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1.
Radiol Case Rep ; 19(11): 5262-5267, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39359876

RESUMEN

Synovial sarcoma is a rare type of soft tissue sarcoma that typically arises in the lower extremities and rarely in the upper extremities. Here, we present an unusual case of a middle-aged man who complained of dyspnea, dry cough, and chest pain and was found to have a mass-like lesion on the ulnar side of his left wrist during physical examination. The patient also exhibited gynecomastia and had elevated ß-human chorionic gonadotropin (ßHCG) levels. Subsequent imaging and histopathological analysis of the wrist mass confirmed the diagnosis of synovial sarcoma with disseminated lung metastasis. This article aims to provide a comprehensive overview of the clinical and pathological characteristics of synovial sarcoma, highlight the importance of considering synovial sarcoma as a differential diagnosis in patients with abnormal hormonal assays, and emphasize the need for clinicians to be vigilant about any pathologic lesions existing on the upper extremity to avoid late diagnosis and the development of advanced cancerous diseases.

2.
Heliyon ; 10(19): e37900, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39386828

RESUMEN

Lung metastasis, a leading cause of breast cancer mortality, lacks effective therapeutic options. Hypoxia-inducible factor 1-alpha (HIF-1α) plays important roles in breast cancer progression, but its direct impact on lung metastasis remains unclear. Herein, in this study, we investigated the role of HIF-1α in breast cancer lung metastasis and the potential of targeting it for therapeutic benefit. HIF-1α expression was knocked down in the 4T1 mouse mammary carcinoma cell line using a lentiviral vector. HIF-1α knockdown significantly reduced the migratory ability of 4T1 cells in vitro and lung metastasis in a mouse model. Mechanistically, HIF-1α knockdown decreased the expression of matrix metalloproteinases (MMP-2 and MMP-9) that degrade the extracellular matrix and suppressed the epithelial-to-mesenchymal transition (EMT) by increasing E-cadherin and decreasing vimentin expression. The findings of this study demonstrate that HIF-1α knockdown effectively inhibits lung metastasis of 4T1 cells both in vitro and in vivo by suppressing EMT. These results underscore a promising new approach for managing breast cancer metastasis.

3.
Cell ; 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39378878

RESUMEN

Breast disseminated cancer cells (DCCs) can remain dormant in the lungs for extended periods, but the mechanisms limiting their expansion are not well understood. Research indicates that tissue-resident alveolar macrophages suppress breast cancer metastasis in lung alveoli by inducing dormancy. Through ligand-receptor mapping and intravital imaging, it was found that alveolar macrophages express transforming growth factor (TGF)-ß2. This expression, along with persistent macrophage-cancer cell interactions via the TGF-ßRIII receptor, maintains cancer cells in a dormant state. Depleting alveolar macrophages or losing the TGF-ß2 receptor in cancer cells triggers metastatic awakening. Aggressive breast cancer cells are either suppressed by alveolar macrophages or evade this suppression by avoiding interaction and downregulating the TGF-ß2 receptor. Restoring TGF-ßRIII in aggressive cells reinstates TGF-ß2-mediated macrophage growth suppression. Thus, alveolar macrophages act as a metastasis immune barrier, and downregulation of TGF-ß2 signaling allows cancer cells to overcome macrophage-mediated growth suppression.

4.
Cureus ; 16(9): e69122, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39398735

RESUMEN

Glomus tumors are typically benign, soft tissue neoplasms composed of thermoregulatory glomus bodies. The more common varieties, such as subungual, are treated surgically and typically have a very low mortality rate. Malignant glomus tumors are very rare, and their pathogenesis is poorly understood. As such, treatment options and prognosis are unclear. We present a 67-year-old female diagnosed with a chest wall glomus tumor with biopsy-proven metastases to her lungs. Her treatment course included neoadjuvant radiation therapy followed by immunotherapy with pembrolizumab. After completion of the initial radiation therapy, imaging showed disease regression. Interval imaging after seven months of immunotherapy showed the resolution of all lung nodules with no reported concerns for disease recurrence. Pembrolizumab was discontinued due to concerns for dermatologic and renal adverse events, and the patient continues to be monitored off therapy. The metastatic glomus tumor described in this case had several unique qualities, including its initial presentation on the chest wall as an aggressive lesion, as well as its spread to multiple locations in the lungs. Glomus tumors are not normally as aggressive as seen in this case, but the genetic profile with high tumor mutational burden allowed for guided treatment. Radiation is often used as neoadjuvant treatment in higher risk glomus tumors, but the addition of immunotherapy such as pembrolizumab represents a potential avenue to manage these patients when surgery is not an option. Malignant glomus tumors are exceptionally rare occurrences that, by nature of their rarity, require protocols or therapies that are not specifically designed for their treatment. The clinical course of these tumors is difficult to predict as most cases of metastatic spread have few examples from which to draw conclusions. This case provided encouraging results for treatment with radiation and, potentially, immunotherapy. Each instance of a malignant glomus tumor and its genetic profile should be closely examined and documented so that sufficient data can be accumulated to guide treatment for this rare cancer.

5.
Cureus ; 16(9): e69196, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39398824

RESUMEN

The role of palliative surgery for excision of metastasis in a patient with nasopharyngeal carcinoma (NPC) is limited. However, judicious patient selection can yield noteworthy long-term survival outcomes. We report a case of the occurrence of isolated lung metastasis and its management in a NPC survivor with a long disease-free interval. The patient underwent radiotherapy and chemotherapy in 2014 for primary NPC cT2N1M0. In November 2019, he presented with a cough and respiratory distress. The investigation unveiled an isolated lung metastasis that partially encased the left upper lobe bronchus and closely abutted the left main bronchus and left pulmonary artery. Following comprehensive multidisciplinary consultations involving the patient and relatives, the patient underwent a left pneumonectomy as an imperative palliative intervention to alleviate the symptomatic respiratory distress and long-term disease control. Remarkably, the patient's disease-free status has persisted post surgery until 2024, evoking consideration of a potential curative trajectory. This case emphasises comprehensive evaluations, multidisciplinary discussions, and individualised treatment plans. It encourages patients to remain optimistic and engaged in their healthcare journey.

6.
Support Care Cancer ; 32(10): 652, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39256234

RESUMEN

OBJECTIVE: Our objective was to evaluate the predictive factors and metastatic time for liver and lung metastasis in locally advanced rectal cancer (RC) patients. METHODS: Univariate and multivariate analysis were performed to identify risk factors and prognostic factors for liver metastasis and lung metastasis in RC. Survival probabilities were calculated using the Kaplan-Meier model and compared using the log-rank test between groups. The probability of time-to-event occurrence was calculated using the random survival forest model. Finally, the SEER database was used to verify our findings. RESULTS: Our results indicated that pathological T stage and pathological N stage were independent predictive factors for liver metastasis. Furthermore, CEA level, pathological T stage, and tumor deposit were independent predictive factors for lung metastasis. Based on the results of a multivariate Cox analysis, we categorized patients with liver and lung metastasis into three groups based on their scores. The results revealed that patients with higher scores had a higher probability of experiencing metastasis. For liver metastasis, Groups 1, 2, and 3 all exhibited higher occurrence rates within the first 24 months. However, for lung metastasis, Group 4 showed the highest occurrence rate at the 12th month, while Groups 5 and 6 exhibited the highest occurrence rates at the 15th month. CONCLUSIONS: In summary, we developed predictive models to determine the likelihood of liver and lung metastasis in RC patients. It is crucial to implement a more intensive surveillance program for patients with unfavorable risk profiles in order to facilitate early detection of metastasis.


Asunto(s)
Neoplasias Hepáticas , Neoplasias Pulmonares , Estadificación de Neoplasias , Neoplasias del Recto , Programa de VERF , Humanos , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Anciano , Factores de Riesgo , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Adulto , Modelos de Riesgos Proporcionales , Pronóstico , Estimación de Kaplan-Meier , Análisis Multivariante , Estudios de Seguimiento , Factores de Tiempo , Estudios Retrospectivos
7.
Cancer Imaging ; 24(1): 119, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39238054

RESUMEN

PURPOSE: To investigate the value of multi-parametric MRI-based radiomics for preoperative prediction of lung metastases from soft tissue sarcoma (STS). METHODS: In total, 122 patients with clinicopathologically confirmed STS who underwent pretreatment T1-weighted contrast-enhanced (T1-CE) and T2-weighted fat-suppressed (T2FS) MRI scans were enrolled between Jul. 2017 and Mar. 2021. Radiomics signatures were established by calculating and selecting radiomics features from the two sequences. Clinical independent predictors were evaluated by statistical analysis. The radiomics nomogram was constructed from margin and radiomics features by multivariable logistic regression. Finally, the study used receiver operating characteristic (ROC) and calibration curves to evaluate performance of radiomics models. Decision curve analyses (DCA) were performed to evaluate clinical usefulness of the models. RESULTS: The margin was considered as an independent predictor (p < 0.05). A total of 4 MRI features were selected and used to develop the radiomics signature. By incorporating the margin and radiomics signature, the developed nomogram showed the best prediction performance in the training (AUCs, margin vs. radiomics signature vs. nomogram, 0.609 vs. 0.909 vs. 0.910) and validation (AUCs, margin vs. radiomics signature vs. nomogram, 0.666 vs. 0.841 vs. 0.894) cohorts. DCA indicated potential usefulness of the nomogram model. CONCLUSIONS: This feasibility study evaluated predictive values of multi-parametric MRI for the prediction of lung metastasis, and proposed a nomogram model to potentially facilitate the individualized treatment decision-making for STSs.


Asunto(s)
Estudios de Factibilidad , Neoplasias Pulmonares , Nomogramas , Sarcoma , Humanos , Femenino , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Masculino , Sarcoma/diagnóstico por imagen , Sarcoma/secundario , Sarcoma/patología , Persona de Mediana Edad , Adulto , Anciano , Estudios Retrospectivos , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Imagen por Resonancia Magnética/métodos , Adulto Joven , Curva ROC , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Neoplasias de los Tejidos Blandos/secundario , Neoplasias de los Tejidos Blandos/patología , Radiómica
8.
Front Immunol ; 15: 1455603, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39253079

RESUMEN

The successful pulmonary metastasis of malignant cancer cells depends on the survival of circulating tumor cells in a distant and hostile microenvironment. The formation of a pre-metastatic niche (PMN) creates a supportive environment for subsequent metastasis. Circular RNAs (circRNAs) are increasingly acknowledged as crucial elements in the mechanisms of metastasis due to their stable structures and functions, making them promising early metastasis detection markers. However, the specific expression patterns and roles of circRNAs in the lungs before metastasis remain largely unexplored. Our research aims to chart the circRNA expression profile and assess their impact on the lung PMN. We developed a lung PMN model and employed comprehensive RNA sequencing to analyze the differences in circRNA expression between normal and pre-metastatic lungs. We identified 38 significantly different circRNAs, primarily involved in metabolism, apoptosis, and inflammation pathways. We then focused on one specific circRNA, circ:chr4:150406196 - 150406664 (circRERE-PMN), which exhibited a significant change in expression and was prevalent in myeloid-derived suppressor cells (MDSCs), alveolar epithelial cells, and macrophages within the pre-metastatic lung environment. CircRERE-PMN was found to potentially regulate apoptosis and the expression of cytokines and chemokines through its interaction with the downstream target HUR in alveolar epithelial cells. Overall, our study highlights the crucial role of circRNAs in the formation of lung PMNs, supporting their potential as diagnostic or therapeutic targets for lung metastasis.


Asunto(s)
Neoplasias Pulmonares , ARN Circular , ARN Circular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Animales , Ratones , Humanos , Microambiente Tumoral , Pulmón/patología , Pulmón/metabolismo , Apoptosis/genética , Regulación Neoplásica de la Expresión Génica , Perfilación de la Expresión Génica , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/metabolismo , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/patología , Transcriptoma , Metástasis de la Neoplasia , Citocinas/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología
9.
Int J Radiat Biol ; : 1-9, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39288285

RESUMEN

OBJECTIVE: To investigate the value and applicability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) radiomics in differentiating primary lung cancer (PLC) from solitary lung metastasis (SLM) in patients with colorectal cancer (CRC). MATERIALS AND METHODS: This retrospective study included 103 patients with CRC and solitary pulmonary nodules (SPNs). The least absolute shrinkage and selection operator (LASSO) was used to screen for optimal radiomics features and establish a PET/CT radiomics model. PET/CT Visual and complex models (combining radiomics with PET/CT visual features) were developed. The area under the receiver operating characteristic (ROC) curve (AUC) was used to determine the predictive value and diagnostic efficiency of the models. RESULTS: The AUC of the PET/CT radiomics model for differentiating PLC from SLM was 0.872 (95% CI: 0.806-0.939), which was not different from that of the visual (0.829 [95% CI: 0.749-0.908; p = .352]). However, the AUC of the complex model (0.936 [95% CI:0.892-0.981]) was significantly higher than that of the PET/CT radiomics (p = .005) and visual model (p = .001). The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) of PET/CT radiomics for differentiating PLC from SLM were 0.720, 0.887, 0.806, 0.857, and 0.770, respectively. CONCLUSION: PET/CT radiomics can effectively distinguish PLC and SLM in patients with CRC and SPNs and guide the implementation of personalized treatment.

10.
Intern Med ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39231661

RESUMEN

A 78-year-old man with a history of pancreatic carcinoma underwent chest computed tomography (CT), which revealed a slowly enlarging consolidation in the right lower lobe. Forceps and percutaneous CT-guided lung biopsies showed no evidence of malignancy; therefore, organizing pneumonia was suspected. However, the patient's serum carbohydrate antigen 19-9 levels increased monthly, raising concerns about malignant lesions. A transbronchial cryobiopsy (TBCB) was performed to confirm the diagnosis of pulmonary metastasis of the pancreatic carcinoma. Pulmonary metastasis is an important differential diagnosis when chest CT shows consolidation, mimicking organized pneumonia. In addition, a TBCB can be a useful diagnostic tool for detecting lepidic growth patterns.

11.
Front Oncol ; 14: 1393990, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39228988

RESUMEN

Purpose: To construct and validate nomograms for predicting lung metastasis probability in patients with malignant primary osseous spinal neoplasms (MPOSN) at initial diagnosis and predicting cancer-specific survival (CSS) in the lung metastasis subgroup. Methods: A total of 1,298 patients with spinal primary osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma were retrospectively collected. Least absolute shrinkage and selection operator (LASSO) and multivariate logistic analysis were used to identify the predictors for lung metastasis. LASSO and multivariate Cox analysis were used to identify the prognostic factors for 3- and 5-year CSS in the lung metastasis subgroup. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCA) were used to estimate the accuracy and net benefits of nomograms. Results: Histologic type, grade, lymph node involvement, tumor size, tumor extension, and other site metastasis were identified as predictors for lung metastasis. The area under the curve (AUC) for the training and validating cohorts were 0.825 and 0.827, respectively. Age, histologic type, surgery at primary site, and grade were identified as the prognostic factors for the CSS. The AUC for the 3- and 5-year CSS were 0.790 and 0.740, respectively. Calibration curves revealed good agreements, and the Hosmer and Lemeshow test identified the models to be well fitted. DCA curves demonstrated that nomograms were clinically useful. Conclusion: The nomograms constructed and validated by us could provide clinicians with a rapid and user-friendly tool to predict lung metastasis probability in patients with MPOSN at initial diagnosis and make a personalized CSS evaluation for the lung metastasis subgroup.

12.
Cancers (Basel) ; 16(17)2024 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-39272818

RESUMEN

Cutaneous squamous cell carcinoma (SCC) is the second most frequent skin cancer, accounting for approximately 20% of all cutaneous malignancies, and with an increasing incidence due to the progressive increment of the average age of life. The diagnosis is usually firstly suspected based on clinical manifestations; however, dermoscopic features may improve diagnostic sensitivity in cases of an uncertain diagnosis and may guide the biopsy, which should be performed to histopathologically prove the tumor. New diagnostic strategies may improve the sensitivity of the cutaneous SCC, such as reflectance confocal microscopy and line-field confocal optical coherence, for which increasing data have been recently published. Imaging has a central role in the staging of the diseases, while its exact role, as well as the choice of the best techniques, during the follow-up are not fully clarified. The aim of this literature review is to describe diagnostic clinical and instrumental tools of cutaneous SCC, with an insight into the role of imaging in the diagnosis and follow-up of cutaneous SCC.

13.
Cancers (Basel) ; 16(17)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39272865

RESUMEN

Oligopulmonary metastases from primary liver tumors are typically treated surgically. We evaluated the clinical outcomes after lung metastasectomy in patients with pulmonary metastases from primary liver tumors. We retrospectively enrolled 147 consecutive patients with lung metastases from liver cancer who had undergone pulmonary metastasectomies at three medical centers between February 2007 and December 2020. All patients were pathologically confirmed to have lung metastases from liver cancer. Among the 147 patients, 110, 17, and 20 initially underwent surgical resection, radiofrequency ablation, and transcatheter arterial embolization, respectively. The 5-year overall survival (OS) in the study cohort was 22%. Univariate analysis revealed four factors associated with better OS: surgical resection as the initial primary liver tumor treatment (p = 0.004), a disease-free interval exceeding 12 months after the initial liver surgery (p = 0.036), a lower Model for End-Stage Liver Disease (MELD)-Na score (≤20) for liver cirrhosis (p = 0.044), and the absence of local liver tumor recurrence at the time of pulmonary metastasectomy (p = 0.004). Multivariate analysis demonstrated that surgical resection as the initial primary liver tumor treatment and lower MELD-Na scores significantly correlated with better OS. Our findings can assist thoracic surgeons in selecting suitable patients for surgery and predicting surgical outcomes.

14.
Heliyon ; 10(17): e36849, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39281479

RESUMEN

Giant cell tumor of bone (GCTB) is a locally aggressive benign neoplasm that is associated with a large biological spectrum ranging from latent benign to highly recurrent and occasionally metastatic tumor. In this article, we present a case of a 37-year-old woman who presented with fracture at the distal femur due to GCTB. Bone segment resection and reconstruction were done, and histopathology showed tumor features for GCTB. Later, multiple lung metastasis was found 22 months post-operation, which was verified by biopsy. Then systemic denosumab therapy with different intervals (1-month and 2-month) was tried as the treatment. It was clarified that monthly denosumab administration, instead of 2-month interval, was required to control the progression of the unresectable multiple lung metastasis from GCTB, which could be a choice for the future treatment of these patients.

15.
Cells ; 13(17)2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39273048

RESUMEN

Neoadjuvant intratumoral (IT) therapy could amplify the weak responses to checkpoint blockade therapy observed in breast cancer (BC). In this study, we administered neoadjuvant IT anti-canine PD-1 therapy (IT acPD-1) alone or combined with IT cowpea mosaic virus therapy (IT CPMV/acPD-1) to companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. CMC patients treated weekly with acPD-1 (n = 3) or CPMV/acPD-1 (n = 3) for four weeks or with CPMV/acPD-1 (n = 3 patients not candidates for surgery) for up to 11 weeks did not experience immune-related adverse events. We found that acPD-1 and CPMV/acPD-1 injections resulted in tumor control and a reduction in injected tumors in all patients and in noninjected tumors located in the ipsilateral and contralateral mammary chains of treated dogs. In two metastatic CMC patients, CPMV/acPD-1 treatments resulted in the control and reduction of established lung metastases. CPMV/acPD-1 treatments were associated with altered gene expression related to TLR1-4 signaling and complement pathways. These novel therapies could be effective for CMC patients. Owing to the extensive similarities between CMC and human BC, IT CPMV combined with approved anti-PD-1 therapies could be a novel and effective immunotherapy to treat local BC and suppress metastatic BC.


Asunto(s)
Comovirus , Inmunoterapia , Neoplasias Pulmonares , Neoplasias Mamarias Animales , Nanopartículas , Terapia Neoadyuvante , Receptor de Muerte Celular Programada 1 , Animales , Perros , Femenino , Inmunoterapia/métodos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/secundario , Nanopartículas/química , Neoplasias Mamarias Animales/terapia , Neoplasias Mamarias Animales/patología , Humanos
16.
Matrix Biol ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39278602

RESUMEN

Osteosarcoma (OS) mortality stems from lung metastases. Matrix metalloproteinases (MMPs) facilitate metastatic dissemination by degrading extracellular matrix components. Herein we studied the impact of targeted MMP downregulation on OS metastasis. Differential gene expression analysis of human OS cell lines revealed high MMP9 expression in the majority of OS cell lines. Furthermore, 143B, a metastatic OS cell line, exhibited increased MMP1 and MMP9 mRNA levels. Gene set enrichment analysis on metastatic and non-metastatic OS patient specimens indicated epithelial-mesenchymal transition as the most enriched gene set, with MMP9 displaying strong association to genes in this network. Using the same dataset, Kaplan-Meier analysis revealed a correlation between MMP1 expression and dismal patient survival. Hence, we undertook targeted suppression of MMP1 and MMP9 gene expression in OS cell lines. The ability of OS cells to migrate and form colonies was markedly reduced upon MMP1 and MMP9 downregulation, whereas their cell proliferation capacity remained intact. MMP9 downregulation decreased tumor growth and lung metastases area in an orthotopic mouse OS model. Consistently, human OS lung metastasis specimens displayed marked MMP9 protein expression. Our findings highlight the role of MMP1 and MMP9 in OS metastasis, warranting further exploration of simultaneous inhibition of MMPs for future OS therapeutics.

17.
Acta Pharm Sin B ; 14(8): 3697-3710, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39220876

RESUMEN

Due to the insufficient Cu+ accumulation, Cu+ efflux mechanism, and highly immunosuppressive tumor microenvironment (TME) in lung metastasis, the cuproptosis efficacy is limited. Herein, an inhalable nanodevice (CLDCu) is constructed to successfully overcome the drawbacks of cuproptosis. CLDCu consists of a Cu2+-chitosan shell and low molecular weight heparin-tocopherol succinate (LMWH-TOS, LT) core with disulfiram (DSF) loading. The prepared CLDCu can be inhaled and accumulate in large amounts in lung lesions (63.6%) with 56.5 times higher than intravenous injection. Within tumor cells, the mild acidity triggers the co-release of DSF and Cu2+, thus generating bis(diethyldithiocarbamate)-copper (CuET) to block Cu+ efflux protein ATP7B and forming toxic Cu+, leading to enhanced cuproptosis. Meanwhile, the released chitosan cooperates with CLDCu-induced cuproptosis to activate stimulator of interferon genes (STING) pathway, which significantly potentiates dendritic cells (DCs) maturation, as wells as evokes innate and adaptive immunity. In lung metastatic mice model, CLDCu is found to induce cuproptosis and reverse the immunosuppressive TME by inhalation administration. Moreover, CLDCu combined with anti-programmed cell death protein ligand-1 antibody (aPD-L1) provokes stronger antitumor immunity. Therefore, nanomedicine that combines cuproptosis with STING activation is a novel strategy for tumor immunotherapy.

18.
Adv Mater ; : e2409618, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225412

RESUMEN

Addressing the inefficiency of current therapeutic approaches for hepatocellular carcinoma is an urgent and pressing challenge. PANoptosis, a form of inflammatory programmed cell death, presents a dependable strategy for combating cancer by engaging multiple cell death pathways (apoptosis, pyroptosis, and necroptosis). In this study, an ultrasmall Bi2Sn2O7 nanozyme with ultrasound-magnified multienzyme-mimicking properties is designed and engineered as a PANoptosis inducer through destroying the mitochondrial function of tumor cells and enhancing the intracellular accumulation of toxic reactive oxygen species, finally triggering the activation of PANoptosis process. The role of PANoptosis inducer has been verified by the expression of related proteins, including cleaved Caspase 3, NLRP3, N-GSDMD, cleaved Caspase 1, p-MLKL, and RIPK3. The inclusion of external ultrasonic irradiation significantly augments the enzyodynamic therapeutic efficiency. In vitro and in vivo antineoplastic efficacy, along with inhibition of lung metastasis, validate the benefits of the Bi2Sn2O7-mediated PANoptosis pathway. This study not only elucidates the intricate mechanisms underlying Bi2Sn2O7 as a PANoptosis inducer, but also offers a novel perspective for the treatment of hepatocellular carcinoma.

19.
Adv Sci (Weinh) ; : e2404904, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225541

RESUMEN

Most deaths in breast cancer patients are attributed to metastasis, and lung metastasis is associated with a particularly poor prognosis; therefore it is imperative to identify potential target for intervention. The transforming growth factor-ß (TGF-ß) pathway plays a vital role in breast cancer metastasis, in which Smad3 is the key mediator and performs specific functions by binding with different cofactors. However, Smad3 cofactors involved in lung metastasis have not yet been identified. This study first establishes the interactome of Smad3 in breast cancer cells and identifies ZNF8 as a novel Smad3 cofactor. Furthermore, the results reveal that ZNF8 is closely associated with breast cancer lung metastasis prognosis, and specifically facilitates TGF-ß pathway-mediated breast cancer lung metastasis by participating in multiple processes. Mechanistically, ZNF8 binds with Smad3 to enhance the H3K4me3 modification and promote the expression of lung metastasis signature genes by recruiting SMYD3. SMYD3 inhibition by BCI121 effectively prevents ZNF8-mediated lung metastasis. Overall, the study identifies a novel cofactor of TGF-ß/Smad3 that promotes lung metastasis in breast cancer and introduces potential therapeutic strategies for the early management of breast cancer lung metastasis.

20.
J Med Case Rep ; 18(1): 452, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39343923

RESUMEN

BACKGROUND: Tenosynovial giant cell tumor is a rare soft tissue tumor of the synovium of joint, bursae, or tendon sheath. It is divided into localized or diffuse types on the basis of the growth pattern. Localized tenosynovial giant cell tumors are usually benign and treated successfully by excision. Diffuse tenosynovial giant cell tumors, in contrast to localized type, can destroy bone and cartilage and are associated with frequent local recurrences and distant metastasis. Localized type tenosynovial giant cell tumors rarely metastasize to distant organs. Here, we report a case of localized tenosynovial giant cell tumor presenting with lung metastases and systematically review literature. CASE PRESENTATION: A 55-year-old Asian male presented with a dry cough, right-sided chest pain and progressive dyspnea for 1 month. At 18 months before this presentation, he had undergone excision of a painless swelling on his right index finger. The swelling recurred within 3 months of excision, and a biopsy was then suggestive of a giant cell tumor. Given the suspicion of a giant cell tumor, a wide excision of the lesion was performed and the excisional biopsy was consistent with a diagnosis of tenosynovial giant cell tumor, localized type. At admission to our hospital, the patient had tachypnoea and absent breath sounds on the right side. A chest radiograph showed a right-sided pleural effusion with a homogenous opacity in the left mid-zone. A contrast-enhanced computed tomography of the chest and abdomen showed right massive pleural effusion and bilateral multiple lobulated heterogeneously enhancing pleural-based masses with areas of internal calcification. Pleural fluid analysis revealed an exudate with no malignant cells on cytology. A lung biopsy showed osteoclast-like giant cells and mononuclear spindle cells with areas of hemorrhage and necrosis, suggesting tenosynovial giant cell tumor metastasis. A final diagnosis of localized type tenosynovial giant cell tumor of the right index finger with metastases to the lungs and pleura was made. The patient passed away after receiving three cycles of denosumab injection owing to progressive disease. CONCLUSION: Lung metastasis is extremely rare in patients with localized tenosynovial giant cell tumor. The survival is usually poor in patients with lung metastasis. A close follow-up of patients with localized type tenosynovial giant cell tumor is necessary for early detection of pleuropulmonary complications.


Asunto(s)
Tumor de Células Gigantes de las Vainas Tendinosas , Neoplasias Pulmonares , Humanos , Masculino , Persona de Mediana Edad , Tumor de Células Gigantes de las Vainas Tendinosas/patología , Tumor de Células Gigantes de las Vainas Tendinosas/cirugía , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/patología , Neoplasias Pleurales/secundario , Neoplasias Pleurales/patología , Tomografía Computarizada por Rayos X , Resultado Fatal
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