RESUMO
Agonists of thyroid hormone receptor ß (THR-ß) decreased LDL cholesterol (LDL-C) and triglyceride (TG) levels in human clinical trials for patients with dyslipidemia. The authors present the highly potent and selective compound ALG-055009 (14) as a potential best in class THR-ß agonist. The high metabolic stability and good permeability translated well in vivo to afford a long in vivo half-life pharmacokinetic profile with limited liability for DDI, and it overcomes certain drawbacks seen in recent clinical candidates.
RESUMO
Respiratory syncytial virus (RSV) is an RNA virus infecting the upper and lower respiratory tract and is recognized as a major respiratory health threat, particularly to older adults, immunocompromised individuals, and young children. Around 64 million children and adults are infected every year worldwide. Despite two vaccines and a new generation monoclonal antibody recently approved, no effective antiviral treatment is available. In this manuscript, we present the medicinal chemistry efforts resulting in the identification of compound 28 (JNJ-8003), a novel RSV non-nucleoside inhibitor displaying subnanomolar activity in vitro as well as prominent efficacy in mice and a neonatal lamb models.
Assuntos
Antivirais , Piridinas , Animais , Antivirais/farmacologia , Antivirais/química , Antivirais/síntese química , Humanos , Camundongos , Piridinas/farmacologia , Piridinas/química , Piridinas/síntese química , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/virologia , Relação Estrutura-Atividade , Ovinos , Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Vírus Sinciciais Respiratórios/efeitos dos fármacosRESUMO
BACKGROUND: Recurrent somatic mutations in the JAK2, CALR, and the MPL genes are noted in BCR: ABL1 negative classic myeloproliferative neoplasms (MPN) that includes polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). MATERIALS AND METHODS: Mutation profile and clinical features of MPN cases diagnosed at a tertiary care center in North India are being described. JAK2V617F mutation was screened using ARMS PCR, and CALR mutation was screened using allele-specific PCR followed by fragment analysis. MPL and JAK2 Exon 12 mutations were screened by Sanger sequencing. Some of the samples were also screened using commercial kits based on single-plex RT PCR. RESULTS: A total of 378 cases (including 124 PV, 121 ET, and 133 PMF cases) were screened over 6.5 years. JAK2V617F mutation was noted in 90.3%, 61.1%, and 69.2% of cases of PV, ET, and PMF, respectively. In PV, JAK2V617F wild-type cases were associated with a significantly lower age (44 yrs vs 54 yrs; P = 0.001), lower TLC (6.3 vs 16.9; P = 0.001), and a lower platelet count (188 × 109/L vs 435 × 109/L; P = 0.009) as compared to the JAK2V617F mutated cases. CALR and MPL mutations were noted in 17.4% and 12% and 0.8% and 5.3% of ET and PMF cases, respectively. Type 1 CALR mutations were commoner in both ET and PMF. The triple negative cases constituted 20.7% and 13.5% cases of ET and PMF, respectively. In ET, the triple negative cases were found to have a significantly lower median age of presentation (42 yrs vs 52 yrs; P = 0.001), lower median TLC (10.2 × 109/L vs 13.2 × 109/L; P = 0.024), and a higher median platelet count (1238 × 109/L vs 906 × 109/L; P = 0.001) as compared to driver genes mutated cases. In PMF, the triple negative cases were found to have a significantly lower hemoglobin level (7.9 g/dl vs 11.0 gl/dl; P = 0.001) and a significant female preponderance (P = 0.05) as compared to the mutated cases. CALR mutations were found to have a significantly lower median age (43 yrs vs 56 yrs; P = 0.001) and lower hemoglobin (9.6 g/dl vs 11.3 g/dl) as compared to the JAK2 mutations. CONCLUSION: Our data on the driver gene mutational profile of BCR: ABL1 negative MPN is one of the largest patient cohorts. The prevalence and clinicopathological features corroborate with that of other Asian studies.
RESUMO
There is an urgent need for antivirals targeting the SARS-CoV-2 virus to fight the current COVID-19 pandemic. The SARS-CoV-2 main protease (3CLpro) represents a promising target for antiviral therapy. The lack of selectivity for some of the reported 3CLpro inhibitors, specifically versus cathepsin L, raises potential safety and efficacy concerns. ALG-097111 potently inhibited SARS-CoV-2 3CLpro (IC50 = 7 nM) without affecting the activity of human cathepsin L (IC50 > 10 µM). When ALG-097111 was dosed in hamsters challenged with SARS-CoV-2, a robust and significant 3.5 log10 (RNA copies/mg) reduction of the viral RNA copies and 3.7 log10 (TCID50/mg) reduction in the infectious virus titers in the lungs was observed. These results provide the first in vivo validation for the SARS-CoV-2 3CLpro as a promising therapeutic target for selective small molecule inhibitors.
Assuntos
Amidas/farmacologia , Tratamento Farmacológico da COVID-19 , Proteases 3C de Coronavírus/antagonistas & inibidores , Inibidores de Cisteína Proteinase/farmacologia , Modelos Animais de Doenças , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/enzimologia , Amidas/farmacocinética , Animais , COVID-19/virologia , Catepsina L/antagonistas & inibidores , Linhagem Celular , Cricetinae , Inibidores de Cisteína Proteinase/farmacocinética , Feminino , Humanos , Concentração Inibidora 50 , Masculino , Mesocricetus/virologia , Reprodutibilidade dos Testes , SARS-CoV-2/crescimento & desenvolvimento , Serina Endopeptidases , Especificidade por Substrato , Replicação Viral/efeitos dos fármacosRESUMO
Thyroid hormones are important modulators of metabolic activity in mammals and alter cholesterol and fatty acid levels through activation of the nuclear thyroid hormone receptor (THR). Currently, there are several THRß agonists in clinical trials for the treatment of non-alcoholic steatohepatitis (NASH) that have demonstrated the potential to reduce liver fat and restore liver function. In this study, we tested three THRß-agonism-based NASH treatment candidates, GC-1 (sobetirome), MGL-3196 (resmetirom), and VK2809, and compared their selectivity for THRß and their ability to modulate the expression of genes specific to cholesterol and fatty acid biosynthesis and metabolism in vitro using human hepatic cells and in vivo using a rat model. Treatment with GC-1 upregulated the transcription of CPT1A in the human hepatocyte-derived Huh-7 cell line with a dose-response comparable to that of the native THR ligand, triiodothyronine (T3). VK2809A (active parent of VK2809), MGL-3196, and VK2809 were approximately 30-fold, 1,000-fold, and 2,000-fold less potent than T3, respectively. Additionally, these relative potencies were confirmed by quantification of other direct gene targets of THR, namely, ANGPTL4 and DIO1. In primary human hepatocytes, potencies were conserved for every compound except for VK2809, which showed significantly increased potency that was comparable to that of its active counterpart, VK2809A. In high-fat diet fed rats, a single dose of T3 significantly reduced total cholesterol levels and concurrently increased liver Dio1 and Me1 RNA expression. MGL-3196 treatment resulted in concentration-dependent decreases in total and low-density lipoprotein cholesterol with corresponding increases in liver gene expression, but the compound was significantly less potent than T3. In conclusion, we have implemented a strategy to rank the efficacy of THRß agonists by quantifying changes in the transcription of genes that lead to metabolic alterations, an effect that is directly downstream of THR binding and activation.
Assuntos
Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Receptores beta dos Hormônios Tireóideos/agonistas , Transcrição Gênica/efeitos dos fármacos , Acetatos/farmacologia , Acetatos/uso terapêutico , Proteína 4 Semelhante a Angiopoietina/metabolismo , Animais , Linhagem Celular Tumoral , LDL-Colesterol/sangue , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Hepatócitos , Humanos , Iodeto Peroxidase/genética , Iodeto Peroxidase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Malato Desidrogenase/genética , Malato Desidrogenase/metabolismo , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Organofosfonatos/farmacologia , Organofosfonatos/uso terapêutico , Fenóis/farmacologia , Fenóis/uso terapêutico , Cultura Primária de Células , Piridazinas/farmacologia , Piridazinas/uso terapêutico , Ratos , Uracila/análogos & derivados , Uracila/farmacologia , Uracila/uso terapêuticoRESUMO
Chronic hepatitis C (CHC) is a major liver disease caused by the hepatitis C virus. The current standard of care for CHC can achieve cure rates above 95%; however, the drugs in current use are administered for a period of 8-16 weeks. A combination of safe and effective drugs with a shorter treatment period is highly desirable. We report synthesis and biological evaluation of a series of 2',3'- and 2',4'-substituted guanosine nucleotide analogues. Their triphosphates exhibited potent inhibition of the HCV NS5B polymerase with IC50 as low as 0.13 µM. In the HCV replicon assay, the phosphoramidate prodrugs of these analogues demonstrated excellent activity with EC50 values as low as 5 nM. A lead compound AL-611 showed high levels of the nucleoside 5'-triphosphate in vitro in primary human hepatocytes and in vivo in dog liver following oral administration.
Assuntos
Antivirais/farmacologia , RNA Polimerases Dirigidas por DNA/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Nucleotídeos de Guanina/farmacologia , Hepacivirus/efeitos dos fármacos , Pró-Fármacos/farmacologia , Animais , Antivirais/síntese química , Antivirais/toxicidade , Cães , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/toxicidade , Feminino , Nucleotídeos de Guanina/síntese química , Nucleotídeos de Guanina/toxicidade , Humanos , Masculino , Pró-Fármacos/síntese química , Pró-Fármacos/toxicidade , Proteínas não Estruturais Virais/antagonistas & inibidores , Replicação Viral/efeitos dos fármacosRESUMO
Juvenile xanthogranulomas (JXG) are the most common type of self-limiting non-Langerhans cell histiocytosis (LCH) usually presenting in infancy and early childhood. Clinically, they present as solitary to multiple rounded cutaneous nodules which resolve over time. Adult type xanthogranulomas (AXG), though histologically similar to JXG, are usually single and do not regress spontaneously. AXG arising in the external auditory canal (EAC) is a rare occurrence with very few cases reported in literature. We present a case of AXG in a 48-year-old man, arising from the right EAC. This case is unique as it is the only case to be described with both cytology and histology correlation. On cytology, smears showed scattered foamy histiocytes, inflammatory cells and thick stromal fragments. Cytology differential diagnoses of xanthomatous lesion, benign fibrous histiocytoma (BFH) and ceruminous adenoma were given; final diagnosis was deferred to histopathology which confirmed it to be an AXG. Thus, it is important to keep the diagnosis of AXG in mind while dealing with solitary polypoidal lesions in EAC showing prominent foam cell component. Lipidised BFH forms a close differential diagnosis, however can be excluded by subtle points on cytology and on histopathology.
Assuntos
Meato Acústico Externo/patologia , Otopatias/patologia , Histiocitose de Células não Langerhans/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Background: AL-794 is an orally active prodrug of ALS-033719, which selectively inhibits the endonuclease domain of influenza virus A and B polymerase. Methods: In a phase 1, double-blinded, randomized, placebo-controlled study, healthy subjects were inoculated intranasally with influenza virus (A/Perth/16/2009 H3N2) after confirmation of infection or on day 4. Subjects received 50 mg of AL-794, 150 mg of AL-794, or placebo twice daily for 5 days. Viral load, influenza symptoms, pharmacokinetics, and safety were evaluated. Results: A total of 61 subjects were inoculated. In 42 infected subjects, the mean peak viral load for 50-mg AL-794 recipients, 150-mg AL-794 recipients, and placebo recipients was 3.54, 2.77, and 3.72 log10 50% tissue culture infectious doses (TCID50)/mL, respectively. The mean influenza viral load area under the curve in the corresponding treatment groups was 137, 87.5, and 142 log10 TCID50/mL·h, respectively, and the median time to virus nondetection was 117, 75.3, and 108 hours, respectively. AL-794 was well tolerated, and no viral resistance to ALS-033719 was identified. Conclusion: Following oral administration of AL-794, significant dose-dependent antiviral activity was noted, with a greater decrease in viral load, symptoms, and mucus weight at the 150-mg dose, compared with the 50-mg dose, and no safety concerns for either dose or placebo. Clinical Trials Registration: NCT02588521.
Assuntos
Antivirais/farmacologia , Antivirais/uso terapêutico , Endonucleases/antagonistas & inibidores , Influenza Humana/tratamento farmacológico , Serina Endopeptidases/farmacologia , Serina Endopeptidases/uso terapêutico , Administração Oral , Adolescente , Adulto , Antivirais/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/enzimologia , Masculino , Pessoa de Meia-Idade , Carga Viral/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: This double-blind, first-in-human Phase I study evaluated pharmacokinetics, safety and tolerability of AL-794 (prodrug of ALS-033719), a potent endonuclease inhibitor of influenza A and B in healthy volunteers. METHODS: Healthy adult volunteers were randomized to AL-794 (50-2,000 mg single ascending doses, fasting) or placebo (5 cohorts, n=6:2 AL-794: placebo/cohort) in part 1, and AL-794 (50-600 mg multiple ascending doses, twice-daily, fed or fasted) or placebo (3 cohorts, n=8:2 AL-794: placebo/cohort) for 7 days in part 2. In part 3, 8 healthy volunteers from part 1 received 450 mg AL-794 (n=6) or placebo (n=2) following a high-fat meal. All dosing was done with an oral suspension. Blood and urine samples for pharmacokinetics were collected at scheduled times and analysed for ALS-033719 and ALS-033927 (inactive glucuronide) plasma concentrations using LC-MS/MS. RESULTS: ALS-033719 plasma concentrations increased dose proportionately up to 150 mg but less than proportionately above 150 mg. Steady-state was generally achieved by the third dose. ALS-033719 exposure increased following administration with a standard meal (19%-33%) or high-fat meal (3-3.6-fold). ALS-033927 was the major metabolite observed. Renal elimination was negligible (0.2%). Seventeen AL-794-treated healthy volunteers reported ≥1 treatment-emergent adverse event (TEAE; part 1: n=6, 24%; part 2: n=11, 69%). The most common TEAEs were headache (part 1: n=3; part 2: n=5) and dizziness (part 1: n=2; part 2: n=6). CONCLUSIONS: AL-794 up to 200 mg twice daily achieved ALS-033719 exposures which are expected to be efficacious and were generally tolerated. Further studies are planned to characterize safety and antiviral activity.
Assuntos
Antivirais/farmacocinética , Inibidores Enzimáticos/farmacocinética , Serina Endopeptidases/farmacocinética , Administração Oral , Adulto , Antivirais/efeitos adversos , Antivirais/sangue , Área Sob a Curva , Tontura/diagnóstico , Tontura/etiologia , Método Duplo-Cego , Esquema de Medicação , Endonucleases/antagonistas & inibidores , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/sangue , Jejum , Cefaleia/diagnóstico , Cefaleia/etiologia , Voluntários Saudáveis , Humanos , Influenza Humana/prevenção & controle , Masculino , Segurança do Paciente , Serina Endopeptidases/efeitos adversos , Serina Endopeptidases/sangue , Proteínas Virais/antagonistas & inibidoresRESUMO
Herein we describe the discovery of IDX21437 35b, a novel RPd-aminoacid-based phosphoramidate prodrug of 2'-α-chloro-2'-ß-C-methyluridine monophosphate. Its corresponding triphosphate 6 is a potent inhibitor of the HCV NS5B RNA-dependent RNA polymerase (RdRp). Despite showing very weak activity in the in vitro Huh-7 cell based HCV replicon assay, 35b demonstrated high levels of active triphosphate 6 in mouse liver and human hepatocytes. A biochemical study revealed that the metabolism of 35b was mainly attributed to carboxyesterase 1 (CES1), an enzyme which is underexpressed in HCV Huh-7-derived replicon cells. Furthermore, due to its metabolic activation, 35b was efficiently processed in liver cells compared to other cell types, including human cardiomyocytes. The selected RP diastereoisomeric configuration of 35b was assigned by X-ray structural determination. 35b is currently in Phase II clinical trials for the treatment of HCV infection.
Assuntos
Antivirais/farmacologia , RNA Polimerases Dirigidas por DNA/antagonistas & inibidores , Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Hepacivirus/efeitos dos fármacos , Uridina Monofosfato/análogos & derivados , Uridina/farmacologia , Animais , Antivirais/síntese química , Antivirais/química , RNA Polimerases Dirigidas por DNA/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Hepacivirus/enzimologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/virologia , Humanos , Fígado/efeitos dos fármacos , Fígado/virologia , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Uridina/síntese química , Uridina/química , Uridina Monofosfato/síntese química , Uridina Monofosfato/química , Uridina Monofosfato/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/metabolismoAssuntos
Hanseníase Virchowiana/diagnóstico , Mycobacterium leprae/isolamento & purificação , Pele/patologia , Coloração e Rotulagem , Adulto , Biópsia por Agulha Fina , Feminino , Humanos , Inflamação , Hanseníase Virchowiana/microbiologia , Hanseníase Virchowiana/patologia , Macrófagos/patologia , Mycobacterium leprae/ultraestrutura , Pele/citologia , Pele/imunologia , Pele/microbiologia , SupuraçãoRESUMO
We present a rare case of a 30-year-old woman who presented with a swelling on the lateral aspect of her left forearm, present since 6 months, adjacent to a 16-year-old burn scar. X-ray of elbow joint and forearm revealed the subcutaneous nature of the swelling. Giemsa and periodic acid-Schiff-stained smears and potassium hydroxide mount of fine-needle aspirate of the swelling revealed dematiaceous, branching, and septate fungal hyphae. Fungal culture of the aspirated pus showed growth of Exophiala jeanselmei. Histopathological examination revealed brown-coloured hyphae with foreign body giant cell reaction and palisading granulomas in the surrounding tissue. The patient was successfully treated with surgical excision of the swelling. All the cases of phaeohyphomycosis due to Exophiala spp. in India are also reviewed.
Assuntos
Dermatomicoses/cirurgia , Exophiala/isolamento & purificação , Feoifomicose/cirurgia , Adulto , Queimaduras/microbiologia , Cicatriz/microbiologia , Dermatomicoses/diagnóstico , Dermatomicoses/microbiologia , Feminino , Humanos , Índia , Feoifomicose/diagnóstico , Feoifomicose/microbiologiaRESUMO
IDX184 is a phosphoramidate prodrug of 2'-methylguanosine-5'-monophosphate, developed to treat patients infected with hepatitis C virus. A mass balance study of radiolabeled IDX184 and pharmacokinetic studies of IDX184 in portal vein-cannulated monkeys revealed relatively low IDX184 absorption but higher exposure of IDX184 in the portal vein than in the systemic circulation, indicating >90 % of the absorbed dose was subject to hepatic extraction. Systemic exposures to the main metabolite, 2'-methylguanosine (2'-MeG), were used as a surrogate for liver levels of the pharmacologically active entity 2'-MeG triphosphate, and accordingly, systemic levels of 2'-MeG in the monkey were used to optimize formulations for further clinical development of IDX184. Capsule formulations of IDX184 delivered acceptable levels of 2'-MeG in humans; however, the encapsulation process introduced low levels of the genotoxic impurity ethylene sulfide (ES), which necessitated formulation optimization. Animal pharmacokinetic data guided the development of a tablet with trace levels of ES and pharmacokinetic performance equal to that of the clinical capsule in the monkey. Under fed conditions in humans, the new tablet formulation showed similar exposure to the capsule used in prior clinical trials.
Assuntos
Guanosina Monofosfato/análogos & derivados , Guanosina/análogos & derivados , Fígado/efeitos dos fármacos , Pró-Fármacos/administração & dosagem , Pró-Fármacos/farmacocinética , Animais , Cápsulas/administração & dosagem , Cápsulas/farmacocinética , Química Farmacêutica/métodos , Guanosina/administração & dosagem , Guanosina/farmacocinética , Guanosina Monofosfato/administração & dosagem , Guanosina Monofosfato/farmacocinética , Haplorrinos , Humanos , Masculino , Comprimidos/administração & dosagem , Comprimidos/farmacocinéticaRESUMO
A conventional, rapid and high throughput method for tissue extraction and accurate and selective LC-MS/MS quantification of 2'-C-methylguanosine triphosphate (2'-MeGTP) in mouse liver was developed and qualified. Trichloroacetic acid (TCA) was used as the tissue homogenization reagent that overcomes instability challenges of liver tissue nucleotide triphosphates due to instant ischemic degradation to mono- and diphosphate nucleotides. Degradation of 2'-MeGTP was also minimized by harvesting livers using in situ clamp-freezing or snap-freezing techniques. The assay also included a sample clean-up procedure using weak anion exchange solid phase extraction followed by ion exchange chromatography and tandem mass spectrometry detection. The linear assay range was from 50 to 10000 pmol/mL concentration in liver homogenate (250-50000 pmol/g in liver tissue). The method was qualified over three intraday batches for accuracy, precision, selectivity and specificity. The assay was successfully applied to pharmacokinetic studies of 2'-MeGTP in liver tissue samples after single oral doses of IDX184, a nucleotide prodrug inhibitor of the viral polymerase for the treatment of hepatitis C, to mice. The study results suggested that the clamp-freezing liver collection method was marginally more effective in preventing 2'-MeGTP degradation during liver tissue collection compared to the snap-freezing method.
Assuntos
Guanosina Monofosfato/análogos & derivados , Guanosina Trifosfato/metabolismo , Guanosina/análogos & derivados , Fígado/metabolismo , Nucleotídeos/metabolismo , Pró-Fármacos/metabolismo , Animais , Antivirais/metabolismo , Antivirais/farmacocinética , Cromatografia por Troca Iônica/métodos , Cromatografia Líquida/métodos , Congelamento , Guanosina/metabolismo , Guanosina/farmacocinética , Guanosina Monofosfato/metabolismo , Guanosina Monofosfato/farmacocinética , Guanosina Trifosfato/análogos & derivados , Hepatite C/tratamento farmacológico , Masculino , Camundongos , Pró-Fármacos/farmacocinética , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Ácido Tricloroacético/químicaRESUMO
Gall bladder carcinoma is the most common cancer of biliary tree, characterized by rapid progression and a very high mortality rate. Detection at an early stage, however, is indicative of a very good prognosis and prolonged survival. The practice of histopathological examination of gall bladder specimens removed for clinically benign conditions and its usefulness has been a subject of controversy. The present prospective study was carried out over a period of four years in order to find out the incidence of unsuspected gallbladder carcinoma in cholecystectomy specimens received in our histopathology laboratory and to analyze their clinico-pathological features. A total of 4,115 cases were examined. Incidentally detected cases comprised 0.44%, which accounted for 72% of all gall bladder carcinomas detected. The majority were in an early, surgically resectable stage. From the results of this study we recommend that in India and other countries with relatively high incidences of gall bladder carcinoma, all cholecystectomy specimens should be submitted to histopathology laboratory, as this is the only means by which malignancies can be detected at an early, potentially curable stage.
Assuntos
Adenocarcinoma/diagnóstico , Carcinoma Adenoescamoso/diagnóstico , Colecistectomia , Diagnóstico Precoce , Neoplasias da Vesícula Biliar/diagnóstico , Vesícula Biliar/patologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoescamoso/epidemiologia , Carcinoma Adenoescamoso/cirurgia , Feminino , Seguimentos , Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Técnicas Imunoenzimáticas , Incidência , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos ProspectivosRESUMO
Congenital mesoblastic nephroma is a stromal neoplasm of infancy. It has been referred to as mesenchymal, cystic or leiomyomatous hamartoma. These tumors are centered around the hilus of the kidney. Mesoblastic nephromas need to be distinguished from other pediatric renal neoplasms as these lesions are treated by complete surgical excision without chemotherapy unless gross residual tumor remains. Here, we describe the gross and microscopic features of mesoblastic nephroma in a twenty-day old infant.