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D Grignon

Publications and source records attributed to D Grignon.

At least 55 records · Page 3Linked to original sources
PubMed1996

Human prostate carcinoma cells express functional alphaIIb(beta)3 integrin.

The integrin alphaIIb(beta)3 was initially believed to be expressed only in cells from the megakaryocytic lineage, such as platelets or HEL cells. In this study, we report for the first time that human prostate carcinoma PC-3 and DU-145 cells express alphaIIb(beta)3. Reverse transcription-PCR from HEL (positive control), PC-3, and DU-145 cells amplified a predicted alphaIIb fragment that hybridized to the full-length alphaIIb cDNA probe. DNA sequencing of the PCR fragments revealed 100% sequence homology to the corresponding extracellular domain of platelet alphaIIb but minimal sequence homology to integrins (alpha)v or a5. An RNase protection assay was used to confirm the results from reverse transcription-PCR. An antisense riboprobe to alphaIIb mRNA hybridized to total RNA from HEL, PC-3, and DU-145 cells, suggesting that alphaIIb mRNA is transcribed in these tumor cells. In situ hybridization on surgical specimens from human prostate tumor tissue stained positive with an antisense riboprobe to alphaIIb mRNA. The expression of alphaIIb(beta)3 protein in PC-3 and DU-145 cells was demonstrated by Western and dot blotting and flow cytometry with monoclonal antibodies (mAbs) to alphaIIb (MAB 1990), beta3, and alphaIIb(beta)3 (AP-2). A protein kinase C activator, phorbol 12-myristate 13-acetate, increased the adhesion of PC-3 cells to PAC-1, a mAb specific to the high-affinity state of alphaIIb(beta)3, by more than 80-fold. The invasion of DU-145 cells through a reconstituted basement membrane was blocked 40-50% by mAbs AP-2 or PAC-1. These data collectively suggest that: (a) prostate tumor cells express alphaIIb(beta)3; (b) surface expression of alphaIIb(beta)3 integrin is regulated by protein kinase C; and (c) mAbs to this receptor inhibit invasion of prostate cancer cells through a reconstituted basement membrane.

Humans↗
PubMed1996

A gene from human chromosomal band 3p21.1 encodes a highly conserved arginine-rich protein and is mutated in renal cell carcinomas.

We have identified a gene, called ARP for Arginine-rich protein, in human chromosomal band 3p21. It is approximately 600 Kb telomeric to the ACY1 locus (Miller et al., 1989) and encodes a previously unidentified 234 amino acid long, highly basic protein. This gene is highly conserved at the DNA and RNA level. It is found in all species including hamster, rat, mouse, bovine and yeast. We have detected a point mutation (ATG50 to AGG) or deletion of ATG50 in 10 of 21 sporadic renal cell carcinomas. The mutable region is in an imperfect trinucleotide repeat in the coding region which is non-polymorphic among 50 normal individuals examined. The point mutation (ATG50 to AGG) or deletion of codon 50 removes a methionine and increases the stretch of arginines encoded by the AGG repeats in the ARP gene.

Amino Acid Sequence↗
PubMed1996

Conformal mixed neutron and photon irradiation in localized and locally advanced prostate cancer: preliminary estimates of the therapeutic ratio.

PURPOSE: To determine the incidence of chronic toxicity and the probability of biochemical and histologic complete response among patients with nonmetastatic prostate cancer, treated with three dimensional (3D) conformal mixed neutron and photon irradiation. METHODS AND MATERIALS: Between November 1991 and December 1994, 151 patients with prostate cancer were entered in three prospective dose-finding studies of conformal mixed neutron and photon irradiation. Patients with low stage, low to intermediate grade prostate cancer (T1-2NXM0, Gleason Score < or = 7) received 38 Photon Gy (PhGy) plus 9 (51 patients) or 10 (53 patients) Neutron Gy (NGy) to the prostate and seminal vesicles. Forty-seven patients with locally advanced prostate cancer (T3-4 N0-1 M0 and/or Gleason Score > or = 8) received 15 NGy + 18 PhGy to the prostate and seminal vesicles and 9 NGy + 18 PhGy to the pelvic lymph nodes. RESULTS: The median follow-up was 16 months (range: 3-30 months). There was no Grade 3-5 GI or GU toxicity recorded. At 20 months, the actuarial rates of Grade 2 GI morbidity were 6 and 29% for the 9-10 and 15 NGy protocols, respectively (p = 0.07). At 20 months, the incidences of Grade 2 GU morbidity were 4 and 16%, respectively (p = 0.08). Stiffness in flexing or abducting the hips was seen in 20 and 42% of patients receiving 9-10 and 15 NGy, respectively (p = 0.01). Potency was maintained in 65% of all patients. Among patients with an initial PSA < or = 10, 100% had a 12-month PSA < 2 and 78% < 1 ng/ml. Negative postradiation biopsies were seen in 30% of patients 6 months, 79% at 12 months, and 84% of patients at 18 months. CONCLUSION: The use of conformal mixed neutron and photon irradiation has been well tolerated with no severe bladder or rectal complications observed. However, because of the enhanced toxicity seen with 15 NGy, the current maximum dose levels of neutron irradiation have been limited to 11 NGy.

Adenocarcinoma↗
PubMed1994

Prostatic cryotherapy: ultrasonographic and pathologic correlation in the canine model.

OBJECTIVES: Cryotherapy of the prostate has been reintroduced clinically due to improved ultrasound guidance and cryotechnology. The purpose of this canine feasibility study was to assess the accuracy of transrectal ultrasound (TRUS) in monitoring iceball progression with histologic correlation. METHODS: Six mongrel dogs received cryotherapy to the entire prostate and were observed for selected periods of 1 day to 12 weeks with TRUS follow-up. Some technical limitations of the canine model prohibited complete comparison with techniques currently used in humans. RESULTS: TRUS monitoring of posterior iceball progression proved to be highly accurate and correlated with subtotal necrosis of the rectal wall, sparing the mucosal layer with millimeter accuracy. The prostate was completely necrotic in three of six dogs. Scattered residual glands remained at the distal apex in one dog and in the posterolateral periphery of a larger-volume prostate. Cryotherapy missed the prostate in one dog due to pelvic hematoma formation and poor TRUS visualization. Without adequate urethral warming, central sloughing was noted in chronic animals. Histologic examination demonstrated hemorrhagic infarction with subsequent ingrowth of transitional epithelium from the urethra producing re-epithelialization of glandular spaces along the residual collagenous architecture. CONCLUSIONS: Accurate TRUS monitoring of prostate cryotherapy allows thorough yet careful extension of the iceball through the posterior aspect of the prostate. Unique histologic changes may account for the unremarkable TRUS appearance following cryotherapy, as well as some of the benign, "atypical" glands seen on follow-up biopsies in humans.

Animals↗
PubMed1994

High frequency of mutator phenotype in human prostatic adenocarcinoma.

Mutator phenotype of nucleotide repeats has been implicated to be involved in human cancer and other diseases. This type of instability may be the direct result of DNA replication and/or repair errors. To examine mutator phenotype during the development of human prostate cancer, we undertook this study to screen 57 patients with prostatic adenocarcinoma for possible mutator phenotype at 18 microsatellite marker loci on 12 chromosomes (3p, 5q, 6p, 7p, 8p, 10q, 11p, 13q, 16q, 17p, 18q and Xq). Overall, in 37 of 57 patients, we have found positive mutator phenotype in at least one of the loci analysed. A significantly greater number of cases were found to be positive for this phenotype among the poorly differentiated than the moderately- and well-differentiated prostatic adenocarcinomas. Our data suggest that mutator phenotype may play an important role in the development and progression of human prostate cancer.

Adenocarcinoma↗
PubMed1993

Frequent loss of expression and loss of heterozygosity of the putative tumor suppressor gene DCC in prostatic carcinomas.

The putative tumor suppressor gene DCC has been shown to be frequently lost or expressed at low levels in colorectal, gastric, pancreatic, and esophageal carcinomas. In the present study, the DCC gene and its mRNA expression in human and rat prostatic carcinoma cells as well as in prostatic carcinoma tissues were examined by reverse transcriptase-polymerase chain reaction and polymerase chain reaction-loss of heterozygosity. The DCC gene was present and expressed in normal prostatic cells. However, its expression was decreased or undetectable in all prostatic carcinoma cells from either humans (4 cell lines) or rats (5 cell lines). In patients, 12 of 14 cases (86%) showed reduced DCC expression and 5 of 11 informative cases (45%) showed loss of heterozygosity at the DCC locus. These results demonstrate that loss of DCC expression and loss of heterozygosity at the DCC locus are a frequent feature of prostatic carcinoma cells.

Alleles↗
PubMed1993

Atypical adenomatous hyperplasia of the prostate: morphologic criteria for its distinction from well-differentiated carcinoma.

Atypical adenomatous hyperplasia (AAH) is a localized proliferation of small glands within the prostate that may be mistaken for carcinoma. To determine the diagnostic criteria for separating AAH from carcinoma, seven observers independently evaluated 54 selected lesions from 44 transurethral resection specimens. Three patterns of glandular proliferation were observed, all arising in association with nodular hyperplasia: AAH (38 foci), atypical small acinar proliferation of uncertain significance (eight foci), and well-differentiated carcinoma (eight foci). Of 24 architectural and cytologic features evaluated, the following were useful in separating these three patterns: variation in nuclear size (14%, 22%, and 25%, respectively), mean nucleolar diameter (0.69 micron, 1.43 microns, and 1.78 microns, respectively), largest nucleolar diameter (mean, 1.66 microns, 2.71 microns, and 2.81 microns, respectively), percentage of nucleoli greater than 1 micron in diameter (17.6%, 58.1%, and 77.5%, respectively), crystalloids within suspicious glands (16%, 13%, and 75%, respectively), luminal basophilic mucinous secretions, infiltrative borders, discontinuity of the basal cell layer in AAH (compared with complete absence in carcinoma; shown with basal cell-specific anti-keratin monoclonal antibody 34 beta E12 immunostaining), and intact basement membrane in AAH (compared with discontinuity in carcinoma; shown with type IV collagen immunostaining). Features that could not reliably separate AAH from carcinoma included lesion shape, circumscription, multifocality, average gland size, variation in gland size and shape, nuclear shape, chromatin pattern, and amount and tinctorial quality of cytoplasm. Although the biologic significance of AAH is uncertain, its light microscopic appearance and immunophenotype allow it to be distinguished from carcinoma in most cases.

Adenoma↗
PubMed1991

Association of germ cell tumors and Hodgkin's disease.

Two patients presented with synchronous Hodgkin's disease and testicular germ cell neoplasms. Both patients are in complete remission following treatment with multidrug chemotherapy and radiation therapy. Despite epidemiologic similarities between Hodgkin's disease and testicular cancer, only 13 cases of their association in the same patient have been reported in the literature, and in all those instances the tumors occurred metachronously. However, the very rare occurrence of synchronous presentation suggests a possible common pathogenetic factor in our 2 patients.

Adult↗
PubMed1988

Partial nephrectomy using the Nd:YAG laser: a comparison of the 1.06 mu and 1.32 mu lasers employing different delivery systems.

A comparative study of the 1.06 mu and the 1.32 mu Nd:YAG laser using a variety of delivery systems (focusing handpiece, freehand GI quartz fiber, or frosted laser scalpel) was undertaken to determine the usefulness of these modalities in performing partial nephrectomies in dogs. Variables evaluated included total operative time, total joules expended, estimated amount of blood loss, and extent of renal tissue damage. The contact laser scalpel provided the greatest precision and speed, but no hemostasis, and is therefore inappropriate for parenchymal renal surgery. Evaluation of the other delivery systems showed no discernible differences in the extent of renal damage that could be attributed to either wavelength or wattage used. The usual depth of acute renal damage ranged from 1.0 mm to 1.8 mm when the tissue was fixed immediately after completing the polar nephrectomy, but the damage had extended to 3.0 mm when tissue was examined after 6 weeks. No consistent differences in extent of cellular damage could be demonstrated between the renal cortex and medulla. The lens system inherent in the focusing handpiece limited the total power (60 watts) that could be employed and surgery proceeded at a slower pace and required a greater expenditure of energy. Likewise, the maximal power that could be applied using the 1.32 mu laser was 25 watts and surgery also proceeded at a slower pace.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum Silicates↗
PubMed1988

Denudation of the entire mucosa of the canine urinary bladder using the neodymium:YAG laser with the MTR 1.5 contact probe.

Although the procedure of mucosal stripping or denudation of the urinary bladder was developed over 25 years ago to treat the potentially neoplastic mucosa in patients with low-grade superficial transitional cell carcinoma of the bladder, the procedure was abandoned because of serious complications, including short-term bladder hemorrhage and urinary extravasation and long-term severe bladder contracture, ureteral reflux, and hydronephrosis. In this study, we used the neodymium:YAG laser with the MTR 1.5 contact probe to denude the entire mucosa of the canine urinary bladder. Evaluation of our results showed that mucosal denudation by this technique can be performed simply and safely without complications. Specifically, we encountered no significant bladder hemorrhage, urinary extravasation, bladder contracture, ureteral reflux, or hydronephrosis. We believe that the denudation procedure may be useful as a surgical means of treating the entire bladder mucosa in patients with proliferative epithelial lesions of the bladder including multifocal carcinoma in situ.

Animals↗
PubMed1985

Changes in immunohistochemical staining in prostatic adenocarcinoma following diethylstilbestrol therapy.

Twenty-eight pretreatment and posttreatment biopsies from 11 cases of prostatic adenocarcinoma were stained for prostate-specific acid phosphatase (PAP), prostate-specific antigen (PSA), and keratin to determine the effect of hormonal (diethylstilbestrol) therapy on these immunological markers. Treatment intervals ranged from 2 to 63 months. All pretreatment tumors were strongly positive for PAP, and nine were strongly positive for PSA. Two were weakly positive for PSA, and all were negative for keratin. In five of the 11 posttreatment group cases, staining with both PAP and PSA was reduced. In three posttreatment cases, the malignant epithelium showed a squamoid appearance, and in these areas the keratin gave a positive reaction. These findings indicate that immunohistochemical staining with PAP and PSA may change in response to hormonal therapy. These alterations may lead to false-negative results when using these techniques to identify the primary tumor source of metastatic deposits of prostatic carcinoma.

Acid Phosphatase↗
PubMedDate not supplied

Prostatic carcinoma.

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Adenocarcinoma↗