Nova Reader - Subject https://www.novareader.co Default RSS Feed en-us Newgen KnowledgeWorks <![CDATA[Therapy resistance on the RADar in ovarian cancer]]> https://www.novareader.co/book/isbn/10.15252/emmm.202114010 Ovarian cancer has the worst prognosis of all gynecological cancers with high‐grade serous ovarian cancer (HGSOC) accounting for the majority of ovarian cancer deaths. Therapy resistance and the selection of effective therapies for patients remains a major challenge. In this issue of EMBO Molecular Medicine, Hoppe et al present RAD51 expression as a biomarker of platinum resistance in high‐grade serous ovarian cancer (HGSOC) patients (Hoppe et al, 2021).

M. Sprick, J. Schwickert and F. Zickgraf discuss the identification of RAD51 as a biomarker of platinum resistance in High‐Grade Serous Ovarian Cancer patients, as reported by A. Jeyasekharan and colleagues in this issue of EMBO Molecular Medicine.

]]> <![CDATA[Therapy resistance on the RADar in ovarian cancer]]> https://www.novareader.co/book/isbn/10.15252/emmm.202114010 Ovarian cancer has the worst prognosis of all gynecological cancers with high‐grade serous ovarian cancer (HGSOC) accounting for the majority of ovarian cancer deaths. Therapy resistance and the selection of effective therapies for patients remains a major challenge. In this issue of EMBO Molecular Medicine, Hoppe et al present RAD51 expression as a biomarker of platinum resistance in high‐grade serous ovarian cancer (HGSOC) patients (Hoppe et al, 2021).

M. Sprick, J. Schwickert and F. Zickgraf discuss the identification of RAD51 as a biomarker of platinum resistance in High‐Grade Serous Ovarian Cancer patients, as reported by A. Jeyasekharan and colleagues in this issue of EMBO Molecular Medicine.

]]> <![CDATA[Motile mosquito stage malaria parasites: ready for their close‐up]]> https://www.novareader.co/book/isbn/10.15252/emmm.202113975 Many stages of the complex Plasmodium parasite life cycle, the eukaryotic pathogen that causes malaria, are extracellular and motile. This motility is essential for life cycle progression, and two studies in this issue of EMBO Molecular Medicine (Hopp et al, 2021; Ripp et al, 2021) examine the motility of two of these life cycle stages. These are the ookinete, which develops in the midgut of an infected mosquito vector, and the sporozoite, which is injected into the skin of an unsuspecting host by an infected mosquito, initiating the parasite life cycle in the human. Therapeutic targeting of the ookinete and sporozoite (Duffy & Patrick Gorres, 2020), which are profound bottlenecks in the life cycle, has recently received a great deal of attention in our battle to prevent the 400,000 deaths from malaria that occur every year (WHO, 2020).

A. Vaughan discusses malaria parasite ookinete and sporozoite motility and two models to pre‐clinically test malaria intervention strategies as reported by Ripp et al (2021) and Hopp et al (2021), in this issue of EMBO Mol Med.

]]> <![CDATA[Motile mosquito stage malaria parasites: ready for their close‐up]]> https://www.novareader.co/book/isbn/10.15252/emmm.202113975 Many stages of the complex Plasmodium parasite life cycle, the eukaryotic pathogen that causes malaria, are extracellular and motile. This motility is essential for life cycle progression, and two studies in this issue of EMBO Molecular Medicine (Hopp et al, 2021; Ripp et al, 2021) examine the motility of two of these life cycle stages. These are the ookinete, which develops in the midgut of an infected mosquito vector, and the sporozoite, which is injected into the skin of an unsuspecting host by an infected mosquito, initiating the parasite life cycle in the human. Therapeutic targeting of the ookinete and sporozoite (Duffy & Patrick Gorres, 2020), which are profound bottlenecks in the life cycle, has recently received a great deal of attention in our battle to prevent the 400,000 deaths from malaria that occur every year (WHO, 2020).

A. Vaughan discusses malaria parasite ookinete and sporozoite motility and two models to pre‐clinically test malaria intervention strategies as reported by Ripp et al (2021) and Hopp et al (2021), in this issue of EMBO Mol Med.

]]> <![CDATA[Wnt signaling inhibition confers induced synthetic lethality to PARP inhibitors]]> https://www.novareader.co/book/isbn/10.15252/emmm.202114002 Despite considerable efforts, therapeutic strategies targeting the Wnt pathway are still not clinically available. The pervasive role of Wnt‐βcatenin signaling for the control of stem cells during normal tissue homeostasis makes the on‐target toxicity of available therapeutic grade molecules an important limitation preventing their clinical introduction. The article in this issue of EMBO Molecular Medicine by Kaur et al (2021) reveals that treatment of Wnt‐addicted cancer cells with inhibitors of Wnt signaling induces a state of BRCAness leading to hypersensitivity to PARP inhibitors. This is a new example of induced synthetic lethality that could pave the way for new indications for PARP inhibitors or may contribute to the long‐awaited clinical introduction of therapeutic agents targeting the Wnt pathway.

S. Angers discusses a new example of induced‐synthetic lethality reported by Kaur et al (this issue of EMBO Mol Med) that shows that treatment of Wnt‐addicted cancer cells with inhibitors of Wnt signaling induces a state of BRCAness leading to hypersensitivity to PARP inhibitors.

]]> <![CDATA[Wnt signaling inhibition confers induced synthetic lethality to PARP inhibitors]]> https://www.novareader.co/book/isbn/10.15252/emmm.202114002 Despite considerable efforts, therapeutic strategies targeting the Wnt pathway are still not clinically available. The pervasive role of Wnt‐βcatenin signaling for the control of stem cells during normal tissue homeostasis makes the on‐target toxicity of available therapeutic grade molecules an important limitation preventing their clinical introduction. The article in this issue of EMBO Molecular Medicine by Kaur et al (2021) reveals that treatment of Wnt‐addicted cancer cells with inhibitors of Wnt signaling induces a state of BRCAness leading to hypersensitivity to PARP inhibitors. This is a new example of induced synthetic lethality that could pave the way for new indications for PARP inhibitors or may contribute to the long‐awaited clinical introduction of therapeutic agents targeting the Wnt pathway.

S. Angers discusses a new example of induced‐synthetic lethality reported by Kaur et al (this issue of EMBO Mol Med) that shows that treatment of Wnt‐addicted cancer cells with inhibitors of Wnt signaling induces a state of BRCAness leading to hypersensitivity to PARP inhibitors.

]]> <![CDATA[iNPH—the mystery resolving]]> https://www.novareader.co/book/isbn/10.15252/emmm.202013720 Idiopathic normal pressure hydrocephalus (iNPH) is characterized clinically by degradation of gait, cognition, and urinary continence. INPH is progressive (Andrén et al, 2014), still probably underdiagnosed (Williams et al, 2019) but potentially treatable by CSF diversion (Kazui et al, 2015). Familial aggregation is a strong indicator of genetic regulation in the disease process iNPH (Fig 1). Enlargement of brain ventricles is associated with failed cerebrospinal (CSF) homeostasis by so far mostly unknown mechanisms. A mutation of the cilia gene CFAP43 in iNPH family, confirmed by a knocked‐out mouse model (Morimoto et al, 2019), allelic variation of NME8 (Huovinen et al, 2017), a segmental copy number loss in SFMBT1 in selected iNPH patients (Sato et al, 2016), and current results by Yang et al (2021) indicate that cilia dysfunction is one of the key mechanisms behind iNPH.

T. Kuulasmaa, M. Hiltunen and V. Leinonen discuss novel genetic and functional findings related to two loss of function deletions in CWH43 gene in patients with Idiopathic normal pressure hydrocephalus by M. Johnson and colleagues, in this issue of EMBO Mol Med.

]]> <![CDATA[iNPH—the mystery resolving]]> https://www.novareader.co/book/isbn/10.15252/emmm.202013720 Idiopathic normal pressure hydrocephalus (iNPH) is characterized clinically by degradation of gait, cognition, and urinary continence. INPH is progressive (Andrén et al, 2014), still probably underdiagnosed (Williams et al, 2019) but potentially treatable by CSF diversion (Kazui et al, 2015). Familial aggregation is a strong indicator of genetic regulation in the disease process iNPH (Fig 1). Enlargement of brain ventricles is associated with failed cerebrospinal (CSF) homeostasis by so far mostly unknown mechanisms. A mutation of the cilia gene CFAP43 in iNPH family, confirmed by a knocked‐out mouse model (Morimoto et al, 2019), allelic variation of NME8 (Huovinen et al, 2017), a segmental copy number loss in SFMBT1 in selected iNPH patients (Sato et al, 2016), and current results by Yang et al (2021) indicate that cilia dysfunction is one of the key mechanisms behind iNPH.

T. Kuulasmaa, M. Hiltunen and V. Leinonen discuss novel genetic and functional findings related to two loss of function deletions in CWH43 gene in patients with Idiopathic normal pressure hydrocephalus by M. Johnson and colleagues, in this issue of EMBO Mol Med.

]]> <![CDATA[The tumor cell‐derived matrix of lobular breast cancer: a new vulnerability]]> https://www.novareader.co/book/isbn/10.15252/emmm.202013807 Invasive lobular carcinoma (ILC) of the breast is a very common disease. Despite its prevalence, these tumors are relatively understudied. One reason for this is a relative lack of models for ILC. This challenge was addressed by Brisken and colleagues through development of an intraductal injection‐based xenograft system for the study of ERα+ breast cancers, including both ILC and more common invasive ductal carcinoma (IDC; Sflomos et al, 2016). In this issue of EMBO Molecular Medicine, the same group have applied intraductal injection‐based xenografts to identify novel tumor cell‐specific transcriptional signatures in ILC (Sflomos et al, 2021). In doing so they found overexpression of lysyl oxidase‐like 1 (LOXL1) to be both responsible for the frequently seen stiff collagen‐rich extracellular matrix of lobular breast cancer and essential for their robust growth and metastatic dissemination in vivo, thereby identifying a novel therapeutic target.

Despite its prevalence, invasive lobular carcinoma (ILC) is relatively understudied. In their recent study, Brisken and colleagues apply intraductal injection based xenografts to characterize tumor‐cell specific transcriptional signatures in ILC and identify a novel therapeutic target.

]]> <![CDATA[The tumor cell‐derived matrix of lobular breast cancer: a new vulnerability]]> https://www.novareader.co/book/isbn/10.15252/emmm.202013807 Invasive lobular carcinoma (ILC) of the breast is a very common disease. Despite its prevalence, these tumors are relatively understudied. One reason for this is a relative lack of models for ILC. This challenge was addressed by Brisken and colleagues through development of an intraductal injection‐based xenograft system for the study of ERα+ breast cancers, including both ILC and more common invasive ductal carcinoma (IDC; Sflomos et al, 2016). In this issue of EMBO Molecular Medicine, the same group have applied intraductal injection‐based xenografts to identify novel tumor cell‐specific transcriptional signatures in ILC (Sflomos et al, 2021). In doing so they found overexpression of lysyl oxidase‐like 1 (LOXL1) to be both responsible for the frequently seen stiff collagen‐rich extracellular matrix of lobular breast cancer and essential for their robust growth and metastatic dissemination in vivo, thereby identifying a novel therapeutic target.

Despite its prevalence, invasive lobular carcinoma (ILC) is relatively understudied. In their recent study, Brisken and colleagues apply intraductal injection based xenografts to characterize tumor‐cell specific transcriptional signatures in ILC and identify a novel therapeutic target.

]]> <![CDATA[Mind your heart: the epigenetic consequences of heart failure on brain function]]> https://www.novareader.co/book/isbn/10.15252/emmm.202013785 The bidirectional link between heart and brain has intrigued scientists for ages, but little is known on the underlying mechanism. In their recent study, Fischer and colleagues (Islam et al, 2021) propose a mechanism by which heart failure‐induced cognitive decline is linked to epigenetic changes that affect gene expression in neurons of hippocampus.

The bidirectional link between heart and brain has intrigued scientists for ages, but little is known on the underlying mechanism. G. Condorelli and M. Matteoli highlight an epigenetic mechanism that may explain the heart‐failure induced cognitive decline (Islam et al, this issue of EMBO Mol Med).

]]> <![CDATA[Mind your heart: the epigenetic consequences of heart failure on brain function]]> https://www.novareader.co/book/isbn/10.15252/emmm.202013785 The bidirectional link between heart and brain has intrigued scientists for ages, but little is known on the underlying mechanism. In their recent study, Fischer and colleagues (Islam et al, 2021) propose a mechanism by which heart failure‐induced cognitive decline is linked to epigenetic changes that affect gene expression in neurons of hippocampus.

The bidirectional link between heart and brain has intrigued scientists for ages, but little is known on the underlying mechanism. G. Condorelli and M. Matteoli highlight an epigenetic mechanism that may explain the heart‐failure induced cognitive decline (Islam et al, this issue of EMBO Mol Med).

]]> <![CDATA[Metabolomics: insights into plant‐based diets]]> https://www.novareader.co/book/isbn/10.15252/emmm.202013568 Plant‐based diets exclude or substantially limit the consumption of meat and animal products and are of growing interest to many due to their sustainability and health benefits (Eshel et al, 2016). Veganism is an extreme type of plant‐based diet which excludes the consumption of all animal‐derived foods such as meat, eggs, and dairy, as well as foods containing animal‐derived ingredients. In adults, for example, certain observational studies have suggested lower body mass index, total cholesterol, LDL‐cholesterol, decreased incidence and mortality from ischemic heart disease, and decreased incidence of cancer in vegans and vegetarians versus omnivores (Dinu et al, 2017). The mechanistic basis for these observations and their generality are unclear.

Allen A. and Locasale J. discuss the the metabolic and nutritional consequences of vegan diets in children, as reported by A. Suomalainen and colleagues, in this issue of EMBO Mol Med.

]]> <![CDATA[Metabolomics: insights into plant‐based diets]]> https://www.novareader.co/book/isbn/10.15252/emmm.202013568 Plant‐based diets exclude or substantially limit the consumption of meat and animal products and are of growing interest to many due to their sustainability and health benefits (Eshel et al, 2016). Veganism is an extreme type of plant‐based diet which excludes the consumption of all animal‐derived foods such as meat, eggs, and dairy, as well as foods containing animal‐derived ingredients. In adults, for example, certain observational studies have suggested lower body mass index, total cholesterol, LDL‐cholesterol, decreased incidence and mortality from ischemic heart disease, and decreased incidence of cancer in vegans and vegetarians versus omnivores (Dinu et al, 2017). The mechanistic basis for these observations and their generality are unclear.

Allen A. and Locasale J. discuss the the metabolic and nutritional consequences of vegan diets in children, as reported by A. Suomalainen and colleagues, in this issue of EMBO Mol Med.

]]> <![CDATA[Turning a pathogen protein into a therapeutic tool for sepsis]]> https://www.novareader.co/book/isbn/10.15252/emmm.202013589 Sepsis causes unacceptably high amounts of deaths worldwide. It is a huge unmet medical need, and new therapeutic interventions for sepsis and septic shock are urgently needed. By studying the mechanism by which a bacterial protein undermines the inflammatory function of macrophages, Kim et al, in the last issue of EMBO Molecular Medicine, have developed a new therapeutic protein drug, which appears to have very promising protective activities in a well‐validated and aggressive polymicrobial sepsis model in mice. The chimeric protein is thought to limit macrophage inflammation while activating phagocytosis, and so, it hits two macrophage pathways at once.

T. Vanderhaeghen, C. Wallaeys and C. Libert discuss the identification of a new therapeutic protein drug against sepsis as reported by CS. Yang and colleagues, in the last issue of EMBO Mol Med.

]]> <![CDATA[Turning a pathogen protein into a therapeutic tool for sepsis]]> https://www.novareader.co/book/isbn/10.15252/emmm.202013589 Sepsis causes unacceptably high amounts of deaths worldwide. It is a huge unmet medical need, and new therapeutic interventions for sepsis and septic shock are urgently needed. By studying the mechanism by which a bacterial protein undermines the inflammatory function of macrophages, Kim et al, in the last issue of EMBO Molecular Medicine, have developed a new therapeutic protein drug, which appears to have very promising protective activities in a well‐validated and aggressive polymicrobial sepsis model in mice. The chimeric protein is thought to limit macrophage inflammation while activating phagocytosis, and so, it hits two macrophage pathways at once.

T. Vanderhaeghen, C. Wallaeys and C. Libert discuss the identification of a new therapeutic protein drug against sepsis as reported by CS. Yang and colleagues, in the last issue of EMBO Mol Med.

]]> <![CDATA[The riddle of the Sphinx: why sphingosine‐1‐phosphate may help define molecular mechanisms underlying risk stratification for serious COVID‐19 infections]]> https://www.novareader.co/book/isbn/10.15252/emmm.202013533 The sphingosine‐1‐phosphate (S1P) is a lysophospholipid signaling molecule with important functions in many physiological and pathological conditions, including viral infection. In this issue of EMBO Molecular Medicine, Marfia et al present a risk stratification based on S1P serum level as a novel prognostic indicator for COVID‐19 severity.

H. Rosen and M. B. A. Oldstone discuss the importance of sphingosine‐1‐phosphate serum level as a novel severity predictor for COVID‐19 identified by G. Marfia and colleagues, in this issue of EMBO Mol Med.

]]> <![CDATA[The riddle of the Sphinx: why sphingosine‐1‐phosphate may help define molecular mechanisms underlying risk stratification for serious COVID‐19 infections]]> https://www.novareader.co/book/isbn/10.15252/emmm.202013533 The sphingosine‐1‐phosphate (S1P) is a lysophospholipid signaling molecule with important functions in many physiological and pathological conditions, including viral infection. In this issue of EMBO Molecular Medicine, Marfia et al present a risk stratification based on S1P serum level as a novel prognostic indicator for COVID‐19 severity.

H. Rosen and M. B. A. Oldstone discuss the importance of sphingosine‐1‐phosphate serum level as a novel severity predictor for COVID‐19 identified by G. Marfia and colleagues, in this issue of EMBO Mol Med.

]]>