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We have identified previously a destabilizing adenine- and uracil-rich element (ARE) in the 3'-UTR of bcl-2 mRNA that interacted with ARE-binding proteins to down-regulate bcl-2 gene expression in response to apoptotic stimuli. We have also described three contiguous 2'-O-methyl oligoribonucleotides (ORNs) in both sense and antisense orientation with respect to the bcl-2 ARE that are able to regulate the bcl-2 mRNA half-life and Bcl-2 protein level in two different cell lines. Here we show that treatment of neuronal cell line (SHSY-5Y) with antisense ORNs targeting the bcl-2 ARE (bcl-2 ARE asORNs) prevents bcl-2 down-regulation in response to apoptotic stimuli with glucose/growth factor starvation (Locke medium) or oxygen deprivation and enhances the apoptotic threshold as evaluated by time-lapse videomicroscopy, fluorescence-activated cell sorting analysis, and caspase-3 activation. Additional effects of bcl-2 ARE asORNs included inhibition of cell cycle entry and a marked increase of cellular neurite number and length, a hallmark of neuronal differentiation resulting from bcl-2 up-regulation. The ability of bcl-2 ARE asORNs to enhance the apoptotic threshold and to induce neuronal differentiation implies their potential application as a novel informational tool to protect cells from ischemic damage and to prevent neuronal degeneration.

The present study was performed to evaluate Ki-67 and B72.3 immunostaining in 20 selected cases of breast cancer. In particular, we have examined the intracellular localization of TAG 72 and the tumour growth fraction, identified by Ki-67 antibody, on frozen sections of mammary carcinoma, by immunohistochemical technique (ABC method sec.Hsu). Immunostaining of TAG 72 and Ki-67 antigen was related to histologic subtype, diameter, nodal involvement, and number of positive axillary nodes. The preliminary results suggest that: (a) the presence of Ki-67 nuclear staining appeared to be associated with a poorer degree of differentiation, but no direct relationships were observed with diameter and nodal involvement; (b) no correlation between Ki-67 labelling rates and B72.3 intracytoplasmic immunostaining was observed; (c) myoepithelial cells show weak intracytoplasmic positivities.

We report results of intraarterial chemotherapy (IAC) in patients with advanced unresectable (T4, N0-3, MO) squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) of the oral cavity, oropharynx, or facial skin, given through a subcutaneously transposed external carotid artery by a fine gauge needle. Forty patients entered the study and 39 were evaluable for clinical response and toxicity. The infusion technique was done in two consecutive series of patients with the same characteristics: 17 had treatment with vincristine, bleomycin, and methotrexate (VBM), and 22 received cisplatin and bleomycin (PB) with a median number of six and five cycles, respectively. The total objective response (OR) rate was 76.9%, which included 12.8% of complete response (CR). A better percentage of OR was attained in BCC than SCC (83.3% versus 75.8%), in tumors of the skin of the face than other sites (87.5% versus 74.2%), and in the group that received PB than the group that received VBM (77.3% versus 76.5%). Our series had an overall technique-related toxicity of 18%; 10.3% with neurologic disturbances and 7.7% with skin inflammation (almost all were reversible). The most common systemic toxic side effects were generally mild and well tolerated (30.8%), whereas major toxicities (severe modifications of the cardiopulmonary function) occurred in four patients (10.3%) in the group that received VBM. After chemotherapy, 28 patients (71.8%) were deemed resectable; 23 of these patients (82.1%) agreed to surgery. Pathologic CR were obtained in 13 patients (56.5%). Our technique has significant advantages over the conventional methods of infusion, because tumor perfusion is feasible and selective, technique-related and catheter-related complications are almost completely eliminated, and fatal drug-related side effects are avoided.

An unusual case of Primary Carcinoma of the vagina was recently observed. The patient was treated surgically in 1981 for squamous cervical carcinoma in situ (CIN 3); eight years later the same patient was treated for squamous carcinoma of the vagina that involved the upper, median and lower tract. She was treated with radical colpectomy and VBP chemotherapy for three courses. The pathology, natural history and treatment are discussed.