Recent advances and pathological mechanisms in photodynamic and sonodynamic therapy in the treatment of bone tumors (Review).

Given the recent advances that have been made with photodynamic therapy (PDT) combined with sonodynamic therapy (SDT) (PDT/SDT; also known as SPDT), the application of this combination therapy in the clinic has provided another major breakthrough in the medical field, especially with regard to the treatment of deep tumors. Concerning its application in the treatment of bone tumors, numerous pathological mechanisms have been taken advantage of to overcome the barrier of tissue hypoxia, and SPDT is expected to achieve radical effects, with high penetration depth and low aggressiveness. In the present review, it is comprehensively shown how, according to the histoanatomy of bone tumors, PDT and SDT target cells in a coordinated manner, affecting such processes as necrotizing apoptosis, pyroptosis, autophagy and ferroptosis on the macroscopic level, and crucially, thrombosis at the vascular level, which leads to the triggering of immunogenic cell death in local and distant locations. Additionally, PDT and SDT have been shown to have roles in: i) degrading the extracellular matrix; ii) influencing the receptor activator of nuclear factor­κB (RANK)/RANK ligand signaling pathway; iii) disrupting the equilibrium between glutathione peroxidase 4 and reactive oxygen species (ROS); and iv) destroying the microscopic structure of the bone tumor. Upon PDT/SDT stimulation, several mechanisms act in concert to ensure that the targeted bone tumor is eliminated. Furthermore, widely distributed ROS have been revealed to promote osteoclast formation and osteogenic mineralization through the regulation of macrophages, processes that greatly improve the effects of postoperative repair. Finally, the developmental prospects of bone tumor engineering in the future are discussed in the present review.

Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins.

Osteosarcoma (OS) is the common primary bone cancer that affects mostly children and young adults. To augment the standard-of-care chemotherapy, we examined the possibility of protein-based therapy using mesenchymal stem cells (MSCs)-derived proteomes and OS-elevated proteins. While a conditioned medium (CM), collected from MSCs, did not present tumor-suppressing ability, the activation of PKA converted MSCs into induced tumor-suppressing cells (iTSCs). In a mouse model, the direct and hydrogel-assisted administration of CM inhibited tumor-induced bone destruction, and its effect was additive with cisplatin. CM was enriched with proteins such as calreticulin, which acted as an extracellular tumor suppressor by interacting with CD47. Notably, the level of CALR transcripts was elevated in OS tissues, together with other tumor-suppressing proteins, including histone H4, and PCOLCE. PCOLCE acted as an extracellular tumor-suppressing protein by interacting with amyloid precursor protein, a prognostic OS marker with poor survival. The results supported the possibility of employing a paradoxical strategy of utilizing OS transcriptomes for the treatment of OS.

Efficacy and safety of apatinib in patients with untreated or chemotherapy-refractory soft tissue sarcoma: a multicenter, phase 2 trial.

Background: Anti-angiogenic agents have been reported to exert promising clinical activity for advanced soft tissue sarcoma (STS). Apatinib, a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, is effective and safe for various solid tumors, but its role in STS remains unclear. The aim of this study was to explore the efficacy and safety of apatinib in patients with untreated or chemotherapy-refractory STS. Methods: In this multicenter, single-arm, phase 2 trial, patients aged 18-70 years with untreated or chemotherapy-refractory STS were enrolled and received 500 mg apatinib per day. During treatment, patients were followed up with imaging every 8 weeks. The primary endpoint was the 6-month progression-free survival (PFS) rate. The secondary endpoints were objective response rate (ORR), overall survival (OS), and adverse events (AEs), which were graded following the National Cancer Institute common terminology criteria for AEs version 4.03. Results: From June 2017 to October 2018, 53 patients were enrolled, 51 of whom received at least one dose of apatinib. Of the 53 patients, 41 (77.4%) had chemotherapy-refractory disease. The median follow-up was 13.3 months. The 6- and 12-month PFS rates were 46.8% and 25.2%, respectively, with a median PFS of 5.6 months [95% confidence interval (CI): 3.8-9.2 months]. The median PFS was 5.5 months for chemotherapy-refractory patients, 9.1 months for untreated patients, 13.9 months for patients with alveolar soft part sarcoma (ASPS), and 3.7 months for patients with clear cell sarcoma (CCS). The 12- and 24-month OS rates were 58.6% and 44.9%, respectively, with a median OS of 20.0 months (95% CI: 9.2-31.1 months). The median OS was 10.7 months for chemotherapy-refractory patients and not estimated for untreated, ASPS, nor CCS patients. In 50 evaluable patients, the ORR was 18.0% and the disease control rate was 86.0%. These results were similar to those of the per-protocol set. The most common grade 3 or 4 AEs included hypertension [30 (58.8%) of 51 patients], leukopenia [12 (23.5%)], proteinuria [8 (15.69%)], and hematuria [8 (15.69%)]. One patient died of unknown cause. Conclusions: This study suggested that apatinib might be effective and tolerable in patients with untreated or chemotherapy-refractory STS (NCT03064243).

Interactive regulation of laryngeal cancer and neuroscience.

Nerve fibres are distributed throughout the body along with blood and lymphatic vessels. The intrinsic morphological characteristics of nerves and the general characteristics of secretions in the tumour microenvironment provide a solid theoretical basis for exploring how neuronal tissue can influence the progression of laryngeal cancer (LC). The central nervous system (CNS) and the peripheral nervous system (PNS) jointly control many aspects of cancer and have attracted widespread attention in the study of the progression, invasion and metastasis of tumour tissue banks. Stress activates the neuroendocrine response of the human hypothalamus-pituitary-adrenal (HPA) axis. LC cells induce nerve growth in the microenvironment by releasing neurotrophic factors (NTFs), and they can also stimulate neurite formation by secreting axons and axon guides. Conversely, nerve endings secrete factors that attract LC cells; this is known as perineural invasion (PNI) and promotes the progression of the associated cancer. In this paper, we summarize the systematic understanding of the role of neuroregulation in the LC tumour microenvironment (TME) and ways in which the TME accelerates nerve growth, which is closely related to the occurrence of LC.

Glycogen synthase kinase 3ß promotes osteosarcoma invasion and migration via regulating PTEN and phosphorylation of focal adhesion kinase.

AIM: Typical features of human osteosarcoma are highly invasive and migratory capacities. Our study aimed to investigate the roles of glycogen synthase kinase 3ß (GSK3ß) in human osteosarcoma metastasis. METHODS: GSK3ß expressions in clinical osteosarcoma tissues with or without metastasis were examined by immunohistochemical staining. The expressions of GSK3ß, p-GSK3ßSer9, and p-GSK3ßTyr216 in human osteoblast cells (hFOB1.19) and human osteosarcoma cells (MG63, SaOS-2, and U2-OS) were detected by Western blotting. The GSK3ß activity was measured by non-radio isotopic in vitro kinase assay. Migration and invasion abilities of MG-63 cells treated with small-molecular GSK3ß inhibitors were respectively examined by monolayer-based wound-healing assay and transwell assay. The mRNA expressions of GSK3ß, matrix metalloproteinase-2 (MMP-2), MMP-9, phosphatase with tensin homology (PTEN), and focal adhesion kinase (FAK) were detected after siRNA transfection for 72 h. Meanwhile, protein expressions of GSK3ß, FAK, p-FAKY397, PTEN, MMP-2, and MMP-9 were measured by Western blotting. RESULTS: Clinical osteosarcoma tissues with metastasis showed higher GSK3ß expressions. MG63 and U2-OS cells that were easy to occur metastasis showed significantly higher expressions and activities of GSK3ß than SaOS-2 cells. Inhibition of GSK3ß with small-molecular GSK3ß inhibitors in MG63 cells significantly attenuated cell migration and invasion. These effects were associated with reduced expressions of MMP-2 and MMP-9. Moreover, increased PTEN and decreased p-FAKY397 expressions were observed following GSK3ß knockdown by siRNA transfection. CONCLUSION: GSK3ß might promote osteosarcoma invasion and migration via pathways associated with PTEN and phosphorylation of FAK.

Phototherapy together with it triggered immunological response for Anti-HPV treatment of oropharyngeal cancer: Removing tumor and pathogenic virus simultaneously.

Oropharyngeal squamous cell carcinoma (OPSCC) is one of most common cancers that often brings lots of inconvenience to the patient in swallowing and phonation even after the operation. Moreover, OPSCC is typically as nodal metastases and high recurrence rate due to the high-risk human papillomavirus (HPV) infection for 90% of patients. Obviously, completely curing OPSCC requires simultaneous removal of solid tumor and related pathogenic virus, which is very indispensable but never be realized by any kind of clinical therapy up to now. In this work, we selected the ZrC nanoparticles as difunctional photoactive substance for synchronous generation of hyperthermia and reactive oxygen species (ROS) under NIR excitation. The resultant synergistic photothermal and photodynamic treatment outcome contributed to an excellent anti-tumor effect. The phototherapy of this work was found not only to be able to damage cancer cells directly, but also could trigger the host immunity for further tumor removal and desirable HPV inactivation. An immunologic mechanism of this work was reasonable proposed by monitoring level of shock protein (HSP), calreticulin (CRT), T lymphocytes and dendritic cells (DCs) and immune check point of B7H3, B7H4 and PD-L1 post phototherapy. It was found that tumor-associated antigens of CRT ("eat-me" signal), HSPs and cell debris were released as cancer cell damage, and then the adaptive immune system and the congenital immunity were triggered to activate DCs maturity, antigen presentation to T cells, proliferation of CD4+ and CD8+ T cells, recruiting macrophages and NK cells and so forth immune responses. Being the first example of using phototherapy for virus-related cancer study, this work opens the door for photo-immunotherapy.

The Relationship Between Human Papillomavirus, OFD1 and Primary Ciliogenesis in the Progression of Oropharyngeal Cancer: A Retrospective Cohort Study.

PURPOSE: Infection with human papillomavirus (HPV) has been indicated to be a important risk factor for oropharyngeal squamous cell carcinoma (OPSCC). Primary ciliogenesis defects contribute to tumorigenesis, and OFD1 at centriolar satellites is a crucial suppressor of primary ciliogenesis. To identify novel markers associated with HPV-induced carcinogenesis, the interactions between HPV infection and primary ciliogenesis in the tumorigenesis and progression of OPSCC were investigated in this study. PATIENTS AND METHODS: The 1530 OPSCC patients recruited in this research were treated from 2000 to 2017. Immunohistochemistry and RT-PCR were performed on tissue samples to compare the expression of p16, TSLP, TGFß1, IFNγ, OFD1, and their relationship with clinical characteristics of patients. RESULTS: We speculate that the positive expression of p16 is related to early primary OPSCC, and the survival rate of p16 positive patients after radiotherapy and surgery is higher. Expression of TSLP on dendritic cells in HPV-positive OPSCC correlated with the expression of OFD1. HPV-positive OPSCC showed increased expression of OFD1 combined with reduced ciliogenesis. Hence, TSLP induced by HPV infection may reduce the invasive potential of OPSCC cells by promoting OFD1 expression, thereby inhibiting primary ciliogenesis. CONCLUSION: Our study demonstrated that HPV may be related to the progression of OPSCC by regulating OFD1 expression and primary ciliogenesis, making this protein a potential therapeutic target.

Pathological Mechanism of Photodynamic Therapy and Photothermal Therapy Based on Nanoparticles.

The ultimate goal of phototherapy based on nanoparticles, such as photothermal therapy (PTT) which generates heat and photodynamic therapy (PDT) which not only generates reactive oxygen species (ROS) but also induces a variety of anti-tumor immunity, is to kill tumors. In addition, due to strong efficacy in clinical treatment with minimal invasion and negligible side effects, it has received extensive attention and research in recent years. In this paper, the generations of nanomaterials in PTT and PDT are described separately. In clinical application, according to the different combination pathway of nanoparticles, it can be used to treat different diseases such as tumors, melanoma, rheumatoid and so on. In this paper, the mechanism of pathological treatment is described in detail in terms of inducing apoptosis of cancer cells by ROS produced by PDT, immunogenic cell death to provoke the maturation of dendritic cells, which in turn activate production of CD4+ T cells, CD8+T cells and memory T cells, as well as inhibiting heat shock protein (HSPs), STAT3 signal pathway and so on.

REG γ knockdown suppresses proliferation by inducing apoptosis and cell cycle arrest in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common malignant bone tumor with high mortality in children and adolescents. REG γ is overexpressed and plays oncogenic roles in various types of human cancers. However, the expression and potential roles of REG γ in osteosarcoma are elusive. This study aims at exploring possible biological functions of REG γ in the pathogenesis of osteosarcoma and its underlying mechanism. METHODS: Quantitativereverse transcription-polymerase chain reaction (qRT-PCR), western blotting andimmunohistochemistry (IHC)were performed to detect the expression levels of REG γ in OS tissues and cell lines. Then, the effects of REG γ expression on OS cell proliferation in vitro were analyzed by Cell Counting Kit-8 (CCK-8), ethylene deoxyuridine (EdU), colony formation, flow cytometry. The protein levels of apoptosis and cell-cycle related proteins were evaluated using western blotting. RESULTS: In present study, we found for the first time that REG γ is overexpressed in osteosarcoma tissues and cell lines and knockdown of REG γ significantly inhibits cell proliferation and induces apoptosis and cell cycle arrest in osteosarcoma cells. Furthermore, we observed that p21, caspase-3 and cleaved caspase-3 are increased while the expression of cycinD1 and bcl-2 are decreased after REG γ depletion in osteosarcoma cells. In conclusion, REG γ may be involved in the proliferation of osteosarcoma and serve as a novel therapeutic target in patients with osteosarcoma.

Identification of Biomarkers for Osteosarcoma Based on Integration Strategy.

BACKGROUND Osteosarcoma (OS) is the most common primary malignant tumor of bone. The identification of novel biomarkers is necessary for the diagnosis and treatment of osteosarcoma. MATERIAL AND METHODS We obtained 11 paired fresh-frozen OS samples and normal controls from patients between September 2015 and February 2017. We used an integration strategy that analyzes next-generation sequencing data by bioinformatics methods based on the pathogenesis of osteosarcoma. RESULTS One susceptibility lncRNA and 7 susceptibility genes regulated by the lncRNA for osteosarcoma were effectively identified, and real-time PCR and clinical index ALP data were used to test their effectiveness. CONCLUSIONS The results showed that the expression levels of the 7 genes were highly consistent in the training and test sample sets, especially between the expression value of the gene ALPL and the plasma detection value of its encoded protein ALP. In particular, both the expression of gene ALPL and the plasma detection values of protein ALP encoded by gene ALPL showed a high degree of consistency among different data types. The identified lncRNA and genes effectively classified the samples proved so that they could be used as potential biomarkers of osteosarcoma. Our strategy may also be helpful for the identification of biomarkers for other diseases.

Cell-cargo mediated ZrN nanoparticle for the synergetic phototherapy on both of mice and rabbits.

Realization of phototherapy on the big animal modal with orthotopic tumor is of considerable significance in view of its great clinical relevance to the human deep tumor treatment. Herein, near infrared (NIR)-active ZrN nanoparticles were chosen for both of photothermal and photodynamic purposes to achieve the synergetic phototherapy on mice with subcutaneous tumor and even rabbits bearing with orthotopic tumor. Broad and strong photoabsorption, photosensitive ROS generation and photothermal effect of ZrN nanoparticles together made it to be ideal candidate for the effective tumor photoablation. Meanwhile, cell-cargo of macrophage enables targeted delivery of ZrN nanoparticles without influence on its photophysical properties. Resultantly, macrophage loaded ZrN could efficiently mediate synergetic phototherapeutic outcome as proved by complete removal of solid tumor from mice and rabbits. In this work, we also introduced B-mode ultrasonography and contrast-enhanced ultrasound technique for monitoring the evolution process of deep orthotopic tumor on rabbits post-treatment and confirmed the pathological changes of vascular degeneration and liquefaction necrosis post phototherapy.

A Retrospective Clinicopathological Study of Osteosarcoma Patients with Metachronous Metastatic Relapse.

Purpose: Although osteosarcoma patients receive a standardized treatment, metachronous metastatic relapse still impairs the overall survival (OS). This study aimed to explore the clinicopathological features and prognostic factors of osteosarcoma patients with metachronous metastatic relapse. Patients and methods: We retrospectively analyzed 59 patients, between January 1st, 2004 and December 31st, 2013. Employed Chi-square test to recognize the differences in clinicopathological characteristics between early and late metastatic patients, and the differences between shorter and longer survival patients. Used the Kaplan-Meier method to evaluate the survival data, cox step proportional hazard test to analyze the prognostic factors associated with OS. Results: We found that early metastatic patients were prominently correlated with the male, tumor size ≥8 cm, histological grade G2, Enneking stages II, anatomic location of the distal femur, pathological of conventional types, and elevated alkaline phosphatase (ALP) level at diagnosis, (p<0.05). In parallel, the shorter survival patients were primarily linked to tumor size ≥8 cm, histological grade G2, Enneking stages II, early metastasis, multiple pulmonary metastases, lack of curative treatment after metastasis, increased level of ALP at diagnosis and LDH after metastasis, (p<0.05). The univariate analyses of the prognostic factors showed that patients who had these clinicopathological characteristics, such as male, tumor size ≥8 cm, Enneking stage IIB, multiple pulmonary metastases, lack of curative treatment after metastasis, the elevated ALP at diagnosis, elevated ALP and LDH after metastasis, had a worse OS in osteosarcoma patient with metachronous metastatic relapse, (p<0.05). The multivariate analyses showed that tumor size, type of metastasis and ALP level at diagnosis were independent factors for OS in osteosarcoma patient with metachronous metastatic relapse (p<0.05). Conclusion: These results indicated that osteosarcoma patients with metachronous metastatic relapse have special features which might be utilized to effectively predict the likelihood of early metastatic relapse and the prognosis.

The expression of Eps15 homology domain 1 is negatively correlated with disease-free survival and overall survival of osteosarcoma patients.

BACKGROUND: Osteosarcoma was locally aggressive and frequently metastasizes to the lung. However, the etiology of osteosarcoma was unknown. Thus, exploring the mechanisms behind the occurrence of osteosarcoma was important for its prediction and prevention. To investigate the usefulness of mammalian Eps15 homology domain 1 (EHD1) as a prognostic marker for osteosarcoma, the expression of EHD1 in 57 osteosarcoma patients was measured using immunohistochemistry techniques and correlated with the clinicopathological features of patients. METHODS: Correlations of EHD1 expression levels with clinicopathological features of patients were assessed using the Pearson χ2 test for categorical variables and the Student t test for continuous variables. Cumulative disease-free survival (DFS) curves and overall survival (OS) curves were plotted using the Kaplan-Meier method, and the relationship between each of the variables and survival was assessed by log-rank tests using univariate analysis. Subsequently, the parameters were tested using the multivariate Cox proportional hazards model, which was used to identify independent variables for predicting survival. EHD1 expression [P = 0.020; HR, 5.582; 95% confidence intervals (CI), 1.314-23.72] was an independent prognostic indicator of DFS in osteosarcoma patients; tumor size and EHD1 expression of osteosarcomas were independent prognostic indicators of OS in osteosarcoma patients. RESULTS: EHD1 protein expression was a positive expression in examined tumor tissues. The median OS time of patients with high expression of EHD1 was 46.8 months (95% CI, 29.8-63.8 months), and the median OS time of patients with low expression of EHD1 was 58.8 months (95% CI, 31.6-86.0 months). The prognosis for patients with low expression of EHD1 in osteosarcomas was significantly better than that for patients with high expression of EHD1 (log-rank test, P = 0.019). CONCLUSION: The expression of EHD1 was negatively correlated with DFS and OS of osteosarcoma patients; therefore, the expression of EHD1 is a prognostic marker for prediction and prevention of osteosarcomas.

Safety and Efficacy of Anlotinib, a Multikinase Angiogenesis Inhibitor, in Patients with Refractory Metastatic Soft-Tissue Sarcoma.

Purpose: The prognosis for patients with refractory soft-tissue sarcoma (STS) is dismal. Anlotinib has previously shown antitumor activity on STS in preclinical and phase I studies.Patients and Methods: Patients 18 years and older, progressing after anthracycline-based chemotherapy, naïve from angiogenesis inhibitors, with at least one measurable lesion according to RECIST 1.1, were enrolled. The main subtypes eligible were undifferentiated pleomorphic sarcoma (UPS), liposarcoma (LPS), leiomyosarcoma (LMS), synovial sarcoma (SS), fibrosarcoma (FS), alveolar soft-part sarcoma (ASPS), and clear cell sarcoma (CCS). Participants were treated with anlotinib. The primary endpoint was progression-free rate at 12 weeks (PFR12 weeks).Results: A total of 166 patients were included in the final analysis. Overall, the PFR12 weeks was 68%, and objective response rate was 13% (95% confidence interval, 7.6%-18%). The median progression-free survival (PFS) and overall survival (OS) were 5.6 and 12 months, respectively. The PFR12 weeks, median PFS and OS were: 58%, 4.1 and 11 months for UPS (n = 19); 63%, 5.6 and 13 months for LPS (n = 13); 75%, 11 and 15 months for LMS (n = 26); 75%, 7.7 and 12 months for SS (n = 47); 81%, 5.6 and 12 months for FS (n = 18); 77%, 21 and not reached for ASPS (n = 13); 54%, 11 and 16 months for CCS (n = 7); and 44%, 2.8 and 8.8 months for other sarcoma (n = 23), respectively. The most common clinically significant grade 3 or higher adverse events were hypertension (4.8%), triglyceride elevation (3.6%), and pneumothorax (2.4%). No treatment-related death occurred.Conclusions: Anlotinib showed antitumor activity in several STS entities. The toxicity was manageable. Clin Cancer Res; 24(21); 5233-8. ©2018 AACR.

The overexpression of MDM4: an effective and novel predictor of gastric adenocarcinoma lymph node metastasis.

BACKGROUND: MDM4 is the important negative regulator of the tumor suppressor protein p53, which is overexpressed in various human cancers. This study evaluates the MDM4 expression in patients with gastric adenocarcinoma (GTAC) at the mRNA and protein levels and examines relationships among MDM4 expression, clinicopathological features, and prognosis. RESULTS: The qRT-PCR and the Western blot analysis showed that the MDM4 expression level was high in GTACN+ but not in GTACN-. The high expression level of MDM4 was significantly associated with age (P = 0.047), lymph node metastasis (LNM) (P < 0.001), pathological stage (P < 0.001), differentiation status (P = 0.001), and preoperative serum CA19-9 level (P < 0.001). Moreover, the survival analysis showed that Borrmann type, depth of invasion, LNM, and preoperative serum CA19-9 level were independent prognostic factors. The univariate analysis revealed that MDM4 expression influenced GTAC prognosis. Furthermore, the influence of overall prognosis relies on whether or not the high MDM4 expression level could lead to LNM. MATERIALS AND METHODS: We investigated MDM4 expression in primary GTAC and paired normal gastric tissues (30 pairs) through qRT-PCR and Western blot analyses. We also performed immunohistochemistry analysis on 336 paraffin-embedded GTAC specimens and 33 matched normal specimens. CONCLUSIONS: MDM4 expression may result in LMN of GTAC. High MDM4 expression levels are associated with LMN of GTAC and influence the prognosis of patients with GTAC.

Clinicopathological features of gastric adenocarcinoma patients with metachronous distant metastasis.

Metachronous distant metastasis influences the postoperative survival of gastric adenocarcinoma patients with radical gastrectomy. We retrospectively reviewed 108 gastric adenocarcinoma patients with metachronous distant metastasis admitted to our hospital between January 2006 and December 2011. First, these patients were divided into two groups according to the time of metastasis: the early metastasis group (EMG) and late metastasis group (LMG). Second, according to the survival time after metastasis, these patients were divided into the longer survival group (LSG) and shorter survival group (SSG). Chi-square and Fisher exact tests were used to analyze associations between categorical variables. Survival data were estimated using the Kaplan-Meier method. Multivariate analyses of the prognostic factors related to overall survival were conducted using the Cox stepwise proportional hazards test. Results shows that the EMG was significantly associated with depth of invasion (p = 0.005), Union for International Cancer Control (UICC) stage (p = 0.003), degree of differentiation (p = 0.002), and vascular invasion (p = 0.001). The SSG was significantly associated with depth of invasion (p = 0.026) and normal carcinoembryonic antigen (CEA) level of after metastasis (p = 0.003). Survival analysis showed that depth of invasion (p < 0.001), degree of differentiation (p = 0.001), and vascular invasion (p = 0.011) were independent prognostic factors for gastric adenocarcinoma patients with metachronous distant metastasis. Gastric adenocarcinoma patients with metachronous distant metastasis exhibit characteristics that can be used to effectively estimate the possibility of early distant metastasis and the prognosis of these patients.

Effects of botulinum toxin type a on collagen deposition in hypertrophic scars.

A recent study reported that Botulinum toxin type A (BTXA) could inhibit the growth of hypertrophic scars and improve their appearance. However, the mechanism of BTXA's action on hypertrophic scars is still unknown. Some in vitro studies had shown BTXA could alleviate hypertrophic scars by acting on the biological behavior of fibroblasts, but there are few in vivo experiments, especially animal model experiments, supporting these findings. The aim of the study reported herein was to investigate the effect of BTXA on collagen deposition on hypertrophic scars in a rabbit ear model and partially clarify the mechanism of BTXA on the hypertrophy of scars. The rabbit hypertrophic scar model was used and eight rabbits were employed. BTXA was injected into the hypertrophic scar tissue of one ear; and the other ear in the same rabbit was the control without BTXA injection. The scar thickness and deposition of collagen was examined through immune histochemistry including haematoxylin and eosin (H&E) and Masson trichrome staining. The thicknesses of hypertrophic scars in the BTXA treatment group were obviously lower than in the control groups (P < 0.01). H&E and Masson staining showed that collagen fibers were stained blue. Compared with the treatment group, the collagen fibers were thicker and the arrangement of collagen fibers were disordered in the control group. This study used the rabbit ear model of hypertrophic scars to assess the effects of BTXA on scar hypertrophy. The application of BTXA may be useful for inhibiting hypertrophic scars.