Toxic Side Effects Research Articles

Research progress on effect evaluation and application status of acupoint drug delivery

Acupoint drug delivery is a traditional external therapy of traditional Chinese medicine(TCM). Guided by the meridian and collateral theory in TCM, it applies medications to the skin at acupoints, exerting a dual therapeutic effect by stimulating the acupoints and the conduction of meridians. Acupoint drug delivery is widely used in clinical practice. Different from traditional oral admi-nistration and injection, it absorbs medications through the skin, effectively avoiding the first-pass effect of drugs and the toxic side effects caused by injection. Acupoint selection and transdermal drug absorption are pivotal factors affecting the efficacy of acupoint drug delivery. Recent research on acupoint drug delivery mainly focuses on the evaluation of clinical efficacy, yet the systematic investigations on acupoint selection and pharmacodynamic factors are scarce. This study reviews the mechanism, efficacy evaluation and application status of acupoint drug delivery. It integrates the theory of TCM with modern medicine to explore the mechanism of acupoint drug delivery, evaluate its clinical efficacy, and assess the transdermal penetration in vivo and in vitro. The application status of acupoint drug delivery is also summarized, including the selection of acupoints, application dosage form, application time and the absorption of acupoints. This review aims to offer insights and references for the research, development and clinical application of acupoint drug delivery products.

Dual-Drug Loaded Nanobubbles Combined with Sonodynamic and Chemotherapy for Hepatocellular Carcinoma Therapy.

Chemotherapy remains the primary therapeutic approach for advanced Hepatocellular Carcinoma (HCC). The therapeutic effect of chemotherapy is limited and the toxic side effects are serious. The aim of this study is to develop a nanobubble that is ultrasonically responsive to reduce the toxic side effects of direct chemotherapy. We developed curcumin/doxorubicin-cis-aconitic anhydride-polyethylene glycol nanobubble (C/DCNB) surface modified with acid-sensitive polyethylene glycol (PEG). And it is loaded with curcumin (CUR) and doxorubicin (DOX), as liposomes at the nanoscale for diagnosis and therapy of tumors. In this study, the acid-sensitive PEG on the surface layer of nanobubbles serves to stabilize them in the blood circulatory system and in normal tissues, while peeling off in the acidic tumor microenvironment (pH 6.8). C/DCNB can identify tumor sites through contrast-enhanced ultrasound (CEUS). And ultrasound-mediated nanobubbles promote permeability of the tumor vascular, thus improving the enhanced permeability and retention (EPR) effects in the tumor, leading to the accumulation of nanobubbles in the tumor. After endocytosis of nanobubbles, drugs are released and curcumin generates reactive oxygen species (ROS) under ultrasound conditions. CUR can enhance the sensitivity of tumor cells to DOX by inhibiting the expression of P-glycoprotein. In vitro and vivo experiments demonstrate that C/DCNB can facilitate contrast-enhanced ultrasound imaging while simultaneously delivering drugs, enabling both imaging and treatment. The combination of C/DCNB and ultrasound provides an effective strategy for improving the efficiency of HCC therapy and imaging.

From Tyrosine Kinases to Tyrosine Phosphatases: New Therapeutic Targets in Cancers and Beyond.

Protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) regulate the level of tyrosine phosphorylation in proteins. PTKs are key enzymes that catalyze the transfer of an ATP phosphoric acid to a tyrosine residue on target protein substrates. Protein tyrosine phosphatases (PTPs) are responsible for the dephosphorylation of tyrosine residues and play a role in countering PTK overactivity. As widespread oncogenes, PTKs were once considered to be promising targets for therapy. However, tyrosine kinase inhibitors (TKIs) now face a number of challenges, including drug resistance and toxic side effects. Treatment strategies now need to be developed from a new perspective. In this review, we assess the current state of TKIs and highlight the role of PTPs in cancer and other diseases. With the advances of allosteric inhibition and the development of multiple alternative proprietary drug strategies, the reputation of PTPs as "undruggable" targets has been overturned, and they are now considered viable therapeutic targets. We also discuss the strategies and prospects of PTP-targeted therapy, as well as its future development.

Iron metabolism in doxorubicin-induced cardiotoxicity: From mechanisms to therapies

Doxorubicin (DOX) is an anti-tumor agent for chemotherapy, but its use is often hindered by the severe and life-threatening side effect of cardiovascular toxicity. In recent years, studies have focused on dysregulated iron metabolism and ferroptosis, a unique type of cell death induced by iron overload, as key players driving the development of DOX-induced cardiotoxicity (DIC). Recent advances have demonstrated that DOX disturbs normal cellular iron metabolism, resulting in excessive iron accumulation and ferroptosis in cardiomyocytes. This review will explore how dysregulated iron homeostasis and ferroptosis drive the progression of DIC. We will also discuss the current approaches to target iron metabolism and ferroptosis to mitigate DIC. Besides, we will discuss the limitations and challenges for clinical translation for these therapeutic regimens.

Coaxial nanofibrous aerogel featuring porous network-structured channels for ovarian cancer treatment by sustained release of chitosan oligosaccharide

Ovarian cancer, the deadliest gynecological malignancy, primarily treated with chemotherapy. However, systemic chemotherapy often leads to severe toxic side effects and chemoresistance. Drug-loaded aerogels have emerged as a promising method for drug delivery, as they can improve drug solubility and bioavailability, control drug release, and reduce drug distribution in non-targeted tissues, thereby minimizing side effects. In this research, chitosan oligosaccharide (COS)-loaded nanofibers composite chitosan (CS) aerogels (COS-NFs/CS) with a porous network structure were created using nanofiber recombination and freeze-drying techniques. The core layer of the aerogel has a COS loading rate of 60 %, enabling the COS-NFs/CS aerogel to significantly inhibit the migration and proliferation of ovarian cancer cells (resulting in a decrease in the survival rate of ovarian cancer cells to 33.70 % after 48 h). The coaxial fiber's unique shell-core structure and the aerogel's porous network structure enable the COS-NFs/CS aerogels to release COS steadily and slowly over 30 days, effectively reducing the initial burst release of COS. Additionally, the COS-NFs/CS aerogels exhibit good biocompatibility, degradability (only retaining 18.52 % of their weight after 6 weeks of implantation), and promote angiogenesis, thus promoting wound healing post-oophorectomy. In conclusion, COS-NFs/CS aerogels show great potential for application in the treatment of ovarian cancer.

Dual-Targeted Zeolitic Imidazolate Frameworks Drug Delivery System Reversing Cisplatin Resistance to Treat Resistant Ovarian Cancer.

Ovarian cancer cells are prone to acquire tolerance to chemotherapeutic agents, which seriously affects clinical outcomes. The development of novel strategies to enhance the targeting of chemotherapeutic agents to overcome drug resistance and minimize side effects is significant for improving the clinical outcomes of ovarian cancer patients. We employed folic acid (FA)-modified ZIF-90 nanomaterials (FA-ZIF-90) to deliver the chemotherapeutic drug, cisplatin (DDP), via dual targeting to improve its targeting to circumvent cisplatin resistance in ovarian cancer cells, especially by targeting mitochondria. FA-ZIF-90/DDP could rapidly release DDP in response to dual stimulation of acidity and ATP in tumor cells. FA-ZIF-90/DDP showed good blood compatibility. It was efficiently taken up by human ovarian cancer cisplatin-resistant cells A2780/DDP and aggregated in the mitochondrial region. FA-ZIF-90/DDP significantly inhibited the mitochondrial activity and metastatic ability of A2780/DDP cells. In addition, it effectively induced apoptosis in A2780/DDP cells and overcame cisplatin resistance. In vivo experiments showed that FA-ZIF-90/DDP increased the accumulation of DDP in tumor tissues and significantly inhibited tumor growth. FA-modified ZIF-90 nanocarriers can improve the tumor targeting and anti-tumor effects of chemotherapeutic drugs, reduce toxic side effects, and are expected to be a novel therapeutic strategy to reverse drug resistance in ovarian cancer.

Research Progress of Treating Turbidity-phlegm Headache with Traditional Chinese Medicine

Headache refers to a common disease with patients' conscious head pain as the main clinical manifestation caused by external sensation or internal injury of deficient or disnourishing vein, and adverse clearing of the body [1]. All diseases are caused by phlegm, and the common pathogenic factor of headache is "phlegm". In dialectical treatment, the syndrome type is phlegm turbid headache. With the continuous development and innovation of traditional Chinese medicine, traditional Chinese medicine has shown unique advantages in the treatment of turbidity-phlegm headache. Due to its good therapeutic effect, low recurrence rate and small toxic side effects, it has been recognized by many patients in clinical practice. This article gives a comprehensive overview on the treatment of turbidity-turbidity-headache by traditional Chinese medicine in terms of the treatment of specific prescriptions and external treatment of traditional Chinese medicine, and provides some ideas for the diagnosis and treatment of this disease.

Novel multi-purpose herbal topical formulation

The commercial need for herbal formulations is increasing now a days as natural remedies are more favored in the belief that they are safer with fewer side effects than synthetic ones. Therefore, it is rational to develop a multipurpose herbal cream that is free from toxic side effects, safe and effective with better patient compliance as compare to allopathic preparations. The present research work related to a multipurpose herbal cream was formulated and subjected to various evaluation parameters, and the findings obtained were evaluated for the limits. The herbal ingredients used to develop the herbal cream comprises aloe vera, Neem oil, turmeric, and rose water. The novel formulations were evaluated for various physicochemical parameters, including appearance, emulsion, pH, texture, homogeneity, irritancy, SPF, antimicrobial studies and identification of constituents. Among all the prepared creams both F1 & F2 were observed as the best formulations. The present research work comprises assessing the moisturizing ability and skin protective ability of the formulated multipurpose herbal topical cream.

Discovery of Positive Allosteric Modulators of α 7 nAChR by an Ensemble-based Virtual Screening Method, Molecular Dynamics Simulation, and in vitro Biological Activity Testing

The [Formula: see text]7 nicotinic acetylcholine receptor (nAChR) is a neurotransmitter receptor and a promising therapeutic target for neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In this study, we used deep learning-based classification modeling, molecular docking, and intracellular calcium signal detection experiments to identify positive allosteric modulators (PAMs) of the [Formula: see text]7 nAChR from natural tobacco products. First, we used a classification prediction model based on the direct message-passing neural network (D-MPNN) and molecular docking to predict potential [Formula: see text]7 PAMs. Subsequently, absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions were performed to determine its pharmacological properties and minimal toxic side effects, leading to the selection of three natural compounds for in vitro activity validation. Calcium signaling assay experiments revealed that diosmetin can enhance nicotine-induced calcium ion signaling. 100 ns molecular dynamics (MD) simulations indicated that diosmetin can form a dense and stable complex with [Formula: see text]7 nAChR. This study provides valuable insights for the design of more effective and selective ligands for the [Formula: see text]7 nAChR.

Preparation of a hydrolyzed yeast β-glucan chromium(III) complex and evaluation of its hypoglycemic activity and sub-acute toxicity

Yeast β-glucan (BYG) possesses extremely low solubility that has limited its applications. In this study, we hydrolyzed BYG using snail enzyme to obtain hydrolyzed yeast β-glucan (HBYG) with desirable water solubility and hypoglycemic activity. On the basis of HBYG, HBYG‑chromium(III) complex (HBYG-Cr) was synthesized. The molecular weight of the complex was 4.41 × 104 Da, and the content of trivalent chromium was 8.95 %. The hydroxyl groups of HBYG participated in the coordination and formed the chromium complex. The space conformations of HBYG exhibited remarkable changes after complex formation. HBYG-Cr existed mainly in an amorphous state and presented good dispersibility, and the surface was uneven. The hypoglycemic activity of HBYG-Cr was studied in db/db and C57 mice. The results showed that HBYG-Cr had good hypoglycemic activity. Histopathological studies demonstrated that the liver, kidney, pancreas, and skeletal muscle in the treatment group were significantly improved compared with those in the diabetic model group. The sub-acute toxicity of HBYG-Cr was studied in KM mice and the results indicated that the complex did not cause adverse reactions or toxic side effects. This study broadened the application of yeast β-glucan and provided an important reference for the development of hypoglycemic functional foods and drugs.

FLASH Radiotherapy: Mechanisms of Biological Effects and the Therapeutic Potential in Cancer.

Radiotherapy is an important treatment for many unresectable advanced malignant tumors, and radiotherapy-associated inflammatory reactions to radiation and other toxic side effects are significant reasons which reduce the quality of life and survival of patients. FLASH-radiotherapy (FLASH-RT), a prominent topic in recent radiation therapy research, is an ultra-high dose rate treatment known for significantly reducing therapy time while effectively targeting tumors. This approach minimizes radiation side effects on at-risk organs and maximally protects surrounding healthy tissues. Despite decades of preclinical exploration and some notable achievements, the mechanisms behind FLASH effects remain debated. Standardization is still required for the type of FLASH-RT rays and dose patterns. This review addresses the current state of FLASH-RT research, summarizing the biological mechanisms behind the FLASH effect. Additionally, it examines the impact of FLASH-RT on immune cells, cytokines, and the tumor immune microenvironment. Lastly, this review will discuss beam characteristics, potential clinical applications, and the relevance and applicability of FLASH-RT in treating advanced cancers.

Эффективность современных методов микробиологической диагностики инфекций в офтальмологии. Клинический пример

Purpose. To demonstrate the interaction of ophthalmic and microbiological services based on the use of technologies to minimize the time of microbiological diagnosis of ocular infection on a clinical example. Methods. A clinical example of an 82-year-old patient who underwent planned cataract phacoemulsification surgery with IOL implantation is presented. On the 3rd day after surgery, the patient was diagnosed with postoperative endophthalmitis. A rapid (48 h) microbiological diagnosis of the pathogen (E. faecalis), which made possible an early etiotropic adjustment of antibacterial treatment, provided maximum therapeutic effect, minimized the toxic side effects of pharmacotherapy and gave a good anatomical and functional result. Results The clinical case demonstrated organization of a precise interaction between ophthalmic service and the laboratory, which made it possible to identify the pathogen and determine the spectrum of its sensitivity to antibiotics during the first two days after diagnosis of postoperative endophthalmitis, prescribe etiotropic treatment with a good clinical and functional outcome. Key words: mass spectrometry; infection; microbiology; endophthalmitis.

Novel Approaches for Diagnosis and Herbal Treatment of Rheumatoid Arthritis - A Review

Background: Rheumatoid Arthritis is a chronic autoimmune disease that affects around 0.5% of the population. Limitations in movement may result from joint damage, which causes inflammation of the joint linings and the gradual deterioration of bone and cartilage. Objective: This article gives a summary of the current understanding of the potential pharmacological processes of herbal drugs, risk factors, and innovative experimental approaches in the management of rheumatoid arthritis. Methodology: A thorough literature search will be performed on five computerized databases, such as PubMed, Google Scholar, Science Direct, Elsevier, and Wiley Online Library (WOL), for review papers published between 1975 and 2023. Results: There are concerns about the current generation of potent synthetic rheumatoid arthritis drugs, including toxic side effects and relapses in symptoms upon withdrawal from therapy. Because of these constraints, RA patients are increasingly turning to herbal therapies. Due to the presence of naturally occurring active components in medicinal plants, herbal treatments are utilized to reduce arthritic pain and other symptoms. Conclusion: It emphasizes the growing significance of herbal medicines in the management of RA. Several plants are mentioned in the research as potential treatments for RA because of their antiinflammatory properties.

Pharmaceutical Potential of Remedial Plants and Helminths for Treating Inflammatory Bowel Disease.

Research is increasingly revealing that inflammation significantly contributes to various diseases, particularly inflammatory bowel disease (IBD). IBD is a major medical challenge due to its chronic nature, affecting at least one in a thousand individuals in many Western countries, with rising incidence in developing nations. Historically, indigenous people have used natural products to treat ailments, including IBD. Ethnobotanically guided studies have shown that plant-derived extracts and compounds effectively modulate immune responses and reduce inflammation. Similarly, helminths and their products offer unique mechanisms to modulate host immunity and alleviate inflammatory responses. This review explored the pharmaceutical potential of Aboriginal remedial plants and helminths for treating IBD, emphasizing recent advances in discovering anti-inflammatory small-molecule drug leads. The literature from Scopus, MEDLINE Ovid, PubMed, Google Scholar, and Web of Science was retrieved using keywords such as natural product, small molecule, cytokines, remedial plants, and helminths. This review identified 55 important Aboriginal medicinal plants and 9 helminth species that have been studied for their anti-inflammatory properties using animal models and in vitro cell assays. For example, curcumin, berberine, and triptolide, which have been isolated from plants; and the excretory-secretory products and their protein, which have been collected from helminths, have demonstrated anti-inflammatory activity with lower toxicity and fewer side effects. High-throughput screening, molecular docking, artificial intelligence, and machine learning have been engaged in compound identification, while clustered regularly interspaced short palindromic repeats (CRISPR) gene editing and RNA sequencing have been employed to understand molecular interactions and regulations. While there is potential for pharmaceutical application of Aboriginal medicinal plants and gastrointestinal parasites in treating IBD, there is an urgent need to qualify these plant and helminth therapies through reproducible clinical and mechanistic studies.

Procyanidin C1 inhibits bleomycin-induced pulmonary fibrosis in mice by selective clearance of senescent myofibroblasts.

Pulmonary fibrosis is a formidable challenge in chronic and age-related lung diseases. Myofibroblasts secrete large amounts of extracellular matrix and induce pro-repair responses during normal wound healing. Successful tissue repair results in termination of myofibroblast activity via apoptosis; however, some myofibroblasts exhibit a senescent phenotype and escape apoptosis, causing over-repair that is characterized by pathological fibrotic scarring. Therefore, the removal of senescent myofibroblasts using senolytics is an important method for the treatment of pulmonary fibrosis. Procyanidin C1 (PCC1) has recently been discovered as a senolytic compound with very low toxicity and few side effects. This study aimed to determine whether PCC1 could improve lung fibrosis by promoting apoptosis in senescent myofibroblasts and to investigate the mechanisms involved. The results showed that PCC1 attenuates bleomycin (BLM)-induced pulmonary fibrosis in mice. In addition, we found that PCC1 inhibited extracellular matrix deposition and promoted the apoptosis of senescent myofibroblasts by increasing PUMA expression and activating the BAX signaling pathway. Our findings represent a new method of pulmonary fibrosis management and emphasize the potential of PCC1 as a senotherapeutic agent for the treatment of pulmonary fibrosis, providing hope for patients with pulmonary fibrosis worldwide. Our results advance our understanding of age-related diseases and highlight the importance of addressing cellular senescence in treatment.

Comparison of single day versus two-and three- day fractionated infusion of peripheral stem cells in autologous transplantation

Bacgroun/Purpose: The aim of this study was to investigate the safety, difference in duration of engraftment and relapse rates between autologous transplant patients who had their stem cell infusions during a single day or multiple days. Methods: In this retrospective study the clinical data of 77 ASCT patients from a single center,30 of whom were transplanted in fractionated infusions were investigated. Duration of engraftment, side effects during the transplant, PFS and OS data of the two groups was compared. Results: There was no statistical difference between single day and fractionated infusion patients regarding neutrophil engraftment, toxic side effects, PFS, OS and relapse rate at 18 months. Platelet engraftment was delayed for one day in the fractionated group, which did not cause prolonged hospitalization. The transplant patients who had multiple day infusion had similar engraftment duration despite their lower average CD34+ cell counts. Conclusion: Fractionated infusions lead to similar engraftment duration to single day infusion for ASCT. The higher CFU cell number seen in the poorly mobilized patients may have a key role in the adequate engraftment. The fractionated infusion approach for such patients was feasible, safe and no increase of the disease relapse was observed with this procedure.

Rational Design and Testing of Antibacterial Aloe Vera Hemostatic Hydrogel.

Bleeding resulting from surgical procedures or trauma, including gunshot wounds, represents a life-threatening health issue. Therefore, the development of safe, effective, and convenient hemostatic agents is critical in securing the "golden time" to save patients' lives. Plant-derived compounds and plant extracts have been regarded as promising sources of hemostatic agents in previous studies, regulating hemostatic function with low toxicity and minimal side effects within the human body. Aloe vera-based hydrogels, which are characterized by flexible strength and high functionality, have emerged as a promising platform for wound applications due to their unique biocompatibility features. This study provides a comprehensive exploration of the utilization of thickening agents and natural agents such as xanthan gum, carrageenan, Carbomer, and alginate in applying aloe vera-based hydrogels as a hemostatic. Furthermore, it also tests the use of aloe vera-based hydrogels for therapeutic delivery at wound sites through the incorporation of various antimicrobial agents to extend the utility of the hydrogels beyond hemostasis. Our novel applied research utilizes aloe vera-based hydrogel as an antimicrobial hemostatic agent, providing valuable insights for a wide range of applications and highlighting its potential to enhance hemorrhage control in various emergency scenarios.

Development of bio sheet using nanoparticles and the confederation of protein for casting wound

This research pioneers a sustainable approach to wound healing by developing a bio sheet for dressings. It ingeniously incorporates healing properties of reduced graphene oxide synthesized via an eco-friendly method, using phytoextracts to eliminate toxic chemicals. Collagen extracted from fish waste and fibrinogen from post-animal waste contribute to the bio sheet's green profile. The study emphasizes the global shift towards utilizing natural materials in therapeutic applications for efficient wound healing while minimizing toxic side effects. The formulation involves a simple muffle treatment for the conversion of carbon to graphene oxide, followed by a greener reduction technique to synthesize rGO. Characterization- by peaks that obtained at 255 nm, 240 nm, 280 nm, 360 nm using UV–Vis analysis were confirmed the presents of desired carbon and glycoproteins, In X-ray diffraction (2θ value) we found peaks at 24.37°, 27.84°, 17.43° which indicated the presents of rGO, Fibrinogen, and Collagen, and FT-IR methods confirms the functional groups like OH, CH2, CC, CHO and NC in the derived materials and Zeta potential distribution were done for Compounds. To add up purity and efficiency analysis via GCMS were done for proteins. The resulting bio sheet, created in a controlled environment with a gelling agent, Undergoes morphological analysis through FESEM-EDX. Additional assessments, including antioxidant, anti-inflammatory, and hemocompatibility assays, illuminate the nature of the formulated bio sheet. To addition, biosheet is analyzed for physical and mechanical properties. Further insight is gained through the analysis of surface plots of the EDX images of both the composite and bio sheet using ImageJ software. This comprehensive approach underscores the potential of sustainable and naturally derived materials in advancing wound care technologies.

Preferential binding of cucurbit[7]uril toward 2-amino-4-chlorophenol in chlorzoxazone

Chlorzoxazone (CLZ) is a centrally acting skeletal muscle relaxant synthesized from 2-amino-4-chlorophenol (ACP). However, due to the toxic side effects of ACP, its concentration in CLZ formulations is strictly regulated (0.5%). In this study, we investigate the preferential binding of cucurbit[7]uril (CB7) toward CLZ and ACP using 1H NMR, isothermal titration calorimetry (ITC) and molecular dynamics (MD) simulations, to explore ​possible future uses of CB7, either for purifying CLZ from its toxic impurity (ACP) or in sensing ACP in CLZ. ITC experiments confirm the formation of 1:1 complexes, with favorable enthalpic and entropic contributions and binding constants of 1.1 × 106 and 4.9 × 104M−1 for ACP and CLZ, respectively, while 1H NMR and MD simulations reveal the guests in the complexes are included within the cavity of CB7. Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) results further confirmed the favorability of CB7 toward ACP. Additional MD simulations reveal that CB6 and CB8 preferentially bind CLZ and ACP, respectively, with CB6 forming inclusion and exclusion complexes with CLZ and ACP, respectively, while CB8 forms stable 1:1 and 1:2 inclusion complexes with each guest.

Synergistic activities of Panobinostat and doxorubicin in soft tissue sarcomas

BackgroundSoft tissue sarcomas (STS) are rare diseases typically arising from connective tissues in children and adults. However, chemotherapies involved in the treatment of STS may cause toxic side effects and multi-drug chemoresistance, making the treatment even more challenging. Histone deacetylase inhibitors (HDACi) are epigenetic agents which have shown anti-tumor effects as single agent as well as combination use with other drugs. Our project intends to prove the same effects in STS. MethodsPanobinostat (LBH589) plus doxorubicin was selected for investigations based on our previous research. Tumor xenografts were tried in an epithelioid sarcoma model to validate good synergy effects in vivo and a leiomyosarcoma model was used as a negative comparison group. Gene profile changes were studied afterwards. The possible pathway changes caused by HDACi were explored and validated by several assays. ResultsSynergy effect of LBH589 plus doxorubicin was successfully validated in STS cell lines and an epithelioid sarcoma mice model. We tried to reduce the dose of doxorubicin to a lower level and found the drug combination can still inhibit tumor size in mice. Furthermore, gene profile changes caused by LBH589 was studied by RNA-Sequencing analysis. Results showed LBH589 can exert effects on a group of target genes which can regulate potential biological functions especially in the cell cycle pathway.