Paul F. Seke Etet

Bio: Paul F. Seke Etet is an academic researcher from University of Ngaoundéré. The author has contributed to research in topics: Cancer & Stromal cell. The author has an hindex of 16, co-authored 46 publications receiving 925 citations. Previous affiliations of Paul F. Seke Etet include University of Yaoundé I & Qassim University.

Insulin resistance and cancer: the role of insulin and IGFs

Abstract: Insulin, IGF1, and IGF2 are the most studied insulin-like peptides (ILPs). These are evolutionary conserved factors well known as key regulators of energy metabolism and growth, with crucial roles in insulin resistance-related metabolic disorders such as obesity, diseases like type 2 diabetes mellitus, as well as associated immune deregulations. A growing body of evidence suggests that insulin and IGF1 receptors mediate their effects on regulating cell proliferation, differentiation, apoptosis, glucose transport, and energy metabolism by signaling downstream through insulin receptor substrate molecules and thus play a pivotal role in cell fate determination. Despite the emerging evidence from epidemiological studies on the possible relationship between insulin resistance and cancer, our understanding on the cellular and molecular mechanisms that might account for this relationship remains incompletely understood. The involvement of IGFs in carcinogenesis is attributed to their role in linking high energy intake, increased cell proliferation, and suppression of apoptosis to cancer risks, which has been proposed as the key mechanism bridging insulin resistance and cancer. The present review summarizes and discusses evidence highlighting recent advances in our understanding on the role of ILPs as the link between insulin resistance and cancer and between immune deregulation and cancer in obesity, as well as those areas where there remains a paucity of data. It is anticipated that issues discussed in this paper will also recover new therapeutic targets that can assist in diagnostic screening and novel approaches to controlling tumor development.

Developmental pathways associated with cancer metastasis: Notch, Wnt, and Hedgehog.

Abstract: Master developmental pathways, such as Notch, Wnt, and Hedgehog, are signaling systems that control proliferation, cell death, motility, migration, and stemness These systems are not only commonly activated in many solid tumors, where they drive or contribute to cancer initiation, but also in primary and metastatic tumor development The reactivation of developmental pathways in cancer stroma favors the development of cancer stem cells and allows their maintenance, indicating these signaling pathways as particularly attractive targets for efficient anticancer therapies, especially in advanced primary tumors and metastatic cancers Metastasis is the worst feature of cancer development This feature results from a cascade of events emerging from the hijacking of epithelial-mesenchymal transition, angiogenesis, migration, and invasion by transforming cells and is associated with poor survival, drug resistance, and tumor relapse In the present review, we summarize and discuss experimental data suggesting pivotal roles for developmental pathways in cancer development and metastasis, considering the therapeutic potential Emerging targeted antimetastatic therapies based on Notch, Wnt, and Hedgehog pathways are also discussed

The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases.

Abstract: The ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT) signaling pathway, a Ca2+/calmodulin-dependent major proinflammatory pathway, in the pathogenesis of these diseases. Neurotoxins such as amyloid-β, tau protein, and α-synuclein trigger abnormal calcineurin/NFAT signaling activities. Additionally increased activities of endogenous regulators of calcineurin like plasma membrane Ca2+-ATPase (PMCA) and regulator of calcineurin 1 (RCAN1) also cause neuronal and glial loss and related functional alterations, in neurodegenerative diseases, psychotic disorders, epilepsy, and traumatic brain and spinal cord injuries. Treatment with calcineurin/NFAT inhibitors induces some degree of neuroprotection and decreased reactive gliosis in the central and peripheral nervous system. In this paper, we summarize and discuss the current understanding of the roles of calcineurin/NFAT signaling in physiology and pathologies of the adult and developing nervous system, with an emphasis on recent reports and cutting-edge findings. Calcineurin/NFAT signaling is known for its critical roles in the developing and adult nervous system. Its role in physiological and pathological processes is still controversial. However, available data suggest that its beneficial and detrimental effects are context-dependent. In view of recent reports calcineurin/NFAT signaling is likely to serve as a potential therapeutic target for neurodegenerative diseases and conditions. This review further highlights the need to characterize better all factors determining the outcome of calcineurin/NFAT signaling in diseases and the downstream targets mediating the beneficial and detrimental effects.

Role of WHO.

Abstract: OVERVIEW The GRA Marketing Internship Program is offered to students who are interested in gaining valuable work experience through efforts in marketing, membership, sales, and events. Interns work directly to assist the Director of Marketing and Communications on various tasks relating to upcoming GRA events. During this internship, students will work a minimum of 10 hours a week and a maximum of 20 hours a week. Students are encouraged to earn credit for their internship, however this is a paid internship. Students interested in obtaining credit for their internship must consult their academic advisor or the intern coordinator at their academic unit.

Complex Trauma in Children and Adolescents

Abstract: Complex trauma events, or chronic interpersonal traumas that begin early in life, are thought to result in profound disruptions, well beyond the symptoms of PTSD. Complex trauma events may be especially toxic for children and adolescents, whose regulatory systems are more vulnerable. This study provides empirical support for the previously unexamined hypothesis that complex trauma events result in broad systemic difficulties, not simply higher levels of PTSD symptoms. This study also offers evidence for a dimensional conceptualization of traumatic events, with acute noninterpersonal trauma residing on one end of the spectrum and complex trauma on the other. 346 treatmentseeking children and adolescents who had experienced a traumatic event were included in this study. Results indicated that children exposed to a complex trauma event had significantly higher levels of trauma-related and generalized difficulties as compared to those exposed to other, less severe traumatic events. Children exposed to successively more severe traumatic events were also reported to have increasingly higher levels of difficulties. The evidence of including an impaired caregiving system, operationalized as the child being removed from the home following the onset of the traumatic event, into the definition of complex trauma was examined, but not supported. The results demonstrate the validity of the concept of complex trauma and point to the need for a diagnostic construct related to complex trauma for children and adolescents. Wamser, Rachel, UMSL, 2012 8 Complex Trauma in Children and Adolescents A substantial number of children and adolescents experience traumatic events such as sexual, physical, or emotional abuse, neglect, domestic violence, natural disasters, school or community violence and serious car accidents and other accidents. It is the unfortunate reality that some of these youth receive more than their fair share, experiencing severe, multiple, prolonged traumas. In fact, one nationally representative sample of over two thousand children found that 22% of surveyed children had experienced four or more different kinds of victimization within a single year (Finkelhor, Ormrod, & Turner, 2007). This suggests that the experience of extensive and repeated trauma is not all uncommon, yet this subset of survivors have not received little attention to their unique needs. Decades of research, however, have been devoted to examining the impact of single types of maltreatment (i.e., sexual or physical abuse) and consistently demonstrate the toxicity of various traumatic events. Childhood traumatic experiences have been linked to a variety of physical and mental health problems, risky and selfinjurious behaviors, negative parenting outcomes, revictimization, and perpetration of interpersonal violence (Abram, Teplin, Longworth, McClelland, & Dulcan, 2004; Anda, 2006; Banyard, Williams, & Siegel, 2003; Felitti et al., 1997; Walsh, Blaustein, Knight, Spinazzola, & van der Kolk, 2007; Whitfield, Dube, Anda, & Felitti, 2003). Clearly, these well-documented symptoms extend far beyond the confines of the diagnostic construct Posttraumatic Stress Disorder (PTSD) even for acute traumatic events. When considering the impact of poly-victimization, then PTSD may be insignificant. A diagnosis of PTSD requires the direct or indirect exposure to a traumatic event that involves an actual or perceived threat to the physical integrity of an individual or others (criterion A1; APA, 2000). Traumatic events commonly observed in childhood Wamser, Rachel, UMSL, 2012 9 include, but are not limited to: child sexual or physical abuse, neglect, domestic violence, life-threatening illness, school or community violence, unexpected death of a family member or close friend, natural disaster, motor vehicle accident or other serious accident. Thus, a wide range of events are captured under the heading of a traumatic event. But would the experience of learning of a friend's non-fatal car accident be expected to result in an identical symptom presentation as chronic sexual abuse perpetrated by one's biological father? According to the PTSD framework, yes. Despite qualitative differences in terms of the degree of involvement, severity, and chronicity of the traumatic event, with the diagnostic construct of PTSD, all traumatic events are assumed to potentially result in the same sequelae. Yet, common sense and clinical lore suggests that survivors of severe traumatic events will have a more complicated symptom presentation. This is affirmed by research. Researchers consistently find that characteristics of the traumatic event are related to a more complicated symptom presentationtypically with non-PTSD symptoms. For example, interpersonal traumas, such as abuse and domestic violence, appear to be particularly harmful, resulting in long-lasting, severe, and more generalized symptoms than non-interpersonal traumas such as motor vehicle accidenets (Briere & Jordan, 2004; Briere, Kaltman, & Green, 2008; Ford, Stockton, Kaltman, & Green, 2006; van der Kolk, 2005). Interpersonal traumas are partly so toxic as they are intentionally perpetrated by another person, thus, the victim’s views regarding safety, intimacy, and trustworthiness are vulnerable to unhelpful or inaccurate alterations (Janoff-Bullman, 1992). The duration and the number of instances of the traumatic event are also related to outcome. Duration and number of incidents are linked together as traumatic events that are chronic, by their nature, have occurred more than once and conversely, multiple incidents of a Wamser, Rachel, UMSL, 2012 10 traumatic event often occur over an extended period of time. Unsurprisingly, the longer and more frequently the trauma occurs, the more severe and varied the post-traumatic sequelae (Blaauw, Winkel, Arensman, Sheridan, & Freeve, 2002; Mechanic, Uhlmansiek, Weaver, & Resick, 2000). Both of these characteristics may contribute to the survivor feeling overwhelmed, helpless, or that the trauma is inescapable. The age of the victim when the trauma begins is important. Traumatic events that begin in childhood result in a more severe symptom presentation compared to those which begin in adulthood (Cloitre, Scarvalone, & Difede, 1997; Roth, Newman, Pelcovitz, van der Kolk, & Mandel, 1997). In sum, all traumatic events are not created equal. Taken together, research would suggest that traumatic events which are interpersonal in nature, chronic or multiple, or begin at an early age are related to a more complex symptom presentation (Herman, 1992; Terr, 1991). Within the current PTSD construct, these differences are not acknowledged and instead are subsumed under a single diagnostic category. PTSD also takes a one-size-fits-all approach to trauma-related symptoms, which is tragic as PTSD is fails to capture the full span of trauma-related sequelae. PTSD is classified as an anxiety disorder and consequently, PTSD describes symptoms of anxiety. Trauma survivors unfortunately have problems beyond that of anxiety. Survivors of childhood sexual abuse, for example, have difficulties in a broad range of domains including serious impairments in affect regulation, self-concept, and interpersonal problems, sexualized behavior, and somatic complaints (Cloitre, Stovall-McClough, Zorbas, & Charuvastra, 2003; Spinazzola, 2005; Stovall-McClough & Cloitre, 2006; Zucker, Spinazzola, Blaustein, & van der Kolk, 2006). These symptoms are notably absent from the list of acceptable symptoms of PTSD. As an anxiety disorder, the construct PTSD is unable to capture these difficulties without violating the organization Wamser, Rachel, UMSL, 2012 11 of the DSM. The non-anxiety symptoms which do not fit are relegated to a variety of “comorbid” conditions, which ostensibly are thought to be unrelated to the trauma. This would be acceptable if few traumatized individuals presented with non-PTSD diagnoses. Unfortunately, non-PTSD symptoms are ubiquitous, with more than 80% of individuals diagnosed with PTSD also receiving a comorbid diagnosis (Foa, Freidman & Keane, 2000). PTSD has one of the highest rates of comorbidity of any DSM diagnostic category (Kessler, Chiu, Demier, Merikangas, & Walters, 2005). This may be problematic, it is implied that some, but not all, of the patient's symptoms may be ascribed to the traumatic experience. Conceptualizing other potential effects of trauma as merely “co-morbid,” as opposed to the “real” trauma disorder may also limit the validity of trauma research; as such co-morbid conditions are often excluded from traumafocused research. In fact, a review of the treatment outcome studies demonstrated that the typical presenting client would be screened out of PTSD studies because of comorbid conditions (Spinazzola, Blaustein, & van der Kolk, 2005). Thus, much of PTSD research may not be even applicable to the typical client. PTSD is, instead, more useful in capturing the effects of single-episode, acute traumas occurring in adulthood (Cloitre, Scarvalone, & Difede, 1997; van der Kolk, 2005). In fact, PTSD is diagnosed more frequently following single instances of trauma than after multiple or chronic traumatic events (Green et al., 2000). Clearly, this does not indicate that individuals who have experienced repeated and severe traumatic events do not present with trauma-related difficulties, but rather, that the PTSD criteria may be insufficient in describing reactions to more severe traumatic events. Since its inception into the DSM in 1980, leaders in the field of traumatic stress have argued that PTSD does not accurately capture the presentation of victims of child abuse, concentration camps, Wamser, Rachel, UMSL, 2012 12 refugee camps, domestic violence, or those that have experienced other repeated and extensive trauma (Herman, 1992; Cook et al., 2005; Courtois, 2004). The shortcomings of PTSD are too great for the most serious of traumas. Diagnostic issues tend to be magnifie

The Sleep-Immune Crosstalk in Health and Disease

Abstract: Sleep and immunity are bidirectionally linked. Immune system activation alters sleep, and sleep in turn affects the innate and adaptive arm of our body’s defense system. Stimulation of the immune s...

Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis.

Abstract: As the most commonly occurring cancer in women worldwide, breast cancer poses a formidable public health challenge on a global scale. Breast cancer consists of a group of biologically and molecularly heterogeneous diseases originated from the breast. While the risk factors associated with this cancer varies with respect to other cancers, genetic predisposition, most notably mutations in BRCA1 or BRCA2 gene, is an important causative factor for this malignancy. Breast cancers can begin in different areas of the breast, such as the ducts, the lobules, or the tissue in between. Within the large group of diverse breast carcinomas, there are various denoted types of breast cancer based on their invasiveness relative to the primary tumor sites. It is important to distinguish between the various subtypes because they have different prognoses and treatment implications. As there are remarkable parallels between normal development and breast cancer progression at the molecular level, it has been postulated that breast cancer may be derived from mammary cancer stem cells. Normal breast development and mammary stem cells are regulated by several signaling pathways, such as estrogen receptors (ERs), HER2, and Wnt/β-catenin signaling pathways, which control stem cell proliferation, cell death, cell differentiation, and cell motility. Furthermore, emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer, especially for triple-negative breast cancer. This review provides a comprehensive survey of the molecular, cellular and genetic aspects of breast cancer.