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1.
Cell Death Discov ; 9(1): 184, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37344500

RESUMO

In conjunction with previous studies, we have noted that ferroptosis, as an emerging mode of regulated cell death (RCD), is intimately related to anthracycline pharmacotherapy. Not only does ferroptosis significantly modulate tumour resistance and drug toxicity, which are core links of the relevant chemotherapeutic process, but it also appears to play a conflicting role that has yet to be appreciated. By targeting the dual role of ferroptosis in anthracycline-based chemotherapy, this review aims to focus on the latest findings at this stage, identify the potential associations and provide novel perspectives for subsequent research directions and therapeutic strategies.

2.
J Clin Transl Res ; 9(2): 93-100, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37033999

RESUMO

Background and Aim: With the greatly prolonged survival of cancer patients, more and more patients develop bone metastasis, especially spinal metastasis. Therefore, it is very important to choose the best surgical plan for patients with spinal metastasis in different conditions. This paper aims to evaluate the clinical efficacy of percutaneous pedicle screw fixation (PPSF) combined with percutaneous vertebroplasty (PVP) for the treatment of thoracic and lumbar metastatic tumors. Methods: Forty patients with thoracic and lumbar metastatic tumors were treated with PPSF combined with PVP and followed up for 6-33 months. The visual analog scale (VAS) and the Barthel Index of activities of daily living (BIADL) were used to evaluate the pain intensity and quality of life before surgery and at 7 days, 3 months, and 6 months after the treatment. Results: In this study, a total of 40 patients were followed up for 6-33 months (the mean time was 14.87 months). The VAS scores of all patients were significantly decreased, while the BIADL scores were significantly increased. No patients suffered from complications such as infection, pedicle screw loosening, or polymethylmethacrylate leakage. Spine stability was observed in all surviving patients during the follow-up. Conclusions: PPSF combined with PVP is a new and viable treatment for thoracolumbar metastases in patients with a poor systemic condition, patients who refuse to undergo a conventional open procedure such as en bloc corpectomy, and in patients with vertebral instability or pathological fracture without significant spinal compression. Relevance for Patients: Patients with spinal metastases have a great risk of spinal instability and even spinal cord compression while enduring pain. Therefore, timely and appropriate surgical treatment is an effective means to stabilize the spine and avoid spinal cord compression. PPSF combined with PVP is an effective new surgical method for the treatment of multilevel spinal metastases.

3.
J Bone Oncol ; 39: 100473, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36915896

RESUMO

Purpose: Proximal femoral replacement (PFR) for oncology patients is gaining interest as a limb salvage operation due to its obvious advantages. However, almost all hip replacement surgeries including PFR, are faced with the challenge of how to reconstruct the functional musculature in an optimal way. To address the challenge, we have developed an innovative eggshell procedure and through this study we aim to investigate the specific efficacy of the procedure. Methods: A total of 44 tumor patients with PFR surgery were incorporated into the study, including 12 who underwent the eggshell procedure and 32 who did not. General characteristics, short-term indicators, long-term indicators and complication outcomes were compared successively between the two groups of patients. Results: No significant differences were identified in general characteristics between the two groups. Overall, in terms of both short-term and long-term indicators, the patients with eggshell procedure performed significantly superior to the patients without it. Moreover, the eggshell procedure significantly reduced the incidence of associated complications, including prosthesis dislocation and hip pain. Conclusions: Our eggshell procedure is convenient and accessible. On the one hand, it can reduce surgical side injuries without adding additional complications, and on the other it allows to improve joint mobility and life quality while diminishing the incidence of prosthesis dislocation and hip pain. Despite it may still remain limitations, we have reasons to believe that this procedure can be further promoted and applied.

4.
Discov Oncol ; 14(1): 31, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36897430

RESUMO

Osteosarcoma (OS) is the most common primary solid malignant tumour of bone, with rapid progression and a very poor prognosis. Iron is an essential nutrient that makes it an important player in cellular activities due to its inherent ability to exchange electrons, and its metabolic abnormalities are associated with a variety of diseases. The body tightly regulates iron content at the systemic and cellular levels through various mechanisms to prevent iron deficiency and overload from damaging the body. OS cells regulate various mechanisms to increase the intracellular iron concentration to accelerate proliferation, and some studies have revealed the hidden link between iron metabolism and the occurrence and development of OS. This article briefly describes the process of normal iron metabolism, and focuses on the research progress of abnormal iron metabolism in OS from the systemic and cellular levels.

5.
Sci Transl Med ; 14(653): eabq2096, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35857643

RESUMO

Chimeric transcription factors drive lineage-specific oncogenesis but are notoriously difficult to target. Alveolar rhabdomyosarcoma (RMS) is an aggressive childhood soft tissue sarcoma transformed by the pathognomonic Paired Box 3-Forkhead Box O1 (PAX3-FOXO1) fusion protein, which governs a core regulatory circuitry transcription factor network. Here, we show that the histone lysine demethylase 4B (KDM4B) is a therapeutic vulnerability for PAX3-FOXO1+ RMS. Genetic and pharmacologic inhibition of KDM4B substantially delayed tumor growth. Suppression of KDM4 proteins inhibited the expression of core oncogenic transcription factors and caused epigenetic alterations of PAX3-FOXO1-governed superenhancers. Combining KDM4 inhibition with cytotoxic chemotherapy led to tumor regression in preclinical PAX3-FOXO1+ RMS subcutaneous xenograft models. In summary, we identified a targetable mechanism required for maintenance of the PAX3-FOXO1-related transcription factor network, which may translate to a therapeutic approach for fusion-positive RMS.


Assuntos
Rabdomiossarcoma Alveolar , Rabdomiossarcoma , Carcinogênese/genética , Linhagem Celular Tumoral , Criança , Proteína Forkhead Box O1/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Fator de Transcrição PAX3/genética , Fator de Transcrição PAX3/metabolismo , Fatores de Transcrição Box Pareados/genética , Fatores de Transcrição Box Pareados/metabolismo , Fatores de Transcrição Box Pareados/uso terapêutico , Rabdomiossarcoma/genética , Rabdomiossarcoma Alveolar/genética , Rabdomiossarcoma Alveolar/metabolismo , Rabdomiossarcoma Alveolar/patologia
6.
Am J Transl Res ; 14(2): 1123-1130, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35273716

RESUMO

BACKGROUND: Breast cancer is the most frequent non-skin cancer in women and bone is its most common site of metastasis. The patella, as the largest sesamoid bone in the human body, is a rare site for cancer metastasis to occur. We reported the comprehensive auxiliary examination data and complete process of diagnosis, management and follow-up for a case of solitary patellar metastasis from breast cancer. CASE PRESENTATION: A 47-year-old woman presented with patellar pain 6 years after breast cancer surgery. Thorough imaging and pathology examinations were carried out leading to a diagnosis of breast-derived patellar metastasis. Subsequent treatment and follow-up were performed. The patient recovered function slightly at 3 months postoperatively, but tibia and femur metastases developed at 6 months postoperatively and the patient started radiotherapy. DISCUSSION: Cases of patellar metastases from malignant tumors are extremely rare but do exist. Due to the insidious onset and non-specific symptoms, it is worthwhile to alert clinicians. The diagnostic value of positron emission tomography/computed tomography for patellar metastases is significant and still provides certain advantages compared to pathologic examination, so it can be given priority. Prompt postoperative radiotherapy is necessary, while imaging should be actively performed with a short review interval.

7.
Sci Rep ; 12(1): 5029, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-35322804

RESUMO

Osteosarcoma (OS) is the most common bone-derived tumor, and chemoresistance is a pivotal factor in the poor prognosis of patients with OS. Ferroptosis, as an emerging modality of regulated cell death, has demonstrated potential value in tumor chemoresistance studies. Through the gene expression omnibus database in conjunction with the FerrDb database, we identified novel ferroptosis-related differentially expressed genes (DEGs) involving chemoresistance in OS patients. Subsequently, enrichment analysis, protein-protein interaction network analysis and survival analysis were performed sequentially to recognize the hub genes and ultimately to construct a predictive model. The model constructed from the TARGET database was exhibited in a nomogram and assessed by calibration curves. The prognostic value of the model and hub genes was validated separately by an independent cohort. Twenty-two ferroptosis-related DEGs were identified, including 16 up-regulated and 6 down-regulated. Among them, expressions of CBS, COCS1, EGFR, as hub genes, were significantly associated with the prognosis of OS patients and were evidenced as independent prognostic factors. An efficient prognostic model covering hub gene expressions and clinical variables was developed and validated. Combining the results of hub genes in differential analysis, the actions of hub genes in ferroptosis, and the prognostic relevance of hub genes in patients, we revealed that CBS, SOCS1 and EGFR might play essential roles in OS and its chemoresistance with potential research and clinical value.


Assuntos
Neoplasias Ósseas , Ferroptose , Osteossarcoma , Biomarcadores Tumorais/genética , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/genética , Ferroptose/genética , Perfilação da Expressão Gênica/métodos , Humanos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Prognóstico
8.
PLoS One ; 17(1): e0262234, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34982796

RESUMO

BACKGROUND: Ferroptosis has exhibited great potential in the treatment of cancer and has gained widespread attention in soft tissue sarcoma (STS). The aim was to explore the immunological and prognostic significance of novel ferroptosis-related genes in STS. METHODS: We identified ferroptosis-related differentially expressed genes (DEGs) in STS to construct the networks of enrichment analysis and protein-protein interaction. Subsequently, hub genes with prognostic significance were localized and a series of prognostic and immune analyses were performed. RESULTS: 40 ferroptosis-related DEGs were identified, of which HELLS, STMN1 EPAS1, CXCL2, NQO1, and IL6 were classified as hub genes and were associated with the prognosis in STS patients. In the results of the immune analysis, PDCD1, CTLA4, TIGIT, IDO1 and CD27 exhibited consistent intense correlations as immune checkpoint genes, as well as macrophage, neutrophil, cytotoxic cell, dendritic cell, interdigitating dendritic cell and plasmacytoid dendritic cell as immune cells. EPAS1 and HELLS might be independent prognostic factors for STS patients, and separate prognostic models were constructed by using them. CONCLUSIONS: We recognized novel ferroptosis-related genes with prognostic value in STS. Furthermore, we searched out potential immune checkpoints and critical immune cells.


Assuntos
Biomarcadores Tumorais/genética , Ferroptose , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Mapas de Interação de Proteínas , Sarcoma/patologia , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sarcoma/genética , Sarcoma/imunologia , Sarcoma/radioterapia , Taxa de Sobrevida
9.
Comb Chem High Throughput Screen ; 25(10): 1767-1777, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34182903

RESUMO

BACKGROUND: Synovial Sarcoma (SS) refers to a malignant Soft Tissue Sarcoma (STS) which often comes about to children and adults and has a poor prognosis in elderly patients. Patients with local lesions can be treated with extensive surgical resection combined with adjuvant or radiotherapy, whereas about half of the cases have recurrent diseases and metastatic lesions, and five-year survival ratio is assessed within the range of 27% - 55% only. METHODS: We downloaded a set of expression profile data (GSE40021) related to SS metastasis based on the Gene Expression Omnibus (GEO) database, and selected distinctly represented genes (DEGs) related to tumor metastasis. WGCNA was used to emphasize the DEGs related to tumor metastasis, and obtain co-expression modules. Then, the module most related to SS metastasis was screened out. The genes of enriched in this module were analyzed by Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway improvement analysis. Cytoscape software was used for constructing protein-protein interaction (PPI) networks, and screening hub genes were made in virtue of Oncomine analysis. RESULT: We selected 514 DEGs, consisting of 210 up-regulated genes and 304 down-regulated genes. Through WGCAN, we got seven co-expression modules and the module most related to SS metastasis was turquoise module, which contained 66 genes. Finally, we screened out five hub genes (HJURP, NCAPG, TPX2, CENPA, NDC80) through CytoHubba and Oncomine analysis. CONCLUSION: In this study, we screened out five hub genes to help clinical diagnosis and serve as the latent purpose of SS treatment.


Assuntos
Redes Reguladoras de Genes , Sarcoma Sinovial , Idoso , Biomarcadores Tumorais/genética , Criança , Biologia Computacional , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Sarcoma Sinovial/genética
10.
J Zhejiang Univ Sci B ; 22(11): 885-892, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34783219

RESUMO

Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents. It is an aggressive tumor with a tendency to spread to the lung, which is the most common site of metastasis. Patients with advanced OS with metastases have poor prognoses despite the application of chemotherapy, thus highlighting the need for novel therapeutic targets. The tumor microenvironment (TME) of OS is confirmed to be essential for and supportive of tumor growth and dissemination. The immune component of the OS microenvironment is mainly composed of tumor-associated macrophages (TAMs). In OS, TAMs promote tumor growth and angiogenesis and upregulate the cancer stem cell-like phenotype. However, TAMs inhibit the metastasis of OS. Therefore, much attention has been paid to investigating the mechanism of TAMs in OS development and the progression of immunotherapy for OS. In this article, we aim to summarize the roles of TAMs in OS and the major findings on the application of TAMs in OS treatment.


Assuntos
Neoplasias Ósseas/imunologia , Osteossarcoma/imunologia , Macrófagos Associados a Tumor/fisiologia , Neoplasias Ósseas/irrigação sanguínea , Neoplasias Ósseas/patologia , Humanos , Metástase Neoplásica , Células-Tronco Neoplásicas/fisiologia , Neovascularização Patológica/etiologia , Osteossarcoma/irrigação sanguínea , Osteossarcoma/patologia , Microambiente Tumoral/fisiologia
11.
J Pers Med ; 11(9)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34575691

RESUMO

Whether smokers respond to anti-cancer drugs differently than non-smokers remains controversial. The objective of this study is to explore whether the better response of the smokers is specific to therapy of anti-PD-1/PD-L1, anti-checkpoint inhibitor, individual drugs on the cell surface, or lung cancer. Our results showed that among all non-small cell lung cancer (NSCLC) patients, when the data from anti-PD-1/PD-L1, anti-CTLA-4, and anti-MUC1 drugs are combined, the mean hazard ratios (HR) of smokers and non-smokers were 0.751 and 1.016, respectively. A meta-analysis with a fixed effect (FE) model indicated that the smokers have an HR value of 0.023 lower than that of the non-smokers. A stratified subgroup meta-analysis indicated that when treated with anti-CTLA-4 drugs, smokers had reduced HR values of 0.152 and 0.165 on average and FE model meta-analysis, respectively. When treated with an anti-MUC1 drug, smokers had reduced HR values of 1.563 and 0.645, on average and FE model meta-analysis, respectively. When treated with a combination of nivolumab and ipilimumab drugs, smokers had, on average, reduced HR and FE model meta-analysis values (0.257 and 0.141), respectively. Smoking is a clinical response predictor for anti-PD/PD-L1 monotherapy or first-line treatment in lung, urothelial carcinoma, and head and neck cancer. Smokers treated with other drugs have shown worse responses in comparison to non-smokers. These data suggest that, along with the progress in the development of new drugs for cancer, drugs acting on specific genotypes of smokers likely will arise.

12.
J Bone Oncol ; 30: 100380, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34345580

RESUMO

Osteosarcoma (OS) is the most common primary bone tumour in children and adolescents, with high degree of malignancy and an extremely poor prognosis. Ferroptosis, a non-traditional mode of regulated cell death (RCD) characterised by iron-dependent accumulation of lipid reactive oxygen species (ROS), is closely associated with a variety of cancers. It has been demonstrated that ferroptosis can regulate OS progression and exert an essential role in the treatment of OS, which is potentially of great value. By targeting ferroptosis in OS, the present review article summarises the relevant mechanisms and therapeutic applications along with discussing current limitations and future directions, which may provide a new strategy for the treatment of OS.

13.
J Int Med Res ; 49(4): 3000605211009812, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33906528

RESUMO

The incidence of tumours found in the patella, including primary and metastatic tumours, is low. Solitary metastasis of oesophageal carcinoma (OC) in the patella is even rarer. A 50-year-old man presented to our clinic because of pain and limited range of motion in the right knee for 4 hours and after a fall. On the basis of the patient's medical history, he was diagnosed with OC 2 months previously and underwent two cycles of paclitaxel liposome combined with tiggio chemotherapy (oral tiggio, 40 mg, two times/day, with a treatment cycle of 3 weeks). A 99mTc-methylene diphosphonate bone scintigraphy scan showed increased radioactivity in the right patella. A right knee biopsy showed the presence of patellar metastasis from OC. Unfortunately, the patient denied additional treatment and was discharged for personal reasons. At the 1-month follow-up, which was conducted by a telephone survey, we learned that the patient had died of acute pulmonary embolism. X-rays and computed tomography are useful for diagnosing patellar metastases, but 99mTc-methylene diphosphonate bone scintigraphy can help physicians diagnose patellar metastasis of OC more rapidly. Biopsy with pathology is the gold standard for diagnosing patellar metastases. Additionally, timely surgical treatment prolongs the survival time of these patients.


Assuntos
Carcinoma , Neoplasias Esofágicas , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Patela/diagnóstico por imagem , Cintilografia , Tomografia Computadorizada por Raios X
14.
World J Clin Cases ; 9(6): 1490-1498, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33644220

RESUMO

BACKGROUND: Gastrointestinal stromal tumor (GIST) usually originates in the stomach, followed by the small intestine, rectum, and other parts of the gastrointestinal tract. The most common sites of metastasis are the liver and peritoneum, whereas spinal metastases from GIST are extremely rare. CASE SUMMARY: We found a case of GIST with the first presentation of multilevel spinal metastases involving the thoracic and lumbar vertebrae. A 61-year-old Chinese man presented to our clinic because of pain in his lower back and hip for 10 d without cause. Subsequently, computed tomography (CT) and magnetic resonance imaging (MRI) revealed abnormal signals in the vertebral appendages of T12 and L4 accompanied by spinal canal stenosis, which was considered as tumor metastasis. As there were no metastases to vital organs, posterior thoracic and lumbar spinal decompression + adnexal mass resection + pedicle internal fixation was adopted to achieve local cure and prevent nerve compression. The results of histopathological studies were consistent with the metastasis of GIST. No local recurrence or new metastases were found at the 6-mo follow-up at the surgical site. The patient has no neurological symptoms at present. It is worth mentioning that a rectal mass was found and surgically removed 1 mo after the patient was discharged from hospital, and the pathological diagnosis of the mass was GIST. CONCLUSION: By reviewing 26 previously reported cases of spinal metastasis in GIST, it was found that spinal metastasis of GIST has become more common in recent years, so the possibility of early spinal metastasis should be recognized. CT and MRI are of great value in the diagnosis of spinal metastatic tumors, and pathological biopsy is the gold standard for the diagnosis of metastatic tumors. It is safe and feasible to treat isolated spinal metastasis in GIST by excising metastatic masses, decompressing the spinal canal, and stabilizing the spine.

15.
Medicine (Baltimore) ; 99(38): e22104, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957330

RESUMO

INTRODUCTION: Smoking is well-known to increase cancer risk, particularly risk of lung cancer, and negatively affects efficacy of cancer treatment. However, recent evidence suggests that among cancer patients, paradoxically, smokers respond to treatment better than non-smokers. We propose to conduct a focused review and meta-analysis to compare response to drug treatment between smoking and non-smoking cancer patients. METHODS AND DESIGN: We will collect data from large clinical trials of therapies for cancer patients which have included smokers and non-smokers. We will search PubMed, PMC/ MEDLINE, SCOPUS, Embase, and the registries for clinical trials and four major clinical journals up to June 30, 2019. Search terms will be "Drug name" phase-3" or "Drug name" phase-III." Data collection will be focused on randomized clinical trials of cancer drugs that enrolled at least 100 participants and reporting treatment results from smoking and nonsmoking patients. Initial selection criteria will be clinical trial studies of drug treatment of 100 or more cancer patients, and reporting hazard ratios (HR) for smokers and non-smokers. Two persons will be searching such publications independently, or data will be provided, double checked, or confirmed by authors. Multiple sub-group analyses will be conducted by at least two persons to avoid bias or experimental errors. DISCUSSION: The results will clarify whether smoking and response to treatment of cancer are linked not. Our results may possibly identify drug/s that work better among cancer patients who are smokers. TRIAL REGISTRATION: PROSPERO registration number: CRD42019146402.


Assuntos
Neoplasias/tratamento farmacológico , Projetos de Pesquisa , Fumantes , Ensaios Clínicos como Assunto , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
16.
Anal Cell Pathol (Amst) ; 2020: 2563208, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802732

RESUMO

BACKGROUND: JMJD2B has been reported to be implicated in malignant tumors. This study is aimed at exploring the expression and prognostic significance of JMJD2B in osteosarcoma and its association with hypoxia-inducible factor 1 (HIF1). METHODS: The histopathological and clinical characteristics were retrospectively reviewed from 53 osteosarcoma patients. JMJD2B and HIF1 were examined by immunohistochemical staining of paraffin-embedded osteosarcoma samples, and their association with clinical characteristics was examined by Spearman's test. Overall survival was examined by Kaplan-Meier analysis, and prognostic factors were identified by univariate and multivariate regression analyses. RESULTS: JMJD2B and HIF1 expression levels were both significantly associated with Enneking stage, distant metastasis, and neoadjuvant chemotherapy, and the JMJD2B and HIF1 expressions were positively correlated (p < 0.001, R = 0.752). In addition, univariate analysis showed that the expression of both JMJD2B and HIF1 was significantly associated with overall survival, but multivariate analysis showed that only JMJD2B expression was significantly associated with overall survival in osteosarcoma patients. CONCLUSIONS: JMJD2B and HIF1 expression levels show significant correlation with osteosarcoma progression, and JMJD2B could predict poor prognosis of osteosarcoma patients.


Assuntos
Fator 1 Induzível por Hipóxia/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Feminino , Humanos , Masculino , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida , Adulto Jovem
17.
J Int Med Res ; 48(6): 300060520926355, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32493092

RESUMO

OBJECTIVES: A relationship exists between sirtuin-1 expression and growth and survival of malignant tumors. This study aimed to investigate the prognostic value of sirtuin-1 and vascular endothelial growth factor (VEGF) expression in patients with liposarcoma by examining associations between their expression levels and clinical outcomes. METHODS: Clinical and histopathological characteristics and follow-up and survival information were retrospectively reviewed for 42 liposarcoma cases. Sirtuin-1 and VEGF protein expression levels were evaluated by immunohistochemistry and their associations with clinical parameters were analyzed using the Spearman-rho test. Univariate and multivariate Cox regression analyses were performed to identify potential prognostic factors. Kaplan-Meier analysis was performed to analyze overall survival. RESULTS: Sirtuin-1 and VEGF protein expression levels were significantly associated with histological grade, metastasis, and American Joint Committee on Cancer stage. A significant positive correlation was observed between sirtuin-1 and VEGF expression levels (R = 0.677). In univariate analysis, sirtuin-1 and VEGF expression were correlated with shorter overall survival, but the association was significant only for sirtuin-1 (hazard ratio = 3.752, 95% confidence interval 1.553-9.062) in multivariate analysis. CONCLUSION: Sirtuin-1 and VEGF expression levels are significantly correlated with progression of liposarcoma, and sirtuin-1 expression significantly predicts a poor prognosis in patients with liposarcoma.


Assuntos
Biomarcadores Tumorais/metabolismo , Lipossarcoma/patologia , Sirtuína 1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Adulto , Biomarcadores Tumorais/análise , Criança , Progressão da Doença , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Lipossarcoma/diagnóstico , Lipossarcoma/mortalidade , Lipossarcoma/cirurgia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Estudos Retrospectivos , Sirtuína 1/análise , Fator A de Crescimento do Endotélio Vascular/análise , Adulto Jovem
18.
Aging (Albany NY) ; 12(7): 6340-6351, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32289750

RESUMO

Leptin signaling influences osteoblastogenesis and modulates the fate of mesenchymal stem cells (MSCs) during bone and cartilage regeneration. Although MSCs abound in the osteosarcoma (OS) microenvironment, and leptin exhibits pro-tumorigenic properties, leptin's influence on OS progression and chemoresistant signaling in MSCs remains unclear. Using cell viability and apoptosis assays, we showed that medium conditioned by leptin-treated human MSCs promotes cisplatin resistance in cultured human OS cells. Moreover, GFP-LC3 expression and chloroquine treatment experiments showed that this effect is mediated by stimulation of autophagy in OS cells. TGF-ß expression in MSCs was upregulated by leptin and suppressed by leptin receptor knockdown. Silencing TGF-ß in MSCs also abolished OS cell chemoresistance induced by leptin-conditioned medium. Cisplatin resistance was also induced when leptin-conditioned MSCs were co-injected with MG-63 OS cells to generate subcutaneous xenografts in nude mice. Finally, we observed a significant correlation between autophagy-associated gene expression in OS clinical samples and patient prognosis. We conclude that leptin upregulates TGF-ß in MSCs, which promotes autophagy-mediated chemoresistance in OS cells.


Assuntos
Neoplasias Ósseas , Carcinogênese/metabolismo , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Leptina/metabolismo , Osteossarcoma , Animais , Antineoplásicos/farmacologia , Apoptose , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Cloroquina/farmacologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Osteossarcoma/patologia , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
19.
BMC Urol ; 20(1): 19, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093684

RESUMO

BACKGROUND: Bone metastasis is known to occur in some patients with cancer, usually in the spine, pelvis or ribs, and less than 0.01% of patients have metastases in the foot bone, so metatarsal metastasis is quite rare. The initial symptoms of osseous metastases are swelling, pain, or both. CASE PRESENTATION: We report a 68-year-old man with solitary metatarsal metastasis 26 months after a diagnosis of renal clear cell carcinoma. The patient suffered intermittent swelling of his right foot and pain for one year due to trauma and was not treated. The doctor attributed the symptoms to trauma, administering massage therapy and a plaster cast to the patient at the local clinic. After reviewing the medical records, we found that this patient had a history of clear cell renal cell carcinoma. The patient underwent radiological examination and open biopsy of the first metatarsal bone of the right foot. These findings confirmed that the patient had a metatarsal metastasis from clear cell renal cell carcinoma. The patient subsequently underwent right foot amputation. No local recurrence or distant metastasis was found after a 6-month follow-up. CONCLUSION: Clinicians should be aware of a history of renal cell carcinoma (RCC) and fully understand the patient's past medical history. When treating patients with clear cell renal cell carcinoma who have unresolving bony pain or swelling, clinicians should always keep in mind the possibility of bone metastasis of RCC.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Carcinoma de Células Renais/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Ossos do Metatarso/diagnóstico por imagem , Idoso , Neoplasias Ósseas/cirurgia , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/cirurgia , Masculino , Ossos do Metatarso/cirurgia
20.
Oncol Lett ; 18(6): 6008-6016, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788075

RESUMO

Ewing's sarcoma (ES) is the second most common bone tumor among children and adolescents worldwide. However, the genes and signaling pathways involved in ES tumorigenesis and progression remain unclear. The present study used two gene-expression profile datasets (GSE17674 and GSE31215) to elucidate key potential candidate genes and pathways in ES. Differentially expressed genes (DEGs) were identified and a functional enrichment analysis was performed. A protein-protein interaction (PPI) network was constructed, and the most significant module in the PPI network was selected from the Search Tool for the Retrieval of Interacting Genes/Proteins database. A total of 278 genes were identified by comparing the tumor samples with non-cancerous samples; these included 272 upregulated and 6 downregulated genes. The pathway analysis demonstrated significant enrichment in the positive regulation of transcription in the DEGs coding for RNA polymerase II promoter, plasma membrane and chromatin binding pathways in cancer in general. There were 269 nodes and 292 edges in the PPI network. Finally, MYC, IGF1, OAS1, EZH2 and ISG15 were identified as the hub genes according to the degree levels. The survival analysis revealed that EZH2 is associated with a poor prognosis in patients with ES. In conclusion, the DEGs, associated pathways and hub genes identified in the present study help elucidate the underlying molecular mechanisms of ES carcinogenesis and progression, and provide potential molecular targets and biomarkers for ES.

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