantitative methods, a mean value of 0.0047%/cm3 of the administered dose was localized in the tumor at peak concentration, which occurred approximately 48 hours post-administration. This has implications for therapy planning.

Antibodies, Monoclonal↗
PubMed1983

Phenotypic characteristics of cells derived from precursors of human melanoma.

Of 66 specimens from benign melanocytic nevi, including common acquired and congenital nevi, Spitz tumors (epithelioid cell nevi), and melanocytic nevi with dysplasia, 57 could be grown in tissue culture. The cultured cells were identified as melanocytes by the presence of premelanosomes and melanosomes. Cells from 28 of 32 nevus cultures grew in an anchorage-independent way in soft agar with a colony-forming efficiency between 0.001 and 1%. Clones derived from single cells and soft agar-selected colonies showed marked phenotypic heterogeneity, but all had a limited life span and did not undergo transformation in culture. These cells were nontumorigenic in nude mice. Cultured nevus cells expressed antigens present on melanoma but absent on normal fibroblasts and/or melanocytes as tested with monoclonal anti-melanoma antibodies. The anti-melanoma antibodies bound equally well to dysplastic, congenital, and common acquired nevi. Antigens are released by nevus cells similar to melanoma cells.

Antigens, Neoplasm↗
PubMed1982

Breast cancer without axillary metastases. Are there high-risk biologic subpopulations?

Two hundred seventy-five patients with breast cancer and no axillary metastases had mastectomies and axillary node dissection performed during the period between 1970 and 1979 at The Fox Chase Cancer Center. They had a mean age of 60 years (range, 21-91) and 38 (14%) patients have had recurrence to date. Poor histologic differentiation and skin involvement were related to a high risk of recurrence. Those patients with skin infiltration by tumor or a poorly differentiated tumor had a 53 +/- 9% expected five-year tumor-free survival, whereas patients without these had a 90 +/- 2% expected five-year tumor-free survival. Tumor involvement of the lymphatic vessels within the breast and estrogen receptor protein positivity or negativity were not helpful for identifying a subpopulation at increased risk of recurrence. Large tumor size was not a poor prognostic indicator for a patient subpopulation. These factors should be considered as indicators for inclusion in clinical trials and adjuvant therapy and used as stratification points for the analysis of the data developed in these trials.

Adult↗
PubMed1982

Phase-I clinical trial of monoclonal antibody in treatment of gastrointestinal tumours.

A phase-I clinical trial of a murine monoclonal antibody that specifically suppresses growth of human gastrointestinal tumours in athymic mice was conducted in four patients, who were given 15-200 mg purified antibody. The monoclonal antibody persisted in the circulation for more than a week when more than 15 mg was given. Antibodies against mouse immunoglobulin developed in three of the four patients. In one patient who received autologous mononuclear cells that had been mixed with monoclonal antibody by way of a hepatic-artery catheter, hepatic metastases became smaller and their echogenic characteristics changed, and there was heavier monocyte infiltration in the histological appearance of a resected metastasis.

Adenocarcinoma↗
PubMed1982

Ex vivo perfusion of human colon with monoclonal anticolorectal cancer antibodies.

The binding of mouse hybridoma monoclonal antibodies directed against human colon carcinomas was studied using an ex vivo perfusion model of a freshly resected human colon segment containing a carcinoma. Tumor and the surrounding normal bowel is exposed to the putative tumor antigen through an intact vascular system without mechanical or enzymatic cellular alteration. An hour of perfusion was conducted on thirty specimens using five different monoclonal anticolorectal cancer (ACRC) antibodies. Three were gamma 1, one gamma 2A and one was IgM isotype. Control anti-influenza virus monoclonal antibodies were used to demonstrate absence of nonspecific binding. Our antibody 17-1A bound to the colon cancer in seven of ten trials, but bound to normal colon cells also in four of these trials. The IgM antibody did not bind to anything. The two gamma 1 antibodies that recognize an antigen shed from the surface of the cell did not demonstrate cell binding under conditions of this study, and conditions to detect this will have to be modified. The ex vivo perfusion model as performed in this study can provide a valuable adjunct to evaluate the potential clinical utility for antibody conjugate radiolocalization or therapy of colon cancer.

Adenocarcinoma↗
PubMed1982

Monoclonal antibody detection of a circulating tumor-associated antigen. I. Presence of antigen in sera of patients with colorectal, gastric, and pancreatic carcinoma.

Hybridoma-secreted monoclonal anti-colorectal carcinoma antibodies 19-9, 52a, and C4 14 bind specifically to cells of colorectal, gastric, and pancreatic carcinoma in tissue culture. The assay for the detection of antigen in human sera is based on the inhibition of binding of monoclonal antibodies to target preparations of colorectal carcinoma cells. Binding of monoclonal antibody 52a was inhibited more than 12% by 163 of 255 sera from patients from various stages of carcinoma of colon and rectum, by 45 of 49 sera from patients with pancreatic carcinoma, and by 8 of 11 sera from patients with gastric carcinoma. By contrast, only 7 of 89 sera from patients with other malignancies and 2 of 108 sera from healthy donors inhibited binding of this monoclonal antibody by more than 12%. These studies show the potential usefulness of monoclonal antibodies in the diagnosis of human malignancy.

Adult↗
PubMed1982

Monoclonal antibody detection of a circulating tumor-associated antigen. II. A longitudinal evaluation of patients with colorectal cancer.

An antigen identified by two monoclonal anti-colorectal cancer antibodies was studied in sera of 85 patients who had a resection of their primary colorectal cancer. Preoperative and postoperative serum samples and sera collected every 3 months for at least 1 year were included in this study. The levels of these antigens were compared to the carcinoembryonic antigen (CEA) levels. Sixty-six patients had at least one antigen elevated in the preoperative period. Malignancy recurred in 10 patients. In 8 of these the recurrence could have been predicted by the persistence or rise in antigen levels 3 to 18 months prior to the detection of the recurrence by current clinical methods. The data suggest that the assays for these antigens are valuable prognostic aids for making clinical therapeutic decisions and appropriately stratifying patients for clinical trials.

Aged↗
PubMed1982

Gastrointestinal cancer-associated antigen in immunoperoxidase assay.

A monosialoganglioside antigen of gastrointestinal adenocarcinomas defined by murine monoclonal antibody was demonstrated by immunoperoxidase (IP) assay in fixed paraffin-embedded tumors in 59% of colonic adenocarcinomas, 86% of pancreatic adenocarcinomas, and 89% of all gastric adenocarcinomas. In all patients with detectable levels of antigen in circulation, the resected tumors also expressed the antigen in IP assay. Six of eight individuals with no detectable levels of antigen in their serum samples expressed the antigen in the tumor tissue. Removal of the sialic acid residue of the antigen abolished the IP reaction. The successful use of the IP assay on fixed tissue to demonstrate the specific sites of gastrointestinal cancer antigen localization in human tumors and normal tissues provides an important tool for the study of developing neoplasia.

Adenocarcinoma↗