PURPOSE: The effects on the side-branch (SB) ostium, following paclitaxel-coated balloon (PCB) treatment of de novo coronary lesions of main vessels have not been previously investigated. This study was aimed at evaluating the serial morphological changes of the SB ostium after PCB treatment of de novo coronary lesions of main vessels using optical coherence tomography (OCT). MATERIALS AND METHODS: This prospective, single-center observational study enrolled patients with de novo lesions, which were traversed by at least one SB (≥1.5 mm) and were treated with PCB. The SB ostium was evaluated with serial angiographic and OCT assessments pre- and post-procedure, and at 9-months follow-up. RESULTS: Sixteen main vessel lesions were successfully treated with PCB, and 26 SBs were included for analysis. Mean SB ostial lumen area increased at 9-months follow-up (0.92±0.68 mm2 pre-procedure, 1.03±0.77 mm2 post-procedure and 1.42±1.18 mm2 at 9-months). The SB ostial lumen area gain was 0.02±0.24 mm2 between pre- and post-procedure, 0.37±0.64 mm2 between post-procedure and 9-months, and 0.60±0.93 mm2 between pre-procedure and 9-months. The ostial lumen area increased by 3.9% [interquartile range (IQR) of -33.3 to 10.4%] between pre- and post-procedure, 52.1% (IQR of -0.7 to 77.3%) between post-procedure and 9-months and 76.1% (IQR of 18.2 to 86.6%) between pre-procedure and 9-months. CONCLUSION: PCB treatment of de novo coronary lesions of main vessels resulted in an increase in the SB ostial lumen area at 9-months.
Aged ; Angioplasty, Balloon, Coronary/*methods ; Coronary Angiography ; Coronary Stenosis/diagnosis/*therapy ; Coronary Vessels/*pathology ; *Drug-Eluting Stents/adverse effects ; Female ; Humans ; Male ; Middle Aged ; Paclitaxel/*administration & dosage ; Prospective Studies ; Tomography, Optical Coherence/*methods ; Treatment Outcome ; Tubulin Modulators/administration & dosage

Podophyllotoxone (1) was isolated from the roots of Dysosma versipellis. The structure was determined by spectroscopic analysis in combination with single-crystal X-ray analysis. The absolute configuration of compound 1 was assigned based on the Flack parameter. It showed significant inhibitory activities against human prostate cancer cells PC3 and DU145 with IC50 values being 14.7 and 20.6 μmol·L(-1), respectively. It also arrested the cells at G2/M phase. Tubulin polymerization assay showed that it inhibited the tubulin polymerization in a dose-dependent manner, and molecular docking analysis revealed a different binding mode with tubulin as compared with those known tubulin inhibitors.
Antineoplastic Agents ; chemistry ; pharmacology ; Berberidaceae ; chemistry ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; G2 Phase ; drug effects ; Humans ; Hydrogen Bonding ; drug effects ; Male ; Molecular Conformation ; Molecular Docking Simulation ; Phytotherapy ; Plant Extracts ; chemistry ; pharmacology ; Plant Roots ; chemistry ; Podophyllotoxin ; chemistry ; pharmacology ; Polymerization ; Prostatic Neoplasms ; drug therapy ; Tubulin ; drug effects ; Tubulin Modulators ; pharmacology

Although previous reports showed drug-eluting stent (DES) could effectively inhibit neointima formation, in-stent restenosis (ISR) remains an important obstacle. The purpose of this study was to investigate different effects of paclitaxel on proliferation and cell cycle regulators between vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs) of rats in vitro. The cultured VSMCs and VECs of rats from the same tissues were examined by using immunohistochemistry, flow cytometry and Western blotting in control and paclitaxel-treated groups. The results showed paclitaxel could effectively inhibit proliferation of VSMCs and VECs. However, as compared with VECs, proliferation of VSMCs in paclitaxel-treated group decreased less rapidly. The percentage of cells in G0-G1 and G2-M phases was reduced, and that in S phase increased after treatment for 72 h. The expression of cyclin D1 and B1, p27 and PCNA in VSMCs of paclitaxel-treated group was up-regulated, but that of p21 down-regulated as compared with VECs. It is concluded that there are significant differences in the expression of cell cycle regulators and proliferation rate between paclitaxel-treated VSMCs and paclitaxel-treated VECs, suggesting that the G1-S checkpoint regulated by paclitaxel may play a critical role in the development of complications of DES, which provides new strategies for treatments of ISR.
Animals ; Blotting, Western ; Cell Cycle ; drug effects ; Cell Cycle Proteins ; metabolism ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cyclin B1 ; metabolism ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p27 ; metabolism ; Endothelial Cells ; drug effects ; metabolism ; Flow Cytometry ; G1 Phase Cell Cycle Checkpoints ; drug effects ; Immunohistochemistry ; Microscopy, Fluorescence ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; Paclitaxel ; pharmacology ; Proliferating Cell Nuclear Antigen ; metabolism ; Rats ; Tubulin Modulators ; pharmacology

New colchicine analogs have been synthesized with the aim of developing stronger potential anticancer activities. Among the analogs, CT20126 has been previously reported to show immunosuppressive activities. Here, we report that CT20126 also shows potential anticancer effects via an unusual mechanism: the modulation of microtubule integrity and cell cycle arrest at the G2/M phase before apoptosis. When we treated COS-7 cells with CT20126 (5 muM), the normal thread-like microtubules were disrupted into tubulin dimers within 10 min and thereafter repolymerized into short, thick filaments. In contrast, cells treated with the same concentration of colchicine exhibited microtubule depolymerization after 20 min and never underwent repolymerization. Furthermore, optical density (OD) analysis (350 nm) with purified tubulin showed that CT20126 had a higher repolymerizing activity than that of Taxol, a potent microtubule-polymerizing agent. These results suggest that the effects of CT20126 on microtubule integrity differ from those of colchicine: the analog first destabilizes microtubules and then stabilizes the disrupted tubulins into short, thick polymers. Furthermore, CT20126 induced a greater level of apoptotic activity in Jurkat T cells than colchicine (assessed by G2/M arrest, caspase-3 activation and cell sorting). At 20 nM, CT20126 induced 47% apoptosis among Jurkat T cells, whereas colchicine induced only 33% apoptosis. Our results suggest that the colchicine analog CT20126 can potently induce apoptosis by disrupting microtubule integrity in a manner that differs from that of colchicine or Taxol.
Acetylation/drug effects ; Animals ; Apoptosis/*drug effects ; COS Cells ; Caspase 3/metabolism ; Cattle ; Cell Division/drug effects ; Cercopithecus aethiops ; Colchicine/*analogs & derivatives/chemistry/pharmacology ; Enzyme Activation/drug effects ; G2 Phase/drug effects ; Humans ; Jurkat Cells ; Microtubules/*metabolism ; Poly(ADP-ribose) Polymerases/metabolism ; Tubulin/metabolism ; Tubulin Modulators/chemistry/*pharmacology

Aged ; Cardiac Catheters ; Combined Modality Therapy ; Coronary Restenosis ; therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Paclitaxel ; administration & dosage ; therapeutic use ; Percutaneous Coronary Intervention ; instrumentation ; Stents ; Treatment Outcome ; Tubulin Modulators ; administration & dosage ; therapeutic use

INTRODUCTIONThough oral aphthosis is common, it has a significant impact on the quality of life in the patients. It is the most common oral ulcerative condition encountered in clinical practice. This study describes the characteristics and patterns of oral aphthosis seen at a tertiary dermatological centre in Singapore, with emphasis in evaluating the management gaps and in identifying underlying systemic diseases and nutritional deficiencies.

MATERIALS AND METHODSThis is a retrospective review of medical records over a 10-year period between June 2000 and June 2010. Two hundred and thirteen patients were identified using the search terms 'oral ulcers', 'aphthous ulcers', 'oral aphthosis', and 'Behcet's disease'. Patients with Behcet's disease without oral ulcers and other diagnoses such as pemphigus vulgaris, lichen planus and herpes simplex were excluded. The remaining patients were evaluated with regard to demographic characteristics, characteristics of oral ulcers, associated connective tissue disorders and nutritional deficiencies, diagnostic tests results, treatment response as well as follow-up duration.

RESULTSOne hundred and seventy-fi ve patients were included in this study. One hundred and one patients had recurrent oral aphthosis, with 77 having simple aphthosis and 24 having complex aphthosis. Fourteen patients (8%) fulfilled the International Study Criteria (ISG) for Behcet's disease, of which, 85.71% had complex aphthosis. The therapeutic ladder for such patients ranged from topical steroids and colchicine through to oral corticosteroids and/or dapsone therapy.

CONCLUSIONRecurrent oral aphthosis is a niche condition in which dermatologists are well-poised to manage. This study demonstrates that a more definitive management and therapeutic algorithm for oral aphthosis are needed for better management patients in the future. In particular, complex aphthosis needs to be monitored for progression onto Behcet's disease.

Adolescent ; Adrenal Cortex Hormones ; therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Anti-Infective Agents ; therapeutic use ; Anti-Inflammatory Agents ; therapeutic use ; Behcet Syndrome ; complications ; Child ; Child, Preschool ; Colchicine ; therapeutic use ; Dapsone ; therapeutic use ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Stomatitis, Aphthous ; diagnosis ; drug therapy ; etiology ; Treatment Outcome ; Tubulin Modulators ; therapeutic use ; Young Adult

We report herein a case of intestinal amyloidosis with grave prognosis that caused intractable diarrhea and intestinal pseudo-obstruction, alternately in spite of intensive conservative treatment. A 44-year-old woman was admitted for fever, diarrhea, and crampy abdominal pain which had been continuned during 6 months. Abdomen CT scan showed edematous wall thickening of the small bowel and right colon, and colonoscopic biopsy revealed amyloid deposition in the mucosa. Monoclonal light chains in serum and/or urine were not detected and highly elevated serum amyloid A was shown. In spite of intensive treatment including oral prednisolone and colchicine, diarrhea and intestinal pseudo-obstruction developed alternately, general status rapidly got worsened and died after two months.
Administration, Oral ; Adult ; Amyloidosis/complications/*diagnosis/drug therapy ; Anti-Inflammatory Agents/therapeutic use ; Colchicine/therapeutic use ; Colonoscopy ; Diarrhea/*etiology ; Female ; Humans ; Intestinal Mucosa/pathology ; Intestinal Pseudo-Obstruction/*diagnosis/etiology ; Prednisolone/therapeutic use ; Serum Amyloid A Protein/metabolism ; Tomography, X-Ray Computed ; Tubulin Modulators/therapeutic use

OBJECTIVETo investigate the effect of trichostatin A (TSA)/paclitaxel on the growth and apoptosis in human lung adenocarcinoma cell line A549 cells.

METHODSHuman lung adenocarcinoma A549 cells were cultured in DMEM in the presence of paclitaxel and the histone deacetylase inhibitor trichostatin A, and the growth curve was obtained by trypan-blue exclusion assay and cell count. Apoptosis was assessed using Hoechst 33258 staining and flow cytometry, and cell cycle was detected by flow cytometry analysis. The proteins of PARP, caspase-3, survivin and tubulin acetylation were detected by Western blotting.

RESULTSSignificant growth reduction was observed in the A549 cells following treatment with paclitaxel or the histone deacetylase inhibitor TSA. The combined treatment with TSA/paclitaxel caused the highest inhibition of cell growth. The apoptosis rate of A549 cells treated with TSA or paclitaxel for 24 hours was (17.6 ± 1.8)% and (39.2 ± 3.7)%, respectively, but a significantly higher apoptosis rate was (64.2 ± 4.2)% was induced by combined treatment with TSA and paclitaxel. In contrast with the control group, the cell cycle was markedly arrested at G2/M phase in the TSA and paclitaxel group (P < 0.05). The Western blot analysis demonstrated that treatment with TSA/paclitaxel led to a synergistic increase of acetylated tubulin, PARP and caspase-3, and reduced the expression of survivin.

CONCLUSIONTSA or paclitaxel alone can inhibit the cell growth and induce apoptosis, and the combination of TSA and paclitaxel exerts a synergistic effect on the growth and apoptosis in lung adenocarcinoma cells.

Acetylation ; Adenocarcinoma ; metabolism ; pathology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Synergism ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Hydroxamic Acids ; pharmacology ; Inhibitor of Apoptosis Proteins ; metabolism ; Lung Neoplasms ; metabolism ; pathology ; Paclitaxel ; pharmacology ; Poly(ADP-ribose) Polymerases ; metabolism ; Tubulin ; metabolism ; Tubulin Modulators ; pharmacology

A series of noscapine analogues have been synthesized via 13-step reaction starting from 2-hydroxy-3-methoxybenzaldehyde. Anti-tumor activities of these compounds were evaluated against HL-60 cell lines in vitro by the standard MTT assay. It was found that most of these derivatives showed appreciable inhibitory activity against HL-60 and tubulin polymerization. The results also indicated that the potency of compound 31 is about three times more than that ofnoscapine against HL-60 cell line and tubulin polymerization. Moreover, it induced a massive accumulation of cells in G2/M phase. These results showed noscapine and its derivatives were worth to be intensively studied further.
Antineoplastic Agents ; chemical synthesis ; pharmacology ; Cell Cycle ; drug effects ; HL-60 Cells ; Humans ; Noscapine ; analogs & derivatives ; chemical synthesis ; pharmacology ; Polymerization ; drug effects ; Tubulin ; metabolism ; Tubulin Modulators ; chemical synthesis ; pharmacology

Pyrimidine derivatives have been the subject of much attention in pesticide and medicine fields owing to their unique biological properties. Particularly, a large number of these compounds have recently been reported to show substantial antitumor activities, and some of them have been investigated in clinical trials. Although these structurally novel compounds have a common chemical moiety of a pyrimidine ring, there are a variety of mechanisms of their antitumor action, such as, inhibition of cyclin-dependent-kinases, inhibition of protein tyrosine kinase, inhibition of carbonic anhydrases, inhibition of dihydrofolate reductase and disruption of microtubule assembly. In this paper, we described the latest advances in the research of such pyrimidine derivatives as antitumor drug according to their action on targets.
Animals ; Antineoplastic Agents ; chemistry ; pharmacology ; therapeutic use ; Carbonic Anhydrase Inhibitors ; pharmacology ; Cell Proliferation ; drug effects ; Cyclin-Dependent Kinases ; antagonists & inhibitors ; Folic Acid Antagonists ; pharmacology ; Humans ; Neoplasms ; drug therapy ; pathology ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Pyrimidines ; chemistry ; pharmacology ; therapeutic use ; Tetrahydrofolate Dehydrogenase ; pharmacology ; Tubulin Modulators ; pharmacology ; therapeutic use