Interplay between inflammation and cancer.

Tumor-promoting inflammation is one of the hallmarks of cancer. It has been shown that cancer development is strongly influenced by both chronic and acute inflammation process. Progress in research on inflammation revealed a connection between inflammatory processes and neoplastic transformation, the progression of tumour, and the development of metastases and recurrences. Moreover, the tumour invasive procedures (both surgery and biopsy) affect the remaining tumour cells by increasing their survival, proliferation and migration. One of the concepts explaining this phenomena is an induction of a wound healing response. While in normal tissue it is necessary for tissue repair, in tumour tissue, induction of adaptive and innate immune response related to wound healing, stimulates tumour cell survival, angiogenesis and extravasation of circulating tumour cells. It has become evident that certain types of immune response and immune cells can promote tumour progression more than others. In this review, we focus on current knowledge on carcinogenesis and promotion of cancer growth induced by inflammatory processes.

The effects of selenium supplementation on biomarkers of inflammation and oxidative stress in patients with diabetic nephropathy: a randomised, double-blind, placebo-controlled trial.

This study was carried out to assess the effects of Se supplementation on biomarkers of inflammation and oxidative stress in patients with diabetic nephropathy (DN). This randomised, double-blind, placebo-controlled clinical trial was conducted among sixty patients with DN. Patients were randomly divided into two groups to take either 200 µg/d Se supplements as Se yeast (n 30) or placebo (n 30) for 12 weeks. In unadjusted analyses, compared with the placebo, Se supplementation led to a significant reduction in high-sensitivity C-reactive protein (hs-CRP) (-1069·2 (sd 1752·2) v. -135·3 (sd 1258·9) ng/ml, P=0·02), matrix metalloproteinase-2 (MMP-2) (-612·3 (sd 679·6) v. +76·0 (sd 309·1) ng/ml, P<0·001) and plasma malondialdehyde (MDA) concentrations (-0·1 (sd 0·7) v. +0·4 (sd 0·9) µmol/l, P=0·01). In addition, a significant increase in plasma total antioxidant capacity (TAC) (+174·9 (sd 203·9) v. +15·8 (sd 382·2) mmol/l, P=0·04) was observed following supplementation with Se compared with the placebo. Subjects who received Se supplements experienced a borderline statistically significant decrease in serum protein carbonyl (PCO) levels (P=0·06) compared with the placebo. When we adjusted the analysis for baseline values of biochemical parameters, age and BMI, serum hs-CRP (P=0·14) and MDA levels (P=0·16) became non-significant, whereas plasma nitric oxide (NO) (P=0·04) and glutathione (GSH) (P<0·001) became statistically significant, and other findings did not change. Supplementation with Se had no significant effect on NO, transforming growth factor ß (TGF-ß), advanced glycation end products (AGE), PCO and GSH compared with the placebo. Overall, our study demonstrated that Se supplementation among DN patients had favourable effects on serum MMP-2, plasma NO, TAC and GSH, but did not affect hs-CRP, TGF-ß, AGE, PCO and MDA.

Black elderberry extract attenuates inflammation and metabolic dysfunction in diet-induced obese mice.

Dietary anthocyanins have been shown to reduce inflammation in animal models and may ameliorate obesity-related complications. Black elderberry is one of the richest sources of anthocyanins. We investigated the metabolic effects of anthocyanin-rich black elderberry extract (BEE) in a diet-induced obese C57BL/6J mouse model. Mice were fed either a low-fat diet (n 8), high-fat lard-based diet (HFD; n 16), HFD+0·25 % (w/w) BEE (0·25 %-BEE; n 16) or HFD+1·25 % BEE (1·25 %-BEE; n 16) for 16 weeks. The 0·25 % BEE (0·034 % anthocyanin, w/w) and 1·25 % BEE (0·17 % anthocyanin, w/w) diets corresponded to estimated anthocyanin doses of 20-40 mg and 100-200 mg per kg of body weight, respectively. After 16 weeks, both BEE groups had significantly lower liver weights, serum TAG, homoeostasis model assessment and serum monocyte chemoattractant protein-1 compared with HFD. The 0·25 %-BEE also had lower serum insulin and TNFα compared with HFD. Hepatic fatty acid synthase mRNA was lower in both BEE groups, whereas PPARγ2 mRNA and liver cholesterol were lower in 1·25 %-BEE, suggesting decreased hepatic lipid synthesis. Higher adipose PPARγ mRNA, transforming growth factor ß mRNA and adipose tissue histology suggested a pro-fibrogenic phenotype that was less inflammatory in 1·25 %-BEE. Skeletal muscle mRNA expression of the myokine IL-6 was higher in 0·25 %-BEE relative to HFD. These results suggest that BEE may have improved some metabolic disturbances present in this mouse model of obesity by lowering serum TAG, inflammatory markers and insulin resistance.

Smad7 regulates terminal maturation of chondrocytes in the growth plate.

Members of the bone morphogenetic protein (BMP) superfamily, including transforming growth factor-betas (TGFß), regulate multiple aspects of chondrogenesis. Smad7 is an intracellular inhibitor of BMP and TGFß signaling. Studies in which Smad7 was overexpressed in chondrocytes demonstrated that Smad7 can impact chondrogenesis by inhibiting BMP signaling. However, whether Smad7 is actually required for endochondral ossification in vivo is unclear. Moreover, whether Smad7 regulates TGFß in addition to BMP signaling in developing cartilage is unknown. In this study, we found that Smad7 is required for both axial and appendicular skeletal development. Loss of Smad7 led to impairment of the cell cycle in chondrocytes and to defects in terminal maturation. This phenotype was attributed to upregulation of both BMP and TGFß signaling in Smad7 mutant growth plates. Moreover, Smad7-/- mice develop hypocellular cores in the medial growth plates, associated with elevated HIF1α levels, cell death, and intracellular retention of types II and X collagen. Thus, Smad7 may be required to mediate cell stress responses in the growth plate during development.

Intraperitoneally Delivered Mesenchymal Stem Cells Alleviate Experimental Colitis Through THBS1-Mediated Induction of IL-10-Competent Regulatory B Cells.

Mesenchymal stem cells (MSCs) show promising therapeutic potential in treating inflammatory bowel disease (IBD), and intraperitoneal delivery of MSCs have become a more effective route for IBD treatment. However, the underlying mechanisms are still poorly understood. Here, we found that intraperitoneally delivered MSCs significantly alleviated experimental colitis. Depletion of peritoneal B cells, but not macrophages, clearly impaired the therapeutic effects of MSCs. Intraperitoneally delivered MSCs improved IBD likely by boosting the IL-10-producing B cells in the peritoneal cavity, and a single intraperitoneal injection of MSCs could significantly prevent disease severity in a recurrent mouse colitis model, with lower proinflammation cytokines and high level of IL-10. The gene expression profile revealed that thrombospondin-1 (THBS1) was dramatically upregulated in MSCs after coculture with peritoneal lavage fluid from colitis mice. Knockout of THBS1 expression in MSCs abolished their therapeutic effects in colitis and the induction of IL-10-producing B cells. Mechanistically, THBS1 modulates the activation of transforming growth factor-ß (TGF-ß), which combines with TGF-ß receptors on B cells and contributes to IL-10 production. Blocking the interaction between THBS1 and latent TGF-ß or inhibiting TGF-ß receptors (TGF-ßR) significantly reversed the THBS1-mediated induction of IL-10-producing B cells and the therapeutic effects on colitis. Collectively, our study revealed that intraperitoneally delivered MSCs secreted THBS1 to boost IL-10+Bregs and control the progression and recurrence of colitis, providing new insight for the prevention and treatment of IBD.

PTP1B Inhibition Improves Mitochondrial Dynamics to Alleviate Calcific Aortic Valve Disease Via Regulating OPA1 Homeostasis.

There are currently no pharmacological therapies for calcific aortic valve disease (CAVD). Here, we evaluated the role of protein tyrosine phosphatase 1B (PTP1B) inhibition in CAVD. Up-regulation of PTP1B was critically involved in calcified human aortic valve, and PTP1B inhibition had beneficial effects in preventing fibrocalcific response in valvular interstitial cells and LDLR-/- mice. In addition, we reported a novel function of PTP1B in regulating mitochondrial homeostasis by interacting with the OPA1 isoform transition in valvular interstitial cell osteogenesis. Thus, these findings have identified PTP1B as a potential target for preventing aortic valve calcification in patients with CAVD.

Blockade of deubiquitinase YOD1 degrades oncogenic PML/RARα and eradicates acute promyelocytic leukemia cells.

In most acute promyelocytic leukemia (APL) cells, promyelocytic leukemia (PML) fuses to retinoic acid receptor α (RARα) due to chromosomal translocation, thus generating PML/RARα oncoprotein, which is a relatively stable oncoprotein for degradation in APL. Elucidating the mechanism regulating the stability of PML/RARα may help to degrade PML/RARα and eradicate APL cells. Here, we describe a deubiquitinase (DUB)-involved regulatory mechanism for the maintenance of PML/RARα stability and develop a novel pharmacological approach to degrading PML/RARα by inhibiting DUB. We utilized a DUB siRNA library to identify the ovarian tumor protease (OTU) family member deubiquitinase YOD1 as a critical DUB of PML/RARα. Suppression of YOD1 promoted the degradation of PML/RARα, thus inhibiting APL cells and prolonging the survival time of APL cell-bearing mice. Subsequent phenotypic screening of small molecules allowed us to identify ubiquitin isopeptidase inhibitor I (G5) as the first YOD1 pharmacological inhibitor. As expected, G5 notably degraded PML/RARα protein and eradicated APL, particularly drug-resistant APL cells. Importantly, G5 also showed a strong killing effect on primary patient-derived APL blasts. Overall, our study not only reveals the DUB-involved regulatory mechanism on PML/RARα stability and validates YOD1 as a potential therapeutic target for APL, but also identifies G5 as a YOD1 inhibitor and a promising candidate for APL, particularly drug-resistant APL treatment.

Transforming growth factor ß latency: A mechanism of cytokine storage and signalling regulation in liver homeostasis and disease.

Transforming growth factor-ß (TGF-ß) is a potent effector in the liver, which is involved in a plethora of processes initiated upon liver injury. TGF-ß affects parenchymal, non-parenchymal, and inflammatory cells in a highly context-dependent manner. Its bioavailability is critical for a fast response to various insults. In the liver - and probably in other organs - this is made possible by the deposition of a large portion of TGF-ß in the extracellular matrix as an inactivated precursor form termed latent TGF-ß (L-TGF-ß). Several matrisomal proteins participate in matrix deposition, latent complex stabilisation, and activation of L-TGF-ß. Extracellular matrix protein 1 (ECM1) was recently identified as a critical factor in maintaining the latency of deposited L-TGF-ß in the healthy liver. Indeed, its depletion causes spontaneous TGF-ß signalling activation with deleterious effects on liver architecture and function. This review article presents the current knowledge on intracellular L-TGF-ß complex formation, secretion, matrix deposition, and activation and describes the proteins and processes involved. Further, we emphasise the therapeutic potential of toning down L-TGF-ß activation in liver fibrosis and liver cancer.

Regenerative medicine strategies for hair growth and regeneration: A narrative review of literature.

Hair loss, or alopecia, is associated with several psychosocial and medical comorbidities, and it remains an economic burden to individuals and the society. Alopecia is attributable to varied mechanisms and features a multifactorial predisposition, and the available conventional medical interventions have several limitations. Thus, several therapeutic strategies for alopecia in regenerative medicine are currently being explored, with increasing evidence suggesting that mesenchymal stem cell (MSC) implantation, MSC-derived secretome treatment, and blood-derived platelet-rich plasma therapies are potential treatment options. In this review, we searched the Cochrane Library, MEDLINE (PubMed), EMBASE, and Scopus using various combinations of terms, such as "stem cell," "alopecia," "hair loss," "Androgenetic alopecia," "male-pattern hair loss," "female-pattern hair loss," "regenerative hair growth," "cell therapy," "mesenchymal stem cells," "MSC-derived extracellular vesicles," "MSC-derived exosomes," and "platelet-rich plasma" and summarized the most promising regenerative treatments for alopecia. Moreover, further opportunities of improving efficacy and innovative strategies for promoting clinical application were discussed.

Dihydrosphingosine driven enrichment of sphingolipids attenuates TGFß induced collagen synthesis in cardiac fibroblasts.

The sphingolipid de novo synthesis pathway, encompassing the sphingolipids, the enzymes and the cell membrane receptors, are being investigated for their role in diseases and as potential therapeutic targets. The intermediate sphingolipids such as dihydrosphingosine (dhSph) and sphingosine (Sph) have not been investigated due to them being thought of as precursors to other more active lipids such as ceramide (Cer) and sphingosine 1 phosphate (S1P). Here we investigated their effects in terms of collagen synthesis in primary rat neonatal cardiac fibroblasts (NCFs). Our results in NCFs showed that both dhSph and Sph did not induce collagen synthesis, whilst dhSph reduced collagen synthesis induced by transforming growth factor ß (TGFß). The mechanisms of these inhibitory effects were associated with the increased activation of the de novo synthesis pathway that led to increased dihydrosphingosine 1 phosphate (dhS1P). Subsequently, through a negative feedback mechanism that may involve substrate-enzyme receptor interactions, S1P receptor 1 expression (S1PR1) was reduced.

MicroRNA-regulated transcriptome analysis identifies four major subtypes with prognostic and therapeutic implications in prostate cancer.

MicroRNA (miRNA) deregulation plays a critical role in the heterogeneous development of prostate cancer (PCa) by tuning mRNA levels. Herein, we aimed to characterize the molecular features of PCa by clustering the miRNA-regulated transcriptome with non-negative matrix factorization. Using 478 PCa samples from The Cancer Genome Atlas, four molecular subtypes (S-I, S-II, S-III, and S-IV) were identified and validated in two merged microarray and RNAseq datasets with 656 and 252 samples, respectively. Interestingly, the four subtypes showed distinct clinical and biological features after comprehensive analyses of clinical features, multiomic profiles, immune infiltration, and drug sensitivity. S-I is basal/stem/mesenchymal-like and immune-excluded with marked transforming growth factor ß, epithelial-mesenchymal transition and hypoxia signals, increased sensitivity to olaparib, and intermediate prognosis. S-II is luminal/metabolism-active and responsive to androgen deprivation therapy with frequent TMPRSS2-ERG fusion and a good prognosis. S-III is characterized by moderate proliferative and metabolic activity, sensitivity to taxane-based chemotherapy, and intermediate prognosis. S-IV is highly proliferative with moderate EMT and stemness, frequent deletions of TP53, PTEN and RB, and the poorest prognosis; it is also immune-inflamed and sensitive to anti-PD-L1 therapy. Overall, based on miRNA-regulated gene profiles, this study identified four distinct PCa subtypes that could improve risk stratification at diagnosis and provide therapeutic guidance.

Sensory nerves: A driver of the vicious cycle in bone metastasis?

Bone is one of the preferential target organs of cancer metastasis. Bone metastasis is associated with various complications, of which bone pain is most common and debilitating. The cancer-associated bone pain (CABP) is induced as a consequence of increased neurogenesis, reprogramming and axonogenesis of sensory nerves (SNs) in harmony with sensitization and excitation of SNs in response to the tumor microenvironment created in bone. Importantly, CABP is associated with increased mortality, of which precise cellular and molecular mechanism remains poorly understood. Bone is densely innervated by autonomic nerves (ANs) (sympathetic and parasympathetic nerves) and SNs. Recent studies have shown that the nerves innervating the tumor microenvironment establish intimate communications with tumors, producing various stimuli for tumors to progress and disseminate. In this review, our current understanding of the role of SNs innervating bone in the pathophysiology of CABP will be overviewed. Then the hypothesis that SNs facilitate cancer progression in bone will be discussed in conjunction with our recent findings that SNs play an important role not only in the induction of CABP but also the progression of bone metastasis using a preclinical model of CABP. It is suggested that SNs are a critical component of the bone microenvironment that drives the vicious cycle between bone and cancer to progress bone metastasis. Suppression of the activity of bone-innervating SNs may have potential therapeutic effects on the progression of bone metastasis and induction of CABP.

Procollagen C-proteinase enhancer-1 (PCPE-1), a potential biomarker and therapeutic target for fibrosis.

The correct balance between collagen synthesis and degradation is essential for almost every aspect of life, from development to healthy aging, reproduction and wound healing. When this balance is compromised by external or internal stress signals, it very often leads to disease as is the case in fibrotic conditions. Fibrosis occurs in the context of defective tissue repair and is characterized by the excessive, aberrant and debilitating deposition of fibril-forming collagens. Therefore, the numerous proteins involved in the biosynthesis of fibrillar collagens represent a potential and still underexploited source of therapeutic targets to prevent fibrosis. One such target is procollagen C-proteinase enhancer-1 (PCPE-1) which has the unique ability to accelerate procollagen maturation by BMP-1/tolloid-like proteinases (BTPs) and contributes to trigger collagen fibrillogenesis, without interfering with other BTP functions or the activities of other extracellular metalloproteinases. This role is achieved through a fine-tuned mechanism of action that is close to being elucidated and offers promising perspectives for drug design. Finally, the in vivo data accumulated in recent years also confirm that PCPE-1 overexpression is a general feature and early marker of fibrosis. In this review, we describe the results which presently support the driving role of PCPE-1 in fibrosis and discuss the questions that remain to be solved to validate its use as a biomarker or therapeutic target.

BMP antagonists in tissue development and disease.

Bone morphogenic proteins (BMPs) are important growth regulators in embryogenesis and postnatal homeostasis. Their tight regulation is crucial for successful embryonic development as well as tissue homeostasis in the adult organism. BMP inhibition by natural extracellular biologic antagonists represents the most intensively studied mechanistic concept of BMP growth factor regulation. It was shown to be critical for numerous developmental programs, including germ layer specification and spatiotemporal gradients required for the establishment of the dorsal-ventral axis and organ formation. The importance of BMP antagonists for extracellular matrix homeostasis is illustrated by the numerous human connective tissue disorders caused by their mutational inactivation. Here, we will focus on the known functional interactions targeting BMP antagonists to the ECM and discuss how these interactions influence BMP antagonist activity. Moreover, we will provide an overview about the current concepts and investigated molecular mechanisms modulating BMP inhibitor function in the context of development and disease.

The role of ALDH2 in tumorigenesis and tumor progression: Targeting ALDH2 as a potential cancer treatment.

A major mitochondrial enzyme for protecting cells from acetaldehyde toxicity is aldehyde dehydrogenase 2 (ALDH2). The correlation between ALDH2 dysfunction and tumorigenesis/growth/metastasis has been widely reported. Either low or high ALDH2 expression contributes to tumor progression and varies among different tumor types. Furthermore, the ALDH2∗2 polymorphism (rs671) is the most common single nucleotide polymorphism (SNP) in Asia. Epidemiological studies associate ALDH2∗2 with tumorigenesis and progression. This study summarizes the essential functions and potential ALDH2 mechanisms in the occurrence, progression, and treatment of tumors in various types of cancer. Our study indicates that ALDH2 is a potential therapeutic target for cancer therapy.

Hedgehog signaling in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment.

The Hedgehog (HH) signaling pathway plays important roles in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment (TME). Aberrant HH signaling activation may accelerate the growth of gastrointestinal tumors and lead to tumor immune tolerance and drug resistance. The interaction between HH signaling and the TME is intimately involved in these processes, for example, tumor growth, tumor immune tolerance, inflammation, and drug resistance. Evidence indicates that inflammatory factors in the TME, such as interleukin 6 (IL-6) and interferon-γ (IFN-γ), macrophages, and T cell-dependent immune responses, play a vital role in tumor growth by affecting the HH signaling pathway. Moreover, inhibition of proliferating cancer-associated fibroblasts (CAFs) and inflammatory factors can normalize the TME by suppressing HH signaling. Furthermore, aberrant HH signaling activation is favorable to both the proliferation of cancer stem cells (CSCs) and the drug resistance of gastrointestinal tumors. This review discusses the current understanding of the role and mechanism of aberrant HH signaling activation in gastrointestinal carcinogenesis, the gastrointestinal TME, tumor immune tolerance and drug resistance and highlights the underlying therapeutic opportunities.

Biological drug and drug delivery-mediated immunotherapy.

The initiation and development of major inflammatory diseases, i.e., cancer, vascular inflammation, and some autoimmune diseases are closely linked to the immune system. Biologics-based immunotherapy is exerting a critical role against these diseases, whereas the usage of the immunomodulators is always limited by various factors such as susceptibility to digestion by enzymes in vivo, poor penetration across biological barriers, and rapid clearance by the reticuloendothelial system. Drug delivery strategies are potent to promote their delivery. Herein, we reviewed the potential targets for immunotherapy against the major inflammatory diseases, discussed the biologics and drug delivery systems involved in the immunotherapy, particularly highlighted the approved therapy tactics, and finally offer perspectives in this field.

The application of nanoparticles in cancer immunotherapy: Targeting tumor microenvironment.

The tumor development and metastasis are closely related to the structure and function of the tumor microenvironment (TME). Recently, TME modulation strategies have attracted much attention in cancer immunotherapy. Despite the preliminary success of immunotherapeutic agents, their therapeutic effects have been restricted by the limited retention time of drugs in TME. Compared with traditional delivery systems, nanoparticles with unique physical properties and elaborate design can efficiently penetrate TME and specifically deliver to the major components in TME. In this review, we briefly introduce the substitutes of TME including dendritic cells, macrophages, fibroblasts, tumor vasculature, tumor-draining lymph nodes and hypoxic state, then review various nanoparticles targeting these components and their applications in tumor therapy. In addition, nanoparticles could be combined with other therapies, including chemotherapy, radiotherapy, and photodynamic therapy, however, the nanoplatform delivery system may not be effective in all types of tumors due to the heterogeneity of different tumors and individuals. The changes of TME at various stages during tumor development are required to be further elucidated so that more individualized nanoplatforms could be designed.

Endothelial-to-Mesenchymal Transition, Vascular Inflammation, and Atherosclerosis.

Atherosclerosis is a chronic progressive disease characterized by vascular inflammation and growth of atherosclerotic plaque that eventually lead to compromise of blood flow. The disease has proven to be remarkably resistant to multiple attempts at meaningful reversal including recent strategies targeting selective inflammatory mediators. Endothelial-to-mesenchymal transition (EndMT) has emerged as a key driver of both vascular inflammation and plaque growth. A deeper understanding of EndMT provides new insights into the underlying biology of atherosclerosis, suggests likely molecular mechanism of atherosclerotic resistance, and identifies potential new therapeutic targets.

Effects of different levels of TGF-ß expression and tumor cell necrosis rates in osteosarcoma on the chemotherapy resistance of osteosarcoma.

PURPOSE: The clinical significance of transforming growth factor ß (TGF-ß) and tumor cell necrosis rate (TCNR) in the expression of osteosarcoma and its effects of chemotherapy resistance on osteosarcoma were explored. PATIENTS AND METHODS: 94 cases of neoadjuvant chemotherapy osteosarcoma patients at the Third Affiliated Hospital of Kunming Medical University between January 2014 and January 2019 were collected. Samples tested for TGF-ß were collected before chemotherapy, the tumor cell necrosis rate of pathological samples before and after chemotherapy was determined. Others analyzed covariates included 12 prognostic factors that may be associated with chemotherapy resistance in previous studies: age, BMI, initial diagnosis time (The time from symptom onset to first medical attention), KPS score, initial tumor size, lymphocytes/leukocytes rate (LWR), neutrophils/lymphocytes rate (NLR), albumin, aspartate transaminase (AST), low density lipoprotein (LDL), blood urea nitrogen (BUN), alkaline phosphatase (ALP), the endpoints included progression-free survival (PFS) and overall survival (OS), response evaluation criteria in solid tumours by RECIST guideline (version 1.1). RESULT: 1. A total of 94 cases were examined for expression of TGF-ß in pathological specimens, 45 cases were TGF-ß high expression (47.9%) and 49 cases were TGF-ß low expression (52.1%); 2. The BMI, LDL, ALP, NLR in TGF-ß high expression group was significantly increased compared to TGF-ß low expression group; the Initial diagnosis time, KPS in TGF-ß high expression group was significantly decreased compared to TGF-ß low expression group, all P < 0.05; 3. Effect of chemotherapy was positively with positive cell rate (P < 0.01 r = 0.337) and TGF-ß total score (P < 0.0001 r = 0.635), while effect of chemotherapy was no correlation with degree of dyeing score (P > 0.05); there was significant difference in change from baseline after chemotherapy between TGF-ß high expression group and TGF-ß low expression group (P = 0.045); 4. Median OS 61.4 months in the TGF-ß high expression group, median OS 68.1 months in the TGF-ß low expression group, one-year survival rate, there was statistically significant difference in two groups (P = 0.045); median PFS 44.8 months in the TGF-ß high expression group, median PFS 56.2 months in the TGF-ß low expression group, There was no statistically significant difference in two groups (P > 0.05); 5. A total of 92 cases were examined for TCNR after chemotherapy, 62 were TCNR ≤ 90% (67.4%), 30 were TCNR > 90% (32.6%); 6. the Initial diagnosis time, KPS, in TCNR > 90% group was significantly increased compared to TCNR ≤ 90% group; the initial tumor size, BUN, ALP in TCNR > 90% group was significantly decreased compared to TCNR ≤ 90% group, all P < 0.05; 7. TCNR was negatively correlated with the change from baseline after chemotherapy (P < 0.001 r = -0.411); there was no statistically significant difference between TCNR > 90% group and TCNR ≤ 90% group in change from baseline after chemotherapy (P > 0.05); 8. Median OS 67.8 months in the TCNR > 90% group, median OS 61.7 months in the TCNR ≤ 90% group, there was statistically significant difference between two groups (P = 0.040); median PFS 57.4 months in the TCNR > 90% group, median PFS 40.5 months in the TCNR ≤ 90% group, there was statistically significant difference between two groups (P = 0.036); 9. TGF-ß total score was negatively correlated with TCNR (P < 0.001 r = -0.571). CONCLUSION: The results of this study suggested that the higher expression of TGF-ß, the lower expression of TCNR, which more likely to induce chemotherapy resistance among patients with osteosarcoma and lead to poor prognosis.