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Biomedical subjects

J Lundy

Publications and source records attributed to J Lundy.

At least 37 records · Page 2Linked to original sources

Monoclonal antibody B72.3 as a diagnostic adjunct in fine needle aspirates of breast masses.

Fine needle aspirations of breast masses were evaluated to establish a cytologic diagnosis. In 45 cases, the sensitivity was 73%, specificity 100%, and diagnostic accuracy 84%. Fifty cases (27 malignant and 23 benign) were evaluated by immunoperoxidase staining of the needle aspirates, using the monoclonal antibody B72.3. Twenty-six of 27 malignant cases stained positively, and 22 of 23 benign cases were negative. The sensitivity was 96%, specificity was 96%, and diagnostic accuracy was 96%. All cases considered malignant cytologically were confirmed by immunocytochemistry. In addition, the B72.3 monoclonal antibody appears to be a valuable diagnostic adjunct in atypical and suspicious cases, particularly those in which hypocellularity and/or cellular monomorphism preclude a diagnosis of malignancy by routine cytologic examination.

Adenocarcinoma↗

Elevated ras oncogene expression correlates with lymph node metastases in breast cancer patients.

The protein product of the ras cellular oncogene(s) (p21) was assayed in primary breast carcinomas from two groups of patients who had different axillary lymph node status. Using an immunohistochemical assay, the intensity and percent of neoplastic cells demonstrating ras p21 antigen staining were significantly higher in the primary tumors from patients with lymph nodes positive (LN+) for malignancy (20 patients) compared with the lymph node negative (LNO) group (21 patients). The expression of p21 also correlated with tumor size. Age and estrogen receptor status did not influence p21 staining. The antigen expression of p21 was similar in intensity and distribution in the primary tumor and regional lymph node metastases. Enhanced expression of p21 in primary breast cancers that metastasize to regional nodes indicates that ras p21 may be a determinant of the malignant potential of breast cancer cells and may represent a new class of more biologically relevant tumor markers.

Antibodies, Monoclonal↗

Monoclonal antibody DF3 correlates with tumor differentiation and hormone receptor status in breast cancer patients.

The murine monoclonal antibody (MAb) designated DF3, reacts with a 300-kd human mammary epithelial antigen which is expressed on apical borders of secretory mammary epithelial cells and in the cytosol of less differentiated malignant cells. Human mammary tumors have been evaluated for the level of DF3 antigen as a correlate to clinicopathologic parameters related to degree of tumor differentiation: nuclear grade (NG), histologic grade (HG), and estrogen receptor status (ER). More DF3 antigen was present in breast carcinomas with NG 1 and 2 as compared to tumors with NG 3 (p = .002). Similarly DF3 antigen presence was greater in HG 1 and 2 tumors than in HG 3 (p less than .001). The results also demonstrate that quantitative differences in the presence of the DF3 differentiation antigen correlate with estrogen receptor status. Twenty-two of 23 ER positive tumors were also DF3 positive. Only 6 of 23 ER negative tumors were reactive to MAb DF3 (p less than .001). There was, however, no correlation between DF3 reactivity and absolute levels of estrogen or progesterone receptor. These findings confirm our hypothesis that MAb DF3 reacts to a differentiation antigen present in some human breast carcinomas. The DF3 antigen phenotype can serve as an independent phenotypic marker with correlations to standard indicators of degree of differentiation and estrogen receptor status of infiltrating ductal carcinomas of the breast, and should thus be evaluated as a prognostic indicator in breast cancer patients. The data also suggests that DF3 histochemistry may be a useful alternative in assessing estrogen receptor status of small breast cancers where there is an insufficient amount of tumor present for biochemical assay of hormone receptor levels.

Antibodies, Monoclonal↗

Definition by monoclonal antibodies of a repertoire of epitopes on carcinoembryonic antigen differentially expressed in human colon carcinomas versus normal adult tissues.

Monoclonal antibodies (MAbs) designated COL-1 through 15 have been generated and characterized and show a strong degree of selective reactivity for human colon carcinomas versus normal adult tissues. To prepare the MAbs, mice were immunized with extracts or membrane-enriched fractions of biopsy material from either primary or metastatic colon carcinoma lesions. The fifteen COL MAbs, all of the immunoglobulin G subclasses 1, 2a, or 2b, reacted with purified carcinoembryonic antigen in solid-phase radioimmunoassay and by immunoblotting, but none reacted with human polymorphonuclear leukocytes or certain spleen preparations previously shown to be rich in carcinoembryonic antigen-related or cross-reactive antigens. MAbs COL-1 through 15 could be divided into at least five groups based on their differential range of reactivities to the surface of colon carcinoma cells or other carcinoma cell preparations. The COL MAbs were tested via immunoperoxidase with a wide range of primary and metastatic colon carcinomas, benign or dysplastic colon lesions, and 34 normal adult tissues. With few exceptions, the COL MAbs tested in this manner showed reactivity only to the primary and metastatic colon carcinomas. These studies thus provide a well-characterized repertoire of MAbs that are well suited for potential clinical trials involving the radiolocalization and possibly therapy of human colon carcinoma lesions. The fact that at least five epitopes are being recognized also provides the opportunity for testing the efficacy of cocktails of the COL MAbs toward these goals.

Adult↗

Beta-endorphin injected into the nucleus of the raphe magnus facilitates metastatic tumor growth.

Electrical stimulation of the periaqueductal gray of the rat's midbrain analgesia leads to an increase in the number of artificial pulmonary metastases from the Walker 256 tumor. In an effort to investigate the influence of the pain suppression system and its associated peptides on this phenomenon, we activated the pain suppression system directly from the Nucleus of the Raphe Magnus, a non-opioid subsystem. After inducing analgesia by direct injection of beta-endorphin on the Nucleus of the Raphe Magnus, we noted an increase in the number of artificial pulmonary metastases. This result could be blocked by pretreatment with naloxone. If the Nucleus of the Raphe Magnus was activated by electrical stimulation sufficient to induce analgesia, the metastatic effect was still present but markedly attenuated.

Animals↗

Suppressor cells and increased primary tumor growth rate induced by thiopental.

A single dose of thiopental (37-42 mg/kg) sufficient to achieve anesthesia induction increased the growth rate of a 3-methylcholanthrene-induced syngeneic murine fibrosarcoma in C57B1/6 mice. While no alterations in in vitro growth kinetics of tumor cells cultured with thiopental could explain these data, significant alterations in cell-mediated immunity were observed. Spleen cells from C57B1/6 mice treated with thiopental were impaired in their ability to respond in a mixed leukocyte culture (MLC) to BALB/c stimulator cells. Spleen cells from thiopental-treated mice suppressed the ability of cells from untreated animals to respond in a third-party MLC. The degree of suppression was directly proportional to the number of cells from thiopental-treated mice in the third party. When these cells were added to an MLC at various times during the culture period, suppression of the early phases of the MLC was seen. Removal of plastic adherent cells from the third party resulted in loss of suppression, but treatment of third-party cells with anti-thy 1.2 serum or irradiation did not prevent suppression. Transfer of spleen cells from thiopental-treated mice enhances growth of the B-16 melanoma. Suppressor-cell activity may be one mechanism by which thiopental promotes tumor growth.

Animals↗

Colorectal cancer in patients under 40 years of age.

A retrospective chart review was undertaken on all Hartford Hospital Tumor Registry patients under age 40 with a diagnosed adenocarcinoma of the colon or rectum between the years 1955 and 1980. Of the 45 patients who could be accurately staged by the Dukes classification, only about one-third had disease localized to the bowel. No unique histological pattern was observed. An excess of multiple primary tumors was observed (13%). Stage of disease at the time of presentation, rather than histology, was the most important prognostic factor in this study. Carcinoma of the rectum in our series had a 5-year survival rate of 8%. This group of young patients should be managed with aggressive multimodal therapy.

Adenocarcinoma↗

Surgery, trauma and immune suppression. Evolving the mechanism.

A major surgical procedure can impair the delayed hypersensitivity response. This impairment is associated with suppressor cell activity that can alter either afferent or efferent responses. Using the third party mixed leukocyte culture to define cell types involved, major immune impairment was seen with the combination of both nonadherent and plastic adherent cells, suggesting that a T cell-macrophage interaction is required. A serum factor(s) is present in operated mice that can impair mixed leukocyte culture reactivity. A serum factor(s) in an adoptive transfer experiment is also capable of enhancing primary tumor growth. A unifying hypothesis, based predominantly on data from the current literature, is presented in an attempt to elucidate the mechanism by which all forms of major trauma are associated in some patients with "paradoxical" immune suppression.

Amputation, Surgical↗

Thiabendazole (TBZ), an immunohemomodulator. I. Effects on lymph node and spleen.

Previous studies in our laboratory with Thiabendazole (TBZ) indicated that the drug significantly augmented cellular immune responses in mice. The purpose of the present and companion study was to determine which of the cell populations in primary and secondary lymphoid organs and in bone marrow were affected by the in-vivo administration of TBZ. Two major changes in lymph nodes and/or spleens of TBZ-treated mice were detected by histological and quantitative planimetric analysis: (1) expansion of T and B lymphocyte compartments and (2) increase in extramedullary hemopoiesis. The effect on T cells and on hemopoiesis were observed only when TBZ was administered with the thymus-dependent neoantigen, dinitrofluorobenzene (DNFB). The effect on B cells appeared to be antigen-independent. Increased extramedullary hemopoiesis in TBZ + DNFB-treated mice was preceded by a significant increase in pluripotent hemopoietic stem cell activity in bone marrow, as measured by the CFU-S assay. This study indicates that TBZ has significant effects on the development and differentiation of both lymphoid and hemopoietic cells.

Adjuvants, Immunologic↗

Thiabendazole (TBZ), an immunohemomodulator. II. Effects on thymocytes and prothymocytes.

The purpose of this study was to document the effects of TBZ on the early stages of T cell maturation. The method utilized to quantify presumptive thymocyte progenitors in the bone marrow used the enzyme terminal deoxynucleotidyl transferase (TdT) as a marker. Shifts in thymocyte populations were determined by quantitative planimetry, immunofluorescence for TdT and tritiated thymidine incorporation. When given alone, TBZ produced a marked increase in the number of large, mitotically active lymphoblasts in the thymus cortex. When given with DNFB, a thymus-dependent neoantigen, TBZ produced a significant increase in TdT-positive bone marrow cells. In a companion study, TBZ + DNFB were found to stimulate T cells in lymph node and spleen. Hence, the results indicate that under appropriate conditions, TBZ can stimulate all stages of T cell differentiation in mice.

Adjuvants, Immunologic↗

A model of tumor cell dormancy: effects of anesthesia and surgery.

Three cloned populations of tumor cells obtained from a murine fibrosarcoma were able to remain viable for a long period of time in syngeneic mice which failed to exhibit clinically evident tumors following tumor cell inoculation. Viable tumor cells under such conditions can be considered to be in a dormant state. On the basis of past studies, two of the lines were shown to have low malignant potential, while the third line was shown to have a higher degree of malignant potential. The rates of spontaneous reactivation of tumor growth in animals carrying the low malignant cells were 3 and 4%, while a rate of 30% was observed in animals with the more malignant cells. Treatment of animals carrying the low malignant cells in a dormant state with anesthesia alone, (thiopental) or with anethesia and surgery, increased the rate of reactivation to 20-22%.

Anesthesia↗

Electrical stimulation of the midbrain mediates metastatic tumor growth.

Pulmonary metastases were counted 10 days after female rats received tail-vein injections of Walker-256 carcinosarcoma cells. Previous observations that halothane anesthesia plus hind-limb amputation increases the number of metastases were confirmed. Amputation under the analgesia of electrical stimulation of the midbrain was found to increase metastatic activity. However, the stimulus-produced analgesia alone also increased the number of metastases. Systemically administered naloxone blocked the analgesic effect of midbrain stimulation but did not block the increase in the number of pulmonary metastases.

Anesthesia↗

Anesthesia and surgery: a double-edged sword for the cancer patient.

All therapeutic modalities used in cancer patients are associated with immunosuppression. Anesthesia and surgery represent a double-edged sword. By removal of gross tumor in many patients a restoration of general immune responses can be documented. In addition, circulating antigen or antigen-antibody complexes which block tumor-specific immune responses can be abrogated by removal of bulk tumor. However, animal data indicates that certain anesthetic agents and major surgical procedures may enhance growth of micrometastatic tumor foci. One mechanism by which this occurs might be immunosuppression. The use of immunorestorative drugs in the perioperative period has been able to reverse this phenomenon in animal tumor models.

Anesthesia↗

Suppressive effects of thiopental and halothane on specific arms of the immune response.

The effect of thiopental, halothane and surgery on specific arms of the immune response of normal mice was studied. These experiments represent the first step in localizing a potentially correctable anesthesia/surgery-induced defect in immune reactivity which may be involved with postoperative increases in tumor growth. The delayed-type hypersensitivity (DTH) response of mice to 2,4-dinitrochlorobenzene (DNCB) was studied. Combinations of induction and inhalation anesthesia and surgery were administered at various phases of the immune response to DNCB. Thiopental impaired the afferent response while halothane impaired the efferent response. When the agents were combined, both arms of the immune response were suppressed. A surgical procedure, in most experiments, did not produce a greater immunosuppression than thiopental and halothane. The administration of an immunorestorative agent, thiabendazole, returned reactivity to normal levels. Thiopental and halothane either affect different immune cell populations or they affect different functions of a cell population active in both arms of the DTH response. In relation to tumor growth, the degree of suppression may not be as significant as the cell population impaired.

Anesthesia↗

In vitro and in vivo adherence of tumor cell variants correlated with tumor formation.

Murine fibrosarcoma variants that differed greatly in tumorgenicity, in vivo growth rate, and rate of spontaneous metastasis formation were compared for their ability to induce tumors in the lungs of syngeneic mice after intravenous injection of a suspension of single cells. Significantly more tumors were observed in the lungs of mice that received 1 x 10(5) of the cells of high malignant potential than in the lungs of animals that received 1 x 10(5) cells of lower malignant potential (54 tumors per animal vs 3 tumors per animal). When the tumor cells were prelabeled in culture for 24 hours with 125I-IUDR prior to intravenous injection, it was found that both the "high" and "low malignant" cells rapidly accumulated in the lungs (55-59% of the radioactivity was found in the lung tissue by 5 minutes after injection). However, by 4 hours only 4% of the low malignant cells (as indicated by the amount of radioactivity present) were still in the lungs, while a significantly higher percentage (13%) of the high malignant cells were still present in the lungs. The difference between the high and low malignant cells with regard to ability to remain sequestered in the lungs of syngeneic mice and to subsequently form tumors in the lungs of these animals correlated with the ability of the cells to form stable attachments to monolayers of endothelial cells in culture. While both the high and low malignant cells attached at the same rate to monolayers of bovine endothelial cells, once the cells were attached, the low malignant cells were released by trypsin treatment more easily than the high malignant cells. These observations suggest that the difference in malignant potential between the variants may be due, at least in part, to differences in ability to form stable attachments.

Animals↗

Immune impairment and metastatic tumor growth: the need for an immunorestorative drug as an adjunct to surgery.

A spontaneous murine metastatic tumor system was used as a model to assess the effects of a major surgical procedure on tumor-specific immune reactivity and the growth of micrometastases. Any major surgical procedure resulted in impaired cell-mediated cytotoxicity postoperatively and an increase in the number of gross pulmonary metastases. The use of an immunorestorative drug, Thiabendazole, in the perioperative period resulted in an improved cytotoxic response and a significant decrease in pulmonary metastases. Perioperative immunotherapy can be an effective adjunct to surgery in preventing the growth of micrometastatic foci.

Animals↗