Investigation of the anti-angiogenesis effects induced by deoxypodophyllotoxin-5-FU conjugate C069 against HUVE cells.

We have found that the deoxypodophyllotoxin-5-fluorouracil conjugate, 4'-O-demethyl-4-deoxyppodophyllotoxin-4'-yl 4-((6-(2-(5-fluorouracil-yl)acetamido) hexyl)amino)-4-oxobutanoate (C069), possessed superior cytotoxicities and less toxicity compared with etoposide. In this paper, the anti-angiogenic and vascular disrupting activities of C069 were examined with several in vitro and in vivo models. First, we demonstrated that C069 significantly inhibited the proliferation, migration, tube formation and disrupted the formed tube-like structures of HUVE cells, and inhibited angiogenesis in chicken chorioallantoic membrane assay. Furthermore, we found that C069 inhibited tube formation of HUVE cells by down-regulating the MMP-2, MMP-9, and phosphorylation of Akt and ß-catenin. These results provided the initial evidence that C069 exerts potent anti-angiogenic and vascular disrupting effects.

Carbamates of 4'-demethyl-4-deoxypodophyllotoxin: synthesis, cytotoxicity and cell cycle effects.

In an attempt to generate compounds with superior bioactivity and reduced toxicity, 12 carbamates of 4'-demethyl-4-deoxypodophyllotoxin, N-(1-oxyl-4'-demethyl- 4-deoxypodophyllic)-α-amino acids amides, were synthesized and evaluated for antiproliferative activity and cell cycle effects. These synthesized compounds proved to be more hydrophilic, as well as improved or comparable in vitro cytotoxicities against four cell lines (A-549, HeLa, SiHa, and HL-60) compared with either parent DPT or anti-cancer drug VP-16. Furthermore, flow cytometric analysis exhibited that N-(1-oxyl-4'-demethyl-4-deoxypodophyllic)-d-α-methine amide (15f) induced cell cycle arrest in the G2/M phase in A-549 cells.

Supercapsular percutaneously assisted total hip arthroplasty versus conventional posterior approach: Comparison of early functional results.

OBJECTIVE: This study aimed to explore the early functional results of total hip arthroplasty (THA) using the supercapsular percutaneously assisted total hip (SuperPATH) microposterior approach. METHODS: In this retrospective study, 58 patients treated with THA from October 2015 to April 2016 in our hospital were enrolled. A total of 28 patients (11 men and 17 women; mean age: 74.95±7.06 years) were operated on using the SuperPATH approach (group 1), and the remaining 30 patients (12 men and 18 women; mean age: 75.63±7.89 years) were operated on using the conventional posterior approach (group 2). To summarize the early functional results of the SuperPATH approach, we retrospectively analyzed the following demographics, perioperative factors, and measures of joint function: age, sex, preoperative diagnosis, preoperative visual analog scale (VAS) for pain, body mass index, the American Society of Anesthesiologists physical status, operation time (skin-to-skin), intraoperative bleeding, incision length, postoperative VAS, Harris Hip Score (HHS), Barthel Index (BI), length of hospital stay, positioning of the implants, and postoperative complications. RESULTS: All 58 operations were successfully completed, and the average follow-up time was 45 (45.03±2.44) months. The patients in group 1 had shorter incision length (8.84±0.59 versus 13.26±2.41 cm) and length of stay (7.86±0.51 versus 10.80±1.93 days), lower postoperative VAS score (2.43±0.69 versus 3.13±0.94), and better postoperative HHS (88.37±4.31 versus 83.81±6.00) and BI (91.47±5.27 versus 83.59±6.83) at 3 months than the patients in group 2; however, group 1 patients had longer operation time (113.95±25.36 versus 87.22±25.43 min) than group 2 patients (all P<0.05). No significant intergroup differences were found with respect to intraoperative bleeding, cup abduction angle, anteversion angle, and stem positioning. During the follow-up, no deep venous thrombosis, postoperative infection, and hip dislocation were observed in any patient. CONCLUSION: Compared with the conventional posterior approach, the SuperPATH approach provided better early functional results with less postoperative pain and shorter hospitalization time. However, the operation time was longer in the SuperPATH approach group. LEVEL OF EVIDENCE: Level III, Therapeutic study.

Synthesis and evaluation of the apoptosis inducing and CT DNA interaction properties of a series of 4ß-carbamoyl 4'-O-demethylepipodophyllotoxins.

A series of carbamate derivatives of 4'-demethylepipodophyllotoxin have been synthesized, and their cytotoxicities against several human cancer cell lines, including HeLa, A549, HCT-8, and HL-60 cells, evaluated. Some of these compounds exhibited higher levels of cytotoxicity than the anticancer drug etoposide. 4ß-4'-Demethylepipodophyllotoxin 1-(4-nitrophenyl) piperazinyl carbamate (19) was found to be the most potent compound of those synthesized in the current study, and induced cell cycle arrest in the G2/M phase in HeLa cells, which was accompanied by apoptosis. Furthermore, this compound activated the expression of Bax, p53 and caspase-3 in HeLa cells, leading to changes in the conformation of calf thymus DNA from the B-form to a more compact C-form.