Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection. Insulin-like growth factor 1 receptor (IGF-1R) signaling plays a very important role in progression, invasion and metastasis of bladder cancer cells. In this study, we investigated whether IGF-1R was involved in the growth stimulating activity and drug resistance of bladder cancer cells. The results showed: The mRNAs of IGF-1, IGF-2 and IGF-1R were strongly expressed in serum-free cultured T24 cell line, whereas normal urothelial cells did not express these factors/receptors or only in trace leve1s; T24 cell responded far better to growth stimulation by IGF-1 than did normal urothelial cells; blockage of IGF1R by antisense oligodeoxynucleotide (ODN) significantly inhibited the growth of T24 cell and enhanced sensitivity and apoptosis of T24 cells to mitomycin (MMC). These results suggested that blockage of IGF-IR signaling might potentially contribute to the treatment of bladder cancer cells which are insensitive to chemotherapy.

A New Dendrobine-Type Alkaloid from Dendrobium nobile

A new dendrobine-type alkaloid has been isolated from stems of Dendrobium nobile lindl.. Its structure has been identified on the basis of spectroscopic method.

Ohmefentanyl stereoisomers induce changes of CREB phosphorylation in hippocampus of mice in conditioned place preference paradigm

The present study was designed to determine the changes of phosphorylation of cAMP- response ele-ment binding protein (CREB) in hippocampus induced by ohmefentanyl stereoisomers (F9202 and F9204)in conditioned place preference (CPP) paradigm. The results showed that mice receiving F9202 and F9204displayed obvious CPP. They could all significantly stimulate CREB phosphorylation and maintained for along time without affecting total CREB protein levels. The effect of F9204 was similar to morphine whicheffect was more potent and longer than F9202. We also examined the effects of ketamine, a noncompetitiveN-mthyl-D-aspartate receptor (NR) antagonist, on morphine-, F9202- and F9204- induced CPP and phos-phorylation of CREB in hippocampus. Ketamine could suppress not only the place preference but also thephosphorylation of CREB produced by morphine, F9202 and F9204. These findings suggest that alterationsin the phosphorylation of CREB be relevant to opiates signaling and the development of opiates dependence.NR antagonists may interfere with opiates dependence and may have potential therapeutic implications.

A New Bibenzyl Glycoside from Dendrobium moniliforme

A new bibenzyl glycoside has been isolated from the stems of Dendrobium moniliforme (L.) Sw. (Orchidaceae). Its structure has been identified on the basis of spectroscopic and chemical methods.

Low dose gossypol for male contraception

Aim: To ascertain whether the side effects of gossypol, hypokalemia and irreversibility, could be avoided on dose re-duction. Methods: Seventy-seven male volunteers were divided into 3 groups: control (22 cases), 10 mg gossypol(29 cases) and 12.5 mg (26 cases). Serum levels of testosterone, FSH and LH were measured by RIA and potassiumby flame photometry. Spema counts and motility were examined before and regularly after treatment for the evaluationof contraceptive efficacy. Results: The average sperm density and motility started to decrease significantly by theend of month 2 of medication and gradually reached the infertility levels ( < 4 million /mL) in both treated groups. Af-ter that the 10 mg group was asked to take the same dose every other day for up to a total observation period of 16-18months for the maintenance of infertility. Subjects in the 12.5 mg group did not take gossypol any more so as to ob-serve the length of the loading dose required, but in a few, a maintenance dose of 12.5 mg every other day was insti-tuted for a few more months. In both treated groups, none of the spouses was pregnant during the maintenance dose pe-riod. Serum levels of potassium, FSH, LH and testosterone were not significantly changed and not a single volunteercomplained of myoasthenia. After cessation of drug administratioin, the semen data returned to pretreatment levels.Conclusion: A regimen with 10 or 12.5 mg of gossypol as the daily loading dose and 35 or 43.75 mg as the week-ly maintenance dose could induce infertility in male volunteers without developing hypokalemia or irreversibility.(Asian J Androl 2000 Dec; 2: 283-287)

A New Picrotoxane Type Sesquiterpene from Dendrobium densiflorum

A new picrotoxane type sesquiterpene named dendrodensiflorol has been isolated from the stems of Dendrobium densiflorum. Its structure was identified on the basis of spectroscopic method.

Synthesis of Alkylene-linked Dimers of (-)-Huperzine A

Six alkylene-linked dimers of (-)-huperzineA (6) were prepared. All these dimers are less potent than (-)-Hup A in inhibition of AChE.

New Asymmetric Synthesis of Alkannin and Shikonin

A new approach for asymmetric synthesis of alkannin and shikonin is presented. The chiral centers of the targets were introduced via an asymmetric C-arylation of protected chiral glyceraldehyde in high de. The two enantiomers were prepared with the D-isopropylidenegly- ceraldehyde as the starting material.

A Convenient Method for the Asymmetric Synthesis of KAD-1229

A new method for preparation of the potent hypoglycemic KAD-1229 was developed. The key step of this method is diasteroselective alkylation in high optical purity and good yield by using easily available Oppolzer’s camphor sultam as chiral auxiliary.

Two New Phenolic Glycosides from the Roots of Rhododendron molle

Two new phenolic glycosides, everninic acid methyl ester-2-O-b-D- xylopyran- osyl-(16)-b-D-glucopyranoside 1 and 7-hydroxy-5-methoxyphthalide-7-b-D- xylopyranosyl- (16)-b-D-glucopyranoside 2 were isolated from the roots of Rhododendron molle G. Don. Their structures were determined by spectral evidence including 2D NMR techniques.

H3, An Acidic Polysaccharide from Cuscuta chinensis

H3, a homogeneous acidic polysaccharide was obtained from the seeds of Cuscuta chinensisLam. Its structure was characterized for the first time by chemical and spectroscopic methods to be a highly branchedheteropolysaccharide with mean molecular weight of more than lxl0^6. It was composed of 1,6-1inked-β-D Galp, 1,4-linked-β-D Galp, 1,4-1inked-β-D GalA, 1,3,6-1inked-β-D Galp and 1,2,4-1inked Rhap, with branching points at O-2or 0-4 of 1,2,4-1inked Rhap and 0-3 of 1,3,6-1inked-β-D Galp. Its side chains included 1-1inked Araf, 1,5-1inked Arafand 1,3,5-1inked Araf at O-3 of 1,6-1inked Galp in the main chain.

A new Furostanoside from Asparagus filicinus

A new furostanoside, aspafilioside D (1) has been isolated from the root of Asparagus filicinus. Its structure was determined by spectral and chemical methods.

Synthesis of Several 3-Oxamoyl-2-phenylindole Derivatives and Their Ability to Inhibit on Cultured Rat Luteal Cell Growth

Recently, it has been reported that the luteolytic ac-tion was the main mechanism of the termination of earlypregnancy by contraceptivest. In addition, some estro-gen receptor ligands such as droloxifene have beenshown to inhibit the growth of cultured rat luteal cells.It has been known that 2-phenylindole derivatives couldcompete with estradiol for the estrogen receptor. Theseresults prompted us to design and synthesize the follow-ing six new 3-oxamoyl-2-phenylindole compounds 1a-fand test their effects on the growth of luteal cells, aimingat seeking new lead compounds possessing antifertility activities.

An Efficient Synthesis of Aromatic 1-Hydroxymethylene-1, 1-bisphosphonates from Aldehydes

A simple and efficient procedure for synthesis of 1-hydroxymethylene-1,1-bisphos- phoates from aldehydes is described. This method was applied to the synthesis of novel catechol substituted bisphosphonates as the anti-osteoporosis agents.