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- Rugwizangoga, Belson, et al.
(författare)
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Experience and Perception of Patients and Healthcare Professionals on Acute Leukemia in Rwanda: A Qualitative Study
- 2022
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Ingår i: Cancer Management and Research. - 1179-1322. ; 14, s. 1923-1934
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To explore challenges associated with the timely diagnosis, therapy, and prognosis of acute leukemia in Rwanda. Methods: This is a qualitative study using a phenomenological approach that involved patients, patients' guardians, and healthcare professionals such as physicians from district hospitals and specialists from referral hospitals, as well as healthcare administrators. The primary data were collected from district and referral hospitals and central healthcare administration in Rwanda. The data were collected between July and October 2019. In-depth interviews were conducted, and thematic analysis was employed to interpret the results. Results: We identified barriers to seeking healthcare such as (i) insufficient knowledge within the population may lead patients and their guardians to consult traditional healers before seeking qualified medical care, and (ii) financial constraints that preclude payment of healthcare fees or other out-of-pocket cost related to diagnosis and treatment. We also observed that the referral system is tedious and primary healthcare facilities lack the competence and resources for the necessary diagnostic practices. Both may further delay diagnosis and therapy. Accordingly, healthcare professionals at the referral hospitals stated that most patients were seen at an advanced stage of the disease. For the treatment of acute lymphoblastic leukemia (ALL), only chemotherapy is utilized in Rwanda, while bone marrow (BM) transplantation is not available. Palliation is the only available treatment for the vast majority of Rwandan acute myeloid leukemia (AML) patients. Conclusion: ALL and AML are likely under-reported in Rwanda and diagnosis may be delayed, which may be explained by patient related factors (lack of knowledge, financial constraints), a tedious referral system, and suboptimal diagnostic resources.
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| 2. |
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| 3. |
- Hegedus, Csaba, et al.
(författare)
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Redox control of cancer cell destruction
- 2018
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Ingår i: Redox Biology. - : Elsevier BV. - 2213-2317. ; 16, s. 59-74
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Tidskriftsartikel (refereegranskat)abstract
- Redox regulation has been proposed to control various aspects of carcinogenesis, cancer cell growth, metabolism, migration, invasion, metastasis and cancer vascularization. As cancer has many faces, the role of redox control in different cancers and in the numerous cancer-related processes often point in different directions. In this review, we focus on the redox control mechanisms of tumor cell destruction. The review covers the tumor intrinsic role of oxidants derived from the reduction of oxygen and nitrogen in the control of tumor cell proliferation as well as the roles of oxidants and antioxidant systems in cancer cell death caused by traditional anticancer weapons (chemotherapeutic agents, radiotherapy, photodynamic therapy). Emphasis is also put on the role of oxidants and redox status in the outcome following interactions between cancer cells, cytotoxic lymphocytes and tumor infiltrating macrophages.
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| 4. |
- Dongre, Anushka, et al.
(författare)
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Direct and Indirect Regulators of Epithelial-Mesenchymal Transition (EMT)-mediated Immunosuppression in Breast Carcinomas.
- 2021
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Ingår i: Cancer discovery. - 2159-8290. ; 11:5, s. 1286-1305
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Tidskriftsartikel (refereegranskat)abstract
- The epithelial-to-mesenchymal transition (EMT), which conveys epithelial (E) carcinoma cells to quasi-mesenchymal (qM) states, enables them to metastasize and acquire resistance to certain treatments. Murine tumors composed of qM mammary carcinoma cells assemble an immunosuppressive tumor microenvironment (TME) and develop resistance to anti-CTLA4 immune checkpoint blockade therapy (ICB), unlike their E counterparts. Importantly, minority populations of qM cells within a tumor can cross-protect their more E neighbors from immune attack. The underlying mechanisms of immunosuppression and cross-protection have been unclear. We demonstrate that abrogation of qM carcinoma cell-derived factors (CD73, CSF1 or SPP1) prevents the assembly of an immunosuppressive TME and sensitizes otherwise refractory qM tumors partially or completely to anti-CTLA4 ICB. Most strikingly, mixed tumors in which minority populations of carcinoma cells no longer express CD73, are now sensitized to anti-CTLA4 ICB. Finally, loss of CD73 also enhances the efficacy of anti-CTLA4 ICB during the process of metastatic colonization.
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| 5. |
- Kiffin, Roberta, et al.
(författare)
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Anti-Leukemic Properties of Histamine in Monocytic Leukemia: The Role of NOX2
- 2018
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- In patients with acute myeloid leukemia (AML), treatment with histamine dihydrochloride (HDC) and low-dose IL-2 (HDC/ IL-2) in the post-chemotherapy phase has been shown to reduce the incidence of leukemic relapse. The clinical benefit of HDC/ IL-2 is pronounced in monocytic forms of AML, where the leukemic cells express histamine type 2 receptors (H2R) and the NAPDH oxidase-2 (NOX2). HDC ligates to H(2)Rs to inhibit NOX2-derived formation of reactive oxygen species, but details regarding the anti-leukemic actions of HDC remain to be elucidated. Here, we report that human NOX2(+) myelomonocytic/monocytic AML cell lines showed increased expression of maturation markers along with reduced leukemic cell proliferation after exposure to HDC in vitro. These effects of HDC were absent in corresponding leukemic cells genetically depleted of NOX2 (NOX2(-/-)). We also observed that exposure to HDC altered the expression of genes involved in differentiation and cell cycle progression in AML cells and that these effects required the presence of NOX2. HDC promoted the differentiation also of primary monocytic, but not non-monocytic, AML cells in vitro. In a xenograft model, immunodeficient NOG mice were inoculated with wild-type or NOX2(-/-) human monocytic AML cells and treated with HDC in vivo. The administration of HDC reduced the in vivo expansion of NOX2(+/+), but not of NOX2(-/-) human monocytic AML cells. We propose that NOX2 may be a conceivable target in the treatment of monocytic AML.
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| 6. |
- Riise, Rebecca E, 1987, et al.
(författare)
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TLR-Stimulated Neutrophils Instruct NK Cells To Trigger Dendritic Cell Maturation and Promote Adaptive T Cell Responses
- 2015
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 195:3, s. 1121-1128
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphonuclear neutrophils (PMNs) are innate effector cells with pivotal roles in pathogen recognition, phagocytosis, and eradication. However, their role in the development of subsequent immune responses is incompletely understood. This study aimed to identify mechanisms of relevance to the cross talk between human neutrophils and NK cells and its potential role in promoting adaptive immunity. TLR-stimulated PMNs were found to release soluble mediators to attract and activate NK cells in vitro. PMN-conditioned NK cells displayed enhanced cytotoxicity and cytokine production, and responded vigorously to ensuing stimulation with exogenous and endogenous IL-12. The neutrophil-induced activation of NK cells was prevented by caspase-1 inhibitors and by natural antagonists to IL-1 and IL-18, suggesting a role for the NOD-like receptor family pyrin domain containing-3 inflammasome. In addition, PMN-conditioned NK cells triggered the maturation of monocyte-derived dendritic cells, which promoted T cell proliferation and IFN-gamma production. These data imply that neutrophils attract NK cells to sites of infection to convert these cells into an active state, which drives adaptive immune responses via maturation of dendritic cells. Our results add to a growing body of evidence that suggests a sophisticated role for neutrophils in orchestrating the immune response to pathogens.
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