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Biomedical subjects

S Toma

Publications and source records attributed to S Toma.

At least 163 records · Page 9Linked to original sources

Isolation of Yersinia enterocolitica from swine.

Data pertaining to 20 strains of Yensinia enterocolitica isolated from the cecal content of swine slaughtered at Toronto Abattoirs are presented. Fifteen of 20 cultures belonged to the two predominant human serotypes in Ontario (i.e., serotype O:3 and O:5,27.) Seven cultures of Y. enterocolitica O:3 belonged to the "Canadian" human phage type 9b. These findings are further proof that swine are reservoirs for Y. enterocolitica human infection. Seventeen Y. enterocolitica cultures were isolated by the cold enrichment method only. Difficulties encountered in isolating Y. enterocolitica from feces specimens are discussed. It would appear that the reported rate of Y. enterocolitica isolation from feces specimens is far below the actual incidence. Fourteen isolates of Y. pseudotuberculosis serotype III were isolated during the same survey.

Animals↗

Survey on the incidence of Yersinia enterocolitica infection in Canada.

Data pertaining to 278 cultures of Yersinia enterocolitica isolated in Canada are summarized in this paper. Of this amount, 256 were isolated from humans, whereas 22 were of nonhuman sources. The typing of these cultures is presented together with their geographical location. Y. enterocolitica serotype O:3 biotype 4, phage type 9b, was practically the only serotype present in the Province of Quebec. This serotype O:3 was also predominant in Ontario, followed by serotypes O:5,27 and O:6,30; other serotypes were seldom isolated. In the central and western areas of Canada, Y. enterocolitica was occasionally isolated; the strains were indole-positive, serotypes O:5,27, O:8, and O:4,32.

Adult↗

Chemoprevention of tumors: the role of RAR-beta.

Chemoprevention can be defined as the use of specific natural or synthetic chemical agents to reverse, suppress, or prevent carcinogenic progression to invasive cancer. The knowledge of carcinogenic mechanisms provides the scientific rationale for chemoprevention. Epithelial carcinogenesis proceeds through multiple discernible stages of molecular and cellular alterations. Understanding of the multistep nature of carcinogenesis has evolved through highly controlled animal carcinogenesis studies, and these studies have identified three distinct phases: initiation, promotion and progression. Animal model studies have provided evidence that the development of cancer involves many different factors, including alterations in the structures and functions of different genes. Transitions between successive stages can be enhanced or inhibited in the laboratory by different types of agents, such activities providing the fundamental basis for chemoprevention.

Anticarcinogenic Agents↗

Combination chemotherapy using vincristine, adriamycin, cyclophosphamide (VAC) alternating with ifosfamide and etoposide (IE) for advanced soft tissue sarcomas: a phase II study.

Chemotherapy options in patients with advanced soft tissue sarcomas (STS) remain presently inadequate. In this phase II study the activity and toxicity of a combined alternating VAC/IE regimen in advanced and/or metastatic STS was evaluated. VAC (vincristine, total dose of 2 mg, adriamycin 70 mg/m2 and cyclophosphamide 600 mg/m2) was given as intravenous bolus infusion on day 1, followed after 21 days by IE (ifosfamide, 1.8 g/m2 infused over 1 h, daily for 5 consecutive days, with mesna uroprotection, plus etoposide at 500 mg/m2 infused over 2 h on the first day). Courses were repeated every 3 weeks. Twenty patients were treated, 12 of whom had previously been given chemotherapy for advanced and/or metastatic disease. Treatment was feasible in ambulatory setting, with good patient compliance. Myelosuppression, overall acceptable, was the major dose-limiting toxicity, while non-hematological side effects were minimal. An overall response rate of 45% was observed (95% CI, 26%-66%), with 2 complete and 7 partial remissions, achieving 75% in the subset of untreated patients. Median survival time was 10 months in the whole group (range, 4-26+ months) and 14 months in responder patients (range, 9-26+ months).

Adult↗

Different effects of the treatment with AGN 193836 and 9-cis-retinoic acid in breast cancer cells.

Retinoid effects have been well studied in different cellular models, and their in vitro action on breast cancer is well known. Much less is known about the function of the different retinoid receptors in mediating retinoid activity in this and other cellular models. In order to better understand these biological mechanisms, several synthetic compounds have been produced, that have specific binding affinity for selected nuclear receptors, and their effect has been evaluated and confronted with that of classic compounds able to bind to different receptors. The aim of this study was the evaluation of the biological activities in breast cancer cell lines of one of these new compounds, AGN 193836, with a very selective binding affinity (selective agonist retinoid) for one single retinoic acid receptor (RAR alpha), in respect to a classic retinoid able to bind to a broad spectrum of retinoic acid receptors (pan-agonist retinoid), 9cRA. Our results clearly indicate that the selective retinoid retains most of the biological activities of the pan-agonist compound, but its effect is probably aggravated by fewer side-effects in vivo: This evidences indicate that selective-agonist retinoids are an interesting research field for the future, not only because of their speculative interest, but also in view of future clinical applications.

Alitretinoin↗

Liposomal doxorubicin (Caelyx) in advanced pretreated soft tissue sarcomas: a phase II study of the Italian Sarcoma Group (ISG).

BACKGROUND: Doxorubicin remains one of the few drugs with consistent single agent activity in advanced Soft Tissue Sarcomas (STS), with a demonstrated dose-response relationship. Liposomal-encapsulated Doxorubicin (LED) has been shown to be at least as active as free doxorubicin in experimental models, and phase I and II human studies indicate that this novel strategy of drug delivery my have less myocardial toxicity. Few clinical trials in adult STS have been published until now, with disappointing and often contrasting results. PATIENTS AND METHODS: Twenty-five consecutive patients with measurable advanced and/or metastatic STS, previously pretreated with anthracycline-based chemotherapy, were enrolled into the trial. LED (Caelyx) was administered over 1-hour intravenous infusion at the dose of 30 mg/m2 in the first 5 patients, then at the fixed dose of 50 mg/m2 in the subsequent 20 patients. Treatment was given on ambulatory basis, at 3-week intervals. Antiemetics were generally not required and only used if indicated. RESULTS: A total of 98 courses of chemotherapy were given (median 4 per patient, range 2 to 5). Amongst the 25 evaluable patients, there were 3 partial responses (12%, 95% confidence interval 4.2% to 29.9%) lasting 3-9+ months and all occurring in patients treated at 50 mg/m2/cycle. In addition, 2 minor responses (4+ months) and 17 stable disease (2-7+ months) were observed; the remaining 3 patients progressed while on therapy. The median delivered drug dose-intensity was 13.3 mg/m2/week (range 10 to 16.6 mg/m2/week). Treatment was well tolerated, with no patient requiring dose reduction or therapy delay because of toxicity. Only 2 cases of WHO grade 3 toxicity occurred, consisting of neutropenia and scrotal skin toxicity; respectively; no cardiotoxicity was seen. CONCLUSIONS: This study shows that Caelyx has some activity in advanced, anthracycline-pretreated STS, with favourable toxic profile. From the analysis of available experiences it emerges that liposomal doxorubicin has not been tested at doses adequate to exploit the antitumor effects of the drug, being the reached dose-intensity being even lower than those deemed critical for obtaining optimal responses to free doxorubicin. We suggest that further and better addressed studies be performed in STS, including patients with less advanced stages of disease, focused on attempting to delivery the drug at optimal doses.

Adult↗

Retinoid receptors: pathways of proliferation inhibition and apoptosis induction in breast cancer cell lines.

In this study we investigated the effects of several selective agonist retinoids (specific for RAR alpha, RAR beta, RAR gamma, and RXR alpha, respectively) on the proliferation and apoptosis of human breast cancer cell lines. All these retinoids inhibit proliferation through apoptosis induction, but with some differences among the tested molecules and the three cell lines. In particular, estrogen receptor positive (ER+) cells display a higher sensitivity to RARs selective compounds, the RAR alpha selective compound being the most effective agent, while estrogen receptor negative (ER-) cells show a greater responsiveness to the RXR alpha selective retinoid. In all tested cell lines a potent antiproliferative and apoptotic effect was also displayed by a high dose of the RAR gamma selective compound. The apoptosis induction is associated with bcl-2 down-regulation, while p53 expression is not modified by any retinoid. Only in one cell line (ZR-75.1), after RAR alpha selective retinoid treatment is there an induction of RAR beta: therefore not only RAR beta induction but also other mechanisms may contribute to the growth inhibitory effect of retinoids in tested breast cancer cell lines.

Antineoplastic Agents↗

Predictive value of some clinical and pathological parameters on upper level axillary lymph node involvement in breast cancer.

The role of radical axillary dissection in breast cancer management is presently under discussion. In this study we have evaluated the relationship between the pattern of metastatic axillary lymph node involvement by level and some of the main prognostic factors (age of the patient, size, grading, estrogen receptor and progesterone receptor status of the primary tumor) in 185 patients with operable breast cancer. The III level appeared to be involved in 31 (16.8%) out the 108 patients with axillary lymph nodes positive for metastases. A discontinuous pattern of axillary involvement (skip metastases) was observed in about 10% of cases. Logistic regression analysis of the data shows that only G3 is significantly correlated with the risk of III level invasion (p less than 0.05). We conclude that, at present, a selection of possible candidates for a less than radical axillary dissection is not as yet feasible. Since the risk for III level invasion cannot be sufficiently defined.

Breast Neoplasms↗

Concomitant radiation-doxorubicin administration in locally advanced and/or metastatic soft tissue sarcomas: preliminary results.

Doxorubicin was administered by continuous infusion at a dosage of 12 mg/sqm/day for 5 days concomitantly with radiation treatment (150 or 200 cGy/day for trunk or extremity lesions, respectively) for 5 days. The 5-day cycles were repeated every 3 weeks. Seventeen patients, 5 of whom were pretreated, entered the study; all were assessable for toxicity and 15 for response. The overall objective response rate was 46% (7/15): 1 complete and 6 partial responses. Response rate reached 54% in only non-pretreated patients (6/11) and 75% in patients with PS less than or = 2 (6/8). No disease progression was observed during treatment. The median duration of complete or partial responses was 28 weeks (range 5-86). Toxicity was low and treatment very well tolerated. In our preliminary analysis, the response rate obtained with this combined chemo-radiotherapic regimen was encouraging and the toxicity was acceptable.

Adult↗