Molecular therapy: clinical applications. intra-arterial adenoviruses administration.

Gene therapy involves the introduction of foreign DNA into somatic cells to produce a therapeutic effect. The therapeutic gene is transferred into the tumor cells using a vector. Transfer may either be in vivo in which the DNA and vector are directly introduced into the body, or ex vivo, in which cells are removed from the body, transfected with DNA and then reintroduced into the patients. The mode of gene transfer can be classified into chemical, physical and viral (1). Viruses are the most popular vectors in clinical trials because they invade cells and manipulate the cell's machinery to make viral protein; but the immune response they provoke can rapidly destroy the viral vector or the infected cells, blocking production of the useful protein. Most nonviral vector fly under the radar of immune system, but most of them have not been as efficient as viruses in shuttling genes into cells and the genes that were delivered didn't remain active for long. Intra-arterial administration can have advantages over intravenous, and intralesion routes.

[Early gastric cancer]. / Early gastric cancer.

The authors perform a retrospective analysis of 46 cases of EGC referred to the Surgical Division of Carrara Civic Hospital during the period 1980-1990 who subsequently underwent surgery. Data relating to age, symptomatology and endoscopic examinations were analysed in order to evaluate the real diagnostic penetration of the method in association with tumour biopsy, site, macroscopic aspect, possible lymph node involvement and the histology of lesions. The most frequent form of surgery in this series was subtotal gastrectomy and the 5- and 10-year survival rates, calculated using an actuarial method, were compared with data reported in the literature. The authors conclude by emphasising the need to improve the frequency of diagnosis of gastric cancer at an "early" stage and affirm that gastric resection associated with lymphoadenectomy of 1st and 2nd level lymph nodes is a sufficiently radical operation and less punitive for the patient compared to total gastrectomy given that the 5- and 10-year survival rates are comparable.

Epidoxorubicin and lonidamine in refractory or recurrent epithelial ovarian cancer.

Lonidamine (150 mg x 3 day orally, days 1-5) plus high dose epidoxorubicin (120 mg/m2 intravenously, day 3) was tested in 26 patients with refractory or recurrent epithelial ovarian cancer, to assess the anti-tumour activity and the toxicity of this combination of drugs. All patients were evaluable for toxicity and 24 for tumour response. Two complete responses (8.3%) and six partial responses (25.0%) were recorded for a total response rate of 33.3%. 6 of 8 responding patients were pretreated with anthracyclines. Stable disease was obtained in 7 patients (29.2%). Toxicity was acceptable; only 1 (3.8%) patient stopped chemotherapy because of a left ventricular ejection rate reduction > 20%. The most relevant side-effect was leucopenia (grade 3-4, 34.6%). In conclusion, the association of lonidamine and high-dose epidoxorubicin has promising activity as second-line treatment in patients with refractory or recurrent epithelial ovarian cancer.

Radio-hyperthermia in post-surgical recurrence of melanoma.

AIMS AND BACKGROUND: Malignant melanoma is one of the most radioresistant tumors. It can be treated with combinated hyperthermia and radiation therapy. METHODS: From January 1991 through June 1992, 7 patients, 1 male and 6 female, aged 40-88 years (mean 75), with skin and nodal post-surgical recurrences of melanoma, were treated with a combination of radiation therapy and hyperthermia. Two patients presented systemic disease when they reached our observation, but all of them were without symptoms. None of them underwent surgical excision of the recurrence before or during thermoradiotherapy. None received chemotherapy for these recurrences or had received radiotherapy in the past. They were irradiated with electron beams, with electron energies selected according to the depth of the lesions. The total dose was 40 Gy in 10 fractions in 5 weeks. Hyperthermia was administered for 10 minutes to 1 hour after irradiation. An inductive method of radiofrequency heating at 434 of 915 MHz was used depending on the depth of the lesions. In all of these treatments a ionized water bolus was used. The prescribed hyperthermic dose was 42 degrees C for half a hour. The treatments were carried out twice a week for 5 weeks. A fiberoptic multichannel thermometer was used for thermometry. RESULTS: Four patients (57%) achieved a complete response, 2 patients (29%) a partial response, and 1 patient (14%) stabilization. We found no correlation between tumor volume and response rate. Site effects and complications of the treatment were minimal (moderate erythema). CONCLUSIONS: Our results are in the wide range of values reported in the literature.

Prediction of survival by thymidine labelling index in patients with resistant ovarian carcinoma.

The relationship between tumour proliferative activity, evaluated by thymidine labelling index (TLI), clinicopathological variables and clinical outcome, was analysed in a series of 64 chemotherapy-resistant, ovarian cancer patients. The median TLI of 4.6% (range 0.01-45.7) was used as the cut-off to discriminate rapidly from slowly proliferating tumours. Univariate analyses showed a significant advantage in survival for patients with TLI less than or equal to 4.6 (P = 0.0004), ECOG performance status less than or equal to 1 (P = 0.0001) and residual disease after primary surgery less than or equal to 2 cm (P = 0.019). Multivariate analysis demonstrated that performance status was the only independent prognostic variable, although TLI was the last covariate removed from the Cox's regression model.