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1.
Front Oncol ; 14: 1412660, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39193386

RESUMEN

Objective: The aim of this study was to investigate whether anlotinib could exert an inhibitory effect on the proliferation and invasion of cervical cancer cells by inhibiting cytokines secreted by activated cancer-associated fibroblasts (CAFs). Methods: CAFs were isolated from cervical cancer tissues and experimentally studied in vivo and in vitro. Molecular biology experimental methods were used to verify whether anlotinib could inhibit the pro-carcinogenic effects of CAFs derived from cervical cancer tissues. Results: CAFs promote the proliferation and invasion of cervical cancer cells. Anlotinib inhibited the activation of CAFs and suppressed the promotion of cervical cancer cells by CAFs. Anlotinib inhibited the expression of multiple cytokines within CAFs and suppressed the release of interleukin (IL)-6 (IL-6) and IL-8. In vivo studies have shown that anlotinib diminished the growth of xenografted cervical cancer cells, and treatment in combination with docetaxel had an even more significant tumor growth inhibitory effect. Conclusion: Anlotinib inhibits the pro-cancer effects of CAFs by suppressing the activation of CAFs and the secretion of pro-cancer cytokines. Our findings suggest that the combination of anlotinib and docetaxel may be a potential strategy for the treatment of refractory cervical cancer.

2.
Mol Carcinog ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38934786

RESUMEN

Cancer-associated fibroblasts (CAFs) are abundant and heterogeneous stromal cells in the tumor microenvironment, which play important roles in regulating tumor progression and therapy resistance by transferring exosomes to cancer cells. However, how CAFs modulate esophageal squamous cell carcinoma (ESCC) progression and radioresistance remains incompletely understood. The expression of fibroblast activation protein (FAP) in CAFs was evaluated by immunohistochemistry in 174 ESCC patients who underwent surgery and 78 pretreatment biopsy specimens of ESCC patients who underwent definitive chemoradiotherapy. We sorted CAFs according to FAP expression, and the conditioned medium (CM) was collected to culture ESCC cells. The expression levels of several lncRNAs that were considered to regulate ESCC progression and/or radioresistance were measured in exosomes derived from FAP+ CAFs and FAP- CAFs. Subsequently, cell counting kit-8, 5-ethynyl-2'-deoxyuridine, transwell, colony formation, and xenograft assays were performed to investigate the functional differences between FAP+ CAFs and FAP- CAFs. Finally, a series of in vitro and in vivo assays were used to evaluate the effect of AFAP1-AS1 on radiosensitivity of ESCC cells. FAP expression in stromal CAFs was positively correlated with nerve invasion, vascular invasion, depth of invasion, lymph node metastasis, lack of clinical complete response and poor survival. Culture of ESCC cells with CM/FAP+ CAFs significantly increased cancer proliferation, migration, invasion and radioresistance, compared with culture with CM/FAP- CAFs. Importantly, FAP+ CAFs exert their roles by directly transferring the functional lncRNA AFAP1-AS1 to ESCC cells via exosomes. Functional studies showed that AFAP1-AS1 promoted radioresistance by enhancing DNA damage repair in ESCC cells. Clinically, high levels of plasma AFAP1-AS1 correlated with poor responses to dCRT in ESCC patients. Our findings demonstrated that FAP+ CAFs promoted radioresistance in ESCC cells through transferring exosomal lncRNA AFAP1-AS1; and may be a potential therapeutic target for ESCC treatment.

3.
JMIR Cancer ; 10: e52156, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38814688

RESUMEN

BACKGROUND: WeChat (Tencent) is one of the most important information sources for Chinese people. Relevantly, various health-related data are constantly transmitted among WeChat users. WeChat public accounts (WPAs) for health are rapidly emerging. Health-related WeChat public accounts have a significant impact on public health. Because of the rise in web-based health-seeking behavior, the general public has grown accustomed to obtaining cancer information from WPAs. Although WPAs make it easy for people to obtain health information, the quality of the information is questionable. OBJECTIVE: This study aims to assess the quality and suitability of cancer-related WeChat public accounts (CWPAs). METHODS: The survey was conducted from February 1 to 28, 2023. Based on the WPA monthly list provided by Qingbo Big Data, 28 CWPAs in the WeChat communication index were selected as the survey sample. Quality assessment of the included CWPAs was performed using the HONcode instrument. Furthermore, suitability was measured by using the Suitability Assessment of Materials. A total of 2 researchers conducted the evaluations independently. RESULTS: Of the 28 CWPAs, 12 (43%) were academic and 16 (57%) were commercial. No statistical difference was found regarding the HONcode scores between the 2 groups (P=.96). The quality of the academic and commercial CWPAs evaluated using the HONcode instrument demonstrated mean scores of 5.58 (SD 2.02) and 5.63 (SD 2.16), respectively, corresponding to a moderate class. All CWPAs' compliance with the HONcode principles was unsatisfactory. A statistically significant difference between the 2 groups was observed in the Suitability Assessment of Materials scores (P=.04). The commercial WPAs reached an overall 55.1% (SD 5.5%) score versus the 50.2% (SD 6.4%) score reached by academic WPAs. The suitability of academic and commercial CWPAs was considered adequate. CONCLUSIONS: This study revealed that CWPAs are not sufficiently credible. WPA owners must endeavor to create reliable health websites using approved tools such as the HONcode criteria. However, it is necessary to educate the public about the evaluation tools of health websites to assess their credibility before using the provided content. In addition, improving readability will allow the public to read and understand the content.

4.
J Pharm Biomed Anal ; 241: 115983, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38301575

RESUMEN

Synotis solidaginea Hand.-Mazz. (SSD) is a commonly used Tibetan medicinal herb with a long history of therapeutic use and has good medicinal value and development and utilization prospects. This study aimed to establish and validate a comprehensive strategy integrating UHPLC-Q Exactive Orbitrap HRMS chemical profiling and UHPLC-DAD multi-components quantification for the holistic quality evaluation of SSD. Using UHPLC-Q Exactive Orbitrap HRMS, a total of 58 components in SSD including flavonoids, organic acids, terpenoids, coumarin, and alkaloids were identified or tentatively characterized by authentic reference standards and accurate masses and characteristic fragment ions. The proportion of flavonoids and organic acids were the most in SSD. Subsequently, 7 characteristic components in SSD were quantified by a newly established UHPLC-DAD method that was validated in terms of linearity and ranges, LOD and LOQ, precision, repeatability, stability, and accuracy. Finally, the method was successfully used for the quality evaluation of 8 batches of SSD collected from 5 production areas in China. ANOVA and post hoc Tukey test are used to evaluate the differences in component content in SSD from different production areas. There are significant differences in the content of SSD from different regions (P < 0.05), which may be related to the climate, altitude, and other natural environments of the regions. This work laid a valuable foundation for further development and comprehensive quality control of SSD.


Asunto(s)
Medicamentos Herbarios Chinos , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Medicina Tradicional Tibetana , Control de Calidad , Flavonoides/química
5.
Neuroreport ; 35(2): 90-97, 2024 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-38109375

RESUMEN

OBJECTIVES: Radiation therapy in the treatment of brain tumors also leads to the occurrence of radiation brain injury (RBI). Anlotinib is a small-molecule inhibitor of multi-receptor tyrosine kinase with high selectivity for vascular endothelial growth factor receptor-2. In this study, we constructed a rat model of RBI and investigated the effect of anlotinib on RBI and its mechanism of action through drug intervention during the acute phase of RBI. METHODS: Six-week-old male (Sprague-Dawley) rats were used to construct an animal model of RBI to evaluate the protective effect of anlotinib on acute RBI by histopathological staining, brain edema determination, blood-brain barrier integrity evaluation and quick real time-polymerase chain reaction , ELISA detection of inflammation-related indexes, and western-blot detection of related gene protein expression. RESULTS: Anlotinib reduced the degree of edema in the hippocampal region of rats, improved the pathological morphology of neural cells and vascular endothelial cells, and decreased blood-brain barrier permeability. Anlotinib reduced glial fibrillary acidic protein protein expression in the hippocampal region of rat brain tissue and inhibited astrocyte activation. It inhibited the release of inflammatory factors (interleukin [IL]-6, IL-8 and vascular endothelial growth factor) and down-regulated the expression of janus kinase-2/signal transducer and activator of transcription-3 (JAK2/STAT3) signaling pathway-related proteins. CONCLUSION: This study found that anlotinib has a protective effect against RBI in rats and anlotinib may be a new candidate for the treatment of RBI.


Asunto(s)
Lesiones Encefálicas , Células Endoteliales , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Células Endoteliales/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Encéfalo/metabolismo , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/etiología , Lesiones Encefálicas/metabolismo , Interleucina-6/metabolismo , Factor de Transcripción STAT3/metabolismo
6.
Front Oncol ; 13: 1257266, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37927475

RESUMEN

Oesophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumours with high morbidity and mortality. Although surgery, radiotherapy and chemotherapy are common treatment options available for oesophageal cancer, the 5-year survival rate remains low after treatment. On the one hand, many oesophageal cancers are are discovered at an advanced stage and, on the other hand, treatment resistance is a major obstacle to treating locally advanced ESCC. Cancer-associated fibroblasts (CAFs), the main type of stromal cell in the tumour microenvironment, enhance tumour progression and treatment resistance and have emerged as a major focus of study on targeted therapy of oesophageal cancer.With the aim of providing potential, prospective targets for improving therapeutic efficacy, this review summarises the origin and activation of CAFs and their specific role in regulating tumour progression and treatment resistance in ESCC. We also emphasize the clinical potential and emerging trends of ESCC CAFs-targeted treatments.

7.
Dose Response ; 19(2): 15593258211024393, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34177398

RESUMEN

The underlying mechanisms of radiation-induced brain injury are poorly understood, although COX-2 inhibitors have been shown to reduce brain injury after irradiation. In the present study, the effect of celecoxib (a selective COX-2 inhibitor) pretreatment on radiation-induced injury to rat brain was studied by means of histopathological staining, evaluation of integrity of blood-brain barrier and detection of the expressions of inflammation-associated genes. The protective effect of celecoxib on human brain microvascular endothelial cells (HBMECs) against irradiation was examined and the potential mechanisms were explored. Colony formation assay and apoptosis assay were undertaken to evaluate the effect of celecoxib on the radiosensitivity of the HBMECs. ELISA was used to measure 6-keto-prostaglandin F1α (6-keto-PGF1α) and thromboxane B2 (TXB2) secretion. Western blot was employed to examine apoptosis-related proteins expressions. It was found that celecoxib protected rat from radiation-induced brain injury by maintaining the integrity of the blood-brain barrier and reducing inflammation in rat brain tissues. In addition, celecoxib showed a significant protective effect on HBMECs against irradiation, which involves inhibited apoptosis and decreased TXB2/6-keto-PGF1α ratio in brain vascular endothelial cells. In conclusion, celecoxib could alleviate radiation-induced brain injury in rats, which may be partially due to the protective effect on brain vascular endothelial cells from radiation-induced apoptosis.

8.
Radiat Oncol ; 16(1): 94, 2021 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-34039375

RESUMEN

BACKGROUND: This retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients with locally advanced ESCC who received CCRT with S-1 (70 mg/m2 twice daily on days 1-14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25 mg/m2) and cisplatin (25 mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Radiotherapy was delivered in 1.8-2.0 Gy per fraction to a total dose of 50-60 Gy. Treatment-related toxicities (Common Terminology Criteria for Adverse Events version 4.0), response rate, and survival outcomes were compared between groups. RESULTS: A total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3-4 adverse events were significantly lower in the S-1 group than that of the DP group (22.2% vs. 45.6%, p = 0.002). In the DP group, elderly patients (> 60 years) had a significantly higher rate of grade 3-4 adverse events than younger patients (58.1% vs. 31.3%, p = 0.01). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% vs. 25.0%, p = 0.275). CONCLUSION: CCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/terapia , Anciano , Quimioradioterapia/efectos adversos , Quimioradioterapia/mortalidad , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Docetaxel/administración & dosificación , Docetaxel/efectos adversos , Fraccionamiento de la Dosis de Radiación , Combinación de Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácido Oxónico/administración & dosificación , Ácido Oxónico/efectos adversos , Estudios Retrospectivos , Tasa de Supervivencia , Tegafur/administración & dosificación , Tegafur/efectos adversos , Resultado del Tratamiento
9.
J Med Internet Res ; 22(9): e19668, 2020 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-32883651

RESUMEN

BACKGROUND: Seeking health information on the internet is a popular trend. Xigua Video, a short video platform in China, ranks among the most accessed websites in the country and hosts an increasing number of videos with medical information. However, the nature of these videos is frequently unscientific, misleading, or even harmful. OBJECTIVE: Little is known about Xigua Video as a source of information on breast cancer. Thus, the study aimed to investigate the contents, quality, and reliability of breast cancer-related content on Xigua Video. METHODS: On February 4, 2020, a Xigua Video search was performed using the keyword "breast cancer." Videos were categorized by 2 doctors based on whether the video content provided useful or misleading information. Furthermore, the reliability and quality of the videos were assessed using the 5-point DISCERN tool and 5-point global quality score criteria. RESULTS: Out of the 170 videos selected for the study, 64 (37.6%) were classified as useful, whereas 106 (62.4%) provided misleading information. A total of 41.8% videos (71/170) were generated by individuals compared to 19.4% videos (33/170) contributed by health care professionals. The topics mainly covered etiology, anatomy, symptoms, preventions, treatments, and prognosis. The top topic was "treatments" (119/170, 70%). The reliability scores and global quality scores of the videos in the useful information group were high (P<.001). No differences were observed between the 2 groups in terms of video length, duration in months, and comments. The number of total views was higher for the misleading information group (819,478.5 vs 647,940) but did not reach a level of statistical significance (P=.112). The uploading sources of the videos were mainly health care professionals, health information websites, medical advertisements, and individuals. Statistical differences were found between the uploading source groups in terms of reliability scores and global quality scores (P<.001). In terms of total views, video length, duration, and comments, no statistical differences were indicated among the said groups. However, a statistical difference was noted between the useful and misleading information video groups with respect to the uploading sources (P<.001). CONCLUSIONS: A large number of Xigua videos pertaining to breast cancer contain misleading information. There is a need for accurate health information to be provided on Xigua Video and other social media; health care professionals should address this challenge.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Medios de Comunicación Sociales/normas , Comunicación por Videoconferencia/normas , China , Femenino , Humanos , Reproducibilidad de los Resultados
10.
Mol Ther Oncolytics ; 18: 1-13, 2020 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-32637576

RESUMEN

Cancer-associated fibroblasts (CAFs), an activated subpopulation of fibroblasts, occupy a central position in the tumor microenvironment and have been shown to promote chemoresistance in multiple cancer types by secreting inflammatory cytokines. Herein, we report that tumor-secreted exosomal long non-coding RNAs (lncRNAs) can regulate cisplatin resistance in esophageal squamous cell carcinoma (ESCC) through transformation of normal fibroblasts (NFs) to CAFs. Primary CAFs and matched NFs were isolated from tumor tissues and matched normal esophageal epithelial tissues of ESCC patients. Fluorescence microscopy and qRT-PCR were used to investigate the transportation of exosomal lncRNAs from ESCC cells to NFs. To identify the specific lncRNAs involved, 14 ESCC-related lncRNAs were measured in NFs after incubation with exosomes from ESCC cells. We demonstrated that lncRNA POU3F3 can be transferred from ESCC cells to NFs via exosomes and that it mediated fibroblast activation. Activated fibroblasts further promoted proliferation and cisplatin resistance of ESCC cells through secreting interleukin 6 (IL-6). Moreover, our clinical data showed that high levels of plasma exosomal lncRNA POU3F3 correlated significantly with lack of complete response and poor survival in ESCC patients. Therefore, these data demonstrate that lncRNA POU3F3 is involved in cisplatin resistance in ESCC and that this effect is mediated through exosomal lncRNA POU3F3-induced transformation of NFs to CAFs.

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