Thrombopoietin: tickling the HSC's fancy

Kim, Ah Ram; Sankaran, Vijay G.

doi:10.15252/emmm.201708450

Cited by 12 publications

(10 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 43 In contrast, in a number of murine tumor models, irradiation induced an immunosuppressive macrophage phenotype. 27–29 44 In these models, macrophages inhibited T-cell activation. Our findings suggest that irradiation repolarizes macrophages to a Th1-oriented phenotype which not just directly promotes pro-inflammatory macrophages but may be able to facilitate anticancer function indirectly via activating T cells.…”

Section: Discussionmentioning

confidence: 99%

“… 26 Other studies suggested that irradiation of tumors was associated with a more immunosuppressive phenotype of TAM. 27–29 Jones et al found that the depletion of macrophages by an anti-CSF antibody greatly increased tumor ablation upon irradiation (10 Gy) in murine tumors generated from a colorectal and a pancreatic cell line. Obviously, the effect of irradiation appears to depend on the model, irradiation dose, tissue as well as on the investigated time point after irradiation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Short-course radiotherapy promotes pro-inflammatory macrophages via extracellular vesicles in human rectal cancer

Stary

Wolf

Unterleuthner

et al. 2020

J Immunother Cancer

View full text Add to dashboard Cite

BackgroundTumor-associated macrophages (TAM) constitute the most abundant immune cells in the tumor stroma initiating pro-inflammatory (M1) or immunosuppressive (M2) responses depending on their polarization status. Advances in tumor immunotherapy call for a detailed understanding of potential immunogenic mechanisms of irradiation routinely applied in rectal cancer patients.MethodsTo test the effects of radiotherapy on TAM, we ex vivo irradiated tissue samples of human rectal cancer and assessed the phenotype by flow cytometry. We furthermore evaluated the distribution of leucocyte subsets in tissue sections of patients after short-course radiotherapy and compared findings to non-pretreated rectal cancer using an immunostaining approach. Organotypic assays (OTA) consisting of macrophages, cancer-associated fibroblast and cancer cell lines were used to dissect the immunological consequences of irradiation in macrophages.ResultsWe demonstrate that short-course neoadjuvant radiotherapy in rectal cancer patients is associated with a shift in the polarization of TAM towards an M1-like pro-inflammatory phenotype. In addition, ex vivo irradiation caused an increase in the phagocytic activity and enhanced expression of markers associated with stimulatory signals necessary for T-cell activation. In OTA we observed that this alteration in macrophage polarization could be mediated by extracellular vesicles (EV) derived from irradiated tumor cells. We identified high mobility group box 1 in EV from irradiated tumor cells as a potential effector signal in that crosstalk.ConclusionsOur findings highlight macrophages as potential effector cells upon irradiation in rectal cancer by diminishing their immunosuppressive phenotype and activate pro-inflammation. Our data indicate that clinically applied short-term radiotherapy for rectal cancer may be exploited to stimulate immunogenic macrophages and suggest to target the polarization status of macrophages to enhance future immunotherapeutic strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Short-course radiotherapy promotes pro-inflammatory macrophages via extracellular vesicles in human rectal cancer

Stary

Wolf

Unterleuthner

et al. 2020

J Immunother Cancer

View full text Add to dashboard Cite

show abstract

“…In our experiment, we used AICAR as a positive control. AICAR, which is an AMPK activator, has been reported as able to recover muscle wasting induced by inflammation [ 22 ]. AICAR was intraperitoneally injected at 250 mg/kg every 2 days.…”

Section: Methodsmentioning

confidence: 99%

The Extract of Arctium lappa L. Fruit (Arctii Fructus) Improves Cancer-Induced Cachexia by Inhibiting Weight Loss of Skeletal Muscle and Adipose Tissue

et al. 2020

View full text Add to dashboard Cite

Background: Cachexia induced by cancer is a systemic wasting syndrome and it accompanies continuous body weight loss with the exhaustion of skeletal muscle and adipose tissue. Cancer cachexia is not only a problem in itself, but it also reduces the effectiveness of treatments and deteriorates quality of life. However, effective treatments have not been found yet. Although Arctii Fructus (AF) has been studied about several pharmacological effects, there were no reports on its use in cancer cachexia. Methods: To induce cancer cachexia in mice, we inoculated CT-26 cells to BALB/c mice through subcutaneous injection and intraperitoneal injection. To mimic cancer cachexia in vitro, we used conditioned media (CM), which was CT-26 colon cancer cells cultured medium. Results: In in vivo experiments, AF suppressed expression of interleukin (IL)-6 and atrophy of skeletal muscle and adipose tissue. As a result, the administration of AF decreased mortality by preventing weight loss. In adipose tissue, AF decreased expression of uncoupling protein 1 (UCP1) by restoring AMP-activated protein kinase (AMPK) activation. In in vitro model, CM increased muscle degradation factors and decreased adipocytes differentiation factors. However, these tendencies were ameliorated by AF treatment in C2C12 myoblasts and 3T3-L1 cells. Conclusion: Taken together, our study demonstrated that AF could be a therapeutic supplement for patients suffering from cancer cachexia.

show abstract

“…Sequencing and follow-up functional assays in a family with three affected members found a previously unknown homozygous mutation in the THPO gene. 9,10 The authors showed that it was disease causing, resulting in impaired secretion of the thrombopoietin hormone. They were able to successfully treat the three patients with romiplostim, a recombinant thrombopoietin receptor agonist.…”

Section: Resultsmentioning

confidence: 99%

Long-Term Patient-Customized Therapy for a Pathogenic EPO Mutation

Ejaz

Özcan

Ünal

et al. 2021

Med

Self Cite

View full text Add to dashboard Cite

Background: Recent advances in genomics have enabled the successful identification of a number of rare pathogenic mutations. Uncovering these mutations is essential as the first step toward devising a cure for the often debilitating and life-limiting diseases arising from them. For many of these mutations, targeted agents do not yet exist. Here, we describe the case of a patient who has a novel pathogenic mutation in the erythropoietin (EPO) gene, which is essential for normal erythropoiesis, and who presented with a profound hypoplastic anemia. Methods: The patient, aged 5 months, was started on recombinant erythropoietin at a standard dose of 500 units (50 U/kg) and subsequently 800 units three times weekly, and her blood counts were monitored over 4 years. Findings: A prompt response to the recombinant erythropoietin was found with an increase in hemoglobin levels to 12.8 g/dL and increase in red cell count to 4.89 3 10 6 /mL. The patient became transfusion independent. The therapy enabled the patient to maintain a hemoglobin level in the normal range without any adverse effects and with no requirement for further blood transfusions. Conclusions: Patient-customized therapies can be highly effective in the treatment of rare genetic disorders, and for many of these disorders, effective treatment may already exist in the clinical domain, as described for the patient in this report.

show abstract

Thrombopoietin: tickling the HSC's fancy

Cited by 12 publications

References 13 publications

Short-course radiotherapy promotes pro-inflammatory macrophages via extracellular vesicles in human rectal cancer

Short-course radiotherapy promotes pro-inflammatory macrophages via extracellular vesicles in human rectal cancer

The Extract of Arctium lappa L. Fruit (Arctii Fructus) Improves Cancer-Induced Cachexia by Inhibiting Weight Loss of Skeletal Muscle and Adipose Tissue

Long-Term Patient-Customized Therapy for a Pathogenic EPO Mutation

Contact Info

Product

Resources

About