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Biomedical subjects

A Macciò

Publications and source records attributed to A Macciò.

40 records · Page 3Linked to original sources

Relationships betxween Fas expression, activation molecule CD25, and functional activity of tumor-associated lymphomonocytes from neoplastic effusions.

Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas bearing cells. In the present study we assessed the expression of Fas, activation molecule interleukin (IL)-2 receptor alpha chain (CD25) and an index of functional activity such as thymidine uptake under mitogen stimulation of tumor associated lymphomonocytes (TALM) from 7 neoplastic effusions of advanced cancer patients. The same parameters were studied in peripheral blood mononuclear cells (PBMC) of 7 patients with cancer of different sites and in 7 normal subjects. The proliferative response to phytohemagglutinin (PHA), measured as [3H]-thymidine uptake, of TALM was significantly lower than that of PBMC of cancer patients. The expression of CD25 on unstimulated fresh TALM was slightly higher than that of PBMC from normal subjects: after 24 h of PHA stimulation the CD25 was expressed both on TALM and PBMC from normal subjects. The expression of Fas was assessed on unstimulated TALM, PBMC from cancer patients and normal subjects immediately after (by 2 h, t0) the cell separation, and at different times (24 h and 48 h) thereafter, and on PHA-stimulated TALM, PBMC from cancer patients and normal subjects after 24 h and 48 h of culture (in RPMI 1640). At all times (t0, 24 h and 48 h) the Fas expression by unstimulated TALM was significantly higher than that of PBMC from normal subjects: the Fas expression by PBMC from cancer patients was roughly in the same range as PBMC from normal subjects. At 24 h the Fas expression by PHA-stimulated TALM was significantly higher than that of PBMC from normal subjects, whereas at 48 h the difference was not significant. The TALM studied by us showed to be functionally defective and expressing relatively high levels of Fas showing the characteristics to be considered as a target for FasL expressing tumor cells, which in this way may escape immune control.

Adult↗

Phase II study of induction chemotherapy followed by concomitant chemoradiotherapy in advanced head and neck cancer: clinical response and organ/function preservation.

We planned to conduct a trial of induction chemotherapy followed by concomitant chemoradiotherapy with the goal of organ-function preservation in advanced head and neck cancer patients with the response rate and local control of disease as primary endpoints and the assessment of toxicity as secondary endpoint. The overall treatment plan consisted of 3 cycles, each q. 28 days, of induction chemotherapy with cisplatin, 5-FU, leucovorin and interferon alpha2b (PFL-IFN), followed by response evaluation and local therapy with concomitant chemoradiotherapy with 5-FU, hydroxyurea and concomitant radiotherapy (FHX). The evaluation of clinical response was performed during the 2nd week after the 3rd cycle of induction chemotherapy and FHX was initiated 28 days after the 3rd cycle of induction chemotherapy. Hydroxyurea was administered orally at doses of 1 g every 12 h x 11, 5-FU was administered on days 1 through 5 at 800 mg/m2/d for 5 days. Daily fraction of radiotherapy were administered at 2.0 Gy on days 1 through 5. FHX cycles were repeated every 14 days until completion of radiotherapy. Total radiotherapy doses consisted of 70 Gy. Seventeen patients (mean age 56.53 years, range 40-73, male/female 15/2, site: oral cavity 6, 35.29%; oropharynx 3, 17.6%; hypopharynx 3, 17.65%; larynx 2, 11.76%; paranasal sinuses 2, 11.76%; salivary glands 1, 5.88%; ECOG PS 0/1: 10/7, stage: III/IV 3/14) were enrolled from January 1998 to August 1998. All 17 patients initiated induction chemotherapy on this protocol. Twelve patients were analyzed for response (5 patients were not evaluable): 2/12 (16.7%) patients achieved a CR and 10/12 (83.3%) achieved a PR for an ORR of 100%. Concomitant chemoradiotherapy was administered on protocol to 10 patients: 4 patients (40%) had CR, 3 patients (30%) had PR >/=70% for an ORR of 70%, 1 patient (10%) had SD and 2 patients (20%) had PD. As for local therapy, according to treatment plan, of the 8 eligible patients who completed chemoradiotherapy, the 4 patients with CR were submitted to random biopsies, which resulted histologically negative, the 3 patients with PR >/=70% underwent conservative organ-preserving surgery, the patient with SD underwent salvage surgery, preserving voice. Thus, organ-preservation was achieved in all 8 patients at the completion of all therapy: 4 patients had no surgical procedure and 3 patients only conservative surgery. Overall, after completion of all therapy, 6/8 (75%) patients were rendered disease-free. Both induction chemotherapy and concomitant chemoradiotherapy resulted in significant toxicity, which consisted mainly of mucositis and thrombocytopenia. In conclusion, in the present study we have achieved a good clinical response and an optimal organ preservation, at the cost of a severe toxicity.

Adult↗

Prevention of nausea and vomiting (N&V) in cancer patients receiving high-dose cisplatin. Assessment of the potential antiemetic activity of transdermal fentanyl (TTS-F) compared to standard antiemetic treatment in acute and delayed N&V: first clinical report.

UNLABELLED: A single-institution, prospective, open crossover study was performed to compare the effectiveness and tolerability of transdermal fentanyl (TTS-F) vs intravenous (i.v.) ondansetron (OND), both combined with i.v. DEX, in the prevention of acute nausea and vomiting (N&V), and TTS-F vs metoclopramide (M), both combined with intramuscular (i.m.) DEX, in the prevention of delayed N&V in patients with advanced stage head and neck squamous cell carcinoma receiving high-dose (> or = 100 mg/m2) cisplatin. This is the first report on the clinical use of TTS-F in this setting. PATIENTS AND METHODS: All patients were adequately informed of the study characteristics and gave their written informed consent before study entry. The antiemetic treatment for acute N&V consisted of A) OND 8 mg plus DEX 20 mg (i.v.) or B) TTS-F 75 micrograms/h plus DEX 20 mg i.v. For prevention of delayed N&V, patients receiving TTS-F for acute N&V were given TTS-F at the same dosage (75 micrograms/h) on days 2-5, whereas patients receiving OND for acute N&V were treated with M 20 mg orally every 6 h on days 2-5, starting 24 h after CDDP. All patients received DEX 8 mg i.m. every 12 h on days 2 and 3, 4 mg i.m. every 12 h on days 4 and 5, starting 24 h after CDDP. From November 1997 to April 1998, 15 consecutive patients entered the study and were assigned to one of the two alternative treatments for acute N&V. All of them were evaluable. Twelve patients were evaluable for delayed N&V. Seven patients were assigned to Group 1 starting with treatment A (OND + DEX) and 8 patients were assigned to Group 2 starting with treatment B (TTS-F + DEX). In the prevention of acute N&V, the overall efficacy of OND + DEX was statistically significantly higher than that of TTS-F + DEX in achieving Complete Response (CR) and Major Efficacy (ME = CR + Major Response, MaR). As for delayed N&V, the overall efficacy of M + DEX, both in achieving CR and ME, although higher, was statistically not significantly different from that of TTS-F + DEX. Unfortunately, due to the small number of patients included in the study, the sophisticated criteria for evaluating response in antiemetic research, such as the persistence of efficacy, the response after crossing-over, did not make it possible for us to draw additional conclusions, although the trend was in favor of "standard" treatments, particularly in acute N&V. The 'response to treatment A (OND + DEX) in the prevention of acute N&V was in the same range as the response to treatment A (M + DEX) for delayed N&V. The response to treatment B (TTS-F) for acute N&V was lower than the response to the same treatment for delayed N&V. The TTS-F treatment was well-tolerated with no significant side-effects including the well-known opioid-related symptoms. Our study confirms that the currently available standard antiemetic treatments both for acute and delayed N&V must be considered by far the most effective ones for clinical use.

Administration, Cutaneous↗