Another interesting study is called, The concept of mesothelioma in situ: implications for diagnosis and histogenesis. By Whitaker D, Henderson DW, Shilkin KB. – Semin Diagn Pathol. 1992 May;9(2):151-61. Department of Histopathology, Sir Charles Gairdner Hospital, Perth, Australia. Here is an excerpt: Abstract – The concept of mesothelioma in situ is explored by a detailed examination of seven patients, subsequently proven to have pleural malignant mesothelioma, who initially had no evidence of gross tumor and for whom biopsy material was available at this early presentation. The tissue was assessed by routine microscopy, the immunoperoxidase technique for epithelial membrane antigen and silver staining for nucleolar organizer regions. Tiny lesions of the pleura that merged with or were adjacent to microscopically flat monolayered or folded mesothelium with cytological atypia were observed. The atypical cells reacted positively to epithelial membrane antigen, and the nucleolar organizer region counts were elevated. These observations are considered to support the possibility of the presence of mesothelioma in situ. These findings are discussed in the light of the proposed concept of mesothelioma in situ, its histogenesis, and its possible clinical relevance.
Another interesting study is called, Phase I Study of Intraperitoneal Recombinant Human Interleukin 12 in Patients with Mllerian Carcinoma, Gastrointestinal Primary Malignancies, and Mesothelioma by Renato Lenzi, Michael Rosenblum, Claire Verschraegen, Andrzej P. Kudelka, John J. Kavanagh, Marshall E. Hicks, Eric A. Lang, Michael A. Nash, Lawrence B. Levy, Michael E. Garcia, Chris D. Platsoucas, James L. Abbruzzese and Ralph S. Freedman – Clinical Cancer Research December 2002 8; 3686. Here is an excerpt: Purpose: The purpose is to determine dose-limiting toxicity, pharmacokinetics,pharmacodynamics, and immunobiology after i.p. injections of recombinant human IL-12 (rhIL-12). Experimental Design: rhIL-12 was administered to 29 previously treated patients with peritoneal carcinomatosis from Mllerian carcinomas, gastrointestinal tract carcinomas and peritoneal mesothelioma in a Phase I trial. rhIL-12 doses were increased from 3 to 600 ng/kg. Three or more patients at each level received weekly i.p. injections of rhIL-12. Results: Dose-limiting toxicity (elevated transaminase) occurred in 2 of 4 patients at the 600 ng/kg dose. More frequent toxicities included fever, fatigue, abdominal pain, nausea, and catheter-related infections. Ten patients received 300 ng/kg with acceptable frequency and severity of side effects. Two patients (one with ovarian cancer and one with mesothelioma) had no remaining disease at laparoscopy. Eight patients had stable disease and 19 progressive disease. At 300 ng/kg i.p., IL-12 was cleared from peritoneal fluid in a biphasic manner with a terminal-phase half-life of 18.7 h; peritoneal fluid levels of IL-12 5 min after i.p. injection were 100200 pg/ml, and serum levels reached 10 pg/ml between 24 and 36 h. IL-1-, IL-2, IL-10, tumor necrosis factor , and IFN- were determined in serum and peritoneal fluid. IFN-, IL-10, and tumor necrosis factor were detected most frequently. Immunobiological effects included peritoneal tumor cell apoptosis, decreased tumor cell expression of basic fibroblast growth factor and vascular endothelial growth factor, elevated IFN- and IFN-inducible protein 10 transcripts in peritoneal exudate cells, and increased proportions of peritoneal CD3+ relative to CD14+ cells.
Conclusions: rhIL-12 at 300 ng/kg by weekly i.p. injection is biologically active and adequately tolerated for Phase II studies.
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