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Biomedical subjects

A Falcone

Publications and source records attributed to A Falcone.

At least 55 records · Page 3Linked to original sources
PubMed1997

Maximum tolerable doses of intravenous zidovudine in combination with 5-fluorouracil and leucovorin in metastatic colorectal cancer patients. Clinical evidence of significant antitumor activity and enhancement of zidovudine-induced DNA single strand breaks in peripheral nuclear blood cells.

BACKGROUND: Experimental studies have demonstrated that 5-fluorouracil (5-FU) enhances zidovudine (AZT)-induced DNA strand breaks and cytotoxicity. Phase I studies have demonstrated that the maximum tolerable dose (MTD) of AZT is 8000 mg/sqm when administered i.v. over two hours after weekly 5-FU + l-leucovorin (LV), and that this combination has promising antitumor activity. The purpose of this study was therefore to evaluate the antitumor activity of weekly bolus 5-FU + LV + AZT, administered at its MTD, and to determine whether 5-FU enhances AZT-induced DNA strand breaks in blood nuclear cells. PATIENTS AND METHODS: Twenty-nine chemotherapy-naïve metastatic colorectal cancer patients with measurable disease entered the study to evaluate the activity of a weekly 5-FU 500 mg/m2 i.v. bolus + LV 250 mg/m2 i.v. two-hour infusion + AZT 8000 mg/m2 i.v. two-hour infusion. In 10 different patients, who during three different weeks received 5-FU + LV, AZT and 5-FU + LV + AZT, DNA strand breaks in blood nuclear cells were determined by a fluorescent analysis of DNA unwinding. RESULTS: Treatment was generally well tolerated and WHO grades III-IV toxicities, consisting mostly of diarrhea (17%), were uncommon. One patient died of severe diarrhea with consequent hypokalemia and cardiac arrhythmia. All patients were considered evaluable for response, and 3 (10%) complete and 10 (35%) partial responses were observed, for an objective response rate of 45% (95% confidence limit interval 26%-64%). Both 5-FU + LV and AZT decreased the percentage of double stranded DNA in nuclear blood cells. The greatest effect was observed with 5-FU + LV + AZT, which reduced the percentage of double stranded DNA to 50% and 36% after 24 and 48 hours, respectively, and this interaction between 5-FU + LV and AZT was found to be cumulative. CONCLUSIONS: These studies demonstrate that the present dose and schedule of AZT in combination with 5-FU + LV has significant activity in metastatic colorectal cancer and that the combination of 5-FU + LV with AZT increases the amount of DNA damage. Therefore, AZT in combination with 5-FU + LV warrants further study in colorectal cancer.

Adult↗
PubMed1997

Clinical results of recombinant erythropoietin in transfusion-dependent patients with refractory multiple myeloma: role of cytokines and monitoring of erythropoiesis.

Recombinant erythropoietin (r-EPO) was administered to 37 patients with advanced, transfusion-dependent and chemo-resistant multiple myeloma (MM), at the fixed dose of 10,000/U s.c., 3 times a week, for 2 months. Thirteen patients (35.1%) achieved a significant response in terms of complete abolition of red cell transfusions. Factors significantly predictive of response were: a) inappropriate production of endogenous EPO, as expressed by a reduced observed/predicted ratio; b) presence of a consistent number of circulating erythroid precursors BFU-E; c) low serum levels of tumor necrosis factor (TNF) and interleukin-1 (IL-1), cytokines with inhibitory activity on erythropoiesis; d) a single line of previously received chemotherapy. Renal failure, bone marrow plasma cell infiltration, serum levels of IL-6 and other main clinical and laboratory parameters did not affect significantly the response to r-EPO. High fluorescence reticulocytes (HFR) and soluble transferrin receptor (sTfR) values were useful to detect an early stimulation of erythropoiesis in responders, while a high percentage of circulating hypochromic erythrocytes (HE), as assessed by an automated counter, identified those patients developing functional iron deficiency during r-EPO treatment. We conclude that about one-third of severely anemic patients with advanced MM, unresponsive to chemotherapy, may benefit by r-EPO therapy. The clinical management of these patients can be accomplished using non-invasive parameters, such as sTfR, HFR and HE.

Adult↗
PubMed1997

Airway eosinophils, T cells, Th2-type cytokine mRNA, and hyperreactivity in response to aerosol challenge of allergic mice with previously established pulmonary inflammation.

Asthma is characterized by acute episodes of nonspecific airway hyperreactivity and chronic pulmonary inflammation exacerbated by stimuli including allergen exposure. In order to reproduce the physiologic and immunologic responses that occur in asthmatic patients, we have characterized a model of antigen-induced inflammation in which allergic mice (B6D2F1) that had been challenged once with aerosolized ovalbumin and had developed a pulmonary cellular infiltrate were rechallenged 1 wk later. Pulmonary inflammation in rechallenged mice was substantially greater than that in single-challenged mice. Eosinophils and activated-memory T cells (CD44+, CD45RBlo) in bronchoalveolar lavage (BAL) fluid accumulated to higher levels and with faster kinetics in response to the second challenge than in response to the first challenge. Eosinophils in lung tissue also accumulated to higher levels but with similar kinetics in response to the second challenge than in response to the first challenge. Similarly, interleukin (IL)-4 and IL-5 steady-state mRNA levels in lung tissue increased after the second challenge and were higher than those measured after a single challenge. Furthermore, treatment of mice with an anti-IL-5 monoclonal antibody 2 h prior to rechallenge inhibited antigen induced eosinophil accumulation in the lungs. In mice challenged twice, peak in vivo bronchoconstrictor responsiveness to acetylcholine was increased following the second challenge compared with that observed following the initial challenge. In contrast, ex vivo tracheal smooth muscle contractile responsiveness to acetylcholine was not altered. Although mucus accumulation and epithelial damage in pulmonary tissue were evident in mice challenged twice, these parameters were slightly reduced compared with those seen at similar times in mice challenged once. Therefore, although these mice exhibit only slight bronchial epithelial damage, the presence of significant inflammation and airway hyperreactivity to acetylcholine as well as slightly increased baseline reactivity demonstrate important similarities with the pathophysiology of asthma.

Administration, Inhalation↗
PubMed1996

Azidothymidine in combination with 5-fluorouracil in human colorectal cell lines: in vitro synergistic cytotoxicity and DNA-induced strand-breaks.

The in vitro cytotoxicity of the combination of azidothymidine (AZT) and 5-fluorouracil (5-FU) against the human colorectal cancer cells SW-480, SW-620 and COLO-320DM was evaluated. The cytotoxic effects of 5-FU and AZT were determined by the assay using 2,3-bis(2-methoxy-4-nitro-5-sulfophenil)-2H-tetrazolium-5-carbo xanilide inner salt (XXT), while drug-induced DNA strand-breaks were measured using a fluorometric analysis of DNA unwinding. After an exposure of 72 h, 5-FU and AZT induced a dose-dependent cytotoxicity against each cell line. The addition of 3, 10 and 30 microM AZT to various concentrations of 5-FU, as well as the addition of 0.5, 1 and 3 microns 5-FU to various concentrations of AZT, resulted in an enhanced cytotoxic effect. Isobologram analysis and the combination index (CI) method demonstrated that the interaction between 5-FU and AZT was clearly synergistic in each cell line, except for the 30% level of effect in SW-620, where borderline synergism was observed. The evaluation of DNA strand-breaks after an exposure of 16 h to 5-FU, AZT or 5-FU + AZT demonstrated that the 5-FU + AZT combination produced the greatest DNA damage, and that this interaction was synergistic in each cell line. In conclusion, our study supports the evidence that the potential antitumour activity of AZT can be modulated by combining it with agents which inhibit thymidylate (dTMP) formation, such as 5-FU, and that the increased cytotoxicity is related to enhanced DNA damage. These findings should encourage further experimental and clinical studies of the potential use of AZT in combination with inhibitors of de novo dTMP synthesis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Treatment of metastatic renal cell carcinoma with constant-rate floxuridine infusion plus recombinant alpha 2b-interferon.

BACKGROUND: Floxuridine (FUDR) and alpha-interferon (IFN) are active agents in advanced renal cell carcinoma, with different dose-limiting toxic effects and antitumor synergism in experimental models. The main purpose of this phase II study was to assess the activity and toxic effects of a combination of FUDR and alpha 2b-IFN in metastatic renal cell carcinoma. PATIENTS AND METHODS: Metastatic renal cell carcinoma patients with measurable disease entered the study. FUDR was administered as a constant-rate continuous infusion for 14 days every 28 days at a starting daily dose of 0.1 mg/kg and with dose escalations of 0.025 mg/kg/day at each subsequent cycle if WHO > or = 2 toxicity had not occurred. IFN-alpha 2b 10 x 10(6) I.U. was administered intramuscularly 3 times per week. RESULTS: Forty-two patients entered the study and a total of 272 cycles of FUDR + alpha 2b-IFN were administered. In 41 evaluable patients WHO grade III-IV toxic effects included nausea and vomiting (22%), diarrhea (32%), stomatitis (12%), fatigue (27%) and anorexia (12%). It was possible to increase the initial FUDR does in 21 (50%) patients; the median FUDR dose intensity was 0.35 mg/kg/week (range 0.18-0.54). Among 39 evaluable patients, 3 (7.5%) complete and 10 (25.5%) partial responses were observed (response rate 33%, 95% confidence interval (CI) 19%-50%) which lasted a median of 13 months (5.5-40+). Responses also occurred in liver (2), in patients pretreated with systemic therapy (5) and in patients who had other unfavourable prognostic characteristics (7). Median progression-free and survival times were 9 and 16 months, respectively. CONCLUSIONS: In this study FUDR + alpha 2b-IFN demonstrated interesting activity in metastatic renal cell carcinoma, showing promise also in patients with unfavourable prognostic characteristics. The antitumor activity of FUDR and alpha 2b-IFN seems to be cumulative, but cumulative toxicity is also observed. These results require confirmation in randomised trials.

Adult↗
PubMed1996

Phase II study of oral doxifluridine in elderly patients with advanced non-small-cell lung cancer.

Elderly patients with advanced non-small-cell lung cancer (NSCLC) are usually excluded from most clinical trials because of the toxicity associated with chemotherapy. About 50% of the new cases of lung cancer occur in patients older than 65 years. Doxifluridine is a fluoropyrimidine derivate which can be administered orally with very low toxicities. This phase II study evaluates the toxicity and activity of a home therapy with oral doxifluridine in elderly advanced NSCLC patients. Thirty-three advanced NSCLC patients, aged 70 years or more, entered the study; median ECOG performance status was 1 (0-2) and 22 patients (66.6%) had metastatic disease. Doxifluridine was given orally in three divided doses, for a total daily dose of 2,250 mg, for 4 consecutive days every week. The treatment was well tolerated; five patients (15%) experienced a grade 3 diarrhea which required doxifluridine dose reduction to 1,500 mg daily. Thirty-one patients are evaluable for response; four partial responses (12.9%) have been observed (95% confidence limit interval 3.6-29.8%); 17 patients (54.8%) had a stabilization of the disease. This study demonstrates that a home therapy with oral doxifluridine in elderly NSCLC patients is feasible and well tolerated and should encourage further studies.

Administration, Oral↗
PubMed1996

T cells are the predominant source of interleukin-5 but not interleukin-4 mRNA expression in the lungs of antigen-challenged allergic mice.

Pulmonary inflammation is characterized by the accumulation of eosinophils and other leukocytes in the lungs of individuals challenged with antigen. Cytokines released by the Th2 lymphocyte subset, especially interleukin-4 (IL-4) and interleukin-5 (IL-5), are also present and thought to play an important role in this process. Previously, we used a model of aerosolized antigen challenge of sensitized mice to show that T cells were necessary for the accumulation of eosinophils and the production of cytokine steady-state messenger ribonucleic acid (mRNA). T cells were isolated from lung tissue at a time (4 h) when high levels of IL-4 and IL-5 mRNAs had accumulated, and from bronchoalveolar lavage fluid (BALF) and lung tissue at a later time (24 h), when inflammation could be detected by lavage. Lung-derived lymphocytes from sensitized challenged mice consisted of approximately 40% Thyl+ T cells (20% CD4+, 13% CD8+, and 6% CD4+/CD8+) and 30% B220+ B cells. Both BALF- and lung-derived T lymphocytes exhibited a similar activated/memory phenotype (CD44+ CD45RBlo), although lung tissue also contained less differentiated cells (CD44+ CD45RBhi). Thyl+ BALF cells isolated by magnetic bead-mediated separation accounted for approximately 88% of the IL-5 mRNA, 21% of the interferon-gamma (IFN-gamma) mRNA, and < 2% of the IL-4 mRNA detected in unseparated samples by reverse transcriptase-polymerase chain reaction (RT-PCR). Thyl+ T cells from lung tissue accounted for approximately 98% and 89% of IL-5 mRNA, 56% and 80% of IFN-gamma mRNA, and 23% and 40% of IL-4 mRNA at 4 h and 24 h after challenge, respectively. These experiments demonstrate that isolated T cells from BALF and lung are responsible for most of the IL-5 mRNA, but not all of the IFN-gamma or IL-4 mRNAs, detected in this model. These results are consistent with human studies indicating T cells as the major source of IL-5 mRNA in the lungs of asthmatic patients.

Animals↗
PubMed1996

Intravenous azidothymidine with fluorouracil and leucovorin: a phase I-II study in previously untreated metastatic colorectal cancer patients.

PURPOSE: To determine the plasma pharmacokinetics and the maximum-tolerated dose (MTD) of intravenous (IV) azidothymidine (AZT) administered 90 to 120 minutes after fluorouracil (5-FU) and leucovorin and to preliminarily evaluate the antitumor activity of this combination in metastatic colorectal cancer. PATIENTS AND METHODS: 5-FU 500 mg/m2 IV bolus was administered once a week in the middle of a 2-hour infusion of leucovorin; AZT was given as a 90 to 120-minute IV infusion 60 minutes after 5-FU. Initial AZT dose was 0.5 g/m2, and it was escalated in successive cohorts of three patients by 0.5 to 2 g/m2. RESULTS: Thirty-five chemotherapy-naive metastatic colorectal cancer patients were entered onto the study, and AZT doses ranged from 0.5 to 10 g/m2. The peak AZT plasma concentration increased from 21.9 to 995.6 micromol/L. The area under the concentration/time curve (AUC) also showed a progressive, but not linear increase from 40.34 to 3,108 h x micromol/L. The most relevant toxicity was diarrhea, which was severe in six patients (17%). Toxicities were not AZT-dose-related, except fpr hypotension, which occurred in patients treated at AZT doses > or = 7 g/m2 and became dose-limiting for AZT 10 g/m2. Among 34 assessable patients, 15 objective responses were observed (44%; 95% confidence interval 27 to 62), lasting a median of 44 weeks; five (15%) were complete. CONCLUSION: AZT doses > or = 6 g/m2 administered IV over 90 to 120 minutes produce maximum plasma concentration and AUC similar to those previously reached in murine tumor models. Dose-limiting toxicity is hypotension, which occurs at AZT 10 g/m2. The recommended AZT dose for further studies is 8 g/m2. The combination of 5-FU plus leucovorin plus AZT is feasible with acceptable toxicities, and has promising activity in metastatic colorectal cancer.

Adult↗
PubMed1996

Biochemical modulation by 5-fluorouracil and 1-folinic acid of tumor uptake of intra-arterial 5-[123I]iodo-2'deoxyuridine in patients with liver metastases from colorectal cancer.

In previous studies we demonstrated a high tumor-targeting value of the 123I-labeled thymidine analogue 5-iodo-2'-deoxyuridine (IUdR) infused intra-arterially in patients with liver metastases from colorectal cancer. In the present study we have explored the possibility of enhancing tumor uptake of [123I]IUdR, by biochemical modulation with 5-fluorouracil (5-FU) and 1-folinic acid (FA), a drug combination known to inhibit thymidylate synthetase in tumor cells. The investigation was carried out employing diagnostic imaging doses of [123I]IUdR, much lower than possible therapeutic levels. In the baseline study, [123I]IUdR was infused into the hepatic artery of patients with inoperable liver metastases from colorectal cancer, and a second infusion was performed one week later, after intra-arterial administration of 5-FU and FA. The effect was evaluated by comparing tumor uptake of [123I]IUdR in the second study with that of the baseline study. The average tumor uptake immediately after [123I]IUdR infusion was 9.1% ID in the baseline study, increasing to 14.9% ID after pretreatment with 5-FU and FA. The average enhancement in early tumor uptake of [123I]IUdR induced by biochemical modulation was 72%. This enhancement was sustained at 18 and 42 hours after infusion (stable uptake). The results encourage the pretreatment of patients with 5-FU and FA prior to radioiodinated IUdR administration and suggest its inclusion in therapeutic protocols employing IUdR labeled with 123I or 125I as a source of highly cytotoxic Auger electrons.

Aged↗
PubMed1996

Tumor targeting by intra-arterial infusion of 5-[123I]iodo-2'-deoxyuridine in patients with liver metastases from colorectal cancer.

UNLABELLED: We previously showed the tumor-targeting potential of the 125I-labeled thymidine analog 5-iodo-2'-deoxyuridine (IUdR) injected intratumorally in patients with high tumor-cell kinetics. In this study, we evaluated the tumor incorporation of [123I]IUdR infused intra-arterially in patients with liver metastases from colorectal cancer. METHODS: Iodine-123-IUdR (110-300 MBq, 3-8 mCi, specific activity, 150-200 Ci/mumole) was infused into the hepatic artery of 16 patients with inoperable liver metastases over 30-45 min through a permanent intra-arterial catheter. A dynamic sequence during infusion, spot images, whole-body scans and SPECT acquisitions were recorded up to 42 hr. Blood and urine samples were obtained for biodistribution and HPLC analyses. RESULTS: In the 14 patients with adequate tumor perfusion patterns, tumor uptake reached 2%-17.6% ID at the end of infusion. After a washout phase that lasted 18-20 hr, incorporated radioactivity remained steadily associated with the tumor lesions until at least 42 hr after infusion (about 1.4%-11.1% ID). HPLC analysis indicated a virtually 100% first-pass hepatic deiodination of unincorporated [123I]IUdR (about 80%-95% ID recovered in the 42-hr urine). No significant uptake was detected in the bone marrow or in other normal dividing tissues. CONCLUSION: These results encourage further studies to enable dosimetric estimates, optimization of dose regimens, and examination of the therapeutic potential of Auger-electron-emitter-labeled IUdR in cancer therapy utilizing this type of approach.

Aged↗
PubMed1995

Suramin in patients with metastatic colorectal cancer pretreated with fluoropyrimidine-based chemotherapy. A phase II study.

BACKGROUND: The results of conventional chemotherapy in metastatic colorectal cancer are discouraging, making it a logical target for new treatment approaches a necessary consideration. Suramin is a polysulfonated naphthylurea that binds to several cellular growth factors and has in vitro activity against human colorectal cancer cells. Therefore, this Phase II study of patients with metastatic colorectal cancer was conducted to evaluate its clinical activity. METHODS: Suramin was administered as a 6-day continuous infusion every week for 8 consecutive weeks by using a computer-assisted dosing of Bayesan pharmacokinetics to maintain suramin plasma concentrations of 200-250 micrograms/ml. Twenty patients with metastatic colorectal cancer who were not responsive or in progression within 6 months after completing fluoropyrimidine-based chemotherapy entered the study. RESULTS: Toxicities included mostly Grade 1 and 2 fatigue, nausea and vomiting, peripheral neurotoxicity, creatinine elevation, and proteinuria. No objective responses were observed, but three of three patients who received 5-fluorouracil plus folinic acid after suramin achieved a partial response. CONCLUSIONS: These results indicate that suramin is inactive in patients with metastatic colorectal cancer pretreated with fluoropyrimidines. Pretreatment with suramin may have changed the biology of the tumor, sensitizing it to fluoropyrimidines. Studies to investigate this possibility are in progress.

Adult↗
PubMed1995

T cells are necessary for Th2 cytokine production and eosinophil accumulation in airways of antigen-challenged allergic mice.

In a murine model of pulmonary inflammation, aerosolized antigen challenge of sensitized B6D2F1 mice leads to eosinophil accumulation within the lungs. Little is known of the role of T cells and their cytokine products in these allergic animals. In this study, we show that T cells migrate into the lungs in response to antigen challenge and are necessary for local production of cytokines (IL-4 and IL-5) important in B and T cell development as well as eosinophil activation and differentiation. Flow cytometry revealed an increase in the percentage of Thy1+ T cells but not in B220+ B cells in bronchoalveolar lavage fluid after challenge when compared to unchallenged mice. Although there was an increase in both T cell subsets, there were twice as many CD4+ cells as CD8+ cells at 24 hr and after 48 hr the CD4+ subset predominated. The CD4+ T lymphocytes were CD44+ CD45RBlo indicating an activated/memory phenotype and tracheobroncheal lymph node cells obtained from challenged mice proliferated in a dose-dependent manner in response to antigen stimulation in vitro. Reverse transcriptase-polymerase chain reaction analysis of lung tissue-derived RNA indicated an increase in Th2-like cytokines. IL-4 and IL-5 steady-state mRNAs were at peak levels 6 hr after challenge, while no consistent increase was found for IFN-gamma mRNA levels. Treatment with the glucocorticoid betamethasone just prior to challenge reduced the levels of cytokine mRNA as well as the eosinophil influx. In vivo depletion of T cells from sensitized mice reduced pulmonary eosinophilia as well as the expression of IL-4, IL-5, and IFN-gamma steady-state mRNAs in the lungs of sensitized and challenged mice. These results indicate that T cells migrating into the lungs of mice after antigen challenge play an important role in the production of Th2-like cytokines and the accumulation of eosinophils in bronchial fluids.

Animals↗
PubMed1995

Prognostic relevance of serum thymidine kinase in primary myelodysplastic syndromes: relationship to development of acute myeloid leukaemia.

The aim of this study was to evaluate the possible prognostic relevance of thymidine kinase serum levels (s-TK), an indirect marker of proliferative activity, in myelodysplastic syndromes (MDS). S-TK levels were monitored by means of a radioenzyme assay in 90 patients affected by MDS (22 refractory anaemia, RA; 17 RA with ring sideroblasts, RARS; 21 RA with blast excess, RAEB; 15 RAEB in transformation, RAEB-T; 15 chronic myelomonocytic leukaemia, CMMoL). Mean s-TK levels (U/microliter) measured at diagnosis were 11.9 +/- 12.6 for RA, 11.4 +/- 13.6 for RARS, 19.9 +/- 28.4 for RAEB, 39.6 +/- 34.3 for RAEB-T and 77.7 +/- 69.7 for CMMoL (normal values < 5 U/microliter). With the only exception of a weak relationship with lactate dehydrogenase, no correlation was found between initial s-TK values and other clinical or laboratory parameters, such as age, haemoglobin, white blood cell or platelet count, percentage of bone marrow blasts. MDS patients with s-TK > 38 U/microliters, a cut-off level selected by means of ROC statistical analysis, showed a significantly shorter survival than those with s-TK < 38 U/microliter (8.2 v 37.4 months, respectively; P < 0.0001). In particular, transformation in acute myeloid leukaemia (AML) occurred in 17/21 (81%) of patients with s-TK > 38 U/microliters and 9/69 (13%) of those with lower levels at diagnosis (P < 0.0001), independently of FAB subtype. High s-TK levels were also useful to predict evolution in AML during the course of the disease in patients with normal initial values. Multivariate analysis confirmed the independent prognostic value of s-TK on both overall survival and risk of acute transformation. We conclude that s-TK may be an important prognostic factor in MDS, strongly correlated with development of AML.

Acute Disease↗
PubMed1995

sVCAM-1 levels after segmental antigen challenge correlate with eosinophil influx, IL-4 and IL-5 production, and the late phase response.

Evidence from in vitro studies suggests a potential role for vascular cell adhesion molecule-1 (VCAM-1) in eosinophil trafficking. We hypothesized that induction of VCAM-1 occurs in the lung during IgE-mediated airway inflammation in humans. The technique of segmental antigen provocation followed by bronchoalveolar lavage (BAL) at 24 h was used to study 27 ragweed-allergic asthmatics (AA) and 18 atopic nonasthmatics (ANA). Total and differential cell counts were performed, and IL-4, IL-5, and soluble (VCAM) (sVCAM) levels in concentrated BAL fluid were measured by ELISA. A large increase in sVCAM levels after segmental challenge in both AA and ANA (1.79 +/- 0.31 to 139.39 +/- 68.58 ng/ml, p < 0.0005 and 2.85 +/- 0.80 to 98.25 +/- 77.35 ng/ml, p < 0.05, respectively) was observed. BAL IL-4 and IL-5 also increased after challenge (IL-4: 51.7 +/- 17.72 to 150.1 +/- 58.82 pg/ml, 0.05 < p < 0.10, n = 20 for AA, and 36.6 +/- 9.05 to 116.8 +/- 51.5 pg/ml, 0.05 < p < 0.10, n = 15 for ANA; IL-5: 0 to 2.67 +/- 1.62 ng/ml, p < 0.01, n = 16 for AA, and 0 to 2.87 +/- 2.16 ng/ml, 0.05 < p < 0.10, n = 10 for ANA). In both groups, the majority of the increase in sVCAM, IL-4, and IL-5 was accounted for by subjects who displayed a dual phase response after whole-lung antigen inhalation. This fact, plus the strong correlation observed between postchallenge sVCAM, IL-4, and IL-5 levels and eosinophil influx, suggests that VCAM, IL-4, and IL-5 play important roles in the recruitment of eosinophils to the lung of humans after antigen challenge.

Adult↗
PubMed1994

Phase II trial of 5-fluorouracil and the natural l isomer of folinic acid in the treatment of advanced colorectal carcinoma.

Between February 1991 and July 1992, 79 previously untreated patients with metastatic colorectal carcinoma were enrolled in a phase II study of combined 5-fluorouracil (5-FU) and l-folinic acid (FA). 5-FU 370 mg/m2/day was administered for 5 consecutive days as an intravenous (i.v.) bolus injection preceded by l-FA 100 mg/m2/day with the same administration modality. Treatment was given every 4 weeks until progression. 79 patients were evaluable for toxicity and 64 for response. 2 patients (3%) achieved a complete remission and 8 (12.5%) a partial remission, 33 (52%) had stable disease and 21 patients (33%) had progressive disease. Median duration of remission was 32.5 weeks and median survival for all evaluable patients was 64.5 weeks. Substantial to severe side-effects occurred in 39% of patients. Dose-limiting toxicity (grade 3-4) was mainly diarrhoea (18%) and mucositis (15%). Nausea/vomiting, cutaneous toxicity, leucopenia, alopecia and conjunctivitis of grade 3-4 occurred respectively in 6, 4, 2.5, 1 and 1% of cases. Toxicity appeared to be substantially similar to that characteristic of combined 5-FU and the chiral mixture of d,l-FA. Efficacy was within the range of that observed with the 5-FU/d,l-FA combination, although at the lower level.

Adult↗
PubMed1994

Synergistic antiproliferative activity of suramin and alpha 2A-interferon against human colorectal adenocarcinoma cell lines: in vitro studies.

Suramin, a polysulphonated naphthylurea proven to be an effective anticancer agent against selected tumours, and alpha 2A-interferon (alpha 2A-IFN) were investigated for their combined effects on HCT-8, HCT-15, CL-D, SW-480 and SW-620 human colorectal adenocarcinoma cell lines. All lines were sensitive to clinically achievable concentrations of suramin in a dose-dependent manner, while alpha 2A-IFN alone induced only a modest reduction of cell growth. Concomitant treatment with suramin and alpha 2A-IFN resulted in a synergistic inhibition of cell viability in each cell line at all doses tested. However, when suramin and alpha 2A-IFN were administered sequentially, inhibition of cell viability was clearly dependent on the timing of treatment schedule, with maximum effect obtained when alpha 2A-IFN was administered prior to suramin. In contrast, pretreatment with suramin was markedly inferior to the former one. In conclusion, suramin and alpha 2A-IFN exert a synergistic effect on human colorectal cell proliferation in vitro at clinically achievable concentrations. This observation may have clinical relevance although the mechanisms of interaction remain to be elucidated.

Adenocarcinoma↗