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1.
Artigo em Inglês | MEDLINE | ID: mdl-38723979
4.
Orthop Surg ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38784971

RESUMO

OBJECTIVE: AO/OTA 31-A3.3 intertrochanteric fracture is the most unstable type of intertrochanteric fracture, with a high rate of postoperative complications and implant failure. We have designed a new intramedullary fixation, proximal femoral totally bionic nail (PFTBN), for the treatment of A3.3 intertrochanteric fracture. To test its biomechanical performance, we adopted the method of finite element analysis and compared PFTBN with proximal femoral nail antirotation (PFNA) and proximal femoral bionic nail (PFBN, another internal fixation we previously designed for stable intertrochanteric fractures). METHODS: Mimics, 3-matic, ANSYS, and other software were used to construct a highly precise and realistic 3D digital model of the human femur. An AO/OTA 31-A3.3 intertrochanteric fracture of the femur was constructed according to the 2018 classification of AO/OTA, and then assembled with PFNA, PFBN and PFTBN models, respectively. The stress distribution and displacement distribution of the three groups of constructs were tested under three times the body weight load and one-foot standing configuration. RESULTS: In terms of maximum stress and maximum displacement, the PFTBN group outperforms the PFBN group, and the PFBN group, in turn, surpasses the PFNA group. The maximum stress of PFTBN group was 408.5 Mpa, that of PFBN group was 525.4 MPa, and that of PFNA group was 764.3 Mpa. Comparatively, the maximum stress in the PFTBN group was reduced by 46.6% when contrasted with the PFNA group. Moreover, the stress dispersion within the PFTBN group was more evenly distributed than PFNA group. Regarding maximum displacement, the PFTBN group displayed the least displacement at 5.15 mm, followed by the PFBN group at 7.32 mm, and the PFNA group at 7.73 mm. Notably, the maximum displacement of the PFTBN group was 33.4% less than that observed in the PFNA group. Additionally, the relative displacement between the fragment and implant at the tip of pressure screw or helical blade was 0.22 mm in the PFTBN group, 0.34 mm in the PFBN group, and substantially higher 0.51 mm in the PFNA group. CONCLUSION: The "lever-reconstruction-balance" theory provides a new perspective for us to understand the mechanical conduction of the proximal femur. Compared with PFNA, in treating A3.3 intertrochanteric fractures PFTBN can better reconstruct the function of lateral wall, restore physiological mechanical conduction, increase postoperative stability, and finally reduce the risk of postoperative cut-out and implant failure. It might be a better alternative for the treatment of A3.3 intertrochanteric fracture.

5.
J Hazard Mater ; 471: 134313, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38669927

RESUMO

Secondary lignification of the root exodermis of Kandelia obovata is crucial for its response to adversity such as high salinity and anaerobic environment, and this lignification is also effective in blocking cadmium transport to the roots. However, how the differences in lignification of root exodermis at different developmental stages respond to Cd stress and its regulatory mechanisms have not been revealed. In this study, after analyzing the root structure and cell wall thickness using a Phenom scanning electron microscope as well as measuring cadmium content in the root cell wall, we found that the exodermis of young and mature roots of K. obovata responded to Cd stress through the polymerization of different lignin monomers, forming two different mechanisms: chelation and blocking. Through small RNA sequencing, RLM-5'-RACE and dual luciferase transient expression system, we found that miR397 targets and regulates KoLAC4/17/7 expression. The expression of KoLAC4/17 promoted the accumulation of guaiacyl lignin during lignification and enhanced the binding of cadmium to the cell wall. Meanwhile, KoLAC7 expression promotes the accumulation of syringyl lignin during lignification, which enhances the obstruction of cadmium and improves the tolerance to cadmium. These findings enhance our understanding of the molecular mechanisms underlying the differential lignification of the root exodermis of K. obovata in response to cadmium stress, and provide scientific guidance for the conservation of mangrove forests under heavy metal pollution.


Assuntos
Cádmio , Lignina , MicroRNAs , Raízes de Plantas , Lignina/química , Cádmio/toxicidade , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , MicroRNAs/metabolismo , MicroRNAs/genética , Estresse Fisiológico/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Polimerização/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Araceae/efeitos dos fármacos , Araceae/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética
6.
Artigo em Inglês | MEDLINE | ID: mdl-38606576

RESUMO

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

7.
Biomater Adv ; 160: 213864, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38642519

RESUMO

Although calcium phosphate has been extensively utilized in orthopedic applications such as spine, limbs, dentistry, and maxillofacial surgery, the lack of osteoinductive properties often hinders its effectiveness in treating bone defects resulting from pathological micro-environment such as tumor surgery, osteoporosis, osteomyelitis, and diabetic. Therefore, a novel bone cement based on magnesium-doped bioactive glass was developed in this study. The moderate release of magnesium ions improved the mechanical properties by controlling the crystal size of hydroxyapatite. Through detailed discussion of element content and heat treatment temperature, it was found that 2Mg-BG-800 was suitable for the construction of bone cement. 2Mg-BG-BC exhibited favorable initial (15 min) and final (30 min) setting time, compressive strength (29.45 MPa), compressive modulus (1851.49 MPa), injectability, and shape-adaptability. Furthermore, Mg-BG-BC demonstrated the ability to enhance the osteogenic differentiation of BMSCs, and induce macrophage polarization towards the M2 phenotype, suggesting its potential for osteoporotic fracture regeneration.


Assuntos
Cimentos Ósseos , Vidro , Magnésio , Osteogênese , Cimentos Ósseos/química , Cimentos Ósseos/farmacologia , Magnésio/química , Magnésio/farmacologia , Osteogênese/efeitos dos fármacos , Animais , Vidro/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/imunologia , Diferenciação Celular/efeitos dos fármacos , Camundongos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Teste de Materiais , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Força Compressiva
8.
Arch Microbiol ; 206(4): 163, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483624

RESUMO

To enhance the quality of tobacco leaves and optimize the smoking experience, diverse strains of functional bacteria and their associated metabolites have been used in tobacco aging. Exogenous cellulase additives are frequently employed to facilitate the degradation of cellulose and other macromolecular matrices and enhance the quality of the tobacco product. However, little is known about how microbial metabolites present in exogenous enzyme additives affect tobacco quality. In this study, crude cellulase solutions, produced by a tobacco-originating bacterium Bacillus subtilis FX-1 were employed on flue-cured tobacco. The incorporation of cellulase solutions resulted in the reduction of cellulose crystallinity in tobacco and the enhancement of the overall sensory quality of tobacco. Notably, tobacco treated with cellulase obtained from laboratory flask fermentation demonstrated superior scent and flavor attributes in comparison to tobacco treated with enzymes derived from industrial bioreactor fermentation. The targeted and untargeted metabolomic analysis revealed the presence of diverse flavor-related precursors and components in the cellulase additives, encompassing sugars, alcohols, amino acids, organic acids, and others. The majority of these metabolites exhibited significantly higher levels in the flask group compared to the bioreactor group, probably contributing to a pronounced enhancement in the sensory quality of tobacco. Our findings suggest that the utilization of metabolic products derived from B. subtilis FX-1 as additives in flue-cured tobacco holds promise as a viable approach for enhancing sensory attributes, establishing a solid theoretical foundation for the potential development of innovative tobacco aging additives.


Assuntos
Bacillus subtilis , Celulase , Bacillus subtilis/metabolismo , Celulase/metabolismo , Celulose/metabolismo
9.
Signal Transduct Target Ther ; 9(1): 73, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528050

RESUMO

Patients with advanced gastric cancer typically face a grim prognosis. This phase 1a (dose escalation) and phase 1b (dose expansion) study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma. The primary endpoints included maximum tolerated dose (MTD) in phase 1a and objective response rate (ORR) across phase 1a and 1b. Phase 1a tested three dose regimens of camrelizumab, apatinib, oxaliplatin, and S-1. Dose regimen 1: camrelizumab 200 mg on day 1, apatinib 250 mg every other day, oxaliplatin 100 mg/m² on day 1, and S-1 40 mg twice a day on days 1-14. Dose regimen 2: same as dose regimen 1, but oxaliplatin 130 mg/m². Dose regimen 3: same as dose regimen 2, but apatinib 250 mg daily. Thirty-four patients were included (9 in phase 1a, 25 in phase 1b). No dose-limiting toxicities occurred so no MTD was identified. Dose 3 was set for the recommended phase 2 doses and administered in phase 1b. The confirmed ORR was 76.5% (95% CI 58.8-89.3). The median progression-free survival was 8.4 months (95% CI 5.9-not evaluable [NE]), and the median overall survival (OS) was not mature (11.6-NE). Ten patients underwent surgery after treatment and the multidisciplinary team evaluation. Among 24 patients without surgery, the median OS was 19.6 months (7.8-NE). Eighteen patients (52.9%) developed grade ≥ 3 treatment-emergent adverse events. Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer (ChiCTR2000034109).


Assuntos
Anticorpos Monoclonais Humanizados , Piridinas , Neoplasias Gástricas , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Oxaliplatina , Piridinas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Quimioterapia Combinada/métodos
10.
Heliyon ; 10(5): e27282, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38463845

RESUMO

Background: Sarcopenia, characterised by an ongoing loss of skeletal muscle mass and reduced strength and function, is frequently observed in patients with non-small cell lung cancer (NSCLC). However, the relationship between sarcopenia and the prognosis of NSCLC treated with immune checkpoint inhibitors (ICIs) remains unclear. This aimed to assess whether sarcopenia is an independent prognostic factor for survival in patients with advanced NSCLC receiving ICIs. Methods: For this retrospective cohort study, we analysed the medical records of patients attending our hospital aged 18-75 years who were newly diagnosed with stage IIIB to stage IV NSCLC, and who had received ICIs as first- or second-line therapy between May 2019 and April 2022. The skeletal muscle index (SMI) was calculated from computed tomography (CT) images and relevant clinical characteristics within 4 weeks of initiating treatment and used to diagnose sarcopenia status. The Kaplan-Meier method and log-rank test were used to calculate and compare patients' progression-free survival (PFS). Cox proportional hazard regression was used to examine the associations between sarcopenia and survival outcomes. The chi-square test was used to compare treatment response outcomes, such as the objective response rate (ORR), disease control rate (DCR), and immunotherapy-related adverse events (irAEs), between individuals with and without sarcopenia. Additionally, the Student's t-test was utilised to compare SMI values between patients by their objective response (OR) and disease control (DC). Finally, the Mann-Whitney U test was used to compare nutritional and inflammatory indicators between the sarcopenia groups. Results: The study enrolled 70 patients, of whom 34 (48.6%) were diagnosed with sarcopenia. The median PFS of patients with and without sarcopenia was 7.5 vs. 13.4 months, respectively (p = 0.006). The proportional hazards regression analysis showed sarcopenia to be an independent prognostic factor for shorter PFS (hazard ratio (HR): 0.504, 95% CI: 0.265-0.962, p = 0.038). Using chi square tests, we found significant differences in the ORR (20.59% vs. 58.33%, p = 0.001) and occurrence of any irAEs (44.1% vs. 22.2%, p = 0.028) between the sarcopenia and the non-sarcopenia groups, respectively. The Student's t-test showed a significant difference in SMI between the ORR group and the non-ORR group (49.99 ± 7.00 vs. 42.98 ± 2.18 cm2/m2, p = 0.0015). While the sarcopenia group were with significantly a lower CD4+/CD8+ ratios and a higher C-reactive protein (CRP) level (p = 0.026, p = 0.011, respectively). Conclusions: This study found that sarcopenia is a significant predictor of a poor prognosis for patients with advanced NSCLC receiving ICIs. Multiple inflammatory and immune functions related to prognosis also differ by sarcopenia status.

11.
Adv Sci (Weinh) ; 11(15): e2307040, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38358087

RESUMO

Chronic inflammation is increasingly considered as the most important component of vascular aging, contributing to the progression of age-related cardiovascular diseases. To delay the process of vascular aging, anti-inflammation may be an effective measure. The anti-inflammatory factor annexin A1 (ANXA1) is shown to participate in several age-related diseases; however, its function during vascular aging remains unclear. Here, an ANXA1 knockout (ANXA1-/-) and an endothelial cell-specific ANXA1 deletion mouse (ANXA1△EC) model are used to investigate the role of ANXA1 in vascular aging. ANXA1 depletion exacerbates vascular remodeling and dysfunction while upregulates age- and inflammation-related protein expression. Conversely, Ac2-26 (a mimetic peptide of ANXA1) supplementation reverses this phenomenon. Furthermore, long-term tumor necrosis factor-alpha (TNF-α) induction of human umbilical vein endothelial cells (HUVECs) increases cell senescence. Finally, the senescence-associated secretory phenotype and senescence-related protein expression, rates of senescence-ß-galactosidase positivity, cell cycle arrest, cell migration, and tube formation ability are observed in both ANXA1-knockdown HUVECs and overexpressed ANXA1-TNF-α induced senescent HUVECs. They also explore the impact of formyl peptide receptor 2 (a receptor of ANXA1) in an ANXA1 overexpression inflammatory model. These data provide compelling evidence that age-related inflammation in arteries contributes to senescent endothelial cells that promote vascular aging.


Assuntos
Anexina A1 , Animais , Humanos , Camundongos , Envelhecimento , Anexina A1/genética , Anti-Inflamatórios/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Inflamação/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
12.
Prostaglandins Other Lipid Mediat ; 172: 106817, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38331090

RESUMO

Cardiovascular disease (CVD) has been the leading cause of death worldwide. As a chronic inflammatory disease, atherosclerosis (AS) acts as the initiating factor for CVD and reactive oxygen species (ROS) play a vital role in its development. Superoxide dismutases (SOD) can alleviate the detrimental effects of ROS and serve as the first line of defense through detoxifying the products derived from oxidative stress in vivo. Considering the potential preventive effects of high-density lipoprotein (HDL) on AS and the close relationship between CuZn superoxide dismutase (CuZnSOD) and HDL, the present work investigated whether CuZnSOD overexpression in swine could improve the function of HDL. Seven CuZnSOD transgenic swine, constructed by sperm and magnetic nanoparticles, demonstrated overexpressed CuZnSOD in the liver (P < 0.01) but comparable level to control in plasma (P > 0.05). CuZnSOD overexpression significantly down-regulated the levels of triglyceride (TG), apolipoprotein A-I (apoA-I) (P < 0.05), and high-density lipoprotein cholesterol (HDL-C) (P < 0.01) in plasma. In the presence of CuZnSOD overexpression, HDL3 significantly inhibited levels of IL-6 and TNF-α induced by oxidized low-density lipoprotein (oxLDL) (P < 0.05), indicating enhanced anti-inflammatory activity of HDL. At the same time, HDL-mediated cholesterol efflux did not decrease (P > 0.05). CuZnSOD overexpression improves the anti-inflammatory function of HDL despite decreased levels of HDL-C. In Conclusion, CuZnSOD overexpression improves HDL function in swine.


Assuntos
Lipoproteínas HDL , Superóxido Dismutase , Animais , Suínos , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genética , Lipoproteínas HDL/metabolismo , Animais Geneticamente Modificados , Interleucina-6/metabolismo , Interleucina-6/genética , Apolipoproteína A-I/metabolismo , Apolipoproteína A-I/genética , Masculino , Fígado/metabolismo , Triglicerídeos/metabolismo , Triglicerídeos/sangue
13.
Glob Med Genet ; 11(1): 86-99, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38414979

RESUMO

The fusion genes NRG1 and NRG2 , members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1 -positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2 . Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

14.
Updates Surg ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418693

RESUMO

BACKGROUND: The number of dissected lymph nodes is closely related to the prognosis of patients with non-small cell lung cancer. This study explored the optimal number of right paratracheal lymph nodes dissected in right upper non-small cell lung cancer patients and its impact on prognosis. METHODS: Patients who underwent radical surgery for right upper lobe cancer between 2012 and 2017 were retrospectively enrolled. The optimal number of right paratracheal lymph nodes and the relationship between the number of dissected right paratracheal lymph nodes and the prognosis of right upper non-small cell lung cancer were analysed. RESULTS: A total of 241 patients were included. The optimal number of dissected right paratracheal lymph nodes was 6. The data were divided according to the number of dissected right paratracheal lymph nodes into groups RPLND + (≥ 6) and RPLND- (< 6). In the stage II and III patients, the 5-year overall survival rates were 39.0% and 48.2%, respectively (P = 0.033), and the 5-year recurrence-free survival rates were 32.8% and 41.8%, respectively (P = 0.043). Univariate and multivariate analyses revealed that among the stage II and III patients, ≥ 6 right paratracheal dissected lymph nodes was an independent prognostic factor for overall survival (HR = 0.53 95% CI 0.30-0.92 P = 0.025) and recurrence-free survival (HR = 1.94 95% CI 1.16-3.24 P = 0.011). CONCLUSIONS: Resection of 6 or more right paratracheal lymph nodes may be associated with an improved prognosis in patients with right upper non-small cell lung cancer, especially in patients with stage II or III disease.

15.
Regen Ther ; 25: 344-354, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38362337

RESUMO

Intervertebral disc degeneration (IDD) is one of the major leading causes of back pain affecting the patient's quality of life. However, the roles of circular RNA (circRNA) in IDD remains unclear. This study aimed to explore the function and underlying mechanism of circ_0036763 in IDD. In this study, expressions of circ_0036763, U2 small nuclear RNA auxiliary factor 2 (U2AF2), miR-583 and aggrecan (ACAN) in primary human nucleus pulposus cells (HNPCs) derived from IDD patients and healthy controls were detected by quantitative real-time reverse transcription-PCR (qRT-PCR) or Western blot (WB). The relationship between pre-circ_0036763 and U2AF2, circ_0036763 and miR-583, miR-583 and ACAN mRNA was determined by bioinformatic analysis, miRNA pull down or RNA immunoprecipitation (RIP) assay. The expressions of Collagen I and Collagen II were evaluated by WB. Co-culture of bone marrow mesenchymal stem cells (bMSCs) or bMSCs-derived exosomes and HNPCs were performed to identify the effect of U2AF2 on the mature of circ_0036763 and ACAN. Results indicated that circ_0036763, U2AF2 and ACAN were downregulated while miR-583 was upregulated in HNPCs derived from IDD patients compared with that in normal HNPCs. Besides, overexpression of circ_0036763 elevated the expressions of ACAN and Collagen II whereas reduced Collagen I expression in HNPCs. Moreover, U2AF2 promoted the mature of circ_0036763, and circ_0036763 positively regulated ACAN by directly sponging miR-583. Furthermore, exosomal U2AF2 derived from bMSCs could increase U2AF2 levels in HNPCs and subsequently regulate the expression of ACAN by circ_0036763/miR-583 axis. In summary, circ_0036763 modified by exosomal U2AF2 derived from bMSCs alleviated IDD through regulating miR-583/ACAN axis in HNPCs. Thus, this study might provide novel therapeutic targets for IDD.

16.
Ann Surg Oncol ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38334847

RESUMO

BACKGROUND: The prognosis of limited-stage small cell lung cancer (LS-SCLC) after surgery usually is estimated at diagnosis, but how the prognosis actually evolves over time for patients who survived for a predefined time is unknown. METHODS: Data on patients with a diagnosis of LS-SCLC after surgery between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The 5-year conditional cancer-specific survival (CCSS) and conditional overall survival (COS) were calculated. RESULTS: This study analyzed 997 patients (555 women, 55.7%) with a median age, of 67 years (interquartile range [IQR], 60-73 years). The 5-year CCSS and COS increased from 44.7% and 38.3%, respectively, at diagnosis to 83.7% and 67.9% at 5 years after diagnosis. Although there were large differences with different stages (stages I, II, and III) at diagnosis (respectively 59.5%, 28.4%; 28.1% for CCSS and 50.6%, 24.8%, and 23.6% for COS), the gap decreased with time, and the rates were similar after 5 years (respectively 85.0%, 80.3%, and 79.4% for CCSS; 65.6%, 56.9%, and 61.3% for COS). The 5-year conditional survival for the patients who received lobectomy was better than for those who received sublobectomy or pneumonectomy. Multivariable analyses showed that only age and resection type were independent predictors for CCSS and COS, respectively, throughout the period. CONCLUSION: Conditional survival estimates for LS-SCLC generally increased over time, with the most significant improvement in patients with advanced stage of disease. Resection type and old age represented extremely important determinants of prognosis after a lengthy event-free follow-up period.

17.
Cell Oncol (Dordr) ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38386231

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA), a primary hepatobiliary malignancy, is characterized by a poor prognosis and a lack of effective treatments. Therefore, the need to explore novel therapeutic approaches is urgent. While the role of Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (PIN1) has been extensively studied in various tumor types, its involvement in CCA remains poorly understood. METHODS: In this study, we employed tissue microarray (TMA), reverse transcription-polymerase chain reaction (RT-PCR), and The Cancer Genome Atlas (TCGA) database to assess the expression of PIN1. Through in vitro and in vivo functional experiments, we investigated the impact of PIN1 on the adhesion and metastasis of CCA. Additionally, we explored downstream molecular pathways using RNA-seq, western blotting, co-immunoprecipitation, immunofluorescence, and mass spectrometry techniques. RESULTS: Our findings revealed a negative correlation between PIN1 overexpression and prognosis in CCA tissues. Furthermore, high PIN1 expression promoted CCA cell proliferation and migration. Mechanistically, PIN1 functioned as an oncogene by regulating ANXA2 phosphorylation, thereby promoting CCA adhesion. Notably, the interaction between PIN1 and ANXA2 was facilitated by RACK1. Importantly, pharmacological inhibition of PIN1 using the FDA-approved drug all-trans retinoic acid (ATRA) effectively suppressed the metastatic potential of CCA cells in a nude mouse lung metastasis model. CONCLUSION: Overall, our study emphasizes the critical role of the PIN1/RACK1/ANXA2 complex in CCA growth and functionality, highlighting the potential of targeting PIN1 as a promising therapeutic strategy for CCA.

20.
Technol Cancer Res Treat ; 23: 15330338231216333, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38258400

RESUMO

BACKGROUND: RAD51 is a central protein involved in homologous recombination, which has been linked to cancer development and progression. systemic inflammatory indicator markers such as neutrophil-to-lymphocyte ratio and lymphocyte-to-monocyte ratio have also been implicated in cancer. However, the relationship between Rad51 and these inflammatory markers in esophageal cancer patients undergoing esophagectomy is not yet understood. METHODS: We retrospectively observed 320 esophageal cancer patients who underwent esophagectomy. We collected clinical characteristics, postoperative complications, and survival analysis data and analyzed the relationship between Rad51 expression, inflammatory markers, and prognosis. RESULTS: We found significant linear relationships among the inflammatory markers. There were also close relationships between Rad51 expression and neutrophil-to-lymphocyte ratio or C-reactive protein. Patients with low lymphocyte percentage were more likely to have low Rad51 expression (P = .026), high C-reactive protein (P = .007), and high neutrophil-to-lymphocyte ratio (P = .006). Low lymphocyte-to-monocyte ratio was associated with poor overall survival and was an independent prognostic factor (HR = 2.214; 95% confidence interval: 1.044-4.695, P = .038). In patients without lymph node metastases, low albumin (HR= 0.131; 95% confidence interval: 0.025-0.687, P = .016), high neutrophil-to-lymphocyte ratio (HR = 0.002; 95% confidence interval: 0.000-0.221, P = .009), and high Rad51 expression (HR = 14.394; 95% confidence interval: 2.217-97.402, P = .006) were associated with poor overall survival. CONCLUSIONS: Our study found a close correlation between elevated Rad51 expression and inflammatory markers. High Rad51 expression, high neutrophil-to-lymphocyte ratio, and low lymphocyte-to-monocyte ratio are associated with lower survival rates. The combined assessment of Rad51 and inflammatory markers can be useful for preoperative assessment and prognostic evaluation in esophageal squamous cell carcinoma patients.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Proteína C-Reativa , Prognóstico , Estudos Retrospectivos
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