scholarly journals MicroRNAs in the Myelodysplastic Syndrome

Acta Naturae ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 4-15
Author(s):  
Yuliya A. Veryaskina ◽  
Sergei E. Titov ◽  
Igor B. Kovynev ◽  
S. S. Fedorova ◽  
Tatiana I. Pospelova ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myelodysplastic Syndrome ◽  
Tumor Development ◽  
Cell Types ◽  
Assessment System ◽  
Expression Levels ◽  
Hematological Disorders ◽  
Prognostic System ◽  
Increased Risk ◽  
New Biomarkers

The myelodysplastic syndrome (MDS) holds a special place among blood cancers, as it represents a whole spectrum of hematological disorders with impaired differentiation of hematopoietic precursors, bone marrow dysplasia, genetic instability and is noted for an increased risk of acute myeloid leukemia. Both genetic and epigenetic factors, including microRNAs (miRNAs), are involved in MDS development. MicroRNAs are short non-coding RNAs that are important regulators of normal hematopoiesis, and abnormal changes in their expression levels can contribute to hematological tumor development. To assess the prognosis of the disease, an international assessment system taking into account a karyotype, the number of blast cells, and the degree of deficiency of different blood cell types is used. However, the overall survival and effectiveness of the therapy offered are not always consistent with predictions. The search for new biomarkers, followed by their integration into the existing prognostic system, will allow for personalized treatment to be performed with more precision. Additionally, this paper explains how miRNA expression levels correlate with the prognosis of overall survival and response to the therapy offered.

scholarly journals Stratification of chemotherapy-treated stage III colorectal cancer patients using multiplexed imaging and single-cell analysis of T-cell populations

2021 ◽  
Author(s):  
Xanthi Stachtea ◽  
Maurice B. Loughrey ◽  
Manuela Salvucci ◽  
Andreas U. Lindner ◽  
Sanghee Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Single Cell ◽  
Immune Cell ◽  
Single Cell Analysis ◽  
Cell Types ◽  
Cell Segmentation ◽  
Stage Iii ◽  
Cell Analysis ◽  
Increased Risk

AbstractColorectal cancer (CRC) has one of the highest cancer incidences and mortality rates. In stage III, postoperative chemotherapy benefits <20% of patients, while more than 50% will develop distant metastases. Biomarkers for identification of patients at increased risk of disease recurrence following adjuvant chemotherapy are currently lacking. In this study, we assessed immune signatures in the tumor and tumor microenvironment (TME) using an in situ multiplexed immunofluorescence imaging and single-cell analysis technology (Cell DIVETM) and evaluated their correlations with patient outcomes. Tissue microarrays (TMAs) with up to three 1 mm diameter cores per patient were prepared from 117 stage III CRC patients treated with adjuvant fluoropyrimidine/oxaliplatin (FOLFOX) chemotherapy. Single sections underwent multiplexed immunofluorescence staining for immune cell markers (CD45, CD3, CD4, CD8, FOXP3, PD1) and tumor/cell segmentation markers (DAPI, pan-cytokeratin, AE1, NaKATPase, and S6). We used annotations and a probabilistic classification algorithm to build statistical models of immune cell types. Images were also qualitatively assessed independently by a Pathologist as ‘high’, ‘moderate’ or ‘low’, for stromal and total immune cell content. Excellent agreement was found between manual assessment and total automated scores (p < 0.0001). Moreover, compared to single markers, a multi-marker classification of regulatory T cells (Tregs: CD3+/CD4+FOXP3+/PD1−) was significantly associated with disease-free survival (DFS) and overall survival (OS) (p = 0.049 and 0.032) of FOLFOX-treated patients. Our results also showed that PD1− Tregs rather than PD1+ Tregs were associated with improved survival. These findings were supported by results from an independent FOLFOX-treated cohort of 191 stage III CRC patients, where higher PD1− Tregs were associated with an increase overall survival (p = 0.015) for CD3+/CD4+/FOXP3+/PD1−. Overall, compared to single markers, multi-marker classification provided more accurate quantitation of immune cell types with stronger correlations with outcomes.

Prognositc Factors and Survival in Patients with Hypocellular Myelodysplastic Syndrome: Development of a Disease Specific Prognostic Score.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3819-3819 ◽  
Author(s):  
Wei-gang Tong ◽  
Tapan Kadia ◽  
Gautam Borthakur ◽  
Elias Jabbour ◽  
Sherry Pierce ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Median Survival ◽  
Prognostic Model ◽  
Prognostic Score ◽  
Test Group ◽  
Increased Risk ◽  
High Risk Disease

Abstract Abstract 3819 Poster Board III-755 Background Myelodysplastic syndrome (MDS) is a heterogeneous group of bone marrow disorders characterized by dysplastic changes in the myeloid lineages, ineffective hematopoiesis, and an increased risk of transformation to acute myeloid leukemia (AML). In most cases, bone marrow is hyperceulluar but in 10 to 20% of cases, bone marrow can be hypocellular (defined as < 30% cellularity in patients < 70 years, or < 20% cellularity in patients 70 years or older), a condition that overlaps and is difficult to differentiate from aplastic anemia (AA). Currently, there are no good prognostic model for patients with hypocellular MDS. Methods In order to improve the prognostic assessment and to better understand the natural history of hypoplastic MDS, we analyzed the associations between disease characteristics and survival in 253 cases of hypocellular MDS presented to MDACC between 1993 and 2007. This is the largest study so far on patients with hypocellular MDS. We also compared the presenting characteristic and survival between these patients and a group of patients with hyper/normocelluar MDS (n=1725) during the same time period. Results Patients with hypocellular MDS usually presented with more significant thrombocytopenia (p< 0.019), neutropenia (p< 0.001), low β-2 microglobulin (p< 0.001), more transfusion dependency (p< 0.001), and more intermediate-2/high risk disease (57% vs. 42%, p= 0.02) compared to their hyper/normocelluar counterparts. There was no difference in overall survival between the hypocellular and the hyper/normocellular groups (p= 0.312). We divided the patients randomly into study and test group, and a multivariate analysis of prognostic factor identified the following adverse, independent factors (p < 0.001): poor performance status (ECOG 2-4), poor bone marrow cytogenetics (chromosome 7 or complex), anemia (< 10 g/dl), increased bone marrow blasts (≥ 5%) and high serum LDH (> 600 IU/l). In this model, each characteristic has a score of 1. A new prognostic model based on these factors could classify this group of patients into three risk categories independent of IPSS score. Patients with low risk (n= 66; scores 0-1) had a median survival of 30 months, and 2-year/3-year survival of 62%/44%. Patients with intermediate risk (n=44; score 2) had a median survival of 19.4 months, and 2-year/3-year survival of 43%/20%. Patients with high risk disease (n= 59; scores 3-5) had a median survival of 7.3 months, and 2-year/3-year survival of 12%/6%. When this new prognostic model was applied to test group (n=84), the median survival was 55.7, 13.5 and 8.6 months (p< 0.0001) for patients in low, intermediate and high risk groups, respectively. Patients that received immunotherapy (ATG/cyclosporine) had a better median survival and overall survival than patients treated with supportive care, hypomethylating agents, or induction chemotherapy (p< 0.0001). Conclusions Here, we proposed a new simple prognostic model that allows to predict prognosis in patients with hypocellular MDS. Analysis of prognostic factors in patients with hypocellular MDS may help us understand the biology of the disease, and develop risk-adapted therapies for this group of patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Localization of Cytochrome P450 CYP2S1 Expression in Human Tissues by In Situ Hybridization and Immunohistochemistry

2005 ◽  
Vol 53 (5) ◽  
pp. 549-556 ◽  
Author(s):  
Sirkku T. Saarikoski ◽  
Harriet A.-L. Wikman ◽  
Gillian Smith ◽  
C. Henrik J. Wolff ◽  
Kirsti Husgafvel-Pursiainen
Keyword(s):  
Cytochrome P450 ◽  
In Situ Hybridization ◽  
Epithelial Cells ◽  
Cellular Localization ◽  
Tumor Development ◽  
Tissue Microarrays ◽  
Cell Types ◽  
Human Tissues ◽  
Expression Levels

CYP2S1 is a recently discovered dioxin-inducible member of the cytochrome P450 superfamily. It has been shown to be involved in the metabolism of some aromatic hydrocarbons as well as retinoic acid, suggesting a role in biotransformation of both exogenous and endogenous compounds. In this study, we used mRNA in situ hybridization and immunohistochemistry to investigate the cellular localization of CYP2S1 in various human tissues using tissue microarrays. High expression levels were observed mainly in epithelial cell types, especially in the epithelia frequently exposed to xenobiotics. In the respiratory tract, the expression was strong in nasal cavity, bronchi, and bronchioli, whereas it was low in the alveolar lining cells. Similarly, CYP2S1 was highly expressed in the epithelial cells throughout the gastrointestinal tract. Strong epithelial expression was also observed in uterine cervix, urinary bladder, and skin. In many exocrine glands (e.g., adrenal gland and pancreas), secretory epithelial cells showed moderate to strong expression levels. In the liver, the expression was low. CYP2S1 was highly expressed in epithelial cells that are major targets for carcinogen exposure and common progenitor cells to tumor development. Indeed, we found strong CYP2S1 expression in many tumors of epithelial origin.

scholarly journals Recruitment of M1 Macrophages May Not Be Critical for Protection against Colitis-Associated Tumorigenesis

2021 ◽  
Vol 22 (20) ◽  
pp. 11204
Author(s):  
Itzel Medina-Andrade ◽  
Jonadab E. Olguín ◽  
Stephanie Guerrero-García ◽  
Jossael A. Espinosa ◽  
Elizabeth Garduño-Javier ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Development ◽  
Cell Types ◽  
Colon Tissue ◽  
M1 Macrophages ◽  
Colon Tumors ◽  
Colon Tumorigenesis ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Specific Deletion

A close connection between inflammation and the risk of developing colon cancer has been suggested in the last few years. It has been estimated that patients diagnosed with some types of inflammatory bowel disease, such as ulcerative colitis or Crohn’s disease, have up to a 30% increased risk of developing colon cancer. However, there is also evidence showing that the activation of anti-inflammatory pathways, such as the IL-4 receptor-mediated pathway, may favor the development of colon tumors. Using an experimental model of colitis-associated colon cancer (CAC), we found that the decrease in tumor development in global IL4Rα knockout mice (IL4RαKO) was apparently associated with an inflammatory response mediated by the infiltration of M1 macrophages (F480+TLR2+STAT1+) and iNOS expression in colon tissue. However, when we developed mice with a specific deletion of IL4Rα in macrophages (LysMcreIL4Rα−/lox mice) and subjected them to CAC, it was found that despite presenting a large infiltration of M1 macrophages into the colon, these mice were as susceptible to colon-tumorigenesis as WT mice. These data suggest that in the tumor microenvironment the absence of IL4Rα expression on macrophages, as well as the recruitment of M1 macrophages, may not be directly associated with resistance to developing colon tumors. Therefore, it is possible that IL4Rα expression in other cell types, such as colonic epithelial cells, could have an important role in promoting the development of colitis-associated colon tumorigenesis.

scholarly journals Loss of Monoacylglycerol O-Acyltransferase 2 can be Compensated for by Diacylglycerol O-Acyltransferases 1 and 2 in High-Fat Diet-Induced Obesity and Mammary Cancer Development

2021 ◽  
Author(s):  
Yan Mei ◽  
Jing Wang ◽  
Jia-Bin Lu ◽  
Guan-Ming Lu ◽  
Li-Xia Peng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mammary Tumor ◽  
High Fat Diet ◽  
Triple Negative ◽  
Tumor Development ◽  
Breast Adenocarcinoma ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Increased Risk ◽  
Deficient Mice

Abstract Background: Dietary fat absorption involves the re-esterification of digested triacylglycerol in the enterocytes, it is a biological process catalyzed by monoacylglycerol O-acyltransferase 2 (MOGAT2, aka MGAT2), which is highly expressed in the small intestine. A previous study showed that the loss of the Mogat2 gene can prevent high-fat diet-induced obesity in mice. Obesity is associated with an increased risk of several types of cancer including postmenopausal breast cancer.Methods: We collected 147 patients with triple negative breast adenocarcinoma to explore the relationship between the expression of MOGAT2 and patient overall survival. And we generated a Mogat2-deficient mouse mammary tumor model by crossing Mogat2-deficient mice with MMTV-PyMT mice to examine the effect of losing MOGAT2 in vivo.Results: Our founding suggest that obesity was induced by a relatively high-fat diet (37% of calories from fat) in the mice with or without Mogat2 knockout. Mammary tumor development was deteriorated by a relatively high-fat diet regardless of Mogat2 deficiency. As a compensation mechanism, upregulation of diacylglycerol O-acyltransferases 1 and 2 (Dgat1 and Dgat2) in the Mogat2 deficient mice was found. Conclusions: Elevated expression of MOGAT2 in triple negative breast adenocarcinoma predicts poorer patient overall survival. With the compensation of Dgat1 and Dgat2, Mogat2 deficiency alone cannot prevent fat diet-induced obesity, nor prevent mammary tumor development in a mouse model.

scholarly journals Loss of Monoacylglycerol O Acyltransferase 2 Can Be Compensated for by Diacylglycerol O Acyltransferases 1 and 2 in High Fat Diet Induced Obesity and Mammary Cancer Development

2021 ◽  
Author(s):  
Yan Mei ◽  
Jing Wang ◽  
Jia-Bin Lu ◽  
Guan-Ming Lu ◽  
Li-Xia Peng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mammary Tumor ◽  
High Fat Diet ◽  
Triple Negative ◽  
Tumor Development ◽  
Breast Adenocarcinoma ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Increased Risk ◽  
Deficient Mice

Abstract Background: Dietary fat absorption involves the re esterification of digested triacylglycerol in the enterocytes, it is a biological process catalyzed by monoacylglycerol O acyltransferase 2 (MOGAT2, aka MGAT2), which is highly expressed in the small intestine. A previous study showed that the loss of the Mogat2 gene can prevent high fat diet induced obesity in mice. Obesity is associated with an increased risk of several types of cancer including postmenopausal breast cancer.Methods: We collected 147 patients with triple negative breast adenocarcinoma to explore the relationship between the expression of MOGAT2 and patient overall survival. And we generated a Mogat2 deficient mouse mammary tumor model by crossing Mogat2 deficient mice with MMTV PyMT mice to examine the effect of losing MOGAT2 in vivo. Results: Our founding suggest that obesity was induced by a relatively high fat diet (37% of calories from fat) in the mice with or without Mogat2 knockout. Mammary tumor development was deteriorated by a relatively high fat diet regardless of Mogat2 deficiency. As a compensation mechanism, upregulation of diacylglycerol O acyltransferases 1 and 2 (Dgat1 and Dgat2) in the Mogat2 deficient mice was found. Conclusions: Elevated expression of MOGAT2 in triple negative breast adenocarcinoma predicts poorer patient overall survival. With the compensation of Dgat1 and Dgat2, Mogat2 deficiency alone cannot prevent fat diet induced obesity, nor prevent mammary tumor development in a mouse model.

scholarly journals The effect of adjuvant radiotherapy on overall survival in adults with intracranial ependymoma

2019 ◽  
Vol 7 (4) ◽  
pp. 391-399
Author(s):  
Roshan S Prabhu ◽  
Christopher D Corso ◽  
Matthew C Ward ◽  
John H Heinzerling ◽  
Reshika Dhakal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Propensity Score ◽  
Adjuvant Radiotherapy ◽  
Subtotal Resection ◽  
National Cancer Database ◽  
Risk Of Death ◽  
Increased Risk ◽  
Intracranial Ependymoma ◽  
Male Sex ◽  
Grade 3

Abstract Background Adult intracranial ependymoma is rare, and the role for adjuvant radiotherapy (RT) is not well defined. Methods We used the National Cancer Database (NCDB) to select adults (age ≥ 22 years) with grade 2 to 3 intracranial ependymoma status postresection between 2004 and 2015 and treated with adjuvant RT vs observation. Four cohorts were generated: (1) all patients, (2) grade 2 only, (3) grade 2 status post–subtotal resection only, (4) and grade 3 only. The association between adjuvant RT use and overall survival (OS) was assessed using multivariate Cox and propensity score matched analyses. Results A total of 1787 patients were included in cohort 1, of which 856 patients (48%) received adjuvant RT and 931 (52%) were observed. Approximately two-thirds of tumors were supratentorial and 80% were grade 2. Cohorts 2, 3, and 4 included 1471, 345, and 316 patients, respectively. There was no significant association between adjuvant RT use and OS in multivariate or propensity score matched analysis in any of the cohorts. Older age, male sex, urban location, higher comorbidity score, earlier year of diagnosis, and grade 3 were associated with increased risk of death. Conclusions This large NCDB study did not demonstrate a significant association between adjuvant RT use and OS for adults with intracranial ependymoma, including for patients with grade 2 ependymoma status post–subtotal resection. The conflicting results regarding the efficacy of adjuvant RT in this patient population highlight the need for high-quality studies to guide therapy recommendations in adult ependymoma.

scholarly journals A Porthole over AKI: Cell Dynamics in Damage and Repair

Nephron ◽  
2020 ◽  
Vol 144 (12) ◽  
pp. 650-654
Author(s):  
Luca Bordoni ◽  
Donato Sardella ◽  
Ina Maria Schiessl
Keyword(s):  
Acute Kidney Injury ◽  
Renal Cell ◽  
Kidney Injury ◽  
Cell Types ◽  
Cell Interactions ◽  
Intravital Imaging ◽  
Cell Dynamics ◽  
Powerful Technique ◽  
Increased Risk ◽  
Cell Crosstalk

Acute kidney injury (AKI) is associated with an increased risk of CKD. Injury-induced multifaceted renal cell-to-cell crosstalk can either lead to successful self-repair or chronic fibrosis and inflammation. In this mini-review, we will discuss critical renal cell types acting as victims or executioners in AKI pathology and introduce intravital imaging as a powerful technique to further dissect these cell-to-cell interactions.

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