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1.
Molecules ; 29(12)2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38930966

RESUMO

Covalent organic frameworks (COFs) have emerged as promising renewable electrode materials for LIBs and gained significant attention, but their capacity has been limited by the densely packed 2D layer structures, low active site availability, and poor electronic conductivity. Combining COFs with high-conductivity MXenes is an effective strategy to enhance their electrochemical performance. Nevertheless, simply gluing them without conformal growth and covalent linkage restricts the number of redox-active sites and the structural stability of the composite. Therefore, in this study, a covalently assembled 3D COF on Ti3C2 MXenes (Ti3C2@COF) is synthesized and serves as an ultralong cycling electrode material for LIBs. Due to the covalent bonding between the COF and Ti3C2, the Ti3C2@COF composite exhibits excellent stability, good conductivity, and a unique 3D cavity structure that enables stable Li+ storage and rapid ion transport. As a result, the Ti3C2-supported 3D COF nanosheets deliver a high specific capacity of 490 mAh g-1 at 0.1 A g-1, along with an ultralong cyclability of 10,000 cycles at 1 A g-1. This work may inspire a wide range of 3D COF designs for high-performance electrode materials.

2.
J Clin Oncol ; 42(12): 1391-1402, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37988648

RESUMO

PURPOSE: To evaluate the efficacy and safety of disitamab vedotin (DV, RC48-ADC), a novel humanized anti-human epidermal growth factor receptor 2 (HER2) antibody conjugated with monomethyl auristatin E, in patients with HER2-positive locally advanced or metastatic urothelial carcinoma (UC) refractory to standard or regular therapies. PATIENTS AND METHODS: The data analyzed and reported are from two phase II, open-label, multicenter, single-arm studies (RC48-C005 and RC48-C009) in patients with HER2-positive (immunohistochemistry 3+ or 2+) locally advanced or metastatic UC who have progressed on at least one previous line of systemic chemotherapy. Patients received DV treatment (2 mg/kg IV infusion, once every 2 weeks). The primary end point was objective response rate (ORR) assessed by a blinded independent review committee (BIRC). Progression-free survival (PFS), overall survival (OS), and safety were also assessed. RESULTS: One hundred and seven patients were enrolled in total. The overall confirmed ORR by BIRC was 50.5% (95% CI, 40.6 to 60.3). Consistent results were observed in prespecified subgroups including patients with liver metastasis and patients previously treated with anti-PD-1/L1 therapies. By the cutoff date of May 10, 2022, the median duration of response was 7.3 months (95% CI, 5.7 to 10.8). The median PFS and OS were 5.9 months (95% CI, 4.3 to 7.2) and 14.2 months (95% CI, 9.7 to 18.8), respectively. The most common treatment-related adverse events (TRAEs) were peripheral sensory neuropathy (68.2%), leukopenia (50.5%), AST increased (42.1%), and neutropenia (42.1%). Fifty-eight (54.2%) patients experienced grade ≥3 TRAEs, including peripheral sensory neuropathy (18.7%) and neutropenia (12.1%). CONCLUSION: DV demonstrated a promising efficacy with a manageable safety profile in patients with HER2-positive locally advanced or metastatic UC who had progressed on at least one line of systemic chemotherapy.


Assuntos
Anticorpos Monoclonais , Carcinoma de Células de Transição , Neutropenia , Oligopeptídeos , Receptor ErbB-2 , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neutropenia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
3.
Cancers (Basel) ; 15(8)2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37190306

RESUMO

Skeletal muscle wasting is the most remarkable phenotypic feature of cancer cachexia that increases the risk of morbidity and mortality. However, there are currently no effective drugs against cancer cachexia. Ursolic acid (UA) is a lipophilic pentacyclic triterpene that has been reported to alleviate muscle atrophy and reduce muscle decomposition in some disease models. This study aimed to explore the role and mechanisms of UA treatment in cancer cachexia. We found that UA attenuated Lewis lung carcinoma (LLC)-conditioned medium-induced C2C12 myotube atrophy and muscle wasting of LLC tumor-bearing mice. Moreover, UA dose-dependently activated SIRT1 and downregulated MuRF1 and Atrogin-1. Molecular docking results revealed a good binding effect on UA and SIRT1 protein. UA rescued vital features wasting without impacting tumor growth, suppressed the elevated spleen weight, and downregulated serum concentrations of inflammatory cytokines in vivo. The above phenomena can be attenuated by Ex-527, an inhibitor of SIRT1. Furthermore, UA remained protective against cancer cachexia in the advanced stage of tumor growth. The results revealed that UA exerts an anti-cachexia effect via activating SIRT1, thereby downregulating the phosphorylation levels of NF-κB and STAT3. UA might be a potential drug against cancer cachexia.

4.
BMJ Support Palliat Care ; 13(e1): e129-e135, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32917649

RESUMO

OBJECTIVES: This study aimed to compare depression, anxiety and quality of life (QoL) between cachexia and non-cachexia patients, and explore the relationship between cachexia and depression, anxiety and QoL in patients with cancer. METHODS: A total of 528 patients from cancer centres of four hospitals were enrolled in this cross-sectional study. All patients were divided into cachexia and non-cachexia according to international consensus definition of cachexia. Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) and Quality of Life Questionnaire-Cancer 30 (QLQ-C30) were used to evaluate depression, anxiety and QoL. RESULTS: 285 patients (53.98%) were classified as cachexia. The prevalence of depression, anxiety, severe depression and severe anxiety in cachexia was 30.2%, 18.6%, 6.7% and 8.4%, respectively, which were significantly higher than in non-cachexia (all p<0.01). Patients with cachexia obviously acquired poorer physical function (PF), role function (RF), cognitive function (CF), emotional function (EF), social function (SF) and overall QoL than non-cachexia patients (all p<0.01). Cachexia was positively associated with depression (unstandardised coefficient (B)=2.123, p<0.001) and anxiety (B=1.123, p=0.024), and had a negative relationship with PF, CF, EF, SF and overall QoL (all B<0, all p<0.05). CONCLUSIONS: Cachexia was associated with greater depression and anxiety and poorer QoL in patients with cancer, which emphasised the importance of timely identification and management of cachexia to improve the psychological problems and QoL among patients with cancer.


Assuntos
Neoplasias , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Depressão/epidemiologia , Depressão/psicologia , Estudos Transversais , Caquexia/epidemiologia , Caquexia/etiologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Transtornos de Ansiedade , Inquéritos e Questionários , Neoplasias/complicações
5.
Virus Genes ; 58(5): 403-413, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35780442

RESUMO

Orf virus (ORFV, species Orf virus) belongs to the typical species of the Parapoxvirus genus of the family Poxviridae, which infects sheep, goats, and humans with worldwide distribution. Although outbreaks of Orf have been reported sequentially in several Chinese provinces, the epidemiology of Orf and genetic diversity of ORFV strains still needs to be further characterized. To further reveal the genomic organization of the ORFV-GZ18 and ORFV-CL18 isolates, the complete genome sequences of two recently obtained ORFV isolates were sequenced using the next-generation sequencing technology and analyzed, which had been deposited in the GenBank database under accession number MN648218 and MN648219, respectively. The complete genomic sequence of ORFV-CL18 was 138,495 bp in length, including 131 potential open reading frames (ORFs) flanked by inverted terminal repeats (ITRs) of 3481 bp at both ends, which has genomic structure typical Parapoxviruses. The overall genomic organization of the fully sequenced genome of ORFV-GZ18 was consistent with ORFV-CL18 genome, with a complete genome size of 138,446 nucleotides, containing 131 ORFs flanked by ITRs of 3469 bp. Additionally, the overall G + C contents of ORFV-GZ18 and ORFV-CL18 genome sequences were about 63.9% and 63.8%, respectively. The phylogenetic analysis showed that both ORFV-GZ18 and ORFV-CL18 were genetically closely related to ORFV-SY17 derived from sheep. In summary, the complete genomic sequences of ORFV-GZ18 and ORFV-CL18 are reported, with the hope it will be useful to investigate the host range, geographic distribution, and genetic evolution of the virus in Southern West and Northern East China.


Assuntos
Ectima Contagioso , Vírus do Orf , Animais , China/epidemiologia , Genômica , Cabras , Humanos , Nucleotídeos , Vírus do Orf/genética , Filogenia , Ovinos
6.
Artigo em Inglês | MEDLINE | ID: mdl-35627668

RESUMO

The extensive pattern of economic growth has an inestimable negative impact on the ecological environment, which causes the soil pollution problem to become increasingly prominent. In order to improve the effectiveness and rationality of prevention and control of heavy metal pollution in regional soil, it is necessary to understand the current situation of pollution, identify pollution sources and clarify future pollution risks. In this paper, an industrially developed city in eastern China was taken as the study region. The positive matrix factorization model (PMF) model and Unmix model was applied to identify and apportion the pollution sources of soil potential toxic elements after evaluating the ecological risk of soil potential toxic elements. The PMF model identified six factors, including single source and composite source. The Unmix model also identified six sources, including sources of nature, industrial discharge and traffic emissions. The comparison between the two models showed that Hg and Ni pollution, as well as Cr enrichment in the study region, were related to the industrial discharge from enterprises and factories. Cd pollution was related to traffic emission sources. Cu and Zn pollution were related to the multiple sources mixed with soil parent material, traffic emissions and industrial discharge from electronic enterprises. Pb pollution was related to natural sources (e.g., soil pH) but also to industrial sources (e.g., industrial wastes discharge). Enrichment was related to soil parent material and agricultural inputs. Our study also implies that soil heavy metal pollution or enrichment in the study region was mainly from anthropogenic sources and supplemented by natural sources.


Assuntos
Metais Pesados , Poluentes do Solo , Monitoramento Ambiental , Indústrias , Metais Pesados/análise , Metais Pesados/toxicidade , Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidade
7.
Oncogene ; 41(6): 782-796, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34853466

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal gastrointestinal malignancies with high mortality. Recurrence develops within only a few years after curative resection and perioperative adjuvant therapy in 30-50% of these patients. Therefore, it is essential to identify postoperative recurrence biomarkers to facilitate selecting the following surveillance and therapeutic strategies. The general transcription factor IIE subunit beta (GTF2E2) is crucial for physiological and pathological functions, but its roles in the aggression and recurrence of ESCC remain ambiguous. In this study, we found that GTF2E2 was highly expressed in ESCC samples, and elevated GTF2E2 expression predicted early recurrence after surgery for ESCC patients. High expression of GTF2E2 associated with more aggressive clinic features and poor prognosis. GTF2E2 promoted the proliferation and mobility of ESCC cells in vitro and in vivo. We further revealed that miR-139-5p repressed GTF2E2 expression by downregulating its mRNA through binding with Argonaute 2 (Ago2). Rescue assays suggested that miR-139-5p affected GTF2E2-mediated ESCC progression. Moreover, GTF2E2 positively interacted with FUS promoter and regulated FUS expression, and the phenotype changes caused by GTF2E2 manipulation were recovered by rescuing FUS expression in ESCC cells. Additionally, we demonstrated that GTF2E2 promotes ESCC cells progression via activation of the AKT/ERK/mTOR pathway. In conclusion, GTF2E2 may serve as a novel biomarker for recurrence after surgery and a potential therapeutic target for ESCC patients, and it promotes ESCC progression via miR-139-5p/GTF2E2/FUS axis.


Assuntos
Carcinoma de Células Escamosas do Esôfago
8.
Front Pharmacol ; 12: 731386, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867338

RESUMO

Background: Cachexia is a multifactorial disorder characterized by weight loss and muscle wasting, making up for about 20% of cancer-related death. However, there are no effective drugs to combat cachexia at present. Methods: In this study, the effect of CT26 exosomes on C2C12 myotubes was observed. We compared serum HMGB1 level in cachexia and non-cachexia colon cancer patients. We further explored HMGB1 expression level in CT26 exosome. We added recombinant HMGB1 to C2C12 myotubes to observe the effects of HMGB1 on C2C12 myotubes and detected the expression level of the muscle atrophy-related proteins. Then, we used the HMGB1 inhibitor glycyrrhizin to reverse the effects of HMGB1 on C2C12 myotubes. Finally, HMGB1 inhibitor glycyrrhizin was utilized to relieve cachexia in CT26 cachexia mouse model. Results: Exosomes containing HMGB1 led to muscle atrophy with significantly decreased myotube diameter and increased expression of muscle atrophy-related proteins Atrogin1 and MuRF1. Further, we detected that HMGB1 induced the muscle atrophy mainly via TLR4/NF-κB pathway. Administration of the HMGB1 inhibitor glycyrrhizin could relieve muscle wasting in vitro and attenuate the progression of cachexia in vivo. Conclusion: These findings demonstrate the cachectic role of HMGB1, whether it is soluble form of HMGB1 or secreted from tumor cells as part of exosomes. HMGB1 inhibitor glycyrrhizin might be a promising drug in colon cancer cachexia.

9.
Libyan J Med ; 16(1): 1957199, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34347581

RESUMO

Psychological distress scale is highly recommended for cancer patients' care. Several psychological scales have been implemented in cancer outpatient clinics. However, the use of the psychological distress scale, particularly distress thermometer (DT), in the inpatient has not been reported. In this study, we report the efficacy of DT in the determination of cancer inpatients' supporting needs.A total of 170 inpatients diagnosed with cancer have been enrolled in this study. Only 132 patients matched the inclusion criteria, while other cases were excluded because of other diseases associated with cancer. The standardized problem list (PL) and Hospital Anxiety and Depression Scale (HADS) were implemented in comparison with DT. Then, the cut-off score of DT was performed to identify clinically significant differences.The analysis of the receiver operating characteristic (ROC) curve revealed that a DT cut-off score of 4 displayed 0.76 under the ROC curve. Sensitivity showed 0.86 sensitivity for cut-off score 4 and a specificity of 0.56 relative to the HADS cut-off score (≥15). DT scores were found independent of medical variables such as cancer type and stage, recurrence, or metastasis. Clinical ECOG-SP showed a significant association with the DT cut-off score (P ≤ 0.05). Regarding PL, patients with scores above DT cut-off were suffering 21 of 40 problems in all categories. Furthermore, patients that scored above the DT cut-off significantly showed an association with high support needs.DT scale showed significant performance in the evaluation of psychological distress among cancer inpatients through the efficient determination of their support needs.


Assuntos
Pacientes Internados , Neoplasias , Depressão , Humanos , Programas de Rastreamento , Psicometria , Estresse Psicológico/diagnóstico , Estresse Psicológico/epidemiologia , Inquéritos e Questionários , Termômetros
11.
Cancer Cell ; 39(9): 1279-1291.e3, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34388377

RESUMO

Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways may delay therapeutic resistance in advanced non-small cell lung cancer (NSCLC). This phase 3 study investigated the efficacy and safety of an erlotinib plus bevacizumab regimen in untreated patients with advanced NSCLC. In total, 311 patients received bevacizumab plus erlotinib (n = 157) or erlotinib only (n = 154). Progression-free survival (PFS) was 17.9 months (95% confidence interval [CI], 15.2-19.9) for bevacizumab plus erlotinib and 11.2 months (95% CI, 9.7-13.8) for erlotinib only (hazard ratio [HR] = 0.55; 95% CI, 0.41-0.73; p < 0.001). A brain metastases subgroup treated with bevacizumab plus erlotinib also showed improved PFS (HR = 0.48; 95% CI, 0.27-0.84; p = 0.008). Grade ≥3 treatment-related adverse events occurred in 86 (54.8%) and 40 (26.1%) patients, respectively. Bevacizumab plus erlotinib significantly improved PFS in patients with untreated metastatic EGFR-mutated NSCLC, including those with brain metastases at baseline.


Assuntos
Bevacizumab/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cloridrato de Erlotinib/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Neoplasias Encefálicas/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Cloridrato de Erlotinib/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Distribuição Aleatória , Análise de Sobrevida , Resultado do Tratamento
12.
Front Pharmacol ; 12: 687491, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093209

RESUMO

The ongoing loss of skeletal muscle is a central event of cancer cachexia, and its consequences include adverse effects on patient's quality of life and survival. Alpinetin (Alp), a natural plant-derived flavonoid obtained from Alpinia katsumadai Hayata, has been reported to possess potent anti-inflammatory and antitumor activities. This study aimed to explore the therapeutic effect and underlying mechanism of Alp in the prevention of cancer cachexia. We found that Alp (25-100 µM) dose-dependently attenuated Lewis lung carcinoma-conditioned medium-induced C2C12 myotube atrophy and reduced expression of the E3 ligases Atrogin-1 and MuRF1. Moreover, Alp administration markedly improved vital features of cancer cachexia in vivo with visible reduction of the loss of tumor-free body weight and wasting of multiple tissues, including skeletal muscle, epididymal fat, and decreased expression of Atrogin-1 and MuRF1 in cachectic muscle. Alp suppressed the elevated spleen weight and serum concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6. Further, Alp treatment remained protective against cancer cachexia in the advanced stage of tumor growth. Molecular docking results suggested that Alp was docked into the active site of PPARγ with the docking score of -7.6 kcal/mol, forming a hydrogen bond interaction with PPARγ protein amino acid residue HIS449 with a bond length of 3.3 Å. Mechanism analysis revealed that Alp activated PPARγ, resulting in the downregulated phosphorylation of NF-κB and STAT3 in vitro and in vivo. PPARγ inhibition induced by GW9662 notably attenuated the improvement of Alp on the above cachexia phenomenon, indicating that PPARγ activation mediated the therapeutic effect of Alp. These findings suggested that Alp might be a potential therapeutic candidate against cancer cachexia.

13.
Front Oncol ; 11: 666446, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968773

RESUMO

Morphine is an analgesic widely adopted to relieve cancer pain. A number of discrepancies, however, are presented by the published literature, with reports suggesting that opioids may either promote or inhibit the spread of cancer. It is of great significance to determine whether morphine may increase the risk of metastasis while utilized in liver cancer surgical treatment. In this study, we explore the effects of morphine on liver cancer cells in vitro and in vivo. Our results showed that morphine does not promote proliferative ability to cultured liver cancer cells. While morphine could increase the apoptosis rate of Hep3B/HepG2 cells. Furthermore, morphine could significantly inhibit the migratory and invasion ability of Hep3B/HepG2 cells. Subsequent investigations disclosed that morphine could inhibit sphere formation ability of Hep3B/HepG2 cells by using sphere formation assay. Based on nude mouse models, we demonstrated that morphine significantly reduced pulmonary tumorigenicity of Hep3B/HepG2 cells. In conclusion, our results found that morphine at clinical concentrations could suppress liver cancer cell tumor properties in vitro and in vivo, indicating the safety of morphine utilization in HCC patients' pain management.

15.
J Clin Psychol Med Settings ; 28(2): 212-220, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32040797

RESUMO

The distress thermometer (DT) is a commonly used tool for screening distress in Asian patients with cancer. However, the optimal cut-off score and discriminative accuracy remain unclear. Hence, this meta-analysis aimed to examine its diagnostic value and optimal cut-off score in Asia. A systematic search was conducted in the PubMed, EMBASE and Cochrane Library databases. The pooled sensitivity, specificity, positive and negative predictive values, and diagnostic odds ratio were calculated. The area under the curve (AUC) was computed from the summary receiver-operating characteristic (SROC) curve. All analyses were performed using STATA 12.0 software. Finally, 10 studies describing 2851 patients were included. After pooling all the results from the 10 studies, the optimal DT cut-off score was 4 with a pooled sensitivity of 0.78 (95% confidence intervals (CI) 0.68-0.86), specificity of 0.73 (95% CI 0.65-0.80) and AUC of 0.82 (95% CI 0.78-0.85). When the DT was compared to the hospital anxiety and depression scale-total (HADS-T), the cut-off score of 4 showed the best balance between the pooled sensitivity (0.81, 95% CI 0.69-0.89) and specificity (0.74, 95% CI 0.59-0.84), and the AUC was 0.84 (95% CI 0.81-0.87). In conclusion, the DT with a cut-off score of 4 was an effective screening tool in Asian patients with cancer.


Assuntos
Neoplasias , Termômetros , Detecção Precoce de Câncer , Humanos , Programas de Rastreamento , Neoplasias/complicações , Neoplasias/diagnóstico , Sensibilidade e Especificidade , Estresse Psicológico
16.
Nutrition ; 82: 111032, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33172686

RESUMO

OBJECTIVES: Sarcopenia is a well-known risk factor for inferior cancer outcomes, but the identification of patients at risk remains challenging. A new sarcopenia index (SI), defined as serum creatinine (Cr) × cystatin C (CysC)-based glomerular filtration rate (eGFRCysC), has been reported to be an objective surrogate marker for sarcopenia. The aim of this study was to assess whether the SI is associated with sarcopenia and cancer-related fatigue (CRF) in patients with advanced cancer. METHODS: This cross-sectional study included 182 patients with different types of cancer (cancer stages III/IV; mean age 55.1 ± 11.1 y). Sarcopenia was defined as the presence of both low muscle mass and low muscle strength. The cross-sectional area of skeletal muscle mass (SMA) at the third lumbar spine was estimated by computed tomography (CT). Low muscle mass was defined as a skeletal muscle index (SMA/height2) <34.9 cm2/m2 for women and 40.8 cm2/m2 for men. Low muscle strength was determined by handgrip strength (HGS) according to the cutoffs of the Asian Working Group for Sarcopenia (<18 kg for women and <26 kg for men). CRF was measured by the Brief Fatigue Inventory (BFI). The associations between SI with both sarcopenia and CRF were investigated. RESULTS: The prevalence of sarcopenia was 27.5%. The SI was significantly lower in both the sarcopenia and severe fatigue groups. The associations between SI and SMA (r = 0.365; P < 0.001), skeletal muscle index (SMI) (r = 0.340; P < 0.001), and HGS (r = 0.414; P <0 .001) were stronger than the associations between the serum creatinine/cystatin C (Cr/CysC) ratio and SMA (r = 0.299; P < 0.001), SMI (r = 0.269; P <0 .001), and HGS (r = 0.364; P <0 .001). Additionally, a decrease in the SI was associated with a higher likelihood of sarcopenia (odds ratio per 10-unit, 1.09; 95% confidence interval, 1.02-1.16) after adjusting for potential confounding factors. However, there was only a weak correlation between the SI and BFI score (r = -0.161, P = 0.045). CONCLUSION: The SI might be a useful objective tool for assessing sarcopenia in patients with advanced cancer. Further studies are warranted to extend the present findings.


Assuntos
Creatinina , Cistatina C , Neoplasias , Sarcopenia , Adulto , Idoso , Creatinina/sangue , Estudos Transversais , Cistatina C/sangue , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Neoplasias/complicações , Neoplasias/patologia , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Sarcopenia/etiologia
17.
Am J Cancer Res ; 10(11): 3947-3972, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294279

RESUMO

The AT-rich Interactive Domain 1A (ARID1A) is one of the most frequently mutated genes in gastric cancer. Here, we found that genetic variants in noncoding regions of ARID1A associated with altered protein levels by target sequencing. Notably, tumors with ARID1A variants in the 3'untranslated region (3'UTR) exhibited remarkably increased heterogeneity of ARID1A protein. In general, genetic variants and protein deficiency of ARID1A in tumors were associated with a better survival. Strikingly, altered patterns and heterogeneity of ARID1A protein expression were observed in peritumor tissues and carried significant implications in defining tumor immune contexture by multiplex immunohistochemistry. By analyzing the spatial distribution of TILs, we showed that reduced ARID1A protein levels in both tumor and peritumor tissues were significantly correlated with increased density and proximity of TILs to tumor cells. In contrast, high heterogeneity of ARID1A expression was associated with increased TIL density, but reduced proximity of TILs to tumor cells. Collectively, our study characterized ARID1A genetic alterations and its protein expression patterns in EOGC, demonstrating new strategies for clinically assessing its molecular impact on tumor onset and progression, tumor immune response, and patient survival.

18.
J Oncol ; 2020: 3293589, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029142

RESUMO

OBJECTIVE: We aimed to examine the performance of the distress thermometer (DT) and identify the prevalence and risk factors associated with psychological distress (PD) in heterogeneous cancer patients. METHODS: This cross-sectional study enrolled 1496 heterogeneous cancer patients from the inpatient and outpatient departments. Receiver operating characteristic analysis (ROC) of DT was evaluated against the Hospital Anxiety and Depression Scale-Total (HADS-T ≥15). An area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and clinical utility index were calculated. Multiple binary logistic regression was used to identify the factors associated with PD. RESULTS: Referring to ROC analysis, DT showed good discriminating accuracy (AUC = 0.88). A cutoff score of 4 was established, and it yielded sensitivity (0.81), specificity (0.88), PPV (0.87), NPV (0.82), and clinical utility indexes (screening utility = 0.71 and case-finding utility = 0.73). 46.5% of our participants was distressed. Lower education levels (odd ratio (OR) = 1.39), advanced stage (OR = 1.85), active disease status (OR = 1.82), lack of exercise (OR = 3.03), diagnosis known (OR = 0.64), emotional problems (OR = 3.54), and physical problems (OR = 8.62) were the predictive factors for PD. CONCLUSION: DT with a cutoff score (≥4) is a comprehensive, appropriate, and practical initial screener for PD in cancer patients. Predicting factors should be considered together for effective management of PD in such population.

19.
Clin Nutr ; 39(11): 3337-3345, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32143888

RESUMO

BACKGROUND & AIMS: Sarcopenia is a commonly prevalent malnutrition condition and serves as a valuable adverse prognostic indicator for survival in patients with cancer. A rapid and convenient screening test for sarcopenia would be helpful for patients. Aim of the study was to evaluate the diagnostic value of SARC-F and SARC-F combined with calf circumference (SARC-CalF) for screening cancer-related sarcopenia in cancer population. METHODS: A total of 309 patients with cancer who had routine abdominal comptued tomography (CT) images within 30 days were enrolled in this cross-sectional cohort. Sarcopenia was determined as the presence of both low muscle mass (LMM) and low muscle strength; muscle mass was evaluated by CT-scan, and muscle strength was evaluated by handgrip strength (HGS). Two different diagnostic criteria (Western criteria and Eastern criteria) were used as the reference standards. The sensitivity and specificity analyses of the SARC-F and SARC-CalF were calculated. The receiver operating characteristic (ROC) curves and the area under the ROC curves (AUC) were used to compare the diagnostic value of SARC-F and SARC-CalF for sarcopenia. RESULTS: The prevalence of LMM and sarcopenia in the patient group was 85.1% and 50.5% by Western criteria. Corresponding figures were lower as 42.4% and 26.2% by Eastern criteria. In the overall study population, when sarcopenia defined by the Eastern criteria, sensitivity and specificity of SARC-CalF were 66.6% and 70.1%, whereas that of SARC-F were 32.1% and 90.7%, respectively. The AUCs for SARC-CalF and SARC-F were 0.75 (95% confidence interval (CI) 0.70-0.80) and 0.70 (95% CI 0.64-0.75), respectively (P = 0.003). Against the Western criteria, SARC-CalF also had better sensitivity (55.1% vs. 22.4%) but lower specificity (76.4% vs. 92.1%) than that of SARC-F. The AUCs of SARC-CalF and SARC-F were 0.70 (95% CI 0.65-0.75) and 0.68 (95% CI 0.62-0.73), respectively, but the difference was not significant (P = 0.211). CONCLUSIONS: SARC-CalF significantly increases the sensitivity and overall diagnostic accuracy of SARC-F for screening sarcopenia. SARC-CalF can be a rapid screening tool for sarcopenia in patients with cancer.


Assuntos
Antropometria/métodos , Programas de Rastreamento/métodos , Neoplasias/fisiopatologia , Sarcopenia/diagnóstico , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Abdome/diagnóstico por imagem , Idoso , Estudos Transversais , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Padrões de Referência , Sarcopenia/etiologia , Sensibilidade e Especificidade , Tíbia/patologia , Tomografia Computadorizada por Raios X/métodos
20.
Support Care Cancer ; 28(2): 581-588, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31102055

RESUMO

PURPOSE: Cancer-related fatigue (CRF) is a pervasive symptom experienced by cancer patients. Sarcopenia has been suggested as a treatment target of CRF. This study aims to assess the differences of CRF and biochemical markers among different stages of sarcopenia which remain poorly delineated. METHODS: A total of 187 patients were included in this cross-sectional study. Based on muscle mass (skeletal muscle index, SMI), muscle strength (handgrip strength), and physical performance (SARC-F score), patients were divided into four groups (non-sarcopenia, pre-sarcopenia, sarcopenia, and severe sarcopenia). Cancer-related fatigue was measured by the Brief Fatigue Inventory (BFI). Biochemical markers were measured by routine blood tests. RESULTS: The BFI score was significantly associated with sarcopenia stage (r=0.500; P<0.001). Cancer patients in severe sarcopenia group suffered from worse CRF than those in non-sarcopenia, pre-sarcopenia, and sarcopenia groups (P<0.001). In the multivariate linear regression model (R2=0.542), CRF was significantly correlated with SARC-F score (standardized B=0.519; P<0.001) and high-sensitivity C-reactive protein (standardized B=0.389; P=0.004). Serum albumin and cholinesterase were statistically correlated with both sarcopenia stage and CRF. CONCLUSIONS: The significantly increased occurrence and severity of CRF in cancer patients with sarcopenia suggest that sarcopenia may be a crucial target to improve the management of CRF. Circulating albumin and cholinesterase have the potential to predicting sarcopenia as biomarkers.


Assuntos
Fadiga/etiologia , Neoplasias/complicações , Sarcopenia/complicações , Estudos Transversais , Fadiga/enzimologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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