Identification of a vicilin-like major allergen from Prosopis juliflora exhibiting cross- reactivity with legume food allergens.

BACKGROUND: Prosopis juliflora is a clinically relevant allergic sensitizer worldwide and shares cross-reactivity with allergens from several tree pollen and food. The present study aims to purify and immunobiochemically characterize a major allergen from Prosopis pollen. The allergen was further investigated for its cross-reactivity with legume allergens. METHODS: Prosopis extract was fractionated by Q Sepharose and Superdex 75 gel filtration column to purify the allergen. Specific IgE against purified protein was estimated via ELISA and immunoblot. The protein was subjected to mass spectrometric analysis. Glycan characterization was performed by Schiff staining and lectin binding assay followed by deglycosylation studies. The functional activity of the purified protein was evaluated by the basophil activation test. Cross-reactivity was assessed by inhibition studies with legume extracts. RESULTS: A 35 kDa protein was purified and showed 75% IgE reactivity with the patients' sera by ELISA and immunoblot. Glycan characterization of protein demonstrated the presence of terminal glucose and mannose residues. A reduction of 40% and 27% in IgE binding was observed upon chemical and enzymatic deglycosylation of the protein, respectively. The glycoprotein allergen upregulates the expression of CD203c on basophils which was significantly reduced upon deglycosylation, signifying its biological ability to activate the effector cells. The identified protein shared significant homology with Lup an 1 from the lupine bean. Immunoblot inhibition studies of the purified allergen with legume extracts underlined high cross-reactive potential. Complete inhibition was observed with peanut and common bean, while up to 70% inhibition was demonstrated with soy, black gram, chickpea, and lima bean. CONCLUSION: A 35 kDa vicilin-like major allergen was isolated from P. juliflora. The protein possesses glycan moieties crucial for IgE binding and basophil activation. Furthermore, the purified protein shows homology with Lup an 1 and exhibits cross-reactivity with common edible legume proteins.

Decreased hospital stay and significant cost savings after routine use of prophylactic gastrostomy for high-risk patients with head and neck cancer receiving chemoradiotherapy at a tertiary cancer institution.

BACKGROUND: Evidence-based nutritional and swallowing guidelines were developed to identify patients at high risk of developing malnutrition during chemoradiation for head and neck cancer. These guidelines recommended a prophylactic gastrostomy and were actively implemented at our institution in January 2007. This study assesses the effect of this policy change on patient outcomes. METHODS: This retrospective cohort study was carried out for the years before (2005) and after (2007) implementation of these guidelines. RESULTS: In all, 165 patients were treated with radical chemoradiation for head and neck cancer at our institution in the years 2005 and 2007. Gastrostomy tube complications were low. Patients in 2007 had significantly fewer hospital admissions, unexpected admissions, and a shorter mean duration of hospital stay in comparison with those in 2005. CONCLUSIONS: Prophylactic gastrostomy tubes in patients with high-risk head and neck cancer resulted in a significant decrease in hospital admissions and length of stay, and led to increased bed availability.

Challenges and opportunities in the targeting of fibroblast growth factor receptors in breast cancer.

Activation of the fibroblast growth factor receptor pathway is a common event in many cancer types. Here we review the role of fibroblast growth factor receptor signalling in breast cancer, from SNPs in FGFR2 that influence breast cancer risk and SNPs in FGFR4 that associate with breast cancer prognosis, and potential therapeutic targets such as receptor amplification and aberrant autocrine and paracrine ligand expression. We discuss the multiple therapeutic strategies in preclinical and clinical development and the current and future challenges to successfully targeting this pathway in cancer.

Preoperative and postoperative chemotherapy for gastric cancer.

Radical surgery offers the only chance of cure for patients with operable gastric cancer; however, outcomes remain generally poor due to a high rate of relapse post gastric surgery. Multimodality therapy using chemotherapy, radiation or a combination of both have been evaluated in different parts of the world to improve outcomes from surgery alone. Perioperative chemotherapy is generally preferred in Europe in contrast to postoperative chemoradiation in the US or adjuvant fluoropyrimidine chemotherapy in East Asia. Regardless of these variations, systemic chemotherapy consistently results in a survival benefit when used in multimodality treatment of operable gastric cancer.

Integration of biologic agents with cytotoxic chemotherapy in metastatic colorectal cancer.

Colorectal cancer (CRC) remains a leading cause of cancer death in the developed world. Metastatic disease eventually develops in nearly 50% of patients with CRC. Chemotherapy is the mainstay of treatment in metastatic CRC (mCRC); however the majority of patients remain incurable with current therapeutic options. Progress made in the field of surgery, locoregional treatment for low-volume metastatic disease, and systemic chemotherapy has created new treatment paradigms and improved survival in mCRC. Development of new cytotoxic drugs and the advent of targeted agents over the past decade have seen the median overall survival (OS) for mCRC increase from 9 months to > 2 years. Data from trials integrating targeted therapies appear to indicate that not all have efficacy as single agents and the choice of chemotherapy used in combination with these agents may impact results. Ongoing research is leading to identification of new biomarkers of response, further defining the subpopulations who achieve greatest benefit. Hence optimizing treatment for this group of patients has become increasingly complex, requiring a multidisciplinary approach not only to identify those who are curable with resectable disease but also to determine when it is best to incorporate targeted drugs, with which chemotherapy, and in whom. Currently bevacizumab, cetuximab, and panitumumab are the only approved biologic agents for use in mCRC. In this article we discuss the evidence supporting the use of biologic agents with chemotherapy and suggested strategies for their integration into the treatment armamentarium of mCRC.

Chemotherapy for operable gastric cancer: current perspectives.

The majority of gastric cancer patients present with advanced, incurable disease and only a minority have localised disease that is suitable for radical treatment. A benefit has generally been demonstrated from adding chemotherapy to surgery for early disease though there are marked differences in how this is done globally. Whilst a perioperative approach, with chemotherapy given before and after gastric surgery is commonly used in the Europe and Australia most patients with operable gastric cancer in North America are treated with surgery and postoperative chemoradiation. In contrast, in East Asia, adjuvant fluoropyrimidine chemotherapy alone is used following D2 gastric resection surgery. However, despite the multimodality treatments, outcomes remain suboptimal as the majority of those treated for localised disease eventually relapse with incurable loco-regional or distant metastases. At the current time, an unmet need exists to further understand the biology of this aggressive disease and develop more efficacious therapies that can improve outcomes from this aggressive disease.

Analysis of IgE binding proteins of mesquite (Prosopis juliflora) pollen and cross-reactivity with predominant tree pollens.

Pollen from the mesquite tree, Prosopis juliflora, is an important source of respiratory allergy in tropical countries. Our aim was to partially characterize the IgE binding proteins of P. juliflora pollen extract and study cross-reactivity with prevalent tree pollen allergens. Intradermal tests with P. juliflora and five other tree pollen extracts were performed on respiratory allergy patients from Bikaner (arid) and Delhi (semi arid). Prosopis extract elicited positive skin reactions in 71/220 of the patients. Sera were collected from 38 of these 71 patients and all demonstrated elevated specific IgE to P. juliflora. Immunoblotting with pooled patients' sera demonstrated 16 IgE binding components, with components of 24, 26, 29, 31, 35, 52, 58, 66 and 95 kDa recognized by more than 80% of individual patients' sera. P. juliflora extract is allergenically potent requiring 73 ng of self-protein for 50% inhibition of IgE binding in ELISA inhibition. Cross-inhibition assays showed close relationship among P. juliflora, Ailanthus excelsa, Cassia siamea and Salvadora persica. IgE binding components of 14, 41, 52 and 66 kDa were shared allergens whereas 26 and 29 kDa were specific to P. juliflora. The findings suggest that purification of cross-reactive allergens will be helpful for diagnosis and immunotherapy of tree pollen allergic patients.