scholarly journals Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity

2020 ◽  
Vol 140 (6) ◽  
pp. 893-906
Author(s):  
Leonille Schweizer ◽  
Felix Thierfelder ◽  
Christian Thomas ◽  
Patrick Soschinski ◽  
Abigail Suwala ◽  
...  

AbstractParagangliomas/pheochromocytomas are rare neuroendocrine tumors that arise from the adrenal gland or ganglia at various sites throughout the body. They display a remarkable diversity of driver alterations and are associated with germline mutations in up to 40% of the cases. Comprehensive molecular profiling of abdomino-thoracic paragangliomas revealed four molecularly defined and clinically relevant subtypes. Paragangliomas of the cauda equina region are considered to belong to one of the defined molecular subtypes, but a systematic molecular analysis has not yet been performed. In this study, we analyzed genome-wide DNA methylation profiles of 57 cauda equina paragangliomas and show that these tumors are epigenetically distinct from non-spinal paragangliomas and other tumors. In contrast to paragangliomas of other sites, chromosomal imbalances are widely lacking in cauda equina paragangliomas. Furthermore, RNA and DNA exome sequencing revealed that frequent genetic alterations found in non-spinal paragangliomas—including the prognostically relevant SDH mutations—are absent in cauda equina paragangliomas. Histologically, cauda equina paragangliomas show frequently gangliocytic differentiation and strong immunoreactivity to pan-cytokeratin and cytokeratin 18, which is not common in paragangliomas of other sites. None of our cases had a familial paraganglioma syndrome. Tumors rarely recurred (9%) or presented with multiple lesions within the spinal compartment (7%), but did not metastasize outside the CNS. In summary, we show that cauda equina paragangliomas represent a distinct, sporadic tumor entity defined by a unique clinical and morpho-molecular profile.

2011 ◽  
Vol 20 (4) ◽  
pp. 225-232 ◽  
Author(s):  
Prerana Jha ◽  
Vaishali Suri ◽  
Geetika Singh ◽  
Pankaj Jha ◽  
Suvendu Purkait ◽  
...  

2020 ◽  
Vol 6 (37) ◽  
pp. eaba7261
Author(s):  
Yasuko Akiyama-Oda ◽  
Hiroki Oda

Hedgehog (Hh) signaling plays fundamental roles in animal body patterning. Understanding its mechanistic complexity requires simple tractable systems that can be used for these studies. In the early spider embryo, Hh signaling mediates the formation of overall anterior-posterior polarity, yet it remains unclear what mechanisms link the initial Hh signaling activity with body axis segmentation, in which distinct periodic stripe-forming dynamics occur depending on the body region. We performed genome-wide searches for genes that transcriptionally respond to altered states of Hh signaling. Characterization of genes negatively regulated by Hh signaling suggested that msx1, encoding a conserved transcription factor, functions as a key segmentation gene. Knockdown of msx1 prevented all dynamic processes causing spatial repetition of stripes, including temporally repetitive oscillations and bi-splitting, and temporally nonrepetitive tri-splitting. Thus, Hh signaling controls segmentation dynamics and diversity via msx1. These genome-wide data from an invertebrate illuminate novel mechanistic features of Hh-based patterning.


1974 ◽  
Vol 31 (02) ◽  
pp. 328-338
Author(s):  
M. M. P Paulssen ◽  
H. L. M. A Vandenbussche-Scheffers ◽  
P. B Spaan ◽  
T de Jong ◽  
M. C Planje

SummaryFactor VIII occurs in the body in two different forms. In lymph factor VIII is bound to chylomicra. In plasma, factor VIII is bound to a protein.After delipidation of chylomicra we obtained a glycoprotein with a high polysaccharide content and a molecular weight of approx. 160,000.In plasma, factor VIII is attached to a protein which is present in normal concentrations in plasma of patients with haemophilia A and in serum (co-factor VIII).This factor is deficient in both the plasma and the serum of patients with von Willebrand’s disease.The binding between factor VIII and co-factor VIII is reversible.Some properties of these two factors are described.


2019 ◽  
Vol 37 (1) ◽  
pp. 59-76
Author(s):  
Monique Lyle

This essay seeks to dispel entrenched critical opinion regarding dance across Nietzsche's writings as representative of Dionysian intoxication alone. Taking as its prompt the riposte of Alain Badiou, ‘Nietzsche is miles away from any doctrine of dance as a primitive ecstasy’ and ‘dance is in no way the liberated bodily impulse, the wild energy of the body’, the essay uncovers the ties between dance and Apollo in the Nietzschean theory of art while qualifying dance's relation to Dionysus. Primarily through an analysis of The Dionysiac World View and The Birth of Tragedy, the essay seeks to illuminate enigmatic statements about dance in Nietzsche (‘in dance the greatest strength is only potential, although it is betrayed by the suppleness of movement’ and ‘dance is the preservation of orderly measure’). It does this through an elucidation of the specific function of dance in Nietzsche's interpretation of classical Greece; via an assessment of the difficulties associated with the Nietzschean understanding of the bacchanal; and lastly through an analysis of Nietzsche's characterization of dance as a symbol. The essay culminates in a discussion of dance's ties to Nietzschean life affirmation; here the themes of physico-phenomenal existence, joy and illusion in Nietzsche are surveyed.


Author(s):  
Bhavani J ◽  
Sunil Kumar Prajapati ◽  
Ravichandran S

Cancer is assemblage diseases involving abnormal cell growth amid the potential of spread to other parts of the body due to tobacco use are the cause of about of cancer deaths. Another 10% is due to obesity, poor diet & drinking alcohol. In 2012 about 14.1 million new cases of cancer occurred globally. In females, the most common type is breast cancer. Cisplatin also known as cytophosphane is a nitrogen mustard alkylating agent from the oxazophosphinans groups were used to treat cancers & autoimmune disorders. Based on the above reasons I will fix the aim Preparation characterization of Cisplatin- nano particles  &  its anticancer activity. Solid tumor volume examination report showed that the assessment of different day indication 15,20,25 & 30th variations of different groups of tumor volumes were decreased CPG Nanoparticles (100 mg/kg)+ DAL(15th day 4.97±0.24↓), (20th day 0.6±0.13↓), (25th day 1.35±0.30↓) & (30th day 1.89±0.13↓).


2020 ◽  
Vol 66 (1) ◽  
pp. 71-78
Author(s):  
Lev Bershteyn ◽  
Aleksandr Ivantsov ◽  
Aglaya Ievleva ◽  
A. Venina ◽  
I. Berlev

The aim of this study was to evaluate steroid receptors’ status of tumor tissue in different molecular biological types of endometrial cancer (EC), subdivided according to the current classification, and their colonization by lymphocytic and macrophage cells, taking into account body mass index of the patients. Materials and methods: Material from treatment-naive patients with EC (total n = 229) was included; the number of sick persons varied depending on the method used. The average age of patients was close to 60 years, and about 90% of them were postmenopausal. It was possible to divide the results of the work into two main subgroups: a) depending on the molecular biological type of the tumor (determined on the basis of genetic and immunohistochemical analysis), and b) depending on the value of the body mass index (BMI). The latter approach was used in patients with EC type demonstrating a defective mismatch repair of the incorrectly paired nucleotides (MMR-D) and with a type without characteristic molecular profile signs (WCMP), but was not applied (due to the smaller number of patients) in EC types with a POLE gene mutation or with expression of the oncoprotein p53. According to the data obtained, when comparing various types of EC, the lowest values of Allred ER and PR scores were revealed for POLE-mutant and p53 types, while the “triple-negative” variant of the tumor (ER-, PR-, HER2/neu-) was most common in POLE-mutant (45.5% of cases) and WCMP (19.4%) types of EC. The p53+ type of EC is characterized by inclination to the higher expression of the macrophage marker CD68 and lymphocytic Foxp3, as well as mRNA of PD-1 and SALL4. In addition to the said above, for WCMP type of EC is peculiar, on the contrary, a decrease in the expression of lymphocytic markers CD8 (protein) and PD-L1 (mRNA). When assessing the role of BMI, its value of >30.0 (characteristic for obesity) was combined with an inclination to the increase of HER-2/neu expression in the case of MMR-D EC type and to the decrease of HER-2 /neu, FOXp3 and ER expression in WCMP type. Conclusions: The accumulated information (mainly describing here hormonal sensitivity of the tumor tissue and its lymphocytic-macrophage infiltration) additionally confirms our earlier expressed opinion that the differences between women with EC are determined by both the affiliation of the neoplasm to one or another molecular biological type (subdivided according to the contemporary classification), as well as by body mass value and (very likely) the associated hormonal and metabolic attributes.


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