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1.
J Stomatol Oral Maxillofac Surg ; : 101868, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38588856

RESUMEN

BACKGROUND AND PURPOSE: Hirudin, a potent anticoagulant, is used in traditional Chinese medicine (TCM) to treat thrombotic conditions and prevent postoperative thrombosis. Coagulation-related vascular complications are a common cause of perforator flaps failure. This study explores hirudin's potential to enhance flap growth by mitigating coagulation-related issues. MATERIALS AND METHODS: Patients were divided into GroupⅠ(hirudin group) and GroupⅡ(control). Laboratory tests covered red blood cell count (RBC), hematocrit (HCT), platelet count (PLT), monocyte count (MONO), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and D-Dimer. Clinical parameters, including capillary refill time (CRT), flap swelling, and survival status, were evaluated. Animal experiments used Sprague-Dawley (SD) rats to establish random skin flaps. The experimental side received hirudin injection, while the control side received saline. Flaps were photographed to calculate survival rate, and CD31 immunohistochemical (IHC) analysis was performed to calculate microvessel density (MVD). RESULTS: The study, with 29 patients, found significant CRT differences between groups on postoperative days 2 and 6 (p = 0.027; p = 0.019), favoring GroupⅠ. Swelling severity varied significantly over time; GroupⅡhad more pronounced swelling. GroupⅠshowed superior flap growth with fewer complications, statistically significant (p = 0.033). Specific lab indicators (MONO, PT, and FIB) were significant at certain times. In animal experiments, the experimental side consistently had higher flap survival and slightly increased CD31 expression at various times, with higher MVD on days 2 and 6. CONCLUSIONS: Hirudin enhances flap survival through diverse mechanisms, supporting its role as a complementary approach in perforator flap surgeries.

2.
Onco Targets Ther ; 17: 313-325, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38617090

RESUMEN

Tumor microenvironment (TME) is a complex and integrated system containing a variety of tumor-infiltrating immune cells and stromal cells. They are closely connected with cancer cells and influence the development and progression of cancer. Traditional Chinese medicine (TCM) is an important complementary therapy for cancer treatment in China. It mainly eliminates cancer cells by regulating TME. The aim of this review is to systematically summarize the crosstalk between tumor cells and TME, and to summarize the research progress of TCM in regulating TME. The review is of great significance in revealing the therapeutic mechanism of action of TCM, and provides an opportunity for the combined application of TCM and immunotherapy in cancer treatment.

3.
Integr Cancer Ther ; 23: 15347354241237973, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38504436

RESUMEN

BACKGROUND: Postoperative non-small cell lung cancer (NSCLC) patients frequently encounter a deteriorated quality of life (QOL), disturbed immune response, and disordered homeostasis. Si-Jun-Zi Decoction (SJZD), a well-known traditional Chinese herbal formula, is frequently employed in clinical application for many years. Exploration is underway to investigate the potential therapeutic effect of SJZD for treating postoperative NSCLC. OBJECTIVE: To assess the efficacy of SJZD on QOLs, hematological parameters, and regulations of gut microbiota in postoperative NSCLC patients. METHODS: A prospective observational cohort study was conducted, enrolling 65 postoperative NSCLC patients between May 10, 2020 and March 15, 2021 in Yueyang Hospital, with 33 patients in SJZD group and 32 patients in control (CON) group. The SJZD group comprised of patients who received standard treatments and the SJZD decoction, while the CON group consisted of those only underwent standard treatments. The treatment period was 4 weeks. The primary outcome was QOL. The secondary outcomes involved serum immune cell and inflammation factor levels, safety, and alterations in gut microbiota. RESULTS: SJZD group showed significant enhancements in cognitive functioning (P = .048) at week 1 and physical functioning (P = .019) at week 4. Lung cancer-specific symptoms included dyspnea (P = .001), coughing (P = .008), hemoptysis (P = .034), peripheral neuropathy (P = .019), and pain (arm or shoulder, P = .020, other parts, P = .019) eased significantly in the fourth week. Anemia indicators such as red blood cell count (P = .003 at week 1, P = .029 at week 4) and hemoglobin (P = .016 at week 1, P = .048 at week 4) were significantly elevated by SJZD. SJZD upregulated blood cell cluster differentiation (CD)3+ (P = .001 at week 1, P < .001 at week 4), CD3+CD4+ (P = .012 at week 1), CD3+CD8+ (P = .027 at week 1), CD19+ (P = .003 at week 4), increased anti-inflammatory interleukin (IL)-10 (P = .004 at week 1, P = .003 at week 4), and decreased pro-inflammatory IL-8 (P = .004 at week 1, p = .005 at week 4). Analysis of gut microbiota indicated that SJZD had a significant impact on increasing microbial abundance and diversity, enriching probiotic microbes, and regulating microbial biological functions. CONCLUSIONS: SJZD appears to be an effective and safe treatment for postoperative NSCLC patients. As a preliminary observational study, this study provides a foundation for further research.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Calidad de Vida , Estudios Prospectivos , Resultado del Tratamiento
4.
Biochem Genet ; 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38509423

RESUMEN

Epithelial-to-mesenchymal transition (EMT) is a developmental program that plays a vital role in gastric cancer, including aspects of tumor progression, the metastatic process, and resistance to treatment. Here, we have designed an in vitro model that mimics the features of EMT as observed in gastric cancer. The results showed that both migration and invasion were enhanced in gastric cancer cells with Brachyury overexpression. Additionally, the expression of IL-8 increased, while IL-8RA and IL-8RB levels significantly decreased in the in vitro model. Overall, the in vitro model offers an opportunity to study these phenomena relevant to EMT as they may occur in vivo in gastric cancer, as well as potential drug interactions that could interfere with these processes.

5.
Int J Mol Sci ; 25(3)2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38339136

RESUMEN

Gynecologic tract melanoma is a malignant tumor with poor prognosis. Because of the low survival rate and the lack of a standard treatment protocol related to this condition, the investigation of the mechanisms underlying melanoma progression is crucial to achieve advancements in the relevant gynecological surgery and treatment. Mitochondrial transfer between adjacent cells in the tumor microenvironment regulates tumor progression. This study investigated the effects of endothelial mitochondria on the growth of melanoma cells and the activation of specific signal transduction pathways following mitochondrial transplantation. Mitochondria were isolated from endothelial cells (ECs) and transplanted into B16F10 melanoma cells, resulting in the upregulation of proteins associated with tumor growth. Furthermore, enhanced antioxidation and mitochondrial homeostasis mediated by the Sirt1-PGC-1α-Nrf2-HO-1 pathway were observed, along with the inhibition of apoptotic protein caspase-3. Finally, the transplantation of endothelial mitochondria into B16F10 cells promoted tumor growth and increased M2-type macrophages through Nrf2/HO-1-mediated pathways in a xenograft animal model. In summary, the introduction of exogenous mitochondria from ECs into melanoma cells promoted tumor growth, indicating the role of mitochondrial transfer by stromal cells in modulating a tumor's phenotype. These results provide valuable insights into the role of mitochondrial transfer and provide potential targets for gynecological melanoma treatment.


Asunto(s)
Melanoma , Animales , Femenino , Humanos , Células Endoteliales/metabolismo , Macrófagos/metabolismo , Melanoma/metabolismo , Mitocondrias/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Microambiente Tumoral , Ratones
6.
Explore (NY) ; 20(1): 126-129, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37286465

RESUMEN

Malignant pleural mesothelioma (MPM) is a severe form of cancer that originates from mesothelium cells. Around 54-90% of mesotheliomas are associated with pleural effusions. Brucea Javanica Oil Emulsion (BJOE) is the processed oil derived from the seeds of Brucea javanica, which has shown potential as a treatment option for several types of cancer. Here, we present a case study of a MPM patient with malignant pleural effusion who received intrapleural injection of BJOE. The treatment resulted in the complete response of pleural effusion and chest tightness. While the precise mechanisms underlying the therapeutic effects of BJOE for pleural effusion are not yet fully understood, it has demonstrated a satisfactory clinical response without significant adverse effects.


Asunto(s)
Brucea , Mesotelioma Maligno , Mesotelioma , Derrame Pleural Maligno , Humanos , Brucea javanica , Emulsiones/uso terapéutico , Mesotelioma/complicaciones , Mesotelioma/tratamiento farmacológico , Aceites de Plantas/uso terapéutico , Derrame Pleural Maligno/tratamiento farmacológico , Derrame Pleural Maligno/patología
7.
Obes Rev ; 25(2): e13656, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37904643

RESUMEN

Studies have reported inconsistent results about the risk of incident chronic kidney disease (CKD) in people with metabolically healthy obesity (MHO). We designed this systematic review and meta-analysis to evaluate the risk of developing CKD in people with MHO and metabolically unhealthy normal weight (MUNW). We used a predefined search strategy to retrieve eligible studies from multiple databases up to June 20, 2022. Random-effects model meta-analyses were implied to estimate the overall hazard ratio (HR) of incident CKD in obesity phenotypes. Eight prospective cohort studies, including approximately 5 million participants with a median follow-up ranging between 3 and 14 years, were included in this meta-analysis. Compared to the metabolically healthy normal weight (MHNW), the mean differences in cardiometabolic and renal risk factors in MHO, MUNW, and metabolically unhealthy obesity (MUO) were evaluated with overall HR of 1.42, 1.49, and 1.84, respectively. Compared to MHNW, the mean estimated glomerular filtration rate (eGFR) and high-density lipoprotein (HDL) were significantly lower, and low-density lipoprotein (LDL), blood pressure, blood glucose, and triglycerides were higher in MHO and MUNW. In conclusion, MHO and MUNW are not benign conditions and pose a higher risk for incident CKD. Obesity, whether in the presence or absence of metabolic health, is a risk factor for CKD.


Asunto(s)
Síndrome Metabólico , Obesidad Metabólica Benigna , Insuficiencia Renal Crónica , Humanos , Obesidad Metabólica Benigna/complicaciones , Obesidad Metabólica Benigna/epidemiología , Estudios Prospectivos , Obesidad/complicaciones , Obesidad/epidemiología , Factores de Riesgo , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/etiología , Fenotipo , Síndrome Metabólico/genética , Índice de Masa Corporal
8.
J Craniomaxillofac Surg ; 52(1): 23-29, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38129182

RESUMEN

The aim of this study was to introduce and report on a 3D-printed perforator navigator and its clinical application. Integrated imaging and 3D printing techniques were employed for the design and manufacture of a perforator navigator. Key techniques included establishing a digital image coordinate system, localizing perforator fascia piercing points, creating a reference plane for the perforator course, and projecting the perforator course onto the body surface. All cases of maxillofacial defect repaired with free fibular myocutaneous flaps, from January 2019 to January 2022, were reinvestigated. Patients treated using traditional perforator localization methods were assigned into group Ⅰ, while those who had a navigator used during treatment were allocated to group Ⅱ. Outcome measurements included perforator positioning accuracy, perforator preparation time (PT), and flap growth score. Capillary refilling time and degree of flap swelling were recorded on the 1st, 3rd, and 7th days after surgery. On the 10th day after surgery, the flap survival situation was graded. In total, 25 patients were included in the study. Perforator preparation time for group Ⅱ was significantly less (p = 0.04) than for group Ⅰ (1038.6 ± 195.4 s versus 1271.4 ± 295.1 s. In group Ⅱ, the mean positioning deviation for the perforator navigator was 2.12 cm less than that for the high-frequency color Doppler (p = 0.001). Group Ⅱ also had a higher score than group Ⅰ for overall flap growth evaluation (nonparametric rank sum test, p = 0.04). Within the scale of the study, it seems that perforator localization and navigation using a 3D-printed navigator is technically feasible, and helps to improve the clinical outcome of free fibular flaps. The perforator navigator will play a useful role in displaying the perforator course, improving the accuracy of perforator localization, reducing surgical injury, and ultimately enhancing flap success rate.


Asunto(s)
Colgajos Tisulares Libres , Colgajo Miocutáneo , Colgajo Perforante , Procedimientos de Cirugía Plástica , Traumatismos de los Tejidos Blandos , Humanos , Trasplante de Piel , Colgajo Perforante/irrigación sanguínea , Colgajo Miocutáneo/cirugía , Colgajos Tisulares Libres/cirugía , Traumatismos de los Tejidos Blandos/cirugía , Resultado del Tratamiento
9.
Front Endocrinol (Lausanne) ; 14: 1167796, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37680890

RESUMEN

Objective: Pheochromocytoma is a rare catecholamine-producing neuroendocrine tumour originating from the chromaffin cells of the adrenal medulla or extra-adrenal paraganglia. However, there are few bibliometric studies on Pheochromocytoma. Therefore, this study was employed to summarize the global trends and current status in pheochromocytoma by bibliometric analysis. Materials and methods: The Web of Science (WOS) core collection database was searched for publications relating to pheochromocytoma from 2001 to 2021. Bibliometric analysis was used to examine the data, and Microsoft Excel was utilized to create bar graphs. In addition, VOSviewer was used to carry out co-authorship analysis, co-citation analysis and co-occurrence analysis. CiteSpace was used to analyze the keywords citation bursts. Results: A total of 8,653 publications published in 1,806 journals by 38,590 authors in 6,117 organizations from 100 countries/regions were included in our study. Among them, USA was the leading countries in terms of total publications and sum of time cited, whereas Eunice Kennedy Shriver Natl Inst Child Hlth & Hum was the leading institutions. The main publications for pheochromocytoma-related articles were Journal of clinical endocrinology &metabolism. Pacak karel and Eisenhofer Graeme were the main contributing authors. The studies on pheochromocytoma could be grouped into five clusters: Treatment, Mechanism, Etiology, Radiology and Hormones study. Moreover, the radiology study, etiology study and some specific keywords such germlines mutation, mesenchymal stem-cells, autophagy, neuroinflammation, neurotoxicity, and hemodynamic instability, may become the hot spots of future. Conclusion: Although the number of articles on pheochromocytoma has fluctuated slightly over the past 20 years, there has been an overall upward trend. In general, precision medicine research on pheochromocytoma, especially metastatic pheochromocytoma, in terms of diagnosis, treatment, and etiology will be a hot research topic in the future. This study helps to understand the research perspectives, hot spots and trends of pheochromocytoma and provide new insight and a basis for future pheochromocytoma research quickly.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Médula Suprarrenal , Dermatitis , Tumores Neuroendocrinos , Feocromocitoma , Niño , Humanos , Bibliometría
11.
J Cancer Res Clin Oncol ; 149(11): 8649-8654, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37103569

RESUMEN

BACKGROUND: There is no research to prove the association between irritability and lung cancer, our study performed a Mendelian randomization (MR) approach to elucidate the causal relationship of irritability with lung cancer risk. METHODS: Genome-wide association studies (GWAS) data of irritability, lung cancer and gastroesophageal reflux disease (GERD) were downloaded from a public database for two-sample MR analysis. Independent single-nucleotide polymorphisms (SNPs) associated with irritability and GERD were selected as instrumental variables (IVs). Inverse variance weighting (IVW) and weighted median method were used to analyze causality. RESULTS: There is an association between irritability and lung cancer risk (ORIVW = 1.01, 95% CI = [1.00, 1.02], P = 0.018; ORweighted median = 1.01, 95% CI = [1.00, 1.02], P = 0.046), and GERD might account for about 37.5% of the association between irritability and lung cancer. CONCLUSIONS: This study confirmed the causal effect between irritability and lung cancer through MR analysis, and found that GERD played an essential mediating role in this relationship, which can partly indicate the role of the "inflammation-cancer transformation" process in lung cancer.


Asunto(s)
Reflujo Gastroesofágico , Neoplasias Pulmonares , Humanos , Análisis de Mediación , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple
12.
J Transl Med ; 21(1): 250, 2023 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-37038181

RESUMEN

BACKGROUND: Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer with high morbidity and mortality rates. Due to the heterogeneity of LUAD, its characteristics remain poorly understood. Exploring the clinical and molecular characteristics of LUAD is challenging but vital for early diagnosis. METHODS: This observational and validation study enrolled 80 patients and 13 healthy controls. Nuclear and mtDNA-captured sequencings were performed. RESULTS: This study identified a spectrum of nuclear and mitochondrial genome mutations in early-stage lung adenocarcinoma and explored their association with diagnosis. The correlation coefficient for somatic mutations in cfDNA and patient-matched tumor tissues was high in nuclear and mitochondrial genomes. The mutation number of highly mutated genes was evaluated, and the Least Absolute Shrinkage and Selection Operator (LASSO) established a diagnostic model. Receiver operating characteristic (ROC) curve analysis explored the diagnostic ability of the two panels. All models were verified in the testing cohort, and the mtDNA panel demonstrated excellent performance. This study identified somatic mutations in the nuclear and mitochondrial genomes, and detecting mutations in cfDNA displayed good diagnostic performance for early-stage LUAD. Moreover, detecting somatic mutations in the mitochondria may be a better tool for diagnosing early-stage LUAD. CONCLUSIONS: This study identified specific and sensitive diagnostic biomarkers for early-stage LUAD by focusing on nuclear and mitochondrial genome mutations. This also further developed an early-stage LUAD-specific mutation gene panel for clinical utility. This study established a foundation for further investigation of LUAD molecular pathogenesis.


Asunto(s)
Adenocarcinoma del Pulmón , Ácidos Nucleicos Libres de Células , Genoma Mitocondrial , Neoplasias Pulmonares , Humanos , Genoma Mitocondrial/genética , Detección Precoz del Cáncer , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , ADN Mitocondrial/genética
13.
Front Oncol ; 13: 1089578, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36937447

RESUMEN

Malignant melanoma is a highly malignant tumor that originates from melanocytes. It has a poor prognosis and rarely occurs on the foot. Diabetic foot ulcer is one of the most serious chronic complications of diabetes. This paper reports two cases of type 2 diabetes patients with malignant melanoma on the foot. Clinicians should improve their understanding of patients with diabetes with acral malignant melanoma. When diabetic foot ulcers occur repeatedly and continue not to heal, the clinical features of the cutaneous lesions are similar to malignant melanoma, and a pathological biopsy of the lesions should be performed promptly to obtain a clear diagnosis, avoid a missed diagnosis and improve the survival rate.

14.
Vet Sci ; 10(3)2023 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-36977266

RESUMEN

The objective of our study was to survey Babesia infection rates by PCR and tick species on stray dogs to correlate the distribution of Babesia with the distribution of ticks infesting dogs in Taiwan. Three hundred eighty-eight blood samples and 3037 ticks were collected from 388 roaming, and free-ranging owned dogs at residential sites in Taiwan between January 2015 and December 2017. The prevalence of B. gibsoni and B. vogeli was 15.7% (61/388) and 9.5% (37/388), respectively. Most positive B. gibsoni dogs were found in the northern part of the country 56/61 (91.8%), whereas a few were found in the middle 5/61 (8.2%). Babesia vogeli infection rates were 10%, 3.6%, and 18.2% in the northern, central, and southern regions, respectively. Five species of ticks were found: Rhipicephalus sanguineus (throughout Taiwan), Rhipicephalus haemaphysaloides (in the north), Haemaphysalis hystricis (in the north and middle of Taiwan), and Amblyomma testidunarium and Ixodes ovatus (both in the north). None of the dogs in the south were infected with B gibsoni, which correlated with the absence of H. hystricis, a tick recently identified as the local vector for B gibsoni. Babesia vogeli was more equally distributed, coinciding with R. sanguineus, a tick that is present throughout Taiwan. Anaemia was detected in 86.9% of infected dogs; among these dogs, approximately 19.7% showed severe anaemia (HCT < 20). These findings provide useful advice for owners regarding outdoor activities with their dogs and local veterinarians with a regional differential diagnosis of babesiosis in Taiwan.

15.
Front Oncol ; 13: 1322421, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38264748

RESUMEN

Up to one-third of colorectal cancer (CRC) patients experience recurrence after radical surgery, and it is still very difficult to assess and predict the risk of recurrence. Angiogenesis is the key factor of recurrence as metastasis of CRC is closely related to copper metabolism. Expression profiling by microarray from two datasets in Gene Expression Omnibus (GEO) was selected for quality control, genome annotation, normalization, etc. The identified angiogenesis-derived and cuproptosis-related Long non-coding RNAs (lncRNAs) and clinical data were screened and used as predictors to construct a Cox regression model. The stability of the model was evaluated, and a nomogram was drawn. The samples were divided into high-risk and low-risk groups according to the linear prediction of the model, and a Kaplan-Meier survival analysis was performed. In this study, a model was established to predict the postoperative recurrence of colon cancer, which exhibits a high prediction accuracy. Furthermore, the negative correlation between cuproptosis and angiogenesis was validated in colorectal cancer cell lines and the expression of lncRNAs in vitro was examined.

16.
Front Pharmacol ; 13: 1019451, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36523489

RESUMEN

Feiyanning Formula (FYN), a Chinese herbal formula derived from summarized clinical experience, is proven to have anti-tumor effects in lung cancer patients. Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), can improve progression-free survival and overall survival of patients but drug resistance is inevitable. The current study evaluated the effects of FYN in osimertinib-resistant HCC827OR and PC9OR cells. FYN preferentially inhibited the proliferation and migration of HCC827OR and PC9OR cells. Moreover, FYN and osimertinib exhibited synergistic inhibitory effects on proliferation and migration. Real-time qPCR (RT-qPCR) and western blotting results indicated that FYN downregulated gene and protein levels of GSK3ß and SRFS1, which are enriched in the Wnt/ß-catenin pathway. Besides, FYN inhibited tumor growth and exhibited synergistic effects with osimertinib in vivo. Collectively, the results suggested that FYN exerted an anti-osimertinib resistance effect via the Wnt/ß-catenin pathway.

17.
Opt Express ; 30(17): 30779-30790, 2022 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-36242175

RESUMEN

In this paper, a new dual-training method for a time-delay reservoir computing (RC) system based on a single vertical-cavity surface-emitting laser (VCSEL) is proposed and demonstrated experimentally for the first time. The prediction performance of the RC system by using the dual-training method has been experimentally and numerically investigated. Here, the dual-training method is defined as performing a further RC based on the difference between the target value and the predicted value of the traditional single training. It is found that enhanced prediction performance of the RC system can be obtained by employing the dual-training method, compared to the traditional single training method. More specifically, the NMSE values of the RC system with the dual-training method applied can be improved to 760% compared with the single training method in experiments. Besides, the effects of injection power, bias currents, feedback strength, and frequency detuning are also considered. The proposed dual-training method is of great significance to the performance enhancement of the RC and has an important promotion effect on the application of the RC in the future.

18.
Cancer Res ; 82(19): 3516-3531, 2022 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-36193649

RESUMEN

Emerging evidence demonstrates that the dysregulated metabolic enzymes can accelerate tumorigenesis and progression via both metabolic and nonmetabolic functions. Further elucidation of the role of metabolic enzymes in EGFR inhibitor resistance and metastasis, two of the leading causes of death in lung adenocarcinoma, could help improve patient outcomes. Here, we found that aberrant upregulation of phosphoserine aminotransferase 1 (PSAT1) confers erlotinib resistance and tumor metastasis in lung adenocarcinoma. Depletion of PSAT1 restored sensitivity to erlotinib and synergistically augmented the tumoricidal effect. Mechanistically, inhibition of PSAT1 activated the ROS-dependent JNK/c-Jun pathway to induce cell apoptosis. In addition, PSAT1 interacted with IQGAP1, subsequently activating STAT3-mediated cell migration independent of its metabolic activity. Clinical analyses showed that PSAT1 expression positively correlated with the progression of human lung adenocarcinoma. Collectively, these findings reveal the multifunctionality of PSAT1 in promoting tumor malignancy through its metabolic and nonmetabolic activities. SIGNIFICANCE: Metabolic and nonmetabolic functions of PSAT1 confer EGFR inhibitor resistance and promote metastasis in lung adenocarcinoma, suggesting therapeutic targeting of PSAT1 may attenuate the malignant features of lung cancer.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/patología , Línea Celular Tumoral , Resistencia a Antineoplásicos , Receptores ErbB , Clorhidrato de Erlotinib/farmacología , Clorhidrato de Erlotinib/uso terapéutico , Humanos , Neoplasias Pulmonares/patología , Inhibidores de Proteínas Quinasas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Transaminasas/metabolismo
19.
Front Microbiol ; 13: 918823, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35774470

RESUMEN

Lung cancer is a malignancy with high incidence and mortality worldwide. Previous studies have shown that the gut microbiome plays an important role in the development and progression of metabolic cancers. However, data on the characteristics of the gut microbiome with different histopathology types of lung cancer remain scant. We collected stool samples from 28 healthy people (HP) and 61 lung cancer patients. The lung cancer patients were classified into three types according to their histopathology: Atypical Adenomatous Hyperplasia/Adenocarcinoma in situ (AAH/AIS), Minimally Invasive Adenocarcinoma (MIA), and Invasive Adenocarcinoma (IA). In addition, we employed 16S rRNA gene amplicon sequencing to analyze the characteristics of the gut microbiome in these patients. Our analysis revealed that the categorized cancer patients had unique intestinal flora characteristics, and had lower density and flora diversity compared to healthy people. Besides, the structure of the flora families and genera was more complex, and each group presented specific pathogenic microbiota. The patients in the AAH/AIS group and HP group had relatively similar flora structure compared with the IA and MIA groups. In addition, we identified several flora markers that showed significant changes with the development of lung cancer. Lung cancer gut microbiota showed a decrease in short-chain fatty acids (SCFAs) producing and anti-inflammatory bacteria compared to healthy people, while some pathogenic bacteria such as proinflammatory or tumor-promoting bacteria were more abundant in lung cancer patients. On the other hand, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Group (COG) annotation demonstrated suppression of some dominant metabolism-related pathways in lung cancer. These findings provide new biomarkers for the diagnosis and prognostic assessment of lung cancer and lay the basis for novel targeted therapeutic strategies for the prevention and treatment of lung cancer. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03244605].

20.
Discov Oncol ; 13(1): 44, 2022 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-35670862

RESUMEN

As a natural flavone, apigenin is abundantly present in vegetables, fruits, oregano, tea, chamomile, wheat sprout and is regarded as a major component of the Mediterranean diet. Apigenin is known to inhibit proliferation in different cancer cell lines by inducing G2/M arrest, but it is unclear whether this action is predominantly imposed on G2 or M phases. In this study, we demonstrate that apigenin arrests prostate cancer cells at G2 phase by flow cytometric analysis of prostate cancer cells co-stained for phospho-Histone H3 and DNA. Concurrently, apigenin also reduces the mRNA and protein levels of the key regulators that govern G2-M transition. Further analysis using chromatin immunoprecipitation (ChIP) confirmed the diminished transcriptional activities of the genes coding for these regulators. Unravelling the inhibitory effect of apigenin on G2-M transition in cancer cells provides the mechanistic understanding of its action and supports the potential for apigenin as an anti-cancer agent.

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