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Biomedical subjects

K J McCormick

Publications and source records attributed to K J McCormick.

At least 19 recordsLinked to original sources

Murine subrenal capsule assay: prediction of chemoresponsiveness in head and neck cancer.

If chemotherapy is to be used with the greatest efficacy in head and neck cancer, a predictive test that will indicate tumor sensitivity or resistance in individual patients may be desirable. This report demonstrates that the in vivo murine subrenal capsule assay was an efficient, sensitive method for retrospectively predicting the clinical response of squamous cell carcinomas of the head and neck to chemotherapy. Twenty-five courses of chemotherapy in 22 patients were compared to responses in the in vivo assay. The assay correctly identified sensitivity to chemotherapy in 86% of clinically responding patients. The specificity of the assay was 78%. A 60% efficiency for predicting clinical response and a 93% efficiency for predicting clinical resistance were demonstrated. Eighty percent of the results were correctly classified. The murine subrenal capsule assay has potential in planning of chemotherapy for selected patients.

Adult↗

Preservation of the supraspinous ligament for spinal stenosis: a technical note.

Laminectomies and bilateral laminotomies for spinal stenosis have been performed over a period of 16 years at the Mercy Catholic Medical Center by preserving the supraspinous ligament along with the tips of the lumbar spines. More recently, this has been done utilizing a unilateral approach. This operation is technically feasible and with practice can be done routinely for extensive spine decompression, even for spinal tumor resection or spinal fusion.

Humans↗

Indomethacin-induced augmentation of lymphoproliferative responses in patients with head and neck cancer.

Augmentation of the phytohemagglutinin (PHA)-induced lymphoproliferation of peripheral blood mononuclear cells by indomethacin, a drug which blocks prostaglandin (PG) synthesis, was assessed in 37 patients with squamous cell carcinoma of the head and neck. Indomethacin enhanced the uptake of 3H-thymidine in stimulated cultures both from patients and normal individuals. However, because lymphoid cells from cancer patients were less reactive than those from normal controls, the proportionate increase in PHA-stimulated 3H-thymidine incorporation caused by indomethacin was greater in this population than in the normal population. The degree of enhancement induced by indomethacin did not correlate with the percent of esterase-positive mononuclear cells in the preparations. The amounts of PGE synthesized at 48 h by patients' or normal cells were similar. Cell populations that exhibited elevated levels of augmentation in the presence of indomethacin were approximately 3 times as sensitive to inhibition by 3 nM PGE2. The degree of augmentation detected in the presence of Ro-20-5720, which also prevents PG synthesis, was related to that produced by indomethacin. These results suggested that: the enhancing effect of indomethacin on lymphoproliferation in vitro was related to its inhibition of PG synthesis; and the sensitivity of lymphoid cells to inhibition by PGE2 was slightly, but significantly, increased in individuals with elevated augmentation values.

Adult↗

Relationship between the amounts of EBV-DNA and EBNA per cell, clonability and tumorigenicity in two ebv-negative lymphoma lines and their EBV-converted sublines.

The effect of EBV-conversion of two EBV-negative lymphoma lines (Ramos and BJAB) on agarose clonability and tumorigenicity in nude mice was explored. The cloning frequency was increased in all 9 sublines investigated, between 1.1 and 4.9 times compared to the original "parental" lines. Tumorigenicity was increased in one out of 2 BJAB-derived, EBV-positive lines and in 3 of 6 Ramos-derived lines, while it was decreased in 3 others. A strong positive correlation between the number of genomes/cell and the amount of EBNA/cell was detected, and in 7 of 9 converted lines the cloning frequency also correlated to the number of EBV genomes. On the other hand, no relation was established between the number of EBV-genomes/cell, the amount of EBNA/cell and tumorigenicity.

Animals↗

Single agent chemotherapy for head and neck cancers. The murine subrenal capsule assay.

The murine subrenal capsule assay was used to determine chemotherapeutic sensitivities of metastatic, primary, or recurrent head and neck cancers. Tumor fragments (1 cu mm) were implanted under the renal capsule of 2- to 4-month-old normal female C57 BL/6 X DBA/2 F1 hybrid mice. Xenografts included 20 squamous cell carcinomas (SCCs), one mucoepidermoid carcinoma, one adenoid cystic carcinoma, and two melanomas. Groups of tumor-bearing mice were treated with chemotherapy daily for five days. Sensitivities of the tumor were assessed on day 6 by comparison of final implant size with initial implant size. Significant oncolytic activity was detected against 16 of 24 tumors (14 of 20 SCCs and both melanomas). Correlations between the in vivo assay and clinical studies are needed to determine its predictive value.

Animals↗

Immunomodulatory activity in regional lymph nodes.

This study is, to our knowledge, the first attempt to evaluate cellular immune mechanisms in regional lymph nodes of patients with head and neck cancer. Twenty lymph nodes from eight patients with stage III-IV squamous cell carcinoma were evaluated using an in vitro culture system. The T-cell mitogenic (concanavalin A) response of patients' peripheral blood mononuclear cells was modulated by the addition of cells from regional lymph nodes removed at neck dissection. Modulatory activity showing augmentation was significantly correlated with the size of the primary tumor and histopathologic grade of the tumor. Modulatory activity did not correlate with the histologic pattern of lymph node reactivity. Although these relationships suggest that regional immunity may be important in tumor-host interactions, further study is necessary to establish their biologic and prognostic importance.

Adult↗

"Hidden" cytotoxic antibodies that react with allogeneic cultured fetal and tumor cells contained in soluble immune complexes from normal human sera.

Hidden complement-dependent cytotoxins were demonstrated in normal donor sera after removing anti-immunoglobulins that normally block the ability of these immunoglobulin Gs to react with surface antigens on tumor cells. The blocking antibodies had certain properties of anti-idiotypes. Immunoglobulin G from Cohn Fraction II, after removing these anti-immunoglobulins, was cytotoxic for cultured fetal cells and for malignant melanoma, breast, lung, colon, and other tumor cells maintained either in tissue culture or by serial passage in nude mice. The cytotoxins were not adsorbed by extracts from normal lymphoid, liver, skin, or red blood cells. These results suggest that a heterogeneous group of natural antibodies reactive with antigens expressed on a variety of neoplastic and fetal cells circulate in normal donor sera as part of a soluble immune complex, together with a blocking anti-immunoglobulin.

Animals↗

Induction of tumor-specific cell-mediated immunity by a noninfectious type-C virus.

Hamsters immunized with either noninfectious hamster type-C virus (D9) or irradiated D9 tumor cells were tested for cell-mediated immune reactivity by the macrophage migration inhibition assay. The migration of peritoneal exudate cells from immunized hamsters was significantly inhibited by either D9 virus or D9 tumor extract, but not by extract of an unrelated CELO virus-induced tumor. The virus and tumor extracts had little or no effect on the migration of peritoneal exudate cells from normal hamsters. Noninfectious D9 virus produces a cell-mediated immune response in the hamster and shares antigenicity with D9 lymphoma, which releases the virus.

Animals↗

An enzymatic assay for the detection of natural cytotoxicity.

The pronase-enhanced release of 14C-labeled DNA was used to assay cytotoxicity of murine natural killer cells. YAC-1 lymphoma cells were labeled with [14C]thymidine and incubated with increasing numbers of spleen cells from nude mice. At harvest, nuclease-free pronase was used to digest damaged target cells. Increases in cytotoxicity of 5--39% were obtained using optimal conditions. The reaction could be successfully inhibited with unlabeled YAC-1 cells. The degree of cytotoxicity was similar to that detected by 51Cr release, but a longer period of incubation was required.

Animals↗

Rheumatoid factor positive plasma and humoral cytotoxicity to malignant melanoma.

Complement dependent cytotoxicity to malignant melanoma tumor cells was demonstrated in incubations that included rheumatoid factor (RF) positive plasma and normal plasma. Cytotoxicity was not demonstrated to cells from a number of normal tissues. The phenomenon involved coating of tumor cells with immunoglobulins and complement fixation. The activity in RF positive plasma was present in high titer an may not be RF. The activity in normal plasma was present in low titer, was found in plasma from eight out of 11 healthy subjects and may be a naturally occurring antibody. This previously undescribed humoral cytotoxicity system may participate in tumor host interactions, especially after therapy, when the majority of patients become RF seropositive.

Animals↗

Virus-specific markers and virus-like particles in cell lines of tumors produced by CELO virus in Syrian golden hamsters.

Cell lines were established from 2 primary hepatocellular carcinomas (HC's) and 3 sarcomas produced in Syrian golden hamsters inoculated as newborns with chicken embryo lethal orphan (CELO) virus. Cell lines from 2 sarcomas (COT, CMT) and 1 HC (CEHEP) produced CELO virus-specific T-antigen. The antigen was not detected in cells of the third sarcoma line (RCT) until they had undergone more than 34 passages in vitro. Although 5-10% of cells in the second HC line (CILT/2) contained T-antigen during early passages, it was not demonstrable after the fifth subculture. Nevertheless, cells of both HC lines possessed CELO virus tumor-specific transplantation antigen. All 5 cell lines also contained hamster type R particles, and both HC lines had type C and intracytoplasmic type A particles. The percentage of carcinoma cells producing type R particles increased during cultivation in vitro, whereas the number of cells with type A particles decreased. Treatment with dibutyryl cyclic AMP and theophylline enhanced the number of cells producing type C particles in 1 HC line and type R particles in 2 sarcoma lines.

Adenoviridae↗

Chicken embyro lethal orphan (CELO) virus DNA present in hamster cell lines derived from CELO-induced hepatomas.

The kinetics of renaturation of the isolated DNA fragments of chicken embryo lethal orphan (CELO) virus generated by the restriction enzyme EcoR1 was measured in the presence of DNA extracted from two lines of CELO virus-induced hamster hepatoma cells and from control hamster cells. One hepatoma cell line (CILT-2), which did not produce the CELO virus tumor (T) antigen, lacked sequences from about one-half the virus genome while the other hepatoma cell line (CEHEP), which did produce the CELO virus T antigen, lacked sequences corresponding to one-fifth of the viral genome.

Adenoviridae↗

Oncogenic and nononcogenic bovine adenoviruses and guanine-cytosine content of their DNA.

Bovine adenoviruses types 1, 2, and 3 were purified and concentrated by polyethylene glycol precipitation and CsCl density-gradient centrifugation. The efficiency of recovery of infective particles was 64 to 80%. The guanine-cytosine contents of DNA of the nononcogenic types 1 and 2 and the highly oncogenic type 3 were found to be 62, 61, and 48%, respectively--a pattern similar to that of nononcogenic and oncogenic human adenoviruses.

Adenoviridae↗