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Biomedical subjects

C Cordon-Cardo

Publications and source records attributed to C Cordon-Cardo.

At least 253 records · Page 14Linked to original sources

Neuronal antinuclear antibody in sensory neuronopathy from lung cancer.

We found an antinuclear antibody highly restricted to nuclei of neurons in two patients with subacute sensory neuronopathy complicating oat cell carcinoma of the lung. Serum was tested by indirect immunofluorescence and immunoperoxidase staining. At low concentrations of antibody, only the nuclei of the neurons were stained. At high concentrations, there was also staining of the nuclei of glial cells and fetal nonneural tissues. The cytoplasm of most neurons was stained with the immunoperoxidase method.

Antibodies, Antinuclear↗

High-molecular-weight glycoproteins of human teratocarcinoma defined by monoclonal antibodies to carbohydrate determinants.

Three mouse monoclonal antibodies to distinct cell surface antigens were derived from immunizations with cells of Tera-1, a human teratocarcinoma cell line, and a membrane preparation of placental tissue. The distribution of the antigens on 165 cultured lines of various human tumors and normal cells was determined by mixed hemadsorption assays and on fresh tissues by immunofluorescence staining. K4 antigen is expressed on cell lines derived from teratocarcinomas but not on any other cultured cell tested. Normal adult colonic epithelium, some fetal tissues, and specimens of testicular teratocarcinoma were also K4 positive. K21 antigen was detected on teratocarcinoma cell lines and, at more than 100-fold lower levels, on cultures of normal and malignant kidney epithelium but not on other cultured cells. K21 expression in normal tissues is restricted to the epithelium of fetal intestine and bronchus. Other fetal tissues and all adult normal tissues tested lacked K21. A subset of teratocarcinoma specimens (5 of 8) was reactive with antibody K21. P12 antigen is represented on a wide range of cell lines and tissues, including a subset of teratocarcinomas. AbK4, AbK21, and AbP12 react with carbohydrate sequences present on high-molecular-weight glycoproteins. AbK21 and AbP12 recognize the lacto-N-tetraose and lacto-N-fucopentaose III (X-hapten) structures, respectively, whereas AbK4 reacts with a neuraminidase-sensitive determinant.

Animals↗

Effect of intravesical Bacillus Calmette-Guérin on detection of a urothelial differentiation antigen in exfoliated cells of carcinoma in situ of the human urinary bladder.

Flow cytometry was used to detect and quantify expression of a urothelial differentiation antigen (Om5) and nuclear DNA in exfoliated epithelial cells of the urinary bladder from 15 patients with nonpapillary carcinoma in situ during and after intravesical therapy with Bacillus Calmette-Guérin (BCG). Before BCG treatment exfoliated cells reacting with the mouse monoclonal antibody Om5 were found in 13 cases. Following treatment Om5 positive cells were still present in 9 cases but 4 patients who had had Om5 positive cells prior to BCG therapy no longer had detectable antigen-positive cells after therapy. Thus intravesical BCG therapy can alter detection of a urothelial differentiation antigen in exfoliated bladder epithelial cells. It is not certain whether this antigen or other differentiation antigens measured by flow cytometry will advance our present techniques for assessing effects of therapy on carcinoma in situ and other bladder tumors. However, five of nine patients showing persistence of Om5 positive cells after therapy were found to have recurrent tumor by biopsy and two others had positive cytology (median follow-up, 13 months). None of the four without detectable antigen-positive cells after therapy had clinical evidence of tumor by cystoscopy, biopsy, or cytology (median follow-up, 12 months). It now appears feasible and desirable to initiate clinical investigations of this and other differentiation antigens in combination with DNA by flow cytometry of bladder irrigation specimens.

Antigens, Neoplasm↗

Surface antigens of melanomas and melanocytes defined by mouse monoclonal antibodies: specificity analysis and comparison of antigen expression in cultured cells and tissues.

Mouse monoclonal antibodies (mAb) detecting 13 distinct systems of surface antigens on cultured melanocytes and melanomas were tested for reactivity with panels of (a) normal and malignant cultured cells; (b) normal adult and fetal tissues; and (c) specimens of metastatic melanoma and other tumor types. The objectives of this study were to compare antigen expression in cultured versus noncultured cells, to develop a panel of mAbs that identify subsets of melanomas, and to provide requisite information about antibody specificity in preparation for the use of antibodies in the diagnosis, imaging, and therapy of melanoma. Five of the melanoma surface antigens have been well characterized biochemically [GD3, chondroitin sulfate proteoglycan, HLA Class II antigens, glycoprotein of molecular weight 130,000 (gp130), and glycoprotein Mr 95,000/protein Mr 97,000 (gp95/p97)]. Three antigens have been related to melanocyte differentiation (HLA Class II, M111/M231, and M144), and six provide additional markers for subsets of cultured melanomas. mAb R24 reacts with the disialoganglioside GD3, a predominant ganglioside on cultured melanoma cells and other cells of neuroectodermal origin. A high proportion of melanoma, astrocytoma, and sarcoma tissue specimens were GD3+. In normal tissues, reactivity of mAb R24 was restricted to melanocytes, neuronal and glial cells in the central nervous system, parotid gland, adrenal medullary cells, and rare cells in the connective tissue. mAb B5 detects a chondroitin sulfate proteoglycan that is expressed by most melanoma and astrocytoma cell lines and by cultured melanocytes. Most of the melanoma and astrocytoma specimens were B5+, whereas other tumor types tested were B5-. mAb 13-17, which detects a monomorphic determinant of HLA Class II antigens, reacted with melanomas, and with a variety of other cancers, but not with normal skin melanocytes. There is considerable variability in the expression of GD3 and HLA Class II antigens in individual melanoma specimens; cotyping for these two antigens showed no evidence for coordinate expression. mAb L101 detects gp130 and mAb L235 detects gp95, antigens that are strongly expressed on a broad range of cultured cell types. In contrast to their wide distribution on cultured cells, gp130 expression in tissues was generally restricted to a subset of melanomas and some normal cells, and gp95 was detected on only a small number of melanomas. mAb M111/mAb M231 and mAb M144 define intermediate and late stage differentiation markers of cultured melanocytes and melanomas.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Distribution of the ganglioside GD3 in the human nervous system detected by R24 mouse monoclonal antibody.

Immunohistochemical staining with mouse monoclonal antibody R24 recognizing the ganglioside GD3 was used to study the distribution of GD3 in the human brain. Positive staining was primarily found in the surrounding neuropil of many neuronal groups in the brainstem and spinal cord, cerebellum, retina and dentate gyrus of hippocampus. In addition, staining was found in ependymal cells and glial processes around blood vessels and in the subependymal region.

Animals↗

Cell surface antigens of human bladder cancer defined by mouse monoclonal antibodies.

Mouse monoclonal antibodies were obtained by immunization with cultured human bladder cancer or lysates of bladder papilloma. They identify 11 distinct antigenic systems as defined by serological analysis of cultured cells and studies of antigen distribution in normal and neoplastic tissues. The most restricted of these antigens, Om5, defines a subset of bladder tumors. Om5 is not detected in normal bladder urothelium or in any other normal or malignant tissue. T101 and JP165 are also subset markers for bladder cancer that are not detected in normal tissues. T16, T43, T87, and J143 (antigens represented on many cultured cells) are found in specific areas of the normal urinary tract and in a distinctive range of other normal and malignant cell types--e.g., T16 expression in pluristratified epithelium of skin, exocervix, and esophagus. T138 antigen is also a common feature of cultured cell lines, but its expression in sections of normal tissues is restricted to endothelial cells. In contrast, T110 is poorly represented on cultured cells but can be detected in culture supernatants. Localization of T110 in normal tissues showed that it is a component of the extracellular matrix. All determinants detected by this series of antibodies are heat labile and not related to A, B, H, I, Lewis blood group antigens. Six of the antibodies immunoprecipitated glycoproteins from radiolabeled cell lysates: AbT16 (Mrs 48,000 and 42,000), AbT87 (Mr 60,000), AbT43 (Mr 85,000), AbJ143 (Mr 140,000, 120,000, 60,000), AbT43 (Mr 85,000), AbJ143 (Mr 140,000, 120,000, and 30,000), and AbT110 (Mr 240,000).

Antibodies, Monoclonal↗

Cell surface antigens of human ovarian and endometrial carcinoma defined by mouse monoclonal antibodies.

Mouse monoclonal antibodies to several cell surface antigens of human ovarian and endometrial carcinomas have been produced. The distribution of the antigens was determined by mixed hemagglutination assays on 153 normal and malignant cell cultures of various types and by immuno-peroxidase staining of frozen sections of 27 normal adult and 24 fetal tissues. Five distinct antigens were characterized. MD144 antigen was detected on only a single ovarian carcinoma cell line and has the biochemical properties of a lipid. MH55 antigen is weakly expressed on ovarian and uterine cancer cell lines but not on other cells and tissues tested. MF61 antigen was detected on an ovarian carcinoma and some renal carcinoma cell lines but not on other cell lines tested. It was also detected by immunoperoxidase staining in the noncellular follicles of the thyroid and in uterine glandular epithelial cells. This antigen also has the properties of a lipid. MF116 antigen was detected on a proportion of ovarian, uterine, renal, and bladder carcinoma and neuroblastoma cell lines and on normal kidney epithelial cell cultures but not on other cell lines tested. It was not detected in sections of any normal tissue tested using the immunoperoxidase method. MF116 was readily detected in the spent culture medium but not in detergent-solubilized extracts of metabolically radiolabeled cells. This shed antigen is a glycoprotein of Mr 105,000 and isoelectric point lower than pH 4.0. MH94 antigen was detected on a proportion of ovarian, uterine, colon, breast, lung, cervical, and pancreatic carcinoma cell lines. In tissue sections it was detected in many but not all epithelia, predominantly in secretory epithelial cells. Antibody MH94 did not immunoprecipitate a detectable antigen.

Antibodies, Monoclonal↗

Immunoanatomic dissection of the human urinary tract by monoclonal antibodies.

The immunoanatomy of the human kidney and urinary tract has been analyzed by a panel of mouse anti-human monoclonal antibodies that define specific domains and structures. The differentiation antigens detected by these monoclonal antibodies represent a series of glycoproteins characteristic of different cell types. They differ from the blood group antigens and appear to be distinct from other antigens previously described within the kidney or urinary tract. The antigens recognized by these monoclonal antibodies represent an immunohistologic dissection of the human nephron. These antibodies have a broad range of potential applications in studying embryogenesis and pathogenesis of nonneoplastic and neoplastic diseases of the human kidney and urothelium.

Antibodies, Monoclonal↗

Growth of a pure population of mouse mast cells in vitro with conditioned medium derived from concanavalin A-stimulated splenocytes.

A pure population of mast cells was obtained after 14 days of culturing mouse bone marrow cells in the presence of medium derived from concanavalin A-stimulated mouse spleen cells. The cells were characterized as mast cells by their morphologic appearance and histologic staining, by their histamine content (450 ng per 10(6) cells) and by the demonstration of IgE receptors on their surface (150,000--440,000 receptor sites per cell). The histamine content and the number of IgE receptors remained constant for at least 7 wk of culture. These mast cells could be passively sensitized to mice hybridoma IgE. They then released 43% of their histamine content upon incubation with anti-mouse hybridoma IgE.

Animals↗

Selective growth of a population of human basophil cells in vitro.

An initially homogeneous population of basophilic polymorphonuclear leukocytes was derived from human fetal liver cells grown in culture for 5-7 days. The cells were characterized as basophils by their morphology, histologic staining characteristics, and histamine content, and by the presence of IgE receptors on their surface. In this culture system the basophils were viable for up to 10 days.

Basophils↗

Genetic studies and molecular markers of bladder cancer.

Target genes implicated in cellular transformation and tumor progression have been divided into two categories: proto-oncogenes which, when activated, become dominant events characterized by the gain of function, and tumor suppressor genes which become recessive events characterized by the loss of function. Alterations in proto-oncogenes and tumor suppressor genes seem equally prevalent among human cancers. Multiple mutations appear to be required to conform the malignant phenotype. Proto-oncogenes are activated mainly by point mutations; however, amplification and translocation events are also common. Tumor suppressor genes are inactivated by an allelic loss followed by a point mutation of the remaining allele. The prototype suppressor genes are the retinoblastoma (RB) gene and the TP53 (also known as p53) genes. Recent studies have shown that inactivation of TP53 and RB occur in bladder tumors that have a more aggressive clinical outcome and poor prognosis. We will review the molecular abnormalities associated with both oncogenes and tumor suppressor genes in bladder tumors, and also discuss the potential clinical use of their detection. The implementation of objective predictive assays to identify these alterations in clinical material will enhance our ability to assess tumor biological activities and to design effective treatment regimes.

Alleles↗

Cell surface differentiation antigens of normal urothelium and bladder tumors.

Bladder cancer ranks as the third most common malignancy among men and tenth among women. Superficial transitional cell carcinomas (stage Ta, Tis, and T1) account for approximately 70-80% of these tumors, while the remaining 20-30% are invasive (T2, T3, and T4). Approximately 70% of superficial tumors will have one or more recurrences, with 25% of these expressing a higher histologic grade and 10-15% subsequently developing invasive and/or metastatic disease. The detection and prediction of tumor recurrence and/or tumor progression is crucially important if timely and appropriate therapy is to be instituted. Conventional histopathologic evaluation usually provides definitive diagnosis upon which therapeutic planning is based. However, at present there are no more reliable morphologic indicator to identify which individuals will have recurrent disease or who will progress to invasive and/or metastatic cancer. Recent advances in tumor biology have identified markers that are good candidates for clinical applications in early tumor detection, as well as for the stratification of patients with like-appearing morphological lesions with different biological and clinical behavior. The ultimate goal is to develop predictive assays that would segregate patients with high probability of failures versus patients who would be cured by localized modes of therapy.

Antibodies, Monoclonal↗

Expression of blood group antigens in bladder cancer: current concepts.

Blood group antigens are a group of carbohydrate structures bound to membrane lipids or proteins of erythrocytes and certain epithelial tissues including urothelium. The Lewis antigens are structures that are genetically and biochemically related to the ABO blood group. The ABO and Lewis blood group systems are differentially expressed in the normal urothelium of "secretors" versus "nonsector" individuals. The normal urothelium of "secretors" is rich ABH, Leb, and Ley antigens while the urothelium of "nonsecretors" does not express these antigens. Therefore, deletion of ABH antigens, commonly noted in TCC, can only be reliably ascertained in "secretor" individuals. Neoexpression of the Lewis X antigen (which is absent in normal urothelium) is noted in over 85% of TCC regardless of tumor stage and grade. Immunocytological detection of the Lewis X antigen on exfoliated bladder epithelial cells enhances the detection of urothelial tumor cells, particularly from low grade and low stage neoplasms.

ABO Blood-Group System↗

Alterations in the retinoblastoma pathway of cell cycle control in parathyroid tumors.

Mutations in proto-oncogenes and tumor suppressor genes have been associated with tumor development and/or progression in many neoplasms. It has been reported that parathyroid tumors have deletions affecting the retinoblastoma gene (RB), and overexpression of cyclin D1 (Cyc D1). The aim of the present study was to evaluate the alterations in the components of the pRB pathway in parathyroid adenomas and parathyroid aggressive tumors, including patterns of expression of pRB, Cyc D1, and p16/INK4A. Paired normal and tumor DNA from 6 parathyroid adenomas and 5 aggressive tumors were analyzed for loss of heterozygosity (LOH) at the RB locus. The expression of pRB, Cyc D1 and p16 was studied in 4 adenomas and 5 aggressive tumors. RB LOH was found in 1 of 6 adenomas, and in 1 of 2 informative aggressive tumors. Immunohistochemical analysis revealed undetectable pRB in 4 of 5 aggressive tumors and presence of pRB in all adenomas. Conversely, Cyc D1 expression was found in 3 of 4 aggressive tumors, but was undetectable in the adenomas. Expression of p16 was identified only in one aggressive tumor. Thus, alterations in the pRB pathway seem to prevail in the aggressive form of parathyroid neoplasms. Our results warrant further investigation of these cell cycle regulators in order to determine their potential role as tumor markers in parathyroid tumors.

Adult↗

Relevance of ploidy related parameters for prognosis in malignant fibrous histiocytomas.

Ploidy associated parameters were determined in 161 malignant fibrous histiocytomas (MFH) by DNA image cytometry. The rate of euploid cases in MFH with histopathological grade I was 42%, grade II 16% and grade III 6%. Univariate analyses showed that cases with a low percentage of diploid cells (< 40%) and cases with high rates of aneuploid cells between 4c and 8c (> 9%), octaploid cells (> 0%) and 16-ploid cells (> 0%), high 2.5c (> 60%) and 5c (> 16%) exceeding rates and cases with high DNA indices of the first (> 1.08) and the second (> 3.78) peak had significantly reduced survival rates. Multivariate analyses with Cox regression demonstrated that in addition to grade, only the percentage of aneuploid cells between 4c and 8c, the 5c exceeding rate and the DNA index of the first peak had independent prognostic impact. It was concluded that besides ploidy status and grading, ploidy associated parameters are suited for prediction of survival in MFH.

Adolescent↗

HER-2/neu amplification and overexpression in primary human breast cancer is associated with early metastasis.

The etiology of human breast cancer is poorly understood and no specific marker of transformation has been identified. Amplification of HER-2/neu, as reported in a comprehensive study by Slamon et al, was found to be the most powerful predictor of disease-free and overall survival after the status of the axillary lymph nodes. Our study examines the HER-2/neu oncogene in 61 primary human breast cancers at both the DNA level (by Southern blotting) and the protein level (by immunohistochemical methods). Of the 61 tumors analyzed in our study, 17 (28%) had amplification of HER-2/neu. There was no significant correlation of HER-2/neu amplification with age, tumor diameter or hormone receptor status; however, amplification and overexpression of HER-2/neu was significantly correlated with the status of the axillary lymph nodes (P = 0.02). Of 16 patients with amplification of HER-2/neu, 14 (88%) had positive regional nodes. One of the two node negative cases with amplified HER-2/neu had bone marrow micrometastasis. Overall, 16 out of 17 (94%) tumors of the patients having amplified HER-2/neu had metastatic disease at the time of diagnosis. In summary, HER-2/neu amplification is associated with early tumor dissemination in primary human breast cancer and may be a marker of poor prognosis.

Breast Neoplasms↗

Enhanced detection of bladder cancer in urine cytology with Lewis X, M344 and 19A211 antigens.

Lewis X, M344 and 19A211, all glycoprotein antigens associated with bladder tumors, were evaluated in urine cytologic specimens from 52 patients with transitional cell bladder neoplasms and from 12 controls. Forty-three of 52 patients had a tumor on a concurrent bladder biopsy, while 9 of 52 patients had a negative biopsy. Of the 43, 27 (62.8%) had positive or suspicious cytology, 35 (81.4%) had positive immunocytochemical reactions with at least one antibody, and 36 (83.7%) had either cytologic or immunocytochemical abnormalities. Of the 15 patients with a low grade tumor (papilloma or grade 1 transitional cell carcinoma), 14 (93.3%) had positive immunohistochemical findings, while 6 (40%) had recognizable abnormal cells on routine cytology. Of 28 patients with a high grade tumor, 21 (75%) had positive immunohistochemical findings, while 21 (75%) had abnormal cytology. Staining of rare epithelial cells was seen in 2 of 12 control cases (specificity, 83.3%). Immunocytochemistry with antibodies to tumor-associated antigens can enhance the cytologic detection of exfoliated low grade bladder epithelial tumor cells.

Antibodies, Monoclonal↗