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MYC is a highly pleiotropic transcription factor whose deregulation promotes cancer. In contrast, we find that Myc haploinsufficient (Myc(+/-)) mice exhibit increased lifespan. They show resistance to several age-associated pathologies, including osteoporosis, cardiac fibrosis, and immunosenescence. They also appear to be more active, with a higher metabolic rate and healthier lipid metabolism. Transcriptomic analysis reveals a gene expression signature enriched for metabolic and immune processes. The ancestral role of MYC as a regulator of ribosome biogenesis is reflected in reduced protein translation, which is inversely correlated with longevity. We also observe changes in nutrient and energy sensing pathways, including reduced serum IGF-1, increased AMPK activity, and decreased AKT, TOR, and S6K activities. In contrast to observations in other longevity models, Myc(+/-) mice do not show improvements in stress management pathways. Our findings indicate that MYC activity has a significant impact on longevity and multiple aspects of mammalian healthspan.
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Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Envejecimiento , Animales , Tamaño Corporal , Femenino , Longevidad , Linfoma/genética , Masculino , Redes y Vías Metabólicas , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , TranscriptomaRESUMEN
Circular RNAs (circRNAs) have been revealed to be involved in the pathology of acute ischemic stroke (AIS). Herein, we aimed to study the role and mechanism of circNCOA4 in ischemic stroke. The neuron-like cell line SK-N-SH of the experiment group was cultured in oxygen-glucose deprivation (OGD) condition. Cell viability and apoptosis were evaluated by cell counting kit-8 and flow cytometry. The oxidative damage and endoplasmic reticulum stress (ERS) were analyzed by measuring the production of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and ERS-related markers. The binding between miR-338-5p and circNCOA4 or PDE4B (Phosphodiesterase 4B) was confirmed using dual-luciferase reporter and RIP assays. The commercial kit was used for exosome separation. The levels of circNCOA4 and PDE4B were increased, while miR-338-5p expression was decreased by OGD stimulation. OGD stimulation resulted in the apoptosis of neurons and induced oxidative damage and ERS, these effects were attenuated by circNCOA4 knockdown, while reinforced by circNCOA4 overexpression. Mechanistically, circNCOA4 acted as a sponge for miR-338-5p, and PDE4B was a target of miR-338-5p. MiR-338-5p inhibition reversed the neuroprotective effects of circNCOA4 silencing on neurons. Besides, miR-338-5p overexpression could abolish OGD-induced neuron injury, which was reversed by PDE4B upregulation. In addition, circNCOA4 was packaged into exosomes and showed potential diagnostic value for acute ischemic stroke (AIS) patients. CircNCOA4 has potential diagnostic value for AIS patients and promoted OGD-induced neuron injury via the miR-338-5p/PDE4B axis, providing a new insight into the pathology of AIS.
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Accidente Cerebrovascular Isquémico , MicroARNs , Humanos , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/genética , Apoptosis , Glucosa , MicroARNs/genéticaRESUMEN
Ceramic membranes have the advantages of high mechanical strength and thermal stability and are promising candidates for membrane distillation. Ceramic membranes are generally designed to have a multilayer structure with different pore sizes to create a high liquid entry pressure and obtain a high permeability. However, these structural characteristics pose significant difficulties in predicting permeate flux in a ceramic membrane contactor for vacuum membrane distillation (VMD). Here, a modeling approach was developed to simulate the VMD process and verified by comparing the simulated results with the experimental data. Furthermore, correlations are proposed to simplify the calculations of permeate flux for VMD using asymmetric ceramic membranes by assuming those multilayers to be an effectively quasi-symmetric layer and by introducing a correction factor. The simulation results indicated that this simplified correlation was effective and enabled a quick estimation of the effect of membrane parameters on permeate flux.
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Although tenascin-C (TNC), an extracellular matrix protein, has been shown to be widely expressed in stromal fibroblasts in various cancers, the role of its expression in esophageal squamous cell carcinoma (ESCC) cells remains unclear. Using immunohistochemistry, we investigated the expression of cancer stem-like cell (CSC) markers, epithelial-to-mesenchymal transition (EMT)-related genes, and the Akt/hypoxia-inducible factor-1α (HIF1α) signal pathway in ESCC tissue specimens from 154 patients. We further addressed the effects of TNC on the Akt/HIF1α axis and its putative association with cancer stemness in several ESCC cell lines by immunofluorescence imaging and western blot analysis. Our data suggest that TNC expression was positively correlated with the expression of the CSC marker SOX2 (pâ¯=â¯.002), and TNC-expressing cancer cells expressed SOX2 in ESCC tissues. Moreover, TNC expression was strongly associated with EMT-related gene Snail (pâ¯=â¯.022) and positively correlated with pAkt-Ser473 (pâ¯=â¯.004) and HIF1α (pâ¯=â¯.003). Furthermore, TNC-silencing down-regulated the expression of CSC marker SOX2 (pâ¯<â¯.001) and EMT-related marker Snail (pâ¯<â¯.001). The Akt inhibitor Perifosine inhibited the protein expression of pAkt-Ser473, Akt, HIF1α, and TNC in TE10 (an ESCC cell line) cells. Short-term exposure of TE10 cells to cobalt chloride caused an increase in protein expression of HIF1α, TNC, and SOX2 in a time-dependent manner. Taken together, these results suggest that TNC may enhance the cancer stem-like properties and promote EMT-like changes via the Akt/HIF1α axis.
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Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Células Madre Neoplásicas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Tenascina/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Supervivencia sin Enfermedad , Transición Epitelial-Mesenquimal/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Células Madre Neoplásicas/patología , Interferencia de ARN , Transducción de Señal , Tenascina/genéticaRESUMEN
The role of Hedgehog (HH)/ glioma-associated oncogene homolog 1 (GLI1) pathway has been implicated in a variety of cancer entities, and the targeted pathway inhibition mediated by GLI1 is of therapeutic relevance. However, its oncogenicity and cross-talks with other cancer pathways including PI3K/Akt/NFκB, which modulates the HH/GLI1 signal strength, have rarely been explored in colorectal adenocarcinoma. We assessed the expression of GLI1 and its relationship with other cancer stemness genes, cell cycle markers, epithelial-mesenchymal transition (EMT), PI3K/Akt/NFκB signaling pathway genes, and HIF1α in 100 paraffin-embedded colorectal adenocarcinoma tissue samples using immunohistochemistry. We further addressed the effect of GLI1 on EMT, cell cycle, and its putative interaction with the PI3K/Akt/NFκB cascade in colorectal adenocarcinoma cell lines. The expression of GLI1 in colorectal adenocarcinoma tissues was found to correlate with the clinical stages, and distant metastasis. Moreover, GLI1 was found to be an independent predictor of poor overall survival and disease-free survival in colorectal adenocarcinoma. GLI1-expressing cancer cells also expressed their representative cancer stem-like cell (CSC) markers (SOX9 and CD133), as well as HIF1α. GLI1 expression was also strongly linked to EMT-related and PI3K/Akt/NFκB signaling genes. Downregulation of GLI1 by inhibitor treatment in colorectal adenocarcinoma cell lines resulted in reduced expression of CSC markers, cell clonogenicity, S-phase subpopulations, as well as the migration and invasion ability. Importantly, Akt inhibitor Perifosine significantly inhibited the expression of pAkt and GLI1 in colorectal adenocarcinoma cells. Combination of GLI1 inhibitor GANT61 and NFκB p65 inhibitor QZN exhibited much higher inhibition compared to using any of them individually on colorectal adenocarcinoma cells. We suggested that GLI1 may be a novel stem cell marker, and cancer stemness was activated via PI3K/Akt/NFκB pathway. In addition, co-targeting GLI1 and PI3K/Akt/NFκB signaling simultaneously might provide an alternative therapeutic strategy for colorectal adenocarcinoma patients.
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Adenocarcinoma/metabolismo , Neoplasias Colorrectales/metabolismo , Células Madre Neoplásicas/metabolismo , Transducción de Señal , Proteína con Dedos de Zinc GLI1/metabolismo , Adenocarcinoma/enzimología , Adenocarcinoma/patología , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal , Femenino , Humanos , Masculino , Persona de Mediana Edad , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Although Tenascin-C (TNC) as an extracellular matrix protein involved in various cancers, the mechanisms by which TNC leads to decreased survival time remain to be clarified in CRC. We assessed the expression of TNC and its relationship with cancer associated fibroblasts (CAFs) markers, epithelial-to-mesenchymal transition (EMT) and cell cycle markers in 100 paraffin-embedded CRC tissue samples using immunohistochemistry. TNC expression was higher in CRC tissue samples than in adjacent non-tumor-tissues (Pâ¯<â¯.001). In addition, TNC was involved in clinical stage (Pâ¯=â¯.030), pT stage (Pâ¯=â¯.049), distant metastasis (Pâ¯=â¯.004), tumor recurrence (Pâ¯=â¯.007), and tumor budding (Pâ¯<â¯.001). TNC play crucial roles in regulating the poor 5-year CRC survival rate by Kaplan-Meier analysis, and was an independent predictor of poor overall survival (Pâ¯=â¯.007) and disease-free survival (Pâ¯=â¯.004) in CRC. Moreover, it was postively correlated with CAF (SMA (Pâ¯<â¯.001) and FSP1 (Pâ¯=â¯.005)) and cell cycle marker p27 (Pâ¯=â¯.013) along with EMT (E-cadherin, Pâ¯=â¯.599; Snail, Pâ¯<â¯.001; vimentin, Pâ¯=â¯.012). TNC may promote EMT-like change and proliferation, which lead to poor prognosis for patients with CRC.
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Neoplasias Colorrectales/genética , Tenascina/metabolismo , Adulto , Anciano , Biomarcadores de Tumor , Cadherinas/metabolismo , Proliferación Celular/genética , China , Neoplasias del Colon/metabolismo , Neoplasias Colorrectales/metabolismo , Supervivencia sin Enfermedad , Transición Epitelial-Mesenquimal/genética , Matriz Extracelular/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Fibroblastos , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Pronóstico , Tenascina/análisis , Tenascina/genéticaRESUMEN
Calorie restriction (CR), a reduction of 1040% in intake of a nutritious diet, is often reported as the most robust non-genetic mechanism to extend lifespan and healthspan. CR is frequently used as a tool to understand mechanisms behind ageing and age-associated diseases. In addition to and independently of increasing lifespan, CR has been reported to delay or prevent the occurrence of many chronic diseases in a variety of animals. Beneficial effects of CR on outcomes such as immune function, motor coordination and resistance to sarcopenia in rhesus monkeys have recently been reported. We report here that a CR regimen implemented in young and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes. Our findings contrast with an ongoing study at the Wisconsin National Primate Research Center (WNPRC), which reported improved survival associated with 30% CR initiated in adult rhesus monkeys (714 years) and a preliminary report with a small number of CR monkeys. Over the years, both NIA and WNPRC have extensively documented beneficial health effects of CR in these two apparently parallel studies. The implications of the WNPRC findings were important as they extended CR findings beyond the laboratory rodent and to a long-lived primate. Our study suggests a separation between health effects, morbidity and mortality, and similar to what has been shown in rodents, study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate.
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Envejecimiento/fisiología , Restricción Calórica , Salud , Longevidad/fisiología , National Institute on Aging (U.S.) , Edad de Inicio , Animales , Glucemia/análisis , Enfermedades Cardiovasculares/sangre , Colesterol/sangre , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Macaca mulatta , Masculino , Modelos Animales , Enfermedades de los Monos/sangre , Neoplasias/sangre , Tasa de Supervivencia , Triglicéridos/sangre , Incertidumbre , Estados UnidosRESUMEN
ABSTRACT: Recent evidence suggests that low-intensity extracorporeal shock wave therapy (Li-ESWT) is a promising treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); however, its safety in pelvic organs, particularly prostate tissues and cells, remains unclear. The current study evaluates the risks of prostate cell damage or oncogenesis following the administration of Li-ESWT for prostatitis. To this end, a robust in vitro model (Cell Counting Kit-8 [CCK-8] assay, clone formation assay, cell scratch assay, lactate dehydrogenase [LDH] release assay, flow cytometry, and immunoblotting assay) was designed to examine the effects of Li-ESWT on cell proliferation, clonogenicity, migration, membrane integrity, and DNA damage. Exome sequencing of Li-ESWT-treated cells was performed to determine the risk of carcinogenesis. Furthermore, an in vivo rat model (n = 20) was employed to assess the effects of Li-ESWT on cancer biomarkers (carcinoembryonic antigen [CEA], Ki67, proliferating cell nuclear antigen [PCNA], and gamma-H2A histone family member X, phosphorylation of the H2AX Ser-139 [γ-H2AX]) in prostate tissue. Based on our findings, Li-ESWT promotes cellular growth and motility without inducing significant cell membrane or DNA damage or alterations. Genetic analyses did not demonstrate an increase in mutations, and no damage to prostate tissue or upregulation of cancer biomarkers was detected in vivo. This comprehensive in vitro and in vivo assessment confirms the safety of Li-ESWT in managing prostate disorders.
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The development of insulin resistance is the primary step in the etiology of type 2 diabetes mellitus. There are several risk factors associated with insulin resistance, yet the basic biological mechanisms that promote its development are still unclear. There is growing literature that suggests mitochondrial dysfunction and/or oxidative stress play prominent roles in defects in glucose metabolism. Here, we tested whether increased expression of CuZn-superoxide dismutase (Sod1) or Mn-superoxide dismutase (Sod2) prevented obesity-induced changes in oxidative stress and metabolism. Both Sod1 and Sod2 overexpressing mice were protected from high fat diet-induced glucose intolerance. Lipid oxidation (F2-isoprostanes) was significantly increased in muscle and adipose with high fat feeding. Mice with increased expression of either Sod1 or Sod2 showed a significant reduction in this oxidative damage. Surprisingly, mitochondria from the muscle of high fat diet-fed mice showed no significant alteration in function. Together, our data suggest that targeting reduced oxidative damage in general may be a more applicable therapeutic target to prevent insulin resistance than is improving mitochondrial function.
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Grasas de la Dieta/efectos adversos , Mitocondrias/metabolismo , Obesidad/enzimología , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Animales , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Obesidad/patología , Superóxido Dismutasa/genética , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Comparing biological processes in closely related species with divergent life spans is a powerful approach to study mechanisms of aging. The oxidative stress hypothesis of aging predicts that longer-lived species would have lower reactive oxygen species (ROS) generation and/or an increased antioxidant capacity, resulting in reduced oxidative damage with age than in shorter-lived species. In this study, we measured ROS generation in the young adult animals of the long-lived white-footed mouse, Peromyscus leucopus (maximal life span potential, MLSP = 8 yr) and the common laboratory mouse, Mus musculus (C57BL/6J strain; MLSP = 3.5 yr). Consistent with the hypothesis, our results show that skeletal muscle mitochondria from adult P. leucopus produce less ROS (superoxide and hydrogen peroxide) compared with M. musculus. Additionally, P. leucopus has an increase in the activity of antioxidant enzymes superoxide dismutase 1, catalase, and glutathione peroxidase 1 at young age. P. leucopus compared with M. musculus display low levels of lipid peroxidation (isoprostanes) throughout life; however, P. leucopus although having elevated protein carbonyls at a young age, the accrual of protein oxidation with age is minimal in contrast to the linear increase in M. musculus. Altogether, the results from young animals are in agreement with the predictions of the oxidative stress hypothesis of aging with the exception of protein carbonyls. Nonetheless, the age-dependent increase in protein carbonyls is more pronounced in short-lived M. musculus, which supports enhanced protein homeostasis in long-lived P. leucopus.
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Envejecimiento/metabolismo , Antioxidantes/metabolismo , Mitocondrias/metabolismo , Músculo Esquelético/metabolismo , Estrés Oxidativo/fisiología , Envejecimiento/patología , Animales , Metabolismo Basal/fisiología , Composición Corporal/fisiología , Catalasa/metabolismo , Complejo I de Transporte de Electrón/metabolismo , Complejo II de Transporte de Electrones/metabolismo , Complejo III de Transporte de Electrones/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Femenino , Glutatión Peroxidasa/metabolismo , Glucólisis/fisiología , Longevidad/fisiología , Ratones , Ratones Endogámicos C57BL , Mitocondrias/enzimología , Fibras Musculares Esqueléticas/enzimología , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patología , Músculo Esquelético/enzimología , Músculo Esquelético/patología , Peromyscus , Especies Reactivas de Oxígeno/metabolismo , Especificidad de la Especie , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa-1 , Glutatión Peroxidasa GPX1RESUMEN
It was investigated whether a standard mouse diet (AIN-76A) supplemented with walnuts reduced the establishment and growth of LNCaP human prostate cancer cells in nude (nu/nu) mice. The walnut-enriched diet reduced the number of tumors and the growth of the LNCaP xenografts; 3 of 16 (18.7%) of the walnut-fed mice developed tumors; conversely, 14 of 32 mice (44.0%) of the control diet-fed animals developed tumors. Similarly, the xenografts in the walnut-fed animals grew more slowly than those in the control diet mice. The final average tumor size in the walnut-diet animals was roughly one-fourth the average size of the prostate tumors in the mice that ate the control diet.
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Adenocarcinoma/tratamiento farmacológico , Antineoplásicos Fitogénicos/administración & dosificación , Juglans , Preparaciones de Plantas/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Animales , Línea Celular Tumoral , F2-Isoprostanos/metabolismo , Humanos , Peroxidación de Lípido , Hígado/metabolismo , Masculino , Ratones , Ratones Desnudos , Estrés Oxidativo , Fitoterapia , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Carga Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Studies on the relationship between thyroid stimulating hormone (TSH) within the reference range and coronary artery disease (CAD) have produced conflicting results. Furthermore, the effect of age on this relationship has never been explored. The aim of this study was to investigate the association between TSH levels and CAD among euthyroid subjects and whether age influenced this relationship. A total of 318 subjects who underwent coronary angiography were included. Serum TSH, T3, T4, lipid, blood glucose and creatinine levels were measured and compared between the groups with and without CAD. Age-stratified analysis and multivariate logistic regression analysis were performed. Levels of TSH, T3 and T4 did not differ significantly between CAD (n=196) and non-CAD group (n=122) (TSH: 1.77 ± 0.99 vs 1.89 ± 0.98 mIU/L, T3: 1.45 ± 0.36 vs 1.51 ± 0.35 nmol/L, T4: 100.06 ± 20.49 vs 103.95 ± 24.06 nmol/L, respectively) when comparisons were performed among all subjects. A significant between-group difference in levels of TSH was observed among subjects less than or equal to 65 years old (CAD group: n=121, non-CAD group: n=106), with higher TSH levels in CAD group (2.03 ± 0.94 vs 1.75 ± 0.97 mIU/L, adjusted p=0.024). Multivariate logistic regression analysis revealed that elevated level of TSH was an independent predictor for CAD (odds ratio: 1.512, p=0.011). No significant between-group difference in TSH levels was observed among subjects older than 65 years (CAD group: n=75, non-CAD group: n=16). The results showed that higher levels of TSH within the reference range were independently associated with the presence of CAD only among subjects less than or equal to 65 years old, suggesting age might influence the relationship.
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Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/epidemiología , Tirotropina/sangre , Adulto , Factores de Edad , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Factores de Riesgo , Pruebas de Función de la Tiroides/normasRESUMEN
Breast tumor segmentation of ultrasound images provides valuable information of tumors for early detection and diagnosis. Accurate segmentation is challenging due to low image contrast between areas of interest; speckle noises, and large inter-subject variations in tumor shape and size. This paper proposes a novel Multi-scale Dynamic Fusion Network (MDF-Net) for breast ultrasound tumor segmentation. It employs a two-stage end-to-end architecture with a trunk sub-network for multiscale feature selection and a structurally optimized refinement sub-network for mitigating impairments such as noise and inter-subject variation via better feature exploration and fusion. The trunk network is extended from UNet++ with a simplified skip pathway structure to connect the features between adjacent scales. Moreover, deep supervision at all scales, instead of at the finest scale in UNet++, is proposed to extract more discriminative features and mitigate errors from speckle noise via a hybrid loss function. Unlike previous works, the first stage is linked to a loss function of the second stage so that both the preliminary segmentations and refinement subnetworks can be refined together at training. The refinement sub-network utilizes a structurally optimized MDF mechanism to integrate preliminary segmentation information (capturing general tumor shape and size) at coarse scales and explores inter-subject variation information at finer scales. Experimental results from two public datasets show that the proposed method achieves better Dice and other scores over state-of-the-art methods. Qualitative analysis also indicates that our proposed network is more robust to tumor size/shapes, speckle noise and heavy posterior shadows along tumor boundaries. An optional post-processing step is also proposed to facilitate users in mitigating segmentation artifacts. The efficiency of the proposed network is also illustrated on the "Electron Microscopy neural structures segmentation dataset". It outperforms a state-of-the-art algorithm based on UNet-2022 with simpler settings. This indicates the advantages of our MDF-Nets in other challenging image segmentation tasks with small to medium data sizes.
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Algoritmos , Neoplasias de la Mama , Humanos , Femenino , Ultrasonografía , Artefactos , Neoplasias de la Mama/diagnóstico por imagenRESUMEN
Background: Lung cancer is a major public health issue and an enormous burden on society in China. Most lung cancers occur in elderly patients with non-small cell lung cancer (NSCLC), and many factors limit their treatment options. Chemotherapy-free therapy can avoid psychological fear, treatment pain, and adverse reactions caused by chemotherapy. Patients with non-small cell lung cancer with tumour protein p53 (TP53) gene mutations or Kirsten rat sarcoma viral oncogene homologue (KRAS) gene mutations tend to be more sensitive to anlotinib or programmed cell death protein 1 (PD-1) drugs. However, Kirsten rat sarcoma viral oncogene homologue is a proto-oncogene downstream of the epidermal growth factor receptor (EGFR) gene; therefore, if the Kirsten rat sarcoma viral oncogene homologue gene has an activating mutation, EGFR-targeted drug resistance may occur. Further studies are needed to explore whether patients with dual Kirsten rat sarcoma viral oncogene homologue and tumour protein p53 mutations can be treated with targeted immunotherapy without chemotherapy. Case presentation: A 74-year-old man was referred to the Lanzhou University Second Hospital due to chest tightness, shortness of breath, and weight loss for 2 months and was diagnosed with moderately to poorly differentiated adenocarcinoma. Laboratory examinations showed increased alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA)-125, and CA199 levels, and gene sequencing indicated mutations in Kirsten rat sarcoma viral oncogene homologue and tumour protein p53. Immunohistochemical analysis showed positive PD-L1 and PD-1 expression. Peripheral blood immune checkpoint test using flow cytometry indicated that the PD-1 + CD8 levels were positive. After multi-disciplinary treatment, therapy with a combination of anlotinib and camrelizumab was initiated. Camrelizumab 200 mg was administered intravenously once every 3 weeks. Anlotinib 12 mg was administered orally daily before breakfast for 2 weeks with a week of rest in every cycle of 21 days. A reduction in alpha-fetoprotein, carcinoembryonic antigen, CA125, CA199, and CA724 levels was observed up to the first cycle, which decreased within the normal limits up to the second cycle and continued until the eighteenth cycle. The patient's chest tightness, shortness of breath, weight loss, and other symptoms significantly improved following treatment. Computed tomography imaging showed that the neoplastic lesion was dramatically reduced. The patient is currently being followed-up for more than 2 years to evaluate the duration of the response. Conclusion: Chemotherapy-free immunotherapy combined with targeted therapy is an effective treatment for advanced non-small cell lung cancer in elderly patients with Kirsten rat sarcoma viral oncogene homologue and tumour protein p53 mutations. Such therapies should be supported with further clinical studies with larger sample sizes.
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OBJECTIVE: There is a high burden of both diabetes (DM) and tuberculosis (TB) in China, and as DM increases the risk of TB and adversely affects TB treatment outcomes, there is a need for bidirectional screening of the two diseases. How this is best performed is not well determined. In this pilot project in China, we aimed to assess the feasibility and results of screening DM patients for TB within the routine healthcare setting of five DM clinics. METHOD: Agreement on how to screen, monitor and record was reached in May 2011 at a national stakeholders meeting, and training was carried out for staff in the five clinics in July 2011. Implementation started in September 2011, and we report on 7 months of activities up to 31 March 2012. DM patients were screened for TB at each clinic attendance using a symptom-based enquiry, and those positive to any symptom were referred for TB investigations. RESULTS: In the three quarters, 72% of 3174 patients, 79% of 7196 patients and 68% of 4972 patients were recorded as having been screened for TB, resulting in 7 patients found who were already known to have TB, 92 with a positive TB symptom screen and 48 of these newly diagnosed with TB as a result of referral and investigation. All patients except one were started on anti-TB treatment. TB case notification rates in screened DM patients were several times higher than those of the general population, were highest for the five sites combined in the final quarter (774/100 000) and were highest in one of the five clinics in the final quarter (804/100 000) where there was intensive in-house training, special assignment of staff for screening and colocation of services. CONCLUSION: This pilot project shows that it is feasible to carry out screening of DM patients for TB resulting in high detection rates of TB. This has major public health and patient-related implications.
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Complicaciones de la Diabetes/diagnóstico , Diabetes Mellitus/diagnóstico , Tamizaje Masivo/métodos , Tuberculosis/diagnóstico , Adolescente , Adulto , Instituciones de Atención Ambulatoria , China/epidemiología , Complicaciones de la Diabetes/epidemiología , Humanos , Proyectos Piloto , Prevalencia , Derivación y Consulta , Tuberculosis/complicaciones , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiologíaRESUMEN
Charcot arthropathy of the shoulder joint is usually referred to as shoulder joint involvement of Charcot arthropathy, which is a chronic, degenerative, destructive condition resulting from decreasing or loss of sensorial innervation. To date, several reports have described the shoulder Charcot arthropathy, caused by malformations of the occipital region with syringomyelia; but nobody has reported the shoulder Charcot arthropathy secondary to hemangioblastoma in conus medullari with syringomyelia. Therefore, we report a 32-year male patient who was diagnosed with Charcot arthropathy of the shoulder joint, which was misdiagnosed as a soft tissue tumor and treated surgically. After the operation, the whole-spine MRI examination was performed as a presenting feature of hemangioblastoma in conus medullari with syringomyelia. Key Words: Arthropathy, Neurogenic, Hemangioblastoma, Syringomyelia.
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Artropatía Neurógena , Hemangioblastoma , Siringomielia , Artropatía Neurógena/diagnóstico , Artropatía Neurógena/etiología , Artropatía Neurógena/cirugía , Hemangioblastoma/complicaciones , Humanos , Masculino , Hombro , Siringomielia/complicaciones , Siringomielia/diagnóstico , Siringomielia/cirugíaRESUMEN
Background: Colorectal cancer (CRC) is a common cancer and has a poor prognosis. The coagulation system and fibrinolysis system are closely related to the progression of malignant tumors and is also related to the immunotherapy of malignant tumors. Herein, we tried to predict survival and the immunotherapy effect for patients with CRC using a novel potential prognostic model. Methods: Through online data of TCGA and GEO, we screened significantly differentially expressed genes (DEGs) to construct a prognostic model, followed by obtaining immune-related genes (IRGs) from the ImmPort database and coagulation- and fibrinolysis-related genes (CFRGs) from the GeneCards database. The predictive power of the model is assessed by Kaplan-Meier survival curves as well as the time-dependent ROC curve. Moreover, univariate and multivariate analyses were conducted for OS using Cox regression models, and the nomogram prognostic model was built. In the end, we further studied the possibility that CXCL8 was associated with immunocyte infiltration or immunotherapy effect and identified it by immunohistochemistry and Western blot. Results: Five DEGs (CXCL8, MMP12, GDF15, SPP1, and NR3C2) were identified as being prognostic for CRC and were selected to establish the prognostic model. Expression of these genes was confirmed in CRC samples using RT-qPCR. Notably, those selected genes, both CFRGs and IRGs, can accurately predict the OS of CRC patients. Furthermore, CXCL8 is highly correlated with the tumor microenvironment and immunotherapy response in CRC. Conclusion: Overall, our established IRGPI can very accurately predict the OS of CRC patients. CXCL8 reflects the immune microenvironment and reveals the correlation with immune checkpoints among CRC patients.
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Neoplasias Colorrectales , Fibrinólisis , Humanos , Coagulación Sanguínea , Inmunoterapia , Microambiente Tumoral/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapiaRESUMEN
Accurate assessment of the tumour immune microenvironment promotes individualized immunotherapy regimens and screens dominant populations suitable for immunotherapy. Therefore, potential molecular markers were investigated to make an overall assessment of the immune microenvironment status of liver hepatocellular carcinoma (LIHC). In this study, a total of 121 differentially expressed genes (DEGs) were identified, and DEGs were enriched in the epithelial-mesenchymal transition, hypoxia, myogenesis, and p53 pathways. A total of 20 hub genes were selected and a strong correlation was identified between these hub genes and prognosis. The expression of budding uninhibited by benzimidazoles 1 (BUB1) was found to be upregulated in LIHC and was strongly related to immune cells and immune checkpoint molecule expression. Immunohistochemistry (IHC) indicated that BUB1 expression was higher in LIHC tissues than in normal liver tissues. BUB1 knockdown resulted in reduced proliferation and vertical migration ability of LIHC cells, and reduced the expression of phospho-SMAD family member 2 and phospho-SMAD family member 3 proteins. IHC showed that BUB1 expression was accompanied by immune cell infiltration into LIHC tissues. These results suggest that BUB1 may serve as a potential prognostic biomarker for LIHC and as an indicator of its immune status.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas Serina-Treonina Quinasas , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Transición Epitelial-Mesenquimal , Humanos , Inmunoterapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Pronóstico , Proteínas Serina-Treonina Quinasas/genética , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: The outbreak of COVID-19 has undoubtedly influenced the normal lifestyle of people worldwide, including the Chinese population. This study attempted to do supplementary research to the current situation of loneliness as well as the related risk factors among the elderly in the province in central Chinese during the COVID-19. METHODS: We conducted a cross-sectional study in one of the central Chinese provinces (Henan Province) from December 2020 to March 2021 using a multistage sampling method, and 568 elderly people without cognitive impairment were interviewed. The UCLA Loneliness Scale, Pittsburgh Sleep Quality Index (PSQI), Physical Activity Rating Scale (PARS-3), and Quality of Life Questionnaire SF-36 were adopted to collect information. We used univariate and multivariate logistic regressions to analyze the factors resulting in severe loneliness among the elderly with seldom or regular participation in physical exercises. RESULTS: During the epidemic in central China, the elderly suffering from loneliness syndrome accounted for 34.2%, of which 15.5% were severely lonely. Risk factors for severe loneliness were quality of life (OR: 7.129), sleep quality (OR: 3.778), seldom exercise (OR: 4.170), poor economic status (OR: 1.769), and negative attitude toward the prospects for the epidemic control (OR: 4.033). By grouping the participants in terms of physical activity, we found that the quality of life (OR:5.778) was a significant risk factor than sleep quality (OR:2.939) in the seldom exercise group, while the only risk factor in the regular exercise group was the quality of life (OR: 5.021). CONCLUSION: There was an increase in the degree of loneliness among the elderly during the epidemic, and physical activity played an active role in relieving the severe loneliness of the elderly. Therefore, for the sake of the elderly, regular participation in physical exercises should be encouraged during the duration of the epidemic.
RESUMEN
Chemotherapeutic drugs play an important role in the treatment of cancer, but the individual differences of patients' sensitivity to chemotherapeutic drugs and the drug resistance of chemotherapeutic drugs have always been a thorny problem in clinical treatment. In recent years, with the progress in research on human microbiota, gut microbiome plays an increasingly important role in the diagnosis and treatment of diseases. Studies have shown that gut microbiota can regulate the tumour microenvironment and affect the efficacy and toxicity of chemotherapy through a variety of mechanisms. This paper focuses on the specific mechanism that gut microbiota uses to influence chemotherapy and the potential therapeutic effect of supplementing with probiotics, to provide an important basis for individualised treatment strategies to be used when treating malignant tumours.