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In this study, lignin nanoparticles (LN) and octadecylamine-modified LN (LN-ODA) were utilized as coating materials to enhance the hydrophobic, antioxidant, and ultraviolet radiation-shielding (UV-shielding) properties of a TEMPO-oxidized nanocellulose film (TOCNF). The water contact angle (WCA) of the TOCNF was approximately 53° and remained stable for 1 min, while the modified LN-ODA-coated TOCNF reached over 130° and maintained approximately 85° for an hour. Pure TOCNF exhibited low antioxidant properties (4.7 %), which were significantly enhanced in TOCNF-LN (81.6 %) and modified LN-ODA (10.3 % to 27.5 %). Modified LN-ODA-coated TOCNF exhibited antioxidant properties two to six times higher than those of pure TOCNF. Modified LN-ODA exhibited thermal degradation max (Tmax) at 421 °C, while pure LN showed the main degradation temperature at approximately Tmax 330 °C. The thermal stability of TOCNF-LN-ODA-coated materials remained consistent with that of pure TOCNF, while the crystallinity index of the sample showed a slight decrease due to the amorphous nature of the lignin structure. The tensile strength of TOCNF was approximately 114.1 MPa and decreased to 80.1, 51.3, and 30.3 MPa for LN-ODA coating at 5, 10, and 15 g/m2, respectively.
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Objectives: This study aimed to summarize the existing literature on risk factors for arrhythmias after chemotherapy in cancer patients. To provide reliable evidence for treating arrhythmias after chemotherapy in oncology patients by assessing multiple biasing factors in the literature and quantifying the risk factors. Methods: The risk factors for arrhythmia following tumor chemotherapy were systematically collected from various reputable databases, including PubMed, Cochrane Library, MEDLINE, EMBASE, and multiple Chinese databases, covering the period from inception to May 2023. Two independent reviewers performed rigorous article screening, data extraction, and assessment of research quality. Data analysis was conducted using Review Manager 5.4 software, ensuring a standardized and robust approach to evaluate the gathered evidence. Results: The analysis of chemotherapy-induced arrhythmias included 16 articles, encompassing 14,785 cancer patients. Among the patients, 3295 belonged to the arrhythmia group, while 11,490 were in the non-arrhythmia group. These studies identified 12 significant risk factors associated with arrhythmias following chemotherapy in cancer patients. The findings of the analysis are as follows. General patient characteristics: The incidence of post-chemotherapy arrhythmias was 14.33 times higher in oncology patients aged ≥60 years compared to patients <60 years of age [OR = 14.33, 95%CI (8.51, 24.13), Pï¼0.00001]. Patients with a smoking history exhibited a 1.67-fold higher risk of arrhythmia after chemotherapy [OR = 1.67, 95%CI (1.24, 2.25), P = 0.0007]. However, there was no significant correlation between gender and body mass index (BMI) with arrhythmia after chemotherapy in oncology patients (P = 0.52; P = 0.19). Disease-related factors: Patients with a history of hypertension, diabetes, and cardiovascular disease had a 1.93-fold, 1.30-fold, and 1.76-fold increased risk of arrhythmia after chemotherapy, respectively [OR = 1.93, 95%CI (1.66, 2.24), Pï¼0.00001; OR = 1.30, 95%CI (1.10, 2.52), P = 0.002; OR = 1.76, 95%CI (1.51, 2.05), Pï¼0.00001]. Additionally, the incidence of arrhythmia increased 1.97 times in patients with electrolyte and acid-base balance disorders following chemotherapy [OR = 1.97, 95%CI (1.41, 2.76), Pï¼0.00001]. Chemotherapy-related factors: Seven articles examined the association between chemotherapy drugs and post-chemotherapy arrhythmias. The results indicated that oncology patients were 3.03 times more likely to develop arrhythmias with chemotherapy drugs compared to non-chemotherapy drugs [OR = 3.03, 95%CI (2.59, 3.54), Pï¼0.00001]. Notably, anthracyclines and fluorouracil chemotherapy demonstrated a 2.98-fold and 3.35-fold increased risk of arrhythmia after chemotherapy, respectively [OR = 2.98, 95%CI (2.51, 3.03), Pï¼0.00001; OR = 3.35, 95%CI (2.20, 5.10), Pï¼0.00001]. The risk of arrhythmia after chemotherapy was 1.72 times higher in patients with chemotherapy cycles longer than 4 weeks than those with cycles shorter than 4 weeks [OR = 1.72, 95%CI (1.30, 2.28), P = 0.0001]. Conclusion: The occurrence of arrhythmia after chemotherapy in cancer patients was significantly associated with the patient's age, history of smoking, history of hypertension, history of diabetes, history of cardiovascular disease, chemotherapy drug use, and cycle. However, further high-quality evidence is needed to support these results.
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Materials and Methods: We analyzed RNA-seq data from the Cancer Genome Atlas (TCGA-STAD) and Gene Expression Omnibus (GEO) datasets, focusing on five cDC1-related genes. The cDC1-related signature was defined and divided into high and low expression groups. We employed gene set variation analysis (GSVA) for oncogenic signaling pathways and conducted comprehensive statistical analyses, including Kaplan-Meier and Cox proportional hazards models. Results: The high cDC1-related gene signature group was associated with poorer overall and disease-free survival in the TCGA-STAD cohort. Significant differences in CD8+ T cell infiltration and cytotoxic capabilities were observed between high and low CDC1-related signature groups. The study also revealed a strong correlation between CDC1-related signature and increased expression of immune checkpoint proteins and oncogenic pathways, suggesting a complex immunosuppressive tumor microenvironment. Conclusions: Our findings indicate the potential of the cDC1-related signature as a prognostic marker in GC, offering insights into the tumor-immune interplay. The study underscores the importance of cDC1s in shaping the tumor microenvironment and their influence on patient prognosis in GC. These results may contribute to the development of novel therapeutic strategies targeting the immune microenvironment in GC.
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Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas , Microambiente Tumoral , Feminino , Humanos , Masculino , Biomarcadores Tumorais/genética , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Perfilação da Expressão Gênica , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Prognóstico , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Transcriptoma , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Células DendríticasRESUMO
Background: Solitary fibrous tumor (SFT) is a rare soft tissue tumor originating from mesenchymal cells. Thus far, there have been no reported cases of SFT closely related to the iliac vessels. Case presentation: An elderly woman was found to have had a lower abdominal mass for more than 20 years. The enhanced computerized tomography (CT) showed a progressively enhanced hypervascular mass. The external iliac blood vessels were closely related to the mass, which was misdiagnosed as an ovarian tumor. During laparotomy, the external iliac vein was seen to penetrate the tumor, and the external iliac artery was seen to penetrate the tumor capsule. The retroperitoneal tumor was diagnosed during the operation. The surgical plan of complete tumor resection, severing of the external iliac arteries and veins, and blood vessel replacement was implemented. Pathological immunohistochemistry showed positive results for STAT6 and CD34, confirming the diagnosis of giant retroperitoneal SFT. The risk is classified as high and requires long-term follow-up. There has been no local recurrence or distant metastasis almost 1 year after surgery. Conclusion: The incidence of giant retroperitoneal SFT is rare, and the diagnosis can be confirmed through preoperative imaging examination and pathological examination. If the SFT capsule is intact, there is a chance of surgical resection. For SFTs that are penetrated by the iliac blood vessels, adequate preparation must be made before the surgery is performed. Removing the tumor and the iliac blood vessels at the corresponding site and then replacing it with artificial blood vessels is a feasible method with less risk of bleeding. In this case, imaging showed a progressively enhancing hypervascular mass in the lower abdomen, which was related to blood vessels. Preoperative biopsy and pathological testing can confirm the diagnosis. Neoadjuvant therapy or interventional therapy before surgery can shrink the tumor, making the surgical procedure relatively easy with less risk of bleeding.
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OBJECTIVES: This study aimed to investigate the histological and molecular characteristics of atypical central neurocytomas (CNs) and evaluate their clinical treatment outcomes, with the aim of identifying reliable biomarkers for differentiation and optimal treatment strategies. METHODS: We conducted a retrospective study including 61 patients diagnosed with CNs. Clinical data, neuroimaging, and pathological findings were analyzed. RNA sequencing was performed on tumor tissues to identify differentially expressed genes. RESULTS: Histological atypia and the Ki-67 index showed no significant impact on progression-free survival (PFS) or overall survival (OS). RNA sequencing identified significant genetic alterations in pathways such as neuroactive ligand-receptor interaction, cAMP, MAPK, and Ras signaling. Differently expressed genes included AMOTL1, PIK3R3, TGFBR1, SMO, COL4A6, MGP, SOX4, IGF2, SLIT1, and CKS2. The five-year OS rate (p = 0.015) and PFS rate (p = 2.00 × 10-6) were significantly higher in the complete resection (CR) group compared to the incomplete resection (IR) group. Postoperative radiotherapy did not affect OS or PFS in the CR group. The five-year PFS rate (p = 3.80 × 10-5) was significantly longer in patients in the CR group who did not receive radiotherapy compared to those in the IR group who did receive radiotherapy. The extent of surgical resection and operative approaches were found to be irrelevant to perioperative complications and dysfunctions at the last follow-up. CONCLUSION: CR is crucial for a better prognosis in patients with atypical CNs. Additional radiotherapy after CR offers little benefit. Histological atypia and the Ki-67 index are not effective in distinguishing between atypical and typical CNs. Identified genetic alterations provide insights into the aggressive behavior of atypical CNs, suggesting potential therapeutic targets and underscoring the need for further research to optimize treatment strategies.
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ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.
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Medicamentos de Ervas Chinesas , Lipopolissacarídeos , Síndrome do Ovário Policístico , Transdução de Sinais , Receptor 4 Toll-Like , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/induzido quimicamente , Animais , Feminino , Receptor 4 Toll-Like/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Resistência à Insulina , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Desidroepiandrosterona/farmacologia , Cápsulas , Intestinos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologiaRESUMO
BACKGROUND/AIM: Apoptosis resistance in cancer cells adapted to acidic microenvironments poses a challenge for effective treatment. This study investigated the potential use of caffeic acid as an adjunct therapy to overcome drug resistance in colorectal cancer cells under acidic conditions. MATERIALS AND METHODS: Long-term exposure to low-pH conditions induced resistance in HCT116 colorectal cancer cells. The effects of caffeic acid on proliferation, clonogenicity, and apoptosis induction were assessed alone and in combination with oxaliplatin and 5-Fluorouracil. The signaling pathways involved in drug resistance were examined by assessing the activities of PI3K/Akt and ERK1/2. RESULTS: Caffeic acid inhibited the proliferation and clonogenicity of acid-adapted cancer cells, and enhanced apoptosis when combined with anticancer drugs. Mechanistically, caffeic acid attenuated the hyperactivation of the PI3K/Akt and ERK1/2 signaling pathways associated with drug resistance. CONCLUSION: Caffeic acid is a promising therapeutic agent for targeting resistant cancer cells in acidic microenvironments. Its ability to inhibit proliferation, sensitize cells to apoptosis, and modulate signaling pathways highlights its potential for overcoming drug resistance in cancer therapy.
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Apoptose , Ácidos Cafeicos , Proliferação de Células , Neoplasias do Colo , Resistencia a Medicamentos Antineoplásicos , Fluoruracila , Humanos , Ácidos Cafeicos/farmacologia , Apoptose/efeitos dos fármacos , Células HCT116 , Proliferação de Células/efeitos dos fármacos , Fluoruracila/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antineoplásicos/farmacologia , Oxaliplatina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Sinergismo Farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Compostos Organoplatínicos/farmacologia , Microambiente Tumoral/efeitos dos fármacosRESUMO
BACKGROUND: Limb ischemia-reperfusion is a common phenomenon in clinical surgery, which disrupts the balanced physiological response process and ultimately leads to changes in intracellular viscosity. Intracellular viscosity is an important microenvironmental parameter that affects the normal function of organisms, and its level is closely related to many diseases. In addition, oxidative stress in the lower limbs can impair body function, and changes in pressure can lead to changes in the viscosity of limb tissues. Therefore, it is necessary to develop effective tools to detect changes in intracellular viscosity and visualize the progression of hind limb ischemia-reperfusion injury. RESULTS: In order to solve this problem, a near infrared viscometry sensitive fluorescence probe (PH-XQ) with long emission wavelength and stable luminescence performance was designed and synthesized by using oxanthracene derivatives and malononitrile. The fluorescence probe (PH-XQ) has excellent selectivity, high sensitivity, low toxicity, high biocompatibility and excellent detection performance. The fluorescence intensity of the PH-XQ probe at 667 nm is highly sensitive to the change of viscosity. With the increase of viscosity, the fluorescence intensity of probe PH-XQ was significantly enhanced, and the fluorescence enhancement ratio was about 14-fold. In addition, PH-XQ can detect not only changes in viscosity between normal cells and drug-induced inflammatory cells, but also changes in the viscosity of the hind limbs of normal mice and mice after ischemia reperfusion. SIGNIFICANCE: In particular, we are the first to successfully detect changes in handlimb viscosity after ischemia-reperfusion in mice using a probe. This study clearly elucidates changes in viscosity during ischemia-reperfusion of mouse limbs, providing favorable support for the relationship between viscosity and related diseases, and further providing a potential tool for the diagnosis of viscosity-related diseases.
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Corantes Fluorescentes , Traumatismo por Reperfusão , Animais , Viscosidade , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Camundongos , Traumatismo por Reperfusão/diagnóstico por imagem , Membro Posterior , Masculino , Imagem Óptica , Raios Infravermelhos , HumanosRESUMO
Verticillium dahliae is a kind of pathogenic fungus that brings about wilt disease and great losses in cotton. The molecular mechanism of the effectors in V. dahliae regulating cotton immunity remains largely unknown. Here, we identified an effector of V. dahliae, VdPHB1, whose gene expression is highly induced by infection. The VdPHB1 protein is localized to the intercellular space of cotton plants. Knock-out of the VdPHB1 gene in V. dahliae had no effect on pathogen growth, but decreased the virulence in cotton. VdPHB1 ectopically expressed Arabidopsis plants were growth-inhibited and significantly susceptible to V. dahliae. Further, VdPHB1 interacted with the type II metacaspase GhMC4. GhMC4 gene-silenced cotton plants were more sensitive to V. dahliae with reduced expression of pathogen defense-related and programmed cell death genes. The accumulation of GhMC4 protein was concurrently repressed when VdPHB1 protein was expressed during infection. In summary, these results have revealed a novel molecular mechanism of virulence regulation that the secreted effector VdPHB1 represses the activity of cysteine protease for helping V. dahliae infection in cotton.
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Ascomicetos , Gossypium , Doenças das Plantas , Gossypium/microbiologia , Gossypium/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Ascomicetos/patogenicidade , Ascomicetos/fisiologia , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Virulência , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Arabidopsis/microbiologia , Arabidopsis/genética , Arabidopsis/imunologia , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Interações Hospedeiro-Patógeno , Plantas Geneticamente Modificadas , VerticilliumRESUMO
Non-small cell lung cancer (NSCLC) has been found to have recurrent genetic abnormalities, and novel therapies targeting these aberrations have improved patient survival. In this study, specimens from benign tissue, primary tumors, and brain metastases were obtained at autopsy from a 55-year-old White female patient diagnosed with NSCLC and were examined using next-generation sequencing (NGS) and chromosomal microarray assay (CMA). No genetic aberrations were noted in the benign tissue; however, NGS identified a mutation in the KRAS proto-oncogene, GTPase (KRAS): KRAS exon 2 p.G12D in primary and metastatic tumor specimens. We observed 7 DNA copy number aberrations (CNAs) in primary and metastatic tumor specimens; an additional 7 CNAs were exclusively detected in the metastatic tumor specimens. These DNA alterations may be genetic drivers in the pathogenesis of the tumor specimen from our patient and may serve as biomarkers for the classification and prognosis of NSCLC.
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Osteoarthritis (OA) is one of the most common degenerative diseases characterised by joint pain, swelling and decreased mobility, with its main pathological features being articular synovitis, cartilage degeneration and osteophyte formation. Inflammatory cytokines and chemokines secreted by activated immunocytes can trigger various inflammatory and immune responses in articular cartilage and synovium, contributing to the genesis and development of OA. A series of monocyte/macrophage chemokines, including monocyte chemotaxis protein (MCP)-1/CCL2, MCP2/CCL8, macrophage inflammatory protein (MIP)-1α/CCL3, MIP-1ß/CCL4, MIP-3α/CCL20, regulated upon activation, normal T-cell expressed and secreted /CCL5, CCL17 and macrophage-derived chemokine/CCL22, was proven to transmit cell signals by binding to G protein-coupled receptors on recipient cell surface, mediating and promoting inflammation in OA joints. However, the underlying mechanism of these chemokines in the pathogenesis of OA remains still elusive. Here, published literature was reviewed, and the function and mechanisms of monocyte/macrophage chemokines in OA pathogenesis were summarised. The symptoms and disease progression of OA were found to be effectively alleviated when the expression of these chemokines is inhibited. Elucidating these mechanisms could contribute to further understand how OA develops and provide potential targets for the early diagnosis of arthritis and drug treatment to delay or even halt OA progression.
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Quimiocinas , Macrófagos , Monócitos , Osteoartrite , Humanos , Osteoartrite/imunologia , Osteoartrite/patologia , Osteoartrite/metabolismo , Quimiocinas/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Animais , Cartilagem Articular/patologia , Cartilagem Articular/imunologia , Cartilagem Articular/metabolismo , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Membrana Sinovial/metabolismoRESUMO
Circulating extracellular vesicles (EVs) have gained significant attention for discovering tumor biomarkers. However, isolating EVs with well-defined homogeneous populations from complex biological samples is challenging. Different isolation methods have been found to derive different EV populations carrying different molecular contents, which confounds current investigations and hinders subsequent clinical translation. Therefore, standardizing and building a rigorous assessment of isolated EV quality associated with downstream molecular analysis is essential. To address this need, we introduce a statistical algorithm (ExoQuality Index, EQI) by integrating multiple EV characterizations (size, particle concentration, zeta potential, total protein, and RNA), enabling direct EV quality assessment and comparisons between different isolation methods. We also introduced a novel capture-release isolation approach using a pH-responsive peptide conjugated with NanoPom magnetic beads (ExCy) for simple, fast, and homogeneous EV isolation from various biological fluids. Bioinformatic analysis of next-generation sequencing (NGS) data of EV total RNAs from pancreatic cancer patient plasma samples using our novel EV isolation approach and quality index strategy illuminates how this approach improves the identification of tumor associated molecular markers. Results showed higher human mRNA coverage compared to existing isolation approaches in terms of both pancreatic cancer pathways and EV cellular component pathways using gProfiler pathway analysis. This study provides a valuable resource for researchers, establishing a workflow to prepare and analyze EV samples carefully and contributing to the advancement of reliable and rigorous EV quality assessment and clinical translation.
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BACKGROUND: Pancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins. METHODS: Tissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath. Levels of inflammation-associated proteins were quantified by multiplexed, enzyme-linked immunosorbent assay panels on matching tumor and tissue samples. RESULTS: Our findings revealed a significant increase in both CD3+ and CD8+ lymphocytes populations in PDAC compared with non-PDAC tissue, except when comparing CD8+ percentages in PDAC versus intraductal papillary mucinous neoplasms (IPMN) (p = 0.5012). Patients with quantitatively assessed CD3+ low tumors (lower 50%) had shorter survival (median 273 days) compared to CD3+ high tumors (upper 50%) with a median overall survival of 642.5 days (p = 0.2184). Patients with quantitatively assessed CD8+ low tumors had significantly shorter survival (median 240 days) compared to CD8+ high tumors with a median overall survival of 1059 days (p = 0.0003). Of 41 proteins assessed in the inflammation assay, higher levels of IL-1B and IL-2 were significantly associated with decreased CD3+ infiltration (r = -0.3704, p = 0.0187, and r = -0.4275, p = 0.0074, respectively). Higher levels of IL-1B were also significantly associated with decreased CD8+ infiltration (r = -0.4299, p = 0.0045), but not IL-2 (r = -0.0078, p = 0.9616). Principal component analysis of the inflammatory analytes showed diverse inflammatory responses in PDAC. CONCLUSION: In this work, we found a marked heterogeneity in infiltrating CD3+ and CD8+ lymphocytes and individual inflammatory responses in PDAC. Future mechanistic studies should explore personalized therapeutic strategies to target the immune and inflammatory components of the tumor microenvironment.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Linfócitos do Interstício Tumoral , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Linfócitos T CD8-Positivos , Inflamação/patologia , Prognóstico , Microambiente TumoralRESUMO
Pancreatic cancer is more prevalent in older individuals and often carries a poorer prognosis for them. The relationship between the microenvironment and pancreatic cancer is multifactorial, and age-related changes in nonmalignant cells in the tumor microenvironment may play a key role in promoting cancer aggressiveness. Because fibroblasts have profound impacts on pancreatic cancer progression, we investigated whether age-related changes in pancreatic fibroblasts influence cancer growth and metastasis. Proteomics analysis revealed that aged fibroblasts secrete different factors than young fibroblasts, including increased growth/differentiation factor 15 (GDF-15). Treating young mice with GDF-15 enhanced tumor growth, whereas aged GDF-15 knockout mice showed reduced tumor growth. GDF-15 activated AKT, rendering tumors sensitive to AKT inhibition in an aged but not young microenvironment. These data provide evidence for how aging alters pancreatic fibroblasts and promotes tumor progression, providing potential therapeutic targets and avenues for studying pancreatic cancer while accounting for the effects of aging. SIGNIFICANCE: Aged pancreatic fibroblasts secrete GDF-15 and activate AKT signaling to promote pancreatic cancer growth, highlighting the critical role of aging-mediated changes in the pancreatic cancer microenvironment in driving tumor progression. See related commentary by Isaacson et al., p. 1185.
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Fibroblastos Associados a Câncer , Neoplasias Pancreáticas , Animais , Camundongos , Fator 15 de Diferenciação de Crescimento/genética , Fator 15 de Diferenciação de Crescimento/uso terapêutico , Proteínas Proto-Oncogênicas c-akt , Neoplasias Pancreáticas/patologia , Pâncreas/patologia , Fibroblastos/patologia , Microambiente Tumoral , Linhagem Celular Tumoral , Fibroblastos Associados a Câncer/patologiaRESUMO
RATIONALE: Intraosseous hemangioma is a rare benign vascular tumor of the bone that can affect any body part; however, the most common site is the vertebra, followed by calvarial bones. PATIENT CONCERNS: We present a case of intraosseous hemangioma in a 23-year-old male who presented a feeling of fullness in the throat for 3 months. The hyoid bone level had a hard mass of about 5 cm. Fine needle aspiration showed 5 mL dark bloody aspirates. Magnetic resonance image showed a 5.3 cm mixed signal intensity lesion in the hyoid body. DIAGNOSIS: Histopathologic examination showed intraosseous hemangioma with aneurysmal bone cyst (ABC)-like changes in the hyoid bone. INTERVENTIONS: The mass was completely removed without significant problems. OUTCOMES: Complete mass excision and symptomatic improvements were achieved, and no subsequent relapses were observed. LESSONS: The authors experienced a case of intraosseous hemangioma with ABC-like changes. There has been no case report of intraosseous hemangioma in the hyoid bone. This case showed a spectral pattern of the ABC-like changes developing from the underlying bone tumor as a secondary change. ABC-like changes in bone tumors can mislead the diagnosis. Careful examination of the tumor is essential for the correct diagnosis of ABC or ABC-like changes.
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Cistos Ósseos Aneurismáticos , Neoplasias Ósseas , Hemangioma , Lesões do Pescoço , Crânio/anormalidades , Coluna Vertebral/anormalidades , Malformações Vasculares , Neoplasias Vasculares , Masculino , Humanos , Adulto Jovem , Adulto , Osso Hioide/diagnóstico por imagem , Osso Hioide/cirurgia , Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Cistos Ósseos Aneurismáticos/cirurgia , Crânio/patologia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Hemangioma/diagnóstico por imagem , Hemangioma/cirurgia , Coluna Vertebral/patologiaRESUMO
This meta-analysis aimed to evaluate the efficacy of Traditional Chinese Medicine (TCM) in enhancing surgical site wound healing following colorectal surgery. We systematically reviewed and analysed randomized controlled trials (RCTs) that investigated the outcomes of TCM interventions in postoperative wound management, adhering to the PRISMA guidelines. The primary outcome was the assessment of wound healing through the REEDA (redness, oedema, ecchymosis, discharge and approximation) scale at two different time points: the 10th day and 1-month post-surgery. Seven RCTs involving 1884 patients were included. The meta-analysis revealed a statistically significant improvement in wound healing in the TCM-treated groups compared to the control groups at both time intervals. On the 10th day post-surgery, the TCM groups exhibited a significant reduction in REEDA scale scores (I2 = 98%; random: SMD: -2.25, 95% CI: -3.52 to -0.98, p < 0.01). A similar trend was observed 1-month post-surgery, with the TCM groups showing a substantial decrease in REEDA scale scores (I2 = 98%; random: SMD: -3.39, 95% CI: -4.77 to -2.01, p < 0.01). Despite the promising results, the majority of the included studies were of suboptimal quality, indicating a need for further high-quality RCTs to substantiate the findings. The results suggest that TCM interventions can potentially enhance wound healing post-colorectal surgery, paving the way for further research in this area to validate the efficacy of TCM in postoperative management.
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Cirurgia Colorretal , Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Medicina Tradicional Chinesa/métodos , CicatrizaçãoRESUMO
OBJECTIVE: The objective of this study was to compare the outcomes of pharmacomechanical thrombolysis and thrombectomy (PCDT) plus catheter-directed thrombolysis (CDT) vs CDT alone for the treatment of acute iliofemoral deep vein thrombosis (DVT) and summarize the clinical experience, safety outcomes, and short- and long-term efficacy. METHODS: We performed a 4-year retrospective, case-control study. A total of 95 consecutive patients with acute symptomatic iliofemoral deep vein thrombosis (DVT) with a symptom duration of ≤7 days involving the iliac and/or common femoral veins underwent endovascular interventions. The patients were divided into two groups according to their clinical indications: PCDT plus CDT vs CDT alone. Statistical analyses were used to compare the clinical characteristics and outcomes between the two groups. Additionally, the patients were followed up for 3 to 36 months after treatment, and the proportions of post-thrombotic syndrome (PTS) and moderate to severe PTS were analyzed using the Kaplan-Meier survival method. RESULTS: A total of 95 consecutive patients were analyzed in this retrospective study, of whom, 51 underwent CDT alone and 44 underwent PCDT plus CDT. Between the two groups, in terms of immediate-term efficacy and safety, significant differences were found in the catheter retention time (60.64 ± 12.04 hours vs 19.42 ± 4.04 hours; P < .001), dosages of urokinase required (5.82 ± 0.81 million units vs 1.80 ± 0.64 million units; P < .001), the detumescence rate at 24 hours postoperatively (48.46% ± 8.62% vs 76.79% ± 7.98%; P = .026), the descent velocity of D-dimer per day (2266.28 ± 1358.26 µg/L/D vs 3842.34 ± 2048.02 µg/L/D; P = .018), total hospitalization stay (6.2 ± 1.40 days vs 3.8 ± 0.70 days; P = .024), number of postoperative angiograms (2.4 ± 0.80 vs 1.2 ± 0.30; P = .042), and grade III venous patency (>95% lysis: 54.5% vs 68.6%; P = .047). Furthermore, during the follow-up period, significant differences were found in the incidence of PTS (Villalta scale ≥5 or a venous ulcer: 47.0% vs 27.7%; P = .037), and the incidence proportion of moderate to severe PTS at 12 months (15.7% vs 4.5%; P = .024) and 24 months (35.3% vs 11.4%; P = .016). CONCLUSIONS: Compared with CDT alone, in the iliofemoral DVT subgroup with a symptom duration of ≤7 days, PCDT plus CDT could significantly relieve early leg symptoms, shorten the hospitalization stay, reduce bleeding complications, promote long-term venous patency, and decrease the occurrence of PTS and the incidence proportion of moderate to severe PTS. Thus, the short- and long-term outcomes both support the superiority of PCDT plus CDT vs CDT in this subgroup.
Assuntos
Síndrome Pós-Trombótica , Trombose Venosa , Humanos , Estudos Retrospectivos , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/métodos , Fibrinolíticos , Estudos de Casos e Controles , Resultado do Tratamento , Veia Ilíaca/diagnóstico por imagem , Veia Ilíaca/cirurgia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/terapia , Trombose Venosa/complicações , Síndrome Pós-Trombótica/diagnóstico por imagem , Síndrome Pós-Trombótica/etiologia , Síndrome Pós-Trombótica/terapia , Catéteres/efeitos adversos , Doença AgudaRESUMO
Angiolipomas are slow-growing benign mesenchymal-derived tumors consisting of mature adipocytes and thin-walled blood vessels. While the majority of angiolipomas are found in subcutaneous tissues, rarely there are case reports of intracranial lesions. We present a case of cisternal angiolipoma in a 10-year-old female. She presented with vague symptoms like dizziness without neurological deficits and radiological evaluation confirmed a left-sided infratentorial cisternal partially enhancing mass. She underwent craniotomy and had complete resection of the mass, which was histologically composed of mature adipocytes and blood vessels, consistent with angiolipoma. A review of the literature found only 18 cases of intracranial angiolipoma ever reported with our case representing the first case of infratentorial cisternal region.
Assuntos
Angiolipoma , Feminino , Humanos , Criança , Angiolipoma/diagnóstico por imagem , Angiolipoma/cirurgia , Radiografia , Tela Subcutânea/patologia , Tela Subcutânea/cirurgia , CraniotomiaRESUMO
BACKGROUND: We reviewed the clinical course and histopathologic findings for cases involving the formation of expanding cysts and/or hematomas after gamma knife surgery (GKS) for arteriovenous malformations (AVMs). METHODS: We report a single-center retrospective review of 18 patients who presented with cyst and/or hematoma expansion after GKS for AVMs between 1993 and 2023. Expanding cysts and hematomas were defined as well-demarcated cavities filled with fluid or well-marginated heterogenous hematomas presenting with expansion proximal to or in the location of the original AVM, respectively. Patient demographics, AVM characteristics, history of interventions and surgeries, and imaging and histopathologic features of expanding cysts and hematomas were collected for analysis. RESULTS: Among 1072 AVM patients treated using GKS, 18 presented with expanding cysts or hematomas during a total follow-up period of 16,757 patient-years (0.11 case/100 persons/patient-year). The time to cyst or hematoma identification was 4-13 years after initial GKS, with a mean duration of 8.6 years. Among the patients examined, 7 (38.9%) presented mainly with hematoma, 10 (55.6%) presented mainly with cysts, and 1 presented with approximately equal components of both. Among the 18 patients, 13 (72.2%) underwent craniotomy to treat cyst or hematoma expansion. All the specimens had similar histopathologic characteristics, including organizing hematoma with fresh and old hemorrhage, fibrinoid necrosis of the vessels, gliosis of normal brain tissue, infiltration of hemosiderin-laden histiocytes, and extravascular protein leakage. CONCLUSIONS: Our findings suggest that the formation of these 2 complications can be attributed to a common mechanism involving radiation-induced vascular damage in brain tissue adjacent to the AVM and subsequent chronic inflammation and capillary dilatation.
Assuntos
Cistos , Malformações Arteriovenosas Intracranianas , Radiocirurgia , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/radioterapia , Malformações Arteriovenosas Intracranianas/cirurgia , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Cistos/diagnóstico por imagem , Cistos/etiologia , Cistos/patologia , Encéfalo/patologia , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Hematoma/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , SeguimentosRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is highly associated with cachexia and weight loss, which is driven by the tumour's effect on the body. Data are lacking on differences in these metrics based on PDAC anatomic location. We hypothesize that the primary tumour's anatomic region influences the prevalence and severity of unintentional weight loss. METHODS: Treatment naïve patients with PDAC who underwent pancreatectomy at a single institution between 2012 and 2020 were identified retrospectively. Patients with pancreatic head or distal tumours were matched by sex, age, N and T stage. Serologic and anthropometric variables were obtained at the time of diagnosis. Skeletal muscle index (SMI), muscle radiation attenuation (MRA) and adiposity were measured. The primary outcome was presence of significant weight loss [>5% body weight (BW) loss in past 6 months]. Signed rank tests, Cochran Mantel Haenszel tests and Kaplan-Meier survival analysis are presented. RNA-seq of tumours was performed to explore enriched pathways related to cachexia and weight loss. RESULTS: Pancreatic head tumours (n = 24) were associated with higher prevalence (70.8% vs. 41.7%, P = 0.081) and degree of weight loss (7.9% vs. 2.5%, P = 0.014) compared to distal tumours (n = 24). BMI (P = 0.642), SMI (P = 0.738) and MRA (P = 0.478) were similar between groups. Combining BW loss, SMI and MRA into a composite score, patients with pancreatic head cancers met more criteria associated with poor prognosis (P = 0.142). Serum albumin (3.9 vs. 4.4 g/dL, P = 0.002) was lower and bilirubin (4.5 vs. 0.4 mg/dL, P < 0.001) were higher with pancreatic head tumours. Survival differed by tumour location (P = 0.014) with numerically higher median overall survival with distal tumours (11.1 vs. 21.8 months; P = 0.066). Transcriptomic analysis revealed inactivation of appetite stimulation, weight regulation and nutrient digestion/metabolism pathways in pancreatic head tumours. CONCLUSIONS: Resectable pancreatic head PDAC is associated with higher prevalence of significant weight loss and more poor prognosis features. Pancreaticobiliary obstruction and hypoalbuminemia in patients with head tumours suggests compounding effects of nutrient malabsorption and systemic inflammation on molecular drivers of cachexia, possibly contributing to shorter survival. Therefore, PDAC-associated cachexia is a heterogenous syndrome, which may be influenced by the primary tumour location. Select patients with resectable pancreatic head tumours may benefit from nutritional rehabilitation to improve outcomes.