Biomedical subjects

S Silverberg

Publications and source records attributed to S Silverberg.

13 recordsLinked to original sources

PubMed1997

K-ras and p53 mutations in aberrant crypt foci and colonic tumors from colon cancer patients.

Aberrant crypt foci (ACF) are microscopic lesions which can be detected, after methylene blue staining, in the overtly normal looking colonic mucosa of cancer patients. ACF have been postulated to be precursor lesions which develop into colorectal cancer. Mutations of K-ras and p53 are two important genetic events implicated in colon carcinogenesis. Mutations in K-ras are detectable at earlier stages, while mutations in p53 are detectable at later stages of colon carcinogenesis. Our objective was to compare the nature of genetic alterations in K-ras (codon 12 and 13) and in p53 (exon 4-9) between ACF and corresponding colonic tumors from cancer patients. ACF with > or =20 crypts/focus were harvested from overtly normal looking colonic mucosa of cancer patients at a distance of (approx.) 5 cm from the site of colonic tumors. The colonic tumors and ACF samples were compared for K-ras codon 12 and 13 base pair sequence, using DNA sequencing and for p53 (exon 5-9) allelic types, using PCR-SSCP and DNA sequencing. The results demonstrated a perfect correlation in terms of the type of K-ras allele (wild or mutated) between the ACF (> or =20 crypts/focus) and corresponding colonic tumors in 11/13 cancer patients. Analyses of p53 mutations demonstrated the presence of p53 mutations in colonic carcinomas from 10/13 patients. However, p53 mutations could be detected in an ACF from only 1/13 patient. The results provides further evidence to the role of ACF as precursor to colon cancer. The presence of an identical K-ras as well as p53 mutation in an ACF and the corresponding colonic carcinoma in a patient suggests the possibility of existence of ACF that may be at a more advanced stage in the sequence of colonic tumorigenesis than others. In conclusion, the results suggest that a subset of ACF with higher multiplicity might be considered more likely to progress to more advanced lesions and should be explored as markers of colon cancer risk.

Adenoma↗

PubMed1991

"Ratchet-type" marginal fracture of the radial head with locked anterior dislocation. A case report.

Locked anterior dislocation of the superior radioulnar joint occurred in a 26-year-old man. The configuration of the associated radial head fracture maintained the locked position and predisposed to recurrence after open reduction. Radial head excision was necessary to resolve the problem. Both medial ligament repair and a radial head prosthesis were necessary to stabilize the elbow.

Adult↗

PubMed1990

Protooncogene amplification and tumor ploidy in human ovarian neoplasms.

DNA from 24 ovarian tumors, including 16 carcinomas, was examined for amplification of the proto-oncogenes c-myc, int-2, and rc-erbB-2. All cases of carcinoma were also examined by flow cytometry for DNA ploidy and cell cycle analysis, and eight cases of carcinoma were examined for estrogen and progesterone receptors. Protooncogene amplification was not detected in the DNA of benign ovarian neoplasms, or of ovarian carcinomas with low malignant potential. Amplification of c-myc was detected in six of 12 cases of invasive carcinoma, int-2 amplification was present in one case, and c-erbB-2 amplification was not detected in any case. Among the seven cases evidencing protooncogene amplification, three cases showed aneuploidy in tumor DNA, while four showed diploidy. Two cases which showed aneuploidy in tumor DNA did not demonstrate any degree of protooncogene amplification. Protooncogene amplification was frequently associated with morphologic nuclear anaplasia and high mitotic count. Six of the seven cases demonstrating c-myc or int-2 were of the serous type or showed some degree of serous differentiation, while none of the four cases of purely mucinous carcinoma had evidence of amplification. While the total number of cases in the study was limited, it would appear from the trend demonstrated by the data that protooncogene amplification (particularly c-myc) may be involved in the pathogenesis of aggressive common epithelial tumors of the ovary.

Adenocarcinoma, Mucinous↗

PubMed1988

Preparation and characterization of antibodies to the urinary fragment of the human chorionic gonadotropin beta-subunit.

hCG is a glycoprotein hormone composed of two dissimilar subunits (alpha and beta) and is normally synthesized by trophoblastic tissue. Its measurement by immunoassay is widely employed as a test for pregnancy, but can be complicated by cross-reactivity with human (h) LH. Immunoassays based on the beta-subunit of hCG have been employed to decrease this cross-reactivity with hLH, but when these assays are used with urine specimens, the antibodies employed also detect a fragment of hCG beta, which can lead to significant differences in measurement. To overcome these problems, we have developed a series of monoclonal antibodies to the beta fragment of hCG recovered from pregnancy urine. Some of the antibodies that bind to this beta fragment are directed to a region of hCG beta that is different from the epitopes recognized by antibodies raised against the intact beta-subunit. The new epitopes available in the hCG beta fragment form the basis for novel immunoassays. These beta fragment antibodies are used in conjunction with other antibodies, directed to different epitopes of the hormone, to produce a series of immunoradiometric assays that can discriminate among intact hormone, free hCG beta, and hCG beta fragment. The hCG beta fragment antibodies described herein have affinities between 10(9) and 10(11) M-1 for the beta fragment and exhibit varying degrees of discrimination between the hCG beta fragment, the beta-subunits of hCG and hLH, and intact hCG and hLH.

Animals↗

PubMed1986

Reliability of endometrial cancer diagnoses in a Swedish Cancer Registry--with special reference to classification bias related to exogenous estrogens.

In this study, various qualitative aspects of endometrial cancer diagnoses were critically evaluated regarding cases included in the Swedish Cancer Registry from the Uppsala Health Care Region. By comparing the number of such cases in the registry with cases reported directly from the departments of pathology and of gynecological oncology in the same region, it was found that approximately 5% of all incident cases had not been notified to the registry. An independent histopathological review of the original specimens showed that almost 9% of the cases did not represent an endometrial neoplastic lesion, the majority of these being reclassified as uterine sarcoma. The review also revealed the problem of a diagnostic bias that might arise in connection with estrogen exposure, in that a significantly higher proportion of the cases observed in a cohort of women who had received estrogen prescriptions were reclassified as a premalignant endometrial lesion than of the cases from the background population without estrogen exposure (33% versus 10%). Additional independent reviews of cases showing discordant diagnoses in the primary review indicated variability in diagnostic criteria among pathologists. It is concluded that when cancer registry data are employed in epidemiological studies of endometrial cancer, the use of additional sources of case recruitment is desirable in order to obtain a complete material; also that an independent histopathological review is necessary to standardize diagnostic criteria and thereby to avoid a classification bias.

Estrogens↗

PubMed1985

A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study.

After hysterectomy, 156 evaluable patients with stage I (limited to the corpus) or stage II (limited to the corpus and cervix) uterine sarcomas were randomly assigned to adjuvant chemotherapy with Adriamycin (Adria Laboratories, Columbus, Ohio) for six months or to no further treatment. Pelvic irradiation (external or intracavitary) was optional before randomization. Of 75 patients receiving Adriamycin, 31 have suffered recurrences compared with 43 of 81 receiving no adjuvant chemotherapy. This difference is not statistically significant. Moreover, there is no difference in progression-free interval or survival. The optional radiotherapy did not influence the outcome although there was a suggestion that vaginal recurrence was decreased by pelvic radiotherapy. The recurrence rates in specific cell types (leiomyosarcoma, homologous mixed mesodermal sarcoma, or heterologous mixed mesodermal sarcoma) were not significantly different although the pattern of recurrence differed, with pulmonary metastases being more common in leiomyosarcoma and extrapulmonary recurrence being more common in mixed mesodermal sarcoma. The outcome with respect to chemotherapy was not altered even after adjusting for maldistribution of cases. Thus, we could not show a benefit for this dose schedule of Adriamycin as adjuvant treatment for uterine sarcomas.

Adolescent↗

PubMed1978

Scintigram in cortical blindness (Anton's syndrome).

Anton's syndrome or cortical blindness consists of blindness, denial of blindness and at times confabulation. Despite the fact that the patient is completely blind, a persistent denial of inability to see is noted and is sometimes accompanied by visual hallucinations. We present a case report and scintigraphic study.

Aged↗

PubMed1977