Immunocryosurgery for basal cell carcinoma: results of a pilot, prospective, open-label study of cryosurgery during continued imiquimod application

Background/aim  Theoretical considerations support the combination of cryosurgery and topical imiquimod to treat basal cell carcinomas (BCC). The aim of the present study was to test the feasibility and efficacy of 'cryosurgery during continued imiquimod application' ('immunocryosurgery') to treat 'high-risk-for-recurrence' BCCs.
Methods  Thirteen patients with 21 biopsy-proven tumours (4 of 21 relapses after prior surgery) were included. After 2–5 weeks (median, 3) of daily 5% imiquimod cream application, the tumours were treated by liquid N₂ cryosurgery (spray, two cycles, 10–20 s) and imiquimod was continued for additional 2–12 weeks (median, 4). The outcome after at least 18 months of follow-up (18–24 months) is currently reported.
Results  Nineteen of 21 tumours responded promptly to immunocryosurgery; two tumours required additional treatment cycles to clear. Thus, the clinical clearance rate was 100%. Only 1 of 21(5%) tumour relapsed after at least 18 months of follow-up (cumulative efficacy: 95%).
Conclusions  'Immunocryosurgery' is a promising non-surgical combination modality to treat 'high-risk-for-recurrence BCCs'. Initial evidence is suggestive of an at least additive effect of the two combined modalities. Further studies comparing immunocryosurgery directly with cryosurgery and imiquimod monotherapies will confirm the reported results.     

The high prognostic value of the histologic grade at the deep invasive front of tongue squamous cell carcinoma

BACKGROUND: Although many histopathologic factors in squamous cell carcinoma of the tongue predict the prognosis, the major predictive factors have not been identified clearly. This study analyzed the prognostic value of the histologic grade at the deep invasive front of tongue squamous cell carcinoma. METHODS: The clinicopathologic features of 124 consecutive patients seen between January 1985 and December 1999 with previously untreated squamous cell carcinoma of the tongue were reviewed. Their mean age was 58.5 years (range: 23-90) and the male-female ratio was 1.8: 1 (79 men and 45 women). There were 41, 40, 30, and 13 cases at stage I to stage IV, respectively. The clinicopathologic factors, especially the histologic grade at the deep invasive front (invasive front grade, IFG), were analyzed to determine factors predicting prognosis. RESULTS: The 5-year disease-free survival rate of the patients treated with curative aim only was 66.7%. Clinicopathologic factors significantly associated with the prognosis were T classification, tumor size, stage classification, tumor depth, macroscopic appearance, cervical lymph node metastasis (nodal metastasis), microvascular invasion, and IFG. In a multivariate analysis, patients with tumor depth >/=4 mm, IFG >/=8 points, and nodal metastasis had a reduced disease-free survival and IFG >/=11 points had a predictive value for nodal metastasis (odds ratio: 7.34; P = 0.0019). CONCLUSION: This study found that a high IFG malignancy score had a high prognostic value for squamous cell carcinoma of the tongue.     

Transplantation of microencapsulated bovine chromaffin cells reduces lesion-induced rotational asymmetry in rats

Surrounding bovine chromaffin cells by a semipermeable membrane may protect the transplanted cells from a host immune response and shield them from the inflammatory process resulting from the surgical trauma. Encapsulation of the chromaffin cells was achieved by inter-facial adsorption of a polycation on a polyanionic colloid matrix in which the chromaffin cells were entrapped. Basal and potassium-evoked release of catecholamines from encapsulated bovine chromaffin cells was analyzed over a 4-week period in vitro. Norepinephrine and dopamine release remained constant over time whereas epinephrine release significantly decreased. The chromaffin cells also retained the capacity for depolarization-elicited catecholamine release 4 weeks following the encapsulation procedure. Morphological analysis revealed the presence of intact chromaffin cells with well-preserved secretory granules. Striatial implantation of chromaffin cell-loaded capsules significantly reduced apomorphine-induced rotation compared to empty polymer capsules in animals lesioned with 6-hydroxydopamne frr at least 4 weeks. Intact chromaffin cells expressing tyrosine hydroxylase and dopamine-β-hydroxylase were observed in all capsules implanted in the striatum for 4 weeks. The assessment of the clinical potential of transplanting encapsulated adrenal chromaffin cells of either allo- or xenogeneic origin for Parkinson's disease will require long-term behavioral studies. The present study suggests, however, that the polymer encapsulation procedure may offer an alternative to adrenal autografts as a source of dopaminergic tissue.     

胰腺癌黏蛋白4基因修饰的树突状细胞疫苗构建及对胰腺癌细胞的免疫效应

Objective To obtain the dendritic cells ( DC)-based vaccine modified by adenovirus containing MUC4 gene , and evaluate the anti-tumor efficacy of DC vaccine to pancreatic tumor cells. Meth-ods The mRNA sequence of tumor associated antigen, MUC4, was obtained from NCBI, and MUC4 se-quence was acquired through the restriction enzyme sites and over lap PCR, then subcloned into adenovirus plasmid to create recombinant adenovirus ( rAd-MUC4) . The DCs were infected by rAd-MUC4 virus and then stimulated the lymph cells from the same donor to induce MUC4 specific cytotoxicity T lympbocytes ( CTL) . The efficacy of CTL was analyzed by LDH releasing assay. Elispot was used to detect the IFN-γ release. Results The recombinant adenovirus containing MUC4 ( sv12) gene was obtained. The MUC4-induced CTL could specifically kill the Capan-1 pancreatic tumor cells [ ( 13. 7±6.0)% , ( 21.4± 4. 7)% , (36.1±9. 5)% at ratios of 10: ,20: ,40: ] , higher than MCF-7 and Bxpc-3 cells respectively, P < 0. 05. The spots number of CTL induced by rAd-MUC4 was ( 139.1±23.3) , more than GFP and PBS control group,P<0.05. Conclusion The Muc4 gene modified DC vaccine could induce the proliferation of CTL, which provided a significant cytotoxicity to HLA-matched MUC4 positive tumor cell lines in vitro.     

Rational design of hypoallergens applied to the major cat allergen Fel d 1

BACKGROUND: Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. OBJECTIVE: The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. METHODS: The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. RESULTS: Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. CONCLUSION: By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.