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1.
J Helminthol ; 98: e25, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38509855

RESUMO

Schistosomiasis is a serious health issue in tropical regions, and natural compounds have gained popularity in medical science. This study investigated the potential effects of pumpkin seed oil (PSO) on Biomphalaria [B.] alexandrina snails (Ehrenberg, 1831), Schistosoma [S.] mansoni (Sambon, 1907) miracidium, and cercariae. The chemical composition of PSO was determined using gas chromatography/mass spectrometry. A bioassay was performed to evaluate the effects of PSO on snails, miracidia, and cercariae. The results showed no significant mortality of B. alexandrina snails after exposure to PSO, but it caused morphological changes in their hemocytes at 1.0 mg/ml for 24 hours. PSO exhibited larvicidal activity against miracidia after 2 hours of exposure at a LC50 of 618.4 ppm. A significant increase in the mortality rate of miracidia was observed in a dose- and time-dependent manner, reaching a 100% death rate after 10 minutes at LC90 and 15 minutes at LC50 concentration. PSO also showed effective cercaricidal activity after 2 hours of exposure at a LC50 of 290.5 ppm. Histological examination revealed multiple pathological changes in the digestive and hermaphrodite glands. The PSO had genotoxic effects on snails, which exhibited a significant increase [p≤0.05] in comet parameters compared to the control. The findings suggest that PSO has potential as a molluscicide, miracidicide, and cercaricide, making it a possible alternative to traditional molluscicides in controlling schistosomiasis.


Assuntos
Biomphalaria , Cucurbita , Moluscocidas , Esquistossomose , Animais , Schistosoma mansoni , Caramujos , Cercárias , Moluscocidas/farmacologia , Óleos de Plantas/farmacologia
2.
J Rheumatol ; 51(5): 452-461, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38359941

RESUMO

OBJECTIVE: This real-world analysis assessed baseline demographics/characteristics and treatment patterns/effectiveness in patients with rheumatoid arthritis (RA) initiating tofacitinib (TOF) in the US CorEvitas RA Registry. METHODS: The primary analysis of this study included patients with RA initiating TOF with a 12-month follow-up visit from November 2012 to January 2021. Outcomes included baseline demographics/characteristics and TOF initiation/discontinuation reasons, treatment patterns, and effectiveness (disease activity and patient-reported outcomes [PROs] at 12 months); the primary effectiveness outcome was Clinical Disease Activity Index low disease activity (CDAI LDA). All data, analyzed descriptively, were stratified by TOF regimen (monotherapy vs combination therapy), line of therapy (second- to fourth-line), time of initiation (2012-2014, 2015-2017, or 2018-2020), and dose (5 mg twice daily vs 11 mg once daily). RESULTS: Of 2874 patients with RA who initiated TOF, 1298 had a qualifying 12-month follow-up visit; of these, 43.1% were monotherapy and 66.5% were fourth-line therapy. Overall, tumor necrosis factor inhibitors (40.8%) were the most common treatment immediately prior to TOF initiation. The most common reason for TOF initiation (among those with a reason) was lack/loss of efficacy of prior treatment (67.7%). Overall, at 12 months, 31.9% and 10.1% had achieved CDAI LDA and remission, respectively; 22.4%, 10.4%, and 5% had achieved ≥ 20%, ≥ 50%, and ≥ 70% improvement in modified American College of Rheumatology core set measures, respectively; and improvements in PROs were observed. Effectiveness was generally similar across TOF stratifications. CONCLUSION: TOF effectiveness (CDAI LDA) was observed in a US real-world setting of patients with RA regardless of TOF regimen, line of therapy, time of initiation, and dose. (ClinicalTrials.gov: NCT04721808).


Assuntos
Antirreumáticos , Artrite Reumatoide , Piperidinas , Pirimidinas , Sistema de Registros , Humanos , Artrite Reumatoide/tratamento farmacológico , Pirimidinas/uso terapêutico , Piperidinas/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Resultado do Tratamento , Idoso , Adulto , Inibidores de Proteínas Quinases/uso terapêutico , Medidas de Resultados Relatados pelo Paciente , Índice de Gravidade de Doença , Quimioterapia Combinada
3.
Braz. j. biol ; 842024.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469279

RESUMO

Abstract Maydis leaf blight, caused by Bipolaris maydis, is an important disease of maize crop in Khyber Pakhtunkhwa (KP) Pakistan. Fifteen isolates of the pathogen, collected across KP, were studied for variability based on phenotypic and molecular markers. Significant variability among the isolates was observed when assessed using phenotypic traits such as radial growth, spore concentration, fungicide sensitivity and virulence. The isolates were classified into six culture groups based on colour, texture and margins of the colony. Conidial morphology was also variable. These were either straight or slightly curved and light to dark brown in colour. Fungicide test showed significant variation in the degree of sensitivity against Carbendazim. Isolate Bm8 exhibited maximum radial growth on carbendazim spiked plates. Conversely, isolate Bm15 showed the lowest radial growth. Variations in virulence pattern of the isolates were evident when a susceptible maize variety Azam was inoculated with spores of B. maydis. Genetic variability amongst the isolates was also estimated by RAPD as well as sequencing of ITS region. The RAPD dendrogram grouped all the isolates into two major clusters. Average genetic distance ranged from 0.6% to 100%, indicating a diverse genetic gap among the isolates. Maximum genetic distance was found between isolates Bm9 and Bm10 as well as Bm2 and Bm8. Conversely, isolates Bm13 and Bm15 were at minimum genetic distance. Phylogenetic dendrogram based on sequencing of ITS region grouped all the isolates into a single major cluster. The clusters in both the dendrogram neither correlate to the geographical distribution nor to the morphological characteristics.


Resumo A ferrugem das folhas de maydis, causada por Bipolaris maydis, é uma doença importante da cultura do milho em Khyber Pakhtunkhwa (KP), Paquistão. Quinze isolados do patógeno, coletados em KP, foram estudados quanto à variabilidade com base em marcadores fenotípicos e moleculares. Variabilidade significativa entre os isolados foi observada quando avaliada por meio de características fenotípicas, como crescimento radial, concentração de esporos, sensibilidade a fungicida e virulência. Os isolados foram classificados em seis grupos de cultura com base na cor, textura e margens da colônia. A morfologia dos conídios também foi variável. Estes eram retos ou ligeiramente curvos e de cor marrom-claro a escuro. O teste de fungicida mostrou variação significativa no grau de sensibilidade ao carbendazim. O isolado Bm8 exibiu crescimento radial máximo em placas com adição de carbendazim. Por outro lado, o isolado Bm15 apresentou o menor crescimento radial. As variações no padrão de virulência dos isolados foram evidentes quando uma variedade de milho suscetível Azam foi inoculada com esporos de B. maydis. A variabilidade genética entre os isolados também foi estimada por RAPD, bem como sequenciamento da região ITS. O dendrograma RAPD agrupou todos os isolados em dois grupos principais. A distância genética média variou de 0,6% a 100%, indicando uma lacuna genética diversa entre os isolados. A distância genética máxima foi encontrada entre os isolados Bm9 e Bm10 e também entre Bm2 e Bm8. Por outro lado, os isolados Bm13 e Bm15 estavam a uma distância genética mínima. O dendrograma filogenético baseado no sequenciamento da região ITS agrupou todos os isolados em um único aglomerado principal. Os agrupamentos em ambos os dendrogramas não se correlacionam com a distribuição geográfica nem com as características morfológicas.

4.
J Neurosurg Spine ; 39(5): 682-689, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37728375

RESUMO

OBJECTIVE: The authors sought to determine how the temporal proximity of lumbar epidural spinal injection prior to surgery impacts clinical outcomes (e.g., 30-day readmission, postoperative complications, CSF leak) in patients undergoing lumbar decompression without fusion. METHODS: The authors queried their institutional registry to identify patients who underwent elective lumbar decompression for spondylotic pathology between January 2019 and March 2022 at multiple centers within the same hospital network. Patients were divided into groups based on the time between their surgical date and the most recent preoperative spinal injection: group 1, patients with duration < 1 month; group 2, 1-3 months; and group 3, no spinal injection within 3 months. Primary outcomes of interest were the length of hospital stay, postoperative complications, rate of intraoperative CSF leak, and rates of reoperation and hospital readmission. For patients in groups 1 and 2, the authors also recorded the number of injections within 12 months prior to surgery to better understand the effect of multiple recent injections. The independent Student t-test and Pearson's chi-square test were mainly performed for univariate analyses of the continuous and categorical variables, respectively. RESULTS: A total of 121 and 283 patients received a spinal injection at < 1 month and 1-3 months prior to surgery, respectively, and were separately matched in a 3:1 ratio with 2562 patients with no history of preoperative spinal injection within 3 months before surgery. Among the matched cohorts, patients who received spinal injections < 1 month before lumbar decompression had significantly higher risks of 30-day complication (7.4% vs 0.8%, OR 9.6, p < 0.001), 30-day readmission (5.8% vs 2.2%, OR 3.5, p = 0.049), and 90-day readmission (9.1% vs 2.8%, OR 3.5, p = 0.003) than patients with no history of spinal injection. However, compared with patients with no history of spinal injection, the patients who received spinal injections 1-3 months before surgery were not at higher risk for postoperative complications or readmission. The CSF leak rates were significantly different between the three patient cohorts (10.7% vs 6.7% vs 4.9% for the < 1 month, 1-3 months, and no injection cohorts, respectively; p = 0.02). CONCLUSIONS: Lumbar decompression within 1 month of preoperative spinal injection was associated with higher risks of readmission and postoperative complications, including CSF leak. However, with the exception of CSF leak, these risks were no longer observed when spinal injection occurred 1-3 months prior to lumbar decompression.


Assuntos
Descompressão Cirúrgica , Fusão Vertebral , Humanos , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Vértebras Lombares/cirurgia , Injeções Espinhais
5.
Mymensingh Med J ; 31(4): 1192-1196, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36189571

RESUMO

Neuroendocrine tumor of the gallbladder is a rare gallbladder tumor with aggressive behavior and poor prognosis. Cholelithiasis is the most important risk factor for it. The clinical presentations of most patients are non-specific and vague abdominal pain is the most common initial symptom followed by cholecystitis, with obstructive jaundice, weight loss, ascites, pruritus or palpable mass and occasional associated endocrine manifestations. Surgery remains the main cornerstone for it. In January 2019, in the department of Hepatobiliary, Pancreatic and Liver transplant surgery in Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, a 30-year-old female presented with incidental finding of gallbladder mass. Extended cholecystectomy was performed. Histopathology examination revealed small cell neuroectodermal tumor of the gallbladder.


Assuntos
Neoplasias da Vesícula Biliar , Tumores Neuroendócrinos , Adulto , Bangladesh , Feminino , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Achados Incidentais , Tumores Neuroendócrinos/diagnóstico
6.
Mymensingh Med J ; 31(3): 872-875, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35780377

RESUMO

Hemosuccus pancreaticus or bleeding from the pancreatic duct into the gastrointestinal tract via the ampulla of Vater is caused by rupture of the pseudoaneurysm of a peripancreatic vessel into pancreatic duct or pancreatic pseudocyst in the context of pancreatitis or pancreatic tumour or trauma. It produces diagnostic and therapeutic dilemma due to its anatomical location and that bleeding into the duodenum is intermittent and cannot be easily diagnosed by endoscopy, often needs CE-CT and angiography. In August 2019, a 60-year-old male presented with intermittent abdominal pain, gastrointestinal bleeding and high serum lipase. Upper GIT endoscopy showed blood mixed bile coming out through ampulla, suspecting Hemosuccus pancreaticus. Contrast-enhanced computed tomography (CT) scan demonstrated pancreatic pseudo cyst with partially thrombosed splenic artery pseudoaneurysm. At laparotomy, splenic artery pseudoaneurysm was ligated along with splenectomy. Later on, the patient had no further occurrence of gastrointestinal bleeding.


Assuntos
Ampola Hepatopancreática , Falso Aneurisma , Falso Aneurisma/complicações , Falso Aneurisma/diagnóstico , Falso Aneurisma/cirurgia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Ductos Pancreáticos , Artéria Esplênica/patologia
7.
Mymensingh Med J ; 28(4): 940-944, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31599265

RESUMO

Hydatid disease is one of the diseases that have been discovered in the ancient times. Liver and lung are the most commonly affected organs, though it can involve any organs. Hydatid disease involving both the liver and the lung is reported about 10% of the cases. Here we report a case of 34 year old male presented with upper abdominal pain and intermittent fever for 3 months admitted in October 2016. His chest radiograph and computed tomography scan revealed large cystic lesion at right lung and another similar large lesion in the right lobe of liver. Echinococcus antibody was found positive. We treated him surgically. Histopathology reports confirmed concomitant hydatid cyst of both the lung and the liver.


Assuntos
Equinococose/cirurgia , Echinococcus , Adulto , Animais , Humanos , Fígado , Pulmão , Masculino
8.
Mymensingh Med J ; 28(3): 694-698, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31391447

RESUMO

"Porcelain gallbladder" term has been used to highlight the blue staining and fragile consistency of the gallbladder wall at surgery. Some authorities avoid these terms and alternately call all calcified gallbladders "porcelain gallbladders". It is a morphological deviation of chronic cholecystitis. Inflammatory scarring of the wall combined with dystrophic calcification inside the wall transforms the gallbladder into a porcelain-like container. In porcelain gallbladder patients are usually asymptomatic and the condition is usually noted incidentally on plain abdominal radiographs, sonograms, or computed tomography (CT) images. Porcelain gallbladder is a rare condition; recognizing the clinical and imaging characteristics of the disease is important because of the high frequency (22%) of adenocarcinoma in porcelain gallbladder. Operation should not be delayed even if the patient is asymptomatic, because the incidence of carcinoma in porcelain gallbladder is extremely high. Here we present a case of 45 years old lady with porcelain gallbladder who was initially diagnosed as a case of carcinoma gallbladder at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh on 5th August 2017. But she was found to have a benign gallbladder after cholecystectomy.


Assuntos
Calcinose , Doenças da Vesícula Biliar , Vesícula Biliar , Bangladesh , Calcinose/diagnóstico , Feminino , Vesícula Biliar/patologia , Doenças da Vesícula Biliar/cirurgia , Humanos , Pessoa de Meia-Idade
10.
Mymensingh Med J ; 28(2): 479-483, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31086171

RESUMO

Solid pseudopapillary tumors (SPT) of the pancreas are rare neoplasms of the pancreas accounting for only 1-2% of all pancreatic neoplasms, often detected initially on imaging. Its histogenesis is still uncertain and it has a low-grade malignant potential but excellent post-surgical curative rates and rare metastasis. Pathological and/or cytological evaluation still remains the gold standard in reaching a definitive diagnosis. It occurs most commonly in young females. We report a case of solid pseudopapillary tumor in the head of the pancreas in a 20 years old female admitted in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh on 5th December 2015. Whipple's operation was done as a definitive treatment.


Assuntos
Pâncreas/patologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Bangladesh , Feminino , Hospitalização , Humanos , Pâncreas/cirurgia , Neoplasias Pancreáticas/patologia , Adulto Jovem
11.
JAMA Oncol ; 5(5): 654-661, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30998808

RESUMO

IMPORTANCE: Radiation therapy (RT) is a critical cancer treatment, but the existing radiation oncologist work force does not meet growing global demand. One key physician task in RT planning involves tumor segmentation for targeting, which requires substantial training and is subject to significant interobserver variation. OBJECTIVE: To determine whether crowd innovation could be used to rapidly produce artificial intelligence (AI) solutions that replicate the accuracy of an expert radiation oncologist in segmenting lung tumors for RT targeting. DESIGN, SETTING, AND PARTICIPANTS: We conducted a 10-week, prize-based, online, 3-phase challenge (prizes totaled $55 000). A well-curated data set, including computed tomographic (CT) scans and lung tumor segmentations generated by an expert for clinical care, was used for the contest (CT scans from 461 patients; median 157 images per scan; 77 942 images in total; 8144 images with tumor present). Contestants were provided a training set of 229 CT scans with accompanying expert contours to develop their algorithms and given feedback on their performance throughout the contest, including from the expert clinician. MAIN OUTCOMES AND MEASURES: The AI algorithms generated by contestants were automatically scored on an independent data set that was withheld from contestants, and performance ranked using quantitative metrics that evaluated overlap of each algorithm's automated segmentations with the expert's segmentations. Performance was further benchmarked against human expert interobserver and intraobserver variation. RESULTS: A total of 564 contestants from 62 countries registered for this challenge, and 34 (6%) submitted algorithms. The automated segmentations produced by the top 5 AI algorithms, when combined using an ensemble model, had an accuracy (Dice coefficient = 0.79) that was within the benchmark of mean interobserver variation measured between 6 human experts. For phase 1, the top 7 algorithms had average custom segmentation scores (S scores) on the holdout data set ranging from 0.15 to 0.38, and suboptimal performance using relative measures of error. The average S scores for phase 2 increased to 0.53 to 0.57, with a similar improvement in other performance metrics. In phase 3, performance of the top algorithm increased by an additional 9%. Combining the top 5 algorithms from phase 2 and phase 3 using an ensemble model, yielded an additional 9% to 12% improvement in performance with a final S score reaching 0.68. CONCLUSIONS AND RELEVANCE: A combined crowd innovation and AI approach rapidly produced automated algorithms that replicated the skills of a highly trained physician for a critical task in radiation therapy. These AI algorithms could improve cancer care globally by transferring the skills of expert clinicians to under-resourced health care settings.


Assuntos
Inteligência Artificial , Crowdsourcing , Invenções , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Carga Tumoral
12.
Cancer ; 125(6): 884-891, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30521084

RESUMO

BACKGROUND: Combined BRAF and MEK inhibition (BRAF-MEK) is a standard therapy for patients with BRAF V600-mutant melanoma, but to the authors' knowledge, the tolerance, adverse event (AE) profile, and efficacy have not been well defined in the post-programmed cell death protein 1 (PD-1) setting. METHODS: Patients with BRAF V600-mutant melanoma who received combined BRAF-MEK after prior PD-1-based therapy were assembled from 4 tertiary care centers in the United States and Australia. Dose modification was defined as a treatment break, dose reduction, or intermittent dosing. Rates of hospitalization and discontinuation due to AEs were collected, and overall survival (OS) was calculated using Kaplan-Meier methods from the time of the initiation of BRAF-MEK therapy. RESULTS: A total of 78 patients were identified as having received a BRAF-MEK regimen at a median of 34 days after the last dose of PD-1-based therapy. The majority of patients (86%) received the combination of dabrafenib and trametinib. Approximately 80% of patients had American Joint Committee on Cancer M1c or M1d disease. Sixty-five regimens (83%) had ≥1 dose modification. The median time to the first dose modification was 14 days; 86% occurred within 90 days and 71% involved pyrexia. Dose modifications were more common in patients receiving BRAF-MEK <90 days after the last dose of PD-1 and who were not receiving steroids. Of the dose modifications, 25 (31%) led to an AE-related hospitalization. Among 55 BRAF-naive patients, the median time receiving BRAF-MEK therapy was 5.8 months and the median OS was 15.6 months. CONCLUSIONS: The majority of patients receiving BRAF-MEK inhibition after PD-1 therapy require dose interruptions, and a significant minority require hospitalization for AEs. In this higher risk population, the median time receiving therapy and OS may be inferior to those presented in published phase 3 trials.


Assuntos
Imidazóis/administração & dosagem , Melanoma/tratamento farmacológico , Oximas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/administração & dosagem , Pirimidinonas/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Austrália , Feminino , Humanos , Imidazóis/efeitos adversos , Masculino , Melanoma/metabolismo , Pessoa de Meia-Idade , Oximas/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Piridonas/efeitos adversos , Pirimidinonas/efeitos adversos , Neoplasias Cutâneas/metabolismo , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento , Estados Unidos
13.
Mymensingh Med J ; 27(1): 196-200, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29459613

RESUMO

Complete Annular pancreas (AP) is a rare congenital anomaly, often presented and operated at the early age of life. Adult presentation group usually presents with either biliary or duodenal or pancreatic symptoms. We report a case of 43 years old female presenting with concurrent enteric, biliary and pancreatic symptoms admitted on April 2016 in Hepatobiliary and Pancreatic Surgery Department of BSMMU, Dhaka, Bangladesh. A complete type of annular pancreas with partial duodenal stenosis and dilated common bile duct was observed during laparotomy. We performed gastrojejunostomy as well as hepaticojejunostomy (Roux-en-Y anastomosis). Patient was discharged in a good symptom free condition. Complete Annular Pancreas can present at any age, with any one or all of the biliary, pancreatic or duodenal symptoms. Surgery is the treatment of choice and has a good outcome.


Assuntos
Obstrução Duodenal , Pâncreas/anormalidades , Pancreatopatias , Adulto , Bangladesh , Feminino , Humanos , Pâncreas/cirurgia , Pancreatopatias/diagnóstico , Pancreatopatias/cirurgia
14.
Mymensingh Med J ; 26(4): 934-938, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29208887

RESUMO

Polycystic disease of the pancreas is very rare and only few cases have been reported in the literature. We report a case of 27 year old female presented with recurrent upper abdominal pain associated with nausea and vomiting. Her ultrasonography of whole abdomen and computed tomography (CT) scan revealed polycystic pancreas associated with hepatic cysts. She underwent distal pancreatectomy with splenectomy. Histological examination revealed typical features of polycystic pancreatic disease in the resected specimen. Previously two of her sisters and her mother were also diagnosed as cases of polycystic pancreatic disease and they all underwent operative treatments. Among them one of those sisters and her mother received treatment under our department in 2009 and 2014 accordingly.


Assuntos
Cisto Pancreático , Adulto , Feminino , Humanos , Pancreatectomia , Cisto Pancreático/diagnóstico por imagem , Cisto Pancreático/cirurgia , Esplenectomia , Tomografia Computadorizada por Raios X , Ultrassonografia
15.
J Invest Dermatol ; 136(4): 838-846, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26827764

RESUMO

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer with profound but poorly understood resistance to chemotherapy, which poses a significant barrier to clinical MCC treatment. Here we show that ATP-binding cassette member B5 (ABCB5) confers resistance to standard-of-care MCC chemotherapeutic agents and provide proof-of-principle that ABCB5 blockade can inhibit human MCC tumor growth through sensitization to drug-induced cell cytotoxicity. ABCB5 expression was detected in both established MCC lines and clinical MCC specimens at levels significantly higher than those in normal skin. Carboplatin- and etoposide-resistant MCC cell lines exhibited increased expression of ABCB5, along with enhanced ABCB1 and ABCC3 transcript expression. ABCB5-expressing MCC cells in heterogeneous cancers preferentially survived treatment with carboplatin and etoposide in vitro and in human MCC xenograft-bearing mice in vivo. Moreover, patients with MCC also exhibited enhanced ABCB5 positivity after carboplatin- and etoposide-based chemotherapy, pointing to clinical significance of this chemoresistance mechanism. Importantly, ABCB5 blockade reversed MCC drug resistance and impaired tumor growth in xenotransplantation models in vivo. Our results establish ABCB5 as a chemoresistance mechanism in MCC and suggest utility of this molecular target for improved MCC therapy.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Carcinoma de Célula de Merkel/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Cutâneas/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Animais , Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma de Célula de Merkel/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Etoposídeo/administração & dosagem , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Subunidade gama Comum de Receptores de Interleucina/genética , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Transplante de Neoplasias , Reação em Cadeia da Polimerase em Tempo Real , Pele/metabolismo , Neoplasias Cutâneas/tratamento farmacológico
16.
Mymensingh Med J ; 23(3): 461-70, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25178597

RESUMO

Despite continued discussion regarding the treatment of displaced femoral neck fractures, controversies continue regarding their optimal treatment, including the choice of implant and fixation method. Hemiarthroplasty is one of the option which eliminate concerns about fixation failure, nonunion, and avascular necrosis and has become the choice of surgery among the aged >60. This prospective interventional study was carried out on 28 cases at the Department of Orthopaedic Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), from July 2009 to April 2012 to evaluate cementless, bipolar prosthesis among the active elderly patients. All subjects were evaluated with regard to postoperative clinical, functional and activity outcome (Modified Harris Hip Scoring and Hip Outcome Scoring), intra and post operative complications. One case was dropped from follow up and 22(81.48%) patients were considered to have satisfactory outcome after statistical analysis by chi-square test on at least 12 months follow up records. Although prosthetic stem valgus and periprosthetic fracture developed in 02 cases and 01 patient had sunken prosthesis, uncemented bipolar hemiarthroplasty can give significantly good functional outcomes with minimal complications for displaced intracapsular femoral neck fracture in active elderly patients.


Assuntos
Fraturas do Colo Femoral/cirurgia , Hemiartroplastia/métodos , Próteses e Implantes , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
17.
Mymensingh Med J ; 23(3): 471-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25178598

RESUMO

Isthmic spondylolisthesis (IS) is the most common spondylolytic disorders and one of the most common causes of low back pain and sciatica in adolescents and adults. Although the initial management is conservative, surgery is often the ultimate solution. Interbody fusion has been found superior and replaced the gold standard postero-lateral fusion. Transforaminal Lumbar Interbody Fusion (TLIF) has been associated with fewer complications and has become the choice of surgery. This study was done to evaluate the clinical, radiological and functional outcome of TLIF in Low Grade Isthmic Spondylolisthesis (LGIS). The clinical records of 46 consecutive patients within the age range of 31 to 60 years, who had symptomatic unstable Low Grade Isthmic Spondylolisthesis (LGIS) with or without unilateral radiculopathy in Bangabandhu Sheik Mujib Medical University (BSMMU) and private settings, from April 2007 to March 2012 were reviewed with 2 year completed follow-up. Patients were evaluated for pain by Visual Analogue Score (VAS), Disability by Oswestry Disability Index (ODI), radiological fusion by Brantigan and Steffee criteria, reduction of listhesis by Taillard's method and the overall functional outcome by the Macnab's criteria. Pain (Low back and leg), disability, neurological status had highly significant (p<0.001, paired t test) improvement. Forty two (91.30%) cases achieved satisfactory radiological fusion with overall 30% reduction of slip. Satisfactory outcome was reached in 45(97.83%) cases. Transforaminal Lumbar Interbody Fusion results in significant improvement of clinical, radiological and functional debility of symptomatic LGIS in adults.


Assuntos
Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Espondilolistese/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escala Visual Analógica
18.
Nature ; 511(7509): 353-7, 2014 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-25030174

RESUMO

Corneal epithelial homeostasis and regeneration are sustained by limbal stem cells (LSCs), and LSC deficiency is a major cause of blindness worldwide. Transplantation is often the only therapeutic option available to patients with LSC deficiency. However, while transplant success depends foremost on LSC frequency within grafts, a gene allowing for prospective LSC enrichment has not been identified so far. Here we show that ATP-binding cassette, sub-family B, member 5 (ABCB5) marks LSCs and is required for LSC maintenance, corneal development and repair. Furthermore, we demonstrate that prospectively isolated human or murine ABCB5-positive LSCs possess the exclusive capacity to fully restore the cornea upon grafting to LSC-deficient mice in xenogeneic or syngeneic transplantation models. ABCB5 is preferentially expressed on label-retaining LSCs in mice and p63α-positive LSCs in humans. Consistent with these findings, ABCB5-positive LSC frequency is reduced in LSC-deficient patients. Abcb5 loss of function in Abcb5 knockout mice causes depletion of quiescent LSCs due to enhanced proliferation and apoptosis, and results in defective corneal differentiation and wound healing. Our results from gene knockout studies, LSC tracing and transplantation models, as well as phenotypic and functional analyses of human biopsy specimens, provide converging lines of evidence that ABCB5 identifies mammalian LSCs. Identification and prospective isolation of molecularly defined LSCs with essential functions in corneal development and repair has important implications for the treatment of corneal disease, particularly corneal blindness due to LSC deficiency.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Limbo da Córnea/citologia , Limbo da Córnea/fisiologia , Regeneração , Células-Tronco/metabolismo , Cicatrização , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/deficiência , Transportadores de Cassetes de Ligação de ATP/deficiência , Animais , Apoptose , Biomarcadores/metabolismo , Diferenciação Celular , Proliferação de Células , Feminino , Humanos , Masculino , Camundongos , Camundongos Knockout , Dados de Sequência Molecular , Transplante de Células-Tronco , Células-Tronco/citologia , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo
19.
Cancer Res ; 74(15): 4196-207, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24934811

RESUMO

The drug efflux transporter ABCB5 identifies cancer stem-like cells (CSC) in diverse human malignancies, where its expression is associated with clinical disease progression and tumor recurrence. ABCB5 confers therapeutic resistance, but other functions in tumorigenesis independent of drug efflux have not been described that might help explain why it is so broadly overexpressed in human cancer. Here we show that in melanoma-initiating cells, ABCB5 controls IL1ß secretion, which serves to maintain slow cycling, chemoresistant cells through an IL1ß/IL8/CXCR1 cytokine signaling circuit. This CSC maintenance circuit involved reciprocal paracrine interactions with ABCB5-negative cancer cell populations. ABCB5 blockade induced cellular differentiation, reversed resistance to multiple chemotherapeutic agents, and impaired tumor growth in vivo. Together, our results defined a novel function for ABCB5 in CSC maintenance and tumor growth.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Melanoma/metabolismo , Melanoma/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Subfamília B de Transportador de Cassetes de Ligação de ATP , Animais , Linhagem Celular Tumoral , Expressão Gênica , Xenoenxertos , Humanos , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Melanoma/imunologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Análise em Microsséries , Células-Tronco Neoplásicas/imunologia , Receptores de Interleucina-8A/imunologia , Receptores de Interleucina-8A/metabolismo , Transdução de Sinais , Transfecção
20.
Mymensingh Med J ; 23(1): 150-3, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24584389

RESUMO

Carcinoid tumors are well differentiated neuroendochrine tumors which most frequently involve the gastrointestinal tract; however duodenal carcinoid tumors are rare. They can present with various clinical symptoms and are difficult to diagnose. A 52 years old lady presented with the symptoms of recurrent upper abdominal pain, burning sensation of whole body and passage of loose stool. On endoscopy of upper GIT, there was a duodenal polyp. Polyp was removed by endoscopic resection and tissue was taken for biopsy. Histological findings of biopsy specimen shows carcinoid tumor. As duodenal carcinoid tumor is a rare presentation so we are going to present this case in this article.


Assuntos
Tumor Carcinoide/diagnóstico , Tumor Carcinoide/cirurgia , Neoplasias Duodenais/diagnóstico , Neoplasias Duodenais/cirurgia , Endoscopia Gastrointestinal/métodos , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade
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