Nanotherapy silencing the interleukin‐8 gene produces regression of prostate cancer by inhibition of angiogenesis

Interleukin‐8 (IL‐8) is a pro‐angiogenic cytokine associated with aggressive prostate cancer (CaP). We detected high levels of IL‐8 in sera from patients with CaP compared with healthy controls and patients with benign prostatic hypertrophy. This study examines the role of IL‐8 in the pathogenesis of metastatic prostate cancer. We developed a biocompatible, cationic polylactide (CPLA) nanocarrier to complex with and efficiently deliver IL‐8 small interfering RNA (siRNA) to CaP cells in vitro and in vivo. CPLA IL‐8 siRNA nanocomplexes (nanoplexes) protect siRNA from rapid degradation, are non‐toxic, have a prolonged lifetime in circulation, and their net positive charge facilitates penetration of cell membranes and subsequent intracellular trafficking. Administration of CPLA IL‐8 siRNA nanoplexes to immunodeficient mice bearing human CaP tumours produced significant antitumour activities with no adverse effects. Systemic (intravenous) or local intra‐tumour administration of IL‐8 siRNA nanoplexes resulted in significant inhibition of CaP growth. Magnetic resonance imaging and ultrasonography of experimental animals demonstrated reduction of tumour perfusion in vivo following nanoplex treatment. Staining of tumour sections for CD31 confirmed significant damage to tumour neovasculature after nanoplex therapy. These studies demonstrate the efficacy of IL‐8 siRNA nanotherapy for advanced, treatment‐resistant human CaP.     

A controlled study of plasma exchange in the treatment of severe rheumatoid arthritis

To learn whether the removal of immune complexes from the circulation by plasma exchange could effect an improvement in disease activity in rheumatoid arthritis (RA) patients, we performed a controlled study of 20 patients with severe progressive disease which had not responded to previous therapy. Ten patients (Group 1) were hospitalized, continued on their regular antiinflammatory medication, and given a graded course of physiotherapy. A further 10 patients (Group 2) received the same treatment as the first group with the addition of a concurrent course of plasmapheresis. Clinical measurement of disease activity after treatment revealed little difference between the two groups with a statistically significant improvement in four measures in Group 1 and in five in Group 2. Laboratory studies suggested that the intensity of plasma exchange was sufficient to remove circulating immune complexes in these patients. Our results confirm that hospitalization in itself is of benefit in the treatment of acute exacerbations of rheumatoid arthritis. The marginal improvement achieved by the addition of plasma exchange in the management of these patients (despite the removal of circulating immune complexes) makes its short-term use of questionable value in the treatment of severe rheumatoid arthritis.     

Sorafenib in Dupuytren and Ledderhose Disease

Palmar and plantar fibromatosis are benign proliferative processes which present as a diffuse thickening or nodules of the hands and/or feet and may lead to flexion contractures, pain, and functional impairment known as Dupuytren and Ledderhose diseases, respectively. Current treatments are noncurative and associated with significant morbidity. Here, we report on the outcomes of 5 patients with advanced disease, no longer surgical candidates, treated with sorafenib. Sorafenib exhibited an expected safety profile. All 5 patients demonstrated objective responses as evaluated by a decrease in tumor size and/or tumor cellularity from baseline and all 5 patients reported subjective pain relief and/or functional improvement. Mechanistically, immunohistochemistry revealed patchy positivity for PDGFRβ, a known target of sorafenib. The outcomes of these 5 patients suggest the safety and efficacy of a relatively well-tolerated oral agent in the treatment of Dupuytren and Ledderhose diseases and suggest the need for future controlled studies.     

Metastasis of lung adenosquamous carcinoma to meningioma: case report with literature review

The occurrence of metastasis of a systemic neoplasm to an intracranial tumor is a rare phenomenon. Meningiomas have been reported as the most common intracranial tumor to harbor a systemic metastasis, with breast and lung carcinomas being the most common sites of origination. Here, we report a case of an adenocarcinoma metastasis of an adenosquamous lung carcinoma found within a meningioma, resulting in the patient’s first clinical manifestations. We also review the literature for other cases of adenocarcinoma metastatic to a meningioma and suggest mechanisms that make meningiomas likely to harbor systemic metastases including increased vascularity, slow growth rate, increased hyaline content and expression of cell-cell adhesion molecules.