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1.
Cureus ; 15(9): e45658, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37868568

RESUMO

Tumour-to-tumour metastases (TTM) are a rare phenomenon in which a primary tumour has metastasised within another distant primary tumour. We present the case of a 63-year-old female who presented with right-sided breast cancer. An incidental left-sided renal mass was detected on staging CT of the thorax, abdomen, and pelvis (CT-TAP). The patient had no evidence of metastases below the diaphragm. Histology following a radical left nephrectomy revealed metastatic breast cancer within a renal cell carcinoma (RCC). The patient underwent chemotherapy and surgery for right-sided breast cancer. Follow-up imaging demonstrated the metastatic spread of the breast cancer. This is an unusual case of TTM from breast to an initially occult RCC primary.

2.
J Clin Pathol ; 74(11): 718-723, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33122190

RESUMO

OBJECTIVE: To compare the whole genomes sequencing (WGS) results in the 100K Genomes project with the results of routine molecular diagnostics in precision medicine. MATERIALS AND METHODS: We analysed 374 cancers including a high tumour mutational burden (TMB-high) subgroup, defined as >10 non-synonymous single nucleotide variations per megabase. Colon cancers were evaluated for microsatellite instability (MSI), mismatch repair (MMR) genes and NRAS, KRAS and BRAF mutations using routine molecular diagnostics. Fluorescence in-situ hybridisation/immunohistochemistry was used to evaluate the Her2Neu status in breast cancers. RESULTS: There was high correlation between WGS and routine diagnostic testing results irrespective of TMB status in colon cancers. Her2Neu status was discordant in 3 out of the 5 TMB-high breast cancers (p=0.049). The presence of ductal carcinoma in-situ correlated significantly with discordance (p=0.04). There were 3 (5%) discordant colorectal cases, all in the KRAS gene, 2 of which were from the non-invasive adenomatous component (p=0.0058). Of the 374 cases we identified 24 tumours with a TMB >10; comprising (colorectal carcinomas (CRCs) n=16, breast carcinomas n=5, bladder urothelial cell cancers n=3). Of the 16 TMB-high colorectal adenocarcinomas, 13 had MSI-high status. The same 13 had defective MMR protein expression. TMB-high colorectal cancers had 100% concordant results between WGS and NGS testing for KRAS, BRAF and NRAS (16/16). CONCLUSION: The microsatellite and mutational status of colorectal cancers evaluated by WGS seem to correlate well with the routine diagnostic testing if it is ensured that the invasive component is sequenced. Evaluation of WGS results need to be carefully correlated with histomorphology, as tumour heterogeneity/contamination with pre-malignant components needs to be taken into account.


Assuntos
Neoplasias/genética , Medicina de Precisão , Sequenciamento Completo do Genoma , Biomarcadores Tumorais/genética , Reparo de Erro de Pareamento de DNA , Feminino , Genes erbB-2 , Genes ras/genética , Humanos , Masculino , Instabilidade de Microssatélites , Mutação , Gradação de Tumores , Patologia Molecular , Medicina de Precisão/métodos
3.
Cell ; 180(5): 895-914.e27, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32142680

RESUMO

A safe and controlled manipulation of endocytosis in vivo may have disruptive therapeutic potential. Here, we demonstrate that the anti-emetic/anti-psychotic prochlorperazine can be repurposed to reversibly inhibit the in vivo endocytosis of membrane proteins targeted by therapeutic monoclonal antibodies, as directly demonstrated by our human tumor ex vivo assay. Temporary endocytosis inhibition results in enhanced target availability and improved efficiency of natural killer cell-mediated antibody-dependent cellular cytotoxicity (ADCC), a mediator of clinical responses induced by IgG1 antibodies, demonstrated here for cetuximab, trastuzumab, and avelumab. Extensive analysis of downstream signaling pathways ruled out on-target toxicities. By overcoming the heterogeneity of drug target availability that frequently characterizes poorly responsive or resistant tumors, clinical application of reversible endocytosis inhibition may considerably improve the clinical benefit of ADCC-mediating therapeutic antibodies.


Assuntos
Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/imunologia , Neoplasias/tratamento farmacológico , Proclorperazina/farmacologia , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados/farmacologia , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Apresentação de Antígeno/efeitos dos fármacos , Biópsia , Cetuximab/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Resistencia a Medicamentos Antineoplásicos/genética , Endocitose/efeitos dos fármacos , Endocitose/imunologia , Xenoenxertos , Humanos , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Células MCF-7 , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Camundongos , Neoplasias/genética , Neoplasias/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Trastuzumab/farmacologia
5.
Int J STD AIDS ; 27(4): 296-304, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25887063

RESUMO

Chorioamnionitis is an important risk factor for vertical transmission of HIV/AIDS. We compared the prevalence and correlates of histologic chorioamnionitis (HCA) in HIV-positive and HIV-negative pregnant women. HIV-positive and -negative parturients were interviewed, examined and had their placentas examined histologically for chorioamnionitis. Data regarding HIV were also retrieved from their hospital records. A total of 298 parturients (150 HIV positive and 148 HIV negative) were enrolled. The two groups were similar in socio-demographic and obstetric parameters except for age. The prevalence of HCA was 57.1% in HIV-positive women and 61.6% in HIV-negative women (p = 0.43). HCA staging was associated with the number of intrapartum vaginal examinations in HIV-positive subjects and nulliparity in HIV-negative subjects. The number of intrapartum vaginal examinations and coitus in the week prior to delivery significantly affected the grade of HCA in HIV-negative subjects. The prevalence of HCA in both HIV-positive and HIV-negative is high. Most variables did not affect the occurrence of HCA in both groups studied except number of intrapartum examinations, coitus in the preceding one week and nulliparity, which were related to severity of the disease.


Assuntos
Corioamnionite/epidemiologia , Infecções por HIV/complicações , Soronegatividade para HIV , HIV-1 , Resultado da Gravidez , Corioamnionite/patologia , Feminino , Ruptura Prematura de Membranas Fetais/epidemiologia , Soropositividade para HIV , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Placenta/patologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia
6.
J Natl Med Assoc ; 100(6): 713-5, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18595574

RESUMO

Rhinosporidiosis is a rare chronic granulomatous infection caused by Rhinosporidium seeberi. It affects mainly the mucosa of the nose, nasopharynx, palate, conjunctiva and the urethra. A seven-year-old girl presented with intranasal polypoid growth with recurrent nose bleeding for one year. Excision biopsy was done, and the tissue was subjected to routine histological processing and stained with hematoxylin and eosin stains with additional mucicarmine special stain. Variable-sized sporangia containing magenta-colored spores and capsule were observed. We hereby present a rare infective disease diagnosed nine years after the first reported case in our center.


Assuntos
Pólipos Nasais/parasitologia , Rinosporidiose/parasitologia , Rhinosporidium/isolamento & purificação , Animais , Criança , Epistaxe/etiologia , Feminino , Humanos , Microscopia , Obstrução Nasal/etiologia , Pólipos Nasais/complicações , Pólipos Nasais/patologia , Pólipos Nasais/cirurgia , Nigéria , Rinosporidiose/complicações , Rinosporidiose/patologia , Rinosporidiose/cirurgia , Rhinosporidium/ultraestrutura
7.
J Natl Med Assoc ; 98(11): 1763-6, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17128685

RESUMO

OBJECTIVE: Studies of frequency of occurrence of diabetic neuropathy are few, and available studies were limited to the southern part of Nigeria. The objectives of the study were to determine the frequency of occurrence and grades of diabetes peripheral neuropathy using clinical measures. PATIENTS AND METHODS: Consecutive patients with diabetes mellitus attending the Jos University Teaching Hospital were recruited as the study population, including 120 diabetics and 60 age-matched, nondiabetic controls. A standard proforma based on the Michigan Neuropathy Screening Instrument (MNSI) was employed to screen for diabetic neuropathy. RESULTS: The frequency of occurrence of diabetic peripheral neuropathy was 75%. For the specific types of peripheral neuropathy, sensorimotor neuropathy was the commonest (40.4%, chi(2)=29.1; p<0.001). There was no significant difference, with severity of peripheral neuropathy among diabetics, when compared by gender. (Chi square=3.03, P value=0.081). CONCLUSION: The frequency of occurrence of peripheral neuropathy among diabetics in Jos University Teaching Hospital from this study is rather high.


Assuntos
Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/epidemiologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia
8.
Trop Doct ; 36(4): 228-31, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17034701

RESUMO

Multi-organ involvement by opportunistic infections and neoplasms is the major cause of morbidity and mortality in people living with HIV/AIDS. We determined the spectrum/frequency of hepatic histopathological lesions in a prospective study of postmortem liver biopsies from 100 patients (50 females and 50 males, age range 18-55 years) who died from HIV/AIDS in Jos university teaching hospital, Nigeria. The majority of the patients, 65 (65%), had clinical tuberculosis. Granulomatous hepatitis, chronic hepatitis, non-specific reactive hepatitis (NSRH) and steatosis were the commonest hepatic histopathologic lesions occurring in 34, 20,15 and 12% of patients, respectively. Seven (7%) had normal histological features. This study shows that the liver is affected in HIV/AIDS as reported elsewhere in the world. Therefore, liver biopsy in HIV patients may be helpful in the management of these patients.


Assuntos
Autopsia , Infecções por HIV/complicações , Hospitais de Ensino , Hospitais Universitários , Hepatopatias/patologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/patologia , Adolescente , Adulto , Biópsia , Feminino , Infecções por HIV/patologia , Humanos , Fígado , Hepatopatias/diagnóstico , Masculino , Pessoa de Meia-Idade
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