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Peritoneal metastasis is one of the most common risk factors contributing to the poor prognosis of gastric cancer. We previously reported that extracellular vesicles from gastric cancer cells could facilitate peritoneal metastasis. However, their impact on gastric cancer-induced peritoneal metastasis under hypoxic conditions remains unclear. This study aims to elucidate how hypoxia-resistant gastric cancer cell-derived extracellular vesicles affect the peritoneal metastasis of normoxic gastric cancer cells. Proteomic analysis revealed elevated levels of Caveolin1 and Laminin ß2 in hypoxia-resistant gastric cancer cells and their corresponding extracellular vesicles. Importantly, Caveolin1 was found to play a central role in mediating Laminin ß2 sorting into extracellular vesicles derived from hypoxia-resistant gastric cancer cells, and subsequently, extracellular vesicle-associated Laminin ß2 promoted peritoneal metastasis in normoxic gastric cancer cells by activating the AKT pathway. Further investigation confirmed that Caveolin1 activation by Rho-related Coiled-coil kinase 1-mediated phosphorylation of Y14 residue is a key factor facilitating Laminin ß2 sorting into extracellular vesicles. Moreover, Y14 phosphorylated- Caveolin1 enhanced Laminin ß2 sorting by activating Rab11. Finally, our study demonstrated that a combined assessment of plasma extracellular vesicle-associated Caveolin1 and extracellular vesicle-associated Laminin ß2 could provide an accurate predictive tool for peritoneal metastasis occurrence in gastric cancer.
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In the present study, the debatable prognostic value of Ki67 in patients with non-small cell lung cancer (NSCLC) was attributed to the heterogeneity between lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). Based on meta-analyses of 29 studies, a retrospective immunohistochemical cohort of 1479 patients from our center, eight transcriptional datasets and a single-cell datasets with 40 patients, we found that high Ki67 expression suggests a poor outcome in LUAD, but conversely, low Ki67 expression indicates worse prognosis in LUSC. Furthermore, low proliferation in LUSC is associated with higher metastatic capacity, which is related to the stronger epithelial-mesenchymal transition potential, immunosuppressive microenvironment and angiogenesis. Finally, nomogram model incorporating clinical risk factors and Ki67 expression outperformed the basic clinical model for the accurate prognostic prediction of LUSC. With the largest prognostic assessment of Ki67 from protein to mRNA level, our study highlights that Ki67 also has an important prognostic value in NSCLC, but separate evaluation of LUAD and LUSC is necessary to provide more valuable information for clinical decision-making in NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Inmunohistoquímica , Antígeno Ki-67 , Neoplasias Pulmonares , Humanos , Antígeno Ki-67/metabolismo , Antígeno Ki-67/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Pronóstico , Femenino , Masculino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Persona de Mediana Edad , Anciano , Nomogramas , Microambiente Tumoral/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Transición Epitelial-Mesenquimal/genética , Estudios RetrospectivosRESUMEN
Extracellular vesicles (EVs) represent a diverse class of nanoscale membrane vesicles actively released by cells. These EVs can be further subdivided into categories like exosomes and microvesicles, based on their origins, sizes, and physical attributes. Significantly, disease-derived EVs have been detected in virtually all types of body fluids, providing a comprehensive molecular profile of their cellular origins. As a result, EVs are emerging as a valuable addition to liquid biopsy techniques. In this collective statement, the authors share their current perspectives on EV-related research and product development, with a shared commitment to translating this newfound knowledge into clinical applications for cancer and other diseases, particularly as disease biomarkers. The consensus within this document revolves around the overarching recognition of the merits, unresolved questions, and existing challenges surrounding EVs. This consensus manuscript is a collaborative effort led by the Committee of Exosomes, Society of Tumor Markers, Chinese anti-Cancer Association, aimed at expediting the cultivation of robust scientific and clinically applicable breakthroughs and propelling the field forward with greater swiftness and efficacy.
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A wealth of evidence has emerged that there is an association between aging, senescence and tumorigenesis. Senescence, a biological process by which cells cease to divide and enter a status of permanent cell cycle arrest, contributes to aging and aging-related diseases, including cancer. Aging populations have the higher incidence of cancer due to a lifetime of exposure to cancer-causing agents, reduction of repairing DNA damage, accumulated genetic mutations, and decreased immune system efficiency. Cancer patients undergoing cytotoxic therapies, such as chemotherapy and radiotherapy, accelerate aging. There is growing evidence that p53/MDM2 (murine double minute 2) axis is critically involved in regulation of aging, senescence and oncogenesis. Therefore, in this review, we describe the functions and mechanisms of p53/MDM2-mediated senescence, aging and carcinogenesis. Moreover, we highlight the small molecular inhibitors, natural compounds and PROTACs (proteolysis targeting chimeras) that target p53/MDM2 pathway to influence aging and cancer. Modification of p53/MDM2 could be a potential strategy for treatment of aging, senescence and tumorigenesis.
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Envejecimiento , Carcinogénesis , Senescencia Celular , Neoplasias , Proteínas Proto-Oncogénicas c-mdm2 , Transducción de Señal , Proteína p53 Supresora de Tumor , Humanos , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Envejecimiento/metabolismo , Animales , Neoplasias/metabolismo , Neoplasias/etiología , Neoplasias/patología , Neoplasias/tratamiento farmacológico , Carcinogénesis/metabolismo , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/genéticaRESUMEN
Lymph node (LN) metastasis is a common mode of metastasis in advanced gastric cancer (GC), while axillary LN metastasis infrequently occurs in GC. There are few reports on this rare type of metastasis - especially its clinicopathological features - and systemic treatment are unclear. We describe a case of GC with extensive metastasis, including the rare axillary LN metastasis. The patient achieved partial response of optimal efficacy, who was treated with combination immunotherapy as second-line treatment for nearly two years. The potential mechanisms were revealed by clinical and immune characteristics, such as high expression of PD-L1, high tumor mutational burden (TMB-H), Epstein-Barr virus (EBV) positive and CD8+ tumor-infiltrating lymphocyte positive.
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Infecciones por Virus de Epstein-Barr , Neoplasias Gástricas , Humanos , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , Metástasis Linfática , Ganglios Linfáticos/metabolismo , InmunoterapiaRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of regorafenib monotherapy or in combination with immune-checkpoint inhibitor while treating Chinese patients with metastatic colorectal cancer (mCRC): a real-world study. METHODS: The data of patients with metastatic colorectal cancer who received regorafenib-containing regimen as the third or later line treatment at ten Chinese hospitals from Aug 2017 to Jun 2020 were retrospectively analyzed, including dosing details, survival data as well as adverse events. Survival analysis was further performed for patients administrated with regorafenib monotherapy and combined with an immune-checkpoint inhibitor based on Kaplan-Meier and Cox regression methods. The primary endpoint was overall survival. RESULTS: A total of 537 patients were included with a median age of 61, among whom 376 received regorafenib monotherapy and 245 received regorafenib combined with immune-checkpoint inhibitors. The clinicopathological characteristics of the two groups at baseline were mainly balanced. No significant difference in progression-free survival (PFS) was observed in patients receiving regorafenib monotherapy or combination therapy (3.8 vs. 5.5 months, p = 0.170). In contrast, patients receiving combination therapy had a more prolonged overall survival (OS) than those receiving regorafenib monotherapy (13.5 vs. 10.0 months, p = 0.001). The treatment regimen and regorafenib dosage were significant prognostic factors in the multivariate analysis. Significant benefits in PFS and OS were achieved in KRAS mutant and anti-angiogenesis treatment-naïve subgroups receiving combination therapy compared to monotherapy. No apparent increase was recorded in treatment-related adverse events in patients receiving combination therapy. CONCLUSION: Regorafenib plus an immune-checkpoint inhibitor has already been a widely adopted strategy in the later-line treatment for mCRC in the real world. The combination therapy yielded a significantly prolonged overall survival than regorafenib alone, with a manageable safety profile in Chinese patients, and warrants further investigation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04835324. Registered 6th April 2021.
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Piridinas/efectos adversos , Compuestos de Fenilurea/efectos adversosRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid tumors. The tumor immune microenvironment (TIME) formed by interactions among cancer cells, immune cells, cancer-associated fibroblasts (CAF), and extracellular matrix (ECM) components drives PDAC in a more immunosuppressive direction: this is a major cause of therapy resistance and poor prognosis. In recent years, research has advanced our understanding of the signaling mechanism by which TIME components interact with the tumor and the evolution of immunophenotyping. Through revolutionary technologies such as single-cell sequencing, we have gone from simply classifying PDACs as "cold" and "hot" to a more comprehensive approach of immunophenotyping that considers all the cells and matrix components. This is key to improving the clinical efficacy of PDAC treatments. In this review, we elaborate on various TIME components in PDAC, the signaling mechanisms underlying their interactions, and the latest research into PDAC immunophenotyping. A deep understanding of these network interactions will contribute to the effective combination of TIME-based therapeutic approaches, such as immune checkpoint inhibitors (ICI), adoptive cell therapy, therapies targeting myeloid cells, CAF reprogramming, and stromal normalization. By selecting the appropriate integrated therapies based on precise immunophenotyping, significant advances in the future treatment of PDAC are possible.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/patología , Neoplasias Pancreáticas/patología , Resultado del Tratamiento , Transducción de Señal , Microambiente TumoralRESUMEN
Kirsten rats sarcoma viral oncogene (KRAS), the first discovered human oncogene, has long been recognized as "undruggable". KRAS mutations frequently occur in multiple human cancers including non-small cell lung cancer(NSCLC), colorectal cancer(CRC) and pancreatic ductal adenocarcinoma(PDAC), functioning as a "molecule switch" determining the activation of various oncogenic signaling pathways. Except for its intrinsic pro-tumorigenic role, KRAS alteration also exhibits an unique immune signature characterized by elevated PD-L1 level and high tumor mutational burden(TMB). KRAS mutation shape an immune suppressive microenvironment by impeding effective T cells infiltration and recruiting suppressive immune cells including myeloid-derived suppressor cells(MDSCs), regulatory T cells(Tregs), cancer associated fibroblasts(CAFs). In immune checkpoint inhibitor(ICI) era, NSCLC patients with mutated KRAS tend to be more responsive to ICI than patients with intact KRAS. The hallmark for KRAS mutation is the existence of multiple kinds of co-mutations. Different types of co-alterations have distinct tumor microenvironment(TME) signatures and responses to ICI. TP53 co-mutation possess a "hot" TME and achieve higher response to immunotherapy while other loss of function mutation correlated with a "colder" TME and a poor outcome to ICI-based therapy. The groundbreaking discovery of KRAS G12C inhibitors significantly improved outcomes for this KRAS subtype even though efficacy was limited to NSCLC patients. KRAS G12C inhibitors also restore the suppressive TME, creating an opportunity for combinations with ICI. However, an inevitable challenge to KRAS inhibitors is drug resistance. Promising combination strategies such as combination with SHP2 is an approach deserve further exploration because of their immune modulatory effect.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neoplasias Pancreáticas , Animales , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/patología , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Microambiente TumoralRESUMEN
The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence-based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti-angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)-positive and deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Oncología Médica , Inmunoterapia , Terapia Neoadyuvante , ChinaRESUMEN
BACKGROUND: The combinations of PD-1 inhibitors with paclitaxel/cisplatinum (PD-1 + TP) and fluoropyrimidine/cisplatinum (PD-1 + FP) both have been shown to improve overall survival (OS) and progression-free survival (PFS) in patients with previously untreated, advanced esophageal squamous cell carcinoma (ESCC). However, there is no consensus on which chemotherapy regimen combined with PD-1 has better efficacy. To deal with this important issue in the first-line treatment of patients with ESCC, a network meta-analysis (NMA) was performed. METHODS: Data were collected from eligible studies searched in Medline, Web of Science, PubMed, the Cochrane Library and Embase. The pooled hazard ratio (HR) for the OS, and PFS, odds ratio (OR) for the objective response rate (ORR) and ≥ 3 grade treatment-related adverse events (≥ 3TRAEs) were estimated to evaluate the efficacy of PD-1 inhibitors combined with TP or FP. RESULTS: Five RCTs and one retrospective study involving 3685 patients and evaluating four treatments were included in this NMA. Compared to other treatments, PD-1 + TP was better. For the PFS, the HRs for PD-1 + TP compared to PD-1 + FP, TP and FP were 0.59 (0.44, 0.80), 0.56 (0.51, 0.61) and 0.45 (0.37, 0.56) respectively. For the OS, PD-1 + TP was also a better treatment compared to other treatments. The HRs were 0.74 (0.56, 0.96), 0.64 (0.57, 0.71), 0.53 (0.43, 0.67) respectively. For the ORR, there was no significant difference between PD-1 + TP and PD-1 + FP, and the ORs were 1.2 (0.69, 2.11). Compare with TP and FP, PD-1 + TP had an obvious advantage, ORs were 2.5 (2.04, 3.04) and 2.95 (1.91, 4.63). For ≥ 3TRAEs, PD-1 + TP compared to other treatments, ORs were 1.34 (0.74, 2.46) and 1.13 (0.92, 1.38) and 2.23 (1.35, 3.69). CONCLUSION: PD-1 + TP significantly improved both PFS and OS compared to PD-1 + FP. Taking into account both efficacy and safety, PD-1 + TP may be a superior first-line treatment option for ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Cisplatino , Paclitaxel , Carcinoma de Células Escamosas de Esófago/etiología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Esofágicas/patología , Metaanálisis en Red , Estudios Retrospectivos , Receptor de Muerte Celular Programada 1/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Hepatic sarcomatoid carcinoma (HSC) is characterized by its aggressive behavior and poor prognosis. As of now, no universally endorsed standard therapeutic approaches for HSC have been established. Herein, we describe the case of a 60-year-old individual diagnosed with HSC, subsequently presenting with multiple metastases postoperatively. Owing to the pronounced expression of programmed cell death protein 1 (PD-1), the individual was subjected to monotherapy utilizing sintilimab for a duration spanning 12 months. Following this regimen, a synergistic treatment approach comprising both anlotinib and sintilimab was instituted, culminating in an ensuing 11 months of efficacious therapeutic response. Throughout the course of treatment, the patient's quality of life remained satisfactory. This particular therapeutic strategy not merely reinforces the efficacy of PD-1 inhibitors in the realm of HSC management, but more pivotally, suggests that tyrosine kinase inhibitors (TKIs) might counteract resistance to PD-1 antagonists, thus offering a potentially augmented treatment paradigm for HSC.
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Carcinoma de Células Renales , Carcinoma , Neoplasias Renales , Humanos , Persona de Mediana Edad , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Receptor de Muerte Celular Programada 1 , Calidad de Vida , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , InmunoterapiaRESUMEN
To develop a long-term drug delivery system for the treatment of primary and metastatic peritoneal carcinoma (PC) by intraperitoneal (IP) injection, a disulfiram (DSF)/copper gluconate (Cu-Glu)-co-loaded bi-layered poly (lactic acid-coglycolic acid) (PLGA) microspheres (Ms) - thermosensitive hydrogel system (DSF-Ms-Cu-Glu-Gel) was established. Rate and mechanisms of drug release from DSF-Ms-Cu-Glu-Gel were explored. The anti-tumor effects of DSF-Ms-Cu-Glu-Gel by IP injection were evaluated using H22 xenograft tumor model mice. The accumulative release of DSF from Ms on the 10th day was 83.79% without burst release. When Ms were dispersed into B-Gel, burst release at 24 h decreased to 14.63%. The results showed that bis (diethyldithiocarbamate)-copper (Cu(DDC)2) was formed in DSF-Ms-Cu-Glu-Gel and slowly released from B-Gel. In a pharmacodynamic study, the mount of tumor nodes and ascitic fluid decreased in the DSF-Ms-Cu-Glu-Gel group. This was because: (1) DSF-Ms-Cu-Glu-Gel system co-loaded DSF and Cu-Glu, and physically isolated DSF and Cu-Glu before injection to protect DSF; (2) space and water were provided for the formation of Cu(DDC)2; (3) could provide an effective drug concentration in the abdominal cavity for a long time; (4) both DSF and Cu(DDC)2 were effective anti-tumor drugs, and the formation of Cu(DDC)2 occurred in the abdominal cavity, which further enhanced the anti-tumor activity. Thus, the DSF-Ms-Cu-Glu-Gel system can be potentially used for the IP treatment of PC in the future.
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Disulfiram , Neoplasias Peritoneales , Humanos , Animales , Ratones , Disulfiram/farmacología , Neoplasias Peritoneales/tratamiento farmacológico , Cobre/farmacología , Línea Celular Tumoral , Sistemas de Liberación de MedicamentosRESUMEN
The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Jing Gong, Yongxi Song, Ling Xu, Xiaofang Che, Kezuo Hou, Tianshu Guo, Yu Cheng, Yunpeng Liu, Xiujuan Qu. Upregulation of Serine Proteinase Inhibitor Clade B Member 3 (SERPINB3) Expression by Stromal Cell-Derived Factor (SDF-1)/CXCR4/Nuclear Factor kappa B (NF-kB) Promotes Migration and Invasion of Gastric Cancer Cells. Med Sci Monit, 2020; 26: e927411. DOI: 10.12659/MSM.927411.
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Cell migration is a pivotal step in metastatic process, which requires cancer cells to navigate a complex spatially-confined environment, including tracks within blood vessels and in the vasculature of target organs. Here it is shown that during spatially-confined migration, the expression of insulin-like growth factor-binding protein 1 (IGFBP1) is upregulated in tumor cells. Secreted IGFBP1 inhibits AKT1-mediated phosphorylation of mitochondrial superoxide dismutase (SOD2) serine (S) 27 and enhances SOD2 activity. Enhanced SOD2 attenuates mitochondrial reactive oxygen species (ROS) accumulation in confined cells, which supports tumor cell survival in blood vessels of lung tissues, thereby accelerating tumor metastasis in mice. The levels of blood IGFBP1 correlate with metastatic recurrence of lung cancer patients. This finding reveals a unique mechanism by which IGFBP1 sustains cell survival during confined migration by enhancing mitochondrial ROS detoxification, thereby promoting tumor metastasis.
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Neoplasias Pulmonares , Animales , Ratones , Supervivencia Celular , Neoplasias Pulmonares/metabolismo , Fosforilación , Especies Reactivas de Oxígeno/metabolismo , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/metabolismoRESUMEN
Objective: Apatinib and irinotecan are used as systematic therapies for advanced gastric adenocarcinoma (GAC) and gastroesophageal junction adenocarcinoma (GEJA), while the evidence for their combination as second-line therapy in these patients is limited. This study aimed to evaluate the efficacy and safety of second-line apatinib plus irinotecan for the treatment of GAC and GEJA. Methods: In this prospective, multicenter phase II clinical study, 28 patients with advanced GAC or GEJA who received second-line apatinib plus irinotecan were recruited. Results: In total, 1 (3.6%) patient achieved complete response, 7 (25.0%) patients achieved partial response, 13 (46.4%) patients had stable disease, and 4 (14.3%) patients showed progressive disease, while clinical response was not evaluable or not assessed in 3 (10.7%) patients. The objective response rate and disease control rate were 28.6% and 75.0%, respectively. Meanwhile, the median (95% confidence interval (CI)) progression-free survival (PFS) was 4.5 (3.9-5.1) months, and the median (95% CI) overall survival (OS) was 11.3 (7.4-15.1) months. By multivariate Cox regression analysis, male sex, liver metastasis, and peritoneal metastasis were independently associated with worse PFS or OS, while treatment duration ≥5 months was independently associated with better OS. In terms of the safety profile, 89.3% of patients experienced treatment-emergent adverse events of any grade, among which 82.1% of patients had grade 1-2 adverse events and 64.3% of patients had grade 3-4 adverse events. Conclusion: Apatinib plus irinotecan as second-line therapy achieves a good treatment response and satisfactory survival with tolerable safety in patients with advanced GAC or GEJA.
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OBJECTIVES: This research aimed to explore the relationship between pre-treatment inflammatory markers and other clinical characteristics and the survival of small-cell lung cancer (SCLC) patients who received first-line platinum-based treatment and to construct nomograms for predicting overall survival (OS) and progression-free survival (PFS). METHODS: A total of 612 patients diagnosed with SCLC between March 2008 and August 2021 were randomly divided into two cohorts: a training cohort (n = 459) and a validation cohort (n = 153). Inflammatory markers, clinicopathological factors, and follow-up information of patients were collected for each case. Cox regression was used to conduct univariate and multivariate analyses and the independent prognostic factors were adopted to develop the nomograms. Harrell's concordance index (C-index) and time-dependent receiver operating characteristic curve were used to verify model differentiation, calibration curve was used to verify consistency, and decision curve analysis was used to verify the clinical application value. RESULTS: Our results showed that baseline C-reactive protein/albumin ratio, neutrophil/lymphocyte ratio, NSE level, hyponatremia, the efficacy of first-line chemotherapy, and stage were independent prognostic factors for both OS and PFS in SCLC. In the training cohort, the C-index of PFS and OS was 0.698 and 0.666, respectively. In the validation cohort, the C-index of PFS and OS was 0.727 and 0.747, respectively. The nomograms showed good predictability and high clinical value. Also, our new clinical models were superior to the US Veterans Administration Lung Study Group (VALG) staging for predicting the prognosis of SCLC. CONCLUSIONS: The two prognostic nomograms of SCLC including inflammatory markers, VALG stage, and other clinicopathological factors had good predictive value and could individually assess the survival of patients.
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Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Pronóstico , Carcinoma Pulmonar de Células Pequeñas/patología , Nomogramas , Procesos de Grupo , Estadificación de NeoplasiasRESUMEN
Transcranial photobiomodulation (tPBM) is an emerging non-invasive light-based neuromodulation technique that shows promising potential for improving working memory (WM) performance in older adults. However, the neurophysiological mechanisms associated with tPBM that underlie the improvement of WM and the persistence of such improvement have not been investigated. Sixty-one healthy older adults were recruited to receive a baseline sham stimulation, followed by one-week active tPBM (12 min daily, 1064-nm laser, 250 mW/cm2) and three-week follow-ups. N-back WM task was conducted on post-stimulation of the baseline, the first (Day 1) and seventh (Day 7) days of the active treatment, and at the follow-ups. During the task, functional near-infrared spectroscopy (fNIRS) imaging was employed to record the cortical hemodynamic changes. Brain activations during the active and follow-up sessions were compared with the baseline to determine how tPBM had changed cortical hemodynamic activity and how long these changes persisted. We found that tPBM stimulation on Day 1 induced significantly decreased activation in the right hemisphere during the 3-back. The decreased activation expanded from only the right hemisphere on Day 1 to both hemispheres on Day 7. The decreased activation persisted for one week in the right supramarginal gyrus and the left angular gyrus and two weeks in the left somatosensory association cortex. These activation changes were accompanied by significantly improved task accuracy during the N-back. These findings provide important evidence for understanding neural mechanisms underlying cognitive enhancement after tPBM.
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Memoria a Corto Plazo , Corteza Prefrontal , Humanos , Anciano , Memoria a Corto Plazo/fisiología , Corteza Prefrontal/fisiología , Hemodinámica , Diagnóstico por ImagenRESUMEN
The amplitude of low-frequency fluctuation (ALFF) describes the regional intensity of spontaneous blood-oxygen-level-dependent signal in resting-state functional magnetic resonance imaging (fMRI). How the fMRI-ALFF relates to the amplitude in electrophysiological signals remains unclear. We here aimed to investigate the neural correlates of fMRI-ALFF by comparing the spatial difference of amplitude between the eyes-closed (EC) and eyes-open (EO) states from fMRI and magnetoencephalography (MEG), respectively. By synthesizing MEG signal into amplitude-based envelope time course, we first investigated 2 types of amplitude in MEG, meaning the amplitude of neural activities from delta to gamma (i.e. MEG-amplitude) and the amplitude of their low-frequency modulation at the fMRI range (i.e. MEG-ALFF). We observed that the MEG-ALFF in EC was increased at parietal sensors, ranging from alpha to beta; whereas the MEG-amplitude in EC was increased at the occipital sensors in alpha. Source-level analysis revealed that the increased MEG-ALFF in the sensorimotor cortex overlapped with the most reliable EC-EO differences observed in fMRI at slow-3 (0.073-0.198 Hz), and these differences were more significant after global mean standardization. Taken together, our results support that (i) the amplitude at 2 timescales in MEG reflect distinct physiological information and that (ii) the fMRI-ALFF may relate to the ALFF in neural activity.