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Biomedical subjects

S Toma

Publications and source records attributed to S Toma.

At least 73 records · Page 4Linked to original sources
PubMed1995

Amyotrophic cervical myelopathy in adolescence.

The clinical and radiological features in seven patients who had asymmetric muscular atrophy of the hand and forearm when young are reported and a new hypothesis for its aetiology is proposed. Investigation of body growth curves (a surrogate for velocity of arm growth) showed close relation between (a) the age when the body height increased most rapidly and the onset age of this disorder, and (b) the age when the rapid body growth period ended and the age when symptom progression ceased. Cervical radiological evidence is provided showing asymmetric anterior cord atrophy, disappearance of slackness of dorsal roots in neck extension, and anterior and lateral displacement of the lower cervical cord against the posterior aspects of the vertebral bodies during neck flexion. These results suggest that disproportionate shortening of the dorsal roots is further accentuated during the juvenile growth spurt, which determines the onset and self limited course of the condition, and that repeated neck flexion causes micro-trauma and relative ischaemia of anterior horn cells, which finally results in atrophy of the muscles innervated by motoneurons with long axons. Predisposing anatomical factors are a straight neck due to lack of physiological cervical lordosis and the presence of foreshortened dorsal roots.

Adolescent↗
PubMed1994

Antiproliferative and synergistic effect of interferon alpha-2a, retinoids and their association in established human cancer cell lines.

The effect of 13-cis-retinoic acid (cRA) and all-trans-retinoic acid (tRA) used alone or in combination with interferon alpha-2a (alpha-IFN 2a) was tested on three established human cell lines: KB (epidermoid carcinoma of the oral cavity), SCC-25 (tongue squamous cell carcinoma) and MCF-7 (mammary carcinoma). Both retinoids significantly decreased cell proliferation (growth curves) and colony forming efficiency (CFE) in all cell lines, in a dose-dependent way (at a concentration ranging from 10(-5) to 10(-9) M) and differing from line to line, following the pattern: MCF-7 > SCC-25 > KB. Retinoids at any concentration (already at 10(-7) M) combined with alpha-IFN 2a (ranging from 100 to 500 IU/ml) were more effective in inhibiting cell proliferation than each of the two compounds alone. This was particularly evident with SCC-25 cells. Concerning MCF-7 cells, on the contrary, the effects produced by the association suggested a possible additive more than synergistic amplification of growth inhibition.

Breast Neoplasms↗
PubMed1994

Supernumerary ring chromosomes containing chromosome 17 sequences. A specific feature of dermatofibrosarcoma protuberans?

Mystery surrounds the mechanisms by which the uncommon cutaneous tumor dermatofibrosarcoma protuberans (DP) arises and progresses. A clue may be at hand in the form of extra abnormal chromosomes (one of three ring chromosomes per case with or without other chromosome abnormalities) seen in some 10 cases, including five cases in our experience. The specificity of the rings to DP would be enhanced if the rings were found to contain a contribution from a constant chromosome. We here report fluorescence in situ hybridization (FISH) results bearing on the chromosomal content of DP rings, together with clinical, pathologic, and cytogenetic documentation of our first two cases, which were briefly reported earlier, and three new DP cases. To dissect a translocation (in our 2nd case), we probed by FISH and discovered chromosome 17 sequences in the rings in all five DP cases. Nonfluorescent bands were seen on some rings painted with a whole chromosome 17 probe, indicating the presence in these rings of foreign chromosome sequences. The complexity of the rings was underscored by the detection in only one case of chromosome 17 centromeric sequences. The situation in DP seems to have parallels to that in well-differentiated liposarcoma, another tumor of intermediate malignancy with extra abnormal marker chromosome containing contributions from a constant chromosome and variable donors. In DP the supernumerary rings are clearly specific and significant.

Adult↗
PubMed1994

Efficacy of recombinant alpha-interferon 2a and 13-cis-retinoic acid in the treatment of squamous cell carcinoma.

BACKGROUND: Recent in vitro and in vivo studies hypothesize a synergistic effect of 13-cis-Retinoic Acid (13cRA) and recombinant alpha-IFN 2a (alpha-IFN) in the treatment of squamous cell carcinoma (SqCC). PATIENTS AND METHODS: 35 patients with SqCC in several sites were treated with 13cRA (0.6-1 mg/kg/day) combined with alpha-IFN (6 x 10(6) I.U./day), continuously for 3 months. RESULTS: We observed an objective response in 41% of cases (13/32 evaluable patients) with 5 complete and 8 partial responses. Toxicity was mild and always rapidly reversible, with no haematological side effects. CONCLUSIONS: These preliminary data confirm the feasibility and effectiveness of the combination of 13cRA and alpha-IFN in the therapy of SqCC, also in pre-treated patients, with acceptable toxicity and good compliance.

Adult↗
PubMed1994

Results, toxicity and compliance in chemoprevention trials of head and neck cancer.

Several clinical trials have demonstrated the efficacy as chemopreventive agents on upper aerodigestive tract (UADT) cancer of vitamin A or its natural precursor, beta-carotene, or its synthetic analogues, retinoids. Particularly, 13-cis-retinoic acid (cRA) has been shown to reverse oral leukoplakia and to reduce the frequency of second primary tumours in patients treated for head and neck cancer. Since chemopreventive treatments must be of very long-term duration (even years), and because of apparent 'good health' of treated patients, the toxicity of used drugs and the compliance with treatment need to be carefully considered. Current clinical research has evaluated the efficacy of low doses of cRA in larger numbers of patients, and the increased effectiveness of cRA when used in combination with recombinant alpha-interferon 2a (r-alpha-IFN 2a) has also produced high objective response rate in patients affected with squamous cell carcinoma of the head and neck. In vitro and in vivo studies to verify the validity of several biomarkers (in particular micronuclei) as intermediate end-points in chemoprevention studies are continuing, to allow the short-term screening of promising chemopreventive drugs to be used in clinical trials. The published literature on this matter is reviewed, with special attention to retinoid treatment and toxicity/compliance-related problems, and compared with our own experience.

Carcinoma, Squamous Cell↗
PubMed1993

Concomitant alpha-interferon and chemotherapy in advanced squamous cell carcinoma of the head and neck.

The combination of chemotherapy and interferons has been tested in several human tumors but, until now, no clinical data have been reported in head and neck cancer. At the Istituto Nazionale per la Ricerca sul Cancro of Genoa, 14 patients with previously treated SCC-HN underwent the following regimen: cisplatin, 20 mg/m2/day, 5-fluorouracil, 200 mg/m2/day i.v. bolus and recombinant interferon-alpha-2b (r-IFN-alpha-2b) (Intron-A, Shering-Plough), 3 MIU/day i.m., for 5 consecutive days. Recombinant IFN-alpha-2b was also administered, at the same dosage, 3 times per week during the 2 weeks interval among cycles. Grade III-IV hematological toxicity was recorded in 43% of patients. Increasing fatigue, anorexia, and flu-like symptoms were experienced by most patients. For these reasons 9 of 14 patients needed a chemotherapy delay and a r-IFN-alpha-2b discontinuation. Therefore, due to the heavy toxicity observed, accural was terminated early. The overall response rate was 54% (31% CR, 23% PR). Among the 5 patients who never delayed chemotherapy and discontinued r-IFN-alpha-2b, all but one responded. In conclusion, a synergistic activity between chemotherapy and r-IFN-alpha-2b in head and neck cancer cannot be excluded, but, in our opinion, further investigations should consider less aggressive regimens and/or more selected patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Sonographic evaluation of local recurrences of soft tissue sarcomas.

The aim of our study was to establish whether ultrasonography can be proposed as the main diagnostic technique for the follow-up of soft tissue sarcoma (STS). In 26 patients with previous history of STS, a sonographic examination was carried out using a 5 MHz linear transducer to identify early local recurrences. Sonography was performed every 3 months and a computed tomographic (CT) control was made when the sonogram showed findings strongly suggestive of recurrence. STS recurrences were detected by sonography in 20 of 26 patients (77%) and were confirmed by histologic examination. In six cases, sonographic results were uncertain and in three of these the recurrence was ascertained by biopsy. CT scan provided a correct diagnosis in 16 patients (61.5%) and only in cases with lesions greater than 5 cm in diameter. From our experience we conclude that high frequency sonography is a most accurate noninvasive approach in early detection of STS recurrences. CT plays an important role in the cases amenable to surgery treatment and is recommended to obtain a better assessment of anatomic connection between tumor and adjacent structures.

Adult↗
PubMed1993

Metastatic bone tumors. Nonsurgical treatment. Outcome and survival.

Of 683 (16.1%) consecutive patients investigated from October 1984 to December 1985, 110 had various malignant tumors and secondary bone involvement. In 82 of 110 patients (74.5%), the primary tumor was located in the breast, and the percentage of clinical and radiographic objective responses (OR) of their bone lesions (42.7% and 22.8%, respectively) was higher than for cancer in other sites (clinical OR, 21.4%; radiographic OR, 15.8%). The average survival time of 82 breast cancer patients was 87.4 months, or 38 months from the diagnosis of the bone metastases. Of the 110 patients with bone metastases, 60 patients (54.5%) had secondary spinal involvement. The clinical and radiographic OR (38.4% and 30.2%) were better in the patients with vertebral metastases than in the patients with bone metastases in other sites (clinical OR, 36%; radiographic OR, 9.1%). The average survival time of the patients with vertebral involvement was 99.4 months, or 40.4 months from the time of diagnosis of the bone metastases. From the results obtained, in terms of OR and survival for patients with bone metastases, early and aggressive treatment should be considered to improve the patients' life quality.

Adolescent↗
PubMed1993

Ifosfamide plus epirubicin at escalating doses in the treatment of locally advanced and/or metastatic sarcomas.

A total of 46 consecutive patients were entered into this study to assess the efficacy and toxicity of an epirubicin/ifosfamide combination in treating locally advanced and/or metastatic adult sarcomas (38 soft-tissue sarcomas and 7 bone sarcomas in 45 evaluable patients). Epirubicin was given at escalating doses (from 50 to 100 mg/m2) as an intravenous (i.v.) bolus on day 1, and ifosfamide was given i.v. at 1.2 g/m2 daily on days 1-5. Cycles were repeated every 4 weeks. The overall response rate was 38% (17 of 45 patients), reaching 42% (16 of 38) in the soft-tissue sarcoma group and 44% (17 of 39) in patients who had not been treated previously. In all, 4 complete responses (CRs, 9%) and 13 partial responses (PRs, 29%) were obtained. Most responses (about 68%) were reached within the first 2 cycles. The high-dose intensity of epirubicin (P < 0.04), the histologic type (P < 0.03), the presence of metastatic lesions only (P < 0.01), and the lack of previous treatment (P < 0.04) were found to be positively correlated with the probability of response. The median duration of response was 8 months. The median survival period was 10 months for all evaluable patients and 21 months for those achieving CRs and PRs (P < 0.01). The tumor grade, performance status, and extent of disease at entry into the study correlated with survival. The treatment was well tolerated; no case of sepsis occurred, and neither acute nor cumulative cardiotoxicity was observed. Epirubicin in combination with ifosfamide is therefore effective in advanced and/or metastatic disease with acceptable toxicity. The activity of this combination as compared with that of either of the two drugs given alone at optimal doses needs to be evaluated in prospective randomized trials.

Adolescent↗
PubMed1992

Expression of epidermal growth factor receptor and transforming growth factor alpha in human larynx carcinoma.

Altered expression of growth factors and growth factor receptors is frequently described in human tumors and human tumor cell lines. This further supports the hypothesis that oncogenesis is due to the subversion of mitogen-responsive pathways. The aim of this study was to investigate the expression of epidermal growth factor receptor (EGFR) and transforming growth factor alpha (TGF alpha) in 13 larynx carcinomas and 2 carcinomas of the oral cavity. We found receptor overexpression in 7 out of 15 tumors at mRNA and/or protein level but low expression in the majority of the normal adjacent tissues. TGF alpha was expressed only in 1 case, but no tyrosine kinase activity of the receptor was detected by antiphosphotyrosine antibody.

Aged↗
PubMed1992

Progressive 13-cis-retinoic acid dosage in the treatment of oral leukoplakia.

16 patients with oral leukoplakia were treated with oral 13-cis-retinoic acid. The initial dose, given for 3 months, was 0.2 mg/kg/day, increasing by a further 0.2 mg/kg/day in successive 3 month cycles. The maximum dosage reached at 1.0 mg/kg/day, was given to only 2 patients (who received a total of 15 months treatment). However, 10 patients completed the cycle at 0.8 mg/kg/day (12 months treatment in total), but treatment could not continue due to toxicity (grade I and II), which was cutaneous, mucosal, and haematological (hypertriglyceridemia and hypercholesterolemia). There was grade III toxicity in the skin and mucosa in only 1 case, a patient treated at a dose of 1.0 mg/kg/day. The toxicity was reversible in all cases. 14 of the patients completed the trial. In 4 there were improvements graded as partial responses (PR) obtained at 0.2 mg/kg/day (3PR) and 0.6 (1PR) and there was one complete response (CR) obtained at 0.4 mg/kg/day. Overall there was thus an objective response rate of 36% who showed 50% or more reduction in lesion size. After the retinoic acid treatment was stopped, patients were followed-up for 12 months; 2 patients showed regression of the responses obtained after 6 and 9 months. This study shows that oral treatment with 13-cis-retinoic acid at low dosages is efficacious and with minimal toxicity. It also shows that it is not feasible to treat these patients at doses above 0.8 mg/kg/day for long periods--mainly due to poor compliance.

Adult↗
PubMed1992

Chemotherapy-induced amenorrhea and other clinical and pathological parameters in the prognosis of breast cancer patients.

147 stage II pre- and perimenopausal breast cancer patients were treated with cyclophosphamide-methotrexate-5-fluorouracil (CMF)- based adjuvant regimens. 103 (72%) patients became amenorrheic during or immediately after the end of the chemotherapy program. Univariate analyses for age, menstrual status, nodal involvement, grading, estrogen and progesterone receptor status indicated no correlation between induction of amenorrhea and a significant prolongation of overall and disease-free survival. Multivariate analyses confirmed that young age at diagnosis, increasing number of infiltrated nodes, negative progesterone receptor status and grade 3 tumors are associated with a worse prognosis. Our results suggest that no benefit is expected in women with drug induced amenorrhea after CMF adjuvant treatment.

Adult↗
PubMed1992

Doxorubicin (or epidoxorubicin) combined with ifosfamide in the treatment of adult advanced soft tissue sarcomas.

The results of the association of doxorubicin plus ifosfamide in the treatment of locally advanced and/or metastatic adult soft tissue sarcomas as reported in the literature from 1986 up to the present time are reviewed. The data confirm the effectiveness of the association doxorubicin plus ifosfamide, with an objective response rate of 33.25% (range, 22% to 42%), with 9.3% of complete responses. The highest percentages were reported in studies using doses of doxorubicin of 60 mg/m2 or higher, with a suggested dose-response correlation. The pattern is generally well tolerated, with a prevalently haematological toxicity. Results being equal, the use of epidoxorubicin seems to allow a lower incidence of high grade leukopenia, and an higher dose-intensity of the drug administered. The two randomized studies by EORTC and ECOG indicate superiority of this combination compared to doxorubicin on its own or with other polychemotherapeutic regimens containing doxorubicin, without ifosfamide. However, the actual contribution of ifosfamide deserves further investigation. The impact on long-term disease-free survival is, however, poor and median survival time ranges from 8 to 12 months in responder patients. Future studies should be aimed at increasing the dosages of the drugs without a significant increase of toxicity, by administering them in continuous infusion or by the use of growth factors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

An outpatient phase I study of a subcutaneous interleukin-2 and intramuscular alpha-2a-interferon combination in advanced malignancies.

The aim of this phase I study was to exploit the potential efficacy of an alpha-2a-interferon (alpha-2a-IFN)-subcutaneous interleukin-2 (IL-2) combination, bypassing the toxicity usually associated with bolus or continuous infusion of IL-2. Therefore, nineteen patients with metastatic malignancies (7 melanomas, 6 renal cell carcinomas and 6 soft tissue sarcomas) were treated according to a dose escalating schedule of subcutaneous IL-2 combined with intramuscular alpha-2a-IFN for 5 days/week for 3 consecutive weeks. Cycles were repeated every 2-4 weeks unless disease progressed. Alpha-2a-IFN (3 MU/die) was given continuously, including during the rest weeks. IL-2 doses were started at 2 MIU/day/sqm and the MTD of 6 MIU/day/sqm was progressively reached. The dose of IL-2 was given twice daily every 12 hours. Both of the cytokines were administered in an outpatient setting. The main side effects were fever, chills, fatigue, hypotension, nausea and vomiting. Toxicity was correlated with IL-2 dose level. It was found to be mild at 2 and 4 MIU/day/sqm, while, in contrast, grade III toxicity was observed only at the highest dose of 6 MIU/day/sqm. However, this grade III toxicity was manageable and did not prevent continuation of the treatment as long as the dose was not increased above 6 MIU/day/sqm. Three patients, one with melanoma and two with renal cell carcinomas, obtained clinical partial responses. In eight patients, stable disease, and in the remaining eight, progression, were observed. The data suggest that the combined use of the two BRMs has manageable side effects and would seem to be efficacious. A phase II study at the recommended dose of 6 MIU/day is now necessary.

Adult↗
PubMed1992

Treatment of oral leukoplakia with beta-carotene.

Over the past few years, beta-carotene has progressively gained ground as a drug chosen in the treatment of oral leukoplakias, thus making it possible to reduce the use of 13-cis-retinoic acid, which was shown by many studies to be highly toxic while beta-carotene has proved to have no significant side effects and hence to be much more suitable in oral premalignancy. In 1989, a phase II study of patients showing oral leukoplakias and treated with beta-carotene (90 mg/day) was begun. A total of 23 patients (aged between 17 and 85) were included in the study and 18 (8 male and 10 female) were evaluated. Eight patients (44.4%) had objective responses (6 complete, 2 partial). Four CR and a PR appeared unexpectedly within 2-7 months after the end of the therapy. The lesions were macroscopically and histologically examined at entry; in the evaluated patients, two types of alterations were found: atypical hyperplasia (16 patients) and dysplasia (2 patients). No signs of significant toxicity were detected; only in 1 patient treatment had to be interrupted for 1 week. The results of this study show the fair efficacy of beta-carotene against oral leukoplakias, but further confirmations through controlled clinical studies are needed.

Adult↗
PubMed1991

Grafting of a calcium-binding loop of thermolysin to Bacillus subtilis neutral protease.

The surface loop which in the Bacillus subtilis neutral protease (NP) extends from amino acid residue 188 to residue 194 was replaced, by site-directed mutagenesis, with the 10-residue segment which in the homologous polypeptide chain of thermolysin (TLN) binds calcium-4 [Matthews, B. W., Weaver, L. H., & Kester, W. R. (1974) J. Biol. Chem. 249, 8030-8044]. The mutant NP was isolated to homogeneity, and its structural, functional, calcium-binding, and stability properties were investigated. Proteolytic fragmentation with Staphylococcus aureus V8 protease of mutant NP was used to isolate and analyze the protein fragment encompassing the site of mutation, unambiguously establishing the effective insertion of the new 10-residue segment. Atomic absorption measurements allowed us to demonstrate that mutant NP binds three calcium ions instead of the two ions bound to wild-type NP, showing that indeed the chain segment grafted from TLN to NP maintains its calcium-binding properties. The mutant NP showed kinetic parameters essentially similar to those of the wild-type NP with Z-Phe-Leu-Ala-OH as substrate. The enzyme inactivation of mutant vs wild-type NP was studied as a function of free [Ca2+]. It was found that mutant NP was much less stable than the wild-type NP when enzyme solutions were dialyzed at neutral pH in the presence of [Ca2+] below 10(-3) M. On the other hand, the kinetic thermal stability to irreversible inactivation of mutant NP, when measured in the presence of 0.1 M CaCl2, was found to be increased about 2-fold over that of the wild-type NP. Thus, modulation of enzyme stability by free [Ca2+] in mutant NP correlates with similar findings previously reported for thermolysin. Overall, the results obtained indicate that protein engineering experiments can be used to prepare hybrid proteins on the basis of sequence and function analysis of homologous protein molecules and show the feasibility of engineering metal ion binding sites into proteins.

Amino Acid Sequence↗
PubMed1991

Attenuation of somatosensory evoked potentials by acupuncture and tactile skin stimulation in man.

The effects of acupuncture and tactile skin stimulation on somatosensory evoked potentials (SEPs), elicited by the median nerve stimulation, were investigated in healthy subjects. Acupuncture needles were inserted into either Hegu plus Shousanli, Hegu plus Waiguan, or Shousanli positions ipsilateral to the median nerve stimulation. Tactile skin stimulation was applied to either the ulnar side of the palm, or the dorsal surface of the hand or forearm ipsilaterally to the nerve stimulation. It was found that acupuncture significantly suppressed the amplitude of P22 and P40, and that the tactile skin stimulation of the ulnar side of the palm significantly suppressed the amplitude of P22 and P40, but that the peak latencies were not affected. Dipole tracing analysis showed that the location and vector direction of P22 were not changed but the vector moment of P22 was changed by both acupuncture and tactile stimulation. Based on these findings the suppressive effect of acupuncture and skin stimulation on P22 was proposed to be due to the afferent inhibition in the somatosensory cortex. Although the suppressive mechanism of P40 by tactile skin stimulation seemed to be similar to that of P22, the suppression of P40 by acupuncture appeared to include different mechanisms.

Acupuncture Therapy↗