scholarly journals Mapping of m6A and Its Regulatory Targets in Prostate Cancer Reveals a METTL3-low Induction of Therapy Resistance

2021 ◽  
Author(s):  
Kellie A. Cotter ◽  
John Gallon ◽  
Nadine Uebersax ◽  
Philip Rubin ◽  
Kate D. Meyer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Potential Role ◽  
Therapy Resistance ◽  
Gene Signature ◽  
Matrix Proteins ◽  
Hepatocyte Nuclear Factor ◽  
Low Levels ◽  
Post Transcriptional Regulation ◽  
The Relationship

ABSTRACTRecent evidence has highlighted the role of N6-methyladenosine (m6A) in the regulation of mRNA expression, stability and translation, supporting a potential role for post-transcriptional regulation mediated by m6A in cancer. Here we explore prostate cancer as an exemplar and demonstrate that low levels of N6-adenosine-methyltransferase (METTL3) is associated with advanced metastatic disease. To explore this relationship, we generated the first prostate m6A maps, and further examined how METTL3 regulates expression at the level of transcription, translation, and protein. Significantly, transcripts encoding extracellular matrix proteins are consistently upregulated with METTL3 knockdown. We also examined the relationship between METTL3 and androgen signaling and discovered the upregulation of a hepatocyte nuclear factor-driven gene signature that is associated with therapy resistance in prostate cancer. Significantly, METTL3 knockdown rendered the cells resistant to androgen receptor antagonists, implicating changes in m6A as a mechanism for therapy resistance in metastatic prostate cancer.

Ups and downs on the roller coaster of task conflict: the role of group cognitive complexity, collective emotional intelligence and team creativity

2020 ◽  
Vol 18 (1) ◽  
pp. 23-37
Author(s):  
Andreea Gheorghe ◽  
Oana Fodor ◽  
Anișoara Pavelea
Keyword(s):  
Emotional Intelligence ◽  
Cognitive Complexity ◽  
Empirical Support ◽  
Task Conflict ◽  
Team Creativity ◽  
Mediating Role ◽  
Low Levels ◽  
Explanatory Mechanism ◽  
The Relationship

This study explores the association between task conflict and team creativity and the role of group cognitive complexity (GCC) as a potential explanatory mechanism in a sample of 159 students organized in 49 groups. Moreover, we analyzed the moderating effect of collective emotional intelligence (CEI)in the relationship between task conflict and GCC.As hypothesized, we found that task conflict has a nonlinear relationship with GCC, but contrary to our expectations, it follows a U-shaped association, not an inversed U-shape. In addition,the moderating role of CEI was significant only at low levels. Contrary to our expectation, the mediating role of GCC did not receive empirical support. Theoretical and practical contributions are discussed.

Cardiac interoception in neurological conditions and its relevance for dimensional approaches

2018 ◽  
Author(s):  
Adrián Yoris ◽  
Adolfo M. García ◽  
Paula Celeste Salamone ◽  
Lucas Sedeño ◽  
Indira García-Cordero ◽  
...  
Keyword(s):  
Potential Role ◽  
Neurocognitive Deficits ◽  
Future Directions ◽  
Treatment And Prevention ◽  
Neurological Conditions ◽  
Key Aspects ◽  
The Relationship ◽  
General Source ◽  
Neuropsychiatric Conditions

Dimensional and transdiagnostic approaches have revealed multiple cognitive/emotional alterations shared by several neuropsychiatric conditions. While this has been shown for externally triggered neurocognitive processes, the disruption of interoception across neurological disorders remains poorly understood. This chapter aims to fill this gap while proposing cardiac interoception as a potential common biomarker across disorders. It focuses on key aspects of interoception, such as the mechanisms underlying different interoceptive dimensions; the relationship among interoception, emotion, and social cognition; and the roles of different interoceptive pathways. It considers behavioral and brain evidence in the context of an experimental and clinical agenda to evaluate the potential role of interoception as a predictor of clinical outcomes, a marker of neurocognitive deficits across diseases, and a general source of insights for breakthroughs in the treatment and prevention of multiple disorders. Finally, future directions to improve the dimensional and transdiagnostic assessment of interoception are outlined.

scholarly journals Genetic Suppressor Element 1 (GSE1) Promotes the Oncogenic and Recurrent Phenotypes of Castration-Resistant Prostate Cancer by Targeting Tumor-Associated Calcium Signal Transducer 2 (TACSTD2)

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3959
Author(s):  
Oluwaseun Adebayo Bamodu ◽  
Yuan-Hung Wang ◽  
Chen-Hsun Ho ◽  
Su-Wei Hu ◽  
Chia-Da Lin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Therapy Resistance ◽  
Calcium Signal ◽  
Signal Transducer ◽  
Castration Resistance ◽  
Castration Resistant

Background: prostate cancer (PCa) is a principal cause of cancer-related morbidity and mortality. Castration resistance and metastasis are clinical challenges and continue to impede therapeutic success, despite diagnostic and therapeutic advances. There are reports of the oncogenic activity of genetic suppressor element (GSE)1 in breast and gastric cancers; however, its role in therapy resistance, metastasis, and susceptibility to disease recurrence in PCa patients remains unclear. Objective: this study investigated the role of aberrantly expressed GSE1 in the metastasis, therapy resistance, relapse, and poor prognosis of advanced PCa. Methods: we used a large cohort of multi-omics data and in vitro, ex vivo, and in vivo assays to investigate the potential effect of altered GSE1 expression on advanced/castration-resistant PCa (CRPC) treatment responses, disease progression, and prognosis. Results: using a multi-cohort approach, we showed that GSE1 is upregulated in PCa, while tumor-associated calcium signal transducer 2 (TACSTD2) is downregulated. Moreover, the direct, but inverse, correlation interaction between GSE1 and TACSTD2 drives metastatic disease, castration resistance, and disease progression and modulates the clinical and immune statuses of patients with PCa. Patients with GSE1highTACSTD2low expression are more prone to recurrence and disease-specific death than their GSE1lowTACSTD2high counterparts. Interestingly, we found that the GSE1–TACSTD2 expression profile is associated with the therapy responses and clinical outcomes in patients with PCa, especially those with metastatic/recurrent disease. Furthermore, we demonstrate that the shRNA-mediated targeting of GSE1 (shGSE1) significantly inhibits cell proliferation and attenuates cell migration and tumorsphere formation in metastatic PC3 and DU145 cell lines, with an associated suppression of VIM, SNAI2, and BCL2 and the concomitant upregulation of TACSTD2 and BAX. Moreover, shGSE1 enhances sensitivity to the antiandrogens abiraterone and enzalutamide in vitro and in vivo. Conclusion: these data provide preclinical evidence of the oncogenic role of dysregulated GSE1–TACSTD2 signaling and show that the molecular or pharmacological targeting of GSE1 is a workable therapeutic strategy for inhibiting androgen-driven oncogenic signals, re-sensitizing CRPC to treatment, and repressing the metastatic/recurrent phenotypes of patients with PCa.

scholarly journals Cell Plasticity and Prostate Cancer: The Role of Epithelial–Mesenchymal Transition in Tumor Progression, Invasion, Metastasis and Cancer Therapy Resistance

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2795
Author(s):  
Sofia Papanikolaou ◽  
Aikaterini Vourda ◽  
Spyros Syggelos ◽  
Kostis Gyftopoulos
Keyword(s):  
Prostate Cancer ◽  
Cancer Therapy ◽  
Tumor Progression ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Tumor ◽  
Therapy Resistance ◽  
Cellular Process ◽  
Cell Plasticity ◽  
Mesenchymal Transition

Prostate cancer, the second most common malignancy in men, is characterized by high heterogeneity that poses several therapeutic challenges. Epithelial–mesenchymal transition (EMT) is a dynamic, reversible cellular process which is essential in normal embryonic morphogenesis and wound healing. However, the cellular changes that are induced by EMT suggest that it may also play a central role in tumor progression, invasion, metastasis, and resistance to current therapeutic options. These changes include enhanced motility and loss of cell–cell adhesion that form a more aggressive cellular phenotype. Moreover, the reverse process (MET) is a necessary element of the metastatic tumor process. It is highly probable that this cell plasticity reflects a hybrid state between epithelial and mesenchymal status. In this review, we describe the underlying key mechanisms of the EMT-induced phenotype modulation that contribute to prostate tumor aggressiveness and cancer therapy resistance, in an effort to provide a framework of this complex cellular process.

scholarly journals Role of Precision Oncology in Type II Endometrial and Prostate Cancers in the African Population: Global Cancer Genomics Disparities

2022 ◽  
Vol 23 (2) ◽  
pp. 628
Author(s):  
Rahaba Marima ◽  
Rodney Hull ◽  
Mandisa Mbeje ◽  
Thulo Molefi ◽  
Kgomotso Mathabe ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Endometrial Cancer ◽  
African Ancestry ◽  
African Population ◽  
Precision Oncology ◽  
Type Ii ◽  
Incidence And Mortality ◽  
Prostate Cancers ◽  
The Relationship

Precision oncology can be defined as molecular profiling of tumors to identify targetable alterations. Emerging research reports the high mortality rates associated with type II endometrial cancer in black women and with prostate cancer in men of African ancestry. The lack of adequate genetic reference information from the African genome is one of the major obstacles in exploring the benefits of precision oncology in the African context. Whilst external factors such as the geography, environment, health-care access and socio-economic status may contribute greatly towards the disparities observed in type II endometrial and prostate cancers in black populations compared to Caucasians, the contribution of African ancestry to the contribution of genetics to the etiology of these cancers cannot be ignored. Non-coding RNAs (ncRNAs) continue to emerge as important regulators of gene expression and the key molecular pathways involved in tumorigenesis. Particular attention is focused on activated/repressed genes and associated pathways, while the redundant pathways (pathways that have the same outcome or activate the same downstream effectors) are often ignored. However, comprehensive evidence to understand the relationship between type II endometrial cancer, prostate cancer and African ancestry remains poorly understood. The sub-Saharan African (SSA) region has both the highest incidence and mortality of both type II endometrial and prostate cancers. Understanding how the entire transcriptomic landscape of these two reproductive cancers is regulated by ncRNAs in an African cohort may help elucidate the relationship between race and pathological disparities of these two diseases. This review focuses on global disparities in medicine, PCa and ECa. The role of precision oncology in PCa and ECa in the African population will also be discussed.

scholarly journals Pathogen Threat and In-group Cooperation

2021 ◽  
Vol 12 ◽  
Author(s):  
Hirotaka Imada ◽  
Nobuhiro Mifune
Keyword(s):  
Selection Pressure ◽  
Potential Role ◽  
Cooperative Behavior ◽  
Future Studies ◽  
Behavioral Immune System ◽  
Group Cooperation ◽  
Group Members ◽  
The Relationship ◽  
Intergroup Behavior

Disease-causing parasites and pathogens play a pivotal role in intergroup behavior. Previous studies have suggested that the selection pressure posed by pathogen threat has resulted in in-group assortative sociality, including xenophobia and in-group favoritism. While the current literature has collated numerous studies on the former, strikingly, there has not been much research on the relationship between pathogen threat and in-group cooperation. Drawing upon prior studies on the function of the behavioral immune system (BIS), we argued that the BIS might facilitate cooperation with in-group members as a reactive behavioral immune response to pathogen threat. More specifically, we held that individuals might utilize cooperative behavior to ensure that they can receive social support when they have contracted an infectious disease. We reviewed existing findings pertaining to the potential role of the BIS in in-group cooperation and discussed directions for future studies.

Computed tomography study of pineal calcification in schizophrenia

1999 ◽  
Vol 14 (3) ◽  
pp. 163-166 ◽  
Author(s):  
G Bersani ◽  
A Garavini ◽  
I Taddei ◽  
G Tanfani ◽  
M Nordio ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Pineal Gland ◽  
Potential Role ◽  
Ct Scans ◽  
Entire Group ◽  
Positive Symptoms ◽  
Healthy Controls ◽  
Mean Size ◽  
The Relationship

SummaryComputed tomography studies concerning pineal calcification (PC) in schizophrenia have been conducted mainly by one author who correlated this calcification with several aspects of the illness. On the basis of these findings the aim of the present study was to analyze size and incidence of pineal gland calcification by CT in schizophrenics and healthy controls, and to verify the relationship between pineal calcification and age, and the possible correlation with psychopathologic variables. Pineal calcification was measured on CT scans of 87 schizophrenics and 46 controls divided into seven age subgroups of five years each. No significant differences in PC incidence and mean size between patients and controls were observed as far as the entire group was considered. PC size correlated with age both in schizophrenics and controls. We found a higher incidence of PC in schizophrenics in the age subgroup of 21–25 years, and a negative correlation with positive symptoms of schizophrenia in the overall group. These findings could suggest a premature calcific process in schizophrenics and a probable association with `non-paranoid' aspects of the illness. Nevertheless the potential role of this process possibly related to some aspects of the altered neurodevelopment in schizophrenia is still unclear.

scholarly journals Individual Expectation: An Overlooked, but Pertinent, Factor in the Treatment of Individuals Experiencing Musculoskeletal Pain

2010 ◽  
Vol 90 (9) ◽  
pp. 1345-1355 ◽  
Author(s):  
Joel E. Bialosky ◽  
Mark D. Bishop ◽  
Joshua A. Cleland
Keyword(s):  
Clinical Practice ◽  
Clinical Outcomes ◽  
Musculoskeletal Pain ◽  
Current Literature ◽  
Potential Role ◽  
Physical Therapists ◽  
Clinical Perspective ◽  
The Relationship

Physical therapists consider many factors in the treatment of patients with musculoskeletal pain. The current literature suggests expectation is an influential component of clinical outcomes related to musculoskeletal pain for which physical therapists frequently do not account. The purpose of this clinical perspective is to highlight the potential role of expectation in the clinical outcomes associated with the rehabilitation of individuals experiencing musculoskeletal pain. The discussion focuses on the definition and measurement of expectation, the relationship between expectation and outcomes related to musculoskeletal pain conditions, the mechanisms through which expectation may alter musculoskeletal pain conditions, and suggested ways in which clinicians may integrate the current literature regarding expectation into clinical practice.

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