Metabolic Activity Of Bone Marrow Research Articles

NFκB- and MAP-Kinase Signaling Contribute to the Activation of Murine Myeloid Dendritic Cells by a Flagellin A:Allergen Fusion Protein.

Fusion proteins incorporating the TLR5-ligand flagellin are currently undergoing clinical trials as vaccine candidates for many diseases. We recently reported a flagellin:allergen fusion protein containing the TLR5-ligand flagellin A (FlaA) from Listeria monocytogenes and the major birch pollen allergen Bet v 1 (rFlaA:Betv1) to prevent allergic sensitization in an experimental mouse model. This study analyzes the signaling pathways contributing to rFlaA:Betv1-mediated pro- and anti-inflammatory cytokine secretion and cell metabolism in myeloid dendritic cells (mDCs) in vitro. The influence of mammalian target of rapamycin (mTOR)-, NFκB-, and MAP kinase (MAPK)-signaling on cytokine secretion and metabolic activity of bone marrow (BM)-derived mDCs stimulated with rFlaA:Betv1 were investigated by pre-treatment with either mTOR- (rapamycin), NFκB- (dexamethason, BMS-345541, TPCA-1, triptolide, or BAY-11) or MAPK- (SP600125, U0126, or SB202190) inhibitors, respectively. rFlaA:Betv1-mediated IL-10 secretion as well as activation of mDC metabolism, rather than pro-inflammatory cytokine secretion, were inhibited by rapamycin. Inhibition of NFκB-signaling suppressed rFlaA:Betv1-induced IL-12, while inhibition of MAPK-signaling dose-dependently suppressed rFlaA:Betv1-induced IL-10 as well as pro-inflammatory IL-6 and TNF-α production. Notably, with the exception of a partial JNK-dependency, rFlaA:Betv1-mediated effects on mDC metabolism were mostly NFκB- and MAPK-independent. Therefore, MAPK-mediated activation of both NFκB- and mTOR-signaling likely is a key pathway for the production of pro- and anti-inflammatory cytokines by flagellin fusion protein vaccines.

Višestruki zloćudni tumori u pacijenta s leukemijom vlasastih stanica: prikaz slučaja

Aim: To present a patient with metachronous occurrence of liposarcoma, HCL (hairy cell leukemia) and renal cell carcinoma and analyze previous literature data about occurrence of multiple malignancies in HCL patients. Case report: We report a case of a 38-year-old patient who operated and treated liposarcoma with radiotherapy and in whom was found pathological metabolic activity of bone marrow on PET/CT (Positron emission tomography/Computed tomography). This finding raised a suspicion about the existence of lymphoproliferative disease and the patient was sent to hematological examination in which was revealed that patient has HCL. The patient was monitored and treatment with cladribine was started after there was deterioration in the blood count. Subsequently remission occured. Abdominal ultrasound was done and focal lesion of left kidney was found. Partial nefrectomy of the left kidney was done. Histopathological analysis revealed clarocellular kidney carcinoma. Conclusion: The patients with HCL have a higher risk of developing other malignant diseases, both solid tumors, and other hematologic neoplasms. It is important to think of secondary malignancies during the patient's monitoring, since secondary malignances are a frequent cause of morbidity and mortality in HCL patients. The patient with this type of limphoproliferative disease needs to be closely monitored and also needs to keep up with primary and secondary measures to prevent cancer development. Further research about the correlation of chemotherapy and incidence of secondary malignancies is needed, but also it is important to research immunological and other pathophysiological mechanisms which can increase the occurence of secondary malignancies.

Correlation of bone marrow cellularity and metabolic activity in healthy volunteers with simultaneous PET/MR imaging.

To evaluate the correlation between bone marrow cellularity (BMC) and metabolic activity in healthy subjects and to see whether yellow marrow is indeed metabolically quiescent. Because metabolic activity can be assumed to reflect vascularity, we assessed the relationship between regional metabolic activity and geographic frequency of metastases as noted in the literature. Two hundred and twenty locations (ten in each side of the pelvis and proximal femur) were evaluated in 11 consecutive healthy volunteers with simultaneous PET/MR. BMC was calculated through precise water-fat fraction quantification with a 6-echo gradient echo. We analyzed correlations between cellularity and SUVr, age, and R2*. We also looked at the relation between our results and the reported prevalence of metastases. There was moderate but statistically significant correlation between BMC and metabolic activity (r = 0.636, p < 0.0001). Interestingly, the iliac and sacrum had higher metabolic activity relative to cellularity, whereas the femoral neck and lesser trochanter showed lower SUVr than other regions with the similar cellularity. The relatively lower metabolic status of the femoral neck conflicted with its reported high frequency of metastasis. Excluding regions with almost no remaining red marrow, cellularity showed inverse relationship with age (r = 0.476, p < 0.0001) and direct relationship with R2* (r = 0.532, p < 0.0010). Metabolic activity of bone marrow was largely dependent on BMC while yellow marrow seems metabolically quiescent. The discrepancy between the assumed vascularity as determined by metabolic activity and reported sites of metastasis suggested that the process of bone metastasis may not depend entirely on vascularity.

Wnt signalling: a mediator of the heart-bone marrow axis after myocardial injury?

Wnt signalling: a mediator of the heart-bone marrow axis after myocardial injury?