Biomedical subjects

K R Cho

Publications and source records attributed to K R Cho.

69 records · Page 4Linked to original sources

PubMed1991

Evidence supporting exclusion of the DCC gene and a portion of chromosome 18q as the locus for susceptibility to hereditary nonpolyposis colorectal carcinoma in five kindreds.

Hereditary non-polyposis colorectal carcinoma (HNPCC) syndrome is characterized by early onset and multiple cancers of predominantly the proximal colon and occasionally other organs. The mode of transmission is compatible with autosomal dominant inheritance but the location and characteristics of the putative susceptibility gene are unknown. We performed linkage analyses with the aim of proving or excluding the existence of a susceptibility locus on 18q. This hypothesis was based on the frequent involvement of the DCC gene in colorectal carcinoma and on the previously reported linkage between HNPCC and the Kidd blood group locus (JK) also on 18q. Seven HNPCC families were tested with eight polymorphisms, including three from within DCC. The DCC locus could be excluded as the HNPCC susceptibility locus in five families in which the two point logarithm-of-odds scores were -3.66, -3.63, -4.12, -7.90, and -3.74 at the recombination fraction of 0.00. In the remaining two families linkage could be neither excluded nor confirmed. The added pairwise logarithm-of-odds score for all seven families was -22.65 at the recombination fraction of 0.00. Multipoint analyses of linkage in the seven families suggested exclusion of some 60 cM in the region DCC-D18S18-D18S22-D18S7 as the site for HNPCC susceptibility locus. In addition to DCC, the excluded portion comprises JK.

Adult↗

PubMed1991

Scrambled exons.

Using a sensitive assay for RNA expression, we identified several abnormally spliced transcripts in which exons from a candidate tumor suppressor gene (DCC) were scrambled during the splicing process in vivo. Cloning and sequencing of PCR-amplified segments of the abnormally spliced transcripts showed that exons were joined accurately at consensus splice sites, but in an order different from that present in the primary transcript. Four scrambled transcripts were identified, each involving a different pair of exons. The scrambled transcripts were found at relatively low levels in a variety of normal and neoplastic cells of rodent and human origin, primarily in the nonpolyadenylated component of cytoplasmic RNA. These results demonstrate that the splicing process does not always pair sequential exons in the order predicted from their positions in genomic DNA, thus creating a novel type of RNA product.

Amino Acid Sequence↗

PubMed1991

Dermatofibrosarcoma protuberans of the vulva.

Dermatofibrosarcoma protuberans of the vulva is an uncommon low-grade sarcoma of dermal origin. Although wide local excision is the treatment of choice, microscopic tumor projections beyond the central tumor nodule explain the tumors' propensity for local recurrence. Frozen sections of margins may be useful to ensure complete resection. The following report contributes two additional patients with this uncommon neoplasm. Notably, one of these two had a fibrosarcomatous area within the dermatofibrosarcoma protuberans. This is the second reported case of a fibrosarcoma arising in a dermatofibrosarcoma protuberans of the vulva.

Adult↗

PubMed1990

Relationship of severe dysplasia to stage A (incidental) adenocarcinoma of the prostate.

Totally embedded radical prostatectomy specimens and their transurethral resections (TUR) from 32 Stage A (incidental) carcinomas were studied for severe dysplasia. These cases were selected to be representative of the majority of Stage A cancers and hence consisted of cases with predominantly low-grade centrally located tumor. In 43.75% of the cases, severe dysplasia was minimal in amount, 43.75% intermediate, and 12.5% extensive. Severe dysplasia was spatially associated with the main tumor in only 31.25% of cases. In 43.75% of the cases all of the severe dysplasia was isolated (i.e., not adjacent or intermingled with any carcinoma). Whereas this study confirms one general association between severe dysplasia and the presence of carcinoma within the gland, the data do not strongly support the concept that the dysplasia is a direct precursor to centrally located low-grade Stage A carcinomas. From a practical viewpoint, severe dysplasia in the TUR was seen in 15.6% of cases and was not predictive of the amount of tumor within the gland.

Adenocarcinoma↗

PubMed1990

Relationship of severe dysplasia to stage B adenocarcinoma of the prostate.

Severe dysplasia was studied in totally embedded radical prostatectomy specimens from 40 Stage B, intermediate-grade prostate cancers. All 40 cases had severe dysplasia which varied in amount (extensive in 35% of cases; intermediate in 55%; minimal in 10%). Severe dysplasia was predominantly concentrated in peripheral and posterior regions of the gland. Those cases with extensive severe dysplasia had more multifocal small cancers (14.6/case) compared with cases with intermediate (7.5/case) or minimal severe dysplasia (5.5/case). Most dominant tumor nodules had some intermingled severe dysplasia, and in 30% of the dominant tumor nodules, intermingled severe dysplasia occupied between 10% and 25% of the tumor nodule. Severe dysplasia was located next to the dominant tumor nodule in all cases. Nineteen percent of dominant tumor nodules had extensive adjacent severe dysplasia ranging from 5 to 14 mm in maximum diameter, showing that the potential exists for needle biopsy of prostate cancers to obtain only severe dysplasia. These data show a close relationship between severe dysplasia and Stage B cancers. In contrast, centrally located low-grade multifocal cancers, as seen in Stage A (incidental) carcinoma, had a significantly weaker association with severe dysplasia as compared with central, intermediate-grade, multifocal tumors or peripheral multifocal tumors of any grade.

Adenocarcinoma↗

PubMed1990

Identification of a chromosome 18q gene that is altered in colorectal cancers.

Allelic deletions involving chromosome 18q occur in more than 70 percent of colorectal cancers. Such deletions are thought to signal the existence of a tumor suppressor gene in the affected region, but until now a candidate suppressor gene on this chromosomal arm had not been identified. A contiguous stretch of DNA comprising 370 kilobase pairs (kb) has now been cloned from a region of chromosome 18q suspected to reside near this gene. Potential exons in the 370-kb region were defined by human-rodent sequence identities, and the expression of potential exons was assessed by an "exon-connection" strategy based on the polymerase chain reaction. Expressed exons were used as probes for cDNA screening to obtain clones that encoded a portion of a gene termed DCC; this cDNA was encoded by at least eight exons within the 370-kb genomic region. The predicted amino acid sequence of the cDNA specified a protein with sequence similarity to neural cell adhesion molecules and other related cell surface glycoproteins. While the DCC gene was expressed in most normal tissues, including colonic mucosa, its expression was greatly reduced or absent in most colorectal carcinomas tested. Somatic mutations within the DCC gene observed in colorectal cancers included a homozygous deletion of the 5' end of the gene, a point mutation within one of the introns, and ten examples of DNA insertions within a 0.17-kb fragment immediately downstream of one of the exons. The DCC gene may play a role in the pathogenesis of human colorectal neoplasia, perhaps through alteration of the normal cell-cell interactions controlling growth.

Alleles↗

PubMed1989

Leiomyoma of the uterus with multiple extrauterine smooth muscle tumors: a case report suggesting multifocal origin.

A 17-year-old woman underwent hysterectomy for removal of a "mitotically active" (six to seven mitoses per 10 high-power fields) yet otherwise benign-appearing cellular smooth muscle tumor. Eleven years later, she developed multiple histologically benign smooth muscle tumors in the posterior mediastinum, deep soft tissues of the neck, paravertebral region, incisional scar, and mesentery. The distribution and histologic appearance of the tumors, as well as the protracted clinical course, suggest multifocal origin rather than widespread metastases from a low-grade uterine leiomyosarcoma. This case raises the possibility that some similar cases reported as so-called benign metastasizing leiomyoma may be more satisfactorily explained by the concept of multifocality.

Adolescent↗

PubMed1989

Morphometric measurement of tumor volume and per cent of gland involvement as predictors of pathological stage in clinical stage B prostate cancer.

Although tumor volume is an important factor in predicting prognosis in carcinoma of the prostate, direct and accurate estimation of tumor volume is not practical clinically at present because the tumor may not always be palpable (stage A) and when palpable it is difficult to estimate volume in 3 dimensions. For this reason the clinical staging of prostate cancer currently is based on estimations of the per cent of gland involved with tumor: in stage A by per cent of tissue involved with cancer and in stage B by digital palpation (less than 1 lobe, 1 lobe and 2 lobes). In stage A prostate cancer the per cent of the specimen involved with tumor and the volume of tumor have been shown to correlate with tumor progression. Our study was designed to determine if either or both of these morphometric factors would be good predictors of pathological stage in stage B prostate cancer. We analyzed 56 step-sectioned radical prostatectomy specimens: 28 without capsular penetration, 15 with capsular penetration only and 13 with seminal vesicle involvement. The per cent of gland involved with tumor (correlation coefficient 0.67, p less than 0.001) and tumor volume (correlation coefficient 0.55, p less than 0.001) correlated well with pathological stage. Stepwise linear regression showed that the combination of the per cent of gland involved with tumor and the total Gleason grade was statistically the best predictor of pathological stage.

Adult↗

PubMed1989

Malignant rhabdoid tumor of the uterus.

Rhabdoid tumors are highly malignant neoplasms resembling rhabdomyosarcomas, which most commonly occur in the kidney in young children. Several cases of extrarenal malignant rhabdoid tumors have been described, many in adolescents and young adults. We describe a 46-year-old woman with a primary uterine tumor that has the histologic, immunohistochemical, and ultrastructural characteristics of a malignant rhabdoid tumor. To our knowledge, this is the first report of a rhabdoid tumor in this site. Furthermore, this woman's age expands the range for which pathologists and clinicians should consider this diagnosis, even in extrarenal sites.

Female↗

PubMed1989

Lipomeningioma: report of three cases and review of the literature.

Lipomeningioma is a benign tumor of the meninges that contains mature adipose tissue. It demonstrates fat density on computed tomographic scan and mixed signal intensities on magnetic resonance imaging scan. Although the pluripotential nature of the mesenchymal cell has long been recognized, only a single case with this diagnosis has been documented in the literature to date. Three patients with this diagnosis seen at the Johns Hopkins Hospital during the last two years are presented, and the literature is reviewed.

Aged↗

PubMed1988

Primitive rhabdomyosarcoma presenting with diffuse bone marrow involvement: an immunohistochemical and ultrastructural study.

We recently identified three cases of primitive rhabdomyosarcoma (PRMS) presenting with diffuse bone marrow infiltration but inconspicuous soft tissue primaries, referred to The Johns Hopkins Hospital (JHH) as acute leukemia. In each case, the diagnosis of rhabdomyosarcoma was established using immunohistochemical staining and electron microscopy. Ultrastructural examination of tumor cells showed a feltwork of thin filaments, discontinuous basal lamina, glycogen, and primitive cell junctions without cell processes or neurosecretory granules. This presentation of PRMS may be more common than recognized, since it can be readily misdiagnosed as a hematopoietic tumor. While positive staining for muscle-specific actin, desmin, myoglobin, or other markers of skeletal muscle differentiation may be diagnostic, negative staining is inconclusive, requiring recognition of the "minimal" ultrastructural findings of primitive rhabdomyosarcomas.

Actins↗

PubMed1987

Growth-related elevations of DNA topoisomerase II levels found in Dunning R3327 rat prostatic adenocarcinomas.

The relationship between DNA topoisomerase II expression and mammalian cell proliferation has been evaluated by determining enzyme levels in normal and neoplastic rat prostate tissues. By activity assay and by immunoblot analysis using anti-topoisomerase II antiserum, topoisomerase II levels were found to be elevated in both the Dunning R3327-H and the Dunning R3327-G rat prostatic adenocarcinomas over levels assayed in the normal rat dorsal prostate. Immunohistochemical studies using the antitopoisomerase II antiserum revealed that a greater fraction of nuclei contained detectable levels of topoisomerase II in tissue sections prepared from each of the Dunning tumors than in rat dorsal prostate tissue sections. The Dunning R3327-H and R3327-G tumors grow at different rates in vivo (J. T. Isaacs and D. S. Coffey, Clin. Oncol., 2: 479-498, 1983). When measured topoisomerase II levels were compared to known growth parameters for each of the tissues studied, topoisomerase II expression was found to be correlated with tissue growth rate.

Adenocarcinoma↗

PubMed1987

Metastatic prostatic carcinoma to supradiaphragmatic lymph nodes. A clinicopathologic and immunohistochemical study.

We identified 26 cases of metastatic prostatic carcinoma in supradiaphragmatic lymph nodes from 1972-1987. All involved nodes (15 supraclavicular, eight cervical, two axillary, and one mediastinal) were taken from the left side. Of those cases with available data, serum acid phosphatase was normal in five of 21 (24%). Seven of 20 (35%) had no evidence of bone metastases. Rectal examination was normal in eight of 19 cases (42%). While seven cases had a history of prostate cancer, the rest presented with enlarged nodes alone or with simultaneous urinary obstructive symptoms. Eighteen patients died following node biopsy (mean 19.8 months, range 1-46 months). Twenty-two of 26 metastases were high grade and often were not histologically suggestive of prostate carcinoma. In general, immunohistochemical staining for prostate-specific acid phosphatase (PSAP) was more intense than for prostate-specific antigen (PSA), in contrast to several other reports using these antisera. Metastatic prostate carcinoma should be ruled out by using immunoperoxidase for PSA and PSAP in all men over 45 presenting with carcinoma of unknown primary origin in left-sided supradiaphragmatic lymph nodes, even in the absence of bony disease, elevated serum acid phosphatase (SAP), abnormal rectal examination, and a histologic picture suggesting prostate carcinoma.

Aged↗

PubMed1984

Monocyte receptors for the Fc portion of IgG are increased in systemic lupus erythematosus.

Defective clearance of IgG-sensitized particles has been documented in systemic lupus erythematosus (SLE). This defect may be of pathogenetic significance because it allows the prolonged circulation of endogenous immune complexes with subsequent tissue deposition. To assess the possible contribution of a genetically determined defect in phagocyte Fc-IgG receptor expression or immune complex saturation of Fc-IgG receptors to impaired clearance, we used a well-characterized monomer binding assay to quantitate monocyte Fc-IgG receptors in normal controls and in 26 patients with SLE. Mean monocyte Fc-IgG receptor numbers were increased in both male and female SLE patients relative to normal controls. Increasing receptor numbers correlated positively with increasing clinical disease activity and increasing titers of antibody to native, double-stranded DNA. No significant correlation was found between any single disease symptom, organ system involvement, drug therapy, antigenic C3 levels, or immune complex levels and receptor number. A negative correlation was noted between Fc-IgG receptor binding affinity constants in SLE patients and clinical disease activity, but none of the observed affinity constants fell outside the 95% confidence normal range, and the mean affinity constants for patients both with and without active disease were not significantly different from controls. Our results are inconsistent with a genetically determined defect in Fc-IgG receptor elaboration by mononuclear phagocytes, and suggest that simple immune complex saturation does not underlie abnormal Fc-IgG-mediated clearance in SLE.

Adult↗

PubMedDate not supplied

DCC: linking tumour suppressor genes and altered cell surface interactions in cancer?

The Deleted in Colorectal Cancer (DCC) gene is a candidate tumour suppressor gene encoding a neural cell adhesion molecule-like transmembrane protein. Over the last year, data supporting DCC inactivation in multiple tumour types have continued to accumulate. Functional studies suggest that DCC may participate in signalling pathways that regulate cell proliferation and/or differentiation, two cellular processes that often go awry during tumorigenesis.

Cell Differentiation↗