[Clinical diagnosis and treatment analysis of 21 cases of intrathyroid thymic carcinoma].

Objective: To analyze the clinical efficacy of intrathyroid thymic carcinoma (ITTC). Methods: This study retrospectively analyzed the clinical data of 21 patients with ITTC diagnosed and treated at the First Affiliated Hospital of Zhengzhou University from January 2018 to July 2023, including 9 males and 12 females, with a median age of 52 years (40-60 years old). Results: There is a correlation between the maximum diameter of the tumor (≥40 mm) and lymph node metastasis (P=0.044). Seventeen patients received surgical treatment, and 4 patients only received chemotherapy. During the follow-up period, a total of 4 patients experienced death or progression, with a 2-year mortality or progression free survival rate of 74.8%. Conclusions: The prognosis of ITTC is good, and surgical treatment is the preferred treatment option, lymph node metastasis is significantly correlated with prognosis. The radiotherapy and chemotherapy of ITTC need to be determined based on the patient's condition.

[An exploratory clinical study of the efficacy and safety of tumor-infiltrating lymphocytes in the treatment of metastatic osteosarcoma].

Objective: To explore the safety and efficacy of tumor-infiltrating lymphocytes (TILs) extracted from tumor tissue in patients with pulmonary metastasis of osteosarcoma, the TILs were amplified in vitro to reach clinical dosage and reinfused to the patients combined with high-dose interleukin 2 (IL-2). Methods: Twelve subjects with pathologically diagnosed osteosarcoma were enrolled from December 2019 to June 20, 2021 in Shanghai General Hospital. All subjects progressed with metastasis after standard chemotherapy and failed multiple lines of treatments. Fresh tumor tissue was obtained from the metastatic site and extracted and amplified by Good Manufacturing Practice (GMP) workshop to produce TILs to clinical treatment dosage (109-1011). High-dose IL-2 (100 000-200 000 U/kg) was administered immediately after autogenous TILs infusion to promote the activation, proliferation and antitumor cytolytic activity in vivo. Adverse events (AE) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) standard and tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Results: One patient did not receive treatment due to failure in isolating TILs, total of 11 patients received a single re-infusion of autologous TILs. There were 10 males and 1 female with a median age of 19.9 years (12-33 years). Six of these patients received higher dose levels of 1.0×1010 TILs. The 11 patients were followed-up for 1 to 13 months and tolerated well. The most common adverse events reported were fever (10/11), constipation (3/11) and elevated gamma-glutamyl transferase (GGT) (3/11). The high incidence of fever was due to the IL-2 infusion. All patients experienced a transient drop in lymphocyte count and leukopenia leading to non-myeloid ablative lymphocyte clearance. The AE included grade 4 hematologic toxicity, including 8 cases of lymphocytopenia, 2 cases of neutropenia and 1 case of thrombocytopenia. No AE of neurotoxicity occurred. Of all the 11 patients, 9 patients got stable disease (SD) and 2 patients had progressive disease (PD). The disease control rate was 9/11. The median duration of SD was more than 4 months, and the maximum tumor volume decreased by close to 20%. Patient number 9 had sustained SD status for more than 6 months. Conclusions: TILs with in vitro expansion ability could be isolated from tumor tissues of advanced osteosarcoma patients. TILs amplified and reinfused in vitro have anti-osteosarcoma activity.

Investigation of dual-wavelength pump schemes for optically pumped rare gas lasers.

Optically pumped rare gas lasers (OPRGLs) have shown great potential to generate high energy laser radiation with high beam quality. As an alternative to the diode-pumped alkali vapor lasers (DPALs), they have similar working principles and characteristics, but OPRGLs have the advantage that the gain medium is chemically inert and is appropriate for closed-cycle operation. One of the challenges OPRGLs are faced with is the bottleneck caused by the slow 1s4-1s5 collisional relaxations at room temperature. A 1s4-2p10 dual-wavelength pump method had been proposed to transfer the populations pooled on the 1s4 level to the lasing cycle using a steady-state laser model. We explored this method further through 1s4-2p8 and 1s4-2p7 dual-wavelength pump schemes. The enhancement efficiencies at room temperature for a repetitively pulsed discharge, CW dual-wavelength pump system were examined using a dynamic model, and an experiment with a pulsed secondary pump was conducted for qualitative evaluations.

Both Caspase and Calpain are Involved in Endoplasmic Reticulum-Targeted BNIP3-Induced Cell Death.

Bcl-2/E1B-19K-interacting protein 3 (BNIP3) is a member of the apoptotic B-cell lymphoma-2 family that regulates cell death. Although BNIP3 targeted normally to the mitochondrial outer membrane by its transmembrane domain was originally considered to be essential for its pro-apoptotic activity, accumulating evidence has shown that BNIP3 is localized to endoplasmic reticulum at physiological conditions and that forced expression of BNIP3 can initiate cell death via multiple pathways depending on the subcellular compartment it targets. Targeting BNIP3 to endoplasmic reticulum has been shown to participate in cell death during endoplasmic reticulum stress. However, the molecular events responsible for BNIP3-induced cell death in the endoplasmic reticulum remain poorly understood. In the present study, the transmembrane domain of BNIP3 was replaced with a segment of cytochrome b5 that targets BNIP3 into endoplasmic reticulum, which induced cell death as effectively as its wild-type molecule in the SW480 cell line (colon carcinoma). Furthermore, a pan-caspase inhibitor, z-VAD-fmk, and PD150606, a specific calpain inhibitor, both significantly suppressed the endoplasmic reticulum-targeted BNIP3-induced cell death. These results suggest that endoplasmic reticulum-targeted BNIP3 induced a mixed mode of cell death requiring both caspases and calpains.

The ANXA1 released from intestinal epithelial cells alleviate DSS-induced colitis by improving NKG2A expression of Natural Killer cells.

Inflammatory bowel disease (IBD) arises when intestinal immune homeostasis is broken, the maintenance of such homeostasis is principally controlled by cross talk between commensal bacteria, mucosal immune cells and intestinal epithelial cells (IECs). IECs can prevent the contact between luminal bacteria with immune cells through the formation of a physical barrier and the expression of antimicrobial peptides to maintain intestinal immune homeostasis. During Colitis the IECs can express increased ANXA1, which is important for regeneration of intestinal mucosa and function as a potent anti-inflammatory protein. Natural Killer (NK) cells can also suppress the progression of colitis. It is uncertain about the effect of the cross-talk between injured IECs and recruited NK cells during colitis. In this study, the expression of ANXA1 in IECS from DSS treated mice was increased, and more NK cells were recruited to intestinal mucosa. In addition, the expression of NKG2A was upregulated when co-cultured with NK cells. The results further proved that overexpression of NKG2A in NK cells was important for inhibiting the recruitment and activity of neutrophils to alleviate DSS-induced colitis. Here, we provide a new anti-inflammation mechanism about ANXA1 secreted from injured IECs, where ANXA1 can stimulate the expression of NKG2A in NK cells that affect the recruitment and activity of neutrophils necessary for pathology of colitis.

[Clinical effect of ultrasound-guided injection of biodegradable poly(lactic-co-glycolic acid)-Fe3O4 in situ implant for magnetic thermal ablation in treatment of nude mice with human liver cancer SMMC-7721 cells].

Objective: To prepare the Fe3O4-loaded biodegradable liquid-solid phase inversion poly(lactic-co-glycolic acid) (PLGA) in situ implant for ultrasound-guided injection into nude mouse tumor model, and to investigate its clinical effect in thermomagnetic treatment of nude mice with human liver cancer SMMC-7721 cells in an alternating magnetic field. Methods: An in situ implant containing 10% Fe3O4 was prepared, and 50 µl Fe3O4-PLGA-NMP gel was injected into the subcutaneous tissue of Kunming mice. The degradation of this material was observed for 2 consecutive months, and the changes in body weight were recorded. HE staining and Prussian blue staining were performed for the heart, liver, spleen, lung, and kidney of Kunming mice. Fresh ex vivo bovine liver was taken and cut into cubes with a dimension of 2 cm×2 cm×2 cm and then 50 µl Fe3O4-PLGA-NMP gel was injected; after phase inversion, the cubes of ex vivo bovine liver were heated for 1, 2, 3, 4, and 5 minutes, respectively, and then cut open for observing the range of ablation; HE staining was also performed. Micro-CT scan was performed after ultrasound-guided injection of 50 µl Fe3O4-PLGA gel into the tumors of the nude mice, and then the nude mice were divided into treatment group and control group. The mice in the treatment group were given thermomagnetic treatment for 3 minutes, and tumor growth was observed daily. Results: The biodegradation of Fe3O4-PLGA-NMP implant showed that the subcutaneously injected material was gradually metabolized at 2 weeks after injection and that the nude mice were in good condition. The bovine liver ablation experiment showed that the range of ablation of 50 µl Fe3O4-PLGA implant reached 1.46 ± 0.11 cm. HE staining showed that part of bovine liver had coagulative necrosis. The phase inversion experiment of Fe3O4-PLGA gel showed quick liquid-solid phase inversion of the material after injection into the tumor, and the process of liquid-solid phase inversion could be monitored by ultrasound and CT. The detachment and incrustation of the tumor started at 2 days after treatment, the wound started to heal 15 days later, and the tumor tissue disappeared completely. Conclusion: Ultrasound-guided injection of biodegradable Fe3O4-PLGA in situ implant combined with magnetic thermal ablation can effectively treat human liver cancer SMMC-7721 cells in nude mice.

Genetic Polymorphisms of 21 STR Loci in Hunan Province-based Han Population.

OBJECTIVES: To investigate the genetic polymorphisms of 21 short tandem repeat （STR） loci （D3S1358, D13S317, D7S820, D16S539, Penta E, D2S441, TPOX, TH01, D2S1338, CSF1PO, Penta D, D10S1248, D19S433, vWA, D21S11, D18S51, D6S1043, D8S1179, D5S818, D12S391 and FGA）. METHODS: A total of 560 blood samples were collected from unrelated healthy individuals of Han population in Hunan Province. Chelex-100 extraction method was applied to the extraction of genomic DNA, and an AGCU EX22 Kit and 9700 STR amplification was used in amplification reactions. The products were separated and analyzed on 310 Genetic Analyzer. RESULTS: A total of 248 alleles were observed, the allelic frequencies ranging from 0.001 to 0.518. Observation of genotype distributions for each locus showed no deviations from Hardy-Weinberg equilibrium except Penta E （P=0.023）. The combined power of discrimination, combined power of exclusion, and combined matching probability of the 21 STR loci were approximately 0.999 999 999 999 999 999 999 999 8, 0.999 999 998, and 1.36×10⁻²5, respectively. CONCLUSIONS: The 21 STR loci show high polymorphisms in the Han population, which can provide valuable data and a theoretical basis for forensic individual identification and paternity testing.

Characteristics of Cyclin B and its potential role in regulating oogenesis in the red claw crayfish (Cherax quadricarinatus).

Cyclin B is a regulatory subunit of maturation-promoting factor (MPF), which has a key role in the induction of meiotic maturation of oocytes. MPF has been studied in a wide variety of animal species; however, its expression in crustaceans is poorly characterized. In this study, the complete cDNA sequence of Cyclin B was cloned from the red claw crayfish, Cherax quadricarinatus, and its spatiotemporal expression profiles were analyzed. Cyclin B cDNA (1779 bp) encoded a 401 amino acid protein with a calculated molecular weight of 45.1 kDa. Quantitative real-time PCR demonstrated that Cyclin B mRNA was expressed mainly in the ovarian tissue and that the expression decreased as the ovaries developed. Immunofluorescence analysis revealed that the Cyclin B protein relocated from the cytoplasm to the nucleus during oogenesis. These findings suggest that Cyclin B plays an important role in gametogenesis and gonad development in C. quadricarinatus.

Shed Syndecan-1 is involved in chemotherapy resistance via the EGFR pathway in colorectal cancer.

BACKGROUND: Syndecan-1 (Sdc-1) shedding induced by matrix metalloproteinase-7 (MMP-7) and additional proteases has an important role in cancer development. However, the impact of Sdc-1 shedding on chemotherapeutic resistance has not been reported. METHODS: We examined Sdc-1 shedding in colorectal cancer by enzyme-linked immunosorbent assay (ELISA), Dot blot, reverse transcription-PCR (RT-PCR), immunohistochemistry and so on, its impact on chemotherapeutic sensitivity by collagen gel droplet embedded culture-drug sensitivity test (CD-DST) and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), and potential mechanisms of action by Dot blot, western blot and immunofluorescence. RESULTS: Sdc-1 shedding was increased in colorectal cancer patients, Sdc-1 serum levels in postoperative patients were lower than in preoperative patients, but still higher than those observed in healthy adults. Patients with high preoperative Sdc-1 serum levels were less responsive to 5-Fluorouracil, Oxaliplatin, Irintecan, Cisplatin or Paclitaxel chemotherapy. Moreover, the disease-free survival of patients with high preoperative Sdc-1 serum levels was significantly poorer. The possible mechanism of chemotherapy resistance in colorectal cancer can be attributed to Sdc-1 shedding, which enhances EGFR phosphorylation and downstream signalling. CONCLUSIONS: Shed Sdc-1 is involved in chemotherapy resistance via the EGFR pathway in colorectal cancer, and Sdc-1 serum levels could be a new prognostic marker in colorectal cancer.

Remarkable undercooling capability and metastable thermophysical properties of liquid Nb84.1Si15.9 alloy revealed by electrostatic levitation in outer space.

The stable manipulation, high undercooling, and thermophysical property measurement of the liquid Nb84.1Si15.9 refractory alloy were successfully achieved by the electrostatic levitation technique on board the China Space Station. By controlling the superheating temperature, a maximum liquid undercooling up to 421 K (0.18 TL) was obtained in the space environment, and two distinct solidification paths with different recalescence features were realized at metastable undercooled states. The liquid density and the ratio of specific heat to emissivity were measured in a wide temperature range from 1841 to 2346 K, which displayed linear and quadratic relations vs temperature, respectively. The liquid emissivity was further deduced from the specific heat of the liquid alloy calculated by molecular dynamics simulation. In addition, both the density and structural characteristics of the undercooled liquid alloy were also analyzed by MD calculations.

Analysis of differentially expressed genes in ductal carcinoma with DNA microarray.

AIM: The aim of this study is to investigate the dysregulated biological functions that play important role in the occurrence and development of breast invasive ductal carcinoma (IDC). MATERIALS AND METHODS: We downloaded the gene expression profile data from gene expression omnibus (GEO) database, including 42 disease samples and 143 adjacent histological normal samples. Significance analysis of microarrays (SAM) was employed to identify differentially expressed genes (DEGs) between the normal and disease samples. Gene ontology (GO) function enrichment analysis was based on Software DAVID, followed by KEGG pathway enrichment analysis. TRANSFAC database and HPRD database were employed to construct the transcriptional regulatory network (Tnet) and protein-protein interaction (PPI) network, respectively. RESULTS: We got a total of 1769 genes significantly differentially expressed, including 907 up-regulated genes and 862 down-regulated genes. Functional analysis revealed that hormone-responsive genes are related with the occurrence of cancer. Then, we successfully constructed IDC-specific Tnet and PPI network with DEGs response to hormone and obtained some hub genes, such as FOS and PIK3R1, in these networks. Besides, ten modules were found in these networks. CONCLUSIONS: Hormone-responsive genes and modules may play an important role in the occurrence and development of IDC. Based on the findings above, we got a preliminary understand of the occurrence, development and metastasis of the IDC and possibly provided effective information on the biogenesis of IDC.

beta1-integrin is dispensable for the induction of ErbB2 mammary tumors but plays a critical role in the metastatic phase of tumor progression.

Cross-talk between integrin receptors and activated growth factor receptors has been hypothesized to play a critical role in the initiation and progression of cancer. Despite in vitro evidence documenting the important role of integrin receptors in the regulation of cancer cell proliferation, the relative contribution of the integrin receptors to the initiation and progression of tumors remains unclear. Previous studies with a polyomavirus middle T mammary tumor model have indicated that targeted disruption of beta1-integrin in the mammary glands of these mice completely blocks tumor induction. To further explore the general significance of these observations, we have crossed these conditional beta1-integrin strains to a strain of mice carrying mouse mammary tumor virus/activated erbB2 (herein referred to as the NIC strain). In contrast to the tumor induction block in the polyomavirus middle T model, tumor onset in the beta1-integrin-deficient NIC mice was delayed by only 30 d and was 100% penetrant. This modest effect on tumor induction was not a result of inefficient excision, as all tumors were confirmed as beta1-integrin-null. Animals bearing beta1-integrin-deficient ErbB2 tumors exhibited significantly reduced tumor volume, which was associated with increased tumor cell apoptosis and a reduction in tumor angiogenesis. In addition, beta1-integrin-deficient tumors were compromised in their capacity to metastasize to the lung, a deficiency associated with abrogation of adhesion signaling. Taken together, these observations suggest that, although beta1-integrin is dispensable for the initiation of ErbB2 tumor induction, it plays a critical role in metastatic phase of tumor progression.

Thermophysical properties and atomic structure of liquid Zr-Nb alloys investigated by electrostatic levitation and molecular dynamics simulation.

The investigation of the thermophysical properties of liquid Zr-Nb alloys holds great significance for theoretical research and technical application in liquid physics. However, the high temperatures involved make their experimental measurement challenging. In this study, the densities of liquid Zr-xwt.% Nb (x= 1.0, 2.5, 6.0) alloys were examined by electrostatic levitation and molecular dynamics calculation. Remarkably, the alloys achieved maximum undercooling of 335 K, 311 K and 326 K, respectively. Correspondingly, the densities are 6.20, 6.22 and 6.26 g·cm-3at the liquidus temperatures (TL), respectively. The corresponding temperature coefficients are 2.61 × 10-4, 2.75 × 10-4and 2.84 × 10-4g·cm-3·K-1, respectively. Notably, the experimental density results align well with the simulated results. Moreover, the molar volume (Vm), thermal expansion coefficient (α) and diffusion coefficient (D) were derived based on the experimental data and simulations. The thermal expansion coefficients reduce linearly with decreasing temperature. The analysis of the pair distribution function, coordination number (CN) and the radial distribution function reveals the temperature-dependent evolution of the atomic structure. TheCNtotalandCNZr-Zrinitially increase and then decrease with decreasing temperature, while the change trends forCNZr-NbandCNNb-Nbvaried among the three alloys. The radial distribution function of three liquid alloys reveals that the atomic number density increases as the temperature drops. Additionally, the total diffusion coefficients decrease with the reduction of temperature and the rise of Nb content from 1.0 wt.% Nb to 6.0 wt.% Nb.

[Icaritin increases radiosensitivity of nasopharyngeal carcinoma cells by regulating iron death].

OBJECTIVE: To explore the radiosensitizing effect of icaritin on nasopharyngeal carcinoma (NPC) cells and the underlying mechanism. METHODS: MTT assay and clonal formation assay were used to evaluate the effect of icaritin on proliferation of human NPC HONE1 and HNE1 cells. The effects of icaritin treatment, γ-ray radiation, or both on production of reactive oxygen species (ROS), cell cycle distribution and apoptosis of the NPC cells were assessed using flow cytometry. The expressions of DNA damage markers γ-H2AX, cycle-related proteins CDC25C, p-CDC25C and cyclin B1, and ferroptosis markers ACSL4 and GXP4 were detected using Western blotting. A nude mouse model bearing subcutaneous HONE1 cell xenograft was used to observe the effect of icaritin and radiation on tumor growth. RESULTS: Icaritin dose-dependently inhibited the viability of the NPC cells and enhanced the inhibitory effect of radiation on cell proliferation. Flow cytometry and Western blotting showed that icaritin treatment prior to radiation significantly promoted ROS production and γ-H2AX expression in the NPC cells (P<0.001). Compared with radiation exposure alone, the combined treatment caused cell cycle arrest in G2 phase, down-regulated CDC25C and cyclin B1 expression, and up-regulated p-CDC25C expression in the cells (P<0.01), resulting also in increased cell apoptosis, enhanced expression of ferroptosis protein ACSL4 and lowered expression of GXP4 (P<0.001). In the tumor-bearing mice, icaritin treatment, compared with radiation alone, significantly reduced the tumor growth rate and decreased tumor weight (P<0.001). CONCLUSION: Icaritin can enhance radiosensitivity of NPC cells both in vitro and in nude mice possibly by enhancing ROS production to promote iron death of the cells.

Correction: Toosendanin demonstrates promising antitumor efficacy in osteosarcoma by targeting STAT3.

Since the publication of this paper, the authors have noticed that the article contains an error in Figure 3e (TSN, 50 nM). As a result of the misfiling of the data, the incorrect image was inadvertently inserted in Figure 3e during figure preparation. The corrected image is shown in this correction.

From Antimicrobial to Anticancer Peptides: The Transformation of Peptides.

BACKGROUND: Antimicrobial peptides play an important role in the innate immune system. Possessing broad-spectrum antibacterial activity, antimicrobial peptides can quickly treat and kill various targets, including gram-negative bacteria, gram-positive bacteria, fungi, and tumor cells. OBJECTIVE: An overview of the state of play with regard to the research trend of antimicrobial peptides in recent years and the situation of targeting tumor cells, and to make statistical analysis of the patents related to anticancer peptides published in recent years, is important both from toxicological and medical tumor therapy point of view. METHODS: Based on the Science Citation Index Expanded version, the Derwent Innovation Index and Innography as data sources, the relevant literature and patents concerning antimicrobial peptides and anticancer peptides were analyzed through the Thomson Data Analyzer. Results of toxicologic and pharmacologic studies that brought to the development of patents for methods to novel tumor drugs were analyzed and sub-divided according to the specific synthesis of anticancer peptides. RESULTS: The literature and patent search data show that the research and development of global antimicrobial peptides and anticancer peptides has been in an incremental mode. Growing patent evidence indicate that bioinformatics technology is a valuable strategy to modify, synthesize or recombine existing antimicrobial peptides to obtain tumor drugs with high activity, low toxicity and multiple targets. CONCLUSION: These findings may have important clinical implications for cancer treatment, especially in patients with conditions that are not currently treatable by other drugs, or that are resistant to existing cancer drugs.

Oncogenic activation of the Met receptor tyrosine kinase fusion protein, Tpr-Met, involves exclusion from the endocytic degradative pathway.

Multiple mechanisms of dysregulation of receptor tyrosine kinases (RTKs) are observed in human cancers. In addition to gain-of-function, loss of negative regulation also contributes to oncogenic activation of RTKs. Negative regulation of many RTKs involves their internalization and degradation in the lysosome, a process regulated through ubiquitination. RTK oncoproteins activated following chromosomal translocation, are no longer transmembrane proteins, and are predicted to escape lysosomal degradation. To test this, we used the Tpr-Met oncogene, generated following chromosomal translocation of the hepatocyte growth factor receptor (Met). Unlike Met, Tpr-Met is localized in the cytoplasm and also lacks the binding site for Cbl ubiquitin ligases. We determined whether subcellular localization of Tpr-Met, and/or loss of its Cbl-binding site, is important for oncogenic activity. Presence of a Cbl-binding site and ubiquitination of cytosolic Tpr-Met oncoproteins does not alter their transforming activity. In contrast, plasma membrane targeting allows Tpr-Met to enter the endocytic pathway, and Tpr-Met transforming activity as well as protein stability are decreased in a Cbl-dependent manner. We show that transformation by Tpr-Met is in part dependent on its ability to escape normal downregulatory mechanisms. This provides a paradigm for many RTK oncoproteins activated following chromosomal translocation.

ErbB2-positive mammary tumors can escape PI3K-p110α loss through downregulation of the Pten tumor suppressor.

Breast cancer is the most common cancer among women and 30% of patients will be diagnosed with an ErbB2-positive tumor. Forty percent of ErbB2-positive breast tumors have an activating mutation in p110α, a catalytic subunit of phosphoinositide 3-kinase. Clinical and experimental data show that breast tumors treated with a p110α-specific inhibitor often circumvent inhibition and resume growth. To understand this mechanism of resistance, we crossed a p110α conditional (p110αflx/flx) mouse model with mice that overexpress the ErbB2/Neu-IRES-Cre transgene (NIC) specifically in the mammary epithelium. Although mammary-specific deletion of p110α dramatically delays tumor onset, tumors eventually arise and are dependent on p110ß. Through biochemical analyses we find that a proportion of p110α-deficient tumors (23%) display downregulation of the Pten tumor suppressor. We further demonstrate that loss of one allele of PTEN is sufficient to shift isoform dependency from p110α to p110ß in vivo. These results provide insight into the molecular mechanism by which ErbB2-positive breast cancer escapes p110α inhibition.

Toosendanin demonstrates promising antitumor efficacy in osteosarcoma by targeting STAT3.

Signal transducer and activator of transcription 3(STAT3) is an emerging target for cancer therapy. In this study, we identify Toosendanin (TSN) is an effective inhibitor of STAT3, leading to the impediment of various oncogenic processes in osteosarcoma. TSN selectively inactivates phospho-STAT3 (Tyr-705); subsequent molecular docking and in vitro SPR analysis uncover TSN directly binds to the SH2 domain of STAT3. Consequently, TSN blocks STAT3 dimerization and impairs the complex formation of STAT3 and epidermal growth factor receptor (EGFR). In an animal tumor model study, TSN is well tolerated, inhibits osteosarcoma growth and metastasis. In another osteosarcoma patient-derived xenografts (PDX) model, we find TSN triggers strong inhibitory effects on patient-derived tumors. Further studies show that TSN also displays activity against other solid tumors. Our preclinical work therefore supports that TSN acts as a novel inhibitor of STAT3 that blocks tumorigenesis in ostoesarcoma.

Erianin induces G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells in vitro and in vivo.

Erianin, a natural product derived from Dendrobium chrysotoxum, has exhibited potential antitumor activity in various malignancies, including hepatocarcinoma, melanoma, and promyelocytic leukemia. Here we explored the effects of erianin on osteosarcoma (OS) in vitro and in vivo and further elucidated the underlying molecule mechanisms. In this study, we found that erianin potently suppressed cell viability in various OS cell lines. Treatment with erianin induced G2/M-phase arrest, apoptosis, and autophagy in OS cells. Further studies showed that erianin-induced apoptosis and autophagy was attributed to reactive oxygen species (ROS), as N-acetyl cysteine (NAC), an ROS scavenger, attenuated them. Moreover, we found that erianin induced activation of c-Jun N-terminal kinase (JNK) signal pathway, which was also blocked by NAC. Downregulation of JNK by its specific inhibitor SP600125 could attenuate apoptosis and autophagy induced by erianin. Finally, erianin in vivo markedly reduced the growth with little organ-related toxicity. In conclusion, erianin induced cell cycle G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human OS. In light of these results, erianin may be a promising agent for anticancer therapy against OS.