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Biomedical subjects

G Giaccone

Publications and source records attributed to G Giaccone.

At least 271 records · Page 15Linked to original sources

Preamyloid deposits in the cerebral cortex of patients with Alzheimer's disease and nondemented individuals.

A polyclonal antibody to a 28 residue synthetic peptide, homologous to the NH2 terminal region of amyloid beta-protein, was employed in a study of the frontal and temporal cortex of 8 Alzheimer patients and 13 non-demented individuals aimed to define the relationship of immunolabelled to argyrophilic, congophilic and thioflavine S-positive cortical lesions. In Alzheimer patients, this antiserum labelled not only senile plaques and congophilic angiopathy, but also cortical deposits that were neither argyrophilic, congophilic nor thioflavine S-positive and were unrelated to degenerating neurites, tangle-bearing neurons or congophilic angiopathy. Similar lesions were observed in 4 of 13 non-demented individuals, in the absence of tangles, plaques or congophilic angiopathy, and in one in association with plaques. Such deposits might have been due to amyloid precursors still lacking the beta-pleated sheet molecular conformation responsible for amyloid tinctorial and optical properties.

Adult↗

Cisplatin and etoposide in chemotherapy-refractory advanced breast cancer.

Fourteen evaluable advanced breast cancer patients, extensively pretreated by chemotherapy, received a combination of cisplatin (DDP) and etoposide (VP 16). DDP was given at 60 or 100 mg/m2 on day 1, and VP 16 at 120 mg/m2 on days 1, 2 and 3; cycles were repeated every 4 weeks. Major responses were never obtained; a minor response in 1 patient, no change in 7 patients, and progression in 6 patients were observed. Main side effects were nausea and vomiting (62% severe), and leukopenia (31% leukocytes less than 2,000/mm3). Two patients refused further treatment due to intense nausea and vomiting. DDP-VP 16 combination chemotherapy is ineffective and poorly tolerated in heavily pretreated breast cancer patients.

Adult↗

Carboplatin (JM 8), adriamycin and cyclophosphamide (JAC) in advanced ovarian carcinoma: a pilot study.

Eleven untreated patients with advanced ovarian cancer were studied for tolerance and response to combination treatment with fixed doses of adriamycin (45 mg/m2) and cyclophosphamide (600 mg/m2) + escalating doses of carboplatin. At the first dose level of carboplatin (200 mg/m2), toxicity was acceptable. With carboplatin at 300 mg/m2, severe hematologic toxicity was observed. The dose-limiting toxicity was leukopenia. Although carboplatin was administered without any hydration, no patient experienced renal toxicity. Eight objective responses were observed in 9 clinically evaluable patients. At second look surgery, 3 complete responses and 4 partial responses were documented. Polychemotherapy with JAC (carboplatin, 200 mg/m2, adriamycin, 45 mg/m2, and cyclophosphamide, 600 mg/m2) is administrable with acceptable toxicity.

Aged↗

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

The pharmacokinetics of a 5-day, continuous infusion of vinblastine have been reproduced by an i.v. divided bolus at 0 and 48 h [10]; this schedule can be easily applied to outpatients. We treated 26 evaluable patients with refractory, advanced breast cancer with 3.5-4 mg/m2 vinblastine given i.v. by a divided bolus at 0 and 48 h of 21-day cycles. Neurotoxicity and myelosuppression were the main side effects: severe constipation and peripheral neurotoxicity developed in 14% and 3% of the patients, respectively; severe leukopenia and thrombocytopenia occurred in 24% and 10% of the patients, respectively. One partial response, 14 no changes, and 11 progressions were obtained. Our results do not support the use of vinblastine in divided doses in treating this disease.

Adult↗

Progressive supranuclear palsy with hypertrophy of the olives. An immunocytochemical study of the cytoskeleton of argyrophilic neurons.

In a patient with progressive supranuclear palsy (PSP) and hypertrophy of the olives, neurons with different forms of argyrophilic degeneration were detected by means of Bodian's silver staining method, i.e., neurofibrillary tangle-bearing neurons in the basal ganglia and brain stem, ballooned argyrophilic neurons in the brain stem, and hypertrophied neurons in the olives. In these cells, the cytoskeleton was investigated to ascertain whether neurons with different cytoskeletal changes contained phosphorylated neurofilaments (P-Nf) in the perikaryon. This study, carried out using two monoclonal antibodies that recognize phosphorylated epitopes of the neurofilament high molecular weight subunits, showed that hypertrophied olivary neurons, most ballooned neurons and a small aliquot of tangle-bearing neurons were labelled. The immunostaining of hypertrophied and ballooned neurons was localized in the whole perikaryon and dendrites, whereas that of tangle-bearing neurons was confined to the tangle. These findings were reproduced in five additional patients (one with hypertrophy of the olives, four with PSP) and demonstrated that, in PSP, the mechanism responsible for tangle formation does not affect the ability of neurons to accumulate P-Nf. This fact suggested that perikaryonal P-Nf accumulation is likely to be part of the cell reaction to abnormal conditions affecting the neuronal cytoskeleton.

Brain↗

Teniposide (VM26): an effective treatment for brain metastases of small cell carcinoma of the lung.

Despite good results of chemotherapy in small cell lung cancer (SCLC), occurrence of brain metastases is frequent and unaffected by commonly employed antineoplastic drugs, mainly because they do not cross the blood-brain barrier. We treated eight patients with SCLC and cerebral metastases with VM26 at 120 mg/m2 given on days 1, 3 and 5 and repeated every 3 weeks. Two patients achieved complete response and one had partial response. Mean response duration was 8.2 months and survival was more than 9 months in responding patients. Toxicity was manageable. VM26 is an active drug in SCLC with brain metastases.

Aged↗

High doses of methylprednisolone with or without alizapride in the prevention of cisplatin-induced emesis. A randomized, double-blind, crossover study.

Fifty-two patients undergoing cisplatin-based chemotherapy were randomized to receive either methylprednisolone (1 g i.v. total dose) or methylprednisolone plus alizapride (800 mg i.v. total dose). Major control of emesis (less than or equal to 2 episodes of vomiting) was obtained in around 30% of patients, without difference between the two arms. The combined antiemetic treatment was significantly superior to the single drug in reducing overall number of vomiting episodes (median: 4 vs. 9), duration of emesis (2 vs. 4.5 h), and number of patients with more than 5 vomiting episodes (47.5 vs. 62.5%). Both antiemetic regimens had negligible toxicity and were easily given to outpatients. Though some superiority has been shown for the combined treatment over the single methylprednisolone, the low rate of major control of emesis does not warrant for further investigations of this regimen in cisplatin-treatment patients.

Adolescent↗

Inverted urothelial papilloma: a lesion with malignant potential.

Two cases of inverted urothelial papilloma are presented. In the first case the inverted papilloma was in the ureter and varying degrees of cellular atypia were demonstrated on histology: 7 years later, a single bladder lesion consisting of papillary transitional cell carcinoma and inverted papilloma developed in the same patient. In the second case a bladder tumor consisting of inverted papilloma mixed with papillary infiltrating transitional cell carcinoma was detected. The peculiar morphological findings, histogenesis and biological behavior of inverted urothelial lesions are discussed.

Aged↗

Teniposide in the treatment of small-cell lung cancer: the influence of prior chemotherapy.

Fifty patients with small-cell lung cancer (SCLC) were treated with teniposide (VM26) at 120 to 140 mg/m2 on days 1, 3, and 5, every 3 weeks. Twelve elderly patients were administered VM26 as first-line chemotherapy. Toxicity was manageable, myelosuppression being the major side effect. The response rate for 44 evaluable patients was 34% (36% for untreated patients); the median durations of response and survival were 230 and 208 days, respectively. Effectiveness of prior chemotherapy and time from last administration was found to influence patient response to VM26: 42% of responders to prior chemotherapy responded to VM26, while 0% of the nonresponders to prior chemotherapy responded to the new agent. Moreover, among patients pretreated with chemotherapy, 12% of those recently treated (earlier chemotherapy ending less than or equal to 2.6 months before administration of VM26) responded to VM26, while 53% of patients treated greater than 2.6 months earlier responded to VM26. Survival was influenced by common prognostic factors (performance status, weight loss, prior chemotherapy exposure). Selection of pretreated patients by type of exposure to prior chemotherapy may help in the testing of new drugs in this disease.

Aged↗

The European Organization for Research and Treatment of Cancer (EORTC) trials of new agents for advanced non-small cell lung cancer.

The Lung Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer (EORTC) has recently completed the study of three new agents in phase II trials to determine their efficacy in non-small cell lung cancer (NSCLC). Elliptinium (an ellipticine alkaloid), ametantrone (an anthracenedione derivative), and mitozolomide (an antitumor imidazotetrazine) were evaluated. Elliptinium, ametantrone, and mitozolomide are not recommended for further trials in NSCLC. A pilot study performed within the group with teniposide (VM-26), a podophyllotoxin derivative, at doses ranging from 120 to 180 mg/m2 given on days 1, 3, and 5 every 3 weeks resulted in a 21% response rate in previously untreated patients. Based on these results, the EORTC has initiated a randomized study using teniposide (VM-26) with or without cisplatin.

Aged↗

4'-Deoxydoxorubicin, an inactive drug in small cell lung cancer.

4'-Deoxydoxorubicin was administered to 27 evaluable patients with refractory small cell lung cancer. The majority of patients had good initial performance status. One third of patients had never received doxorubicin before, and six had received a single drug alone (VM26). Myelotoxicity was the main side-effect, and leukopenia was more pronounced than thrombocytopenia. No significant non-hematological toxicity occurred apart from skin necrosis due to drug extravasation in one case. Two patients had partial response (7.4%; 95% confidence limits 0-17.2%). The low response rate obtained in this good prognosis patient population does not support further testing of this drug in small cell lung cancer.

Aged↗

Reinduction chemotherapy in small cell lung cancer.

Thirteen patients with small cell lung cancer responsive to chemotherapy were retreated with the same regimen at relapse, after a median off-therapy time of 30 weeks. Fifty per cent responded to reinduction; two out of six patients who had complete response to first chemotherapy obtained complete response again at reinduction. Median survival time from start of any therapy was 94 weeks. When induction chemotherapy has been effective and of short duration, the same chemotherapy can be attempted again with success at relapse and it may affect survival of relapsing small cell lung cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗

Mitomycin C, vinblastine and cis-platin. An active regimen for advanced non-small cell lung cancer.

Fifty-one patients with advanced non-small cell lung carcinoma were treated with a combination of mitomycin C, vinblastine and cis-platin (MVP). Most cycles were given on an out-patient basis. Major side effects were leukopenia and peripheral neurotoxicity; one patient died of sepsis while leukopenic. In 44 evaluable patients the response rate was 50%, with one complete response. Overall median survival time was 280 days and median duration of responses was 232 days. A better performance status, disease limited to one hemithorax and no prior exposure to chemotherapy positively influenced the survival. MVP is an effective chemotherapy for non-small cell lung cancer and further experience with this combination is warranted.

Adult↗

Bone marrow evaluation in small cell carcinoma of the lung.

Bone marrow examination is commonly included in the staging of small cell lung carcinoma (SCLC). We reviewed marrow samples of 103 patients. Marrow examination was mainly performed by unilateral or bilateral biopsy of iliac crests, using a Jamshidi needle. Only 6 of 97 evaluable cases (6.2 per cent) were positive for marrow metastases at staging, and in 3 cases (3 per cent) bone marrow was the only metastatic site. No focal metastases were found in additional sections made from the blocks of negative samples. In our experience bone marrow biopsy was of little value in staging SCLC. Bilateral biopsy plus aspirate, with the addition of more sophisticated staining techniques might, however, provide a higher yield of positive marrow involvement.

Adult↗

Teniposide in the treatment of non-small cell lung carcinoma.

Forty-two evaluable patients with advanced non-small cell lung cancer were treated with teniposide at doses ranging from 120 to 180 mg/m2 on Days 1, 3, and 5 every 3 weeks. Thirty-four patients had received no prior chemotherapy. Seven partial responses (16.6%) were obtained (21% in chemotherapy-unexposed patients). Marrow toxicity was the main side effect: life-threatening thrombocytopenia occurred in 9% of patients, and 54.5% experienced severe leukopenia. Teniposide, at the doses and schedule employed, has moderate activity in non-small cell lung cancer.

Adult↗

Thymomas. A review of 169 cases, with particular reference to results of surgical treatment.

One hundred sixty-five patients with surgically treated thymoma were followed over 28 years; 73% had myasthenia gravis at presentation. Invasiveness was based on macroscopic findings at operation. Postsurgical radiotherapy or chemotherapy were not routinely used. Overall survival was 84%, 79%, and 65% at 3, 5, and 10 years, respectively. Patients with invasive thymoma survived for a shorter period than patients with noninvasive tumors (67% versus 85% at 5 years); when radical excision was possible, no difference was detectable between the two groups. Patients with subtotally resected or only biopsied invasive thymomas survived 59% and 42% at 5 years, respectively. Lymphoepithelial cases had the worst prognosis of the histologic types considered. Myasthenia gravis did not adversely affect survival. Surgery is the basic treatment of thymomas. Macroscopic invasiveness and degree of excision judged by the surgeon have prognostic value and are reliable criteria of malignancy. Radiotherapy and chemotherapy may be effective, but their use should be limited to controlled trials.

Adolescent↗