Porto Alegre, Brazil
Porto Alegre, Brazil

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Martinez-Sanchez M.V.,Hospital Clinico Universitario Virgen Of La Arrixaca Hcuva | Periago A.,Hospital Rafael Mendez | Legaz I.,Hospital Clinico Universitario Virgen Of La Arrixaca Hcuva | Gimeno L.,Hospital Clinico Universitario Virgen Of La Arrixaca Hcuva | And 15 more authors.
OncoImmunology | Year: 2016

ABSTRACT: Missing self recognition makes cancer sensitive to natural killer cell (NKc) reactivity. However, this model disregards the NKc licensing effect, which highly increases NKc reactivity through interactions of inhibitory killer cell immunoglobulin-like receptors (iKIR) with their cognate HLA-I ligands. The influence of iKIR/HLA-ligand (HLA-C1/C2) licensing interactions on the susceptibility to and progression of plasma cell (PC) dyscrasias was evaluated in 164 Caucasian patients and 286 controls. Compared to controls, myeloma accumulates KIR2DL1−L2+L3− genotypes (2.8% vs. 13.2%, p < 0.01, OR = 5.29) and less diverse peripheral repertoires of NKc clones. Less diverse and weaker-affinity repertoires of iKIR2D/HLA-C licensing interactions increased myeloma susceptibility. Thus, the complete absence of conventional iKIR2D/HLA-C licensing interactions (KIR2DL1−L2+L3−/C2C2, 2.56% vs. 0.35%; p < 0.05; OR = 15.014), single-KIR2DL3+/C1+ (20.51% vs. 10.84%; p < 0.05; OR = 2.795) and single-KIR2DL2+/C1+ (12.82% vs. 4.9%; p < 0.01; OR = 5.18) interactions were over-represented in myeloma, compared to controls. Additionally, KIR2DL1−L2+L3− (20% vs. 83%, p < 0.00001) as well as KIR3DL1− (23% vs. 82%, p < 0.00001) genotypes had a dramatic negative impact on the 3-y progression-free survival (PFS), particularly in patients with low-tumor burden. Remarkably, myeloma-PCs, compared to K562 and other hematological cancers, showed substantial over-expression of HLA-I (“increasing-self” instead of missing-self), including HLA-C, and mild expression of ligands for NKc activating receptors (aRec) CD112, CD155, ULBP-1 and MICA/B, which apparently renders myeloma-PCs susceptible to lysis mainly by licensed NKc. KIR2DL1−L2+L3−/C2C2 patients (with no conventional iKIR2D/HLA-C licensing interactions) lyse K562 but barely lyse myeloma-PCs (4% vs. 15%; p < 0.05, compared to controls). These results support a model where immunosurveillance of no-missing-self cancers, e.g., myeloma, mainly depends on NKc licensing. © 2016, © Taylor & Francis Group, LLC.


PubMed | Hospital Rafael Mendez, Hematology Service, Hospital General Universitario Santa Lucia, Hospital Clinico Universitario Virgen Of La Arrixaca Hcuva and Pediatric oncology Service
Type: Journal Article | Journal: Oncoimmunology | Year: 2016

Missing self recognition makes cancer sensitive to natural killer cell (NKc) reactivity. However, this model disregards the NKc licensing effect, which highly increases NKc reactivity through interactions of inhibitory killer cell immunoglobulin-like receptors (iKIR) with their cognate HLA-I ligands. The influence of iKIR/HLA-ligand (HLA-C1/C2) licensing interactions on the susceptibility to and progression of plasma cell (PC) dyscrasias was evaluated in 164 Caucasian patients and 286 controls. Compared to controls, myeloma accumulates KIR2DL1


Giacomazzi C.R.,Complexo Hospitalar Santa Casa | Giacomazzi J.,Core Oncology | Netto C.B.O.,Hospital Of Clinicas Of Porto Alegre Hcpa | Santos-Silva P.,Pediatric Oncology Service | And 6 more authors.
Revista da Associacao Medica Brasileira | Year: 2015

Introduction: cancer is the second leading cause of death in children between the ages of 0 and 14 years, corresponding to approximately 3% of all cases diagnosed in Brazil. A significant percentage (5-10%) of pediatric cancers are associated with hereditary cancer syndromes, including Li-Fraumeni/Li-Fraumeni-like syndromes (LFS/LFL), both of which are caused by TP53 germline mutations. Recent studies have shown that a specific TP53 mutation, known as p.R337H, is present in 1 in 300 newborns in Southern and Southeast Brazil. In addition, a significant per-centage of children with LFS/LFL spectrum tumors in the region have a family history compatible with LFS/LFL. Objective: To review clinical relevant aspects of LFS/LFL by our multidisciplinary team with focus on pediatric cancer. Methods: The NCBI (PubMed) and SciELO databases were consulted using the keywords Li-Fraumeni syndrome, Li-Fraumeni-like syndrome and pediatric cancer; and all manuscripts published between 1990 and 2014 using these keywords were retrieved and reviewed. Conclusion: Although LFS/LFL is considered a rare disease, it appears to be substantially more common in certain geographic regions. Recognition of population-specific risks for the syndrome is important for adequate management of hereditary cancer patients and families. In Southern and Southeastern Brazil, LFS/ LFL should be considered in the differential diagnosis of children with cancer, especially if within the spectrum of the syndrome. Due to the complexities of these syndromes, a multidisciplinary approach should be sought for the counseling, diagnosis and management of patients and families affected by these disorders. Pediatricians and pediatric oncologists in areas with high prevalence of hereditary cancer syndromes have a central role in the recognition and proper referral of patients and families to genetic cancer risk evaluation and management programs.


PubMed | Federal University of Rio Grande do Sul, Bioethics Research Laboratory, Oncology Service, Pediatric Oncology Service and 5 more.
Type: Journal Article | Journal: Revista da Associacao Medica Brasileira (1992) | Year: 2015

cancer is the second leading cause of death in children between the ages of 0 and 14 years, corresponding to approximately 3% of all cases diagnosed in Brazil. A significant percentage (5-10%) of pediatric cancers are associated with hereditary cancer syndromes, including Li-Fraumeni/Li-Fraumeni-like syndromes (LFS/LFL), both of which are caused by TP53 germline mutations. Recent studies have shown that a specific TP53 mutation, known as p.R337H, is present in 1 in 300 newborns in Southern and Southeast Brazil. In addition, a significant percentage of children with LFS/LFL spectrum tumors in the region have a family history compatible with LFS/LFL.to review clinical relevant aspects of LFS/LFL by our multidisciplinary team with focus on pediatric cancer.the NCBI (PubMed) and SciELO databases were consulted using the keywords Li-Fraumeni syndrome, Li-Fraumeni-like syndrome and pediatric cancer; and all manuscripts published between 1990 and 2014 using these keywords were retrieved and reviewed.although LFS/LFL is considered a rare disease, it appears to be substantially more common in certain geographic regions. Recognition of population- specific risks for the syndrome is important for adequate management of hereditary cancer patients and families. In Southern and Southeastern Brazil, LFS/ LFL should be considered in the differential diagnosis of children with cancer, especially if within the spectrum of the syndrome. Due to the complexities of these syndromes, a multidisciplinary approach should be sought for the counseling, diagnosis and management of patients and families affected by these disorders. Pediatricians and pediatric oncologists in areas with high prevalence of hereditary cancer syndromes have a central role in the recognition and proper referral of patients and families to genetic cancer risk evaluation and management programs.


Weaver M.S.,St Jude Childrens Research Hospital | Yao A.J.J.,Pediatric Oncology Service | Renner L.A.,University of Ghana | Harif M.,Cheikh Khalifa Hospital | And 2 more authors.
British Journal of Cancer | Year: 2015

Background: Given the burden of childhood cancer and palliative care need in Africa, this paper investigated the paediatric and palliative care elements in cancer control plans. Methods: We conducted a comparative content analysis of accessible national cancer control plans in Africa, using a health systems perspective attentive to context, development, scope, and monitoring/evaluation. Burden estimates were derived from World Bank, World Health Organisation, and Worldwide Palliative Care Alliance. Results: Eighteen national plans and one Africa-wide plan (10 English, 9 French) were accessible, representing 9 low-, 4 lower-middle-, and 5 upper-middle-income settings. Ten plans discussed cancer control in the context of noncommunicable diseases. Paediatric cancer was mentioned in 7 national plans, representing 5127 children, or 13% of the estimated continental burden for children aged 0-14 years. Palliative care needs were recognised in 11 national plans, representing 157 490 children, or 24% of the estimated Africa-wide burden for children aged 0-14 years; four plans specified paediatric palliative needs. Palliative care was itemised in four budgets. Sample indicators and equity measures were identified, including those highlighting contextual needs for treatment access and completion. Conclusions: Recognising explicit strategies and funding for paediatric and palliative services may guide prioritised cancer control efforts in resource-limited settings. © 2015 Cancer Research UK. All rights reserved.


PubMed | University of Ghana, Cheikh Khalifa Hospital, Pediatric Oncology Service, St Jude Childrens Research Hospital and Outreach
Type: Journal Article | Journal: British journal of cancer | Year: 2015

Given the burden of childhood cancer and palliative care need in Africa, this paper investigated the paediatric and palliative care elements in cancer control plans.We conducted a comparative content analysis of accessible national cancer control plans in Africa, using a health systems perspective attentive to context, development, scope, and monitoring/evaluation. Burden estimates were derived from World Bank, World Health Organisation, and Worldwide Palliative Care Alliance.Eighteen national plans and one Africa-wide plan (10 English, 9 French) were accessible, representing 9 low-, 4 lower-middle-, and 5 upper-middle-income settings. Ten plans discussed cancer control in the context of noncommunicable diseases. Paediatric cancer was mentioned in 7 national plans, representing 5127 children, or 13% of the estimated continental burden for children aged 0-14 years. Palliative care needs were recognised in 11 national plans, representing 157490 children, or 24% of the estimated Africa-wide burden for children aged 0-14 years; four plans specified paediatric palliative needs. Palliative care was itemised in four budgets. Sample indicators and equity measures were identified, including those highlighting contextual needs for treatment access and completion.Recognising explicit strategies and funding for paediatric and palliative services may guide prioritised cancer control efforts in resource-limited settings.

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