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Biomedical subjects

J M Jessup

Publications and source records attributed to J M Jessup.

At least 91 records · Page 5Linked to original sources
PubMed1988

Ulex europeus type I agglutinin detects carcinoembryonic antigen in extracts of human colorectal carcinoma.

Recent interest has focused on fucosylated epitopes expressed on human neoplasms. The plant lectin Ulex europus agglutinin, Type I (UEA) binds fucosylated oligosaccharides, while UEA-reactive substances have a tissue distribution similar to carcinoembryonic antigen (CEA). We sought to determine if UEA reacted with CEA in extracts of fresh primary and metastatic colorectal carcinomas and paired normal tissues. The extracts were electrophoretically transferred to nitrocellulose membranes after the proteins were separated by SDS-PAGE in 10% polyacrylamide gels. The transfer membranes were then stained with peroxidase-conjugated UEA (UEA-P) or antibody to CEA (CEA-P). UEA-P reacted with a 170-190-kDa band in extracts of 22 of 30 primary tumors, 10 of 12 metastases, but only 1 of 5 villous adenomas. UEA-P generally did not react with normal colon or liver extracts. UEA-P also did not bind to 170-190-kDa molecules in Western transfers of a breast carcinoma metastatic to bowel and a focal nodular hyperplasia of liver. CEA-P displayed similar reactivity and detected CEA in a tumor extract negative for UEA. Fucose blocked binding of UEA-P to Western transfers of tumor extracts. CEA-P reacted with a 170-190-kDa substance in tumor extracts eluted with fucose from a column of immobilized UEA. Thus, UEA reacts with fucosylated oligosaccharides on most, but not all, species of CEA and may be a useful adjunct to anti-CEA immunohistochemistry.

Adult↗
PubMed1987

Expression of autoantigens in human colorectal carcinomas. Implications for a generic vaccine.

The antibody response of patients was used to characterize the autoantigens in human colorectal carcinoma. Twenty-seven primary and 13 metastatic carcinomas with paired normal tissues were extracted and transferred onto nitrocellulose membranes by the Western transfer technique. After the transfers were incubated with the serum of the patient from whom the tumor was derived, autoantigens were identified by indirect immunoperoxidase staining. All tumors contained at least one autoantigen. Six tumor-associated autoantigens, ranging in molecular weight from 26 to 58 kilodaltons (kD), were identified by antibodies in 25% or more of the sera. Eleven metastases expressed a 41-kD autoantigen that was present in only a third of the extracts of normal liver or lung. Thus, the number of dominant polypeptide autoantigens in colorectal carcinoma is restricted to six molecules. These autoantigens may be organ-associated antigens that are expressed by neoplastic cells. The 41-kD autoantigen may be a potential marker for metastases. A generic vaccine appears to be feasible for colorectal carcinoma since the number of dominant antigens is limited.

Antigens, Neoplasm↗
PubMed1986

Active specific immunotherapy of Dukes B2 and C colorectal carcinoma: comparison of two doses of the vaccine.

The ability of active specific immunotherapy to enhance immune responses to autologous tumor-associated antigens (TAA) and to prolong the disease-free interval was evaluated in patients with Dukes B2 and C colorectal carcinoma who had undergone potentially curative resections. Patients were sensitized in the early postoperative period with irradiated autologous adenocarcinoma cells mixed with bacillus Calmette-Guérin (BCG) to yield either a low-dose vaccine (3 X 10(6) tumor cells) or a high-dose vaccine (1 X 10(7) tumor cells). Six of seven patients who received the low-dose vaccine developed delayed-type hypersensitivity (DTH) responses to autologous tumor cells upon completion of the vaccination, whereas all four patients receiving high-dose vaccine displayed a positive DTH response. However, DTH responses to autologous TAA waned within 3 months in all patients receiving the low-dose vaccine; DTH responses persisted for 3 months in three of the four high-dose vaccine patients. In vitro lymphoproliferative responses to TAA correlated with DTH responses to autologous tumor cells. Active specific immunotherapy appeared to induce specific immune responses either in vitro or in vivo to autologous TAA because it did not induce responses to autologous mucosa cells. There were no complications caused by BCG or tumor cells. This series demonstrates that active specific immunotherapy is a nontoxic treatment that augments immunity to autologous TAA.

Adult↗
PubMed1986

Tumor-derived suppressor factors (TDSFs) in normal and neoplastic colon and rectum.

Acid tumor-derived suppressor factors (TDSFs, isoelectric pH less than 3.0) in extracts of murine fibrosarcomas and human colorectal adenocarcinoma cell lines induce normal murine spleen cells to inhibit delayed-type hypersensitivity (DTH) to the sensitizer dinitrochlorobenzene (DNCB). We sought to determine if TDSF from normal and neoplastic human colon and rectum also inhibited normal human peripheral blood mononuclear cells (PBMC) responses to mitogen and to alloantigens. Collagenase-DNase digests of five freshly isolated carcinomas and paired autologous normal tissues were subjected to preparative isoelectric focusing (pIEF) over a pH range of 2.5 to 9.5. Fractions with isoelectric pH less than 3.0 from three of the five tumors induced normal C3H/HeN spleen cells to inhibit DTH to DNCB. Acid fractions from three tumors and four normal tissues also significantly inhibited the PBMC proliferative response to mitogen and alloantigens. However, the ability of acid fractions to suppress lymphocyte proliferation did not correlate with the induction of suppression of DTH to DNCB. Incubation of human PBMC with acid proliferation inhibitors did not induce suppressor cells that would inhibit the subsequent proliferative response of fresh, autologous PBMC. The acid suppressant from colorectal carcinoma was sensitive to treatment with trypsin but not RNase or DNase, whereas murine TDSF is sensitive to RNase and resistant to treatment with trypsin. The suppressive moiety from one tumor had an apparent mass of 45 kDa by gel filtration chromatography, in contrast to murine TDSF that has a mass of more than 300 kDa. Thus, the acid inhibitor in digests of human colorectal carcinoma is distinct from the TDSF that induces suppressor cells for DTH to DNCB.

Animals↗
PubMed1986

Activation of tumoricidal properties in peripheral blood monocytes of patients with colorectal carcinoma.

The purpose of these studies was to determine whether blood monocytes of patients with different stages of colorectal carcinoma could be activated by various immunomodulators to become tumor cytolytic. Monocytes obtained from 12 colorectal carcinoma patients and 8 normal donors were incubated in vitro with free or liposome-encapsulated agents. The cytotoxic properties of the monocytes were determined subsequent to interaction with radioactively labeled allogeneic colon carcinoma cells, melanoma cells, glioblastoma cells, and allogeneic nontumorigenic skin cells. Blood monocytes from normal donors and all colorectal carcinoma patients were activated in vitro to become tumoricidal by immunomodulators in free form or entrapped within liposomes; i.e., the monocytes recognized and lysed tumorigenic cells but not nontumorigenic cells. The tumoricidal activity of monocytes was observed in blood monocytes obtained from patients even after multiple doses of radiotherapy and chemotherapy, and that fact suggests that the in vivo activation of macrophages may be feasible.

Adult↗
PubMed1986

Experimental nude mouse model of human colorectal cancer liver metastases.

A nude mouse model (BALB/c) was established for investigating the production of hepatic metastases by human colorectal carcinoma (HCC) cells. The malignant potentials of 3 different HCCs derived from a primary tumor (HCC-P4733), a lymph node metastasis (HCC-M14328), and a hepatic metastasis (HCC-M1410) were investigated following implantation into the spleens of athymic nude mice. Cells of the HCC-M1410 line produced extensive liver tumors in all mice by 30 days after injection. Cells of the HCC-M14328 and HCC-P4733 lines produced few liver tumors in the inoculated mice and then only after a 90-day period. Isozyme and karyotype analyses ascertained the human origin of all the tumors. Studies with [125I]IdUrd-labeled HT-29 carcinoma cells suggested that tumor cells reached the liver shortly after injection into the spleen. Thus the production of HCC tumors in livers of nude mice was determined by the ability of HCC cells to proliferate in the liver parenchyma rather than by the ability of the cells to reach the liver. The results suggest that the intrasplenic injection of HCC cells can provide a valuable model for the study of the biology and therapy of the liver metastases.

Animals↗
PubMed1986

Metastatic behavior of tumor cells isolated from primary and metastatic human colorectal carcinomas implanted into different sites in nude mice.

The purpose of these studies was to examine the growth characteristics and metastatic behavior of freshly isolated human colorectal carcinomas implanted into athymic nude mice. Four tumor lines were derived from primary colorectal carcinomas, three lines from hepatic metastases, and one line from a metastasis to a mesenteric lymph node. Subsequent to implantation into the subcutis or the muscularis, tumor lines derived from metastases grew faster in the nude mice than did cells isolated from the primary neoplasms. Regardless of the source of the cells, however, little or no visceral organ metastasis was found. Subsequent to i.v. injection, experimental lung colonies could be produced by some of the cells, but there was no correlation between lung tumor colony formation and the origin of the human colorectal cells. The intrasplenic injection of colorectal carcinoma cells provided a useful procedure to identify human colorectal carcinoma cells with metastatic potential to liver. Extensive tumor burdens in the liver were observed as early as 30 days after injection with two of the three liver metastasis-derived tumor lines. No liver metastases were found after the intrasplenic injection of cells isolated from the lymph node-derived tumor line. Ninety days after the intrasplenic injection of cells from the four primary colorectal carcinomas, limited liver metastases were observed. We conclude that metastasis of human colorectal carcinomas can be studied in nude mice, and its outcome depends upon both the intrinsic metastatic capacity of the human tumor cells and the organ environment of implantation.

Adult↗
PubMed1985

Induction of suppressor cells by a tumor-derived suppressor factor.

Murine fibrosarcomas produce a factor that activates suppressor cells to inhibit expression of delayed-type hypersensitivity (DTH) responses to dinitrochlorobenzene (DNCB). This tumor-derived suppressor factor (TDSF) was partially purified by preparative isoelectric focusing of spent medium and 3 M KCl extracts of cultured methylcholanthrene-induced and spontaneous fibrosarcomas of C3H/He mice. Incubation of 1 micrograms/ml of a fraction, isoelectric pH less than 2.9, with normal syngeneic spleen cells for 1-6 hr at 37 degrees C induced suppressor cells that inhibited the primary DTH response to DNCB upon intraperitoneal transfer to normal C3H/HeJ mice. TDSF was not present in extracts of either syngeneic embryonic fibroblasts or normal spleen cells or in medium conditioned by normal peritoneal exudate cells but was present in 3 M KCl extracts of and the spent medium from four different cultured murine fibrosarcomas. TDSF activity was not restricted at the major histocompatibility complex. The suppressor cells inhibited the efferent limb of the DTH response because (1) hyporesponsive recipients of TDSF-treated spleen cells had splenic effector T cells capable of transferring DTH to DNCB into naive secondary recipients and (2) the ability of Lyt 1+,2- effector Tdth cells to transfer a secondary DTH response to DNCB was inhibited by co-incubation with macrophages or Lyt 1-,2+ T cells treated with TDSF. Preliminary biochemical analysis suggested that TDSF was an RNA- protein complex. Thus, several murine fibrosarcomas produced a soluble factor that activated splenic suppressor cells to depress the immune response to nonneoplastic antigens. These suppressor factors represent a novel group of regulatory molecules which may be ribonucleoprotein complexes.

Animals↗
PubMed1985

Management of inflammatory carcinoma of the breast. A combined modality approach.

From May 1973 to December 1981, 63 patients with inflammatory carcinoma of the breast were treated with a doxorubicin-containing chemotherapy regimen (FAC). After a median of three cycles of FAC, 41 patients received primary therapy with irradiation; more recently, 21 had mastectomy as primary therapy. One patient relapsed following a treatment delay and did not receive local therapy. Fourteen of 21 patients who underwent mastectomy had subsequent consolidation therapy with irradiation. At median follow-up of 60 months, median relapse-free survival (RFS) and survival were 24 and 43 months, respectively. The initial site of recurrence was locoregional in eight patients (20%). In addition, two of seven uncensored patients (18%) who suffered initial recurrence in the contralateral breast remained disease-free at 28 and 55 months with further surgery. While no locoregional recurrences were seen in the 14 mastectomy patients who completed comprehensive irradiation, no RFS nor survival advantage was noted for either initial local therapy. Sixteen patients with dermal lymphatic carcinomatosis and 10 patients with negative skin biopsies had median RFS of 31 and 46 months, respectively (p = 0.45). Median RFS was 36 months in patients greater than or equal to 50 years of age and 19 months in patients less than 50 (p = 0.05). Response to FAC was the most significant predictor of RFS and survival. Patients who achieved complete or partial remission (PR) with induction FAC as compared to patients who achieved less than PR had median RFS of 31 vs. 19 months (p = 0.01) and median survivals of 60 vs. 27 months (p = 0.05), respectively. Categorization of patients according to clinical, mammographic, and pathologic criteria facilitated identification of potential long-term responders. With combined modality approach to inflammatory carcinoma of the breast, we can expect an estimated 31% of patients to be relapse-free at 5 years after treatment.

Adult↗
PubMed1984

Soluble factors from murine and human tumors induce suppressor cells.

A tumor-derived suppressor factor ( TDSF ) has been isolated from 3 M KCl extracts of a chemically induced fibrosarcoma of C3H/HeJ mice by preparative isoelectric focusing. Incubation of TDSF with normal spleen cells induces suppressor cells that enhance tumor growth and inhibit DTH to the chemical sensitizer 2,4-dinitro-1-chlorobenzene (DNCB). Similar suppressogenic activity has been detected in extracts of the 10T1/2 fibroblast line, an ultraviolet-induced fibrosarcoma of C3H/HeN mice, the C57B1/6J Lewis lung carcinoma, and four human colonic adenocarcinoma. TDSF activity was not found in extracts of syngeneic muscle or spleen cells. Chemical characterization of TDSF from the murine fibrosarcoma MCA-F revealed sensitivity to treatment with heat and RNase, partial sensitivity to treatment with trypsin, but resistance to treatment with DNase, pronase, and neuraminidase. TDSF has an apparent molecular weight of greater than 300 kDa by high-performance gel permeation chromatography. Acidic soluble factors isolated from murine and human tumors induce suppressor cells to inhibit cell-mediated immunity in an intact host.

Adenocarcinoma↗
PubMed1982

Mechanisms of immunosuppression in tumor-bearing mice: a multifactorial analysis.

Neoplastic growth results not only from the inherent proliferative potential of the neoplasm, but also from the neoplasm's ability to survive within a host whose immune responses may be activated to destroy it. It has been proposed that several mechanisms enable a neoplasm to outgrow the host. The present work describes a system for probing tumor-associated immunosuppression by utilization of the delayed hypersensitivity response to dinitrochlorobenzene (DNCB). Mice of the Balb/c and C3H/HeJ strains were sensitized with a subcutaneous injection of 2 mg DNCB followed 5-10 days later by the subcutaneous injection of a 0.05 mg challenge dose of DNCB in the hind footpad. The footpad response measured 24 hours after challenge is a delayed hypersensitivity reaction by virtue of the histology and kinetics of that response and because it is transferred by spleen cells but not by serum. DNCB sensitization is inhibited by spontaneous, chemical- and virus-induced syngeneic tumors in Balb/c and C3H/HeJ mice. Three mechanisms of immunosuppression are elucidated in the present experiments: (1) serum from tumor-bearing mice inhibits primary sensitization of normal mice to DNCB upon passive transfer; (2) spleen cells from tumor-bearing mice inhibit primary sensitization of normal mice to DNCB and appear to be macrophages in the C3H/HeJ system; and (3) an alteration of lymphocyte migration patterns exists in tumor-bearing mice that removes effector cells from the blood and prevents the initiation of a footpad response. The interrelationships of these three mechanisms are discussed. Correlations are also made with tumor-associated immunosuppression observed in cancer patients.

Animals↗
PubMed1982

Inflammatory breast cancer treated with surgery, chemotherapy and allogeneic tumor cell/BCG immunotherapy.

Thirteen consecutive patients with inflammatory breast cancer were treated with a regimen consisting of cyclic chemotherapy, extended simple mastectomy, and immunotherapy utilizing irradiated allogeneic breast cancer cells admixed with BCG. When surgery was performed after two or more cycles of 5-U, doxorubicin hydrochloride, and cyclophosphamide, there was complete eradication of detectable tumor in three of 11 operative specimens. Two patients had surgery prior to our evaluation and four had prior chemotherapy. Chest wall radiation was initiated after 8-10+ months of chemotherapy at the doxorubicin cardiotoxicity limits. Seven untreated patients, all premenopausal, were compared to our previous series which employed either irradiation after several courses of chemotherapy or irradiation alone. The current series has two relapses (eight months, 25 months) at a median follow-up time of 21 months (range, 8-26 months). In the previous chemoradiotherapy trial, all nine premenopausal patients had relapsed within 25 months, with a median disease free interval of 17 months. In the trial using radiotherapy alone, all ten patients had relapsed by 19 months (median disease free interval, nine months). The present regimen appears to improve control of the disease and further investigation of both surgery and immunotherapy intercalated with cyclic chemotherapy appears warranted in this disease.

Adult↗
PubMed1981

Effect of murine tumors upon delayed hypersensitivity to dinitrochlorobenzene. III. In vivo activity of the nonspecific suppressor cell.

Tumor-induced immunosuppression was investigated in an in vivo model of delayed hypersensitivity (DH) to the chemical sensitizer, dinitrochlorobenzene (DNCB). DH to DNCB as measured in a footpad assay was decreased in C3H/HeJ mice bearing MCA-F, a 3-methylcholanthrene-induced syngeneic fibrosarcoma. Suppressor cells from the spleens of tumor-bearing mice inhibited the induction of DH to DNCB in otherwise normal syngeneic C3H/HeJ recipients. Ten million spleen cells (SpC) harvested from mice bearing MCA-F for 10 days and adoptively transferred to tumor-free mice at the time of sensitization with DNCB suppressed the response to the sensitizer. The suppressor cells were macrophages, since they were adherent to plastic, removed by treatment with a magnet after phagocytosis of carbonyl iron, resistant to exposure to gamma radiation and to treatment with anti-Thy 1.2 serum and complement. Further, the nonspecific suppressor cells were activated by progressive tumor growth rather than by induction of tumor-specific immunity using irradiated tumor cells. Titration studies revealed that suppression of DH occurred with the transfer of as few as 10(6) SpC. Thus, nonspecific suppressor cells are effective at inhibiting in vivo DH to DNCB and suggest that nonspecific suppression in the intact host occurs through mechanisms different from those involved in suppression in vitro.

Animals↗
PubMed1978

Accelerated growth of syngeneic tumors in mice treated with methylcholanthrene.

BALB/c and C3H- mice were given a single injection of methylcholanthrene (MCA) and were tested at various times thereafter for immunologic reactivity and resistance to syngeneic tumor challenge. MCA treatment did not affect the rejection of H-2-incompatible tumor allografts, the rejection of H-2-compatible skin allografts, or the induction of delayed hypersensitivity to DNCB as measured by footpad challenge. In contrast, mice treated with MCA exhibited an increase susceptibility to challenge with several syngeneic ultraviolet-induced and MCA-induced fibrosarcomas. These studies demonstrate that in the autochthonous host the measurement of host immune status by in vivo cell-mediated immune responses to exogenous antigens does not necessarily predict the host response to tumor growth.

Animals↗
PubMed1978

Severe complications of intralesional BCG therapy in an unsensitized patient. Case report and clinical implications.

Since the introduction of BCG intralesional immunotherapy for melanoma, severe complications, including death, have been reported after treatment in hypersensitized individuals. This is a case report of BCG dissemination with ulceration, skin necrosis, lymphadenitis, and abscess formation following the first intralesional injection of a minimal dose of BCG in a PPD-negative patient. The case demonstrates that severe complications can occur in patients who are not hypersensitized, anergic, or debilitated or who have been treated multiple times. This patient's complication further suggests that migration of BCG after intralesional therapy may play a role in the regression of uninjected nodules seen in some patients.

BCG Vaccine↗
PubMed1978

Intralesional treatment of recurrent metastatic cutaneous malignant melanoma: a randomized prospective study of intralesional Bacillus Calmette-Guerin versus intralesional dinitrochlorobenzene.

Eighteen patients with multiple recurrences of malignant melanoma without evident distant spread were randomly assigned to treatment with either intralesional Bacillus Calmette-Guerin (BCG) or intralesional dinitrochlorobenzene (DNCB). Both agents were able to destroy approximately 90% of the injected intradermal nodules. Intradermal disease was more easily obliterated than subcutaneous disease with intralesional treatment with either agent, and local control of satellitosis with elimination of all clinically evident tumor was achieved in the patients who had intradermal without subcutaneous satellitosis, regardless of whether the patient was receiving BCG or DNCB. The clinical courses of the treated patients were essentially the same. Although PHA reactivity was depressed, the patients in both groups were responsive to recall and melanoma skin test antigens, demonstrated leukocyte migration inhibition with melanoma antigen and were generally within normal limits when assayed for 29 degrees C E rosettes. Our study demonstrated a dramatic difference in toxicity between the two intralesional agents without a similar difference in therapeutic efficacy or immune testing.

Adult↗