[Tamibarotene induces MHC II in MM cells]
>> Haematologica. 2007 Jan;92(1):115-20.
Induction of class II major histocompatibility complex expression in human multiple myeloma cells by retinoid.
Sanda T, Iida S, Kayukawa S, Ueda R.
Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, Japan. tsanda@med.nagoya-cu.ac.jp
Class II major histocompatibility complex (MHC II) is normally silenced in plasma/multiple myeloma (MM) cells at the transcriptional level through downregulation of class II transactivator (CIITA), allowing MM cells to escape from immunological responses. Here we demonstrate that a retinoic acid receptor-alpha/beta-selective retinoid Am80 (tamibarotene) could induce the expression of functional MHC II molecules in human MM cell lines. Am80 upregulated expression of the interferon regulatory factor-1 gene, followed by enhancement of CIITA expression. This is the first report demonstrating that retinoid can induce the expression of MHC II in terminally-differentiated plasma/MM cells.<<
Full-text freebie:
haematologica.org
Figured this would be up your immunological alley. Thinking this may be a small jewel, obtained pawn shop cheap. If this is good against MM, that'd be a huge additional value, compared to just the APL market currently talked about.
And it's not just MM, but other blood cancers. Here, a recent study in several blood cancer cell lines:
>>Int J Oncol. 2007 Aug;31(2):397-404.
RARalpha is a regulatory factor for Am-80-induced cell growth inhibition of hematologic malignant cells.
Jimi S, Mashima K, Matsumoto T, Hara S, Suzumiya J, Tamura K.
Central Laboratory of Pathology and Morphology, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan. sjimi@fukuoka-u.ac.jp
Retinoids are used for treatment of acute promyelocytic leukemia (APL). Am-80, Tamibarotene, binds to retinoic acid receptor alpha (RARalpha) more specifically than all-trans retinoic acid. We studied the tumor cell suppressive effects of Am-80, with respect to cytotoxicity and growth inhibition using eight myeloid and lymphoid malignant cells in culture (HL-60, HL-60R, K-562, Kasumi-1, MEG01, Raji, U266B1, and U937). The effects of Am-80 were examined during 9 days of incubation with 10(-7)-10(-5) M of Am-80 in culture medium, which was changed every 3 days. HL-60 were the only cells sensitive to Am-80-induced cytotoxicity; the latter reached more than 95% after 9 days of incubation, and death was primarily through apoptosis. The total mass of RARalpha in HL-60 was significantly greater (p<0.006) than in ATRA-resistant HL-60 (HL-60R) as well as all of other cells tested. However, in all cells excluding HL-60, Am-80 induced time- and dose-dependent cell growth inhibition without noticeable cytotoxicity. TGF-beta2 was released into the media containing cells incubated with Am-80 for 3 days. A dose-dependent increment of phosphorylation of Smad-2 was also detected. The relative amount of secreted TGF-beta2 correlated with the growth inhibition rates in all cells tested excluding HL-60, and with the total mass of RARalpha in the cells (p=0.0137). Our results indicate that Am-80-induced cell-type non-specific growth inhibition is mediated by TGF-beta2, where the total mass of RARalpha could be an important regulatory factor in hematologic malignant cells.<<
The IP situation should be checked, perhaps: I see papers about Tamibarotene going back to 1990. The progression seems to indicate a drug in search of an indication. It's been studied in atherosclerosis, psoriasis, dermatitis, MS, even neuro indications. Possible red flag, aside from the checkered history of retinoids in general? It would appear that IVPH only has the oncology rights, though.
So, done any studying of your own yet?
Cheers, Tuck |
