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Biomedical subjects

D Coppola

Publications and source records attributed to D Coppola.

71 records · Page 4Linked to original sources
PubMed1994

Effect of a null mutation of the insulin-like growth factor I receptor gene on growth and transformation of mouse embryo fibroblasts.

Fibroblast cell lines, designated R- and W cells, were generated, respectively, from mouse embryos homozygous for a targeted disruption of the Igf1r gene, encoding the type 1 insulin-like growth factor receptor, and from their wild-type littermates. W cells grow normally in serum-free medium supplemented with various combinations of purified growth factors, while pre- and postcrisis R- cells cannot grow, as they are arrested before entering the S phase. R- cells are able to grow in 10% serum, albeit more slowly than W cells, and with all phases of the cell cycle being elongated. An activated Ha-ras expressed from a stably transfected plasmid is unable to overcome the inability of R- cells to grow in serum-free medium supplemented with purified clones. Nevertheless, even in the presence of serum, R- cells stably transfected with Ha-ras, alone or in combination with simian virus 40 large T antigen, fail to form colonies in soft agar. Reintroduction into R- cells (or their derivatives) of a plasmid expressing the human insulin-like growth factor I receptor RNA and protein restores their ability to grow with purified growth factors or in soft agar. The signaling pathways participating in cell growth and transformation are discussed on the basis of these results.

Animals↗
PubMed1994

A functional insulin-like growth factor I receptor is required for the mitogenic and transforming activities of the epidermal growth factor receptor.

When wild-type mouse embryo cells are stably transfected with a plasmid constitutively overexpressing the epidermal growth factor (EGF) receptor (EGFR), the resulting cells can grow in serum-free medium supplemented solely with EGF. Supplementation with EGF also induces in these cells the transformed phenotype (growth in soft agar). However, when the same EGFR expression plasmid is introduced and overexpressed in cells derived from littermate embryos in which the insulin-like growth factor I (IGF-I) receptor genes have been disrupted by homologous recombination, the resulting cells are unable to grow or to be transformed by the addition of EGF. Reintroduction into these cells (null for the IGF-I receptor) of a wild-type (but not of a mutant) IGF-I receptor restores EGF-mediated growth and transformation. Our results indicate that at least in mouse embryo fibroblasts, the EGFR requires the presence of a functional IGF-I receptor for its mitogenic and transforming activities.

Animals↗
PubMed1993

Basaloid squamous cell carcinoma of floor of mouth.

BACKGROUND: Only five cases of basaloid squamous cell carcinoma (BSCC), a rare tumor of head and neck, have been reported to involve the floor of mouth. METHODS: Clinicopathologic and immunohistochemical features of eight BSCC of floor of mouth were studied to evaluate the significance of the basaloid features. RESULTS: Five patients were male and three were female. Their mean age was 52 years (range, 39-59). At presentation, one patient was diagnosed with Stage II disease, four were diagnosed with Stage III disease, and three were diagnosed with Stage IV disease. Aside from typical squamous differentiation, each patient had a component of basaloid cells arranged in irregular nests, cords, or pseudoglandular spaces with a brisk mitotic rate, myxoid stroma, and marked tendency for perineural invasion. A panel of immunostains yielded the following results: keratin, +8/8; carcinoembryonic antigen, +3/8; and S-100, chromogranin, and neuron-specific enolase were negative. Mucin stains were negative in all cases. Ultrastructural characterization of three BSCC revealed squamous differentiation of the basaloid cells and a peculiar basal membrane-like material in between them. No neurosecretory granules were present. Seven patients underwent surgery; six of them were also treated with postoperative radiation therapy. In two cases, chemotherapy was added at recurrence. One nonresectable patient received radiation and chemotherapy. At the last follow-up, five patients were dead of disease within 13 months from the diagnosis. One patient died of an unknown cause. Two patients were still alive at the time of this report, 4 and 2 months after treatment. Seven patients had recurrent disease. The authors compared these data with a control group of patients with conventional squamous cell carcinoma (SCC). CONCLUSIONS: The authors' results indicate that BSCC of floor of mouth is an aggressive variant of SCC and is prognostically worse than the conventional SCC, regardless of the grade of the latter.

Adult↗
PubMed1993

Bednar tumor pattern in recurring giant cell fibroblastoma.

Giant cell fibroblastoma (GCF) and Bednar tumor (BT) have been perceived as two rare, not directly related, soft tissue neoplasms. Recent studies, separately conducted on each process, have presented evidence indicating that, in each instance, the tumor seemed to be related to the dermatofibrosarcoma protuberans. The case being reported provides additional evidence supporting those previous results and, for the first time, documents a direct link between GCF and BT, as seen in this girl who had a vulvar GCF resected at 1-year of age, with recurrence, 1.5 years later, as a mixed BT-GCF.

Female↗
PubMed1993

Serum albumin and prealbumin as predictors of clinical outcomes of hospitalized elderly nursing home residents.

OBJECTIVE: To investigate the prevalence of hypoalbuminemia and hypoprealbuminemia in hospitalized, elderly, skilled nursing facility residents and to correlate these findings with clinical outcomes. DESIGN: Prospective cohort study. SETTING: A 300-bed community hospital. PARTICIPANTS: Eighty-one hospitalized, skilled nursing facility patients, average age 83.1 years. INTERVENTIONS: None. OUTCOME MEASURES: Serum albumin and prealbumin (transthyretin) were measured at admission, mid-week, 1 week, and 1 month. Patients were followed for 90 days for the outcomes of length of hospitalization and mortality. RESULTS: The prevalence of hypoalbuminemia was 99% and of hypoprealbuminemia, 79%. Both means dropped significantly from admission to midweek nadirs of 25 g/L for albumin and 14 mg/L for prealbumin. Severe hypoalbuminemia at mid-week predicted mortality (RR = 4.1 95%, CI 2.0-8.5) and extended length of hospitalization (RR = 5.2 95%, CI 2.8-9.8). Severe hypoprealbuminemia predicted extended hospitalization (RR = 3.2, CI 1.5-6.7) but not mortality. CONCLUSIONS: Hypoalbuminemia and hypoprealbuminemia are very common in this clinical setting and vary in parallel fashion over time. Severe hypoalbuminemia was a stronger predictor than hypoprealbuminemia of 90-day mortality and extended length of stay. Serum albumin on admission was not as strong a predictor of outcomes as serum albumin at mid-week.

Aged↗
PubMed1993

Aortic dissection in cardiac allograft recipients. A report of two cases.

Aortic dissection in cardiac allograft recipients has not been reported previously, to our knowledge. We have observed two fatal aortic dissections in heart transplant recipients: one in the immediate postoperative period and one occurring 5 years after transplantation. We discuss the clinical presentations, pathologic findings, possible pathogenetic mechanisms, and risk factors. Because the frequency of aortic dissection after heart transplantation appears to be relatively low (< 1%), such disease may be clinically unsuspected. Given the uniformly poor outcome observed in our two patients, we suggest that increased awareness of the possible development of aortic dissection after heart transplantation may result in improved survival of affected patients.

Aortic Dissection↗
PubMed1993

Insulin-like growth factor-1 and its receptor mediate the autocrine proliferation of human ovarian carcinoma cell lines.

BACKGROUND: IGF-1 regulates the growth of diverse mammalian cell types including several human carcinoma cell lines. The IGF-1 receptor is a glycosylated heterodimer which, upon binding with IGF-1, undergoes tyrosine autophosphorylation. The autophosphorylation of the beta-receptor subunit is a strict requirement for its mitogenic properties. EXPERIMENTAL DESIGN: In this study, we have assessed the role of the IGF-1 receptor in the proliferation of ovarian carcinoma cell lines in culture. Effects of anti-sense and sense oligodeoxynucleotides to IGF-1 receptor RNA were tested. RESULTS: The human ovarian carcinoma cell lines OVCAR-3 and CaOV-3 both grew autonomously in serum-free medium, and their growth was further stimulated by the addition of IGF-1. Incubation of cells with anti-sense oligodeoxynucleotides corresponding to the IGF-1 receptor RNA markedly inhibited cell proliferation both in serum-free medium and in the presence of IGF-1. The inhibition of cell growth by the oligodeoxynucleotides corresponded to a reduction in the amount of detectable phosphorylated IGF-1 receptor. CONCLUSIONS: The findings indicate that IGF-1 and its specific receptor mediate the autocrine proliferation of human ovarian carcinoma cell lines.

Animals↗
PubMed1990

[Amoxicillin associated with clavulanic acid. Clinical efficacy and tolerance].

The Authors, after having analysed the problems involving the choice of an antibiotical therapy in the odontostomatological field, present a study concerning the evaluation of the clinical efficacy and tolerability of Amoxycillin associated with clavulanic acid. This drug has been orally administered to 154 ambulatorial patients. The results thus obtained in this clinical sperimentation show that Stacillin is a good and efficacious antibiotic in odontostomatologic affections, and that it is also well tolerated. These characteristics make it a first choice antibiotic in the odontostomatologic sphere.

Adolescent↗
PubMed1989

[Structural changes in the jaws. Differential diagnosis].

In this work the Authors have considered the causes of changes in the structure of maxillary bones. They have also discussed the available diagnostic means useful to make a correct diagnosis and the importance of a right differential diagnosis of the causes in order to have a better treatment.

Diagnosis, Differential↗
PubMed1982

Treatment of fractures of the lower limbs with functional braces.

Closed treatment of fractures has recently used the method of functional braces. If well applied, these clear many patients with fractures from indication for surgery. The results reported for 118 cases show the utility and practicability of this method, especially in leg fractures and fractures of the femur with more than two fragments.

Adolescent↗
PubMedDate not supplied

Significance of Fas and retinoblastoma protein expression during the progression of Barrett's metaplasia to adenocarcinoma.

BACKGROUND: Barrett's esophagus (BE) is a premalignant lesion characterized by replacement of normal squamous epithelium with columnar epithelium. This lesion can progress to dysplasia and adenocarcinoma. Recently, the Fas receptor and retinoblastoma (Rb) protein have been described as important mediators of apoptosis and tumor suppression, respectively. This study was undertaken to examine their expression during the progression of metaplasia to adenocarcinoma in BE. METHODS: In a review of 56 adenocarcinomas arising in BE, the specimen blocks were examined using the immunohistochemical avidin-biotin-peroxidase complex technique. For each specimen, areas of normal epithelium were compared with areas of metaplasia, dysplasia, or carcinoma (when present). Monoclonal mouse anti-human antibodies were used to identify Rb protein (Rb-Ab5, 1/50 dilution; Oncogene Science) and the 40-50-kDa cell membrane Fas protein (APO-1/Fas, 1/5 dilution; DAKO Corp.). RESULTS: Loss of Rb staining was observed as the metaplasia progressed to dysplasia and carcinoma, indicating accumulation of unstainable aberrant protein. Conversely, Fas protein staining was undetectable or weak in normal or metaplastic epithelium, increasing in the areas of high-grade dysplasia and carcinoma. These differences were statistically significant (P < .001). CONCLUSIONS: The accumulation of abnormal Rb protein during the progression of Barrett's metaplasia to carcinoma leads to unsuppressed tumor growth. Fas overexpression may represent a cellular attempt to balance the uncontrolled tumor proliferation by promoting apoptosis.

Adenocarcinoma↗
PubMedDate not supplied

Molecular prognostic markers in pancreatic cancer.

BACKGROUND: Pancreatic cancer is one of the most aggressive human tumors and is virtually incurable. Its incidence in the United States has tripled in the past 50 years. The tumor is a frequent cause of cancer death in both men and women. The current treatment options are inadequate and probably reflect the fact that the etiologic factors and the pathogenesis of pancreatic cancer are unknown. METHODS: The author reviewed recent studies describing some of the molecular alterations that may play a role in pancreatic carcinogenesis. RESULTS: Most pancreatic tumors arise in the ductal epithelium. Cytogenetic abnormalities and alterations in proliferation, oncogenes and tumor suppressor genes, cell receptors, and growth factors are described. CONCLUSIONS: Preliminary studies have implicated, among others, the insulin-like growth factor-1 receptor, Src, and Stat3 proteins in human pancreatic carcinogenesis. These molecules may represent important predictors of tumor behavior and targets of novel therapeutic modalities in human pancreatic cancer.

Biomarkers, Tumor↗