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Biomedical subjects

V Papavasiliou

Publications and source records attributed to V Papavasiliou.

12 recordsLinked to original sources
PubMed2000

The vitamin D analogue EB 1089 prevents skeletal metastasis and prolongs survival time in nude mice transplanted with human breast cancer cells.

1,25-Dihydroxyvitamin D has potent antiproliferative and anti-invasive properties in vitro in cancer cells. However, its calcemic effect in vivo limits its therapeutic applications. Here, we report the efficacy of EB 1089, a low calcemic analogue of vitamin D, on the development of osteolytic bone metastases after intracardiac injection of the human breast cancer cell line MDA-MB-231 in nude mice. Animals injected with tumor cells were implanted simultaneously with osmotic minipumps containing either EB 1089 or vehicle. Both groups remained normocalcemic for the duration of the experiment. The total number of bone metastases, the mean surface area of osteolytic lesions, and tumor burden within bone per animal were markedly decreased in EB1089-treated mice. Furthermore, longitudinal analysis revealed that mice treated with EB1089 displayed a marked increase in survival and developed fewer bone lesions and less hind limb paralysis over time as compared with untreated animals. These results suggest that EB1089 may be beneficial in the prevention of metastatic bone lesions associated with human breast cancer.

Animals↗
PubMed2000

Expression and regulation of parathyroid hormone-related peptide in normal and malignant melanocytes.

We examined parathyroid hormone-related peptide (PTHrP) production and regulation in both normal human melanocytes and in a human amelanotic melanoma cell line (A375). Northern blot and immunocytochemical analysis demonstrated that both cultured A375 cells and normal human melanocytes express PTHrP, but A375 cells expressed much higher levels of the peptide. PTHrP secretory rate increased at least 10-fold after treatment with 10% fetal bovine serum (100.2 +/- 2.8 pmol/10(6) cells vs. basal <15 pmol/10(6) cells) in proliferating A375 cells but only twofold in confluent cells. Treatment of A375 cells with increasing concentrations of 1, 25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] or its low-calcemic analog EB-1089 revealed that EB-1089 was 10-fold more potent than 1, 25-(OH)(2)D(3) on inhibition of both cell proliferation and PTHrP expression. Furthermore, inoculation of A375 cells into the mammary fat pad of female severe combined immunodeficiency mice resulted in the development of hypercalcemia and elevated concentrations of plasma immunoreactive PTHrP in the absence of detectable skeletal metastases. Our study, therefore, demonstrates a stepwise increase in PTHrP expression when cells progress from normal to malignant phenotype and suggests that EB-1089 should be further evaluated as a therapeutic agent in human melanoma.

Animals↗
PubMed1999

Reversal of hypercalcemia with the vitamin D analogue EB1089 in a human model of squamous cancer.

EB1089, an analogue of 1,25 dihydroxyvitamin D with low calcemic activity is a potent inhibitor of parathyroid hormone-related peptide (PTHRP) production in vitro. The purpose of the present study was to determine whether EB1089 could reverse established hypercalcemia in BALB C nude mice implanted s.c. with a human epithelial cancer previously shown to produce high levels of PTHRP in vitro. Total plasma calcium was monitored before and after tumor development and increased steadily when the tumor reached > or =0.5 cm3. When total calcium was 22.85 mmol/liter, animals were treated with a constant infusion of EB1089 or vehicle alone for a period of 2 weeks. A significant and sustained reduction of plasma calcium from 3.2+/-0.1 to 2.7+/-0.08 (P < 0.01) mmol/liter was observed during infusion with EB1089. In contrast, calcium levels in vehicle-treated animals continued to rise during the infusion period. Tumor growth velocity also slowed significantly after the administration of EB1089 as compared with vehicle-treated animals. Plasma PTHRP levels measured at the end of the 2 weeks' infusion period were significantly lower in animals treated with EB1089 as compared with animals treated with vehicle alone (44+/-8 pg/ml versus 194+/-35 pg/ml, P < 0.001). These results, therefore, demonstrate that EB1089 can reverse established hypercalcemia in a human model of squamous cancer.

Animals↗
PubMed1999

Changing patterns in advanced gastric carcinoma.

A retrospective study on patients with gastric cancer during the periods 1984-88 (n = 63 patients) and 1989-93 (n = 59 patients) was made. The aim of the study was to assess any changing patterns in tumour distribution, surgical management and survival during the two periods. When the diagnosis was made, the majority of tumours were advanced: 58 were stage IV and 21 were stage IIIB, with 43 tumours at earlier stages. The incidence of proximally located gastric adenocarcinomas increased from 15.9 to 27.1%, while the incidence of carcinomas located in the body decreased from 34.9 to 23.7%. The majority of patients underwent conservative gastrectomy. The proportion of proximal gastrectomies increased from 3.2 to 15.3 per cent (p = 0.02), whereas the proportion of combined resection of adjacent organs decreased from 38.1 to 22.0 per cent (p = 0.04). Perioperative mortality rate decreased from 17.5 to 1.7 per cent (p = 0.003). Prognosis remained unchanged in the two periods; overall 5-year survival is calculated as 12 per cent.

Adenocarcinoma↗
PubMed1996

Parathyroid-hormone-related peptide in hematologic malignancies.

PURPOSE: To determine whether parathyroid-hormone-related peptide (PTHRP) is an important pathogenetic mediator of hypercalcemia in patients with hematologic malignancies. PATIENTS AND METHODS: We conducted a cohort analytic study in 76 consecutive patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease, multiple myeloma, and Waldenstrom's macroglobulinemia, 14 of which were hypercalcemic. Thirty normal subjects served as a control group. RESULTS: Using the NH2 -terminal radioimmunoassay, PTHRP concentrations in heavy controls were undetectable (<7.5 pmol equivalents of PTHRP [fragment 1-34] per liter). The majority of hypercalcemic patients (8/14) had non-Hodgkin's lymphoma, and 62.5% of these (5/8) had significant elevations of circulating PTHRP concentrations (mean 70.5 +/- 38.5 pmol equivalents of PTHRP per liter) (P <0.01). In non-Hodgkin's lymphoma, 11 of 30 patients with advanced disease (stage IV) had elevated PTHRP concentrations, and of these, 8 of 11 had high-grade pathology. In contrast, only 3 or 21 patients with less advanced disease (stage I to III) had elevated PTHRP concentrations. In 4 NHL patients with less advance PTHRP concentrations sampled prior to cytotoxic chemotherapy, tumor response was associated with a decrease in PTHRP. Concomitant suppression of 1,25(OH)2D3 concentrations was observed in 66% of hypercalcemic patients with non-Hodgkin's lymphoma. CONCLUSIONS: These results suggest that PTHRP may be an important pathogenetic factor in the development of hypercalcemia in hematologic malignancies, notably in non-Hodgkin's lymphoma.

Antineoplastic Agents↗
PubMed1996

Cystic angiomatosis of bone: a case report.

Diffuse skeletal cystic angiomatosis is an extremely rare disorder that has not previously been reported in detail in the dental literature. This case report deals with the oral manifestations in a 10-year-old boy. Clinical, radiographic, and computed tomographic examinations showed hyperplasia of the right side of the face. The computed tomographic imaging studies revealed the extent of the jawbone lesions and the adjacent hyperplastic soft tissues. The histologic appearance of the lesions, the course of the disease, and the differential diagnosis are discussed.

Angiomatosis↗
PubMed1995

Vitamin D analogs: new therapeutic agents for the treatment of squamous cancer and its associated hypercalcemia.

We have examined the in vitro effects of 1,25 dihydroxy-vitamin D3 [1,25(OH)2D3] and of two side-chain modified analogs of 1,25(OH)2D3 (EB1089 and MC903) on cell growth and parathyroid hormone related peptide (PTHRP) production in immortalized (HPK1A) and neoplastic (HPK1A-ras) keratinocytes. Cell proliferation was strongly inhibited by 1,25(OH)2D3 and its analogs in HPK1A cells, and in this system EB1089 was 10-100 times more potent than 1,25(OH)2D3 or MC903. A similar effect on cell proliferation was observed in HPK1A-ras cells; however, 10-fold higher concentrations of 1,25(OH)2D3 or its analogs were required. We also observed a strong and dose-dependent inhibitory effect of these compounds on PTHRP secretion and gene expression. In both immortalized and neoplastic keratinocytes, EB1089 was 10-100 times more potent than 1,25(OH)2D3 or MC903 on inhibiting PTHRP production. However, although effective in HPK1A-ras cells, 10-fold higher concentrations of 1,25(OH)2D3 or its analogs were required to produce similar actions in this neoplastic model. These studies therefore demonstrate that a 1,25(OH)2D3 analog with low calcemic potency in vivo (EB1089) can inhibit keratinocyte proliferation and PTHRP production by such cells with greater potency than 1,25(OH)2D3. The observed effects of such analogs in neoplastic keratinocytes predicts their potential usefulness in vivo in inhibiting squamous cancer growth and its associated hypercalcemia.

Animals↗
PubMedDate not supplied

Ipsilateral injuries of the elbow and forearm in children.

Fracture of the forearm with ipsilateral injury of the elbow joint is a rare traumatic entity in children. Twenty-four such cases were treated in our clinic during the last 4 years (1981-1984). The treatment was surgical in six cases and related to the elbow injuries, while the forearm underwent closed treatment. The results of these cases, regardless of treatment and severity of the injury, did not differ appreciably from the results of common forearm or elbow injuries.

Accidents↗
PubMedDate not supplied

Fractures of the medial condyle of the humerus in childhood.

Fifteen cases of medial humeral condylar fracture are presented. Average patient age was 9.5 years, and the follow-up period ranged from 1 to 3 years. This type of fracture is very rare, and it seldom appears in the international literature. Treatment in our cases was based on the displaced or undisplaced nature of the fragment, i.e., the displaced fractures were operated on and fixed with Kirschner wires, whereas the undisplaced ones were immobilized in plaster casts. The treatment of choice in our series gave quite satisfactory results.

Casts, Surgical↗