Two phase I studies of low dose recombinant human IL-12 with Melan-A and influenza peptides in subjects with advanced malignant melanoma.

Preclinical studies have shown that low dose IL-12 can potentiate cytotoxic lymphocyte responses. Since previous trials have demonstrated significant toxicity from high dose recombinant human IL-12 (rhIL-12), we sought to determine an optimal biological dose for rhIL-12 at lower doses when combined with peptide antigens. Two studies were undertaken. The rhIL-12 was administered at doses of 0 (placebo), 10, 30 and 100 ng/kg, subcutaneously in one study and intravenously in the other. Apart from IL-12 dosing, the studies were identical. Subjects had evaluable stage III or IV melanoma which expressed Melan-A by RT-PCR or immunohistochemistry. Melan-A (26-35) (EAAGIGILTV) and influenza matrix (58-66) (GILGFVFTL) peptides were administered intradermally on weeks 1, 2, 3, 4 and 9. Twenty-eight subjects were enrolled, of whom 24 were evaluable for clinical and immunological responses. Therapy was well tolerated, the main adverse event being influenza-like symptoms. Immunological monitoring included the evaluation of cutaneous reactions and assays for antigen-specific T-cells. Clinical responses included a complete response in a subject with small volume subcutaneous disease, a partial response in a subject with hepatic metastases, and mixed responses in pulmonary, pleural and nodal disease. Biopsies of accessible tumors showed infiltration with CD4+ and CD8+ lymphocytes capable of lysing Melan-A peptide-pulsed targets in vitro. No clear dose-dependent effect of rhIL-12 could be determined. The rhIL-12 given either s.c. or i.v. was well tolerated at doses of 10-100 ng/kg. Clinical and immunological activity has been observed in this study where peptides were administered either with or without low dose rhIL-12.

Appearance of angiotensin II expression in non-basal epithelial cells is an early feature of malignant change in human prostate.

BACKGROUND: Despite increasing interest in the renin-angiotensin system in cancer, little is known about angiotensin II (Ang II) expression in human prostate tumors. METHODS: Using immunohistochemistry, we examined Ang II expression in prostate cancer (Gleason grades 2-5), benign prostatic hyperplasia (BPH), and high-grade prostatic intraepithelial neoplasia (HGPIN). RESULTS: Ang II was present in proliferating neoplastic cells in HGPIN, in malignant cells in all grades of prostate cancer examined, in basal but not luminal epithelial cells in BPH, and in the cytoplasm of LNCaP, DU145, and PC3 prostate cancer cells. CONCLUSIONS: The data establishes the presence of Ang II in pre-malignant and malignant prostate cells, suggests Ang II staining in non-basal epithelial cells is an early sign of malignant change, and supports suggestions that HGPIN and malignant prostate cells both arise from transformed basal cells. Using immunohistochemistry we examined Ang II expression in proliferative disorders of the prostate and concluded that Ang II staining in non-basal epithelial cells is evidence of early malignant change.

Severe renal failure and nephrocalcinosis in anorexia nervosa.

Two patients with anorexia nervosa and raised serum creatinine levels were found to have nephrocalcinosis on renal biopsy, an association not previously described.

A case of mucormycosis limited to the parotid gland.

BACKGROUND: Mucormycosis is a rare fungal infection commonly affecting structures in the head and neck such as air sinuses, orbits, and the brain. Common predisposing factors include diabetes and immunosuppression. To date, only one case of mucormycosis involving the parotid gland has been reported, and this infection was associated with a fatal outcome. METHODS: We report a case of parotid gland mucormycosis in a 45-year-old woman with type 2 diabetes, who was successfully treated with a superficial parotidectomy and intravenous amphotericin B. RESULTS: After initial surgical and antifungal therapy, the patient was left with a residual facial nerve palsy for which multiple sling procedures were performed. She is currently alive and well 6 years after the diagnosis of mucormycosis. CONCLUSIONS: Mucormycosis of the parotid gland is a rare form of this often-fatal infection. In this case, infection remained isolated to the parotid gland and was diagnosed soon after presentation. The patient most likely survived because of the early diagnosis, successful surgical removal of all infected tissue, use of intravenous amphotericin therapy, and the aggressive management of comorbidities such as her diabetes.

Successful treatment of Langerhans cell histiocytosis with 2-chlorodeoxyadenosine.

Langerhans cell histiocytosis (LCH) is a rare disorder which frequently involves the lungs of affected adults. Recent evidence suggests it is a clonal neoplastic disorder. Prognosis in this disease is variable, but in its multisystem form or when associated with progressive respiratory dysfunction, prognosis is poor. Recent case reports and a phase II trial of the antimonocyte drug 2-chlorodeoxy-adenosine (2CDA) have described success in treating LCH. We used 2CDA to treat a young Australian man with LCH involving lungs and bone. A complete symptomatic remission was achieved with no evidence of recurrence some 5 years after completion of chemotherapy.