1.Either cyclin B1 or B2 is necessary and sufficient for inducing germinal vesicle breakdown during frog (Rana japonica) oocyte maturation.
Ihara J;Yoshida N;Tanaka T;Mita K;Yamashita M Mol Reprod Dev. 1998 Aug;50(4):499-509.
Oocyte maturation is finally triggered by the maturation-promoting factor (MPF), which consists of Cdc2 and cyclin B. We have cloned cDNAs encoding frog (Rana japonica) cyclins B1 and B2 and produced antibodies against their products. Using the antibodies, we investigated changes in protein states and levels of Cdc2 and cyclins B1 and B2 during oocyte maturation. In immature oocytes, all Cdc2 was a monomeric unphosphorylated inactive 35 kDa form and neither cyclin B1 nor cyclin B2 was present. Mature oocytes contained the MPF complex consisting of an active 34 kDa Cdc2 phosphorylated on threonine161 and a 49 kDa cyclin B1 or a 51 kDa cyclin B2. After progesterone stimulation, both cyclins B1 and B2 were synthesized from their stored mRNAs and bound to the preexisting 35 kDa Cdc2. The binding of Cdc2 with cyclin B and its activation probably through the phosphorylation on threonine161 occurred at almost the same time, in accordance with an electrophoretic mobility shift of Cdc2 from 35 to 34 kDa. Microinjection into immature oocytes of cyclin B1 or B2 mRNA alone, or a mixture of them, induced germinal vesicle breakdown (GVBD) with similar dose-dependence. When the translation of endogenous mRNAs of both cyclins B1 and B2 was inhibited with antisense RNAs, progesterone failed to induce GVBD in the oocytes, but the inhibition of only one of the two was unable to inhibit the progesterone-induced GVBD.
2.Versatile and facile synthesis of diverse semisynthetic tetracycline derivatives via Pd-catalyzed reactions.
Nelson ML;Ismail MY;McIntyre L;Bhatia B;Viski P;Hawkins P;Rennie G;Andorsky D;Messersmith D;Stapleton K;Dumornay J;Sheahan P;Verma AK;Warchol T;Levy SB J Org Chem. 2003 Jul 25;68(15):5838-51.
A diverse collection of tetracycline derivatives has been synthesized utilizing Heck, Suzuki, and other palladium-coupling reactions via tetracycline arenediazonium and iodoarene salts. Large numbers of tetracyclines are now possible via these reactions, including numerous upper periphery derivatives of doxycycline, minocycline, sancycline, and methacycline modified at positions C7, C9, and C6-C13 on the tetracycline naphthacene ring. Application of palladium-coupling reactions to the tetracyclines has yielded new tetracycline classes with differing structural attributes, greatly increasing the structural diversity of this family of antibiotics, one of the last of the early antibiotic families to be expanded by organic and medicinal chemistry.
3.Immunohistochemical analysis of thymidylate synthase, p16(INK4a), cyclin-dependent kinase 4 and cyclin D1 in colorectal cancers receiving preoperative chemotherapy: significance of p16(INK4a)-mediated cellular arrest as an indicator of chemosensitivity to 5-fluorouracil.
Kamoshida S;Matsuoka H;Shiogama K;Matsuyama A;Shimomura R;Inada K;Maruta M;Tsutsumi Y Pathol Int. 2004 Aug;54(8):564-75.
High expression of thymidylate synthase (TS) is allegedly associated with the chemoresistance to 5-fluorouracil (5-FU) in colorectal cancers. However, low TS expression does not necessarily imply chemosensitivity. Inactivation of p16(INK4a) correlates with poor prognosis in various cancers. We immunohistochemically evaluated the relationship between the expression of TS, p16(INK4a), CDK4 and cyclin D1 and the effect of 5-FU-based chemotherapy in colorectal cancers. After antigen retrieval, immunoperoxidase staining was performed on the paraffin-embedded, biopsy and surgical specimens of 37 advanced colorectal cancers preoperatively treated with peroral administration of 5-FU derivatives. As a control group, 31 colorectal cancers without preoperative treatment were analyzed. High TS expression was found in 23 (74%) of 31 tumors resected from histological non-responders and in 19 (61%) of 31 controls but in none of six responders. High p16(INK4a) expression was seen in 83% of the responders, 52% of the non-responders and 32% of the controls. The TS-low/p16(INK4a)-high phenotype was noted in 83% of the responders, but only in 3% of the non-responders (P = 0.0001). Induction of p16(INK4a) expression after chemotherapy was predominantly seen in the responders.