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1.
Artículo en Chino | MEDLINE | ID: mdl-38686470

RESUMEN

Objective:To summarize the results of different facial nerve management modalities applied to tumor resection in the jugular foramen region. Methods:The clinical data of 54 patients with tumors in the jugular foramen region who underwent surgery from January 2015 to March 2023 were retrospectively analyzed: 18 males and 36 females; Age ranges from 21 to 67 years, with an average age of 44.4 years; and median follow-up time: 12 months. The House-Brackmann(HB) grading system was applied to assess the patients' facial nerve function before surgery, 1-2 weeks after surgery and at the final follow-up (HBⅠ-Ⅱ grade for good function): 42 cases with preoperative HB grades Ⅰ-Ⅱ; partial facial nerve transposition(9 cases), complete facial nerve transposition(28 cases), and facial nerve excision and re-construction(17 cases) were used, respectively(stage Ⅰor Ⅱ). Relevant factors affecting postoperative facial nerve function were analyzed. Results:Postoperative pathology confirmed 39 cases of paraganglioma, 9 cases of nerve sheath tumor, 3 cases of meningioma, and 1 case each of fibromucinous sarcoma, chondrosarcoma, and intravascular myofibroma. Facial nerve function after partial facial nerve transposition was HB grade Ⅰ-Ⅱ in 89%(8/9); after complete facial nerve transposition was HB grade Ⅰ-Ⅱ in 86%(24/28) in 28 cases; after facial nerve severance and reconstruction was HB grade Ⅰ-Ⅱ in 2/7(Stage Ⅰ) and 0/3(Stage Ⅱ), respectively. Tumor size and surgical approach were correlated with postoperative facial nerve function in patients with facial nerve transposition(P<0.05). There was no statistically significant difference in facial nerve function after complete and partial facial nerve transposition(P>0.05). Conclusion:Intraoperative stretching of the facial nerve may be an important factor affecting facial nerve function during surgical treatment of tumors in the jugular venous foramen region; for patients with facial nerve dissection, facial nerve reconstruction should be adopted according to the situation, aiming at the recovery of facial nerve function.


Asunto(s)
Nervio Facial , Foramina Yugular , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Nervio Facial/cirugía , Estudios Retrospectivos , Anciano , Foramina Yugular/cirugía , Adulto Joven , Meningioma/cirugía , Paraganglioma/cirugía , Periodo Posoperatorio
2.
Int Dent J ; 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38677972

RESUMEN

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in the oral and maxillofacial region. Lactic acid accumulation in the tumour microenvironment (TME) has gained attention for its dual role as an energy source for cancer cells and an activator of signalling pathways crucial to tumour progression. This study aims to reveal the impact of lactate-related genes (LRGs) on the prognosis, TME, and immune characteristics of OSCC, with the ultimate goal of developing a novel prognostic model. METHODS: Unsupervised clustering analysis of LRGs in OSCC patients from The Cancer Genome Atlas database was conducted to evaluate and compare TME, immune features, and clinical characteristics across various lactate subtypes. A refined prognostic model was developed through the application of Cox and Least absolute shrinkage and selection operator (LASSO) regression techniques. External validation sets were then utilised to improve model accuracy, along with a detailed correlation analysis of drug sensitivity. RESULTS: The Cancer Genome Atlas-OSCC patients were categorised into 4 distinct lactate subtypes based on LRGs. Notably, patients in subtype 1 and subtype 2 exhibited the least and most favourable prognoses, respectively. Subtype 1 patients showed elevated expression levels of immune checkpoint genes. Further analysis identified 1086 genes with significant expression differences between cancer and noncancer tissues, as well as between subtype 1 and subtype 2 patients. Selected genes for the prognostic model included ZNF662, CGNL1, VWCE, and ZFP42. The high-risk group defined by this model had a significantly poorer prognosis (P < .0001) and functioned as an independent prognostic factor (P < .001), accurately predicting 1-, 3-, and 5-year survival rates. Additionally, individuals in the high-risk category exhibited heightened sensitivity to chemotherapy drugs such as AZ6102 and Venetoclax. CONCLUSIONS: The predictive model based on the genes ZNF662, CGNL1, VWCE, and ZFP42 can serve as a reliable biomarker, providing accurate prognostic predictions for OSCC patients and potential opportunities for pharmaceutical interventions.

3.
Nat Commun ; 15(1): 2292, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38480740

RESUMEN

Triple-negative breast cancer (TNBC) is a highly metastatic and heterogeneous type of breast cancer with poor outcomes. Precise, non-invasive methods for diagnosis, monitoring and prognosis of TNBC are particularly challenging due to a paucity of TNBC biomarkers. Glycans on extracellular vesicles (EVs) hold the promise as valuable biomarkers, but conventional methods for glycan analysis are not feasible in clinical practice. Here, we report that a lectin-based thermophoretic assay (EVLET) streamlines vibrating membrane filtration (VMF) and thermophoretic amplification, allowing for rapid, sensitive, selective and cost-effective EV glycan profiling in TNBC plasma. A pilot cohort study shows that the EV glycan signature reaches 91% accuracy for TNBC detection and 96% accuracy for longitudinal monitoring of TNBC therapeutic response. Moreover, we demonstrate the potential of EV glycan signature for predicting TNBC progression. Our EVLET system lays the foundation for non-invasive cancer management by EV glycans.


Asunto(s)
Vesículas Extracelulares , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/terapia , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Biomarcadores de Tumor , Proyectos Piloto , Vesículas Extracelulares/patología , Polisacáridos
4.
Osteoporos Int ; 35(4): 727-731, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38062162

RESUMEN

Gorham-Stout syndrome is an aggressive, non-hereditary, and rare disease affecting bone metabolism. Its etiology and pathogenesis remain elusive. The syndrome manifests with diverse clinical symptoms, often leading to frequent misdiagnoses and presenting challenges in treatment. In this study, we report a case of cranial and maxillary osteolysis in a 47-year-old female patient with somatic mutations in the VEGF-A, VEGF-B, and VEGF-C genes and the EPHB4 gene. After treatment with bisphosphonates, this patient still had persistent resorption of the mandible, but switching to a teriparatide and denosumab combination yielded substantial improvement. This study is the first report to show that teriparatide combined with denosumab can be used to treat Gorham-Stout syndrome.


Asunto(s)
Osteólisis Esencial , Femenino , Humanos , Persona de Mediana Edad , Osteólisis Esencial/diagnóstico por imagen , Osteólisis Esencial/tratamiento farmacológico , Teriparatido/uso terapéutico , Denosumab/uso terapéutico , Difosfonatos/uso terapéutico , Síndrome
5.
Lab Med ; 55(1): 1-7, 2024 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-37172311

RESUMEN

OBJECTIVE: To evaluate the diagnostic value of circulating microRNA-29 (miR-29) in digestive system malignant neoplasms by meta-analysis. METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science to collect studies, published through September 2022, on the diagnostic value of miR-29 in digestive system tumors. RESULTS: We included 7 studies in this meta-analysis, including colorectal cancer, esophageal squamous cell carcinomas, and cholangiocarcinoma. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.64 (95% CI, 0.53-0.74), 0.83 (0.60-0.94), 3.75 (1.42-9.91), 0.44 (0.31-0.61), and 8.63 (2.54-29.26), respectively. The area under the summary receiver operating characteristic curve was 0.75. The sensitivity of miR-29 derived from serum was higher than that of miR-29 derived from plasma for malignant digestive system tumors (0.71 vs 0.54; P = .04). CONCLUSION: This meta-analysis suggests that the circulating miR-29 family has good diagnostic performance for digestive system malignant tumors, with moderate sensitivity and good specificity.


Asunto(s)
Neoplasias del Sistema Digestivo , MicroARNs , Humanos , Biomarcadores de Tumor , Neoplasias del Sistema Digestivo/diagnóstico , Curva ROC , Sensibilidad y Especificidad
6.
Autophagy ; 20(1): 4-14, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37594406

RESUMEN

Macroautophagy/autophagy, is widely recognized for its crucial role in enabling cell survival and maintaining cellular energy homeostasis during starvation or energy stress. Its regulation is intricately linked to cellular energy status. In this review, covering yeast, mammals, and plants, we aim to provide a comprehensive overview of the understanding of the roles and mechanisms of carbon- or glucose-deprivation related autophagy, showing how cells effectively respond to such challenges for survival. Further investigation is needed to determine the specific degraded substrates by autophagy during glucose or energy deprivation and the diverse roles and mechanisms during varying durations of energy starvation.Abbreviations: ADP: adenosine diphosphate; AMP: adenosine monophosphate; AMPK: AMP-activated protein kinase; ATG: autophagy related; ATP: adenosine triphosphate; ER: endoplasmic reticulum; ESCRT: endosomal sorting complex required for transport; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GD: glucose deprivation; GFP: green fluorescent protein; GTPases: guanosine triphosphatases; HK2: hexokinase 2; K phaffii: Komagataella phaffii; LD: lipid droplet; MAP1LC3/LC3: microtubule-associated protein1 light chain 3; MAPK: mitogen-activated protein kinase; Mec1: mitosis entry checkpoint 1; MTOR: mechanistic target of rapamycin kinase; NAD (+): nicotinamide adenine dinucleotide; OGD: oxygen and glucose deprivation; PAS: phagophore assembly site; PCD: programmed cell death; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; ROS: reactive oxygen species; S. cerevisiae: Saccharomyces cerevisiae; SIRT1: sirtuin 1; Snf1: sucrose non-fermenting 1; STK11/LKB1: serine/threonine kinase 11; TFEB: transcription factor EB; TORC1: target of rapamycin complex 1; ULK1: unc-51 like kinase 1; Vps27: vacuolar protein sorting 27; Vps4: vacuolar protein sorting 4.


Asunto(s)
Autofagia , Saccharomyces cerevisiae , Animales , Saccharomyces cerevisiae/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Metabolismo Energético , Proteínas Quinasas Activadas por AMP/metabolismo , Glucosa , Mamíferos/metabolismo
7.
Onco Targets Ther ; 16: 1061-1071, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38144904

RESUMEN

Background: Endometrial cancer (EC) is one of the most prevalent gynecologic cancers, which poses a serious threat to women's health worldwide. Olaparib, the first FDA-approved PARP inhibitor for the treatment of BRCA-mutated breast, ovarian and pancreatic cancers, triggers apoptosis of cancer cells through synthetic lethality by inhibiting PARP1/2 enzymatic activity and BRCA1/2-dependent homologous recombination (HR) repair deficiency. However, the synergistic lethal effects between Olaparib and inhibitors of other DNA damage response proteins, such as ATM, PTEN and RAD51, are still unknown. Aim: Exploring the synergistic lethal effect between Olaparib and KU-55933 on EC. Methods: The GEPIA database was used to test EC patient survival rate. CCK8 was used for cell viability assays. Western blot was used for examining gene levels. The wound healing assay was used to detect cell migration ability. Flow cytometry was used for detecting the apoptosis rate. All experimental conditions were repeated independently in triplicate and analyzed in three separate experiments. Results: In this study, we discovered that the frequency of ATM alterations in endometrial cancer reaches nearly 20% and that there is a positive correlation between ATM alterations and prognosis. Furthermore, we discovered that endometrial cells with low expression levels of ATM are sensitive to Olaparib. Treatment with KU-55933, a specific inhibitor of ATM, significantly enhanced the sensitivity of endometrial cancer cells to Olaparib, as evidenced by colony formation, cell migration and apoptosis assay. Further analysis revealed that KU-55933 potentiates Olaparib-induced cell apoptosis by inhibiting ATM phosphorylation. Conclusion: Our study demonstrates that inhibiting ATM could enhance the sensitivity of endometrial cancer to Olaparib, thereby providing a potential alternative treatment for the clinical treatment of endometrial cancer.

8.
Clin Lab ; 69(5)2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37145084

RESUMEN

BACKGROUND: Defined as rare large azurophilic cytoplasmic inclusions, Pseudo-Chediak-Higashi granules mimic those in granulocytes cytoplasm of Chediak-Higashi syndrome. Rare cases of hematopoietic and lymphoid tissues tumors showed Pseudo-Chediak-Higashi inclusions in cytoplasm, some of which presented with unusual morphological characteristics. METHODS: Herein, we report the first case, in which rare pseudo-Chediak-Higashi inclusions were observed in therapy-related acute myeloid leukemia with myelodysplasia-related changes (t-AML-MRC). RESULTS: The rare pseudo-Chediak-Higashi inclusions may be positive for Sudan black, and some scholars think that these rare inclusions are a kind of dysgranulopoiesis. CONCLUSIONS: The case highlights the significance of an integrated diagnostic work-up, with an interesting effect for morphology.


Asunto(s)
Síndrome de Chediak-Higashi , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Gránulos Citoplasmáticos/patología , Leucemia Mieloide Aguda/diagnóstico , Síndrome de Chediak-Higashi/diagnóstico , Síndrome de Chediak-Higashi/patología , Granulocitos , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/patología , Cuerpos de Inclusión/patología
9.
Ear Nose Throat J ; : 1455613231158800, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36919575

RESUMEN

External auditory canal adenoid cystic carcinoma (EAC) is rare and is associated with nonspecific clinical manifestations such as early ear pain. We report a patient with advanced lung metastases from adenoid cystic carcinoma (ACC) of the EAC, which is difficult to diagnose. Under general anesthesia, lengthened right temporal bone resection, parotidectomy, facial nerve resection, cervical lymph node dissection (I-III), partial mandibular resection, tumor resection in the inferior temporal fossa and lateral femoral flap repair were performed, followed by regular radiotherapy and chemotherapy. During 2 years of postsurgical follow-up, there was no recurrence. The combination of early detection, resection, postoperative radiotherapy, and chemotherapy can result in a good therapeutic effect.

11.
Front Microbiol ; 13: 1022200, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36504795

RESUMEN

Microbial fermentation is a useful method for improving the biological activity of Chinese herbal medicine. Herein, we revealed the effects of solid-state fermentation by Lactiplantibacillus plantarum, Bacillus licheniformis, Saccharomyces cerevisiae, Eurotium cristatum and multiple strains on total flavonoid content, total phenol content, as well as antioxidants, α-amylase inhibitory activities and α-glucosidase inhibitory activities in white ginseng (WG). Metabolite differences between non-fermented and fermented WG by different probiotics were comprehensively investigated using ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS). Results showed that the total flavonoid content, ferric reducing antioxidant power, scavenging activities of DPPH radical and ABTS radical, α-amylase inhibitory activities and α-glucosidase inhibitory activities of WG were considerably enhanced after processing by solid-state fermentation in all strains. The total phenol content was increased by E. cristatum and B. licheniformis fermentation, but decreased by L. plantarum, S. cerevisiae and multi-strain fermentation. Additionally, E. cristatum exhibited stronger biotransformation activity on WG compared to other strains. Significant differential metabolites were mainly annotated as prenol lipids, carboxylic acids and derivatives, flavonoids, polyphenols, coumarins and derivatives. Correlation analysis further showed that changes of these metabolites were closely related to antioxidant and hypoglycemic effects. Our results confirmed that fermentation of WG by different probiotics has distinct effects on biological activities and metabolite composition, and indicating fermentation as an important novel strategy to promote components and bioactivities of WG.

12.
Virol J ; 19(1): 182, 2022 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-36357910

RESUMEN

BACKGROUND: Chrysanthemum virus B (CVB), a key member of the genus Carlavirus, family Betaflexiviridae, causes severe viral diseases in chrysanthemum (Chrysanthemum morifolium) plants worldwide. However, information on the mechanisms underlying the response of chrysanthemum plants to CVB is scant. METHODS: Here, an integrated next-generation sequencing and comparative transcriptomic analysis of chrysanthemum leaves was conducted to explore the molecular response mechanisms of plants to a Chinese isolate of CVB (CVB-CN) at the molecular level. RESULTS: In total, 4934 significant differentially expressed genes (SDEGs) were identified to respond to CVB-CN, of which 4097 were upregulated and 837 were downregulated. Gene ontology and functional classification showed that the majority of upregulated SDEGs were categorized into gene cohorts involved in plant hormone signal transduction, phenylpropanoid and flavonoid biosynthesis, and ribosome metabolism. Enrichment analysis demonstrated that ethylene pathway-related genes were significantly upregulated following CVB-CN infection, indicating a strong promotion of ethylene biosynthesis and signaling. Furthermore, disruption of the ethylene pathway in Nicotiana benthamiana, a model plant, using virus-induced gene silencing technology rendered them more susceptible to cysteine-rich protein of CVB-CN induced hypersensitive response, suggesting a crucial role of this pathway in response to CVB-CN infection. CONCLUSION: This study provides evidence that ethylene pathway has an essential role of plant in response to CVB and offers valuable insights into the defense mechanisms of chrysanthemum against Carlavirus.


Asunto(s)
Carlavirus , Chrysanthemum , Chrysanthemum/genética , Chrysanthemum/metabolismo , Carlavirus/genética , Transcriptoma , Etilenos/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento , Hojas de la Planta , China , Regulación de la Expresión Génica de las Plantas
13.
J Antibiot (Tokyo) ; 75(11): 650-653, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36109668

RESUMEN

Two new 22-membered macrolide metabolites, phthoramycins B (1) and C (2), were isolated from the fermentation broth of Streptomyces sp. HU210. Their structures were elucidated based on extensive spectroscopic techniques including 1D, 2D NMR and HRESIMS data. Compounds 1 and 2 showed moderate cytotoxic activity against human leukemia cell line K562 and lung carcinoma cell line A549.


Asunto(s)
Macrólidos , Streptomyces , Antibacterianos/química , Dronabinol/análogos & derivados , Humanos , Macrólidos/química , Espectroscopía de Resonancia Magnética , Streptomyces/metabolismo
14.
Biochem Biophys Res Commun ; 630: 92-100, 2022 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-36152350

RESUMEN

PURPOSE: We aim to investigate the potential role and underlying mechanisms of linc00174 on pyroptosis in the pathogenesis of DR. METHODS: Expression patterns of linc00174, miR-26a-5p and PTEN in human retinal microvascular endothelial cells (hRMECs) were detected by quantitative real-time PCR (qRT-PCR) and Western blot, respectively. Biological functions of linc00174 on cell proliferation and pyroptosis were evaluated by CCK-8, flow cytometry, caspase-1 activity assays, respectively. Luciferase reporter assay was employed to verify the interaction between miR-26a-5p and linc00174/PTEN. Streptozotocin (STZ)-induced DR in mice was further constructed to verify the potential role of linc00174 in vivo. Hematoxylin and eosin (H&E) and immunohistochemical staining were performed to assess the pathological changes and caspase-1 expression in retinal tissues. RESULTS: Up-regulated linc00174 and PTEN and down-regulated miR-26a-5p were uncovered in hRMECs treated with high glucose (HG). Mechanistically, linc00174 served as a sponge of miR-26a-5p to facilitate PTEN expression. Functionally, knockdown of linc00174 inhibited HG-induced pyroptosis of hRMECs via targeting miR-26a-5p. Moreover, linc00174/miR-26a-5p axis participated in HG-induced pyroptosis via PTEN/Akt signaling cascade. Further, silencing of linc00174 attenuated pyroptosis via regulating miR-26a-5p/PETN axis in DR mice. CONCLUSIONS: Collectively, our study reveals that linc10074 deteriorates the pathogenesis of DR via miR-26a-5p/PTEN/Akt signalling cascade, which may shed light on the discovery of potential therapeutic agents for DR treatment.


Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , MicroARNs , Animales , Caspasas/metabolismo , Proliferación Celular , Diabetes Mellitus/metabolismo , Retinopatía Diabética/metabolismo , Células Endoteliales/metabolismo , Eosina Amarillenta-(YS)/metabolismo , Glucosa/metabolismo , Hematoxilina/metabolismo , Humanos , Ratones , MicroARNs/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Piroptosis , Sincalida/metabolismo , Estreptozocina
15.
World J Clin Cases ; 10(15): 4991-4997, 2022 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-35801038

RESUMEN

BACKGROUND: Paraganglioma occurring at the lateral skull base is a rare tumor. Surgery is the primary treatment of benign paragangliomas. Postoperative infection of the surgical site at the lateral skull base is very dangerous and hard to manage. CASE SUMMARY: A 30-year-old man with a 1-year history of left-side progressive hearing loss, tinnitus, facial palsy, and choking failed conventional treatment and is the focus of this case report. Imaging revealed a mass around the left jugular foramen that was approximately 47 mm × 38 mm × 34 mm in size and had eroded the bone of the vertebral and horizontal segments of the internal carotid artery. The tumor breached the meninges and occupied the cerebella pontine region. A two-stage surgery was designed for the resection of the mass. In the first-stage, the epidural portion of the mass was removed. The abdominal fat and the temporal muscle flap were transposed within the surgical site. The surgery was successful; however, 25 d after surgery, he developed suppurative parotitis, and the infection spread to the surgical site at the skull base. Broad-spectrum antibiotics were used, and debridement was deployed. After that, the wound was cleaned daily. Five months after the first-stage surgery, the wound was still unclosed, and there was intermittent purulent exudation within the surgical site. vacuum sealing drainage (VSD) was used, and the wound healed in a month. One year after the first surgery, the second-stage of the operation was performed to remove the intracranial portion of the tumor. Recurrence of the tumor was not detected after a 6-month follow-up. CONCLUSION: After a lateral skull base surgery, suppurative parotitis can spread into the operative cavity leading to infection of the surgical site. VSD can help to effectively heal the infected wound. A two-stage surgical approach offers a safer option for removing the lateral skull base paraganglioma that involves the meninges.

16.
Transl Lung Cancer Res ; 11(5): 832-844, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35693282

RESUMEN

Background: A paucity of strategies exist for extensive-stage small cell lung cancer (ES-SCLC) patients who fail the first-line chemotherapy. Apatinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor receptor-2 (VEGFR-2), which has been demonstrated to have active anti-tumor activity in ES-SCLC when used only or combined with PD-1 inhibitors or chemotherapy with good tolerance. However, the efficacy and safety of apatinib monotherapy is unclear in second-line or beyond treatment of ES-SCLC. Methods: In this prospective, exploratory, single-arm, multi-center study, eligible patients were aged 18 years or older with histologically confirmed ES-SCLC, and had progressed on, or were intolerant to previous systemic treatment. Patients received apatinib 500 mg (orally qd, every 4 weeks a cycle). The efficacy was assessed after 1 cycle and then every 2 cycles based on computed tomography imaging per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). The primary endpoint was progression-free survival (PFS). The adverse events (AEs) were assessed per the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 (NCI-CTCAE 4.0). This study is registered in the Chinese Clinical Trial Registry, number ChiCTR-OPC-17013964. Results: From 28 July 2017 to 21 June 2019, 62 patients were screened for eligibility, among whom 57 patients were available for efficacy and safety analysis. The objective response rate (ORR) was 14.3% and disease control rate (DCR) was 79.6%. The median PFS was 5.6 months [95% confidence interval (CI): 3.3-8.0 months] and the median overall survival (OS) was 11.2 months (95% CI: 7.5-24.0 months). Among the participants who received apatinib as second-line treatment, the median PFS and OS were 6.1 months (95% CI: 2.6-7.6 months) and 12.0 months (95% CI: 7.9 months to not reached), respectively. The most common AEs of all grades were anemia (36.8%), hypertension (33.3%), fatigue (31.6%), blood bilirubin increased (22.8%), elevated transaminase (19.3%), and hand-foot syndrome (17.54%). Grade 3 AEs included 2 (3.5%) cases of hypertension and 1 (1.8%) case of fatigue. No grade 4/5 AEs were observed. Conclusions: Apatinib showed encouraging anti-tumor activity in pretreated ES-SCLC patients with tolerable toxicities. Further larger scale studies are warranted to demonstrate the efficacy of apatinib.

17.
J Nat Prod ; 85(4): 1167-1173, 2022 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-35213166

RESUMEN

A chemical investigation of Streptomyces sp. Hu186 afforded two known quinone antibiotics, sarubicin A (1) and sarubicin B (2), together with three unusual variants, sarubicinols A-C (3-5), and two new 1,4-naphthoquinone metabolites, sarubicin B1 (6) and sarubicin B2 (7). Compounds 3-5 possess a rare 2-oxabicyclo [2.2.2] substructure and a benzoxazole ring system. Their structures were elucidated using 1D and 2D nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data. The absolute configurations of the side-chain moieties in 4 and 5 were solved by electronic circular dichroism calculations. Compounds 1-7 showed moderate cytotoxic activity against four tumor cell lines.


Asunto(s)
Antineoplásicos , Streptomyces , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Benzoxazoles/farmacología , Línea Celular Tumoral , Estructura Molecular , Espectrometría de Masa por Ionización de Electrospray , Streptomyces/química
18.
Nat Prod Res ; 36(1): 482-487, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32586138

RESUMEN

Two new threonine-containing metabolites, N-[4-hydroxy-3-prenyl-benzoyl]-L-threonine (1) and N-[2,2-dimethyl-2H-chromene-6-carbonyl]-L-threonine (2), were isolated from the fermentation broth of the soil fungus Curvularia inaequalis strain HS-FG-257. Their structures were elucidated through the interpretation of HR-ESIMS and extensive NMR spectroscopic data. Both compounds exhibited no cytotoxic activity against the test cell lines A549 and HCT-116.


Asunto(s)
Antineoplásicos , Treonina , Curvularia , Espectroscopía de Resonancia Magnética
19.
Biochim Biophys Acta Rev Cancer ; 1876(2): 188629, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34610420

RESUMEN

Lung cancer is caused by several environmental and genetic variables and is globally associated with elevated morbidity and mortality. Among these variables, membrane-bound ion channels have a key role in regulating multiple signaling pathways in tumor cells and dysregulation of ion channel expression and function is closely related to proliferation, migration, and metastasis of lung cancer. This work reviews and summarizes current knowledge about the role of ion channels in lung cancer, focusing on the changes in the expression and function of various ion channels in lung cancer and how these changes affect lung cancer cell biology both in vitro and in vivo as evidenced by both genetic and pharmacological studies. It can help understand the molecular mechanisms of various ion channels influencing the initiation and progression of lung cancer and shed new insights into their roles in the development and treatment of this deadly disease.


Asunto(s)
Canales Iónicos/metabolismo , Neoplasias Pulmonares/terapia , Proliferación Celular , Humanos , Neoplasias Pulmonares/genética , Invasividad Neoplásica
20.
Hematology ; 26(1): 734-740, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34555308

RESUMEN

Objectives: Immune thrombocytopenia (ITP) is an autoimmune disease. T helper cell 17 (Th17) cells are increased in peripheral blood of ITP patients. NOTCH signaling is involved in Th17 cell differentiation and function. Besides, lncRNA Plasmacytoma variant translocation 1 (PVT1) was decreased in experimental autoimmune encephalomyelitis, and overexpressing PVT1 inhibited Th17 cell differentiation. Here, we aimed to investigate the effect of lncRNA PVT1 on ITP and its related mechanism.Methods: The number of Th17 cells and Treg cells was carried out using flow cytometry. PVT1 levels were detected by quantitative real-time PCR. Interleukin-17 (IL-17) levels and transforming growth factor-ß (TGF-ß) levels were detected by enzyme-linked immunosorbent assay. Protein levels of retinoid acid-related orphan receptor γ t (RORγt), forkhead box P3 (Foxp3), and NOTCH1 were carried out by western blot. NOTCH1 ubiquitylation was detected by ubiquitination assay.Results: PVT1 was down-regulated and Th17 cells were up-regulated in ITP patients. Overexpression of PVT1 decreased the number of Th17 cells, and also decreased the levels of IL-17, RORγt, and NOTCH1. Besides, PVT1 could bind to NOTCH1 and mediated NOTCH1 degradation by increasing its ubiquitination. Additionally, excessive expression of PVT1 could increase the levels of PVT1, reduce the amount of Th17 cells, as well as the levels of IL-17, RORγt, and NOTCH1, while co-overexpressing NOTCH1 reversed the results.Conclusion: PVT1 was down-regulated in ITP patients. Overexpressing PVT1 might reduce Th17 cell differentiation by down-regulating NOTCH1, and further alleviated the development of ITP.


Asunto(s)
Púrpura Trombocitopénica Idiopática/genética , ARN Largo no Codificante/genética , Receptores Notch/metabolismo , Linfocitos T Reguladores/patología , Células Th17/patología , Células Cultivadas , Regulación hacia Abajo , Humanos , Púrpura Trombocitopénica Idiopática/metabolismo , Púrpura Trombocitopénica Idiopática/patología , Transducción de Señal , Linfocitos T Reguladores/metabolismo , Células Th17/metabolismo
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