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Frontiers in Bioscience (Landmark... Jun 2024Transcription factors (TFs) are essential proteins regulating gene expression by binding to specific nucleotide sequences upstream of genes. Among TF families, the... (Review)
Review
Transcription factors (TFs) are essential proteins regulating gene expression by binding to specific nucleotide sequences upstream of genes. Among TF families, the forkhead box (FOX) proteins, characterized by a conserved DNA-binding domain, play vital roles in various cellular processes, including cancer. The FOXA subfamily, encompassing FOXA1, FOXA2, and FOXA3, stands out for its pivotal role in mammalian development. FOXA1, initially identified in the liver, exhibits diverse expression across multiple organ tissues and plays a critical role in cell proliferation, differentiation, and tumor development. Its structural composition includes transactivation domains and a DNA-binding domain, facilitating its function as a pioneer factor, which is crucial for chromatin interaction and the recruitment of other transcriptional regulators. The involvement of FOXA1 in sex hormone-related tumors underscores its significance in cancer biology. This review provides an overview of multifaceted roles of FOXA1 in normal development and its implications in the pathogenesis of hormone-related cancers, particularly breast cancer and prostate cancer.
Topics: Humans; Hepatocyte Nuclear Factor 3-alpha; Male; Female; Breast Neoplasms; Prostatic Neoplasms; Gonadal Steroid Hormones; Neoplasms; Animals; Gene Expression Regulation, Neoplastic
PubMed: 38940052
DOI: 10.31083/j.fbl2906225 -
Frontiers in Pharmacology 2024Urologic oncology is a significant public health concern on a global scale. Recent research indicates that long chain non-coding RNAs (lncRNAs) and autophagy play... (Review)
Review
Urologic oncology is a significant public health concern on a global scale. Recent research indicates that long chain non-coding RNAs (lncRNAs) and autophagy play crucial roles in various cancers, including urologic malignancies. This article provides a summary of the latest research findings, suggesting that lncRNA-mediated autophagy could either suppress or promote tumors in prostate, kidney, and bladder cancers. The intricate network involving different lncRNAs, target genes, and mediated signaling pathways plays a crucial role in urological malignancies by modulating the autophagic process. Dysregulated expression of lncRNAs can disrupt autophagy, leading to tumorigenesis, progression, and enhanced resistance to therapy. Consequently, targeting particular lncRNAs that control autophagy could serve as a dependable diagnostic tool and a promising prognostic biomarker in urologic oncology, while also holding potential as an effective therapeutic approach.
PubMed: 38939836
DOI: 10.3389/fphar.2024.1405199 -
Molecular Therapy. Oncology Jun 2024Advancing chimeric antigen receptor (CAR)-engineered T cells for the treatment of solid tumors is a major focus in the field of cellular immunotherapy. Several hurdles...
Advancing chimeric antigen receptor (CAR)-engineered T cells for the treatment of solid tumors is a major focus in the field of cellular immunotherapy. Several hurdles have hindered similar CAR T cell clinical responses in solid tumors as seen in hematological malignancies. These challenges include on-target off-tumor toxicities, which have inspired efforts to optimize CARs for improved tumor antigen selectivity and overall safety. We recently developed a CAR T cell therapy targeting prostate stem cell antigen (PSCA) for prostate and pancreatic cancers, showing improved preclinical antitumor activity and T cell persistence by optimizing the intracellular co-stimulatory domain. Similar studies were undertaken to optimize HER2-directed CAR T cells with modifications to the intracellular co-stimulatory domain for selective targeting of breast cancer brain metastasis. In the present study, we evaluate various nonsignaling extracellular spacers in these CARs to further improve tumor antigen selectivity. Our findings suggest that length and structure of the extracellular spacer can dictate the ability of CARs to selectively target tumor cells with high antigen density, while sparing cells with low antigen density. This study contributes to CAR construct design considerations and expands our knowledge of tuning solid tumor CAR T cell therapies for improved safety and efficacy.
PubMed: 38939825
DOI: 10.1016/j.omton.2024.200789 -
Frontiers in Oncology 2024[This corrects the article DOI: 10.3389/fonc.2024.1368926.].
[This corrects the article DOI: 10.3389/fonc.2024.1368926.].
PubMed: 38939340
DOI: 10.3389/fonc.2024.1427226 -
Cureus May 2024Palmar fasciitis and polyarthritis syndrome (PFPAS) is an exceedingly rare rheumatologic condition characterized by fibrotic changes in the palmar fascia with joint...
Palmar fasciitis and polyarthritis syndrome (PFPAS) is an exceedingly rare rheumatologic condition characterized by fibrotic changes in the palmar fascia with joint pains. It is known to be associated with gynecological malignancy, especially ovarian adenocarcinoma, gastric cancer, pancreatic, prostate, breast, and lung cancer. We present a unique case of a 75-year-old Caucasian female with PFPAS preceding the diagnosis of ovarian cancer by eight months. Our case highlights the importance of considering PFPAS as a potential paraneoplastic syndrome. It underscores the need for increased awareness and further studies to enhance the early detection of underlying malignancies in patients presenting with similar nonspecific hand symptoms.
PubMed: 38939277
DOI: 10.7759/cureus.61248 -
Annals of Laparoscopic and Endoscopic... Jan 2024Flaps and grafts are used for filling dead space, ureteral substitution, and as mesh alternatives. The surgical robot is invaluable in urologic reconstructive surgery...
BACKGROUND AND OBJECTIVE
Flaps and grafts are used for filling dead space, ureteral substitution, and as mesh alternatives. The surgical robot is invaluable in urologic reconstructive surgery due to the ability of the robot to reach the deep pelvis, its minimally invasive access, the ability to use indocyanine green to identify structures and assess tissue perfusion and viability, and ergonomics for the surgeon. Robotic reconstruction can involve tissue transfer in the form of flaps and grafts to provide form and function to organs that have been damaged by iatrogenic injuries, trauma, infections, cancer, radiation injury, or congenital abnormalities. Common flaps and grafts can be readily adapted to the robotic approach. In this literature review, we examine the robotic use of flaps and grafts in reconstructive urology.
METHODS
A thorough literature review was conducted via a PubMed search for predefined terms.
KEY CONTENT AND FINDINGS
Flaps and grafts in reconstructive urology are used for interposition, ureteral substitution, and as mesh alternatives. Omental flaps are used for tissue interposition, or to provide structure and nutrients, and are easily employed with the robot. Various robotic applications of peritoneal flaps have been described. Vascular rectus abdominis musculocutaneous flaps are well-vascularized flaps that occupy dead space and provide structural support, which can be harvested readily with the robot. Sigmoid epiploica are an excellent flap for pelvic reconstruction. Gracilis flaps and fascia lata grafts are well-tolerated and provide space occupying tissue. Boari flaps aid in robotic ureteral reconstruction, especially in the setting of long defects. Oral mucosa is excellent for ureteral or bladder neck reconstruction. Rectal mucosa is well-tolerated and easy to harvest robotically for a variety of urinary tract reconstructive applications. The appendix or ileum can be interposed for repair of damaged ureters.
CONCLUSIONS
Various flaps and grafts have been adapted for robotic reconstructive urology. As the field develops, refinement of techniques and innovation in flaps and employment of the robot will propel this field forward. More studies, especially comparative studies, are needed to elucidate the flaps and grafts that are most likely to be successful with the least morbidity for each use case.
PubMed: 38938988
DOI: 10.21037/ales-23-36 -
Journal of Extracellular Biology Dec 2023Extracellular vesicles (EVs) are important mediators of intercellular communication involved in local and long-range signalling of cancer metastasis. The onset of...
Extracellular vesicles (EVs) are important mediators of intercellular communication involved in local and long-range signalling of cancer metastasis. The onset of invasion is the key step of the metastatic cascade, but the secretion of EVs has remained unexplored at that stage due to technical challenges. In this study, we present a platform to track EVs over the course of invasive development of human prostate cancer cell (PC3) tumoroids utilizing in vivo-mimicking extracellular matrix-based 3D cultures. Using this EV production method, combined with proteomic profiling, we show that PC3 tumoroids secrete EVs with previously undefined protein cargo. Intriguingly, an increase in EV amounts and extensive changes in the EV protein composition were detected upon invasive transition of the tumoroids. The changes in EV protein cargo were counteracted by chemical inhibition of invasion. These results reveal the impact of the tumoroids' invasive status on EV secretion and cargo, and highlight the necessity of in vivo-mimicking conditions for uncovering novel cancer-derived EV components.
PubMed: 38938900
DOI: 10.1002/jex2.124 -
Journal of Extracellular Biology Jan 2024Urinary extracellular vesicles (uEVs) are rich in valuable biomolecule information which are increasingly recognized as potential biomarkers for various diseases. uEV...
Urinary extracellular vesicles (uEVs) are rich in valuable biomolecule information which are increasingly recognized as potential biomarkers for various diseases. uEV long RNAs are among the critical cargos capable of providing unique transcriptome information of the source cells. However, consensus regarding ideal reference genes for relative long RNAs quantification in uEVs is not available as of date. Here we explored stable reference genes through profiling the long RNA expression by RNA-seq following unsupervised analysis and validation studies. Candidate reference genes were identified using four algorithms: NormFinder, GeNorm, BestKeeper and the Delta Ct method, followed by validation. RNA profile showed uEVs contained abundant long RNAs information and the core transcriptome was related to cellular structures, especially ribosome which functions mainly as translation, protein and RNA binding molecules. Analysis of RNA-seq data identified RPL18A, RPL11, RPL27, RACK1, RPSA, RPL41, H1-2, RPL4, GAPDH, RPS27A as candidate reference genes. RT-qPCR validation revealed that RPL41, RPSA and RPL18A were reliable reference genes for long RNA quantification in uEVs from patients with diabetes mellitus (DM), diabetic nephropathy (DN), IgA nephropathy (IgAN) and prostate cancer (PCA). Interestingly, RPL41 also outperformed traditional reference genes in renal tissues of DN and IgAN, as well as in plasma EVs of several types of cancers. The stable reference genes identified in this study may facilitate development of uEVs as novel biomarkers and increase the accuracy and comparability of biomarker studies.
PubMed: 38938675
DOI: 10.1002/jex2.136 -
Open Veterinary Journal May 2024Canine prostatic carcinoma (cPC) is a urogenital tumour with a poor prognosis, for which no effective treatment has been established. Recently, it has been shown that...
BACKGROUND
Canine prostatic carcinoma (cPC) is a urogenital tumour with a poor prognosis, for which no effective treatment has been established. Recently, it has been shown that human epidermal growth factor receptor type 2 (HER2) is overexpressed in cPC cells; however, the efficacy of HER2-targeted therapy remains unclear.
AIM
Investigate the anti-tumour effect of lapatinib on HER2-positive cPC cell lines.
METHODS
Two cell lines (muPC and bePC) were established from two dogs with cPC and the effects of lapatinib treatment on cell proliferation, apoptosis, and HER2 downstream signalling were investigated. Furthermore, muPC was used to generate tumour-bearing mice, and the anti-tumour effects of lapatinib were examined .
RESULTS
Lapatinib treatment inhibited the proliferation and phosphorylation of Erk1/2 and Akt, which are downstream signals of HER2. Furthermore, the TUNEL assay showed that lapatinib induced apoptosis in both cell lines. The muPC-engrafted nude mouse model showed that lapatinib significantly inhibited tumour growth and increased the area of necrotic tumour tissue compared to the vehicle-treated groups.
CONCLUSION
Lapatinib exerts anti-tumour effects on cPC cells by inhibiting HER-2 signalling.
Topics: Lapatinib; Animals; Dogs; Male; Cell Line, Tumor; Dog Diseases; Prostatic Neoplasms; Antineoplastic Agents; Receptor, ErbB-2; Mice; Mice, Nude; Apoptosis; Cell Proliferation; Quinazolines
PubMed: 38938437
DOI: 10.5455/OVJ.2024.v14.i5.21 -
Journal of Translational Medicine Jun 2024Over the last two decades, tumor-derived RNA expression signatures have been developed for the two most commonly diagnosed tumors worldwide, namely prostate and breast...
BACKGROUND
Over the last two decades, tumor-derived RNA expression signatures have been developed for the two most commonly diagnosed tumors worldwide, namely prostate and breast tumors, in order to improve both outcome prediction and treatment decision-making. In this context, molecular signatures gained by main components of the tumor microenvironment, such as cancer-associated fibroblasts (CAFs), have been explored as prognostic and therapeutic tools. Nevertheless, a deeper understanding of the significance of CAFs-related gene signatures in breast and prostate cancers still remains to be disclosed.
METHODS
RNA sequencing technology (RNA-seq) was employed to profile and compare the transcriptome of CAFs isolated from patients affected by breast and prostate tumors. The differentially expressed genes (DEGs) characterizing breast and prostate CAFs were intersected with data from public datasets derived from bulk RNA-seq profiles of breast and prostate tumor patients. Pathway enrichment analyses allowed us to appreciate the biological significance of the DEGs. K-means clustering was applied to construct CAFs-related gene signatures specific for breast and prostate cancer and to stratify independent cohorts of patients into high and low gene expression clusters. Kaplan-Meier survival curves and log-rank tests were employed to predict differences in the outcome parameters of the clusters of patients. Decision-tree analysis was used to validate the clustering results and boosting calculations were then employed to improve the results obtained by the decision-tree algorithm.
RESULTS
Data obtained in breast CAFs allowed us to assess a signature that includes 8 genes (ITGA11, THBS1, FN1, EMP1, ITGA2, FYN, SPP1, and EMP2) belonging to pro-metastatic signaling routes, such as the focal adhesion pathway. Survival analyses indicated that the cluster of breast cancer patients showing a high expression of the aforementioned genes displays worse clinical outcomes. Next, we identified a prostate CAFs-related signature that includes 11 genes (IL13RA2, GDF7, IL33, CXCL1, TNFRSF19, CXCL6, LIFR, CXCL5, IL7, TSLP, and TNFSF15) associated with immune responses. A low expression of these genes was predictive of poor survival rates in prostate cancer patients. The results obtained were significantly validated through a two-step approach, based on unsupervised (clustering) and supervised (classification) learning techniques, showing a high prediction accuracy (≥ 90%) in independent RNA-seq cohorts.
CONCLUSION
We identified a huge heterogeneity in the transcriptional profile of CAFs derived from breast and prostate tumors. Of note, the two novel CAFs-related gene signatures might be considered as reliable prognostic indicators and valuable biomarkers for a better management of breast and prostate cancer patients.
Topics: Humans; Prostatic Neoplasms; Male; Breast Neoplasms; Female; Cancer-Associated Fibroblasts; Gene Expression Regulation, Neoplastic; Prognosis; Transcriptome; Gene Expression Profiling; Cluster Analysis; Treatment Outcome; Middle Aged; Kaplan-Meier Estimate
PubMed: 38937754
DOI: 10.1186/s12967-024-05413-2