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1.
Immunol Invest ; 53(6): 962-974, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38847319

RESUMO

First described in 2020, multi-system inflammatory syndrome in children (MIS-C) is an, initially life-threatening, disease characterised by severe inflammation and following exposure to SARS-CoV-2. The immunopathology of MIS-C involves a hyperinflammation characterised by a cytokine storm and activation of both the innate and adaptive immune system, eventually leading to multi-organ failure. Several etiological theories are described in literature. Firstly, it is suggested that the gut plays an important role in the translocation of microbial products to the systemic circulation. Additionally, the production of autoantibodies that develop after the initial infection with SARS-CoV-2 might lead to many of its broad clinical symptoms. Finally, the superantigen theory where non-specific binding of the SARS-CoV-2 spike glycoprotein to the T-cell receptor leads to a subsequent activation of T cells, generating a powerful immune response. Despite the sudden outbreak of MIS-C and alarming messages, as of 2024, cases have declined drastically and subsequently show a less severe clinical spectrum. However, subacute cases not meeting current diagnostic criteria might be overlooked even though they represent a valuable research population. In the future, research should focus on adjusting these criteria to better understand the broad pathophysiology of MIS-C, aiding early detection, therapy, and prediction.


Assuntos
COVID-19 , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica , Humanos , COVID-19/imunologia , COVID-19/complicações , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Criança , SARS-CoV-2/imunologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Autoanticorpos/imunologia , Imunidade Inata , Glicoproteína da Espícula de Coronavírus/imunologia
2.
Chaos ; 34(1)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38166172

RESUMO

Nonlinear dynamical systems, such as climate systems, often switch from one metastable state to another when subject to noise. The first occurrence of such state transition, which is usually characterized by the first passage time, has gained enormous interest in many engineering and scientific fields. We develop an efficient numerical method to compute the probability density of the first passage time for state transitions in stochastic dynamical systems driven by Brownian motions. The proposed method involves solving a singular integral equation, which determines probability density of the first passage time. Some numerical examples, with application to a simplified thermohaline circulation system, are provided to illustrate and verify the proposed method.

3.
J Vis ; 24(6): 9, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38856981

RESUMO

Four experiments were conducted to gain a better understanding of the visual mechanisms related to how integration of partial shape cues provides for recognition of the full shape. In each experiment, letters formed as outline contours were displayed as a sequence of adjacent segments (fragments), each visible during a 17-ms time frame. The first experiment varied the contrast of the fragments. There were substantial individual differences in contrast sensitivity, so stimulus displays in the masking experiments that followed were calibrated to the sensitivity of each participant. Masks were displayed either as patterns that filled the entire screen (full field) or as successive strips that were sliced from the pattern, each strip lying across the location of the letter fragment that had been shown a moment before. Contrast of masks were varied to be lighter or darker than the letter fragments. Full-field masks, whether light or dark, provided relatively little impairment of recognition, as was the case for mask strips that were lighter than the letter fragments. However, dark strip masks proved to be very effective, with the degree of recognition impairment becoming larger as mask contrast was increased. A final experiment found the strip masks to be most effective when they overlapped the location where the letter fragments had been shown a moment before. They became progressively less effective with increased spatial separation from that location. Results are discussed with extensive reference to potential brain mechanisms for integrating shape cues.


Assuntos
Sensibilidades de Contraste , Percepção de Forma , Reconhecimento Visual de Modelos , Mascaramento Perceptivo , Estimulação Luminosa , Humanos , Mascaramento Perceptivo/fisiologia , Sensibilidades de Contraste/fisiologia , Estimulação Luminosa/métodos , Adulto , Reconhecimento Visual de Modelos/fisiologia , Percepção de Forma/fisiologia , Masculino , Feminino , Sinais (Psicologia) , Adulto Jovem
4.
Curr Oncol Rep ; 24(7): 819-824, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35305210

RESUMO

PURPOSE OF REVIEW: Lung neuroendocrine tumors (NETs)-typical carcinoids and atypical carcinoids-have unique molecular alterations that are distinct from neuroendocrine carcinomas of the lung and non-small cell lung cancers. Here, we review the role of molecular profiling in the prognosis and treatment of lung NETs. RECENT FINDINGS: There have been no recently identified molecular prognostic factors for lung NETs and none that have been routinely used to guide management of patients with lung NETs. Previous findings suggest that patients with loss of chromosome 11q may have a worse prognosis along with upregulation of anti-apoptotic pathways (e.g., loss of CD44 and OTP protein expression). Lung NETs rarely harbor driver mutations commonly found in non-small cell lung cancer (NSCLC) or TP53/RB1 mutations found universally in small cell lung cancer. Lung NETs also have low tumor mutation burden and low PD-L1 expression. Everolimus, an mTOR inhibitor and the only FDA approved therapy for unresectable lung NETs, is an effective treatment but the presence of a molecular alteration in the PI3K/AKT/mTOR pathway is not known to predict treatment response. The predominant mutations in lung NETs occur in genes regulating chromatin remodeling and histone modification, with potential targeted therapies emerging in clinical trials. Lung NETs have recurring alterations in genes that regulate the epigenome. Future targeted therapy interfering with epigenetic pathways may hold promise.


Assuntos
Antineoplásicos , Tumor Carcinoide , Carcinoma Neuroendócrino , Carcinoma Pulmonar de Células não Pequenas , Everolimo , Neoplasias Pulmonares , Tumores Neuroendócrinos , Antineoplásicos/uso terapêutico , Tumor Carcinoide/tratamento farmacológico , Tumor Carcinoide/genética , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Everolimo/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia/metabolismo , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/genética , Fosfatidilinositol 3-Quinases/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores
5.
Nature ; 522(7554): 94-7, 2015 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-25849774

RESUMO

Tissue homeostasis is achieved through a balance of cell production (growth) and elimination (regression). In contrast to tissue growth, the cells and molecular signals required for tissue regression remain unknown. To investigate physiological tissue regression, we use the mouse hair follicle, which cycles stereotypically between phases of growth and regression while maintaining a pool of stem cells to perpetuate tissue regeneration. Here we show by intravital microscopy in live mice that the regression phase eliminates the majority of the epithelial cells by two distinct mechanisms: terminal differentiation of suprabasal cells and a spatial gradient of apoptosis of basal cells. Furthermore, we demonstrate that basal epithelial cells collectively act as phagocytes to clear dying epithelial neighbours. Through cellular and genetic ablation we show that epithelial cell death is extrinsically induced through transforming growth factor (TGF)-ß activation and mesenchymal crosstalk. Strikingly, our data show that regression acts to reduce the stem cell pool, as inhibition of regression results in excess basal epithelial cells with regenerative abilities. This study identifies the cellular behaviours and molecular mechanisms of regression that counterbalance growth to maintain tissue homeostasis.


Assuntos
Morte Celular , Células Epiteliais/citologia , Folículo Piloso/citologia , Fagocitose , Nicho de Células-Tronco/fisiologia , Células-Tronco/citologia , Animais , Apoptose , Derme/citologia , Derme/metabolismo , Células Epiteliais/metabolismo , Folículo Piloso/metabolismo , Homeostase , Camundongos , Fagócitos/citologia , Regeneração , Transdução de Sinais , Células-Tronco/metabolismo , Fator de Crescimento Transformador beta/metabolismo , beta Catenina/metabolismo
6.
J Cell Mol Med ; 23(3): 1784-1797, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30548903

RESUMO

Aberrant regulation of programmed cell death (PCD) has been tied to an array of human pathologies ranging from cancers to autoimmune disorders to diverse forms of neurodegeneration. Pharmacologic modulation of PCD signalling is therefore of central interest to a number of clinical and biomedical applications. A key component of PCD signalling involves the modulation of pro- and anti-apoptotic Bcl-2 family members. Among these, Bax translocation represents a critical regulatory phase in PCD. In the present study, we have employed a high-content high-throughput screen to identify small molecules which inhibit the cellular process of Bax re-distribution to the mitochondria following commitment of the cell to die. Screening of 6246 Generally Recognized As Safe compounds from four chemical libraries post-induction of cisplatin-mediated PCD resulted in the identification of 18 compounds which significantly reduced levels of Bax translocation. Further examination revealed protective effects via reduction of executioner caspase activity and enhanced mitochondrial function. Consistent with their effects on Bax translocation, these compounds exhibited significant rescue against in vitro and in vivo cisplatin-induced apoptosis. Altogether, our findings identify a new set of clinically useful small molecules PCD inhibitors and highlight the role which cAMP plays in regulating Bax-mediated PCD.


Assuntos
Proliferação de Células/efeitos dos fármacos , Proteínas de Fluorescência Verde/antagonistas & inibidores , Ensaios de Triagem em Larga Escala/métodos , Transporte Proteico/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Proteína X Associada a bcl-2/antagonistas & inibidores , Animais , Células CHO , Cricetulus , Proteínas de Fluorescência Verde/metabolismo , Humanos , Proteína X Associada a bcl-2/metabolismo
7.
J Cell Sci ; 130(7): 1201-1207, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28365593

RESUMO

Cells exhibit morphological and molecular asymmetries that are broadly categorized as cell polarity. The cell polarity established in early embryos prefigures the macroscopic anatomical asymmetries characteristic of adult animals. For example, eggs and early embryos have polarized distributions of RNAs and proteins that generate global anterior/posterior and dorsal/ventral axes. The molecular programs that polarize embryos are subsequently reused in multiple contexts. Epithelial cells require apical/basal polarity to establish their barrier function. Migrating cells polarize in the direction of movement, creating distinct leading and trailing structures. Asymmetrically dividing stem cells partition different molecules between themselves and their daughter cells. Cell polarity can develop de novo, be maintained through rounds of cell division and be dynamically remodeled. In this Cell Science at a Glance review and poster, we describe molecular asymmetries that underlie cell polarity in several cellular contexts. We highlight multiple developmental systems that first establish cell/developmental polarity, and then maintain it. Our poster showcases repeated use of the Par, Scribble and Crumbs polarity complexes, which drive the development of cell polarity in many cell types and organisms. We then briefly discuss the diverse and dynamic changes in cell polarity that occur during cell migration, asymmetric cell division and in planar polarized tissues.


Assuntos
Polaridade Celular , Animais , Divisão Celular Assimétrica , Caenorhabditis elegans/citologia , Caenorhabditis elegans/metabolismo , Movimento Celular , Humanos , Complexos Multiproteicos/metabolismo , Transdução de Sinais
8.
Mol Cell ; 40(4): 619-31, 2010 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-21055983

RESUMO

Genome integrity is jeopardized each time DNA replication forks stall or collapse. Here we report the identification of a complex composed of MMS22L (C6ORF167) and TONSL (NFKBIL2) that participates in the recovery from replication stress. MMS22L and TONSL are homologous to yeast Mms22 and plant Tonsoku/Brushy1, respectively. MMS22L-TONSL accumulates at regions of ssDNA associated with distressed replication forks or at processed DNA breaks, and its depletion results in high levels of endogenous DNA double-strand breaks caused by an inability to complete DNA synthesis after replication fork collapse. Moreover, cells depleted of MMS22L are highly sensitive to camptothecin, a topoisomerase I poison that impairs DNA replication progression. Finally, MMS22L and TONSL are necessary for the efficient formation of RAD51 foci after DNA damage, and their depletion impairs homologous recombination. These results indicate that MMS22L and TONSL are genome caretakers that stimulate the recombination-dependent repair of stalled or collapsed replication forks.


Assuntos
Replicação do DNA , Proteínas de Ligação a DNA/metabolismo , Complexos Multiproteicos/metabolismo , NF-kappa B/metabolismo , Proteínas Nucleares/metabolismo , Recombinação Genética , Estresse Fisiológico , Sobrevivência Celular , Quebras de DNA de Cadeia Dupla , Células HeLa , Humanos , NF-kappa B/química , Ligação Proteica , Fase S , Moldes Genéticos
12.
N Engl J Med ; 379(11): 1004-1005, 2018 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-30207908
13.
J Infect Dis ; 207(10): 1491-7, 2013 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-23431033

RESUMO

Bacterial vaginosis is a highly prevalent and poorly understood polymicrobial disorder of the vaginal microbiota, with significant adverse sequelae. Gardnerella vaginalis predominates in bacterial vaginosis. Biofilms of G. vaginalis are present in human infections and are implicated in persistent disease, treatment failure, and transmission. Here we demonstrate that G. vaginalis biofilms contain extracellular DNA, which is essential to their structural integrity. Enzymatic disruption of this DNA specifically inhibits biofilms, acting on both newly forming and established biofilms. DNase liberates bacteria from the biofilm to supernatant fractions and potentiates the activity of metronidazole, an antimicrobial agent used in the treatment of bacterial vaginosis. Using a new murine vaginal colonization model for G. vaginalis, we demonstrate >10-fold inhibition of G. vaginalis colonization by DNase. We conclude that DNase merits investigation as a potential nonantibiotic adjunct to existing bacterial vaginosis therapies in order to decrease the risk of chronic infection, recurrence, and associated morbidities.


Assuntos
Biofilmes/crescimento & desenvolvimento , Desoxirribonucleases/metabolismo , Gardnerella vaginalis/fisiologia , Vaginose Bacteriana/tratamento farmacológico , Animais , Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Gardnerella vaginalis/efeitos dos fármacos , Metagenoma , Metronidazol/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Vagina/microbiologia , Vaginose Bacteriana/microbiologia , Vaginose Bacteriana/prevenção & controle
14.
Eur J Clin Nutr ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39179654

RESUMO

Vitamin C deficiency, otherwise known as scurvy, is one the oldest known diseases. Although its prevalence has substantially diminished, certain populations such as smokers, alcoholics, elderly, and those with malabsorptive syndromes remain at risk. Deficiency presents with perifollicular hemorrhage, corkscrew hairs, and petechiae that can evolve into ecchymoses and purpura. Diagnosis starts with clinical suspicion and is confirmed with plasma and leukocyte ascorbic acid levels. Early suspicion is key. Treatment with vitamin C offers an excellent prognosis and avoids unnecessary workup for differential diagnoses. In our case, a 45-year-old male alcoholic with progressively worsening symptoms was found to have scurvy. Treatment was initiated with vitamin C supplementation, and he had remarkable improvement in his symptoms within weeks. This case demonstrates that scurvy is not a disease of history and must be considered in modern medicine, especially as homelessness with concomitant poor nutrition continues to increase.

15.
Sci Rep ; 14(1): 5575, 2024 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448481

RESUMO

Wastewater surveillance has proven a cost-effective key public health tool to understand a wide range of community health diseases and has been a strong source of information on community levels and spread for health departments throughout the SARS- CoV-2 pandemic. Studies spanning the globe demonstrate the strong association between virus levels observed in wastewater and quality clinical case information of the population served by the sewershed. Few of these studies incorporate the temporal dependence present in sampling over time, which can lead to estimation issues which in turn impact conclusions. We contribute to the literature for this important public health science by putting forward time series methods coupled with statistical process control that (1) capture the evolving trend of a disease in the population; (2) separate the uncertainty in the population disease trend from the uncertainty due to sampling and measurement; and (3) support comparison of sub-sewershed population disease dynamics with those of the population represented by the larger downstream treatment plant. Our statistical methods incorporate the fact that measurements are over time, ensuring correct statistical conclusions. We provide a retrospective example of how sub-sewersheds virus levels compare to the upstream wastewater treatment plant virus levels. An on-line algorithm supports real-time statistical assessment of deviations of virus level in a population represented by a sub-sewershed to the virus level in the corresponding larger downstream wastewater treatment plant. This information supports public health decisions by spotlighting segments of the population where outbreaks may be occurring.


Assuntos
COVID-19 , Águas Residuárias , Humanos , Fatores de Tempo , RNA Viral/genética , SARS-CoV-2/genética , Estudos Retrospectivos , COVID-19/epidemiologia , Vigilância Epidemiológica Baseada em Águas Residuárias
16.
Nat Commun ; 15(1): 8224, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300098

RESUMO

Severe febrile illnesses in children encompass life-threatening organ dysfunction caused by diverse pathogens and other severe inflammatory syndromes. A comparative approach to these illnesses may identify shared and distinct features of host immune dysfunction amenable to immunomodulation. Here, using immunophenotyping with mass cytometry and cell stimulation experiments, we illustrate trajectories of immune dysfunction in 74 children with multi-system inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2, 30 with bacterial infection, 16 with viral infection, 8 with Kawasaki disease, and 42 controls. We explore these findings in a secondary cohort of 500 children with these illnesses and 134 controls. We show that neutrophil activation and apoptosis are prominent in multi-system inflammatory syndrome, and that this is partially shared with bacterial infection. We show that memory T cells from patients with multi-system inflammatory syndrome and bacterial infection are exhausted. In contrast, we show viral infection to be characterized by a distinct signature of decreased interferon signaling and lower interferon receptor gene expression. Improved understanding of immune dysfunction may improve approaches to immunomodulator therapy in severe febrile illnesses in children.


Assuntos
COVID-19 , Neutrófilos , Síndrome de Resposta Inflamatória Sistêmica , Humanos , Criança , Neutrófilos/imunologia , COVID-19/imunologia , COVID-19/virologia , COVID-19/complicações , Masculino , Feminino , Pré-Escolar , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Febre/imunologia , SARS-CoV-2/imunologia , Lactente , Interferons/metabolismo , Infecções Bacterianas/imunologia , Linfócitos T/imunologia , Síndrome de Linfonodos Mucocutâneos/imunologia , Adolescente , Apoptose , Ativação de Neutrófilo
17.
Water Res ; 231: 119648, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36702023

RESUMO

Wastewater surveillance is a passive and efficient way to monitor the spread of infectious diseases in large populations and high transmission areas such as preK-12 schools. Infections caused by respiratory viruses in school-aged children are likely underreported, particularly because many children may be asymptomatic or mildly symptomatic. Wastewater monitoring of SARS-CoV-2 has been studied extensively and primarily by sampling at centralized wastewater treatment plants, and there are limited studies on SARS-CoV-2 in preK-12 school wastewater. Similarly, wastewater detections of influenza have only been reported in wastewater treatment plant and university manhole samples. Here, we present the results of a 17-month wastewater monitoring program for SARS-CoV-2 (n = 2176 samples) and influenza A and B (n = 1217 samples) in 51 preK-12 schools. We show that school wastewater concentrations of SARS-CoV-2 RNA were strongly associated with COVID-19 cases in schools and community positivity rates, and that influenza detections in school wastewater were significantly associated with citywide influenza diagnosis rates. Results were communicated back to schools and local communities to enable mitigation strategies to stop the spread, and direct resources such as testing and vaccination clinics. This study demonstrates that school wastewater surveillance is reflective of local infections at several population levels and plays a crucial role in the detection and mitigation of outbreaks.


Assuntos
COVID-19 , Influenza Humana , Criança , Humanos , Influenza Humana/epidemiologia , SARS-CoV-2 , Águas Residuárias , COVID-19/epidemiologia , RNA Viral , Vigilância Epidemiológica Baseada em Águas Residuárias
18.
ACS Macro Lett ; 12(5): 605-611, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37071887

RESUMO

A method for the acyclic diene metathesis polymerization of semiaromatic amides is described. The procedure uses second-generation Grubbs' catalyst and N-cyclohexyl-2-pyrrolidone (CHP), a high boiling, polar solvent capable of solubilizing both monomer and polymer. The addition of methanol to the reaction was found to significantly increase polymer molar mass although the role of the alcohol is currently not understood. Hydrogenation with hydrogen gas and Wilkinson's catalyst resulted in near-quantitative saturation. All polymers synthesized here exhibit a hierarchical semicrystalline morphology driven by ordering of aromatic amide groups via strong nonbonded interactions. Furthermore, the melting points can be tuned over a >100 °C range by precise substitution at just one of the backbone positions on each mer (<5% of the total).

19.
JTO Clin Res Rep ; 4(4): 100498, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37020927

RESUMO

Introduction: CD47 is a tumor antigen that inhibits phagocytosis leading to immune evasion. Anti-CD47 therapy is a promising new immunotherapy across numerous tumor types, but it has not been tested in thymic epithelial tumors (TETs): thymomas and thymic carcinomas. TETs are rare tumors that are difficult to treat, especially with programmed cell death protein 1/programmed death-ligand 1 checkpoint inhibitors, owing to the excessive rates of immune-related adverse events. This study investigated the levels of CD47 expression in TETs to explore the possibility of anti-CD47 therapy. Methods: A total of 67 thymic tumors (63 thymomas and 4 thymic carcinomas) and 14 benign thymus controls and their clinical data were included. Samples were stained for CD47 expression (rabbit monoclonal antibody SP279, Abcam, Waltham, MA) and scored for both intensity and H-score (intensity multiplied by the percentage of tumor involved). Intensity was defined as follows: 0 = none, 1 = weak, 2 = moderate, and 3 = strong. H-scores ranged from 0 to 300. Samples with an intensity score below 2 or an H-score below 150 were considered CD47low, whereas the rest were CD47high. Results: Compared with normal thymic tissues, TETs were more frequently CD47 positive and had significantly higher levels of CD47 expression. CD47 was positive in 79.1% of TETs compared with 57.1% of normal thymus. The level of CD47 expression was 16-fold higher in TETs (mean H-score 75.0 versus 4.6, p = 0.003). Multivariate analysis adjusted for age, sex, stage, resection status, and performance status revealed that CD47-high tumors were highly correlated with WHO histology type (p = 0.028). The most frequent CD47high tumors, in contrast to CD47low tumors, were types A (28.6% versus 7.5%) and AB (57.1% versus 13.2%), and the least frequent were B1 (7.1% versus 24.5%), B2 (0% versus 35.8%), B3 (7.1% versus 11.3%), and C (0% versus 7.5%). Conclusions: In contrast to normal thymus, TETs had significantly higher levels of CD47 expression. Tumor samples with high CD47 expression were mostly WHO types A and AB. This is the first study to explore CD47 expression in thymic cancers and lends support for ongoing investigation of anti-CD47 macrophage checkpoint inhibitor therapy in these tumors.

20.
Am J Case Rep ; 23: e936288, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35927927

RESUMO

BACKGROUND Primary retroperitoneal choriocarcinoma is a rare form of extragonadal germ cell tumor that is highly aggressive and responds poorly to chemoradiation. Extragonadal choriocarcinomas are notoriously challenging to diagnose, and have often progressed to advanced disease by the time of diagnosis. The survival rate for extragonadal choriocarcinoma is approximately 30%, which is much lower than that of extragonadal non-seminomatous germ cell tumors (GCT) in general. CASE REPORT A 24-year-old man with no significant past medical history presented with left-sided, pleuritic chest pain and back pain radiating down his left leg, of 1-year duration. Computed tomography (CT) of the chest revealed multiple bilateral pulmonary nodules and a CT of the abdomen and pelvis showed a large heterogeneous soft tissue mass measuring 9.3×8×10.5 cm. A CT-guided core needle biopsy of a lung nodule was performed and the findings were consistent with the diagnosis of metastatic choriocarcinoma. Magnetic resonance imaging (MRI) of the brain was negative for metastatic disease. Tumor markers were significant for a markedly elevated beta human chorionic gonadotropin (B-hCG) of 104 712 mIU/mL. He was diagnosed with a stage IIIC germ cell tumor, further classified as a primary retroperitoneal choriocarcinoma with lung metastasis, and was started on urgent inpatient chemotherapy. CONCLUSIONS Due to the poor outcomes associated with extragonadal choriocarcinoma, it is important to promptly and correctly identify this malignancy in order to initiate treatment in a timely manner. The following case report explores the histopathologic characterization of this malignancy and describes the clinical course and outcomes from treatment for this patient.


Assuntos
Coriocarcinoma , Neoplasias Pulmonares , Neoplasias Embrionárias de Células Germinativas , Neoplasias Retroperitoneais , Neoplasias Testiculares , Adulto , Coriocarcinoma/diagnóstico , Coriocarcinoma/patologia , Feminino , Humanos , Neoplasias Pulmonares/secundário , Masculino , Neoplasias Embrionárias de Células Germinativas/complicações , Neoplasias Retroperitoneais/patologia , Neoplasias Testiculares/patologia , Adulto Jovem
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