Current forms of allergy diagnosis and specific immunotherapy are performed with allergen extracts. Allergen extracts contain a variety of allergenic and nonallergenic components and their allergen content is often cumbersome to standardize. If used for diagnostic purposes, positive reactions to a given allergen extract will thus provide the information that an allergic subject is sensitized against extract components, but without identifying them. Likewise, extract-based immunotherapy cannot be adapted to the individual patient's sensitization pattern. Here we review progress in the field of molecular allergen characterization by recombinant DNA technology, leading to novel forms of component-resolved diagnostics (CRD) and immunotherapy (CRIT) based on recombinant allergens. Several studies have demonstrated advantages of recombinant allergenbased diagnosis. Using recombinant allergens in in vitro diagnostic devices, a patient's individual IgE reactivity profile can be quantitatively established. The presence of IgE to cross-reactive allergen components can thus be determined and used to predict clinically relevant sensitization to allergen sources which contain immunologically related allergens. Moreover it has been demonstrated that cocktails of recombinant allergens, matching the IgE epitope complexity present in natural allergen extracts, can be assembled. Component-resolved diagnosis will thus allow the precise selection of those molecules for specific immunotherapy to which a patient is actually sensitized. Recently, several recombinant hypoallergenic allergen derivatives have been developed for immunotherapy. The progress in allergen research achieved by the use of recombinant DNA technology holds promise that component-resolved diagnosis and immunotherapy may help refine the procedures of allergy diagnosis and immunotherapy in the coming decade and beyond.

In this preliminary study, an extract of the phytotherapeutic agent PC-SPES was active in suppressing the growth of cultured hormone-sensitive and -insensitive prostate cancer cell lines. In the small clinical study, PC-SPES therapy decreased serum PSA levels in most patients. However, a longer follow-up and more patients will be required to evaluate the long-term efficacy of this new phytotherapy.

Prostate Cancer (PCa) is the most commonly diagnosed cancer and the third leading cause of death for men in the United States. Suppression of androgen receptor (AR) expression is a desirable mechanism to manage PCa. Our studies showed that AR expression was reduced in LAPC4 and LNCaP PCa cell lines treated with nanomolar concentrations of the V-ATPase inhibitor concanamycin A (CCA). This treatment decreased PSA mRNA levels, indicative of reduced AR activity. V-ATPase-dependent repression of AR expression was linked to defective endo-lysosomal pH regulation and reduced AR expression at the transcriptional level. CCA treatment increased the protein level and nuclear localization of the alpha subunit of the transcription factor HIF-1 (HIF-1α) in PCa cells via decreased hydroxylation and degradation of HIF-1α. The addition of iron (III) citrate restored HIF-1α hydroxylation and decreased total HIF-1α levels in PCa cells treated with CCA. Moreover, iron treatment partially rescued CCA-mediated AR repression. Dimethyloxalylglycine (DMOG), which prevents HIF-1α degradation independently of V-ATPase, also decreased AR levels, supporting our hypothesis that HIF-1α serves as a downstream mediator in the V-ATPase-AR axis. We propose a new V-ATPase-dependent mechanism to inhibit androgen receptor expression in prostate cancer cells involving defective endosomal trafficking of iron and the inhibition of HIF-1 α-subunit turnover.