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1.
Am J Nephrol ; 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38493776

RESUMO

BACKGROUND: Cancer, hypertension, and kidney disease are closely interrelated. Knowledge of the potential hypertensive and nephrotoxic effects of antineoplastic medications is critical to minimizing interruptions in cancer treatment. SUMMARY: Antineoplastic medications can cause hypertension, proteinuria, and kidney injury, often mediated by common mechanisms. Notably, inhibitors of the vascular endothelial growth factor pathway have the strongest association with both hypertension and proteinuria, typically acute in onset and often reversible after drug discontinuation. The abrupt rise in blood pressure can cause clinically significant hypertensive syndromes and contribute to overall morbidity. Significant proteinuria can herald kidney failure. Close monitoring of blood pressure and renal function during antineoplastic therapy and appropriate hypertension treatment are important. This article reviews available literature and proposes a step-by-step approach to manage cancer patients with concurrent hypertension and kidney disease. KEY MESSAGES: For antineoplastic medications with known hypertensive effect, blood pressure should be checked at baseline and serially during cancer treatment. Hypertensive crisis with end-organ damage, significant proteinuria, microscopic hematuria, or unexplained acute kidney injury necessitates drug cessation until further evaluation and resolution. In patients with chronic kidney disease and cancer therapy-related hypertension, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker is the preferred antihypertensive choice. Finally, multidisciplinary collaboration in these patients will yield the best results.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38427744

RESUMO

ABSTRACT: The papillary glioneuronal tumor is a WHO grade 1, rare neuronal-glial tumor and comprises 0.02% of all CNS tumors. Histologically, it is a mixture of glial and neuronal components showing a pseudopapillary pattern with hyalinized vessels. PGNT is considered a low-grade neoplasm, and surgical excision has been curative in most cases. In this paper, we report a new case of papillary glioneuronal tumor in a 44-year-old male having a divergent presentation, to analyze it due to the rarity of its occurrence as per the latest classification.

3.
Clin Kidney J ; 16(12): 2336-2348, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38046043

RESUMO

The survival rates of many cancers have significantly improved due to recent advancements in cancer screening and therapeutics. Although better cancer outcomes are encouraging, additional health challenges have surfaced, the utmost of which is the burden imposed by various cardiovascular and renal toxicities of anticancer therapies. To improve the overall outcome of patients with cancer, it is essential to understand and manage these treatment-related adverse effects. The cardiovascular side effects of antineoplastic therapies are well-known and include left ventricular dysfunction, heart failure, myocardial ischaemia, QT prolongation, arrhythmia and hypertension. Among these, hypertension is the most common complication, prevalent in about 40% of all cancer patients, yet frequently overlooked and undertreated. This review explores the intricate connection between cancer and hypertension and provides distinct approaches to diagnosing, monitoring and managing hypertension in patients with cancer. We also outline the challenges and considerations that are relevant to the care of patients receiving anticancer drugs with prohypertensive potential.

4.
Mol Cell ; 81(22): 4605-4621.e11, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34582793

RESUMO

G-protein-coupled receptors (GPCRs), also known as seven transmembrane receptors (7TMRs), typically interact with two distinct signal-transducers, i.e., G proteins and ß-arrestins (ßarrs). Interestingly, there are some non-canonical 7TMRs that lack G protein coupling but interact with ßarrs, although an understanding of their transducer coupling preference, downstream signaling, and structural mechanism remains elusive. Here, we characterize two such non-canonical 7TMRs, namely, the decoy D6 receptor (D6R) and the complement C5a receptor subtype 2 (C5aR2), in parallel with their canonical GPCR counterparts. We discover that D6R and C5aR2 efficiently couple to ßarrs, exhibit distinct engagement of GPCR kinases (GRKs), and activate non-canonical downstream signaling pathways. We also observe that ßarrs adopt distinct conformations for D6R and C5aR2, compared to their canonical GPCR counterparts, in response to common natural agonists. Our study establishes D6R and C5aR2 as ßarr-coupled 7TMRs and provides key insights into their regulation and signaling with direct implication for biased agonism.


Assuntos
Membrana Celular/metabolismo , Conformação Proteica , Transdução de Sinais , beta-Arrestinas/química , Animais , Proteínas de Ligação ao GTP/química , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação , Ligação Proteica , Domínios Proteicos , Estrutura Secundária de Proteína , Transporte Proteico , Receptor da Anafilatoxina C5a/metabolismo
5.
J Biol Chem ; 294(24): 9416-9429, 2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31036565

RESUMO

The human complement component, C5a, binds two different seven-transmembrane receptors termed C5aR1 and C5aR2. C5aR1 is a prototypical G-protein-coupled receptor that couples to the Gαi subfamily of heterotrimeric G-proteins and ß-arrestins (ßarrs) following C5a stimulation. Peptide fragments derived from the C terminus of C5a can still interact with the receptor, albeit with lower affinity, and can act as agonists or antagonists. However, whether such fragments might display ligand bias at C5aR1 remains unexplored. Here, we compare C5a and a modified C-terminal fragment of C5a, C5apep, in terms of G-protein coupling, ßarr recruitment, endocytosis, and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase activation at the human C5aR1. We discover that C5apep acts as a full agonist for Gαi coupling as measured by cAMP response and extracellular signal-regulated kinase 1/2 phosphorylation, but it displays partial agonism for ßarr recruitment and receptor endocytosis. Interestingly, C5apep exhibits full-agonist efficacy with respect to inhibiting lipopolysaccharide-induced interleukin-6 secretion in human macrophages, but its ability to induce human neutrophil migration is substantially lower compared with C5a, although both these responses are sensitive to pertussis toxin treatment. Taken together, our data reveal that compared with C5a, C5apep exerts partial efficacy for ßarr recruitment, receptor trafficking, and neutrophil migration. Our findings therefore uncover functional bias at C5aR1 and also provide a framework that can potentially be extended to chemokine receptors, which also typically interact with chemokines through a biphasic mechanism.


Assuntos
Complemento C5a/metabolismo , Endocitose , Receptor da Anafilatoxina C5a/metabolismo , beta-Arrestinas/metabolismo , Sequência de Aminoácidos , Movimento Celular , Complemento C5a/genética , Células HEK293 , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Neutrófilos/metabolismo , Fosforilação , Ligação Proteica , Receptor da Anafilatoxina C5a/genética , Homologia de Sequência , Transdução de Sinais , beta-Arrestinas/genética
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