scholarly journals Notch1 switches progenitor competence in inducing medulloblastoma

2021 ◽  
Vol 7 (26) ◽  
pp. eabd2781
Author(s):  
Claudio Ballabio ◽  
Matteo Gianesello ◽  
Chiara Lago ◽  
Konstantin Okonechnikov ◽  
Marica Anderle ◽  
...  
Keyword(s):  
Brain Cancer ◽  
Poor Prognosis ◽  
Critical Role ◽  
Cell Of Origin ◽  
Pathway Activity ◽  
Mouse Cerebellum ◽  
Cells Of Origin ◽  
Cancer Subtype ◽  
Prognosis Group ◽  
Group 3

The identity of the cell of origin is a key determinant of cancer subtype, progression, and prognosis. Group 3 medulloblastoma (MB) is a malignant childhood brain cancer with poor prognosis and few candidates as putative cell of origin. We overexpressed the group 3 MB genetic drivers MYC and Gfi1 in different candidate cells of origin in the postnatal mouse cerebellum. We found that S100b+ cells are competent to initiate group 3 MB, and we observed that S100b+ cells have higher levels of Notch1 pathway activity compared to Math1+ cells. We found that additional activation of Notch1 in Math1+ and Sox2+ cells was sufficient to induce group 3 MB upon MYC/Gfi1 expression. Together, our data suggest that the Notch1 pathway plays a critical role in group 3 MB initiation.

scholarly journals Notch1 switches progenitor competence in inducing medulloblastoma

2020 ◽  
Author(s):  
Claudio Ballabio ◽  
Matteo Gianesello ◽  
Chiara Lago ◽  
Konstantin Okonechnikov ◽  
Marica Anderle ◽  
...  
Keyword(s):  
Brain Cancer ◽  
Poor Prognosis ◽  
Cell Of Origin ◽  
Pathway Activity ◽  
Mouse Cerebellum ◽  
Cells Of Origin ◽  
Cancer Subtype ◽  
Prognosis Group ◽  
Group 3 ◽  
Cellular Identity

SummaryThe identity of the cell of origin is a key determinant of cancer subtype, progression and prognosis. Group 3 Medulloblastoma (MB) is a malignant childhood brain cancer with poor prognosis and unknown cell of origin. We overexpressed the Group 3 MB genetic drivers MYC and Gfi1 in different candidate cells of origin in the postnatal mouse cerebellum. We found that S100b+ cells are competent to initiate Group 3 MB, while Math1+, Sox2+ or Ascl1+ cells are not. We noted that S100b+ cells have higher levels of Notch1 pathway activity compared to Math1+ cells. Interestingly, we found that additional activation of Notch1 in Math1+ cells was sufficient to induce Group 3 MB upon MYC/Gfi1 expression. Taken together, our data suggest that the MB cell of origin competence depends on the cellular identity, which relies on Notch1 activity.Graphical Abstract

scholarly journals Research on the Correlation of Serum PCT and Plasma GSN Levels with the Prognosis of Urosepsis Patients

2020 ◽  
Vol 36 (5) ◽  
Author(s):  
Na Cui ◽  
Zhanbiao Yu ◽  
Zhi Chen ◽  
Ning Chen
Keyword(s):  
Poor Prognosis ◽  
Original Work ◽  
Protective Factor ◽  
Good Prognosis ◽  
Control Group ◽  
Creative Commons ◽  
The Poor ◽  
Prognosis Group ◽  
Good Prognosis Group ◽  
Open Access Article

Objective: To explore the correlation of procalcitonin (PCT) and gelsolin (GSN) with the prognosis of urosepsis patients. Method: The data of 71 urosepsis patients from March 2015 to April 2019 who were admitted to and treated in Affiliated Hospital of Hebei University were analyzed and compared with those of 92 healthy persons. Serum PCT and plasma GSN levels at different times after treatment were detected. According to prognosis, patients were classified into the good prognosis group or the poor prognosis group. The serum PCT and plasma GSN levels of both groups were compared. Result: The serum PCT level of the urosepsis group on the 1st, 3rd, 5th and 7th days was obviously higher than that of the control group (P<0.05). The plasma GSN levels of the urosepsis group on the 1st, 3rd, 5th and 7th days were obviously lower than those of the control group (P<0.05).The serum PCT level of the poor prognosis group on the 1st, 3rd, 5th and 7th days was obviously higher than that of the good prognosis group (P<0.05). The plasma GSN level of the poor prognosis group on the 1st, 3rd, 5th and 7th days was obviously lower than that of the good prognosis group (P<0.05). PCT was an independent risk factor influencing the prognosis of urosepsis patients and that GSN was a protective factor (P<0.05). Conclusion: The serum PCT and plasma GSN levels can accurately predict the severity and prognosis of urosepsis patients and reflect the disease state of early urosepsis patients. High PCT levels and low GSN levels indicate poor prognosis, and clinicians should consider these values. doi: https://doi.org/10.12669/pjms.36.5.2143 How to cite this:Cui N, Yu Z, Chen Z, Chen N. Research on the Correlation of Serum PCT and Plasma GSN Levels with the Prognosis of Urosepsis Patients. Pak J Med Sci. 2020;36(5):---------. doi: https://doi.org/10.12669/pjms.36.5.2143 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals The prognosis prediction significance of Hounsfield unit value for stroke patients treated by intravenous thrombolysis

2020 ◽  
Author(s):  
Zhengqi Zhu ◽  
Ru Zhang ◽  
Kaixuan Ren ◽  
Ruochen Cong ◽  
Xiangyang Zhu ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Early Stage ◽  
Infarct Volume ◽  
Intravenous Thrombolysis ◽  
Hounsfield Unit ◽  
Good Prognosis ◽  
Stroke Patients ◽  
Clinical Prognosis ◽  
Prognosis Group ◽  
Good Prognosis Group

Abstract Background: Intravenous thrombolysis (IVT) is a rapid and effective treatment in the early stage of ischemic stroke patients and the purpose of this work is to explore the significance of Hounsfield unit(HU) value in Alberta Stroke Program Early CT Score (ASPECTS) for predicting the clinical prognosis of stroke patients with middle cerebral artery occlusion (MCAO) treated by IVT. Methods: The 84 stroke patients with MCAO treated by IVT were divided into good prognosis group (48 cases) and poor prognosis group (36 cases). HU ratio and HU difference calculated from non-contrast computed tomography (NCCT) between groups were analyzed. Results: The HU ratio of good prognosis group was higher than that in poor prognosis group and the HU difference of good prognosis group was lower than that in poor prognosis group (P＜0.05). The HU ratio was negatively correlated with the infarct volume, and the HU difference was positively correlated with the infarct volume (P＜0.05). HU difference was an independent risk factor for prognosis of patients with MCAO treated by IVT. The area under the curve (AUC) of HU ratio and HU difference for prognosis was 0.743 and 0.833 respectively (P＜0.05). Conclusion: The HU value changes are related to the clinical prognosis of stroke patients with MCAO treated by IVT, HU value may be a prognostic indicator for stroke patients with MCAO treated by IVT.

scholarly journals The Role of Monocytes/Macrophages In The Pathogenesis of Immune Associated Diffuse Alveolar Hemorrhage

2021 ◽  
Author(s):  
Qing Wei ◽  
Xun Chen ◽  
Jing Liu ◽  
Yan Li ◽  
Guangmin Nong
Keyword(s):  
Flow Cytometry ◽  
Critical Role ◽  
Lavage Fluid ◽  
Peripheral Blood Monocyte ◽  
Healthy Children ◽  
Group 3 ◽  
Group 2 ◽  
Stimulation Of

Abstract Backgroud The studies in the immnue associated diffuse alveolar hemorrahge (DAH) animal models showed that monocytes/macrophages played an critical role in the pathogenesis.Whether monocytes/macrophages contribute to the pathogenesis of immune associated DAH in human is still unknow. The aim of this study was to explore the role of monocytes/macrophages in the pathogenesis of immune associated DAH in human.Methods This study was conducted in two parts. In the first part, 37 children with immune associated DAH were included (DAH group), and 18 healthy children were recruited as the controls (HC group). Peripheral blood monocyte subtype was analyzed using flow cytometry. In the second part, 24 children with immune associated DAH were included (DAH group), and 13 children with acute airway foreingn body or mild benign airway stenosis were included as the controls (HC group). Bronochoalveolar lavage fluid (BALF) was collected using bronchoscope. Cytokines in the BALF supernatant were detected using cytometric bread array. BALF supertanant was used to stimulated the macrophages in vitro. The mRNA relative expressions of IL-1β, TNFα, IL-6, TGM2, CD163 and MRC1 were detected using quantitative real-time PCR, and the expressions of CD14, CD80, CD86, CD163 and CD206 were detected using flow cytometry. Results 1. The percentage of classical monocyte was significantly increased, whereas the percentages of intermediate and non-classical monocyte were significantly decreased in the DAH group, when compared to those in the HC group. 2. The levels of MCP-1, IL-6 and IL-8 were all significantly higher in the BALF supernatant from the DAH group, when compared to those form the HC group. 3. The mRNA relative expressions of IL-1β and IL-6 as well as the expression of CD86 were significantly higher, whereas the mRNA relative expression of MRC1 as well as the expressions of CD163 and CD206 were significantly lower under the stimulation of BALF supernatant from the DAH group, when compared to that from the HC group. Conclusions Monocytes/macrophages might participate in the pathogenesis of immune associated DAH in human by enhanced M1 polarization.

scholarly journals Role of Diffusion Tensor Imaging Combined with Neuron-Specific Enolase and S100 calcium-binding protein B Detection in Predicting the Prognosis of Moderate and Severe Traumatic Brain Injury

2021 ◽  
Keyword(s):  
Poor Prognosis ◽  
Neuron Specific Enolase ◽  
Good Prognosis ◽  
S100b Protein ◽  
Control Group ◽  
The Poor ◽  
Severe Tbi ◽  
Prognosis Group ◽  
Good Prognosis Group

Background Traumatic brain injury (TBI) seriously affects the quality of life of patients. The present study evaluated the role of diffusion tensor imaging (DTI) combined with Neuron-Specific Enolase (NSE) and S100 calcium-binding protein B (S100B) protein in predicting the prognosis of moderate and severe TBI. Methods The TBI patients were divided into moderate TBI (TBIm) and severe TBI (TBIs) groups according to the Glasgow Coma Scale (GCS) after admission. The patients were then divided into good and poor prognosis groups according to the Glasgow Outcome Scale (GOS); moreover, their follow-ups were recorded at 3 and 6 months after injury. This study also included 65 healthy individuals with matched age and gender as the control group. The fractional anisotropy (FA) values of DTI, serum neuron-specific enolase (NSE), and S100B protein levels were detected in this study. The data were analyzed in SPSS software (version 22.0) to evaluate the role of DTI combined with NSE and S100B protein in predicting the prognosis in TBIm and TBIs. Results: After TBI, the FA values of DTI in the TBI group were lower than those in the control group (P<0.05); moreover, the serum NSE and S100B values in the TBI group were higher than those in the control group (P<0.05). In the TBIm patients, the FA values of the corpus callosum in the good prognosis group were higher than that in the poor prognosis group (P<0.05); however, there was no significant difference between the two groups regarding the FA values of the internal capsule and the cerebral peduncle (P>0.05). The serum levels of NSE and S100B in the good prognosis group were significantly lower than those in the poor prognosis group (P<0.05). In the TBIs patients, the FA value of all areas in the good prognosis group was significantly higher than that in the poor prognosis group (P<0.05). However, there was no significant difference between the two prognosis groups regarding the serum levels of NSE and S100B (P>0.05). Conclusion Although DTI combined with NSE and S100B protein can effectively predict the prognosis of patients with moderate and severe TBI in the early stages, various other measures have been used in the studies to predict the prognosis of TBI patients. Accordingly, comparison with other measures is essential in further studies.

Adaptation of chemotherapy to the decline tumor markers in patients with poor prognosis nonseminomatous germ cell tumors:Real-world French experience.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 385-385
Author(s):  
Marion Rolland ◽  
Sara Faouzi ◽  
Leonor Chaltiel ◽  
Clement Dumont ◽  
Lionnel Geoffrois ◽  
...  
Keyword(s):  
Germ Cell ◽  
Tumor Marker ◽  
Tumor Markers ◽  
Poor Prognosis ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
French Experience ◽  
Prognosis Group

385 Background: Personalized chemotherapy based on tumor marker decline is the new standard in poor prognosis germ-cell tumor in Europe since 2014 (GETUG 13, Lancet, Fizazi et al). The purpose of this study was to analyze the reproducibility of the princeps study in patients not selected in clinical routine between 2014 and 2018. Methods: Patients (pts) were eligible if they had at least one criteria of IGCCCG classification for poor prognosis group. They had to be treated according the study terms of GETUG 13 study and did not received prior treatment. They had to received 1 BEP (Bleomycin, Etoposide, Cisplatin). Tumor markers (HCG and AFP) were dosed between day 18 and 21. Then, they received 3 additional BEP if they had favorable tumor marker decline or intensive chemotherapy if they had unfavorable decline. Results: This retrospective study included 104 patients in 14 french centers treated between 2013 and 2018: 22,1 % (n = 23) in the favorable group (Fav), 77,9 % (n = 81) in the unfavorable group (Unfav). Thirty-two pts had PS ≥ 2. In Unfav, there were more pts with HCG > 50 000 UI/L (44,2 % vs 13 %, p = 0,0067), neutrophil-to-lymphocyt ratio was also higher (median 6,4 vs 4,5, p = 0,0199). At cycle 1, all pts received BEP in Fav and 87,5 % (n = 70) in Unfav. After chemotherapy and surgery, 65,2 % in Fav and 41,3 % in Unfav obtained complete response. At 30 months (median follow-up), Fav-OS was 80,5 % (IC95% 55,8 – 92,2) and Unfav-OS was 64,4 % (IC95% 52 – 74,4). At 30 months, rates were 69,6 % (IC95% 46,6 -84,2) and 63.5 % (IC95% 51,9 – 73) respectively. In GETUG 13 study, 3-years OS was 84 % in Fav and 73 % on Unfav; 3-years PFS was 70 % and 59 % respectively. Seven pts died because of toxicity in Unfav (No one in Fav). Neuropathy, anemia and thrombopenia were more frequent in Unfav. Salvage high-dose chemotherapy with stem-cell transplant was required in 4 (66,7 %) pts in Fav and 8 (36,4 %) pts in Unfav. Conclusions: This study showed a reproducibility of the princeps study in terms of PFS and OS. Toxicity seemed more important in real world. For the congress, results will be reported with 50 additional pts.

scholarly journals A cell type-selective apoptosis-inducing small molecule for the treatment of brain cancer

2019 ◽  
Vol 116 (13) ◽  
pp. 6435-6440 ◽  
Author(s):  
Natasha C. Lucki ◽  
Genaro R. Villa ◽  
Naja Vergani ◽  
Michael J. Bollong ◽  
Brittney A. Beyer ◽  
...  
Keyword(s):  
Small Molecule ◽  
Brain Cancer ◽  
Critical Role ◽  
Tumor Formation ◽  
Tumor Xenograft ◽  
Drug Candidate ◽  
Cell Type ◽  
Caspase 1 ◽  
A Cell

Glioblastoma multiforme (GBM; grade IV astrocytoma) is the most prevalent and aggressive form of primary brain cancer. A subpopulation of multipotent cells termed GBM cancer stem cells (CSCs) play a critical role in tumor initiation, tumor maintenance, metastasis, drug resistance, and recurrence following surgery. Here we report the identification of a small molecule, termed RIPGBM, from a cell-based chemical screen that selectively induces apoptosis in multiple primary patient-derived GBM CSC cultures. The cell type-dependent selectivity of this compound appears to arise at least in part from redox-dependent formation of a proapoptotic derivative, termed cRIPGBM, in GBM CSCs. cRIPGBM induces caspase 1-dependent apoptosis by binding to receptor-interacting protein kinase 2 (RIPK2) and acting as a molecular switch, which reduces the formation of a prosurvival RIPK2/TAK1 complex and increases the formation of a proapoptotic RIPK2/caspase 1 complex. In an orthotopic intracranial GBM CSC tumor xenograft mouse model, RIPGBM was found to significantly suppress tumor formation in vivo. Our chemical genetics-based approach has identified a drug candidate and a potential drug target that provide an approach to the development of treatments for this devastating disease.

scholarly journals Overexpression of IQGAP1 in advanced colorectal cancer correlates with poor prognosis-critical role in tumor invasion

2010 ◽  
pp. NA-NA ◽  
Author(s):  
Hiroyuki Hayashi ◽  
Kazuki Nabeshima ◽  
Mikiko Aoki ◽  
Makoto Hamasaki ◽  
Sotaro Enatsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Invasion ◽  
Poor Prognosis ◽  
Advanced Colorectal Cancer ◽  
Critical Role

Heat Shock Protein Vaccine Therapy for Ovarian Cancer

2018 ◽  
Author(s):  
Hiroyuki Abe ◽  
Amane Sasada ◽  
Shigeki Tabata ◽  
Minako Abe
Keyword(s):  
Ovarian Cancer ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Immune Suppression ◽  
Poor Prognosis ◽  
Critical Role ◽  
Combination Immunotherapy ◽  
Protein Vaccine ◽  
Key Technologies ◽  
Method Of Production

Despite advances in chemotherapeutic regimens, ovarian cancer has a poor prognosis. Therefore important effective treatments are urgently needed. Many studies have reported that the immune system plays a critical role in disease progression and overall survival. One known effective immunotherapy is the dendritic cell (DC)-based vaccine pulsed with tumor-associated antigens. This chapter reports on a method of production of a novel DC-based vaccine. The key technologies are (a) monocyte collection without leukapheresis, (b) monocyte expansion, (c) production of dendritic cells, (d) multiple overlapping long peptides with heat shock protein 70, and (e) combination immunotherapy approach. The next generation of immunotherapy for ovarian cancer will be focused on combination approaches that simultaneously augment immunity while preventing local immune suppression. Possible combinations which might be useful to help patients with ovarian cancer are summarized in this chapter.

scholarly journals Increased levels of XPA might be the basis of cisplatin resistance in germ cell tumours

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zuzana Cierna ◽  
Vera Miskovska ◽  
Jan Roska ◽  
Dana Jurkovicova ◽  
Lucia Borszekova Pulzova ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Lines ◽  
Poor Prognosis ◽  
Damage Identification ◽  
Excision Repair ◽  
Germ Cell Tumours ◽  
Expression Levels ◽  
Nucleotide Excision ◽  
Visceral Metastases ◽  
Prognosis Group

Abstract Background Germ cell tumours (GCTs) represent a highly curable malignity as they respond well to cisplatin (CDDP)-based chemotherapy. Nevertheless, a small proportion of GCT patients relapse or do not respond to therapy. As this might be caused by an increased capacity to repair CDDP-induced DNA damage, identification of DNA repair biomarkers predicting inadequate or aberrant response to CDDP, and thus poor prognosis for GCT patients, poses a challenge. The objective of this study is to examine the expression levels of the key nucleotide excision repair (NER) factors, XPA, ERCC1 and XPF, in GCT patients and cell lines. Methods Two hundred seven GCT patients’ specimens with sufficient follow-up clinical-pathological data and pairwise combinations of CDDP-resistant and -sensitive GCT cell lines were included. Immunohistochemistry was used to detect the ERCC1, XPF and XPA protein expression levels in GCT patients’ specimen and Western blot and qRT-PCR examined the protein and mRNA expression levels in GCT cell lines. Results GCT patients with low XPA expression had significantly better overall survival than patients with high expression (hazard ratio = 0.38, 95% confidence interval: 0.12–1.23, p = 0.0228). In addition, XPA expression was increased in the non-seminomatous histological subtype, IGCCCG poor prognosis group, increasing S stage, as well as the presence of lung, liver and non-pulmonary visceral metastases. Importantly, a correlation between inadequate or aberrant CDDP response and XPA expression found in GCT patients was also seen in GCT cell lines. Conclusions XPA expression is an additional independent prognostic biomarker for stratifying GCT patients, allowing for improvements in decision-making on treatment for those at high risk of refractoriness or relapse. In addition, it could represent a novel therapeutic target in GCTs.

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