Transforming growth factor β (TGF-β) has long been identified with its intensive involvement in early embryonic development and organogenesis, immune supervision, tissue repair, and adult ...homeostasis. The role of TGF-β in fibrosis and cancer is complex and sometimes even contradictory, exhibiting either inhibitory or promoting effects depending on the stage of the disease. Under pathological conditions, overexpressed TGF-β causes epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, cancer-associated fibroblast (CAF) formation, which leads to fibrotic disease, and cancer. Given the critical role of TGF-β and its downstream molecules in the progression of fibrosis and cancers, therapeutics targeting TGF-β signaling appears to be a promising strategy. However, due to potential systemic cytotoxicity, the development of TGF-β therapeutics has lagged. In this review, we summarized the biological process of TGF-β, with its dual role in fibrosis and tumorigenesis, and the clinical application of TGF-β-targeting therapies.
Research on tumor immunotherapy has made tremendous progress in the past decades, with numerous studies entering the clinical evaluation. The cancer vaccine is considered a promising therapeutic ...strategy in the immunotherapy of solid tumors. Cancer vaccine stimulates anti-tumor immunity with tumor antigens, which could be delivered in the form of whole cells, peptides, nucleic acids, etc. Ideal cancer vaccines could overcome the immune suppression in tumors and induce both humoral immunity and cellular immunity. In this review, we introduced the working mechanism of cancer vaccines and summarized four platforms for cancer vaccine development. We also highlighted the clinical research progress of the cancer vaccines, especially focusing on their clinical application and therapeutic efficacy, which might hopefully facilitate the future design of the cancer vaccine.
Epigenetic alternations concern heritable yet reversible changes in histone or DNA modifications that regulate gene activity beyond the underlying sequence. Epigenetic dysregulation is often linked ...to human disease, notably cancer. With the development of various drugs targeting epigenetic regulators, epigenetic-targeted therapy has been applied in the treatment of hematological malignancies and has exhibited viable therapeutic potential for solid tumors in preclinical and clinical trials. In this review, we summarize the aberrant functions of enzymes in DNA methylation, histone acetylation and histone methylation during tumor progression and highlight the development of inhibitors of or drugs targeted at epigenetic enzymes.
Objective:
To investigate the role of myeloid-derived suppressor cells (MDSC) in cancer progression after the stress of operative removal and the potential treatment value of MDSC depletion.
Summary ...Background Data:
Surgery is the most important treatment strategy in breast cancer. Recent research has provided evidence that operations may promote cancer metastases under some circumstances.
Methods:
A mouse model of breast cancer (administration of the murine breast cancer 4T1 cells subcutaneously) and the stress of operation were used to compare immune responses and survival outcomes. Flow cytometry was performed to detect the expression of CD11b and Gr1 MDSCs in tumor tissues and lung metastases. Cytokine levels were detected with three-color flow cytometry and enzyme-linked immunosorbent assay (ELISA). MDSCs were isolated and co-cultured with 4T1 cells to identify any morphological change with immunofluorescence. The anti Gr-1 antibody was used to detect the function of the anti-Gr1 treatment in breast cancer.
Results:
The operative stress impaired the overall survival, leading to an increased number of MDSCs that preferentially infiltrated the tumor microenvironment and promoted tumor metastasis. In both
in vitro
and
in vivo
assays, MDSCs induced the epithelial-mesenchymal transition (EMT) of tumor cells through the up-regulation of TGF-beta1, VEGF, and IL-10. Furthermore, a treatment strategy of MDSC depletion was found to reduce pulmonary metastases after operations.
Conclusions:
The stress of operation could impair the overall survival in mice. The infiltrated MDSCs appear to induce EMT of tumor cells and increase metastases through the up-regulation of TGF-beta1, VEGF, and IL-10 levels. MDSC depletion could be a promising treatment strategy to prevent immune evasion after operations.
Over the last decades, the growing understanding on DNA damage response (DDR) pathways has broadened the therapeutic landscape in oncology. It is becoming increasingly clear that the genomic ...instability of cells resulted from deficient DNA damage response contributes to the occurrence of cancer. One the other hand, these defects could also be exploited as a therapeutic opportunity, which is preferentially more deleterious in tumor cells than in normal cells. An expanding repertoire of DDR‐targeting agents has rapidly expanded to inhibitors of multiple members involved in DDR pathways, including PARP, ATM, ATR, CHK1, WEE1, and DNA‐PK. In this review, we sought to summarize the complex network of DNA repair machinery in cancer cells and discuss the underlying mechanism for the application of DDR inhibitors in cancer. With the past preclinical evidence and ongoing clinical trials, we also provide an overview of the history and current landscape of DDR inhibitors in cancer treatment, with special focus on the combination of DDR‐targeted therapies with other cancer treatment strategies.
In this review, we sought to summarize the complex network of DNA repair machinery in cancer cells and discuss the underlying mechanism for the application of DDR inhibitors in cancer. With the past preclinical evidence and ongoing clinical trials, we also provide an overview of the history and current landscape of DDR inhibitors in cancer treatment, with especial focus on the combination of DDR‐targeted therapies with other cancer treatment strategies.
As one of the most common metastatic sites of malignancies, bone has a unique microenvironment that allows metastatic tumor cells to grow and flourish. The fenestrated capillaries in the bone, bone ...matrix, and bone cells, including osteoblasts and osteoclasts, together maintain the homeostasis of the bone microenvironment. In contrast, tumor-derived factors act on bone components, leading to subsequent bone resorption or excessive bone formation. The various pathways involved also provide multiple targets for therapeutic strategies against bone metastases. In this review, we summarize the current understanding of the mechanism of bone metastases. Based on the general process of bone metastases, we specifically highlight the complex crosstalk between tumor cells and the bone microenvironment and the current management of cancer bone metastases.
To estimate the prognostic value of inflammatory markers in patients with laryngeal squamous cell carcinoma (LSCC).
A total of 361 resected LSCC patients were included. The preoperative and ...postoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), alkaline phosphatase (ALP) and l actate dehydrogenase (LDH) were assessed. The Kaplan-Meier survival analysis and Cox regression analysis were conducted on overall survival (OS) and progression-free survival (PFS).
Both Kaplan-Meier analysis and univariate analysis demonstrated significant prognostic value of preoperative and postoperative NLR, PLR and MLR. However, only preoperative ALP was predictive of OS and PFS, and LDH failed to be predictor of OS and PFS. The multivariate analysis showed that preoperative NLR (OS: HR = 1.64, 95%CI: 1.06-2.54, p = 0.026; PFS: HR = 1.52, 95%CI: 1.04-2.23, p = 0.029) and postoperative MLR (OS: HR = 2.02, 95%CI: 1.29-3.14, p = 0.002; PFS: HR = 1.57, 95%CI: 1.05-2.34, p = 0.026) were independently related with survival.
The elevated preoperative NLR, PLR, MLR and ALP were significantly associated with worse survival and cancer progression. The preoperative NLR and postoperative MLR might be independent prognostic markers of OS and PFS in LSCC patients undergoing surgical resection.
Targeting inflammation as cancer therapy Wang, Manni; Chen, Siyuan; He, Xuemei ...
Journal of hematology & oncology,
03/2024, Letnik:
17, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Inflammation has accompanied human beings since the emergence of wounds and infections. In the past decades, numerous efforts have been undertaken to explore the potential role of inflammation in ...cancer, from tumor development, invasion, and metastasis to the resistance of tumors to treatment. Inflammation-targeted agents not only demonstrate the potential to suppress cancer development, but also to improve the efficacy of other therapeutic modalities. In this review, we describe the highly dynamic and complex inflammatory tumor microenvironment, with discussion on key inflammation mediators in cancer including inflammatory cells, inflammatory cytokines, and their downstream intracellular pathways. In addition, we especially address the role of inflammation in cancer development and highlight the action mechanisms of inflammation-targeted therapies in antitumor response. Finally, we summarize the results from both preclinical and clinical studies up to date to illustrate the translation potential of inflammation-targeted therapies.
A significant proportion of non-small cell lung cancer (NSCLC) patients experience accumulating chemotherapy-related adverse events, motivating the design of chemosensitizating strategies. The main ...cytotoxic damage induced by chemotherapeutic agents is DNA double-strand breaks (DSB). It is thus conceivable that DNA-dependent protein kinase (DNA-PK) inhibitors which attenuate DNA repair would enhance the anti-tumor effect of chemotherapy. The present study aims to systematically evaluate the efficacy and safety of a novel DNA-PK inhibitor M3814 in synergy with chemotherapies on NSCLC. We identified increased expression of DNA-PK in human NSCLC tissues which was associated with poor prognosis. M3814 potentiated the anti-tumor effect of paclitaxel and etoposide in A549, H460 and H1703 NSCLC cell lines. In the four combinations based on two NSCLC xenograft models and two chemotherapy, we also observed tumor regression at tolerated doses in vivo. Moreover, we identified a P53-dependent accelerated senescence response by M3814 following treatment with paclitaxel/etoposide. The present study provides a theoretical basis for the use of M3814 in combination with paclitaxel and etoposide in clinical practice, with hope to aid the optimization of NSCLC treatment.
This study elucidates the chemosensitization effect of M3814, a new-generation DNA-PK inhibitor on non-small cell lung cancer, providing theoretical bases for the clinical application of M3814-chemotherapy synergy. Display omitted
Background
Deep learning methods have great potential to predict treatment response. The objective of this study was to evaluate and validate the predictive performance of the computed tomography ...(CT)-based model using deep learning features for identification of responders and nonresponders to induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC).
Materials and methods
All eligible patients were included retrospectively between January 2012 and December 2018, and assigned to the training (
n
= 208) or the testing cohort (
n
= 89). We extracted deep learning features of six pretrained convolutional neural networks (CNNs) via transfer learning method, and handcrafted radiomics features manually. Support vector machine (SVM) was adopted as the classifier. All predictive models were evaluated using the area under the receiver operating characteristics curve (AUC), by which an optimal model was selected. We also built clinical and clinical–radiological models for comparison.
Results
The model with features extracted from ResNet50 (RN-SVM) had optimal performance among all models with features extracted from pretrained CNNs with an AUC of 0.811, accuracy of 68.54%, sensitivity of 61.54%, specificity of 87.50%, positive predictive value (PPV) of 93.02%, and negative predictive value (NPV) of 45.65% in the testing cohort. The handcrafted radiomics model was slightly inferior to the RN-SVM model with an AUC of 0.663 and accuracy of 60.67% in the testing cohort. All the imaging-derived models had better predictive performance than the clinical model.
Conclusion
The noninvasive deep learning method could provide efficient prediction of treatment response to IC in locally advanced NPC and might be a practicable approach in therapeutic strategy decision-making.
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