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Biomedical subjects

L DeMarco

Publications and source records attributed to L DeMarco.

17 recordsLinked to original sources
PubMed1998

Maximal cytoreductive surgery as a reasonable therapeutic alternative for recurrent endometrial carcinoma.

OBJECTIVE: The objective was to determine if maximal cytoreductive surgery could carry any benefit in pelvic and abdominal recurrent endometrial carcinoma. METHODS: Twenty women at their first large pelvic or abdominal recurrence from endometrial carcinoma were treated with maximal cytoreductive surgery. Women were classified as R1 (residual tumor) or R0 (no residual tumor) by tumor left at the end of surgery. Adjuvant postoperative therapy was undertaken upon clinical judgement. Progression-free, overall, and cancer-related survivals were analyzed with the product-limit method and compared with the log-rank test. The Cox regression model was used to study the variables involved in progression-free and overall survival. RESULTS: Complete macroscopic resection of tumor was feasible in 13 women (65%). R0 group women had a significant both progression-free (median reached at 9.1 months) and overall survival (median reached at 11.8 months) compared to R1 group women. There were 2 (10%) perioperative deaths. Eight women died of cancer, 5 in the R1 group and 3 in the R0 group. There were four intercurrent deaths in women still free from the disease. Local control of neoplasia was achieved in 84.6% of R0 women and their survival was affected mostly by distant recurrences or intercurrent deaths. Residual tumor at the end of surgery was the only significant variable to affect both progression-free and overall survival. CONCLUSION: Intensive surgery is a valid treatment option in women with large pelvic or abdominal recurrence from endometrial carcinoma. Tumor can be completely resected and local control of the disease can be achieved in most of the patients, although survival could be affected by distant recurrence and intercurrent deaths.

Aged↗
PubMed1998

Somatic mutation analysis of the APP and Presenilin 1 and 2 genes in Alzheimer's disease brains.

The molecular basis for sporadic Alzheimer disease (AD) remains largely unknown. We hypothesized that in some cases of sporadic AD, a somatic mutation in an embryonic cell committed to neuronal development within the amyloid precursor protein (APP), the presenilin 1 (PS-1) or the presenilin 2 (PS-2) genes (genes known to be involved in familial AD) may result in AD phenotype. Using PCR, denaturing gradient gel electrophoresis (DGGE), restriction enzyme digest and direct DNA sequencing, we analyzed these genes in 99 brain tissues from patients with histopathologically proven AD. One brain sample showed a mutation within the PS-1 gene, His163 Arg, later shown to be a germline mutation. No other migration abnormalities were demonstrated in any sample in exon 16 or 17 of the APP gene or the coding exons of the PS-1 gene. Restriction digest pattern was normal with regard to the predominant PS-2 gene mutation (N141I). A known mutation in the APP gene, as well as novel mutations within the PS-1 gene were easily detected by DGGE (Reznick Wolf et al. manuscript submitted). We conclude that the genes that are involved in familial AD do not display somatic mutations in the brains of sporadic AD patients, and that other molecular mechanisms are probably involved in the pathogenesis of sporadic AD.

Alzheimer Disease↗
PubMed1996

Sporadic cardiac myxomas and tumors from patients with Carney complex are not associated with activating mutations of the Gs alpha gene.

Cardiac myxomas are rare tumors that may be encountered sporadically or in the context of the Carney complex. The molecular basis for the development of cardiac myxomas and Carney complex tumors is unclear. Pathological myocardial function and myocardial hypertrophy have been associated with alterations in the heterotrimeric GTP-binding proteins. The postulated proto-oncogenic character of the gene encoding the alpha sub-unit of the stimulatory GTP-binding protein Gs alpha (gsp) in pituitary and thyroid tumors, the finding of identical somatic gsp mutations in the myocardium of patients with McCune-Albright syndrome, and the associated endocrine anomalies of the Carney complex prompted us to investigate the occurrence of activating missense mutations in the Gs alpha gene in 10 sporadically occurring atrial myxomas and in 8 tumors from 7 patients with Carney complex. No gsp mutations could be demonstrated by using the polymerase chain reaction and denaturing gradient gel electrophoresis complemented by direct DNA sequencing. Thus, activating Gs alpha mutations neither are associated with the development of atrial myxomas, nor can be demonstrated in other tumors from patients with Carney complex. The significance of these mutations in the myocardium of asymptomatic patients with McCune-Albright syndrome remains to be determined.

Adult↗
PubMed1996

Carcinoid tumors frequently display genetic abnormalities involving chromosome 11.

Carcinoid tumors are neuroendocrine neoplasms that are encountered either sporadically or as part of a familial syndrome, most notably-multiple endocrine neoplasia type 1 (MEN1). The MEN1 gene localizes to chromosome 11 (11q13) and presumably functions as a tumor suppressor gene. The molecular mechanisms underlying carcinoid tumor development and their clonal composition remain largely unknown. To establish whether carcinoid tumors develop via a mechanism similar to other MEN1-associated tumors, and indirectly determine their clonal composition, we analyzed 36 sporadically occurring carcinoid tumors with 16 chromosome 11 microsatellite markers, mostly from around the MEN1 region for loss of heterozygosity (LOH). Twenty one tumors (58%) displayed LOH of at least three markers, five lost almost an entire allele and the rest displayed a discontinuous pattern. Similar, but less extensive analysis was also carried out for 10 additional carcinoid tumors from Brazil, 6 of the 10 showed LOH with at least one marker. Overall, 36 of 46 tumors (78%) displayed LOH. In addition, 20 of 46 (43%) tumors exhibited a pattern of genomic instability. Thus, the majority of sporadically occurring carcinoid tumors are monoclonal whose tumorigenesis involves inactivation of a tumor suppressor gene on chromosome 11 and DNA mismatch repair genes mutations.

Adolescent↗
PubMed1995

Decreased expression of Ras GTPase activating protein in human trophoblastic tumors.

The normally developing placenta undergoes extensive but regulated noninvasive cellular proliferation. Various proto-oncogenes and growth factors have been associated with the regulation of trophoblastic placental growth. Activation of some oncogenes and altered expression of growth factors have been demonstrated in trophoblastic tumors (hydatidiform mole and choriocarcinoma). The ras proto-oncogene plays a key role in the signal transduction cascade of activated growth factors, and is known to be activated or overexpressed in multiple tumor types. Ras GTPase activating protein (RasGAP), a major down-regulator of ras activity, is present at high levels in placenta. To assess the role that Ras-GAP plays in the development of trophoblastic tumors, we performed immunohistochemical analyses with anti RasGAP antibodies of normal placentas, hydatidiform moles, invasive moles, and malignant choriocarcinomas. Normal placentas and noninvasive hydatidiform mole displayed intense positive staining confined to trophoblasts, whereas no staining was observed in the trophoblasts of invasive moles or choriocarcinomas. Thus, there was an inverse correlation between expression levels of RasGAP protein and the invasive potential and malignant phenotype in human trophoblastic tumors. The data indicate that RasGAP may play a regulatory role in trophoblast proliferation and that abolishing its activity may be associated with malignant transformation of these cells.

Cell Transformation, Neoplastic↗
PubMed1992

Comprehensive management including interstitial brachytherapy for locally advanced or recurrent gynecologic malignancies.

Radical therapy for locally advanced or recurrent gynecologic malignancies (LARGM) may include interstitial brachytherapy (IB) when intracavitary brachytherapy is impossible or inadequate and external beam teletherapy would be limited by surrounding normal tissue tolerance. Sixteen women received IB as all or part of their treatment at North Shore University Hospital for the treatment of locally advanced primary or recurrent tumors of gynecologic origin from May 1988 through September 1990. Primary sites included the vulva (3), vagina (2), cervix (7), and endometrium (4). Radiosensitizing chemotherapy was used in 8 patients. With a median follow-up of 23 months (range, 12-44 months), 11 patients (69%) have experienced continuous local control of their tumor and 4 patients (25%) have experienced severe complications. While significant risks may attend the use of IB, IB is an integral part of management for select patients with LARGM.

Adult↗
PubMed1992

Use of cisplatin for elderly patients.

The ageing of the population has resulted in a greater emphasis on cancer treatment effects in elderly patients. This population has often had arbitrary dose modification of chemotherapy owing to fear of excessive side-effects. A review was undertaken to evaluate cisplatin toxicity in patients of 70 years of age or older. Thirty-four patients were evaluated. Their mean age was 72.8 years and 85.3% were women. Fourteen of 34 (41%) patients completed the planned therapy. Treatment was terminated because of disease progression (35%), renal toxicity (9%) and non-renal toxicity (15%). Our conclusion is that cisplatin can safely be administered to elderly patients. Arbitrary dose modification or elimination of cisplatin from a treatment programme on the grounds of patient age alone is not justified.

Acute Kidney Injury↗
PubMed1985

A monoclonal antibody to human platelet glycoprotein IIIa detects a related protein in cultured human endothelial cells.

We have previously described a series of monoclonal antibodies against platelet membrane glycoproteins. Two of the antibodies, B59.2 and B2.12, recognize the glycoprotein IIb-IIIa complex. These two antibodies react specifically with glycoprotein (GP) IIIa, as shown by immunoblotting of sodium dodecyl sulfate-polyacrylamide gels of solubilized platelet membranes. Monoclonal B2.12, but not B59.2, binds to cultured human endothelial cells obtained from umbilical vein, internal iliac artery, and inferior vena cava. At saturation approximately 100,000 binding sites were detected per human umbilical vein endothelial cell. When solubilized radioiodinated cells were chromatographed on a column of agarose-bound B2.12, a single radiolabeled protein was obtained whose apparent molecular weight is slightly larger than that of platelet GP IIIa. This protein incorporated [35S]methionine when endothelial cells were labeled metabolically. These results demonstrate that human endothelial cell membranes synthesize a protein immunologically related to platelet GP IIIa.

Antibodies, Monoclonal↗
PubMedDate not supplied

Effect of fibrin on endothelial cell production of prostacyclin and tissue plasminogen activator.

Fibrin formed on endothelial cells has previously been shown to have deleterious effects on the cells. Additionally, substances that cause endothelial cell damage have been reported to induce cultured endothelial cells to synthesize prostacyclin and tissue plasminogen activator (t-PA). The present studies were undertaken to determine whether fibrin formed on cultured human umbilical vein endothelial cells would alter synthesis of prostacyclin and t-PA by the cells. Fibrin was found to increase synthesis of both prostacyclin and t-PA in a dose and time dependent manner. Stimulation of prostacyclin synthesis was completely inhibited by indomethacin; partially inhibited by actinomycin D, cycloheximide, and trifluoperazine; and not affected by cytochalasin D or vinblastine. In contrast, stimulation of t-PA synthesis was completely inhibited by actinomycin D and cycloheximide; partially inhibited by cytochalasin D, vinblastine, and trifluoperazine; and not affected by indomethacin. Fibrin I, formed with Reptilase, caused only slight stimulation of t-PA production, but virtually no stimulation of prostacyclin synthesis. Neither collagen polymerization on the cells nor thrombin added in concentrations that did not induce fibrin polymer formation stimulated production of either substance. Furthermore, soluble fibrin II generated in the presence of the fibrin polymerization inhibitor gly-pro-arg-pro also failed to stimulate either prostacyclin or t-PA production. The presence of platelets in the plasma from which the fibrin was formed did not affect the amount of stimulation of the cells. Fibrin-induced stimulation of endothelial cell production of prostacyclin and t-PA could act to limit vascular occlusion in vivo by inhibiting platelet function and by stimulating fibrinolysis via t-PA.

6-Ketoprostaglandin F1 alpha↗