Multifunctional biocompatible Ni/Ni-P nanospheres for anti-tumor "neoadjuvant phototherapy" combining photothermal therapy and photodynamic therapy.

Gastric cancer, a gastrointestinal tumor with high morbidity and lethality, is often treated using strategies that are not as effective as they could be due to the locally advanced stage. Although pre-operative neoadjuvant chemotherapy can degrade the tumor stage to afford the possibility of surgery, it still possesses the problems of high systemic toxicity and low selectivity. In this work, we constructed an intelligent multi-functional nanoplatform (NNPIP NPs) with synergistic effects of photothermal therapy (PTT) and photodynamic therapy (PDT), which consisted of the nickel/nickel phosphide (Ni/Ni-P) nanosphere as the core, polyethyleneimine (PEI) as the shell, and the loaded indocyanine green (ICG). The mutual reinforcement of heat generated by the core and photosensitizer under 808 nm NIR laser irradiation is highly effective in the synergistic action of PTT. And co-delivery of ICG with nanoparticles into the cell enhances the PDT effect by reducing the consumption of singlet oxygen (1O2). Ultimately, this therapeutic strategy in vivo not only shrunk tumors but even eliminated tumors completely in a quarter of samples, which may be considered as a potential alternative to neoadjuvant chemotherapy and called "neoadjuvant phototherapy". In addition, as a nanoplatform based on transition metal nickel, NNPIP NPs could also be considered as a potential contrast agent for T1-weighted magnetic resonance imaging (MRI). Herein, we can diagnose and achieve pre-surgical downstaging of tumors and hope to improve R0 resection rates with lower toxicity and higher selectivity.

Colorectal cancer therapy mediated by nanomedicines.

Colorectal cancer is the third most malignant gastrointestinal tumor. Although traditional chemotherapy and radiotherapy have been widely used for treating colorectal cancer, the treatment effect is still unsatisfactory, resulting in a high mortality rate and a low 5-year survival rate. In recent years, with the development of molecular biology of colorectal cancer, many promising therapeutic strategies based on nanomaterials have been developed for colorectal cancer. In this review, we focus on recent advances in colorectal cancer treatment-related nanomedicines. We first discuss the exploration of stimuli-responsive drug delivery systems (DDSs) for colorectal cancer treatment using pH, hypoxia, glutathione (GSH), enzymes, light, magnetic fields (MF), and ultrasound (US) as stimuli. Moreover, the latest progress in emerging therapy for colorectal cancer is further summarized, including photothermal therapy (PTT), magnetothermal therapy (MTT), photodynamic therapy (PDT), sonodynamic therapy (SDT), and chemodynamic therapy (CDT). Finally, we explore the existing challenges and future directions for the better design and development of nanomedicines for clinical colorectal cancer treatment.

Simple construction of Cu2-xS:Pt nanoparticles as nanotheranostic agent for imaging-guided chemo-photothermal synergistic therapy of cancer.

Synergistic therapy has attracted intense attention in medical treatment because it can make up for the disadvantages of single therapy and greatly improve the efficacy of cancer treatment. However, it remains a challenge to build a simple system to achieve synergistic therapy. In this study, X-ray computed tomography (CT) imaging-guided chemo-photothermal synergistic therapy can be easily achieved by simple construction of Cu2-xS:Pt(0.3)/PVP nanoparticles (NPs). Cu2-xS:Pt(0.3)/PVP NPs can passively accumulate within the tumor sites, thus ensuring that many Cu2-xS:Pt(0.3)/PVP NPs are brought into the tumor cells, which can be confirmed by the results of cellular uptake, imaging, and nanoparticle biodistribution. It can be verified that the platinum ions can be released from Cu2-xS:Pt(0.3)/PVP NPs under 808 nm laser irradiation. Simultaneously, Pt(iv) ions are reduced to Pt(ii) ions by excess glutathione and then, they exhibit chemo-anticancer activities. In addition, Cu2-xS:Pt(0.3)/PVP NPs can be used as an effective photothermal agent. The results demonstrate that the efficient tumor growth inhibition effect can be realized from the mice treated with Cu2-xS:Pt(0.3)/PVP NPs under 808 nm laser irradiation by chemo-photothermal synergistic therapy. Furthermore, Cu2-xS:Pt(0.3)/PVP NPs can be thoroughly cleared through feces in a short time, showing high biosafety for further potential clinical translations.

Preliminary study on the treatment of vitiligo with carbon dioxide fractional laser together with tacrolimus.

BACKGROUND: Tacrolimus is a conventional medication for the treatment of vitiligo, but the effect of a single medication is limited. OBJECTIVE: This paper aims at observing the effects, adverse responses, and repigmentation results of the joint treatment of vitiligo by Carbon dioxide (CO2 ) fractional laser together with tacrolimus. METHODS: Forty-five patients with vitiligo were randomly divided into two groups: treatment (T) group and control (C) group, and each group was further divided into three subgroups (face, torso and limbs, and hand and foot) according to the location of the skin defect. Both groups used topical 0.1% tacrolimus cream, but the T group was given one CO2 fractional laser treatment each month. We observed the clinical efficacy, adverse responses, and repigmentation results after 6 months. RESULTS: Compared to the C group, the T group showed better improvement in both objective and subjective assessments. When the treatment time was increased, the efficacy was also improved, and the repigmentation in the T group occured in three ways: perifollicular repigmentation, marginal repigmentation and diffuse repigmentation. There were three cases of isomorphic responses (2 cases in the rapid progression stage, one case in the progression stage), and 1 case formed scarring on the neck in the T group. CONCLUSIONS: The treatment of vitiligo by CO2 fractional laser together with tacrolimus is significantly effective and is most suitable for patients in the progression stage. Patients in the rapid progression stage should use this approach with caution, and its efficacy was limited for patients in the stable stage. An extended course of treatment is helpful for the repigmentation of white patches. All three forms of repigmentation can occur in the joint treatment of vitiligo by CO2 fractional laser together with tacrolimus. Lasers Surg. Med. 50:829-836, 2018. © 2018 Wiley Periodicals, Inc.

A New Co-P Nanocomposite with Ultrahigh Relaxivity for In Vivo Magnetic Resonance Imaging-Guided Tumor Eradication by Chemo/Photothermal Synergistic Therapy.

Design of new nanoagents that intrinsically have both diagnostic imaging and therapeutic capabilities is highly desirable for personalized medicine. In this work, a novel nanotheranostic agent is fabricated based on polydopamine (PDA)-functionalized Co-P nanocomposites (Co-P@PDA) for magnetic resonance imaging (MRI)-guided combined photothermal therapy and chemotherapy. The ultrahigh relaxivity of 224.61 mm-1 s-1 can enable Co-P@PDA to be applied as an excellent contrast agent for MRI in vitro and in vivo, providing essential and comprehensive information for tumor clinical diagnosis. Moreover, Co-P@PDA exhibit excellent photothermal performance owing to the strong near-infrared (NIR) absorbance of both Co-P nanocomposite and PDA. Highly effective ablation of tumors is achieved in a murine tumor model because the NIR laser not only induces photothermal effects but also triggers the chemotherapeutic drug on-demand release, which endows the Co-P@PDA with high curative effects but little toxicity and few side effects. These findings demonstrate that Co-P@PDA are promising agents for highly effective and precise antitumor treatment and warrant exploration as novel theranostic nanoagents with good potential for future clinical translation.

[Study of introperitoneal hyperthermic perfusion chemotherapy combined with systemic neoadjuvent chemotherapy in treatment of gastric cancer patients with peritoneal carcinomatosis].

OBJECTIVE: The aim of this study is to discuss the curative effect of introperitoneal hyperthermic perfusion chemotherapy(IHPC) combined with systemic neoadjuvant chemotherapy on the gastric cancer patients with peritoneal carcinomatosis. METHODS: Sixty-four patients with gastric cancer and peritoneal carcinomatosis who were hospitalized in the Department of Gastrointestinal Surgery of First Hospital of Jilin University from December 2006 to December 2013. After peritoneal carcinomatosis was confirmed during laparoscopic exploration, FOLFOX6 (oxaliplatin and calcium folinate and 5-Fu) was performed for systemic chemotherapy. One course was 14 days and a complete treatment includes four courses. At the same time, patients underwent peritoneal catheter insertion and received IHPC(5-Fu 1 500 mg/m(2) and Cisplatin 35 mg/m(2) were added into 0.9% NaCl solution 2 000 ml, the infusion velocity was 35-45 ml/min, infusion time was 45-60 minutes, the temperature was controlled to 41°C). A comprehensive evaluation was taken after the fourth course of treatment before operation. Further surgical therapy was performed according to the assessment result. RESULTS: Sixty-four patients received IHPC combined with systemic chemotherapy. Thirty-two patients(50.0%) had partial response, 18(28.1%) stable disease, and 14(21.9%) progressive disease after chemotherapy. No severe complications or death occurred during the neoadjuvant chemotherapy. Thirty-two patients(50.0%) received radical resection, 10(15.6%) palliative operation, and another 22 patients(37.4%) didn't comply with inclusion criteria of operation. Patients receiving operation had a median survival time of 678 days, which was significantly longer than patients without operation, with a median survival time of 251(χ(2)=23.34, P=0.02). CONCLUSIONS: IHPC combined with systemic chemotherapy is an effective therapeutic method for gastric cancer patients with peritoneal carcinomatosis in terms of reducing preoperative tumor load and achieving radical resection.

[Effects of omega-3 polyunsaturated fatty acids on postoperative inflammatory reaction and clinical efficacy].

OBJECTIVE: To investigate the effect of omega-3 polyunsaturated fatty acids (PUFA) on postoperative inflammatory response and clinical efficacy in gastric cancer patients with nutritional risk. METHODS: All patients with gastric cancer in our department from June 2013 to January 2014 undergoing radical gastrectomy were prospectively enrolled in the study. Patients who matched the selection criteria were randomly divided into two groups: trial group (with omega-3 PUFA in parenteral nutrition) and control group (without omega-3 PUFA in parenteral nutrition). Levels of inflammatory factors (serum CRP, TNF-α, IL-1, IL-6, IL-10) and nutrition-related proteins (prealbumin, retinol conjugated protein and transferrin) were compared between the two groups before operation and 2, 4 and 6 days after operation. Incidence of postoperative systemic inflammatory response syndrome (SIRS) and other indicators associated with efficacy were compared between the two groups as well. RESULTS: Forty-seven patients were finally included in this study with 21 patients in the trial group and other 26 in the control group. There were no significant differences of inflammatory factors and nutrition-related proteins between the two groups before operation (all P>0.05). In the 6th days after operation, the levels of proinflammatory cytokines, including CRP, IL-1 and IL-6 were significantly lower in the trial group as compared to the control group, while the level of IL-10 (inhibiting inflammatory cytokine) was higher in the trial group, as well as levels of nutrition proteins(all P<0.05). The trial group had significantly lower rate of SIRS than the control group [57.1%(12/21) vs. 84.6% (22/26), P=0.036]. Compared with the control group, patients in the trial group had shorter bowel sound recovery time [(12.3±1.1) d vs. (3.1±1.3) d, P=0.025], earlier passage of flatus [(3.1±1.0) d vs. (3.9±1.2) d, P=0.025] and shorter hospital stay [(9.4±2.1) d vs. (10.9±2.5) d, P=0.038], but there was no difference in postoperative complication rate between the two groups (P=0.678). CONCLUSIONS: Omega-3 PUFA can reduce the release of inflammatory promoters, promote the release of inhibiting inflammatory cytokine IL-10, decrease the incidence of SIRS, improve patients' nutritional state, expedite the recovery of gastrointestinal function and shorten patients' recovery time.

Rhesus monkey alpha7 nicotinic acetylcholine receptors: comparisons to human alpha7 receptors expressed in Xenopus oocytes.

An alpha7 nicotinic acetylcholine receptor sequence was cloned from Rhesus monkey (Macaca mulatta). This clone differs from the mature human alpha7 nicotinic acetylcholine receptor in only four amino acids, two of which are in the extracellular domain. The monkey alpha7 nicotinic receptor was characterized in regard to its functional responses to acetylcholine, choline, cytisine, and the experimental alpha7-selective agonists 4OH-GTS-21, TC-1698, and AR-R17779. For all of these agonists, the EC(50) for activation of monkey receptors was uniformly higher than for human receptors. In contrast, the potencies of mecamylamine and MLA for inhibiting monkey and human alpha7 were comparable. Acetylcholine and 4OH-GTS-21 were used to probe the significance of the single point differences in the extracellular domain. Mutants with the two different amino acids in the extracellular domain of the monkey receptor changed to the corresponding sequence of the human receptor had responses to these agonists that were not significantly different in EC(50) from wild-type human alpha7 nicotinic receptors. Monkey alpha7 nicotinic receptors have a serine at residue 171, while the human receptors have an asparagine at this site. Monkey S171N mutants were more like human alpha7 nicotinic receptors, while mutations at the other site (K186R) had relatively little effect. These experiments point toward the basic utility of the monkey receptor as a model for the human alpha7 nicotinic receptor, albeit with the caveat that these receptors will vary in their agonist concentration dependency. They also point to the potential importance of a newly identified sequence element for modeling the specific amino acids involved with receptor activation.