scholarly journals A Physiological Role for a Moonlighting Protein in Lipopolysaccharide-induced Endotoxemia

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Kirsten Zborek ◽  
Daniel Lee ◽  
Adam Pajakowski ◽  
Jacob Slack ◽  
Joseph Park ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Median Survival ◽  
Lethal Dose ◽  
Survival Rates ◽  
Physiological Role ◽  
Myeloid Cell ◽  
Peritoneal Macrophages ◽  
Clinical Scores ◽  
Emap Ii ◽  
And Gender

Background and Hypothesis: The pathogenesis of Bronchopulmonary Dysplasia (BPD) is multifactorial leading to inflammation. In BPD, Endothelial-Monocyte Activating Polypeptide II (EMAP II, encoded by Aimp1), a moonlighting pro-inflammatory cytokine, is initially found in bronchiolar club cells followed by intra-alveolar GAL-3+ macrophages. Sustained EMAP II mimics BPD, invoking inflammation, alveolar simplification, and macrophage recruitment. Targeted ablation of EMAP II in the recruited macrophages may dampen innate immune response.  Experimental Design: Gender-matched, aged-matched littermate mice with myeloid-cell specific ablation of Aimp1 (Lyz2-Cre;Aimp1flox/flox, denoted as Aimp1Δ/Δ) or without (control) were subjected to lipopolysaccharide (LPS)-endotoxemia. Survival rates of co-housed or singly housed mice were measured over 72 hours following a lethal dose (15 mg/kg). Clinical scores (0-6) based on the integrity of their locomotion, fur, and eyes were assigned every 2 hours. Blood and bone marrow smears, average bodyweights, spleen-weights to bodyweights and liver-weights to bodyweights were analyzed.  Results: There were no baseline differences in bodyweight, spleen weight:bodyweight, liver weight:bodyweight (p-val = 0.42, 0.46, 0.64). Representative bone marrow and blood smears showed no notable difference. Aimp1[Symbol]/[Symbol] male mice co-housed (dose 15 mg/kg) but not singly housed survived longer than their littermates (median survival: hours); Aimp1[Symbol]/[Symbol] female mice showed a survival advantage (median survival: hours) with lower clinical scores than their littermates. The kinetics of NFKBIA/I[Symbol]B degradation was similar between Aimp1[Symbol]/[Symbol] and control peritoneal macrophages in response to LPS, although there was a higher basal amount in Aimp1[Symbol]/[Symbol].  Conclusion and Potential Impact: Aimp1/EMAP II does play a positive feedback role in innate immunity, potentially in a metabolically and gender-specific role of Aimp1 which remain to be explored.

Outcome of Patients (pts) with Myelodysplastic Syndrome (MDS) and Chronic Myelomonocytic Leukemia (CMML) Post Decitabine Failure.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1659-1659 ◽  
Author(s):  
Elias Jabbour ◽  
Guillermo Garcia-Manero ◽  
Jianqin Shan ◽  
Susan O’Brien ◽  
Jorge Cortes ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Median Survival ◽  
Objective Response ◽  
Survival Rates ◽  
Low Risk ◽  
Published Data ◽  
High Risk Disease ◽  
Investigational Agents ◽  
Bone Marrow Blasts

Abstract Background and aims: Prognosis in pts with MDS post decitabine failure is reported to be poor, but there are no published data pertaining to survival, particularly in relation to pts who might benefit from specific strategies such as allogeneic stem cell transplantation (SCT) or investigational agents. In this regard, we report the results from our institution. Materials and Methods: A total of 87 pts with MDS (n=67) and CMML (n=20) after failure of decitabine regimens from 2003 until June 2007 were analyzed. Responses to decitabine and subsequent therapies were coded according to the modified International Working Group criteria (IWG). Acute myeloid leukemia (AML) was defined by 30% or more of bone marrow blasts. Ps were classified according to the IPSS score and the MD Anderson score (MDAS) at the time of start of decitabine therapy and at the time of failure. Results: Twenty-five (29%) pts had secondary MDS. Among 49 evaluable pts for IPSS risk category at the start of decitabine, 13 (26%) were int-1, 23 (48%) int-2, and 13 (26%) high-risk disease. According to the MDAS, 32 (37%) were high-risk, 31 (36%) int-2, 17 (19%) int-1, and 7 (8%) low-risk disease. Cytogenetics were diploid in 35 (40%) pts; 39 (45%) pts had ≥ 10% bone marrow blasts; 35 (40%) pts had primary resistance to decitabine and 52 (60%) had disease recurrence. Best response to decitabine was complete response (CR) in 21 (24%) pts, partial response (PR) in 2 (2%) pts, a bone marrow CR in 14 (16%) pts, and hematologic improvement (HI) in 14 (16%) pts. The median number of cycles of decitabine administered was 7 (range, 1–20). After a median of 21 months (range, 6 to 39) from decitabine failure, 13 (15%) pts remained alive. The median survival post decitabine failure was 4.3 months; the estimated 12-month survival was 28%. Upon failure, 22 (25%) pts transformed into AML, of whom only 3 were alive. At failure 15 (42%) were high-risk, 15 (42%) were int-2, and 6 (8%) were int-1 among 36 patients assessed for the IPSS score. Among 58 pts assessed by the MDAS, 32 (55%) were high-risk, 17 (29%) int-2, 7 (12%) int-1, and 2 (4%) were low-risk disease. The estimated 12-month survival rates were 27%, 33%, and 33% for respectively, patients with high-risk, int-2, and int-1 risk disease (p=0.99). The 12-month survival rates were 100%, 54%, 41%, and 18% for respectively, pts with low, int-1, int-2, and high-risk disease according to the MDAS (p=0.01). Post decitabine failure, 20 pts received idarubicin and cytarabine (IA); the objective response rate (ORR) was 20%; 39 pts received investigational agents with an ORR of 26%; 5 pts received an allogeneic SCT: 3 achieved and remained in CR. At the last follow-up, 13 pts were alive, 5 in CR post allogeneic SCT in 2, post clofarabine in 1, and post IA in 1, and 1 in marrow CR post IA. Conclusion: Outcome of pts post decitabine failure is poor with a median survival of 4.3 months. The MDAS can predict survival at the start of decitabine therapy and upon decitabine failure, with patients with low-risk disease having favorable outcome.

Early responder myeloma: kinetic studies identify a patient subgroup characterized by very poor prognosis.

1989 ◽  
Vol 7 (1) ◽  
pp. 119-125 ◽  
Author(s):  
M Boccadoro ◽  
F Marmont ◽  
M Tribalto ◽  
G Fossati ◽  
V Redoglia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Median Survival ◽  
Plasma Cell ◽  
Survival Rates ◽  
Mass Reduction ◽  
Poor Prognostic Factor ◽  
Tumor Mass ◽  
Remission Duration ◽  
Early Responder ◽  
Bone Marrow Plasma

In order to assess the prognostic value of rapid tumor mass reduction in responding multiple myeloma (MM) patients, 100 consecutive patients were analyzed, and bone marrow plasma cell kinetic characteristics were evaluated at diagnosis. Forty-two patients obtained a tumor mass reduction greater than or equal to 50% with three cycles of chemotherapy and within 3 months (early responder myeloma [ERM]), and 23 in greater than 3 months (slow responder myeloma [SRM]). Survival rates in these two groups were not statistically different (P = .07). The labeling index (LI) of bone marrow plasma cells was significantly higher in ERM patients than in SRM patients (1.8 +/- 2.0 v 0.8 +/- 0.7, P = .006). The LI was used to separate the ERM patients into two well-defined subgroups. ERM patients with a LI greater than or equal to 2% showed a median survival of 16.4 months, whereas ERM patients with a LI less than 2% did not reach the median survival at 46.9 months (P less than .0044). Remission duration was also significantly different: 12.2 months in the high LI subgroup and 26.3 months in the low LI subgroup (P less than .0025). Early response itself does not correspond to shorter remission duration and shorter survival, but it is a poor prognostic factor if associated with a high plasma cell proliferative activity.

scholarly journals Survival after surgery among patients with cholangiocarcinoma in Northeast Thailand according to anatomical and morphological classification

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chaiwat Tawarungruang ◽  
Narong Khuntikeo ◽  
Nittaya Chamadol ◽  
Vallop Laopaiboon ◽  
Jaruwan Thuanman ◽  
...  
Keyword(s):  
Survival Rate ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Cox Regression ◽  
Survival Rates ◽  
Care Program ◽  
Tumor Location ◽  
Northeast Thailand ◽  
Curative Surgery

Abstract Background Cholangiocarcinoma (CCA) has been categorized based on tumor location as intrahepatic (ICCA), perihilar (PCCA) or distal (DCCA), and based on the morphology of the tumor of the bile duct as mass forming (MF), periductal infiltrating (PI) or intraductal (ID). To date, there is limited evidence available regarding the survival of CCA among these different anatomical and morphological classifications. This study aimed to evaluate the survival rate and median survival time after curative surgery among CCA patients according to their anatomical and morphological classifications, and to determine the association between these classifications and survival. Methods This study included CCA patients who underwent curative surgery from the Cholangiocarcinoma Screening and Care Program (CASCAP), Northeast Thailand. The anatomical and morphological classifications were based on pathological findings after surgery. Survival rates of CCA and median survival time since the date of CCA surgery and 95% confidence intervals (CI) were calculated. Multiple cox regression was performed to evaluate factors associated with survival which were quantified by hazard ratios (HR) and their 95% CIs. Results Of the 746 CCA patients, 514 had died at the completion of the study which constituted 15,643.6 person-months of data recordings. The incidence rate was 3.3 per 100 patients per month (95% CI: 3.0–3.6), with median survival time of 17.8 months (95% CI: 15.4–20.2), and 5-year survival rate of 24.6% (95% CI: 20.7–28.6). The longest median survival time was 21.8 months (95% CI: 16.3–27.3) while the highest 5-year survival rate of 34.8% (95% CI: 23.8–46.0) occurred in the DCCA group. A combination of anatomical and morphological classifications, PCCA+ID, was associated with the longest median survival time of 40.5 months (95% CI: 17.9–63.0) and the highest 5-year survival rate of 42.6% (95% CI: 25.4–58.9). The ICCA+MF combination was associated with survival (adjusted HR: 1.45; 95% CI: 1.01–2.09; P = 0.013) compared to ICCA+ID patients. Conclusions Among patients receiving surgical treatment, those with PCCA+ID had the highest 5-year survival rate, which was higher than in groups classified by only anatomical characteristics. Additionally, the patients with ICCA+MF tended to have unfavorable surgical outcomes. Showed the highest survival association. Therefore, further investigations into CCA imaging should focus on patients with a combination of anatomical and morphological classifications.

The Impact of Age and Gender on Hematopoietic Stem Cells and Immune Contexture of the Bone Marrow Microenvironment

2020 ◽  
pp. 1-6
Author(s):  
Rebar N. Mohammed
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Immune Cells ◽  
Absolute Number ◽  
Cell Number ◽  
Hematopoietic Stem ◽  
The Absolute ◽  
And Gender ◽  
The Impact

Hematopoietic stem cells (HSCs) are a rare population of cells that reside mainly in the bone marrow and are capable of generating and fulfilling the entire hematopoietic system upon differentiation. Thirty-six healthy donors, attending the HSCT center to donate their bone marrow, were categorized according to their age into child (0–12 years), adolescence (13–18 years), and adult (19–59 years) groups, and gender into male and female groups. Then, the absolute number of HSCs and mature immune cells in their harvested bone marrow was investigated. Here, we report that the absolute cell number can vary considerably based on the age of the healthy donor, and the number of both HSCs and immune cells declines with advancing age. The gender of the donor (male or female) did not have any impact on the number of the HSCs and immune cells in the bone marrow. In conclusion, since the number of HSCs plays a pivotal role in the clinical outcome of allogeneic HSC transplantations, identifying a younger donor regardless the gender is critical.

scholarly journals Bone marrow niche crosses paths with BMPs: a road to protection and persistence in CML

2019 ◽  
Vol 47 (5) ◽  
pp. 1307-1325 ◽  
Author(s):  
Caroline Busch ◽  
Helen Wheadon
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Morphogenetic Proteins ◽  
Kinase Inhibitor ◽  
Survival Rates ◽  
High Survival ◽  
Bone Marrow Niche ◽  
Matrix Deposition ◽  
Bmp Receptors ◽  
Number Of Patients

Abstract Chronic myeloid leukaemia (CML) is a paradigm of precision medicine, being one of the first cancers to be treated with targeted therapy. This has revolutionised CML therapy and patient outcome, with high survival rates. However, this now means an ever-increasing number of patients are living with the disease on life-long tyrosine kinase inhibitor (TKI) therapy, with most patients anticipated to have near normal life expectancy. Unfortunately, in a significant number of patients, TKIs are not curative. This low-level disease persistence suggests that despite a molecularly targeted therapeutic approach, there are BCR-ABL1-independent mechanisms exploited to sustain the survival of a small cell population of leukaemic stem cells (LSCs). In CML, LSCs display many features akin to haemopoietic stem cells, namely quiescence, self-renewal and the ability to produce mature progeny, this all occurs through intrinsic and extrinsic signals within the specialised microenvironment of the bone marrow (BM) niche. One important avenue of investigation in CML is how the disease highjacks the BM, thereby remodelling this microenvironment to create a niche, which enables LSC persistence and resistance to TKI treatment. In this review, we explore how changes in growth factor levels, in particular, the bone morphogenetic proteins (BMPs) and pro-inflammatory cytokines, impact on cell behaviour, extracellular matrix deposition and bone remodelling in CML. We also discuss the challenges in targeting LSCs and the potential of dual targeting using combination therapies against BMP receptors and BCR-ABL1.

scholarly journals Green Brazilian Propolis Action on Macrophages and Lymphoid Organs of Chronically Stressed Mice

2008 ◽  
Vol 5 (1) ◽  
pp. 71-75 ◽  
Author(s):  
Fabiane Missima ◽  
José Maurício Sforcin
Keyword(s):  
Bone Marrow ◽  
Adrenal Glands ◽  
Well Being ◽  
Peritoneal Macrophages ◽  
Histopathological Analysis ◽  
No Production ◽  
Generic Term ◽  
Brazilian Propolis ◽  
Immunomodulatory Action ◽  
New Research

Stress is a generic term that summarizes how psychosocial and environmental factors influence physical and mental well-being. The interaction between stress and immunity has been widely investigated, involving the neuroendocrine system and several organs. Assays using natural products in stress models deserve further investigation. Propolis immunomodulatory action has been mentioned and it has been the subject of scientific investigation in our laboratory. The aim of this study was to evaluate if and how propolis activated macrophages in BALB/c mice submitted to immobilization stress, as well as the histopathological analysis of the thymus, bone marrow, spleen and adrenal glands. Stressed mice showed a higher hydrogen peroxide (H2O2) generation by peritoneal macrophages, and propolis treatment potentiated H2O2generation and inhibited nitric oxide (NO) production by these cells. Histopathological analysis showed no alterations in the thymus, bone marrow and adrenal glands, but increased germinal centers in the spleen. Propolis treatment counteracted the alterations found in the spleen of stressed mice. New research is being carried out in order to elucidate propolis immunomodulatory action during stress.

scholarly journals Transcription factor Gfi-1 induced by G-CSF is a negative regulator of CXCR4 in myeloid cells

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2276-2285 ◽  
Author(s):  
Maria De La Luz Sierra ◽  
Paola Gasperini ◽  
Peter J. McCormick ◽  
Jinfang Zhu ◽  
Giovanna Tosato
Keyword(s):  
Bone Marrow ◽  
Dna Sequences ◽  
Peripheral Blood ◽  
Cell Function ◽  
Myeloid Cell ◽  
Cxcr4 Expression ◽  
Negative Regulator ◽  
Hematopoietic Stem

The mechanisms underlying granulocyte-colony stimulating factor (G-CSF)–induced mobilization of granulocytic lineage cells from the bone marrow to the peripheral blood remain elusive. We provide evidence that the transcriptional repressor growth factor independence-1 (Gfi-1) is involved in G-CSF–induced mobilization of granulocytic lineage cells from the bone marrow to the peripheral blood. We show that in vitro and in vivo G-CSF promotes expression of Gfi-1 and down-regulates expression of CXCR4, a chemokine receptor essential for the retention of hematopoietic stem cells and granulocytic cells in the bone marrow. Gfi-1 binds to DNA sequences upstream of the CXCR4 gene and represses CXCR4 expression in myeloid lineage cells. As a consequence, myeloid cell responses to the CXCR4 unique ligand SDF-1 are reduced. Thus, Gfi-1 not only regulates hematopoietic stem cell function and myeloid cell development but also probably promotes the release of granulocytic lineage cells from the bone marrow to the peripheral blood by reducing CXCR4 expression and function.

scholarly journals p38/AP-1 Pathway in Lipopolysaccharide-Induced Inflammatory Responses Is Negatively Modulated by Electrical Stimulation

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Deok Jeong ◽  
Jaehwi Lee ◽  
Young-Su Yi ◽  
Yanyan Yang ◽  
Kyoung Won Kim ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Physiological Role ◽  
Peritoneal Macrophages ◽  
Cellular Level ◽  
Transcriptional Level ◽  
Weak Current ◽  
Anti Inflammatory

Electrical stimulation with a weak current has been demonstrated to modulate various cellular and physiological responses, including the differentiation of mesenchymal stem cells and acute or chronic physical pain. Thus, a variety of investigations regarding the physiological role of nano- or microlevel currents at the cellular level are actively proceeding in the field of alternative medicine. In this study, we focused on the anti-inflammatory activity of aluminum-copper patches (ACPs) under macrophage-mediated inflammatory conditions. ACPs generated nanolevel currents ranging from 30 to 55 nA in solution conditions. Interestingly, the nanocurrent-generating aluminum-copper patches (NGACPs) were able to suppress both lipopolysaccharide-(LPS-) and pam3CSK-induced inflammatory responses such as NO and PGE2production in both RAW264.7 cells and peritoneal macrophages at the transcriptional level. Through immunoblotting and immunoprecipitation analyses, we found that p38/AP-1 could be the major inhibitory pathway in the NGACP-mediated anti-inflammatory response. Indeed, inhibition of p38 by SB203580 showed similar inhibitory activity of the production of TNF-αand PGE2and the expression of TNF-αand COX-2 mRNA. These results suggest that ACP-induced nanocurrents alter signal transduction pathways that are involved in the inflammatory response and could therefore be utilized in the treatment of various inflammatory diseases such as arthritis and colitis.

scholarly journals CALLA-positive myeloma: an aggressive subtype with poor survival

Blood ◽  
1985 ◽  
Vol 66 (1) ◽  
pp. 229-232
Author(s):  
BG Durie ◽  
TM Grogan
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Cell Lines ◽  
Median Survival ◽  
Lymphoblastic Leukemia ◽  
Myeloma Cell ◽  
Negative Group ◽  
Poor Survival ◽  
Aggressive Subtype ◽  
Leukemia Antigen

Detailed immunotyping was carried out on 21 direct myeloma bone marrow aspirates and eight human myeloma cell lines. Four previously untreated common acute lymphoblastic leukemia antigen (CALLA)-positive myeloma patients were identified and six of eight cell lines (75%) were also positive. CALLA positivity, as part of an immature B phenotype, was found to correlate with very aggressive clinical disease: median survival six months v 56 months for the CALLA-negative group.

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