Epithelial ovarian cancer is aggressive and causes high mortality among women worldwide. Members of the plakin family are essential to maintain cytoskeletal integrity and key cellular processes. In this study we characterised the expression of plakins, particularly plectin (PLEC), periplakin (PPL), envoplakin (EVPL), and EMT-related proteins by immunohistochemistry in n = 48 patients' samples to evaluate a potential correlation of plakin expression with EMT as EOC progresses.
View Article and Find Full Text PDFInhibitory receptors are critical for regulating immune cell function. In cancer, these receptors are often over-expressed on the cell surface of T and NK cells, leading to reduced anti-tumor activity. Here, through the analysis of 11 commonly studied checkpoint and inhibitory receptors, we discern that only (TIM3) and (CD39) display significantly greater gene expression in glioblastoma compared to normal brain and lower grade glioma.
View Article and Find Full Text PDFThe zeolitic imidazolate framework (ZIF) is one of the most explored metal-organic-framework-based systems for nucleic acid delivery to cancer cells. Current nucleic acid delivery tools exhibit several drawbacks, such as high manufacturing costs, endosomal entrapment, toxicity, and immunogenicity. However, the biomimetic mineralization of Zn-based ZIFs offers a low-cost and facile encapsulation of nucleic acids at room temperature in aqueous conditions.
View Article and Find Full Text PDFPregnancy associated plasma protein-A (PAPP-A) plays an integral role in breast cancer (BC), especially triple negative breast cancer (TNBC). This subtype accounts for the most aggressive BC, possesses high tumor heterogeneity, is least responsive to standard treatments and has the poorest clinical outcomes. There is a critical need to address the lack of effective targeted therapeutic options available.
View Article and Find Full Text PDFGlioblastoma is highly proliferative and invasive. However, the regulatory cytokine networks that promote glioblastoma cell proliferation and invasion into other areas of the brain are not fully defined. In the present study, we define a critical role for the IL-11/IL-11Rα signalling axis in glioblastoma proliferation, epithelial to mesenchymal transition, and invasion.
View Article and Find Full Text PDFSkin-resident CD8 T cells include distinct interferon-γ-producing [tissue-resident memory T type 1 (T1)] and interleukin-17 (IL-17)-producing (T17) subsets that differentially contribute to immune responses. However, whether these populations use common mechanisms to establish tissue residence is unknown. In this work, we show that T1 and T17 cells navigate divergent trajectories to acquire tissue residency in the skin.
View Article and Find Full Text PDFVγ9Vδ2 T cells are the largest population of γδ T cells in adults and can play important roles in providing effective immunity against cancer and infection. Many studies have suggested that peripheral Vγ9Vδ2 T cells are derived from the fetal liver and thymus and that the postnatal thymus plays little role in the development of these cells. More recent evidence suggested that these cells may also develop postnatally in the thymus.
View Article and Find Full Text PDFCancer Med
June 2023
Background: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are approved for the treatment of various solid tumors. In gastric cancer, genes commonly harbor mutations in the homologous recombination DNA repair pathway, potentially increasing sensitivity to PARPi. Pamiparib (BGB-290) is a small molecule inhibitor of PARP1 and PARP2.
View Article and Find Full Text PDFThe process of epithelial-mesenchymal transition (EMT) involves the phenotypic transformation of cells from epithelial to mesenchymal status. The cells exhibiting EMT contain features of cancer stem cells (CSC), and the dual processes are responsible for progressive cancers. Activation of hypoxia-inducible factors (HIF) is fundamental to the pathogenesis of clear cell renal cell carcinoma (ccRCC), and their role in promoting EMT and CSCs is crucial for ccRCC tumour cell survival, disease progression, and metastatic spread.
View Article and Find Full Text PDFGlioblastoma cells adapt to changes in glucose availability through metabolic plasticity allowing for cell survival and continued progression in low-glucose concentrations. However, the regulatory cytokine networks that govern the ability to survive in glucose-starved conditions are not fully defined. In the present study, we define a critical role for the IL-11/IL-11Rα signalling axis in glioblastoma survival, proliferation and invasion when cells are starved of glucose.
View Article and Find Full Text PDFBackground: The endogenous tissue inhibitor of metalloproteinase-2 (TIMP-2), through its homeostatic action on certain metalloproteinases, plays a vital role in remodelling extracellular matrix (ECM) to facilitate cancer progression. This study investigated the role of TIMP-2 in an ovarian cancer cell line in which the expression of TIMP-2 was reduced by either siRNA or CRISPR/Cas9.
Methods: OVCAR5 cells were transiently and stably transfected with either single or pooled TIMP-2 siRNAs (T2-KD cells) or by CRISPR/Cas9 under the influence of two distinct guide RNAs (gRNA1 and gRNA2 cell lines).
Background: Epithelial ovarian cancer is the most lethal gynaecological cancer worldwide. Chemotherapy resistance represents a significant clinical challenge and is the main reason for poor ovarian cancer prognosis. We identified novel expression of markers related to epithelial mesenchymal transitions (EMT) in a carboplatin resistant ovarian cancer cell line by proteomics.
View Article and Find Full Text PDFBreast cancer is one of the major causes of mortality in women worldwide. Accounting for 15-20% of all breast cancer diagnoses, the triple-negative breast cancer (TNBC) subtype presents with an aggressive clinical course, heightened metastatic potential and the poorest short-term prognosis. TNBC does not respond to hormonal therapy, only partially responds to radio- and chemotherapy, and has limited targeted therapy options, thus underlining the critical need for better therapeutic treatments.
View Article and Find Full Text PDFLangerhans cell histiocytosis (LCH) lesions contain an inflammatory infiltrate of immune cells including myeloid-derived LCH cells. Cell-signaling proteins within the lesion environment suggest that LCH cells and T cells contribute majorly to the inflammation. Foxp3+ regulatory T cells (Tregs) are enriched in lesions and blood from patients with LCH and are likely involved in LCH pathogenesis.
View Article and Find Full Text PDFRenal cell cancer (RCC) is a heterogeneous tumor that shows both intra- and inter-heterogeneity. Heterogeneity is displayed not only in different patients but also among RCC cells in the same tumor, which makes treatment difficult because of varying degrees of responses generated in RCC heterogeneous tumor cells even with targeted treatment. In that context, precision medicine (PM), in terms of individualized treatment catered for a specific patient or groups of patients, can shift the paradigm of treatment in the clinical management of RCC.
View Article and Find Full Text PDFBackground: The tissue inhibitors of metalloproteinase (TIMPs) and their associated metalloproteinase (MMPs) are essential regulators of tissue homeostasis and are essential for cancer progression. This study analyzed the expression of TIMP-1,-2,-3 and the associated MMPs (MMP-2,-9,-11,-14) in different Stages, Grades and World Health Organization (WHO) classifications of serous ovarian tumors, ascites, ascites-derived cells from chemo-naïve (CN) and relapsed (CR) patients, and in ovarian cancer cell lines. The status of TIMPs and associated MMPs in response to chemotherapy treatment was assessed in cancer cell lines; TCGA data was interrogated to gauge TIMPs and associated MMPs as prognostic and platinum-response indicators.
View Article and Find Full Text PDFTissue-resident memory T (TRM) cells provide long-lasting immune protection. One of the key events controlling TRM cell development is the local retention of TRM cell precursors coupled to downregulation of molecules necessary for tissue exit. Sphingosine-1-phosphate receptor 5 (S1PR5) is a migratory receptor with an uncharted function in T cells.
View Article and Find Full Text PDFVascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) have been the mainstay of treatment for patients with advanced renal cell carcinoma (RCC). Despite its early promising results in decreasing or delaying the progression of RCC in patients, VEGF-TKIs have provided modest benefits in terms of disease-free progression, as 70% of the patients who initially respond to the treatment later develop drug resistance, with 30% of the patients innately resistant to VEGF-TKIs. In the past decade, several molecular and genetic mechanisms of VEGF-TKI resistance have been reported.
View Article and Find Full Text PDFThe plakin family of cytoskeletal proteins play an important role in cancer progression yet are under-studied in cancer, especially ovarian cancer. These large cytoskeletal proteins have primary roles in the maintenance of cytoskeletal integrity but are also associated with scaffolds of intermediate filaments and hemidesmosomal adhesion complexes mediating signalling pathways that regulate cellular growth, migration, invasion and differentiation as well as stress response. Abnormalities of plakins, and the closely related spectraplakins, result in diseases of the skin, striated muscle and nervous tissue.
View Article and Find Full Text PDFAim: To present the first case series of patients with Langerhans cell histiocytosis (LCH) also affected by Crohn's disease (CD), both of which are granulomatous diseases, and in LCH investigate the role of interleukin (IL)-23, which is a well-described disease mediator in CD.
Methods: A case series of three patients with LCH and CD were described; a cohort of LCH patients (n = 55) as well as controls (n = 55) were analysed for circulating IL-23 levels; and the relation between the percentage of LCH cells in lesions and circulating IL-23 levels was analysed in seven LCH patients.
Results: Differential diagnostic challenges for these two granulomatous diseases were highlighted in the case series, and it took up to 3 years to diagnose CD.
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