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Biomedical subjects

G Giaccone

Publications and source records attributed to G Giaccone.

At least 253 records · Page 14Linked to original sources
PubMed1990

Neurofibrillary tangles of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease share antigenic determinants with those of Alzheimer disease.

In the Indiana kindred of Gerstmann-Sträussler-Scheinker disease, neurofibrillary tangles (NFT) with paired helical filaments (PHF) are numerous, widespread and consistently present in the cerebral cortex and several subcortical nuclei. Such tangles share antigenic determinants with those of Alzheimer disease; in fact, they are recognized by Alz50, anti-PHF and anti-ubiquitin antibodies. Thus, NFT with structural and immunocytochemical similarities are present in two distinct forms of amyloidosis of the central nervous system, i.e. the Indiana kindred of Gerstmann-Sträussler-Scheinker disease and Alzheimer disease.

Aged↗
PubMed1990

Effects of tumor necrosis factor, alone or in combination with topoisomerase-II-targeted drugs, on human lung cancer cell lines.

Tumor necrosis factor alpha (TNF) exhibits cytotoxic activity on some solid tumors and has been reported to be synergistic with topoisomerase-II-targeted antineoplastic agents. A wide range of TNF concentrations (from 10 to 10,000 U/ml) was tested in 9 human lung cancer cell lines (5 small-cell and 4 non-small-cell carcinomas) using a semi-automated MTT assay. TNF was not cytotoxic in 8 cell lines, while an adenocarcinoma cell line was marginally sensitive to the cytokine. Using 125I-TNF we were able to show the presence of specific binding sites for TNF in 4/9 human lung cancer cell lines. Scatchard analysis of the marginally sensitive cell line showed high-affinity, saturable binding. With 5 cell lines we also tested whether TNF affected the cytotoxicity of doxorubicin and etoposide, 2 topoisomerase II-targeted drugs which are widely used in the therapy of lung cancer. No significant increase in cytotoxicity was seen when TNF was added to the 2 anti-neoplastic agents. In contrast to certain other human and mouse lines, human lung cancer cell lines appear to be resistant to TNF, despite the presence of the receptor in some of them; moreover, no synergistic effect of TNF and 2 topoisomerase-II-targeted drugs was evident in these human cell lines.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Cerebral preamyloid deposits and congophilic angiopathy in aged dogs.

The brains of 7 dogs aged 6 to 18 years have been histochemically and immunohistochemically investigated at the light- and electron microscopy levels for preamyloid deposits and amyloid fibrils to verify the hypothesis that the accumulation of cleavage products of amyloid precursor protein is related not only to Alzheimer's disease but also to the normal aging of the brain. Preamyloid deposits were detected in the neuropil of the cerebral cortex and neostriatum, whereas amyloid fibrils were found in the walls of parenchimal and leptomeningeal vessels. The densities of preamyloid deposits in the neuropil and of deposits of amyloid fibrils in the vessel walls were higher in the brains of the most aged dogs. These findings suggest that aging of the canine brain is characterized by an accumulation of intermediate cleavage products of the amyloid precursor protein in both the neuropil and the vessel walls, and by processing of these products to amyloid fibrils in the vessel walls.

Aging↗
PubMed1990

4'-EPI-doxorubicin in advanced lung cancer. A phase II trial.

Fifty evaluable patients with advanced lung cancer (28 small cell and 22 non-small cell carcinomas), mainly pretreated by chemotherapy, received 4'-epi-doxorubicin 90 mg/m2 every 3 weeks. Two partial responses were obtained in small cell lung cancer patients, which lasted 153 and 168 days. Leukopenia, emesis and alopecia were the most frequent side effects. Two patients who previously received anthracyclines died suddenly of cardiac failure, another patient had severe congestive heart failure, and four others had minor cardiac dysfunctions. 4'-epi-doxorubicin has a modest activity in advanced lung cancer, mainly pretreated by chemotherapy and is not devoid of significant cardiotoxicity in this patient population.

Adult↗
PubMed1990

Reconstituted basement membrane (matrigel) and laminin can enhance the tumorigenicity and the drug resistance of small cell lung cancer cell lines.

Small cell lung cancer (SCLC) is a fatal malignancy due to its propensity to metastasize widely and to reoccur after chemotherapy in a drug-resistant form. While most SCLC cell lines are anchorage independent for growth, laminin induced the attachment of five of six SCLC cell lines tested (NCI-N417, NCI-H345, NCI-H146, NCI-H187, NCI-H510, and NCI-H209). NCI-N417 SCLC cells adopted a flattened morphology on laminin, and a classic SCLC cell line (NCI-H345) demonstrated a neuron-like appearance while the other SCLC cell lines except NCI-H187 cells, attached but did not spread. Adhesion to laminin was associated with increased resistance to several cytotoxic drugs. Matrigel, an extract of basement membrane proteins, greatly accelerated tumor growth when coinjected with SCLC cells in athymic mice. A synthetic peptide from the B1 chain of laminin, cyclic-YIGSR (Tyr-Ile-Gly-Ser-Arg), inhibited laminin-induced SCLC cell adhesion and migration in vitro and reduced the size of the tumors they formed when coinjected with matrigel and YIGSR. These results suggest that the interaction of SCLC cells with laminin and possibly with other basement membrane proteins can enhance their tumorigenicity and drug resistance.

Amino Acid Sequence↗
PubMed1990

Doxorubicin and etoposide in the treatment of advanced measurable breast cancer.

Nineteen evaluable patients with advanced breast cancer were treated with a combination of doxorubicin and etoposide. Patients had measurable disease, received only mild pretreatment and most had good general conditions at start of therapy. Strict criteria for dose adjustments according to nadir counts were applied. A 42% response rate was obtained. Toxicity was mild and treatment well-tolerated. Doxorubicin-etoposide is an active regimen for patients with breast cancer and warrants further testing in a larger patient population with less stringent criteria for evaluation and treatment monitoring.

Adult↗
PubMed1990

Coexistence of Alzheimer's amyloid precursor protein and amyloid protein in cerebral vessel walls.

Polyclonal antibodies to synthetic peptides homologous to amino acid residues 45-62, 597-624, and 676-695 of the predicted sequence of Alzheimer's amyloid precursor protein (APP) were used to investigate the site of origin of APP, and the relationship between APP and amyloid protein in Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D). Cortical sections as well as homogenates of isolated leptomeningeal and cortical microvessels from three patients with AD, two patients with HCHWA-D, and two nondemented controls were probed. In vessel extracts of both groups of patients and the controls, APP was detected as a set of proteins with electrophoretic mobility of 105 to 135 kilodaltons. In cortical sections of all subjects, APP immunoreactivity was found in leptomeningeal and cortical vessel walls. In patients with AD and HCHWA-D, APP and amyloid fibrils coexisted in the same vessels. Moreover, APP immunoreactivity was found in association with 50% of senile plaques in AD brains, but was not evidenced in parenchymal amyloid deposits in patients with HCHWA-D. These data suggest that the vascular system is a source of APP and that the processing of APP into insoluble fibrils in AD and HCHWA-D may take place in situ.

Aged↗
PubMed1989

Alzheimer patients and Down patients: cerebral preamyloid deposits differ ultrastructurally and histochemically from the amyloid of senile plaques.

The preamyloid deposits found in the cerebral grey matter of Alzheimer patients and Down patients following immunostaining with anti-beta-protein antisera are neither birefringent following Congo red staining nor fluorescent after thioflavine S treatment. Further, they contain small amounts of alpha 1-antichymotrypsin, sulfated glycosaminoglycans and complement fraction C3d, but not the P component. As suggested previously, the material accumulated in these deposits may lack the molecular conformation responsible for the properties of amyloid fibrils. To test this hypothesis, we selected cortical samples from 6 Alzheimer and 4 Down patients for an electronmicroscopical study of senile plaques and of preamyloid deposits, both identified by indirect immunogold staining with anti-beta-protein antiserum. We observed the labelling of 4-8 nm wide amyloid fibrils in the plaque cores and of extracellular electrondense, flaky and irregularly distributed material in the preamyloid deposits. In the latter, amyloid fibrils were very rarely detected. These findings support the view that preamyloid deposits mostly contain amyloid precursors that are not yet organized in fibrils.

Alzheimer Disease↗
PubMed1989

Alzheimer patients: preamyloid deposits are more widely distributed than senile plaques throughout the central nervous system.

In Alzheimer's disease, anti-beta-protein antisera label not only amyloid deposits accompanied by degenerating neurites (neuritic and mature plaques) and amyloid deposits without degenerating neurites, but also preamyloid deposits lacking the optical properties of amyloid fibrils. We have carried out a study of the brains of 13 patients with Alzheimer's disease (one with the familial and 12 with the sporadic form), using anti-beta-protein and anti-paired helical filament antisera, thioflavine S, Congo red and Gallyas' silver impregnation, in order to determine whether the distribution of preamyloid deposits and amyloid deposits without degenerating neurites differs from that of amyloid deposits with degenerating neurites. Preamyloid deposits and amyloid deposits with or without degenerating neurites were present in cortex, neostriatum, medial geniculate body and thalamic (anterior and extralaminar) nuclei, whereas preamyloid deposits and amyloid deposits without degenerating neurites, but not amyloid deposits with degenerating neurites, were present in other thalamic nuclei, in the globus pallidus, brainstem, cerebellar cortex and upper spinal cord. These results support the view that preamyloid deposits evolve to senile (neuritic and mature) plaques only in specific brain regions, where neurites vulnerable to amyloid fibrils are widely distributed.

Adult↗
PubMed1989

Phase II study of divided-dose vinblastine in advanced cancer patients.

A better therapeutic index has been obtained in breast cancer patients when vinblastine is given by a 5-day continuous infusion program than by i.v. bolus; the continuous infusion pharmacokinetics has been reproduced by an iv divided bolus at 0 and 48 h, which may be more easily applied to outpatients. We performed a broad phase II study in 97 advanced cancer patients in which vinblastine was administered by i.v. divided bolus at 0 and 48 h at the starting dose of 3.5-4 mg/m2, every 3 weeks. Our aim was to confirm the results achieved by continuous infusion and to investigate the toxicity pattern of this novel administration schedule. Neurotoxicity and myelosuppression were the main side effects: constipation and peripheral neurotoxicity respectively developed in 28% and 38% of patients and were severe in 5% and 1%. Leukopenia and thrombocytopenia respectively occurred in 70% and 40% of patients and were severe in 11% and 4%. Four partial responses, 38 no changes and 42 progression were obtained out of 84 evaluable patients. Responses were seen in tumors of breast, lung, and head and neck. Our results do not support the use of vinblastine in divided doses in advanced cancer patients.

Adult↗
PubMed1989

Isolated central nervous system metastasis from ovarian carcinoma: a case report.

Ovarian adenocarcinoma usually disseminates and recurs the abdominal cavity. The detection of central nervous system metastases is rare. In this report we describe a case of intracranial recurrence that developed during a complete local surgical and pathological response and was treated radically with surgery followed by radiation.

Adenocarcinoma↗
PubMed1989

Lonidamine versus polychemotherapy in advanced non-small-cell lung cancer. A preliminary analysis.

No clear evidence of survival benefit has been definitely shown by chemotherapy in advanced non-small-cell lung cancer. We evaluated in a randomized trial the activity of the new drug lonidamine (up to 1050 mg/day) versus MVP (mitomycin C, 10 mg/m2, vinblastine, 5 mg/m2, cisplatin, 100 mg/m2). The preliminary findings on 25 patients showed that lonidamine can be easily administered at these dose ranges, and main toxicity was represented by myalgia and testicular pain. Tolerance to combination chemotherapy (MVP) was superimposable to our prior experience. Responses were recorded in both arms, and no survival difference was apparent. The study is in progress.

Adult↗
PubMed1989

Down patients: extracellular preamyloid deposits precede neuritic degeneration and senile plaques.

Using anti-SP28 (a polyclonal antibody to a 28 residue synthetic peptide homologous to the NH2-terminal region of the Alzheimer amyloid beta-protein) to investigate the cerebral cortex of 6 Down patients aged 6-55 y, we found that, besides senile plaques and congophilic vessels, extracellular deposits unrelated to degenerating neurites, tangle-bearing neurons or congophilic vessels were labelled. These deposits were similar to the extracellular deposits previously observed in the cerebral cortex of Alzheimer patients and non-demented individuals. The material accumulated in the deposits did not react with Congo red, thioflavine S or, on some occasions, silver salts and therefore might have been constituted by beta-protein precursors lacking the molecular conformation of amyloid fibrils. Age-related analysis of the cortical lesions in Down patients suggested that such extracellular deposits precede degenerating neurites and evolve into senile plaques.

Adult↗
PubMed1989

Phase II study of esorubicin in the treatment of patients with advanced sarcoma.

Esorubicin was administered to 12 patients with soft tissue sarcoma, 1 osteosarcoma and 1 desmoid tumor. Seven patients had never received chemotherapy before. Myelotoxicity was the main side effect, leukopenia being more pronounced than thrombocytopenia. No significant nonhematological toxicity occurred. Six patients had no change of median duration of 98 days and 7 patients progressed. The patient suffering from multiple-site lesions of a desmoid tumor obtained a long-lasting partial response. This study does not support further testing of esorubicin in sarcoma patients.

Antibiotics, Antineoplastic↗
PubMed1989

Gerstmann-Sträussler-Scheinker disease. II. Neurofibrillary tangles and plaques with PrP-amyloid coexist in an affected family.

Azzarelli et al reported an Indiana kindred affected by a hereditary disorder, characterized clinically by ataxia, parkinsonism, and dementia. Recently, we studied neuropathologically the 3rd and 4th cases that came to autopsy among the patients of this family. As in 2 patients examined previously, amyloid plaques were widespread throughout the cerebrum and the cerebellum, whereas neurofibrillary tangles were numerous in the cerebral cortex, the hippocampus, and the substantia innominata. Amyloid plaques were not recognized by polyclonal antibodies against the Alzheimer's disease amyloid A4 protein, but did contain epitopes recognized by antibodies against a prion protein. Spongiform changes were occasionally observed and were mild. Our findings indicate that this familial disorder is a form of or is related to Gerstmann-Sträussler-Scheinker disease. The consistent presence of numerous neurofibrillary tangles may be important in differentiating a distinct subgroup of patients with familial Gerstmann-Sträussler-Scheinker disease, and indicates that a disturbance of the cytoskeleton might be part of the neuronal pathology of Gerstmann-Sträussler-Scheinker disease.

Amyloid↗
PubMed1989

Cerebral extracellular preamyloid deposits in Alzheimer's disease, Down syndrome and nondemented elderly individuals.

Using anti-SP28 (a polyclonal antibody to a 28 residue synthetic peptide homologous to the NH2-terminal region of Alzheimer amyloid beta-protein) to investigate the cerebral cortex of 8 Alzheimer and 6 Down patients and 13 nondemented individuals, we found that, besides senile plaques and congophilic vessels, extracellular deposits unrelated to degenerating neurites, tangle-bearing neurons or congophilic vessels were labelled. These deposits were observed in all Alzheimer and 4 Down patients, and in 5 nondemented individuals. The material accumulated in these deposits did not react with Congo red, thioflavine S or, on some occasions, silver salts and therefore might have been constituted by beta-protein and/or beta-protein precursors lacking the conformation of amyloid fibrils.

Aged↗