scholarly journals Molecular and Cellular Mechanisms of Human Astrocytoma Progression: Advances in Knowledge to Reach Therapeutic Horizons

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2216
Author(s):  
Sergio Comincini
Keyword(s):  
Human Tumor ◽  
Transformation Process ◽  
Wide Field ◽  
High Grade ◽  
Astrocytic Tumors ◽  
Economic Costs ◽  
Special Issue ◽  
Cellular Mechanisms ◽  
Incidence Studies ◽  
Human Astrocytoma

Human astrocytic tumors are primary central nervous system (CNS) tumors that arise either from astrocytes or from precursor cells. A growing number of epidemiological and incidence studies in different countries underlined that, in addition to increasing economic costs for health systems, these cancers are still representing one of the main hurdles in developing a successful therapeutic goal for patients. On the other hand, new-omics technologies are offering customized instruments and more and more advantageous results toward personalized medicine approaches, underlining the concept that each tumor mass undergoes a peculiar transformation process under the control of specific genes’ and proteins’ functional signatures. The main aim of this Special Issue was to collect novel contributions in the wide field of human tumor astrocytic basic and translational research, to suggest further potential therapeutic targets/strategies that might interfere, possibly at the earliest stage of transformation, with the tumor progression, and to increase the molecular-based arsenal to counteract the prognostic poverty of high-grade astrocytic tumors.

The Pikwitonei Granulite Domain, Manitoba: a giant Neoarchean high-grade terrane in the northwest Superior ProvinceThis article is one of a series of papers published in this Special Issue on the theme of Geochronology in honour of Tom Krogh.N. Machado, T.E. Krogh, and W. Weber are deceased.

2011 ◽  
Vol 48 (2) ◽  
pp. 205-245 ◽  
Author(s):  
L. M. Heaman ◽  
Ch. O. Böhm ◽  
N. Machado ◽  
T. E. Krogh ◽  
W. Weber ◽  
...  
Keyword(s):  
Granulite Facies ◽  
Superior Province ◽  
High Grade ◽  
Metamorphic Zircon ◽  
Special Issue ◽  
Metamorphic History ◽  
Zircon Growth ◽  
The World ◽  
Northwestern Margin ◽  
History Of

The Pikwitonei Granulite Domain located at the northwestern margin of the Superior Province is one of the largest Neoarchean high-grade terranes in the world, with well-preserved granulite metamorphic assemblages preserved in a variety of lithologies, including enderbite, opdalite, charnockite, and mafic granulite. U–Pb geochronology has been attempted to unravel the protolith ages and metamorphic history of numerous lithologies at three main localities; Natawahunan Lake, Sipiwesk Lake, and Cauchon Lake. The U–Pb age results indicate that some of the layered enderbite gneisses are Mesoarchean (3.4–3.0 Ga) and the more massive enderbites are Neoarchean. The high-grade metamorphic history of the Pikwitonei Granulite Domain is complex and multistage with at least four episodes of metamorphic zircon growth identified: (1) 2716.1 ± 3.8 Ma, (2) 2694.6 ± 0.6 Ma, (3) 2679.6 ± 0.9 Ma, and (4) 2642.5 ± 0.9 Ma. Metamorphic zircon growth during episodes 2 and 3 are interpreted to be regional in extent, corresponding to M1 amphibolite- and M2 granulite-facies events, respectively, consistent with previous field observations. The youngest metamorphic episode at 2642.5 Ma is only recognized at southern Cauchon Lake, where it coincides with granite melt production and possible development of a major northeast-trending deformation zone. The timing and multistage metamorphic history recorded in the Pikwitonei Granulite Domain is similar to most Superior Province high-grade terranes and marks a fundamental break in Archean crustal evolution worldwide at the termination of prolific global Neoarchean greenstone belt formation.

scholarly journals Renewed tectonic extrusion of high-grade metamorphic rocks in the MCT footwall since Late Miocene (Sutlej Valley, India)

2008 ◽  
Vol 2 (4) ◽  
pp. 102-103 ◽  
Author(s):  
Vincent Baudraz ◽  
Jean-Claude Vannay ◽  
Elizabeth Catlos ◽  
Mike Cosca ◽  
Torsten Vennemann
Keyword(s):  
Late Miocene ◽  
Metamorphic Rocks ◽  
High Grade ◽  
Special Issue ◽  
Tectonic Extrusion

Himalayan Journal of Sciences Vol.2(4) Special Issue 2004 pp. 102-3

scholarly journals NIMG-09. iPROMPT: INTEGRATED PREDICTIVE RADIOGRAPHIC BIOMARKERS OF PROGRESSED HIGH GRADE ASTROCYTIC TUMORS

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi177-vi177
Author(s):  
Na Tosha Gatson ◽  
Joseph Vadakara ◽  
Erika Leese ◽  
Tierney McGee ◽  
T Linda Chi ◽  
...  
Keyword(s):  
High Grade ◽  
Astrocytic Tumors

scholarly journals PODO447: a novel antibody to a tumor-restricted epitope on the cancer antigen podocalyxin

2020 ◽  
Vol 8 (2) ◽  
pp. e001128
Author(s):  
Diana Canals Hernaez ◽  
Michael R Hughes ◽  
Pamela Dean ◽  
Peter Bergqvist ◽  
Ismael Samudio ◽  
...  
Keyword(s):  
B Cells ◽  
Tumor Cell ◽  
Cell Lines ◽  
Human Tumor ◽  
Human Tumor Xenograft ◽  
High Grade ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Vascular Endothelia ◽  
Restricted Epitope

BackgroundThe success of new targeted cancer therapies has been dependent on the identification of tumor-specific antigens. Podocalyxin (Podxl) is upregulated on tumors with high metastatic index and its presence is associated with poor outcome, thus emerging as an important prognostic and theragnostic marker in several human cancers. Moreover, in human tumor xenograft models, Podxl expression promotes tumor growth and metastasis. Although a promising target for immunotherapy, the expression of Podxl on normal vascular endothelia and kidney podocytes could hamper efforts to therapeutically target this molecule. Since pathways regulating post-translational modifications are frequently perturbed in cancer cells, we sought to produce novel anti-Podxl antibodies (Abs) that selectively recognize tumor-restricted glycoepitopes on the extracellular mucin domain of Podxl.MethodsSplenic B cells were isolated from rabbits immunized with a Podxl-expressing human tumor cell line. Abs from these B cells were screened for potent reactivity to Podxl+ neoplastic cell lines but not Podxl+ primary endothelial cells. Transcripts encoding heavy and light chain variable regions from promising B cells were cloned and expressed as recombinant proteins. Tumor specificity was assessed using primary normal tissue and an ovarian cancer tissue microarray (TMA). Mapping of the tumor-restricted epitope was performed using enzyme-treated human tumor cell lines and a glycan array.ResultsOne mAb (PODO447) showed strong reactivity with a variety of Podxl+ tumor cell lines but not with normal primary human tissue including Podxl+ kidney podocytes and most vascular endothelia. Screening of an ovarian carcinoma TMA (219 cases) revealed PODO447 reactivity with the majority of tumors, including 65% of the high-grade serous histotype. Subsequent biochemical analyses determined that PODO447 reacts with a highly unusual terminal N-acetylgalactosamine beta-1 (GalNAcβ1) motif predominantly found on the Podxl protein core. Finally, Ab–drug conjugates showed specific efficacy in killing tumor cells in vitro.ConclusionsWe have generated a novel and exquisitely tumor-restricted mAb, PODO447, that recognizes a glycoepitope on Podxl expressed at high levels by a variety of tumors including the majority of life-threatening high-grade serous ovarian tumors. Thus, tumor-restricted PODO447 exhibits the appropriate specificity for further development as a targeted immunotherapy.

scholarly journals The impact of the ovarian microenvironment on the anti-tumor effect of SPARC on ovarian cancer1This article is part of Special Issue entitled Asilomar Chromatin and has undergone the Journal’s usual peer review process.

2012 ◽  
Vol 90 (1) ◽  
pp. 96-107 ◽  
Author(s):  
James B. Greenaway ◽  
Anne Koehler ◽  
Christopher A. McCulloch ◽  
James Petrik ◽  
Theodore J. Brown ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mouse Model ◽  
Review Process ◽  
Peer Review Process ◽  
High Grade ◽  
Wild Type ◽  
Special Issue ◽  
Reactive Stroma ◽  
Abdominal Lesions ◽  
The Impact

A lack of host-derived SPARC promotes disease progression in an intraperitoneal (IP) ID8 mouse model of epithelial ovarian cancer (EOC). Since orthotopic injection (OT) of ID8 cells better recapitulates high-grade serous cancer, we examined the impact of host-derived SPARC following OT injection. Sparc−/− and wild-type (WT) mice were injected with ID8 cells either OT or IP and tumors were analyzed at the moribund stage. Sparc−/− mice had reduced survival and fewer well-defined abdominal lesions compared with WT controls after IP injection, whereas no differences were observed in survival or abdominal lesions between Sparc−/− and WT mice after OT injection. No differences in mass or collagen content were observed in ovarian tumors between OT-injected Sparc−/− and WT mice. The abdominal wall of the IP-injected Sparc−/− mice exhibited immature and less abundant collagen fibrils compared with WT mice both in injected and non-injected controls. In contrast to human EOC, SPARC was expressed by the tumor cells but was absent in reactive stroma of WT mice. Exposure to the ovarian microenvironment through OT injections alters the metastatic behaviour of ID8 cells, which is not affected by the absence of host-derived SPARC.

Differentiation between Supratentorial Single Brain Metastases and High Grade Astrocytic Tumors: An Evaluation of Different DSC MRI Measurements

2009 ◽  
Vol 22 (4) ◽  
pp. 369-377 ◽  
Author(s):  
H. Zhang ◽  
L.A. Rödiger ◽  
G. Zhang ◽  
M. Oudkerk
Keyword(s):  
Brain Metastases ◽  
Cerebral Blood Volume ◽  
Mean Transit Time ◽  
Correct Diagnosis ◽  
Threshold Value ◽  
High Grade ◽  
Diagnostic Efficiency ◽  
Astrocytic Tumors ◽  
Dsc Mri ◽  
Mri Measurements

This study evaluated the role of different perfusion MRI measurements in the pre-operative differentiation between single brain metastases and high grade astrocytic tumors. 24 high-grade astrocytic tumors and 29 single metastases were studied. A gradient echo-planar sequence was used for DSC MRI. Relative cerebral blood volume, cerebral blood flow and mean transit time in both tumor parenchyma (T rCBV, T rCBF and T rMTT) and peritumoral edema (P rCBV, P rCBF and P rMTT) were measured. Mann-Whitney tests were used to assess differences between single brain metastases and high grade astrocytic tumors. Receiver operating characteristic analyses were performed to determine optimum thresholds for tumor differentiation. Sensitivity, specificity and accuracy for identifying brain metastases were calculated. Mean T rCBV, T rCBF, P rCBV and P CBF of brain metastases (2.75±1.72, 2.51±2.09, 1.05±0.53, 0.87±0.40) differed statistically (P <0.05) from those of high grade astrocytic tumors (6.00±2.17, 5.68±2.35, 1.77±1.19 and 1.58±0.99). No statistical difference was found between mean rMTTs of these two entities (P >0.05). Based on the area under the ROC curves (AUC), the efficiency of T rCBV and T rCBF for correct diagnosis of brain metastases is almost identical (AUC: 0.899, 0.890 respectively) and superior to other measurements. A threshold value of 3.50 for T rCBF provided the same specificity (86.7) as that of T rCBV but higher sensitivity (86.2) and accuracy (86.3). Different perfusion measurements can be used to differentiate single metastases from high-grade astrocytic tumors. T rCBF showed the highest diagnostic efficiency among these measurements.

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