Mesenchymal stem cells (MSCs) have the inherent tumor-homing ability with the attraction of multiple chemokines released by tumor tissues or tumor microenvironments, which can be utilized as promising cellular carriers for targeted delivery of anti-tumor drugs and genes. In most circumstances, large amount of systemicly administrated MSCs will be firstly trapped by lungs, following with re-distribution and homing to tumor tissues after lung clearance. Several approaches like enhanced interactions between chemokines and receptors on MSCs or reducing the retention of MSCs by changes of administration methods are firstly reviewed for improving the homing of MSCs towards tumor tissues. Additionally, the potentials and gains of utilizing MSCs to carry several chemotherapeutics, such as doxorubicin, paclitaxel and gemcitabine are summarized, showing the advantages of overcoming the short half-life and poor tumor targeting of these chemotherapeutics. Moreover, the applications of MSCs to protect and deliver therapeutic genes to tumor sites for selectively tumor cells eliminating or promoting immune system are highlighted. In addition, the potentials of using MSCs for tumor-targeting delivery of diagnostic and therapeutic agents are addressed. We believed that the continuous improvement and optimization of this stem cells-based cellular delivery system will provide a novel delivery strategy and option for tumor treatment.
Antineoplastic Agents ; administration & dosage ; Doxorubicin ; administration & dosage ; Drug Delivery Systems ; Gene Transfer Techniques ; Humans ; Mesenchymal Stem Cells ; Neoplasms ; therapy ; Paclitaxel ; administration & dosage ; Research ; trends

OBJECTIVETo evaluate the short-term efficacy and safety of neoadjuvant synchronous chemoradiotherapy (paclitaxel plus carboplatin regimen) in stage III adenocarcinoma of esophagogastric junction (AEG).

METHODSForty cases clinically diagnosed as stage III AEG were prospectively enrolled at the Department of Gastrointestinal Oncology Surgery, the First Affiliated Hospital of Hebei North University from December 2014 to November 2017 and then were randomly divided into paclitaxel plus carboplatin combined with synchronous radiotherapy group(neoadjuvant group) and direct operation group. Inclusion criteria was as follows:(1) AEG was diagnosed by gastroscopic biopsy and III stage was confirmed by ultrasound endoscopy and spiral CT;(2) physical strength score ≥70, and age ≤75 years old; (3) no contraindications of chemoradiotherapy and operation. Exclusion criteria was as follows:(1) patients voluntarily withdrew or refused the treatment;(2) occurrence of severe anaphylaxis; (3) uncontrollable events happened during treatment and treatment was unable to continue;(4) tumor developed obviously during treatment. Preoperative neoadjuvant synchronous chemoradiotherapy used TP regimen: paclitaxel 80 mg/m², drug concentration-time area under curve of carboplatin= 1.5 mg×ml⁻¹×min⁻¹, once per week for 9 weeks; radiotherapy began at the second week, 40 Gy/20 F, completed within 4 weeks. Operative procedure of both groups was radical resection of cardiac cancer(D2). Postoperative chemotherapy regimen was oral Tegafur(Gimeracil and Oteracil potassium). The side effects, diet situation, change of gastroscopic image after treatment in patients of neoadjuvant group were observed and efficacy evaluation of chemotherapy was performed according to solid tumor efficacy evaluation criteria of US National Cancer Institute. Operation-associated parameters, including R0 resection rate, lymph node metastasis, operative mortality and postoperative complications, were compared between two groups.

RESULTSThere were no significant differences in baseline information between the two group (all P>0.05). One case in neoadjuvant group was excluded because of perforation at lesion site 7 weeks after chemotherapy. The side effects of 19 cases in neoadjuvant group were mainly alopecia (100%) and marrow inhibition (68.4%), while 3-4 degree side effects were alopecia(8/19,42.1%), leukopenia (3/19, 15.8%) and neutropenia(3/19, 15.8%). Complete remission was observed in 4 cases; partial remission was observed in 13 cases and stable disease in 2 cases, with an objective response rate of 89.5% and a disease control rate of 100%. Before neoadjuvant chemotherapy, 16 cases were difficult to take liquid diet and 3 cases received liquid diet only, while after 12 weeks of neoadjuvant chemotherapy, all the 19 cases received normal diet. Besides, after neoadjuvant chemotherapy, gastroscopic examination showed close healing of cardiac ulcer, disappearance of swelling, and renewal of normal mucosa. Compared to direct operation group, neoadjuvant group had less number of positive lymph node (4.9±3.6 vs. 8.8±2.8, P<0.05) and higher R0 resection rate (94.7% vs. 50.0%, P<0.05). Total number of harvested lymph node was not significantly different between two groups (19.1±2.5 vs. 18.6±7.0, t=0.326, P=0.746). There was no surgical death in either group. One case in direct operation group developed postoperative inflammatory obstruction. No associated complication was found in neoadjuvant group.

CONCLUSIONPaclitaxel plus carboplatin combined with synchronous radiotherapy can elevate the R0 resection rate of patients with stage III esophagogastric junction adenocarcinoma, without increasing operative mortality and postoperative complications.

Adenocarcinoma ; drug therapy ; therapy ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; administration & dosage ; Chemoradiotherapy ; Esophageal Neoplasms ; therapy ; Esophagogastric Junction ; Humans ; Neoadjuvant Therapy ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Stomach Neoplasms ; therapy ; Survival Rate

OBJECTIVETo investigate the effect of Shaoyao Gancao Decoction (, SGD) on the pharmacokinetics of intravenously administered paclitaxel in rats.

METHODSPaclitaxel was intravenously administered to rats (3 mg/kg) with or without the concomitant administration of SGD (752 mg/kg, a single day or 14 consecutive days pretreatment). The paclitaxel in the serum was quantified using a simple and rapid ultra performance liquid chromatography (UPLC) method for the pharmacokinetic study. The pharmacokinetic parameters were calculated via a non-compartment model using the computer program DAS 2.0.

RESULTSThe pharmacokinetic parameters of paclitaxel were significantly altered in response to 14 consecutive days of pretreatment with SGD. The area under the curve (AUC, from 4 820±197 to 4 205±186 ng·mL·) and AUC(from 5 237±280 to 4 514±210 ng·mL·) significantly decreased in response to the 14-day pretreatment with SGD. The values of V(L/kg) were 10.74±1.08 and 9.35±0.49, those of CL (L/kg) were 0.67±0.03 and 0.57±0.03 and the t(h) values were 11.17±0.84 and 11.32±0.93, respectively, for the 14-day SGD pretreatment and intravenous paclitaxel alone. The AUCand AUCvalues decreased by 13% and 14% (P<0.01), respectively. The area under the curve decreased signifificantly (P<0.01), and the total clearance increased by 1.2-fold (P<0.01), after 14 consecutive days of pretreatment with SGD. A single-day pretreatment with SGD did not signifificantly affect the pharmacokinetic parameters of paclitaxel.

CONCLUSIONSSGD administration for 14 consecutive days increased the metabolism of paclitaxel, while a 1-day pretreatment had little effect. The results would contribute important information to the study on interaction between Chinese medicines and chemotherapy and also help to utilize SGD better in the adjunctive therapy of cancer patients.

Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Injections, Intravenous ; Male ; Paclitaxel ; administration & dosage ; blood ; chemistry ; pharmacokinetics ; Rats, Sprague-Dawley ; Reference Standards ; Time Factors

Paclitaxel (PTX) is one of the most frequently used anticancer agent for treating refractory ovarian cancer, metastatic breast cancer and non-small cell lung cancer. However, its oral administration is impeded by very low bioavailability (<5%) due to the P-glycopprotein (P-gp) efflux pump effect. This study investigated in vitro and in vivo P-gp inhibitory effects of adamantyl derivatives AC-603 and AC-786 in rats. Two adamantyl derivatives tested in this study increased the cytotoxicity of daunomycin (DNM) in P-gp overexpressed cell line by inhibiting P-gp efflux function. Pharmacokinetics of PTX with orally co-administered P-gp inhibitors were assessed in rats to improve PTX absorption. The pharmacokinetic parameters of PTX were determined in rats after intravenous (2 mg/kg) or oral (25 mg/kg) administration in the presence or absence of verapamil (a positive control), AC-603 or AC-786 (0.5 mg/kg or 5 mg/kg). Compared to control group (PTX alone), experimental groups (PTX with AC-603 or AC-786) significantly increased the area under the plasma concentration-time curve of PTX following oral administration by 1.7–2.2 fold. The volume of distribution and total clearance of PTX were decreased, while other parameters were not significantly changed. In conclusion, co-administration of AC-603 or AC-786 enhanced the relative bioavailability of orally administered PTX as compared to control.
Absorption ; Administration, Oral ; Animals ; Biological Availability ; Breast Neoplasms ; Carcinoma, Non-Small-Cell Lung ; Cell Line ; Daunorubicin ; In Vitro Techniques ; Ovarian Neoplasms ; P-Glycoprotein ; Paclitaxel* ; Pharmacokinetics ; Plasma ; Rats* ; Verapamil

OBJECTIVE: Rikkunshito, an herbal medicine, is widely prescribed in Japan for the treatment of anorexia and functional dyspepsia, and has been reported to recover reductions in food intake caused by cisplatin. We investigated whether rikkunshito could improve chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients treated with cisplatin. METHODS: Patients with uterine cervical or corpus cancer who were to receive cisplatin (50 mg/m² day 1) and paclitaxel (135 mg/m² day 0) as first-line chemotherapy were randomly assigned to the rikkunshito group receiving oral administration on days 0–13 with standard antiemetics, or the control group receiving antiemetics only. The primary endpoint was the rate of complete control (CC: no emesis, no rescue medication, and no significant nausea) in the overall phase (0–120 hours). Two-tailed p<0.20 was considered significant in the planned analysis. RESULTS: The CC rate in the overall phase was significantly higher in the rikkunshito group than in the control group (57.9% vs. 35.3%, p=0.175), as were the secondary endpoints: the CC rate in the delayed phase (24–120 hours), and the complete response (CR) rates (no emesis and no rescue medication) in the overall and delayed phases (63.2% vs. 35.3%, p=0.095; 84.2% vs. 52.9%, p=0.042; 84.2% vs. 52.9%, p=0.042, respectively), and time to treatment failure (p=0.059). Appetite assessed by visual analogue scale (VAS) appeared to be superior in the rikkunshito group from day 2 through day 6. CONCLUSION: Rikkunshito provided additive effect for the prevention of CINV and anorexia.
Administration, Oral ; Anorexia* ; Antiemetics ; Appetite ; Cisplatin* ; Drug Therapy ; Dyspepsia ; Eating ; Herbal Medicine* ; Humans ; Japan ; Nausea* ; Paclitaxel* ; Time-to-Treatment ; Vomiting*

PURPOSE: This study compared the angiographic outcomes of paclitaxel-coated balloon (PCB) versus plain old balloon angioplasty (POBA) treatment for de novo coronary artery lesions. At present, there is no available data comparing the efficacy of PCB versus POBA for the treatment of de novo coronary lesions. MATERIALS AND METHODS: This multicenter retrospective observational study enrolled patients with de novo coronary lesions with a reference vessel diameter between 2.5 mm and 3.0 mm and lesion length < or =24 mm who were successfully treated with PCB or POBA. Angiographic measurements and quantitative coronary analysis were performed before and after the procedure, and at 9 months follow-up. RESULTS: A total of 72 patients (49 receiving PCB and 23 receiving POBA) were enrolled in this study. Late luminal loss was -0.12+/-0.30 mm in the PCB group and 0.25+/-0.50 mm in the POBA group (p<0.001). There was a higher percentage of binary restenosis (diameter stenosis > or =50%) in POBA, compared to PCB (30.4%, n=7 vs. 4.1%, n=2, p<0.001). Target vessel revascularization was higher in the POBA group (13.0%, n=3 vs. 0%, p=0.033). CONCLUSION: PCB treatment of de novo coronary lesions showed better 9-month angiographic outcomes than POBA treatment alone.
Aged ; Angioplasty, Balloon, Coronary/*instrumentation/methods ; Coronary Angiography ; Coronary Artery Disease/therapy ; Coronary Stenosis/*therapy ; Coronary Vessels/pathology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Paclitaxel/*administration & dosage/therapeutic use ; Retrospective Studies

Benign cicatricial airway stenosis (BCAS) is a potentially life-threatening disease. Recurrence occurs frequently after endoscopic treatment. Paclitaxel is known to prevent restenosis, but its clinical efficacy and safety is undetermined. Therefore, in this study, we investigated the efficacy and associated complications of paclitaxel as adjuvant treatment for BCAS of different etiologies. The study cohort included 28 patients with BCAS resulting from tuberculosis, intubation, tracheotomy, and other etiologies. All patients were treated at the Department of Respiratory Diseases, Beijing Tian Tan Hospital, Capital Medical University, China, between January 2010 and August 2014. After primary treatment by balloon dilation, cryotherapy, and/or high-frequency needle-knife treatment, paclitaxel was applied to the airway mucosa at the site of stenosis using a newly developed local instillation catheter. The primary outcome measures were the therapeutic efficacy of paclitaxel as adjuvant treatment, and the incidence of complications was observed as well. According to our criteria for evaluating the clinical effects on BCAS, 24 of the 28 cases achieved durable remission, three cases had remission, and one case showed no remission. Thus, the durable remission rate was 85.7%, and the combined effective rate was 96.4%. No differences in outcomes were observed among the different BCAS etiologies (P=0.144), and few complications were observed. Our results indicated that paclitaxel as an adjuvant treatment has greater efficacy than previously reported BCAS treatment methods.
Adolescent ; Adult ; Aged ; Bronchi ; pathology ; Chemotherapy, Adjuvant ; adverse effects ; Cicatrix ; complications ; drug therapy ; surgery ; Female ; Humans ; Male ; Middle Aged ; Paclitaxel ; administration & dosage ; adverse effects ; therapeutic use ; Postoperative Complications ; Respiratory Insufficiency ; drug therapy ; etiology ; surgery ; Tracheal Stenosis ; drug therapy ; etiology ; surgery ; Tracheotomy ; adverse effects

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

MicroRNAs (miRNAs) are a set of non-coding small RNA molecules that play a critical role in regulation of protein coding genes in cells. MiRNAs have been extensively studied as novel biomarkers, therapeutic targets, and new drugs in various human diseases. Breast cancer is a one of the leading tumor types significantly affecting women health worldwide. Over the past decade, a number of natural agents, such as paclitaxel and curcumin, have been applied for treatment and prevention of breast cancer due to their relatively low toxicity. However, the mechanisms of action have not been completely understood. Investigation on miRNAs is able to potentially provide a novel insight into better understanding the anticancer activities of these natural products. Given that a single miRNA can target multiple genes, theoretically, those genes involved in a certain phenotype can be clustered with one or a few miRNAs. Therefore, pleiotropic activities of natural agents should be interpreted by interactions between selected miRNAs and their targets. In this review, we summarize the latest publications related to the alterations of miRNAs by two natural agents (paclitaxel and curcumin) that are currently used in intervention of breast cancer, and conclude that the mechanism involving the regulation of miRNA expression is one of the keys to understand pleiotropic activities of natural agents.
Animals ; Antineoplastic Agents ; administration & dosage ; Biological Products ; administration & dosage ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; prevention & control ; Curcumin ; administration & dosage ; Female ; Humans ; MicroRNAs ; genetics ; metabolism ; Paclitaxel ; administration & dosage

OBJECTIVETo evaluate the effect of Radix euphorbiae pekinensis extract on the permeability and bioavailability of paclitaxel co-administered orally.

METHODSBased on Ussing Chamber and in vivo experiment, the permeability and bioavailability of paclitaxel were evaluated after oral co-administration with radix euphorbiae pekinensis in rats. The contents of paclitaxel in the permeates and the blood samples were determined using HPLC and LC-MS/MS method, respectively.

RESULTSIn Radix euphorbiae pekinensis co-administration group, the Papp of the mucosal-to-serosal (M-S) transport or serosal-to-mucosal transport (S-M) of paclitaxel in the jejunum or ileum segment differed significantly from those in verapamil co-administration group and blank control group (P<0.05), but the Papp of S-M transport in the colon showed no significant difference from that in the blank control group. In the blank group, the average absolute bioavailability (AB%) of orally administered paclitaxel was only 2.81%, compared to that of 7.63% in radix euphorbiae pekinensis group. The average AB% in verapamil group was about 1.5 times that of the blank group.

CONCLUSIONCo-administration of Radix euphorbiae pekinensis extract can increase the bioavailability of orally administered paclitaxel.

Administration, Oral ; Animals ; Biological Availability ; Biological Transport ; Chromatography, High Pressure Liquid ; Euphorbiaceae ; chemistry ; Paclitaxel ; pharmacokinetics ; Permeability ; Plant Extracts ; pharmacology ; Plant Roots ; chemistry ; Rats ; Tandem Mass Spectrometry ; Verapamil