Biomedical subjects

J Lundy

Publications and source records attributed to J Lundy.

At least 19 recordsLinked to original sources

PubMed1992

Enhancement of in vitro tumor-infiltrating lymphocyte cytotoxicity by heteroconjugated antibodies.

Tumor-infiltrating lymphocytes (TIL) were obtained from a mouse melanoma cell line (CL 62) transfected with the gene for the human melanoma Ag p97. TIL were cultured with anti-CD3 antibody and IL-2 for up to 38 days. Flow cytometry identified these TIL as Thy-1.2 + ve/CD4-ve/CD8 + ve cells. A heteroconjugated antibody 500A2 x 96.5, specific for both the CD3 Ag on TIL and the p97 Ag on CL 62 melanoma cells, was prepared using N-succinimidyl-3-(2-pyridyldithio)-propionate as a linking agent. TIL alone demonstrated low levels of cytotoxicity against autologous CL 62 tumor and also against the parental K1735 tumor and an allogeneic murine melanoma (B16). The addition of 500A2 x 96.5 heteroconjugated antibody enhanced TIL-mediated lysis of CL 62 tumor, but not of the K1735 or B16 tumors. This enhanced cytotoxicity was elicited at E:T ratios as low as 0.4:1, and in TIL cultured for 7 to 38 days. These results suggest that hetero-conjugated antibody may enhance the anti-tumor effect of TIL in vivo.

Animals↗

PubMed1992

Heteroconjugated antibodies enhance lymphocyte-mediated tumour cell lysis in vitro and in vivo.

Covalent linkage of an antitumour antibody specific for a tumour cell surface antigen to an antilymphocyte antibody specific for the T lymphocyte receptor complex produces a heteroconjugated antibody that can activate and redirect cytotoxic T lymphocytes to lyse tumour cells. The ability of an antilymphocyte-antitumour heteroconjugate (500A2 x 96.5) to direct the lysis of murine melanoma cells by cultured murine lymphocytes was tested in vitro using a 4-h chromium release assay and in vivo with a tumour neutralization assay. In vitro, the addition of heteroconjugated antibody significantly increased tumour lysis by murine C3H/HeN lymphocytes (median specific lysis 82.7 per cent with lymphocytes plus heteroconjugate versus 9.5 per cent for lymphocytes alone, P less than 0.001). In vivo, treatment with heteroconjugated antibody plus lymphocytes significantly reduced the development of pulmonary metastases after intravenous tumour administration (median number of pulmonary metastases 28.5 for combined treatment versus 250 for heteroconjugate or lymphocytes alone, P less than 0.001).

Animals↗

PubMed1991

Expression of neu protein, epidermal growth factor receptor, and transforming growth factor alpha in breast cancer. Correlation with clinicopathologic parameters.

The major objectives of this study were twofold: to determine 1) if growth factors or growth factor receptors were expressed similarly or differently in a clinically well-characterized group of breast cancer patients and 2) if these phenotypic characteristics were associated with any of the commonly used prognostic parameters. Formalin-fixed paraffin-embedded tumor tissue from 51 node-positive breast cancer patients were analyzed for the expression of neu, epidermal growth factor-receptor (EGF-R), and transforming growth factor alpha (TGF alpha) using immunoperoxidase staining. Positive membranous staining for neu was observed in 15 (29%) tumors. Over-expression of neu was observed in high-grade, estrogen-receptor-negative tumors (P less than 0.05). Epidermal growth factor receptor was expressed in 22 (43%) of the tumors analyzed and found to a greater degree in estrogen-receptor-negative and high-grade tumors (P less than 0.025). A significant correlation between neu and EGF-R expression was also noted. Tumors expressing membranous staining of neu had a greater than 70% chance of expressing EGF-R (P less than 0.01). Expression of TGF alpha was found in 68% of tumors and TGF alpha was detected in grade 1 and 2 tumor to a greater degree than EGF-R. The authors conclude that assaying tumors for these antigens may give additional phenotypic characteristics that can give further insight into the biology of breast cancer.

Adult↗

PubMed1990

Evidence for an enkephalinergic system in the nervous system of the pond snail, Lymnaea stagnalis.

Evidence for the presence of an enkephalinergic system in the ganglia of the pond snail, Lymnaea stagnalis, has been obtained with 3 experimental approaches. Scatchard analysis with [3H]etorphine reveals a monophasic high-affinity opiate binding site (Kd 2.3 nM) which is naloxone-sensitive. Immunocytochemical localization of Met- and Leu-enkephalin-like substances as well as alpha-MSH- and ACTH-like materials was demonstrated within specific populations of neurons. Substances with Met- and Leu-enkephalin and Met-enkephalin sulfoxide RIA reactivities were detected also in HPLC fractions corresponding to the retention times of authentic enkephalin standards. Together, the results provide strong evidence for the presence of enkephalinergic mechanisms in the nervous system of Lymnaea stagnalis. Additionally, the report provides indirect evidence for the existence of a macromolecular opioid precursor. This enkephalinergic system shows striking similarities to opioid mechanisms found in vertebrates and bespeaks a common evolutionary origin.

Animals↗

PubMed1990

The use of fine-needle aspirates of breast cancers to evaluate hormone-receptor status.

The objective of this study was to determine the reliability of immunocytochemical assays of hormone receptors using specimens obtained by fine-needle aspiration of breast cancers. A peroxidase-antiperoxidase immunocytochemical assay was used on 96 aspirates from 47 patients to determine estrogen and progesterone receptor status. Of 27 estrogen receptor-positive cases by steroid-binding analysis, 25 were positive by immunocytochemical assay. Of 21 estrogen receptor-negative cases, 17 were negative by immunocytochemical assay. Of 21 progesterone receptor-positive cases 19 were positive by immunocytochemical assay. Of 27 progesterone receptor-negative cases 25 were negative by immunocytochemical assay. An additional 11 small tumors were evaluated by immunocytochemical assay alone and results were interpretable based on our prior data. With the caveat that a cellular aspirate is obtained, immunocytochemical assay can distinguish hormone receptor-negative and hormone receptor-positive tumors and can be used to assay tumors too small for standard steroid-binding analysis.

Aged↗

PubMed1989

Monoclonal antibody B72.3. An adjunct for evaluation of suspicious aspiration biopsy cytology from the breast.

Monoclonal antibody B72.3 (MoAb B72.3) is a potentially valuable diagnostic adjunct when applied to aspiration biopsy cytology (ABC). In this prospective study, its reactivity was tested on the ABC from 25 breast lesions interpreted as suspicious. The stain was applied directly to the Papanicolaou-stained specimen by the avidin-biotin peroxidase methodology at a concentration of 40 micrograms/ml. In 11 aspirates from invasive carcinomas, the reactivity to MoAb B72.3 was strongly positive in nine cases and weakly positive in two. Ten of these tumors were homogeneous or heterogeneous infiltrating lobular neoplasms, tumors causing special diagnostic pitfalls by ABC. The cells from seven of the nine benign lesions were nonreactive, and in two cases from fibrocystic change, weakly reactive. The ABC from five patients with noninvasive carcinomas or atypical lobular hyperplasia showed a variety of responses. The findings indicate that in select circumstances, MoAb B72.3 used in conjunction with clinical and cytologic findings may be a useful diagnostic adjunct.

Antibodies, Monoclonal↗

PubMed1988

Immunoperoxidase studies by monoclonal antibody B72.3 applied to breast aspirates: diagnostic considerations.

The purpose of this study was to determine the reactivity of monoclonal antibody (MAb) B72.3 when applied directly to aspiration biopsy cytology (ABC) of the breast in the following conditions: (1) infiltration lobular carcinoma; (2) fibrocystic disease; (3) fibroadenoma; and (4) apocrine cysts. Nine of ten aspirates from infiltrating lobular carcinoma were positive in these assays, while 21 of 22 benign cases reacted negatively. The single false-positive benign aspirate manifested a staining pattern characteristic of apocrine cells. This study demonstrates that the MAb B72.3 can be employed as a potentially valuable diagnostic adjunct. It can be used on stained aspirates to assist in the interpretation of ABC from breast lesions.

Antibodies, Monoclonal↗

PubMed1988

Immunocytochemistry with monoclonal antibody B72.3 applied to a spectrum of benign and malignant breast aspirates--strengths and pitfalls.

Fine needle aspiration cytology (FNA) was performed on 168 breast masses. In all cases aspirates were reacted with monoclonal antibody (MAb) B72.3 using the ABC immunoperoxidase technique. MAb B72.3 demonstrated reactivity in nine of 90 malignant cases in which the cytologic diagnosis was not positive. In eight benign cases in which the cytopathologist made a suspicious diagnosis, MAb B72.3 demonstrated cytoplasmic reactivity in only one case. In three cytologically benign cases MAb B72.3 reacted strongly positive. The overall diagnostic accuracy of this immunoperoxidase technique was approximately 95 percent. In about five to 10 percent of cases, monoclonal antibody B72.3 can be a valuable diagnostic adjunct to routine cytopathologic diagnosis. False positives present pitfalls that must be considered.

Adenofibroma↗

PubMed1988

Phenotypic markers for a spectrum of colonic polyps and cancers. The malignancy potential ratio.

The purpose of this study was to determine if a panel of monoclonal antibodies could define phenotypic markers that could be used in risk assessment of a spectrum of colonic polyps and colon cancers. Using the ABC immunoperoxidase technique on formalin-fixed sections of surgical specimens, the following results were obtained: 1) Mab B72.3 demonstrated increased reactivity in villous lesions and cancers compared with hyperplastic polyps and tubular adenomas; 2) Mab anti-CAA demonstrated increased reactivity in polyps compared with colon cancers; and 3) using the two antibodies (Mab B72.3 and Mab anti-CAA), a malignancy ratio was obtained that determined malignancy risk for individual polyps. No hyperplastic polyp gave a positive ratio, but about 30 percent of villous lesions were positive. Over 50 percent of villous lesions greater than 2 cm in size had a positive ratio. The malignancy potential ratio may be a valuable marker in assessing risk of malignancy in an individual case.

Adenomatous Polyposis Coli↗

PubMed1988

A tumor-associated antigen in carcinoma of the pancreas defined by monoclonal antibody B72.3.

A retrospective analysis of 25 primary adenocarcinomas of the pancreas, 16 metastatic pancreatic tumors, 8 cases of chronic pancreatitis, and 3 adult normal pancreas was performed to ascertain the reactivity of monoclonal antibody (MAb) B72.3 to malignant and nonneoplastic pancreatic lesions. Formalin-fixed, paraffin-embedded sections of pancreas were evaluated by immunohistochemical techniques (avidin-biotin-peroxidase complex [ABC] method). Twenty-one of 25 malignant primary tumors were reactive, and all 16 metastatic sites expressed the B72.3 antigen. In contrast, all cases of pancreatitis and normal pancreas were either weakly reactive or nonreactive. Ten malignant and two benign pancreatic fine-needle aspirates provided results similar to those seen with fixed tissues. Because MAb B72.3 has selective reactivity for primary and metastatic pancreatic cancer, it may be of value as a diagnostic adjunct in cytologic examination or for radioimmunodetection of regional and/or distant metastases of adenocarcinoma of the pancreas.

Adenocarcinoma↗

PubMed1988

Reactivity of the monoclonal antibody B72.3 with fetal antigen: correlation with expression of TAG-72 in human carcinomas.

The monoclonal antibody (MAb) B72.3 recognizes a mucin-like glycoprotein, TAG-72, which has been detected in a spectrum of human carcinomas, but not in the normal tissue counterparts. Using avidin-biotin-peroxidase complex (ABC) immunohistochemical techniques, MAb B72.3 was reacted with formalin-fixed, paraffin-embedded fetal and pediatric tissue sections to determine the extent of expression of the recognized antigen in these tissues. First trimester fetal tissues failed to express detectable antigen. Gastrointestinal epithelia from 13 to 34 weeks gestation demonstrated the most immunoreactivity with B72.3 although bronchial respiratory epithelium of the lung, transitional epithelium from the kidney, Hassall's corpuscles of the thymus, and gonadal tissues from fetuses of both sexes were also reactive. The TAG-72 antigen was not detected in fetal breast, pancreas, liver, spleen, adrenal, or heart. Expression of the TAG-72 antigen in malignancy appears to correlate well with fetal tissue reactivity with B72.3.

Antibodies, Monoclonal↗

PubMed1987

Tumor-associated antigens in bilateral breast cancer.

The purpose of our present study is to determine whether monoclonal antibodies can define an antigenic phenotype which expresses itself in a concordant fashion in synchronous bilateral breast cancer. The monoclonal antibodies DF.3 and B72.3 were reacted (ABC immunoperoxidase) with formalin-fixed, paraffin-embedded sections of bilateral synchronous breast cancers from 19 patients. MAb DF.3 demonstrated a P less than .01 correlation of right-sided vs left-sided reactivity. This suggested that MAb DF.3 could be used as a biologic marker for synchronous bilateral breast cancer. We hypothesized that the majority of clinically asynchronous breast cancers are really biologically synchronous. We used the immunoperoxidase technique in a similar fashion on bilateral metachronous tumors in 17 patients. DF.3 antigen expression correlated (right to left side) at P less than .01 value. This data, supported by previous information, suggests that the term "metachronous" breast cancer is a clinically arbitrary definition but that biologically most "metachronous" cancers may well be synchronous.

Antibodies, Monoclonal↗

PubMed1987

Management of endoscopically removed malignant colon polyps.

The medical records of 87 patients with 89 malignant colorectal polyps removed endoscopically between 1971 and 1983 were reviewed retrospectively. Fifty-five polyps contained carcinoma-in-situ. Four polyps had "pseudo-invasion" by displaced mucosal glands. Thirty polyps contained invasive carcinoma. No patients with carcinoma-in-situ or "pseudo-invasion" had either local residual disease or metastatic disease at the time of colectomy or which was detected during subsequent follow-up. Four patients (14%) with invasive cancer would have been inadequately treated by polypectomy alone, since one had residual disease at the polypectomy site, one had nodal metastases, one had liver metastases at the time of colectomy, and one subsequently developed liver metastases. Three histologic criteria correctly predicted all four cases where residual or recurrent disease was present: involvement of the polypectomy resection margin, lymphatic invasion within the polyp, and poorly differentiated histology. Polyp size, histology (villous adenoma, adenomatous polyp, or villo-adenomatous polyp), or anatomic location did not identify those patients who warranted further therapy. We conclude that polypectomy alone is adequate treatment for polyps containing carcinoma-in-situ. Polypectomy alone is also adequate treatment for most polyps containing invasive carcinoma. However, patients with lymphatic involvement within the polyp, poorly differentiated cancer, or resection margin involvement should probably undergo colectomy.

Adult↗

PubMed1987

ras p21 expression in the progression of breast cancer.

The differential expression of the ras oncogene product p21 in the primary tumor, regional nodes, and distant metastatic sites in patients with disseminated breast cancer was examined to define the biologic and clinical significance of the ras oncogene in the progression of breast cancer. The avidin-biotin peroxidase complex method was used on formalin-fixed, paraffin-embedded tissues from 16 patients with metastatic disease. The primary antibody used in this protocol was RAP-5, an anti-p21 murine monoclonal IgG2a. p21 antigen staining was similar in the primary tumor and regional nodes from the same patient (P less than 0.05), but the staining of distant metastases was more variable. Expression of ras p21 was consistently increased in invasive components of the primary tumor as compared with intraductal tumor. In addition, a high level of p21 expression was seen in tumor emboli in lymphatics and blood vessels as compared with contiguous tumor in parenchymal tissue. Although p21 staining is present in aggressive primary breast cancers and most metastatic sites, our findings indicate that markedly enhanced p21 expression is associated with the earlier stages (invasion and dissemination) of aggressive breast cancers.

Breast Neoplasms↗

PubMed1986

Radioimmunodetection of human colon carcinoma xenografts in visceral organs of congenitally athymic mice.

The LS-174T human colon carcinoma line and A375 human melanoma line were used to establish primary tumor xenografts at three sites (subcutaneous, spleen, and kidney) in congenitally athymic mice. A monoclonal antibody (MAb) reactive with the LS-174T line, B72.3 IgG, was labeled with iodine 125, and an isotype-identical control antibody MOPC-21, was labeled with iodine 131. Labeled antibodies were injected intravenously in tumor-bearing mice, and animals were killed at varying intervals. Tumor-to-blood and tumor-to-organ ratios of MAb 72.3 indicated no significant difference at any of the three primary tumor sites in LS-174T tumor-bearing mice. The percent injected dose per gram was higher at visceral sites on day 3, but was similar on days 5 and 7 at all sites. Localization indices on all days ranged from 4 to 1 to greater than 16 to 1, confirming the specificity of the B72.3 reactivity at all sites. Athymic mice bearing tumor xenografts were scanned on day 7, and the LS-174T spleen and kidney tumors were imaged, with efficacy similar to that of the subcutaneous site. The visceral tumor model is more representative of the human disease, and may therefore be a better model for evaluation of monoclonal antibodies for radioimmunodetection and therapy for cancer in intra-abdominal organs.

Animals↗

PubMed1986

Expression of ras oncogene p21 in prostate cancer.

The major neoplastic transformation-inducing genes of human solid tumors are members of the ras oncogene family. We used an immunohistochemical assay to assess expression of both the unaltered and the mutated ras oncogene protein (p21) in normal and neoplastic prostatic cells. With the concentration of monoclonal antibody used in this study, epithelial and stromal cells from subjects with normal prostates and from 19 patients with benign prostatic hyperplasia were negative for p21 antigen. This antigen was detected in 2 of 6 prostates with Grade I carcinoma, 4 of 6 with Grade II, and all of 17 with higher grades. A semiquantitative immunohistochemical method demonstrated that expression of the p21 antigen in a carcinoma strongly correlated with nuclear anaplasia and was inversely related to the degree of glandular differentiation. However, markedly anaplastic tumors were often more heterogeneous in expression of p21 and contained areas of low staining for the antigen. Comparison of p21 antigen with tumor carcinoembryonic antigen and prostate-specific antigen demonstrated that ras p21 was the only phenotypic marker that correlated with histologic tumor grade. Thus, ras oncogene p21 may represent a new class of biologically relevant tumor markers and may be a useful adjunct to histopathologic examination in determining the prognosis of patients with prostate cancer.

Antigens, Neoplasm↗

PubMed1986

Development of a metastatic human colon cancer xenograft model in the nude mouse.

The objective of our experimental protocols was to develop a metastatic model for a human colon carcinoma xenograft in congenitally athymic nude mice. This model would be useful in evaluating the efficacy of radiolabeled monoclonal antibodies for detection and treatment of regional and distant metastases. The LS-174T human colon carcinoma line was used to establish primary subcutaneous tumors in nude mice. Mice were killed at varying time intervals to establish the incidence of spontaneous metastases. Only lung micrometastases were observed during the 2-month observation period. To increase the metastatic rate, the site of primary implantation was varied and/or surgical manipulations were performed. Excision of small primary tumors resulted in a low incidence of local recurrence and no distant metastases. However, with excision of large primary tumors, a high local recurrence rate was noted and over 30% of mice had gross metastases. Mice bearing hind footpad tumors underwent excision when tumors were at least 1 cm in size. There were no local recurrences, but by 8 weeks over 40% had large pulmonary metastases. The LS-174T tumor was also established as a primary implant in the spleen from which 10 to 15% of the mice developed liver or lung metastases. The LS-174T tumor can metastasize in the nude mice and the latter two models may prove very useful in imaging and therapy studies.

Adenocarcinoma↗

PubMed1986

A comparison of tumor-related antigens in male and female breast cancer.

A retrospective analysis was undertaken in which 15 female and 15 male breast cancers were matched by age, stage, estrogen receptor status, and histologic type. Our protocol compares male and female breast cancers for reactivity with antibodies against tumor-associated antigens known to be present on female breast cancer cells. Formalin-fixed sections of each primary tumor were reacted in the ABC immunoperoxidase assay against antibodies B72.3 and DF.3 and an antibody to the ras p21 antigen. Reactivity to B72.3 and DF.3 was similar. However, the ras p21 antigen was expressed to a significantly greater extent in female breast cancers (p = .0008). Thus, although there are similarities in antigenic phenotype of male and female breast cancers, some female breast cancers may have a different pathogenesis as demonstrated by increased amounts of a specific oncogene product.

Adult↗