Dual variable of drug loaded micelles in both particle and electrical charge on gastric cancer treatment.

Gastric cancer is a malignant tumour characterised by the uncontrolled cell growth. The incidence and mortality of gastric cancer remain high for the invasion and metastasis. We are urgently seeking a risk-free and effective treatment strategy for gastric cancer. In this study, paclitaxel and tetrandrine were encapsulated in the inner core of micelles, and DSPE-PEG2000-CPP and HA were modified on the micellar surface. HA/CPP modified paclitaxel plus tetrandrine micelles had a suitable particle size (90 nm) for permeating tumour tissue. The zeta potential of the targeting micelles was 8.37 mV after hydrolysis by HAase solution. Results of in vitro experiments indicated that HA/CPP modified paclitaxel plus tetrandrine micelles + HAase could enhance the intracellular uptake, inhibit the formation of neovascularization, block the process of EMT and destroy the invasion and metastasis. In vivo assays indicated that HA/CPP modified paclitaxel plus tetrandrine micelles could be selectively accumulated into tumour sites and exhibited the strong antitumor activity with negligible toxicity. These results suggested that HA/CPP modified paclitaxel plus tetrandrine micelles might provide a new strategy for treating gastric cancer.

Totally implantable venous access devices: The supraclavicular percutaneous approach and early complications.

BACKGROUND: The background of this study was to explore the success rate and early complications concerning the implantation of totally implantable venous access devices (TIVADs) by percutaneous venipuncture and management strategies for early complications. MATERIALS AND METHODS: This was a retrospective study of 1923 patients who received TIVAD implantation by percutaneous venipuncture (mostly via the supraclavicular route). The percutaneous access sites were internal jugular vein (810 patients; right/left: 158/652) or proximal right internal jugular vein, brachiocephalic vein, and proximal subclavian vein (1113 patients). Success rates and early complications related to TIVAD placement techniques were summarized, and strategies for managing complications were also analyzed. RESULTS: In 627 patients, TIVAD implantation was first performed by interventional radiologists using a "blind" approach relying on anatomical landmarks, having a 91.9% success rate. In contrast, there was a 100% success rate among the remaining 1296 patients who received ultrasound-guided implantation, a difference which was statistically significant (P < 0.05). Ultrasound-guided implantation was also successful for the 51 patients for whom the first attempt failed using the blind technique. Further, we found that the incidence of early complications was 5.41% (104/1923) and that the occurrence of immediate complications was significantly higher in the blind technique group compared to the ultrasound-guided group (37 vs. 12; P < 0.05). CONCLUSIONS: It is safe and feasible to implant TIVADs by supraclavicular venipuncture. Ultrasound guidance combined with X-ray monitoring during operation significantly improves the surgery success rate and reduces the risk of early complications. Unclear anatomical landmarks and vascular variation are the main factors affecting success using a blind (nonguided) technique.

Application of multifunctional targeting epirubicin liposomes in the treatment of non-small-cell lung cancer.

Chemotherapy for aggressive non-small-cell lung cancer (NSCLC) usually results in a poor prognosis due to tumor metastasis, vasculogenic mimicry (VM) channels, limited killing of tumor cells, and severe systemic toxicity. Herein, we developed a kind of multifunctional targeting epirubicin liposomes to enhance antitumor efficacy for NSCLC. In the liposomes, octreotide was modified on liposomal surface for obtaining a receptor-mediated targeting effect, and honokiol was incorporated into the lipid bilayer for inhibiting tumor metastasis and eliminating VM channels. In vitro cellular assays showed that multifunctional targeting epirubicin liposomes not only exhibited the strongest cytotoxic effect on Lewis lung tumor cells but also showed the most efficient inhibition on VM channels. Action mechanism studies showed that multifunctional targeting epirubicin liposomes could downregulate PI3K, MMP-2, MMP-9, VE-Cadherin, and FAK and activate apoptotic enzyme caspase 3. In vivo results exhibited that multifunctional targeting epirubicin liposomes could accumulate selectively in tumor site and display an obvious antitumor efficacy. In addition, no significant toxicity of blood system and major organs was observed at a test dose. Therefore, multifunctional targeting epirubicin liposomes may provide a safe and efficient therapy strategy for NSCLC.

Antitumor efficacy of Lf modified daunorubicin plus honokiol liposomes in treatment of brain glioma.

Malignant brain glioma is the most common and aggressive type of primary intracranial neoplasm. Regular chemotherapy cannot eradicate brain glioma cells and the residual glioma cells could form vasculogenic mimicry (VM) channels under hypoxic conditions to provide nutrients for tumor cell invasion. In addition, the existence of the blood-brain barrier (BBB) restricts most antitumor drugs into brain glioma. In this study, we developed a kind of lactoferrin (Lf) modified daunorubicin plus honokiol liposomes to transport antitumor drugs across BBB, eliminate the VM channels and block tumor cell invasion. The evaluations were performed on BBB model, brain glioma cells and glioma-bearing mice. In vitro results showed that the targeting liposomes with suitable physicochemical property could enhance the drug transportation acrossing the BBB, inhibit C6 cells invasion and destroy VM channels. Action mechanism studies indicated that Lf modified daunorubicin plus honokiol liposomes could activate apoptotic enzymes caspase 3 as well as down-regulate VM protein indicators (PI3K, MMP-2, MMP-9, VE-Cadherin and FAK). In vivo results displayed the targeting liposomes improved accumulation in brain tumor tissue and exhibited obvious antitumor efficacy. Therefore, Lf modified daunorubicin plus honokiol liposomes could be used as a potential therapy for treatment of brain glioma.

Targeting vincristine plus tetrandrine liposomes modified with DSPE-PEG2000-transferrin in treatment of brain glioma.

Glioma is the most frequent primary tumor, and the treatment efficiency is unsatisfactory for the obstacle of the blood brain barrier (BBB), the multidrug resistance (MDR) and the properties of cancer cell invasion and vasculogenic mimicry (VM) formation. In this study, a kind of TF modified vincristine plus tetrandrine liposomes was developed to overcome those limitations. In vitro results showed that TF modified vincristine plus tetrandrine liposomes with suitable physicochemical property could enhance the transport across the BBB, increase the cellular uptake, inhibit the MDR, and block the cancer cell invasion and VM channels. In vivo results demonstrated that TF modified vincristine plus tetrandrine liposomes could significantly prolong the circulation time, obviously accumulate in brain tumor location, thus leading to a robust anticancer efficacy in glioma-bearing mice. These data suggest that TF modified vincristine plus tetrandrine liposomes offer a promising strategy for treating brain glioma.

Increased risk of severe infections in cancer patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a meta-analysis.

BACKGROUND: Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) have been widely used in a variety of solid malignancies. Concerns have arisen regarding the risk of severe infections (≥grade 3) with use of these drugs, but the contribution of VEGFR-TKIs to infections is still unknown. METHODS: The databases of PubMed and abstracts presented at oncology conferences' proceedings were searched for relevant studies from January 2000 to December 2014. Summary incidences, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were calculated by using either random-effects or fixed-effects models according to the heterogeneity of included studies. RESULTS: A total of 16,488 patients from 27 randomized controlled trials were included. The risk of developing severe (Peto OR 1.69, 95% CI: 1.45-1.96, P<0.001) and fatal infections (Peto OR 1.78, 95% CI: 1.13-2.81, P=0.013) was significantly increased in patients treated with VEGFR-TKIs when compared to controls. Exploratory subgroup analysis showed no effect of tumor types, phase of trials, or agent used on the Peto OR of severe infections. When stratified according to specific infectious events, the risks of high-grade febrile neutropenia, pneumonia, fever, and sepsis were increased compared with controls, with Peto ORs of 1.57 (95% CI: 1.30-1.88, P<0.001), 1.79 (95% CI: 1.29-2.49, P<0.001), 5.35 (95% CI: 1.47-19.51, P=0.011), and 3.68 (95% CI: 1.51-8.99, P=0.004), respectively. Additionally, VEGFR-TKIs significantly increased the risk of fatal sepsis (OR 3.66, 95% CI: 1.47-9.13, P=0.005) but not fatal pneumonia (OR 1.34, 95% CI: 0.80-2.25, P=0.26). CONCLUSION: The use of VEGFR-TKIs significantly increases the risk of developing severe and fatal infectious events in cancer patients. A close monitoring for any signs of infections is recommended for patients treated with VEGFR-TKIs.

[Effects of acupuncture on kidney morphological structure and expression of TGF-beta1 mRNA in rats with spontaneous hypertension].

OBJECTIVE: To explore mechanism of acupuncture for renal interstitial fibrosis (RIF) in hypertension rats. METHODS: Twenty-four 24-week-old male spontaneously hypertensive rats were randomly divided into a model group, a perindopril group and an acupuncture group, eight cases in each one. In the acupuncture group, with rats tied up, electroacupuncture was applied at bilateral "Quchi" (LI 11) and "Zusanli" (ST 36) under mild vibration of needle handle for 20 min, once a day. In the perindopril group, perindopril (0.4 mg/kg) suspension liquid was applied for intragastric administration, once a day. In the model group, rats were tied up for 20 min a day without any treatment. Eight same-age same-race Wistar Kyoto (WKY) rats with normal blood pressure were taken as a control group, which was given with free diet but no treatment. The treatment was reuqired for six weeks. The systolic blood pressure of caudal artery was tested. Kidney morphological structure was observed by HE coloration. Deposition optical density of type I and III collagen in kidney was tested by immunohistochemistry. Expression of transforming growth factor-beta1 (TGF-beta1) mRNA was tested by reverse transcription polymerase chain reaction (RT-PCR) method. RESULTS: Compared with the model group, the blood pressure was significantly decreased in the acupuncture group (P < 0.01), the damage of kidney morphology was minor, positive depositional area of type I and III collagen was obviously decreased (both P < 0.05), and the expression of semi-quantitative analysis of TGF-beta1 mRNA was decreased (P < 0.05), which had similar effect as western medication perindopril. CONCLUSION: Acupuncture at "Quchi" (LI 11) and "Zusanli" (ST 36) probably intervenes the process of RIF by reducing synthesis of kidney type I , III collagen and restraining expression of TGF-beta1.

5-(4-Chloro-phen-yl)-1H-tetra-zole.

The two independent mol-ecules of the title compound, C(7)H(5)ClN(4), both lie on a twofold rotation axis that passes through the centroids of the five- and six-membered rings and the attached Cl C atom. One molecule is nearly planar [dihedral angle between rings = 0.22 (6)°], whereas the other is significantly twisted [dihedral angle = 17.38 (6)°]. In the crystal, adjacent mol-ecules are linked by N-H⋯N hydrogen bonds into a chain structure.

{2-[2-(Carb-oxy-meth-oxy)-phen-oxy]acetato}[2,2'-(o-phenyl-enedi-oxy)diacetic acid]sodium 4,4'-bipyridine hemisolvate monohydrate.

In the title compound, [Na(C(10)H(9)O(6))(C(10)H(10)O(6))]·0.5C(10)H(8)N(2)·H(2)O, the Na atom is eight-coordinated in an distorted dicapped-octa-hedral geometry by eight O atoms from a 2-(2-carb-oxy-meth-oxy-phen-oxy)acetate (o-BDOAH) anion and a 2,2'-(o-phenyl-enedi-oxy)diacetic acid (o-BDOAH(2)) mol-ecule. The uncoordinated 4,4'-bipyridine mol-ecule is arranged around an inversion center and exhibits rotational disorder. A three-dimensional supra-molecular network is built up in the crystal through O-H⋯O and O-H⋯N hydrogen bonds between the uncoordinated water mol-ecule, the uncoordinated 4,4'-bipyridine mol-ecule and the sodium complex mol-ecule.