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Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, presenting limited therapeutic options and a grim prognosis due to its aggressive nature. Despite ongoing exploration of various combination therapies, a standardized treatment approach after the first-line treatment progress remains elusive. This report details the cases of two patients with unresectable advanced PDAC who underwent distinct conversion treatment regimens involving immune checkpoint inhibitors (ICIs). Remarkably, both patients became eligible for surgery following different anti-PD-1 antibody-based conversion therapies, ultimately achieving R0 resection. In essence, our findings highlight the efficacy of the anti-PD-1 antibody combined with a tyrosine kinase inhibitor (TKI) regimen and chemotherapy alongside anti-PD-1 antibody as viable conversion therapies for preoperative advanced PDAC. Tumor immune microenvironment (TIME) analysis underscores the intratumoral and intertumoral heterogeneity observed in the postoperative immune landscape of surgical specimens. This insight contributes to a deeper understanding of the potential benefits of these conversion therapies in addressing the challenging landscape of advanced PDAC.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Prognóstico , Imunidade , Microambiente TumoralRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is notorious for its resistance to various treatment modalities. The genetic heterogeneity of PDAC, coupled with the presence of a desmoplastic stroma within the tumor microenvironment (TME), contributes to an unfavorable prognosis. The mechanisms and consequences of interactions among different cell types, along with spatial variations influencing cellular function, potentially play a role in the pathogenesis of PDAC. Understanding the diverse compositions of the TME and elucidating the functions of microscopic neighborhoods may contribute to understanding the immune microenvironment status in pancreatic cancer. As we delve into the spatial biology of the microscopic neighborhoods within the TME, aiding in deciphering the factors that orchestrate this intricate ecosystem. This overview delineates the fundamental constituents and the structural arrangement of the PDAC microenvironment, highlighting their impact on cancer cell biology.
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Pancreatoblastoma (PB), a neoplasm derived from pancreatic follicular cells, primarily affects the pediatric population. Although infrequent in adults, it is associated with a considerably worse prognosis. Approximately one-third of patients are diagnosed with metastatic disease, with liver metastases being the most prevalent. Diagnosis relies on histopathological alterations including squamous vesicles, positive staining for CK8/CK18/CK19, and nuclear displacement of ß-catenin. Additionally, liver metastases demonstrate substantial enhancement during the arterial phase of a contrast-enhanced computed tomography (CT) scan. Surgical resection serves as the principal therapeutic approach for addressing primary lesions and liver metastatic PB. In instances where surgical intervention is not viable, patients may derive benefits from systemic therapy and radiotherapy. This particular case report presents the clinical details of a 27-year-old female patient diagnosed with PB, who subsequently developed multiple liver metastases following a pancreaticoduodenectomy. Genomic examinations revealed the presence of ERBB2 amplification, RAD54L deletion, low TMB-L, and MSS in the patient. Despite the patient undergoing chemotherapy and Her-2 targeted therapy in conjunction with immunotherapy, no reduction in lesion size was observed until the administration of surufatinib. Subsequently, a notable outcome ensued, where the metastatic lesions were effectively excised via surgical intervention. Surufatinib has demonstrated a progression-free survival (PFS) of no less than 14 months, and the patient's survival has endured for a duration of 33 months. This indicates the potential efficacy of surufatinib as a viable therapeutic alternative for adult patients afflicted with PB.
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BACKGROUND: Polysaccharides from Grifola frondosa(GFP) have gained worldwide attention owing to their promising biological activities and potential health benefits. PURPOSE: This study aimed to investigate the effects of GFP on alleviation of osteoporosis in ovariectomized (OVX) mice and examine the underlying mechanism. METHOD: A mouse model of postmenopausal osteoporosis was established by OVX method, Forty eight C57BL/6 female mice were randomly divided into Normal group, OVX alone (Model group, n = 8), OVX + 10 mg/kg GFP (GFP-L group, n = 8), OVX + 20 mg/kg GFP (GFP-M group, n = 8), OVX + 40 mg/kg GFP (GFP-H group, n = 8), OVX + 10 mg/kg Estradiol valerate (Positive group, n = 8). RESULTS: The results showed that compared with Model group, the concentrations of interleukin (IL)-1ß, interleukin (IL)-6 and Tumor necrosis factor-α (TNF-α) were significantly reduced, the activity of superoxide dismutase (SOD) and glutathione (GSH) were significantly increased, the content of myeloperoxidase (MPO) and malondialdehyde (MDA) were significantly reduced, and the proteins levels of PINK1, Parkin, Beclin-1 and LC3-II were significantly decreased in the GFP groups. CONCLUSION: This study demonstrates that GFP alleviates ovariectomy-induced osteoporosis via reduced secretion of inflammatory cytokines, improvement in the oxidative stress status in the body, and inhibition of the PINK1/Parkin signaling pathway.
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Grifola , Inflamação , Osteoporose , Ovariectomia , Estresse Oxidativo , Proteínas Quinases , Transdução de Sinais , Ubiquitina-Proteína Ligases , Animais , Ovariectomia/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Feminino , Camundongos , Transdução de Sinais/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Osteoporose/prevenção & controle , Osteoporose/metabolismo , Proteínas Quinases/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Grifola/química , Camundongos Endogâmicos C57BL , Citocinas/metabolismo , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/química , Modelos Animais de DoençasRESUMO
INTRODUCTION: Patients with pancreatic ductal adenocarcinoma (PDAC) remain a poor prognosis despite the development of chemotherapy. Although programmed cell death 1 (PD-1) blockade has shown great efficacy in various solid tumours, its application in treating PDAC is limited. Recent studies have indicated that chemotherapy or stereotactic body radiotherapy (SBRT) may improve the antitumour effect of PD-1 blockade in patients with PDAC. The objective of this study is to evaluate the efficacy and safety of combined therapy comprising PD-1 blockade, gemcitabine plus nab-paclitaxel chemotherapy and SBRT for patients with metastatic PDAC. METHODS AND ANALYSIS: This is a multicentre, single-arm, prospective phase II clinical trial. Forty-three patients diagnosed with metastatic PDAC will be enrolled. The eligible patients will be intravenously administered 1000 mg/m2 gemcitabine and 125 mg/m2 nab-paclitaxel on days 1 and 8 of the 21-day cycle. Serplulimab (200 mg) will be administered intravenously on day 1 of the 21-day cycle. Furthermore, during the second cycle, the patients will undergo SBRT with doses of 33 Gy in five fractions for primary lesions or doses of 24 Gy in three fractions for metastases. The primary endpoint is the 6-month progression-free survival (PFS) rate. The secondary endpoints overall survival, PFS, overall response rate, disease control rate, time to progression, duration of response, duration of disease control and safety. Moreover, this trial seeks to investigate biomarkers such as circulating tumour DNA and circulating hybrid cells in patients diagnosed with metastatic PDAC. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University. The study results will be presented at international conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2300073237.
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Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina , Gencitabina , Paclitaxel , Neoplasias Pancreáticas , Radiocirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/terapia , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Albuminas/uso terapêutico , Albuminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/patologia , China , Ensaios Clínicos Fase II como Assunto , Terapia Combinada , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Desoxicitidina/administração & dosagem , Estudos Multicêntricos como Assunto , Paclitaxel/uso terapêutico , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Intervalo Livre de Progressão , Estudos Prospectivos , Radiocirurgia/métodosRESUMO
RATIONALE AND OBJECTIVES: Clinicians must precisely pinpoint the etiology of low back pain as the number of people suffering from it increases to provide targeted care. The purpose of this paper was to use MR imaging radiomics based on lumbar soft tissue to analyze changes in the lumbar fascia of patients with low back pain. MATERIALS AND METHODS: We retrospectively analyzed the lumbar MRI of 197 patients with low back pain. Patients were randomly assigned to either the training (n = 138) or validation (n = 59) cohorts. Multivariate logistic regression analysis was used to create radiomics model and combined nomogram model and their predictive performance were evaluated using receiver operating characteristic curves. RESULTS: Seven radiomics features based on lumbar soft tissue MRI images were established, which performed well in distinguishing between low back pain patients with fascial changes and normal individuals demonstrated an excellent ability to identify differences, with an Area Under Curve (AUC) of 0.92 (95% CI, 0.88-0.96) in the training cohort and 0.84 (95% CI, 0.73-0.96) in the validation cohort, which performed better than the clinical model significantly only. CONCLUSION: The nomogram based on clinical features and radiomics features of MR images had a good predictive ability to differentiate fascial alterations in patients with low back pain from normal subjects. It had the potential to be used as a decision support tool to assist clinicians in determining the etiology of patients with lower back pain and managing patients promptly, particularly in the early stage of the fasciitis when significant abnormalities on imaging were difficult to detect.
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Solute carrier family 31 member 1 (SLC31A1) encodes a protein that functions as a homotrimer for the uptake of dietary copper. As a vital member of the cuproptosis gene family, it plays an essential role in both normal tissues and tumors. In this study, we analyzed SLC31A1 across human cancer types to gain a better understanding of SLC31A1's role in cancer development. We searched for information using online databases to analyze, systematically and comprehensively, the role of SLC31A1 in tumors. Amongst nine cancer types, the expression of SLC31A1 was significantly different between tumors and normal tissues. According to further analysis, pancreatic cancer had the highest mutation rate of the SLC31A1 gene, and the methylation levels of the gene were significantly reduced in seven tumors. The expression of SLC31A1 is also linked to the infiltration of tumors by immune cells, the expression of immune checkpoint genes, and immunotherapy markers (TMB and MSI), suggesting that SLC31A1 may be of particular relevance in immunotherapy. This thorough analysis of SLC31A1 across different types of cancer gives us a clear and comprehensive insight into its role in causing cancer on a systemic level.
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Epstein-Barr virus-associated lymphoepithelioma-like intrahepatic cholangiocarcinoma (EBVa LEL-ICC) is a rare tumor, characterized by a rich tumor immune microenvironment (TIME). While this tumor is reportedly sensitive to immunotherapy, its response has been inconsistent. This decreased sensitivity was associated with reduced TIME abundance. We report the case of a 53-year-old woman with EBVa LEL-ICC having reduced TIME abundance. The patient presented with a liver lesion, which was detected using ultrasound. Initially, the tumor was sensitive to immunotherapy and chemotherapy (IC), but resistance developed after a short interval. Subsequently, stereotactic ablative radiotherapy (SABR) was added to the patient's treatment, which now consisted of ICSABR. Successful tumor shrinkage was achieved with the combination therapy regimen. Thus, surgery and ICSABR are effective adjuncts to the first-line IC therapy in improving the survival rate of patients with EBVa LEL-ICC. The results of this study support multidisciplinary treatment as a viable treatment strategy for EBVa LEL-ICC.