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Hydrogels are promising candidates for the delivery of therapeutics in the treatment of human cancers. Regarding to the biocomaptiiblity, high drug and encapsulation efficacy and adjustable physico-chemical features, the hydrogels have been widely utilized for the delivery of chemotherapy drugs. Doxorubicin (DOX) is one of the most common chemotherapy drugs used in cancer therapy through impairing topoisomerase II function and increasing oxidative damage. However, the tumor cells have developed resistance into DOX-mediated cytotoxic impacts, requiring the delivery systems to increase internalization and anti-cancer activity of this drug. The hydrogels can deliver DOX in a sustained manner to maximize its anti-cancer activity, improving cancer elimination and reduction in side effects and drug resistance. The natural-based hydrogels such as chitosan, alginate and gelatin hydrogels have shown favourable biocompatibility and degradability in DOX delivery for tumor suppression. The hydrogels are able to co-deliver DOX with other drugs or genes to enhance drug sensitivity and mediate polychemotherapy, synergistically suppressing cancer progression. The incorporation of nanoparticles in the structure of hydrogels can improve the sustained release of DOX and enhancing intracellular internalization, accelerating DOX's cytotoxicity. Furthermore, the stimuli-responsive hydrogels including pH-, redox- and thermo-sensitive platforms are able to improve the specific release of DOX at the tumor site. The DOX-loaded hydrogels can be further employed in the clinic for the treatment of cancer patients and improving efficacy of chemotherapy.
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Doxorrubicina , Liberación de Fármacos , Hidrogeles , Neoplasias , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Doxorrubicina/química , Humanos , Hidrogeles/química , Neoplasias/tratamiento farmacológico , Animales , Sistemas de Liberación de MedicamentosRESUMEN
BACKGROUND: MiRNAs was recognized as vital regulators involved in cancer development. Radioresistance remains a major obstacle for effective treatment of cancers. The mechanisms on the miRNA-mediated radioresistance of cancers are still poorly understood. The main subject of this study is to find new miRNA biomarker that regulates the radioresistance of esophageal cancer (EC). METHODS: The cumulative dose of radiation assays were used to screen the EC radioresistant cell lines. Wound-healing and invasion assays were used to characterize the properties of these cell lines. The following survival fraction experiments were performed to test the effects of miR-199a-3p and AK4 in the radioresistance of EC. In addition, we used the luciferase reporter assays to identify the putative underlying mechanism that relates to the miR-199a-3p regulated radio-resistance. RESULTS: We found that the AK4 gene is one of the targets of miR-199a-3p, which promotes the radioresistance of EC cells. The following experiments by force reversal of the miR-199a-3p or AK4 levels confirmed the relationship of miR-199a-3p and AK4 with the radioresistance of EC cells. In addition, the activities of several signaling pathway were drastically altered by the forced changes of the miR-199a-3p level in EC cells. CONCLUSION: Taken together, we found that miR-199a-3p can be potentially used as a biomarker for the EC radioresistance. Moreover, these results provides new insights into the mechanism on the radioresistance of EC cells, and also might guide the clinical therapy of EC.
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INTRODUCTION: Osteosarcoma (OS) drug resistance often leads to a poor prognosis. Recent evidence suggests that long non-coding RNAs play a crucial role in regulating tumor drug resistance. METHOD: This study aims to investigate the involvement of lncRNA LAMTOR5-AS1 in OS. RNA-seq and qRT-PCR were performed, and the relationship between LAMTOR5- AS1, miR-34a-3p, SIRT1, and HNF4A was determined using Dual-luciferase reporter assays and RNA immunoprecipitation assays. Gain- and loss-of-function assays were measured using CCK-8, cell proliferation, and colony formation assays. RESULT: The study found that the dysregulated LAMTOR5-AS1 acts as a competing endogenous RNA (ceRNA) and competitively protects the HNF4A mRNA 3' UTR from miR-34a-3p. In addition, in vitro functional studies showed that HNF4A can physically interact with SIRT1 to synergistically inhibit osteosarcoma drug resistance. The study found that LAMTOR5-AS1 regulates drug resistance in osteosarcoma through the miR-34a-3p/HNF4A or miR-34a-3p/SIRT1/HNF4A axis. CONCLUSION: These findings offer new insights into lncRNA-mediated drug resistance in cancer and may serve as potential biomarkers for cancer therapy.
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BACKGROUND: Primary cutaneous mucinous carcinoma is a rare neoplasia of the sweat gland. The age-adjusted incidence was 0.024 tumors per 100,000 person-years. It is possible that the actual number of tumors may be slightly higher than previously estimated as some cases of primary cutaneous mucinous carcinoma may have been mistaken for benign tumors and removed by laser therapy without histologic examination. CASE PRESENTATION: We report a 58-year-old Chinese man with primary cutaneous mucinous carcinoma. The patient presented to our care with an indolent nodule on the left cheek, which was proven to be a mucinous adenocarcinoma by excisional biopsy and immunohistochemical staining. Following a comprehensive evaluation, including whole-body computed tomography and positron emission tomography, metastases from other sites were ruled out and the patient was diagnosed with primary cutaneous mucinous carcinoma. The patient underwent an additional wide resection surgery to ensure a safe margin and was then recommended to undergo regular follow-up. CONCLUSION: This case is one of the few published Chinese cases in literature of primary cutaneous mucinous carcinoma. Diagnosis of primary cutaneous mucinous carcinoma is challenging, and treatment options are limited. Collaboration between clinicians and pathologists is crucial for optimal outcomes. Further studies with longer follow-up periods are necessary to provide evidence for the management of this disease.
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Adenocarcinoma Mucinoso , Mejilla , Neoplasias Cutáneas , Humanos , Masculino , Persona de Mediana Edad , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/diagnóstico por imagen , Adenocarcinoma Mucinoso/cirugía , Mejilla/patología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/diagnóstico , Tomografía Computarizada por Rayos X , Neoplasias Faciales/patología , Neoplasias Faciales/cirugía , Neoplasias Faciales/diagnóstico por imagen , Neoplasias Faciales/diagnósticoRESUMEN
BACKGROUND: As the most abundant modification in eukaryotic messenger RNAs (mRNAs), N6-methyladenosine (m6A) plays vital roles in many biological processes. METHODS: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptomic RNA sequencing (RNA-seq) were used to screen for m6A targets in esophageal cancer cells and patients. The role of m6A RNA methylase in esophageal cancer was also analyzed using bioinformatics. In vitro and in vivo experiments were used to analyze gene expression and function. CCK-8, colony formation, cell apoptosis and immunofluorescence staining assays were performed to evaluate the proliferation, migration and invasion of esophageal cancer cells, respectively. Western blot analysis, RNA stability, RIP and luciferase reporter assays were performed to elucidate the underlying mechanism involved. RESULTS: We found that the m6A demethylase FTO was significantly upregulated in esophageal cancer cell lines and patient tissues. In vivo and in vitro assays demonstrated that FTO was involved in the proliferation and apoptosis of esophageal cancer cells. Moreover, we found that the m6A methyltransferase METTL14 negatively regulates FTO function in esophageal cancer progression. FTO alone is not related to the prognosis of esophageal cancer, and its function is antagonized by METTL14. By using transcriptome-wide m6A-seq and RNA-seq assays, we revealed that AKT3 is a downstream target of FTO and acts in concert to regulate the tumorigenesis and metastasis of esophageal cancer. Taken together, these findings provide insight into m6A-mediated tumorigenesis in esophageal cancer and could lead to the design of new therapeutic strategies.
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Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Neoplasias Esofágicas , Metiltransferasas , Humanos , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Carcinogénesis , Transformación Celular Neoplásica , Desmetilación , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Metiltransferasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
BACKGROUND: An estimated 119,300 new cases of cervical cancer occur annually in China, accounting for 372,00 deaths. Cutaneous metastasis from cervical cancer is a rare event, with an incidence of 0.1-1.3% and typically a preterminal occurrence. Scalp metastasis from cervical cancer is exceptionally anecdotal, with only a dozen examples well documented. CASE PRESENTATION: The patient is a 33-year-old Chinese woman who was diagnosed with International Federation of Gynecology and Obstetrics stage IVB cervical cancer in November 2021. From December 2021 to April 2022, the patient was enrolled in the clinical trial of sintilimab combined with chemotherapy and radiotherapy for treatment of stage IV cervical cancer and underwent six cycles of immunotherapy and chemotherapy (sintilimab plus paclitaxel liposome and cisplatin). Treatment was well tolerated and led to a partial response. The masses adjacent to the spine and iliac bone was largely reduced. Thus, radiotherapy of the metastatic residues was carried out and followed by radiotherapy to the primary tumor at the cervix uteri. However, by the time of the radiotherapy completion in October 2022, the patient noticed painless nodules at the left scapular region and the right hypochondrium. The following month, more nodules occurred on the scalp and trunk, including the left axilla, anterior abdomen, and left back, along with a lesion invading the sternum that caused acute bone pain. The cutaneous masses were white, discrete with a rubbery consistency, and fixed to the skin. Several nodules increased in size and eventually ulcerated. Fineneedle aspiration cytology of the left back swellings revealed metastatic squamous cell carcinoma, P16 positive. No visceral or brain metastasis was observed at this point. CONCLUSIONS: Cervical cancer metastases to the scalp are extremely uncommon. When a scalp metastasis is present, it might be the only symptomatic sign of disease progression or widespread metastatic lesions. So far, there is no clear guideline regarding skin metastases treatment. Such skin lesions warrant a thorough radiologic and pathologic workup to form a comprehensive management plan.
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Carcinoma de Células Escamosas , Neoplasias Cutáneas , Neoplasias del Cuello Uterino , Femenino , Humanos , Adulto , Neoplasias del Cuello Uterino/patología , Cuero Cabelludo/patología , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/secundario , Carcinoma de Células Escamosas/patología , CisplatinoRESUMEN
OBJECTIVE: The aim of this study was to compare the advantages and disadvantages of intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in patients with left-sided breast cancer who underwent hypofractionated IMRT after a modified radical mastectomy. MATERIALS AND METHODS: Twenty patients who required adjuvant radiotherapy after modified radical mastectomy were randomly selected, and a specified dose of 43.5 Gy/15 F was used to plan for IMRT or VMAT. Dose-volume histograms (DVHs) were utilized to evaluate the dose distribution of the planning target volumes (PTVs) and organs at risk (OARs). RESULTS: VMAT demonstrated a greater and more uniform dose distribution of PTVs and lower number of monitor units. No significant differences were found in V5 of the affected lung and heart between the two techniques (P > 0.05). The V10, V20, V30, and Dmean of the affected lung and V10, V20, V30, V40, Dmean, and Dmax of the whole heart were better in the VMAT than in the IMRT (P < 0.05). The Dmean and Dmax of the left anterior descending (LAD) branch of the coronary artery of the heart were better in the VMAT (P < 0.05), and the use of the VMAT effectively reduced the cardiopulmonary dose. A significant advantage of V30 and Dmean was also found in VMAT (P < 0.05). CONCLUSION: These findings indicate that VMAT has higher clinical significance than IMRT, because it improved the dose distribution in the target area, reduced the cardiopulmonary dose, protected the OARs (e.g. thyroid), and shortened the treatment duration.
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Neoplasias de la Mama , Radioterapia de Intensidad Modulada , Humanos , Femenino , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Radioterapia de Intensidad Modulada/métodos , Mastectomía Radical Modificada , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Mastectomía , Órganos en RiesgoRESUMEN
PURPOSE: To identify the feasibility and value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and magnetic resonance imaging (MRI)-based radiomics combined with clinical prognostic factors (CPF) in predicting concurrent chemoradiotherapy (CCRT) sensitivity of locally advanced cervical cancer (LACC). METHODS: A retrospective analysis of 163 patients (assigned to training or test groups) who underwent conventional MRI and IVIM-DWI before CCRT were divided into sensitive and resistant groups according to their efficacy at 6 months after CCRT. Per-treatment IVIM-DWI parameters (ADC, D, Dâ and f value), 3D texture features (from axial T2WI) and CPF were measured, analyzed and screened. The prediction model and its nomogram were developed by combining screened parameters and then validated internally and externally. RESULTS: Clinical stage, f value, D value, InverseVariance, SizeZoneNonUniformity, and Minimum were selected to construct prediction model. All parameters except D value showed independent diagnostic value in multivariate Logistic regression analysis and composed prediction model, with AUCs of 0.987 and 0.984 for training and test groups, respectively. The calibration curve (Brier score of 0.042, C-index of 0.987), decision curve and clinical impact curve further demonstrated the reliability and clinical value of prediction model. CONCLUSION: IVIM-DWI, MRI-based radiomics and CPF showed high clinical value in predicting CCRT sensitivity for LACC with better predictive performance when combined.
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Neoplasias del Cuello Uterino , Quimioradioterapia/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Humanos , Imagen por Resonancia Magnética , Pronóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/terapiaRESUMEN
Objective: To explore the effect and safety of avatrombopag for chemotherapy-induced thrombocytopenia (CIT). Methods: This multicenter, open-label, single-arm trial enrolled CIT patients in eight centers from October 2020 to April 2021. The participants received avatrombopag tablets 60 mg once a day for 5-10 days. The main endpoint was the proportion of patients with platelet count ≥100×109/L or increased by ≥ 50×109/L or increased by ≥ 100% in the cycle after the start of treatment. Results: Seventy-four participants were enrolled with a mean age of 59.8 ± 11.62.2% were males. The cumulative effective rate (any criteria) was 70.3% at 4 weeks. 42 (56.8%) achieved platelet count ≥100×109/L, 44 (59.5%) increased by ≥ 50×109/L, and 27 (36.5%) increase by ≥ 100% from baseline. The duration of grade III and IV platelet reduction was 4.2 ± 5.3 days. The time of PLT recovery to ≥75×109/L was 9.4 ± 6.6 days. The time of PLT recovery to ≥100×109/L was 10.2 ± 6.4 days. The platelet count nadir was 57.9 ± 45.3×109/L. The most common adverse events were nausea (8.1%), fatigue (5.4%), and abdominal pain (1.4%). There were no cases of fever, headache, or peripheral edema. Conclusion: Although it was a single-arm trial without a control group, the application of avatrombopag in patients with CIT can increase the platelet count of the patients compared with baseline. Avatrombopag is safe and tolerable. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04609891?term=04609891&draw=2&rank=1, identifier [NCT04609891].
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N6-methyladenosine (m6A) is the most prevalent and internal modification that occurs in the messenger RNAs of eukaryotes. However, knowledge of the impact of these modifications on gene expression regulation remains limited. By using the in vitro MeRIP-seq and RNA-seq assays, we discovered that the mRNA demethylase FTO was significantly up-regulated in esophageal squamous cell carcinoma (ESCC) tissues and cells. Knockdown of FTO drastically suppressed the proliferation, migration, and invasion of ESCC cells. Furthermore, by using transcriptome-wide m6A-seq and RNA-seq assays, we identified ERBB2 is the target of FTO, which acts in concert in ESCC tumorigenesis and metastasis. Moreover, loss and gain functional studies suggested that the m6A reader YTHDF1 stabilizes ERBB2 mRNA via decoding the m6A modification. All these results uncovered a new signaling cascade, including FTO, YTHDF1, and ERBB2, which finely regulates the ESCC progression.
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Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Receptor ErbB-2 , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Desmetilación , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Humanos , ARN Mensajero/genética , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismoRESUMEN
BACKGROUND: Bladder cancer is the second most common urological cancer worldwide, with low early diagnosis and high mortality. The limited progress in diagnostics and treatment greatly impedes the survival of bladder cancer patients. OBJECTIVE: Potential therapeutic biomarkers are urgently needed for future clinical treatment. METHODS: We analyzed the sequencing data and corresponding clinicopathological features and survival information of bladder cancer patients in the TCGA database and identified a new zinc finger protein 485 gene, termed ZNF485, which is highly expressed in the tissues of bladder cancer patients and was verified in cells, animal models and tissue microarrays. RESULTS: We found that inhibition of ZNF485 in the bladder cancer cell lines T24 and 5637 obviously inhibited proliferation and promoted the apoptosis of cancer cells. Furthermore, wound healing and invasion assays showed that downregulation of ZNF485 significantly decreased the mobility and invasion of T24 and 5637 cells. In addition, ZNF485-shRNA transfection obviously inhibited tumor growth in nude mice. Immunohistochemical results of clinical samples showed that the expression level of ZNF485 protein in cancer tissues was higher than that in adjacent tissues. Mechanistic analysis identified possible downstream target genes. CONCLUSIONS: Taken together, the results provide evidence that ZNF485 is involved in bladder cancer proliferation and might be a potential therapeutic biomarker for the treatment of this disease.
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OBJECTIVE: To investigate the preventive and therapeutic effects of Xiaobanxia Fuling Decoction (XBFD) on cisplatin-induced pica rats and to study its mechanism. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into the following 7 groups, i.e., the blank control group, the model group, the high-, middle-, and low-dose XBFD groups (at the daily dose of 30, 15, and 7. 5 g/kg, respectively), the aprepitant (at the daily dose of 13 mg/kg), and pure Chinese medicine group (at the daily dose of XBFD 15 g/kg), 6 in each group. On the 3rd day of this study, 3 mg/kg cisplatin was intraperitoneally injected to rats except the blank control group and the model group to establish the pica rat model. The consumptions of kaolin, food, and the general situation of rats were observed. The protein and mRNA expressions of neurokinin 1 receptor (NK1R) in both the medulla oblongata and the gastric antrum were measured by immunohistochemical assay and Real-time fluorescent quantitative PCR respectively on the sixth day of this study. RESULTS: On the third, fourth, and fifth day of this study, the consumption of kaolin of rats significantly increased when compared with the blank control group (P<0.01). Compared with the model group, the consumption of kaolin significantly decreased in the high-, middle-, and low-dose XBFD groups on the third, fourth, and fifth day of this study (P<0.05). The food intake of rats in the high-dose XBFD groups significantly increased when compared with the model group on the third day of this study (P<0.05). The protein and mRNA expressions of NK, R in the medulla oblongata and the gastric antrum significantly decreased in the high- and middle-dose XBFD groups when compared with the model group (P<0.05). CONCLUSIONS: XBFD could prevent and treat cisplatin-induced pica in rats. Its effect might be correlated with decreasing expressions of NK, R in the medulla oblongata and the gastric antrum.
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Cisplatino/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Pica/inducido químicamente , Pica/prevención & control , Animales , Masculino , Pica/tratamiento farmacológico , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Receptores de Neuroquinina-1/metabolismoRESUMEN
OBJECTIVE: To investigate the effect of dose-painted intensity-modulated radiotherapy (DP-IMRT) combined with chemotherapy on stage IIIB cervical cancer. METHODS: A total of 107 stage IIIB cervical cancer patients were treated with DP-IMRT combined with chemotherapy. The planning target volume (PTV) was divided into regions with different prescribed absorbed doses (so-called PTV-subvolume [PTVsv]): PTVsv1 (the part of the PTV that overlaps with the organ at risk (OAR)) received 39.6-45 Gy, 1.8 Gy/fraction (fx); and PTVsv2 (the part of the PTV that does not overlap with the OAR) received 44-50 Gy, 2.0 Gy/fx. The lymph nodes were simultaneously boosted; lymph nodes with a short axis dimension <1 cm received 50-55 Gy, 2.0-2.4 Gy/fx, while nodes with a short axis dimension >1 cm received 55-66 Gy, 2.2-2.6 Gy/fx. External radiotherapy was followed by intracavitary brachytherapy. Patients were followed up regularly to collect the survival information. RESULTS: Five years after therapy, the overall survival rate and progression-free survival rate were 61.0% and 55.0%, respectively. The cumulative rates for total grade 3 or higher chronic gastrointestinal or genitourinary toxicity were 4.67% and 1.9% respectively. CONCLUSION: Without compromising the primary PTV, DP-IMRT achieved good outcomes for stage IIIB cervical cancer patients with a favorable gastrointestinal toxicity profile.
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Osteosarcoma (OS) is a common malignant bone tumor that commonly occurs in children and adolescents. Long noncoding RNAs (lncRNAs) are recognized as a novel class of regulators of gene expression associated with tumorigenesis. However, the effect and mechanism of lncRNAs in OS tumorigenesis and drug resistance have not been characterized. The purpose of the study is to screen potential biomarker and therapeutic target against OS. We compared the lncRNA expression profiles between OS cell lines with different drug resistance levels using RNA-seq analysis and found that lncRNA DICER1-AS1 was significantly differentially expressed in multi-drugresistant OS cells SJSA-1 versus multi-drugsensitive OS cells G-292. Bisulfite Sequencing PCR (BSP) assay was performed to analyze the differential methylation status of the promoter region of DICER1-AS1 in four OS cells. Subsequently, in vitro gain- and loss-of-function experiments demonstrated the roles of DICER1-AS1 and miR-34a-5p in the multi-drugresistance of OS cells. The main findings is that DICER1-AS1 directly binds to miR-34a-5p, and their expression has a negative correlation with each other. The hypermethylation of the promoter region of DICER1-AS1 silenced its expression in the drugresistant cells SJSA-1 and MNNG/HOS. Moreover, we found that growth arrest and DNA damage-inducible alpha (GADD45A) participates in the DICER1-AS1/miR-34a-5p-regulated drug resistance of OS cells, probably via the cell cycle/pRb-E2F pathway. Our results revealed DICER1-AS1/miR-34a-5p-regulated drug resistance of OS cells, a new lncRNA-regulated network in OS tumorigenesis, suggested that DICER1-AS1 can be considered as a potential biomarker and therapeutic target against OS cells.
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Long-noncoding RNAs (lncRNAs) play roles in regulating cellular functions. High-throughput sequencing analysis identified a new lncRNA, termed LAMTOR5-AS1, the expression of which was much higher in the chemosensitive osteosarcoma (OS) cell line G-292 than in the chemoresistant cell line SJSA-1. Further investigations revealed that LAMTOR5-AS1 significantly inhibits the proliferation and multidrug resistance of OS cells. In vitro assays demonstrated that LAMTOR5-AS1 mediates the interaction between nuclear factor erythroid 2-related factor 2 (NFE2L2, NRF2) and kelch-like ECH-associated protein 1 (KEAP1), which regulate the oxidative stress. Further mechanistic studies revealed that LAMTOR5-AS1 inhibited the ubiquitination degradation pathway of NRF2, resulting in a higher level of NRF2 but a loss of NRF2 transcriptional activity. High level of NRF2 in return upregulated the downstream gene heme oxygenase 1 (HO-1). Moreover, NRF2 controls its own activity by promoting LAMTOR5-AS1 expression, whereas the feedback regulation is weakened in drug-resistant cells due to high antioxidant activity. Overall, we propose that LAMTOR5-AS1 globally regulates chemotherapy-induced cellular oxidative stress by controlling the expression and activity of NRF2.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Osteosarcoma/genética , Animales , Humanos , Ratones , Osteosarcoma/mortalidad , Osteosarcoma/patología , Estrés Oxidativo , Transducción de Señal , Análisis de SupervivenciaRESUMEN
OBJECTIVES: Esophageal cancer (EC) is one of the most difficult malignancies to cure. The radioresistance remains a major obstacle for effective treatment of EC. METHODS: Esophageal cancer radioresistant cell lines were screened by the cumulative dose of radiation assays. qRT-PCR and Western blotting assays were used to detect the expression of LMXIB in EC. The survival fraction experiments were performed to test the effects of LMXIB in the radioresistance of EC. Following, the ionizing radiation and clonogenic, cell proliferation, wound healing and Flow cytometry apoptosis assays were used to characterize the properties of these cell lines. RESULTS: We found that the LMX1B gene, encoding a LIM-homeodomain transcription factor, is expressed in a higher level in the radio-resistant EC cell lines. The following radiation assays revealed that LMX1B promotes the radioresistance of EC cells. Moreover, LMX1B plays roles in the proliferation, cell migration and apoptosis of EC cells. CONCLUSION: All these results indicated that LMX1B is a key regulator involved in the radioresistance of EC, which might be used as a biomarker to guide the clinical therapy of EC.
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Movimiento Celular , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Proteínas con Homeodominio LIM/metabolismo , Tolerancia a Radiación , Factores de Transcripción/metabolismo , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Silenciador del Gen , Humanos , Rayos XRESUMEN
MicroRNAs (miRNAs) are key players of gene expression involved in diverse biological processes including the cancer radio-resistance, which hinders the effective cancer therapy. Here we found that the miR-20a-5p level is significantly up-regulated in radio-resistant nasopharyngeal cancer (NPC) cells via an RNA-seq and miR-omic analysis. Moreover, we identified that the neuronal PAS domain protein 2 (NPAS2) gene is one of the targets of miR-20a-5p. The involvement of miR-20a-5p and NPAS2 with NPC radio-resistance was further validated by either down- or up-regulation of their levels in NPC cell lines. Taken together, these results not only reveal novel insights into the NPC radio-resistance, but also provide hints for an effective therapeutic strategy to fight against NPC radio-resistance.
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The acquisition of radioresistance by esophageal squamous carcinoma (ESC) cells during radiotherapy may lead to cancer recurrence and poor survival. Previous studies have demonstrated that ionizing radiation (IR) induces epithelial-mesenchymal transition (EMT) of ESC cells accompanied by increased migration, invasion, and radioresistance. However, the underlying molecular mechanisms of IR-induced EMT and radioresistance are not well established, hampering the development of potential solutions. To address this issue, we investigated the role of the IL-6/STAT3/TWIST signaling pathway in IR-induced EMT. We found not only the pathway was activated during IR-induced EMT but also STAT3 inhibition or Twist depletion reversed the EMT process and attenuated radioresistance. These results improve our understanding of the underlying mechanisms involved in IR-induced EMT and suggest potential interventions to prevent EMT-induced acquisition of radioresistance.
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Carcinoma de Células Escamosas/genética , Transición Epitelial-Mesenquimal/genética , Neoplasias Esofágicas/genética , Interleucina-6/genética , Proteínas Nucleares/genética , Factor de Transcripción STAT3/genética , Proteína 1 Relacionada con Twist/genética , Animales , Apoptosis/genética , Apoptosis/efectos de la radiación , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Supervivencia Celular/genética , Supervivencia Celular/efectos de la radiación , Transición Epitelial-Mesenquimal/efectos de la radiación , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Humanos , Interleucina-6/metabolismo , Ratones Endogámicos BALB C , Ratones Desnudos , Microscopía Fluorescente , Proteínas Nucleares/metabolismo , Interferencia de ARN , Radiación Ionizante , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/genética , Transducción de Señal/efectos de la radiación , Trasplante Heterólogo , Proteína 1 Relacionada con Twist/metabolismoRESUMEN
BACKGROUND: Associations between transforming growth factor (TGF)-ß1 polymorphisms and hepatocellular carcinoma (HCC) risk remained controversial. Therefore, we performed this meta-analysis to investigate these associations. METHODS: We searched Pubmed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases for studies before March 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association. RESULTS: A total of 14 studies were included in this meta-analysis. TGF-ß1 +869C/T polymorphism was significantly associated with HCC risk (OR=1.74, 95% CI: 1.22-2.47, p=0.002). In addition, a significant association between -509C/T polymorphism and HCC risk was observed (OR=1.40, 95% CI: 1.15-1.70, p=0.0007). Furthermore, significant associations between these polymorphisms and HCC risk were found in Asians and population-based studies. CONCLUSIONS: Our meta-analysis suggested that the TGF-ß1 +869C/T and -509C/T polymorphisms may be risk factors for developing HCC.