Preliminary Validation of Tumor Cell Attachment Inhibition Assay for Developmental Toxicants With Mouse S180 Cells

This study was designed to explore the possibility of using ascitic mouse sarcoma cell line (S180) to validate the mouse tumor cell attachment assay for developmental toxicants, and to test the inhibitory effects of various developmental toxicants. The results showed that 2 of 3 developmental toxicants under consideration, sodium pentobarbital and ethanol, significantly inhibited S180cells attachment to Concanavalin A-coaed surfaces. Inhibition was dependent on concentration, and the IC50 (the concentration tha reduced attachment by 50% ), of these 2 chemicals was 1.2×10-3mol/L and 1 .0 mol/L, respectively. Anoher developmental toxiant, hydmiortisone, did not show inhibitory activity. Two non-developmental toxicants, sodium chloride and glycine were also tested and these did not decrease attachment rates. The main results reported here were generally sindlar to those obtained with ascitic mouse ovdrian tumor cells as a model. Therefore, this study added further evidence to the conclusion that cell specificity does not lindt attachment inhibition to Con A-coated surfaces, so S180 cell may serve as an altemative cell model, especially when other cell lines are unavailable. Furthermore, after optimal validation, it can be suggested that an S180 cell attachment assay may be a candidate for a series of assays to detect developmental toxicants.

Tumor microenvironment-activatable neuropeptide-drug conjugates enhanced tumor penetration and inhibition via multiple delivery pathways and calcium deposition

Peptide-drug conjugates have achieved considerable development and application as a novel strategy for targeted delivery of anticancer drugs. Bioactive peptides induced calcium deposition can irreversibly assist inhibition of tumors. However, active regulation of calcium level through signal transduction of bioactive substances has not been reported yet. In this study, novel neuropeptide-doxorubicin conjugates(NP-DOX) with lysosome-specific acid response were described for neuropeptide Y_1 receptor(Y_1R)-overexpressed triple-negative breast cancer. The delivery mechanism of NP-DOX was clarified that diverse pathways were involved, including intracellular and intercellular transport. Importantly, up-regulation of Y_1 R-mediated intracellular calcium level via second messenger inositol triphosphate was presented in NP-DOX treated MDA-MB-231 cells. In vivo antitumor efficacy demonstrated that NP-DOX showed less organ toxicity and enhanced tumor inhibition benefited from its controlled release and Y_1R-mediated calcium deposition, compared with free DOX. This bioconjugate is a proof-of-concept confirming that neuropeptide-mediated control of signaling responses in neuropeptide-drug conjugates enables great potential for further applications in tumor chemotherapy.

ANTITUMOR MECHANISM OF GEM10 BY THE NATURAL KILLER ACTIVITY AND INTERLEUKIN-2 PRODUCTION

Objective To investigate th e anti-tumor effects of GeM10 by the natural killer(NK) cells activities and th e production of Interleukin-2 (IL-2) in peripheral blood mononuclear cells (PB MNCs). Methods Assay of human NK cells activities by dye reject ion assay in vitro and production of IL-2 in PBMNC by IL-2 bioassay with I L-2 dependent cell line CTLL2 and MTT colorometric method. Results GeM10 could significantly stimulate NK activities (60μg·mL -1 G eM10: 17.077±7.665, 120μg·mL -1 GeM10: 24.9±13.04; control: 7.72±4 .64, P< 0.05). GeM10 could up-regulate the production of IL-2 of PBMNCs in tumor patients(60μg·mL -1 GeM10: 2.965± 1.183; 120μg·mL -1 GeM10: 2.28±0.847; control: 1.792±0.823, P<0.05).Conclu si on The GeM10 not only can stimulate the NK activities but also increase the IL-2 production by PBMNCs in tumor patients. These findings indicate that the GeM10 may have promise as an anti-tumor drug and a biological response modi fier in clinic.

Nanomaterials for visualized tumor surgical navigation and postoperative recurrence inhibition

Preoperative localization of the tumor sites and intraoperative real-time monitoring are essential for precise surgery but are meanwhile challenging due to the lack of high-resolution,easy-to-operate,and fast visualization techniques.On the other hand,tumor recurrence and metastasis after surgery greatly reduce the survival rate of patients.Intervening tumor recurrence during surgery is a future direction of tumor treatment.Nanomaterials with external condition responsiveness(light,ultrasound,and magnetic field)can accurately assist intraoperative detection and surgical resection due to their functions such as tumor cell targeting,fluorescence imaging,and real time monitoring,providing a more accurate,shorter duration,and visualization method of surgical resection.Moreover,nanomaterials are versatile and can easily be tailored for application in different tumors.Locally filled or systemically circulating nanomaterials with slow drug release and residual tumor cell-targeting ability have promising applications in inhibiting tumor recurrence.Here,we review surgical navigation and postoperative recurrence interventional nanomaterials and their landscape in guiding tumor treatment.We summarize the classification and characteristics of these nanomaterials and discuss their application in the surgical navigation and recurrence inhibition of different tumors.We also provide an outlook on the challenges and future development of nanomaterials for visualized tumor surgical navigation and postoperative recurrence inhibition.

Ensemble of single-atom catalysis and defect engineering in Cu_(1)/CeO_(2) nanozymes for tumor therapy

As a class of nanomaterials with natural enzyme-like characteristics, nanozymes have shown their great potential in various applications. Reducible metal oxides featured with defect structures, and single-atom catalysts with isolated metal sites are regarded as two of the most promising nanozymes. However, the strategies to construct highly performed nanozymes by combining these advantages are rarely reported. Herein, we report the coordination-unsaturated single-atomic Cu species supported on sintered CeO_(2), which combines the advantages of defect engineering and single-atom catalysis, exhibiting a largely enhanced peroxidase(POD)-like activity. The high-temperature calcination induces the transformation of inert Cu_(1)O_(4) species into coordination-unsaturated Cu_(1)O_(3) sites. This novel Cu_(1)O_(3) active sites with an unsaturated coordination work as a new type of defect sites to greatly activate the isolated Cu atoms and accelerate the dissociation of H_(2)O_(2) to form hydroxyl radicals(·OH). The obtained nanozyme with a high POD-like activity possesses low cytotoxicity, showing potential applications for the tumor inhibition in vitro and in vivo.

Ovarian growing teratoma syndrome with multiple metastases in the abdominal cavity and liver:A case report

BACKGROUND Growing teratoma syndrome(GTS)is an unusual presentation of an amazing transformation of teratoma from malignant to benign on pathology during or after systemic or intraperitoneal chemotherapy.The definitive pathogenesis is still not fully understood due to the lack of large-sample studies.CASE SUMMARY A 53-year-old woman underwent radical surgery and postoperative intraperitoneal chemotherapy due to immature teratoma of the right ovary at the age of 28.She remained well during a 25-year follow-up period after surgery.Multiple asymptomatic solid masses were found in the liver on ultrasonography a month ago.Enhanced computed tomography(CT)of the abdomen revealed multiple masses in the abdominal cavity.The largest one was located in the posterior peritoneum next to the sixth segment of the right liver,about 7.9 cm×7.5 cm in size.Three masses were present inside the liver,and one mass was in the right pelvic floor.Multiple lumps in the abdominal cavity were completely removed by surgery.During the operation,multiple space-occupying lesions were seen,ranging in size from 0.5 to 3 cm,and grayish white in color and hard in texture.Ovarian GTS was finally diagnosed based on postoperative pathology.After surgery,she recovered uneventfully.During a 3-year follow-up,the patient remained free of the disease without any recurrence on CT scan.CONCLUSION GTS is a rare phenomenon characterized by conversion of immature teratoma to mature one during or after chemotherapy and presents as growing and metastasizing masses.The pathogenesis of GTS is unclear,and the prognosis is good after surgical resection.

Preparation of chitosan-Epigallocatechin-3-O-gallate nanoparticles and their inhibitory effect on the growth of breast cancer cells

In this paper,we prepared the nanoparticle drug carrier system between nanoparticles chitosan and Epigallocatechin-3 O-gallate(EGCG)for breast cancer cell inhibiting application.For this drug carrier system,chitosan acts as a carrier and EGOG as a drug.Which were systematically characterized and thoroughly evaluated in terms of their inhibition rate and biocompatibility.We also did a cell scratch test and the result indicated that the chitosan EGCG nanoparticles have inhibitory effect on the growth of breast cancer cells.The inhibition rate could reach up to 21.91%.This work revealed that the modification of nanopartidles paved a way for specific biomedical applications.

Comparative antitumor and anti-proliferative activities of Hippophae rhamnoides L. leaves extracts

Objective:To evaluate the antitumor and anti-proliferative activities of methanol,aqueous,acetone,ethyl acetate,ethanol,chloroform and n-hexane extracts of Hippophae rhamnoides leaves.Methods:Antitumor activities were evaluated by using the antitumor potato disc assay by using inoculums(Agrobacterium tumefaciens)with three different concentrations of test samples(10,100 and 1000 mg/L).Anti-proliferative activity was evaluated by the given method of methyl thiazolyl tetrazolium assay.The concentrations of the extract ranging from 0.039 to 10 mg/mL were tested against HeLa cells.Results:Highest tumors inhibition activity(60.9%and 55.8%)was shown by methanol and ethanol extracts,with EC_(50) values of 424.41 and 434.61 mg/L respectively.At 10 mg/mL,The highest cell inhibition 75.61%was observed in methanol extract and the lowest 36.59%were calculated in n-hexane extract.The difference in tumor and cell inhibition(%)may be due to the different concentration of active compounds responsible for antitumor and anti-proliferative activities.All extracts have considerable level of tumor and cell inhibitiory effect in a dose dependent manner.Conclusions:Our finding showed that Hippophae rhamnoides leaves are a potent natural source of antitumor and antiproliferative agent.

Anti-melanoma effect and action mechanism of a novel chitosan-based composite hydrogel containing hydroxyapatite nanoparticles

Hydroxyapatite nanoparticles(HANPs)have been increasingly regarded and reported due to their potential anti-tumor ability.Previously,we found that the rod-like HANPs had good application potential for cutaneous melanoma(CMM).To satisfy the actual requirements in repairing post-operative skin defects and inhibiting CMM recurrence after tumorectomy,we constructed a novel chitosan/alginate(CS/Alg)hydrogel containing the aforementioned HANPs.The in vitro cell experiments confirmed that activated mitochondrial-dependent apoptosis was tightly related to the anti-tumor ability of HANPs.Specifically,we further discovered several target proteins might be involved in abnormal activating Wnt,proteoglycans in cancer,oxidative phosphorylation and p53 signaling pathways.The in vivo animal experiments demonstrated that the HANPsloaded CS/Alg hydrogel(CS/Alg/HANPs)had a similar effect on inhibiting tumor growth as HANPs,and CS/Alg hydrogel as well as phosphate buffered saline(PBS)group(control)not showed any effect,proving the key role of HANPs.The immunohistochemical staining demonstrated a tumor inhibition via the mitochondria-mediated apoptosis pathway,consistent with the in vitro evaluation.Moreover,CS/Alg/HANPs exhibited no additional biosafety risk to the functions of major organs.Overall,this CS/Alg/HANPs hydrogel has substantial application potential for treating CMM.

主动穿细胞转运的定向纳米载体用于化学-免疫治疗抑制肿瘤生长及转移

目前免疫治疗已经显示出了极大的肿瘤治疗潜力,然而纳米载体较低的转运能力以及肿瘤免疫响应性低等问题严重阻碍了免疫治疗的临床应用.为了解决这些问题,本课题研制了一种具有主动穿细胞转运能力的定向纳米载体用于化疗增强的免疫治疗.当该纳米载药系统到达肿瘤部位,金属基质蛋白酶2响应的纳米外壳崩解,释放出带有正电荷的纳米内核.正电荷促使纳米内核产生吸附介导的胞吞,进而促进纳米载药系统的跨血管内皮细胞运输和跨细胞药物递送,并最终将药物递送到远端肿瘤细胞中. PD-L1抗体和化疗药物分别被载于纳米载体的外壳和内核中进行精准递送,从而达到对具有不同治疗靶点的药物同步递送、定向释药的目的.肿瘤微环境中释放的PD-L1抗体作用于T细胞表面的特异性受体,阻断了T细胞与肿瘤细胞的结合.正电荷纳米内核同步运载奥沙利铂和吲哚美辛进入深层肿瘤细胞,在整个肿瘤组织中引发免疫原性死亡、逆转免疫抑制作用,招募大量的T细胞并最终增强免疫治疗疗效.本研究中所构建的纳米载药体系不仅能够抑制原位瘤生长,还能够阻止肿瘤的转移.这为化疗增强的免疫治疗提供了一种新的纳米递送方案,提高了免疫治疗在免疫响应率低的肿瘤中的疗效.