Reports of spontaneous regressions of metastases and the demonstration of tumor-reactive cytotoxic T lymphocytes indicate the importance of the host's immune system in controlling the devastating course of metastatic renal cell carcinoma1,2,3. Recent research indicates that immunization with hybrids of tumor and antigen presenting cells results in protective immunity and rejection of established tumors in various rodent models4,5,6,7,8. Here, we present a hybrid cell vaccination study of 17 patients. Using electrofusion techniques5, we generated hybrids of autologous tumor and allogeneic dendritic cells that presented antigens expressed by the tumor in concert with the co-stimulating capabilities of dendritic cells. After vaccination, and with a mean follow-up time of 13 months, four patients completely rejected all metastatic tumor lesions, one presented a ‘mixed response’, and two had a tumor mass reduction of greater 50%. We also demonstrate induction of HLA-A2-restricted cytotoxic T cells reactive with the Muc1 tumor-associated antigen and recruitment of CD8+ lymphocytes into tumor challenge sites. Our data indicate that hybrid cell vaccination is a safe and effective therapy for renal cell carcinoma and may provide a broadly applicable strategy for other malignancies with unknown antigens.

Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids.

Context: Adrenocortical carcinoma (ACC) is a rare and heterogeneous malignancy with incompletely understood pathogenesis and poor prognosis Patients present with hormone excess (eg virilization, Cushing’s syndrome) or a local mass effect (median tumor size at diagnosis > 10 cm) This paper reviews current diagnostic and therapeutic strategies in ACC Evidence Acquisition: Original articles and reviews were identified using a PubMed search strategy (http://wwwncbinlmnihgov/entrez/queryfcgi) covering the time period up until November 2005 The following search terms were used in varying combinations: adrenal, adrenocortical, cancer, carcinoma, tumor, diagnosis, imaging, treatment, radiotherapy, mitotane, cytotoxic, surgery Evidence synthesis: Tumors typically appear inhomogeneous in both computerized tomography and magnetic resonance imaging with necroses and irregular borders and differ from benign adenomas by their low fat content Hormonal analysis reveals evidence of steroid hormone secretion b

Clinical review: Adrenocortical carcinoma: clinical update.

Thiazolidinediones (TZDs) are widely used to treat type 2 diabetes mellitus; however, their use is complicated by systemic fluid retention. Along the nephron, the pharmacological target of TZDs, peroxisome proliferator-activated receptor-gamma (PPARgamma, encoded by Pparg), is most abundant in the collecting duct. Here we show that mice treated with TZDs experience early weight gain from increased total body water. Weight gain was blocked by the collecting duct-specific diuretic amiloride and was also prevented by deletion of Pparg from the collecting duct, using Pparg (flox/flox) mice. Deletion of collecting duct Pparg decreased renal Na(+) avidity and increased plasma aldosterone. Treating cultured collecting ducts with TZDs increased amiloride-sensitive Na(+) absorption and Scnn1g mRNA (encoding the epithelial Na(+) channel ENaCgamma) expression through a PPARgamma-dependent pathway. These studies identify Scnn1g as a PPARgamma target gene in the collecting duct. Activation of this pathway mediates fluid retention associated with TZDs, and suggests amiloride might provide a specific therapy.

Thiazolidinediones expand body fluid volume through PPARγ stimulation of ENaC-mediated renal salt absorption

THE MANAGEMENT OF chordomas and chondrosarcomas involving the cranial base remains controversial. The options for therapy include biopsy, partial resection, radical resection, and various forms of radiotherapy. In this article, we analyze the outcome of 60 patients with cranial base chordoma

Chordomas and chondrosarcomas of the cranial base: results and follow-up of 60 patients.

Background
Fungal (rhino-) sinusitis encompasses a wide spectrum of immune and pathological responses, including invasive, chronic, granulomatous, and allergic disease. However, consensus on terminology, pathogenesis, and optimal management is lacking. The International Society for Human and Animal Mycology convened a working group to attempt consensus on terminology and disease classification.

/pdf/fungal-rhinosinusitis-a-categorization-and-definitional-llkbo2u47m.pdf

Fungal rhinosinusitis: A categorization and definitional schema addressing current controversies

A case of the chondroid variant of chordoma is presented. The differentiating features of this entity are discussed on a clinical and histopathologic basis. A review of the topic of chordoma is also provided.

Emory D. Warner

Papers

Case Report and Literature Review