[Clinical experience with the use of dopamine in pre-term neonates with the respiratory syndrome].
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Dopamine↗
Biomedical subjects
G Giaccone
Publications and source records attributed to G Giaccone.
[Spontaneous chylothorax in intensive therapy of a very low-weight newborn infant with septicemia caused by Enterobacter cloacae].
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Chylothorax↗
Combination chemotherapy for metastatic brain tumors.
Forty-four patients with central nervous system metastases were treated with combination chemotherapy (adriamycin, VM 26 and CCNU). The best results were obtained in breast adenocarcinoma and small cell lung carcinoma with multiple, small cerebral metastases and without concomitant visceral involvement at other sites. The potential effectiveness of this regimen to prevent cerebral metastases is discussed.
Adenocarcinoma↗
MDR1/P-glycoprotein expression in colorectal cancer.
Drug resistance to multiple chemotherapeutic agents is considered a major cause of chemotherapy failure. An extensively studied and relatively well understood type of cellular drug resistance is P-glycoprotein (Pgp)-mediated multidrug resistance (MDR). Pgp acts as an energy-dependent drug efflux pump, thereby decreasing the intracellular drug concentration and causing drug resistance, in in vitro experiments. Colorectal cancer and colorectal mucosa generally express high levels of Pgp, and this may contribute to the general unresponsiveness of colorectal cancer to natural product, anticancer drugs. The controversies concerning the prognostic role of Pgp expression and its contribution to tumour aggressiveness, and possible reasons for the disappointing results of clinical MDR reversal trials in colorectal cancer are discussed.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Combination of gemcitabine and cisplatin for advanced non-small cell lung cancer: a phase II study with emphasis on scheduling.
BACKGROUND: Many regimens of gemcitabine-cisplatin chemotherapy have proven activity in patients with advanced non-small cell lung cancer (NSCLC). However, the optimal dose and schedule still have to be established. PATIENTS AND METHODS: We conducted a phase II study with administration of cisplatin 50 mg/m(2) on days 1 and 8 and gemcitabine 800 mg/m(2) on days 2, 9 and 15. This schedule was selected to optimise the synergism between the two drugs and reduce toxicity due to high dose cisplatin. RESULTS: Thirty-six chemo-naive patients with stage IIIA, IIIB or IV NSCLC entered the study (26 men, 10 women; median age 58 years, range 29-74). Twenty patients achieved a partial response: 7 out of 10 stage IIIA patients, 7 out of 13 stage IIIB patients and 6 out of 13 stage IV patients. On intent-to-treat basis, the overall response rate (RR) was 58% (95% confidence interval, 42-74%). Ninety percent of stage IIIA patients and 46% of stage IIIB patients received adjuvant surgery or radiotherapy. Overall median duration of response was 28 weeks (range 6-147 weeks). For stage IIIA, IIIB and IV patients, these numbers were 91, 13 and 23 weeks, respectively. One-year survival was 49% with 90%, 23% and 42% for stage IIIA, IIIB and IV patients, respectively. The main toxicity was myelosuppression. WHO grades 3 and 4 leukopenia occurred in 67% of patients, whereas 61% experienced grade 3 or 4 thrombocytopenia. Although hematological toxicity was clinically tolerable, it frequently led to omission of gemcitabine administration on day 15. The incidence of non-hematological toxicity was very low. CONCLUSION: This regimen of cisplatin on days 1 and 8 and gemcitabine on days 2, 9 and 15 induced a high RR in patients with advanced NCSLC. Frequent omission of gemcitabine day 15 is a limitation of this schedule. This should be an important factor in a practical approach to decide on the most optimal schedule of the cisplatin plus gemcitabine combination.
Adolescent↗
The multilayered postconfluent cell culture as a model for drug screening.
New drug development requires simple in vitro models that resemble the in vivo situation more in order to select active drugs against solid tumours and to decrease the use of experimental animals. In this paper, we review the characteristics and scope of a relatively simple cell-culture system with a three-dimensional organisation pattern - the multilayered postconfluent cell culture model. Solid tumour cell lines from diverse origins when grown in V-bottomed microtiter plates reach confluence in 3-5 days and then start to form multilayers. The initial exponential growth of the culture is followed by a plateau phase when cells reach confluence. This produces changes in the morphology of the cells. For some cell lines, it is possible to observe cell differentiation. A substantial advantage of the system is the use of the sulforodamine B (SRB) assay to determine relative cell growth or viability, which allows semiautomation of the experiments. Several experiments were performed to assess the differences and similarities between cells cultured as monolayers and multilayers, and eventually, compared with the results for solid tumours and some other models such as spheroids. Cell-cycle analysis for multilayers showed a lower S-phase arrest, which is accompanied by a decrease in the expression of cell-cycle-related proteins and a decrease in cellular nucleotide pools. Gene and protein expression of topoisomerase I, topoisomerase II and thymidylate synthase expression were lower for multilayers, but no substantial changes were observed for the expression of DT-diaphorase. P53 expression increased. Multilayer cultures present distinctive properties for drug transport across the membrane, drug accumulation and retention. In fact, the transport of antifolates across the membrane, accumulation of topotecan and gemcitabine-triphosphate are reduced in multilayers when compared with monolayers, which may be related to a decrease in drug penetration to the inner regions of the multilayers. Alteration of these pharmacodynamic parameters is directly related to a decrease in drug activity. The most powerful application of multilayers is in the assessment of cytotoxicity. Solid tumour cell lines from different origins have been treated with several conventional and investigational anticancer drugs. The data show that multilayers are more resistant to the drugs than the corresponding monolayers, but there are substantial differences between the drugs depending on culture conditions, e.g. the difference was rather small for a drug such as cisplatin, miltefosine and EO9, a drug, which is activated under hypoxic conditions. Gemcitabine was active against ovarian cancer but not against colon cancer, resembling the in vivo situation. This observation was not evident with monolayer experiments. Another interesting application is the possibility to perform drug combination studies. The combination of gemcitabine and cisplatin proved to produce selective cell kill in H322 cells (non-small cell lung cancer cell line). Neither of the drugs was independently able to produce similar effects. In summary, multilayer cultures are relatively simple three-dimensional systems to study the effect of microenvironmental conditions on anticancer drug activity. The model might serve as a base for a more rigorous secondary in vitro screening.
Animals↗
Chest irradiation as an attempt to improve the response after induction chemotherapy in small cell lung carcinoma.
Forty-six patients with small cell lung carcinoma received cyclic chemotherapy with cisplatin-VP 16 and vincristine, doxorubicin, and cyclophosphamide. The responding patients were given prophylactic cranial irradiation. Patients without metastases not achieving a complete response (CR) following induction chemotherapy were given chest irradiation. The response rate was 73.9 per cent. Response was improved by radiation therapy in only 9 per cent of the patients with limited disease. Median survival was 39 weeks, with 2 patients surviving for longer than 24 months. The duration of response and survival in complete and partial responders was similar; absence of radiation therapy in the patients with CR might explain this finding.
Antineoplastic Combined Chemotherapy Protocols↗
A PCR-aided transcript titration assay (PATTY) to measure topoisomerase I gene expression in human tumor specimens.
UNLABELLED: Topoisomerase I (topo I) inhibitors are promising anticancer agents with demonstrated activity against a wide range of solid tumors. Quantitative information on topol mRNA levels in tumor biopsies may predict response to topo I inhibitors. MATERIALS AND METHODS: A polymerase chain reaction aided transcript titration assay (PATTY) was developed to allow quantitation of topol mRNA in small samples. Concentrations of topol mRNA in total RNA samples were estimated by RT-PCR analysis in a human small cell lung cancer (SCLC) cell line (GLC,) and its topotecan (GL2C/SK and F) and camptothecin (GL2C/Campt) resistant sublines, human non-small cell lung cancer (NSCLC) and ovarian carcinoma samples. RESULTS: Topol PATTY showed a decreased topo I mRNA level in GLC2/SK and F (4.5 pg/100 ng total RNA) and GLC,/Campt (2.2 pg/100 ng total RNA), respectively, compared to the parent cell line GLC2 (5.4 pg/100 ng total RNA). Topol protein levels as measured by Western blotting were compatible with topol mRNA levels. Median (range) topol mRNA levels were 3.23 (2.33-5.10) pg/100 ng total RNA in resected NSCLC specimen (n = 6), and 2.03 (0.54-0.95) pg/100 ng total RNA in resected ovarian cancer specimen (n = 6). CONCLUSION: We conclude that topol PATTY is a new assay that quantitates topol mRNA levels in cell lines and small tumor samples.
Blotting, Northern↗
Validation of a polymerase chain reaction aided transcript titration assay (PATTY) for topoisomerase II in lung cancer samples.
This report describes the validation of a polymerase chain reaction aided transcript titration assay (PATTY) for tumor samples. The results obtained with the PATTY were compared to those of RNase protection in a set of 7 human lung cancer cell lines and in 23 non-small cell lung cancer samples derived from resected patients. Whereas between PATTY and RNase protection assay a good correlation was observed in the cell lines (r = 0.74, p = 0.057), no correlation was observed within the tumor samples (r = 0.06, p = 0.78). This was also the case when only tumors with a high percentage of tumor cells (> 90%) were selected. Although PATTY is a valuable tool to measure mRNA expression in cell lines, our results caution the use of PATTY in human tumor samples without proper validation. The possible causes of these results are discussed.
Antigens, Neoplasm↗
In vitro chemosensitivity testing of multilayered microcultures.
A potential limitation of in vitro microtiter cytotoxicity assays as compared to in vivo antitumor studies is that the complex three-dimensional structure of the solid tumor is lost in monolayer cultures in vitro. We investigated whether more in vivo like cell-cell interactions could be easily and reproducibly obtained in an in vitro cytotoxicity assay. HT29 human colon adenocarcinoma cells were seeded in 96-well microtiter plates with "V"-shaped wells and allowed to form postconfluent multilayered cultures. Cross-sections of microcultures fixed after 2 and 3 weeks following plating revealed approximately 7 and 35 cell layers, respectively. Using a tetrazolium assay to assess cytotoxicity, the EC50 (drug concentration which gives absorbance readings 50% lower than those of non-treated wells) of multilayered cultures exposed to doxorubicin for 24 h was 12 times higher (p less than 0.05) than that determined for subconfluent monolayered cells simultaneously exposed to the drug. This system offers an alternative to study the chemosensitivity of three-dimensionally organized cells using semiautomated microtiter plate technology.
Colonic Neoplasms↗
FOLFOX3 in heavily pretreated patients with metastatic colorectal cancer.
BACKGROUND: The combination of oxaliplatin, 5-fluorouracil (5FU) and leucovorin (LV) has shown to be active and safe as first- or second-line chemotherapy for metastatic colorectal cancer (MCC). PATIENTS AND METHODS: The outcome of patients with MCC who had progressive disease after at least two lines of palliative chemotherapy and who were subsequently treated with oxaliplatin, 5FU and LV was reviewed. Patients received FOLFOX3 consisting of oxaliplatin (85 mg/m2) on day 1, LV (500 mg/m2) as a two-hour infusion on days 1 and 2, and 5FU (3000 mg/m2) as a 46-hour infusion starting on day 1 in a cycle of two weeks. RESULTS: A total of 28 patients were treated with a median number of 9.5 cycles (range 1-24) at a mean dose intensity of 73%. Six patients discontinued treatment due to toxicity, of whom three had sensory neuropathy grade 2. Six patients experienced grade 3 toxicity: nausea (1), vomiting (1), diarrhoea (1), leucopenia (2) and thrombocytopenia (1); grade 4 toxicity was not observed. Twenty-five patients were evaluable for response, of whom four achieved a partial response (response rate 14%, based on intention to treat). The median progression-free survival was 5.8 months and the median overall survival was 8.5 months. CONCLUSION: For heavily pretreated patients with MCC, the FOLFOX3 regimen is a fairly safe and effective treatment.
Adult↗
Phase II study of alpha-interferon plus bleomycin in advanced non-small cell lung cancer.
A synergistic effect between alpha-Interferon and Bleomycin has been recently shown in in vitro and in vivo experimental systems. Although active, Bleomycin and other antineoplastic drugs give low response rates in non-small cell lung cancer, but, like the other antineoplastic agents, responses are short-lived. We treated 13 patients with advanced non-small cell lung cancer with the combination Bleomycin 15 mg/m2 i.v. at hour 0 and alpha-Interferon 9 X 10(6) U i.m. given at hours 6, 30 and 54. Major side effects were pyrexia, astenia and anorexia; only one case of moderate leukopenia was observed. No major responses were obtained and stable disease lasted a median of 5 months. Further study of this combination is not warranted in patients with pretreated non-small cell lung cancer.
Antineoplastic Combined Chemotherapy Protocols↗
[Piperacillin and amikacin in the treatment of infections in neoplasm patients with granulocytopenia].
Infections are the most common cause of death in tumor patients. The risk of infection is progressively increased in relation to the severity of neutropenia. It is therefore essential to start empirical antibiotic therapy in these patients at the first sign of infection. Forty-three neutropenic tumor patients were entered into the above study when it was assumed that they had bacterial infections (temperature above 38.5 degrees C and/or signs and symptoms of infection). Patients with greater than 1000 neutrophils/mm3 were given piperacillin alone while those with more severe neutropenia (less than 1000/mm3) were given a combination of piperacillin plus amikacin. Of the 43 patients who had entered the study, 41 could be evaluated whereas the remaining two were considered dropouts either because of non-compliance with the study protocol or because the infection was found to be non-bacterial. In both groups of patients (greater than 1000 and less than 1000 neutrophils/mm3) infection resolved completely in a large percentage of cases (92% and 82%, respectively). The efficacy of piperacillin was therefore reconfirmed for the management of infection in oncologic patients with neutropenia, and proved to be an effective therapeutic resource in patients with both slight and severe neutropenia.
Adolescent↗
[Monitoring of neuron specific enolase (NSE) in patients with a diagnosis of pulmonary microcytoma. Preliminary results].
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Adult↗
Small cell lung cancer and topoisomerases.
Topoisomerases are nuclear enzymes involved in steps of DNA metabolism which require topological modifications. Interestingly, these enzymes have been discovered to be targets of several anticancer drugs in common clinical use. Alterations of the topoisomerase enzymes have been described as associated with the development of drug resistance to topoisomerase inhibitors. The best known alterations are reduced gene expression and mutations in the genes. The present knowledge of the role of topoisomerases in lung cancer, and in small cell lung cancer in particular, is described here.
Carcinoma, Small Cell↗
[The partial parenteral nutrition of preterm infants with a body weight < 1000 g: the effects of an infusion of human albumin on plasma amino acid concentration].
This paper concerns with the changes of plasma amino acid (AA) concentrations of N. 10 ELBW infants receiving a regimen of partial parenteral nutrition including human serum albumin (HSA) as a protein supply. The plasma AA concentration has been compared with VLBW infants orally fed with human milk (HM) or human milk supplemented with human milk protein (HMP). As for the essential AA: in comparison to VLBW infants fed HM, the plasma concentration of VAL, PHE and LYS is significantly higher, that of THR, MET, LEU and HIS is similar, whereas that of ILE is significantly lower; in comparison to VLBW infants fed HMP, with the exception of PHE whose plasma concentration is higher, concentration of essential AA significantly lower; the percentage ratio between plasma concentration and intake is in the range of 1,4 to 3,3, except for LYS (= 0.83), indicating a good efficacy of the i.v. administered HSA as AA source, or a slow plasma clearance or a sustained flux of AA from body protein catabolism. Further researches are needed to investigate these aspects and the intermediate steps between i.v. infusion of HSA and the utilization of the component AA for body protein synthesis.
Amino Acids↗
New drugs for the management of lung cancer.
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Antimetabolites, Antineoplastic↗
Clinical neuropathology of Creutzfeldt-Jakob disease.
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Adolescent↗