RESUMO
The increasing cases of NSCLC and improved understanding of its molecular biology has lead to identification of its varied driver mutations. cMET amplification has an important role as resistance mechanism for EGFR TKIs. Crizotinib is a drug which shows its anti-tumoral effect in cMET positive cases. Here we present a case series of three such patients who achieved were cMET amplified and showed partial response on Crizotinib.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Proteínas Proto-Oncogênicas c-met/genética , Pirazóis/administração & dosagem , Piridinas/administração & dosagem , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Inibidores de Proteínas Quinases/administração & dosagemRESUMO
The structure of Msmeg_6760, a protein of unknown function, has been determined. Biochemical and bioinformatics analyses determined that Msmeg_6760 interacts with a protein encoded in the same operon, Msmeg_6762, and predicted that the operon is a toxin-antitoxin (TA) system. Structural comparison of Msmeg_6760 with proteins of known function suggests that Msmeg_6760 binds a hydrophobic ligand in a buried cavity lined by large hydrophobic residues. Access to this cavity could be controlled by a gate-latch mechanism. The function of the Msmeg_6760 toxin is unknown, but structure-based predictions revealed that Msmeg_6760 and Msmeg_6762 are homologous to Rv2034 and Rv2035, a predicted novel TA system involved in Mycobacterium tuberculosis latency during macrophage infection. The Msmeg_6760 toxin fold has not been previously described for bacterial toxins and its unique structural features suggest that toxin activation is likely to be mediated by a novel mechanism.
Assuntos
Antitoxinas/química , Toxinas Bacterianas/química , Regulação Bacteriana da Expressão Gênica , Mycobacterium smegmatis/química , Sistemas Toxina-Antitoxina/genética , Sequência de Aminoácidos , Antígenos de Bactérias , Antitoxinas/genética , Antitoxinas/metabolismo , Proteínas de Bactérias , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Sítios de Ligação , Clonagem Molecular , Cristalografia por Raios X , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Modelos Moleculares , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/metabolismo , Mycobacterium tuberculosis/química , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Óperon , Plasmídeos/química , Plasmídeos/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas RepressorasRESUMO
INTRODUCTION: Chronic lymphocytic leukaemia (CLL) is the most prevalent leukaemia in the Western Hemisphere. Cytogenetic abnormalities in CLL are used for diagnosis, prognosis and treatment. However, detecting these is difficult because mature B cells do not readily divide in culture. Here, we present data on two mitogen cocktails: CpG-oligonucleotide DSP30/Interleukin-2 (IL-2) and DSP30/IL-2 in combination with 12-O-tetradecanoylphorbol-13-acetate (TPA). METHODS: We analysed 165 cases of CLL with FISH and cytogenetics from January 2011 to June 2013. In 2011, three cultures were set-up: unstimulated, DSP30/IL-2-stimulated and TPA-stimulated. In 2012-2013, two cultures were set-up: unstimulated and stimulated with TPA/DSP30/IL-2. RESULTS: In 2011, FISH had a detection rate of 91% and cytogenetics using DSP30/IL2 had a detection rate of 91% (n = 22). In 2012-2013, FISH had a detection rate of 79% and cytogenetics using TPA/DSP30/IL-2 had a detection rate of 98% (n = 40). The percentage of cases with normal FISH but abnormal cytogenetics increased from 9% in 2011 to 21% in 2012-2013. The TPA/DSP30/IL-2 cultures in 2012-2013 detected more novel abnormalities (n = 5) as compared to DSP30/IL-2 alone (n = 3). CONCLUSIONS: TPA/DSP30/IL2 was as good as or better than DSP30/IL2 alone. TPA/DSP30/IL-2 offers a high detection rate for CLL abnormalities with a single stimulated culture and may increase detection of clinically significant abnormalities.
Assuntos
Aberrações Cromossômicas , Hibridização in Situ Fluorescente , Interleucina-2/farmacologia , Leucemia Linfocítica Crônica de Células B , Oligonucleotídeos/farmacologia , Acetato de Tetradecanoilforbol/farmacologia , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Células Tumorais CultivadasRESUMO
BACKGROUND: Rigosertib (ON 01910.Na), a first-in-class Ras mimetic and small-molecule inhibitor of multiple signaling pathways including polo-like kinase 1 (PLK1) and phosphoinositide 3-kinase (PI3K), has shown efficacy in preclinical pancreatic cancer models. In this study, rigosertib was assessed in combination with gemcitabine in patients with treatment-naïve metastatic pancreatic adenocarcinoma. MATERIALS AND METHODS: Patients with metastatic pancreatic adenocarcinoma were randomized in a 2:1 fashion to gemcitabine 1000 mg/m(2) weekly for 3 weeks of a 4-week cycle plus rigosertib 1800 mg/m(2) via 2-h continuous IV infusions given twice weekly for 3 weeks of a 4-week cycle (RIG + GEM) versus gemcitabine 1000 mg/m(2) weekly for 3 weeks in a 4-week cycle (GEM). RESULTS: A total of 160 patients were enrolled globally and randomly assigned to RIG + GEM (106 patients) or GEM (54). The most common grade 3 or higher adverse events were neutropenia (8% in the RIG + GEM group versus 6% in the GEM group), hyponatremia (17% versus 4%), and anemia (8% versus 4%). The median overall survival was 6.1 months for RIG + GEM versus 6.4 months for GEM [hazard ratio (HR), 1.24; 95% confidence interval (CI) 0.85-1.81]. The median progression-free survival was 3.4 months for both groups (HR = 0.96; 95% CI 0.68-1.36). The partial response rate was 19% versus 13% for RIG + GEM versus GEM, respectively. Of 64 tumor samples sent for molecular analysis, 47 were adequate for multiplex genetic testing and 41 were positive for mutations. The majority of cases had KRAS gene mutations (40 cases). Other mutations detected included TP53 (13 cases) and PIK3CA (1 case). No correlation between mutational status and efficacy was detected. CONCLUSIONS: The combination of RIG + GEM failed to demonstrate an improvement in survival or response compared with GEM in patients with metastatic pancreatic adenocarcinoma. Rigosertib showed a similar safety profile to that seen in previous trials using the IV formulation.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Glicina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Sulfonas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Proteínas de Ciclo Celular/antagonistas & inibidores , Classe I de Fosfatidilinositol 3-Quinases , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Glicina/efeitos adversos , Glicina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/genética , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras)/genética , Sulfonas/efeitos adversos , Proteína Supressora de Tumor p53/genética , Gencitabina , Quinase 1 Polo-Like , Neoplasias PancreáticasRESUMO
An 89-year-old woman came with symptoms of progressively worsening dyspnoea at rest over the preceding week. She was normotensive, had elevated jugular venous pressure and clear lungs. ECG revealed atrial fibrillation with the rapid ventricular rate. Labs were significant for markedly elevated pro-brain natriuretic peptide of 43,000 pg/mL and troponin-T of 1 ng/mL. An urgent 2D echocardiogram was obtained, which revealed the severely dilated right atrium and a large linear mobile mass in the right atrium consistent with a thrombus. An emergent CT scan revealed multiple bilateral pulmonary emboli. She received intravenous tissue plasminogen activator. Repeat echocardiogram performed 6 h later showed no evidence of the right atrial thrombus. She was subsequently maintained on intravenous heparin and transitioned to Coumadin. Early recognition of this rare but potentially fatal complication is important as prompt treatment measures can help in preventing life-threatening complications of the right atrial thrombus.
Assuntos
Fibrinolíticos/administração & dosagem , Embolia Pulmonar/tratamento farmacológico , Trombose/tratamento farmacológico , Ativador de Plasminogênio Tecidual/administração & dosagem , Doença Aguda , Idoso de 80 Anos ou mais , Feminino , Átrios do Coração , Humanos , Infusões IntravenosasRESUMO
Brown rice after germinating for 24 and 48 h was milled into flour and incorporated in whole wheat flour at a level of 10% to prepare chapattis. The objective was to use chapatti as a delivery vehicle for germinated brown rice. The flour blends and chapattis made from the flour blends were evaluated for their antioxidant properties. Incorporating germinated brown rice flour increased the total phenolic content of the flour blend from 1897 to 2144 µg FAE/g. The total flavonoids content increased significantly from 632.3 to1770.9 µg CAE/g and metal chelating activity significantly increased by 71.62%. Antioxidant activity increased significantly by the addition of brown rice flour and addition of 24- and 48-h germinated brown rice flour further increased the antioxidant activity significantly. The total phenolic content and total flavonoids content decrease significantly in all the blends after baking the flour into chapatti. A decrease of 3% to 29% was observed in the total phenolic content and a decrease of 25% to 42% was observed in the total flavonoids content. However, baking of the flour blends into chapatti increased the reducing power, metal chelating activity by three folds and antioxidant activity from 64% to 104%.
Assuntos
Antioxidantes/química , Farinha/análise , Manipulação de Alimentos/métodos , Germinação , Oryza/química , Antioxidantes/análise , Flavonoides/análise , Flavonoides/química , Aditivos Alimentares/análise , Aditivos Alimentares/química , Quelantes de Ferro/química , Fenóis/análise , Fenóis/química , Sementes/química , Triticum/químicaRESUMO
This study examined 215 samples of soil from burrows of rats, other sites in bamboo plantations in different parts of India and Nepal by dilution plating and mouse passage technique for occurrence of Penicillium marneffei and other pathogenic fungi. None of the samples including 25 collected from the burrows of a bamboo rat (Cannomys badius) known to be a carrier of P. marneffei, was positive for the fungus. Among the pathogenic fungi recovered were four isolates of Pseudallescheria boydii (including one from Nepal), two of Trichosporon asteroides, one of Scytalidium hyalinum, 23 isolates of Trichophyton mentagrophytes var. mentagrophytes (including two from Nepal), and two of Microsporum gypseum. Fourteen of the 23 isolates of T. mentagrophytes var. mentagrophytes when tested with the mating types of Arthroderma vanbreuseghemii were found to be of the '+' mating type. The frequent recovery of this dermatophyte from soils of bamboo plantations in several parts of India is remarkable. The study also demonstrates for the first time the occurrence of P. boydii and T. mentagrophytes var. mentagrophytes in Nepalese soil. Among the other fungi recovered were several isolates of species of Aspergillus, Penicillium, Paecilomyces, Fusarium, Chrysosporium, Acremonium, Rhizopus, Mucor, Geotrichum, Trichosporon and Rhodotorula.
Assuntos
Reservatórios de Doenças , Ecossistema , Fungos/isolamento & purificação , Roedores , Microbiologia do Solo , Animais , Ascomicetos/classificação , Ascomicetos/isolamento & purificação , Ascomicetos/patogenicidade , Basidiomycota/classificação , Basidiomycota/isolamento & purificação , Basidiomycota/patogenicidade , Fungos/classificação , Fungos/patogenicidade , Índia , Camundongos , Nepal , Ratos , Roedores/classificação , Sasa/crescimento & desenvolvimentoAssuntos
Arritmias Cardíacas/fisiopatologia , Marca-Passo Artificial/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Tontura/etiologia , Tontura/fisiopatologia , Eletrocardiografia , Humanos , Hipotensão/etiologia , Hipotensão/fisiopatologia , Masculino , Síncope/etiologia , Síncope/fisiopatologia , SíndromeRESUMO
The present study was undertaken to evaluate the knowledge, attitude and practices about neonatal hypothermia among medical and paramedical staff dealing with newborn care. A total of 160 subjects were assessed (40 pediatric medicine residents, 40 obstetric residents, 40 private practitioners and 40 paramedical staff working in labor room and postnatal wards) A pre-tested structured questionnaire was used. Only 47.8% of the subjects defined neonatal hypothermia correctly. As many as 52.2% of the interviewees considered it to be an uncommon problem. Lethargy, refusal for feed and cold to touch were mentioned as common symptoms of neonatal hypothermia by 97.5%, 80% and 77.5% of the respondents respectively. Decreased body temperature, cyanosis, apnea and edema of feet were found as common signs. Only 18.6% of the interviewees had knowledge about correct method of recording the temperature in a newborn. The present study reveals the gross lacunae in the knowledge regarding various aspects of neonatal hypothermia among pediatric and obstetric residents and paramedical staff working in labor room and postnatal wards. To reduce the neonatal morbidity and mortality due to neonatal hypothermia, greater emphasis should be laid on this problem while designing curriculum for training of undergraduate and postgraduate doctors, paramedical staff and traditional birth attendants.
Assuntos
Competência Clínica , Conhecimentos, Atitudes e Prática em Saúde , Hipotermia , Pessoal Técnico de Saúde , Humanos , Hipotermia/diagnóstico , Hipotermia/etiologia , Hipotermia/terapia , Recém-Nascido , Internato e Residência , Obstetrícia , PediatriaRESUMO
This case details the development of a rapidly growing polypoid mass in the proximal stomach in a patient with known attenuated familial adenomatous polyposis. Surgical resection was required and histology showed hyperplasia with extensive areas of dysplastic adenomatous change. This case illustrates that patients with the attenuated form of familial adenomatous polyposis are at risk for multiple neoplasia distinct from those patients with the classic form of familial adenomatous polyposis.
Assuntos
Polipose Adenomatosa do Colo/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Pólipos/diagnóstico , Neoplasias Gástricas/diagnóstico , Feminino , Fundo Gástrico , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: In symptomatic and asymptomatic patients with significant carotid artery stenosis, surgical endarterectomy has been shown to be beneficial when compared with medical management. Carotid stenting is evolving as an alternative technique for treating such patients. This prospective study was designed to assess the feasibility and safety of carotid angioplasty and stenting. METHODS: Fourteen patients (15 carotid arteries) with significant carotid artery stenosis were enrolled. These patients were in the age range 46 to 84 years (mean 60.9 +/- 7 years) and there were 12 males (86%). All of these patients were symptomatic with either TIA (n = 8) or stroke (n = 6). Wallstents were used in all the cases to stent the carotid arteries. One patient underwent bilateral carotid artery stenting. RESULTS: Carotid angioplasty and stenting was successful in 13 out of 14 (92.8%) patients and 14 out of 15 (93.3%) carotid arteries, with reduction in mean (+/- SD) stenosis from 86 +/- 6% to 3 +/- 3%. There was one episode of minor stroke, no major stroke or death during the initial hospitalization. Another patient had a minor stroke with patent ipsilateral carotid artery (on repeat angiography) during the first 30 days after the procedure. This patient was also found to have asymptomatic thrombus formation in the contralateral carotid stent which resolved with intravenous anticoagulation. During a mean follow up of 6 +/- 2 months there has been no recurrence of symptoms. CONCLUSIONS: Based upon our limited experience we believe that percutaneous carotid angioplasty with stenting is feasible with low periprocedural complication rate.
Assuntos
Estenose das Carótidas/terapia , Cateterismo , Stents , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
A 20-day-old female presented in acute renal failure with an absent bladder and vaginal atresia. The right ureter opened into the uterus, resulting in a urometrocolpos, and the left ureter opened through a stenotic opening into the introitus. The literature is reviewed for reported cases and the embryo-pathology of bladder agenesis is discussed.
Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/cirurgia , Ureter/anormalidades , Bexiga Urinária/anormalidades , Útero/anormalidades , Vagina/anormalidades , Anormalidades Múltiplas/embriologia , Injúria Renal Aguda/etiologia , Cloaca/embriologia , Evolução Fatal , Feminino , Humanos , Hidronefrose/etiologia , Recém-Nascido , Nefrostomia PercutâneaRESUMO
Traumatic pseudoaneurysms are rare in civilian trauma, more so in childhood. A case of anterior tibial artery pseudoaneurysm is described which was successfully treated non surgically by percutaneous coil embolisation, thus questioning the need for surgery in peripheral pseudoaneurysms.
Assuntos
Falso Aneurisma/terapia , Embolização Terapêutica/métodos , Artérias da Tíbia , Falso Aneurisma/diagnóstico , Criança , Feminino , Humanos , Radiografia , Artérias da Tíbia/diagnóstico por imagemRESUMO
We report a male child with Thrombocytopenia and Absent Radii (TAR) syndrome but with single absent radius and associated tracheoesophageal fistula which has never been reported till date.
Assuntos
Atresia Esofágica/patologia , Rádio (Anatomia)/anormalidades , Trombocitopenia/congênito , Evolução Fatal , Humanos , Recém-Nascido , Masculino , Síndrome , Fístula Traqueoesofágica/patologiaRESUMO
A 7-year-old female with a type I choledochal cyst underwent an exploratory laparotomy. A Roux-en-Y choledochojejunostomy was done following cyst excision. The patient was re-explored 8 days later for an anastomotic bile leak and high fever. A round-worm was found obstructing the jejunal lumen at the porta hepatis, resulting in a biliary leak. Various aspects of biliary ascariasis are discussed along with the case report.
Assuntos
Anastomose em-Y de Roux , Ascaríase/complicações , Obstrução Intestinal/parasitologia , Doenças do Jejuno/parasitologia , Complicações Pós-Operatórias/parasitologia , Criança , Cisto do Colédoco/cirurgia , Feminino , HumanosRESUMO
A case of covered exstrophy without sequestration of a bowel segment is reported. A 4-year-old female presented with dribbling of urine. Treatment to date has been simple excision of the covered membrane with functional closure of the bladder and bilateral posterior iliac osteotomies, with reconstruction of the bladder neck and genitalia to be performed at a later date. The embryogenesis of this rare variant, a review of the reported cases, and management options are discussed. Keyword Covered exstrophy. Exstrophy. Bladder variants
Assuntos
Extrofia Vesical/patologia , Extrofia Vesical/cirurgia , Extrofia Vesical/embriologia , Pré-Escolar , Feminino , HumanosRESUMO
PURPOSE: Mutations in c-Ki-ras2 (ras) occur in about 40% of patients with colorectal cancers and occur early in the pathogenesis of this disease. To evaluate the prognostic value of mutations in ras, the Eastern Cooperative Oncology Group (ECOG) conducted a retrospective study (EST 2292) to determine the frequency of mutations in patients with advanced colorectal cancer, and to determine whether ras mutations were associated with altered response to therapy and survival. PATIENTS AND METHODS: Patients were enrolled from four studies: P-Z289, an ECOG phase II trial of 5-fluorouracil (5-FU) and interferon (IFN) in patients with advanced colorectal cancer; P-Z991, an ECOG phase I trial of 5-FU and IFN in patients with advanced malignancies; and two trials from the Albert Einstein College of Medicine in patients with advanced colorectal cancer treated with 5-FU and either IFN-alpha or IFN-beta. All patients had advanced colorectal carcinoma and had sufficient histologic material available for analysis for the presence and type of ras, using polymerase chain reaction and dot-blot analysis with sets of probes sufficient to detect all the common mutations of ras at codons 12, 13, and 61. RESULTS: Seventy-two patients were enrolled in this trial. Mutations in ras were detected in 25 (35%), including 17 (23%) in codon 12, four (6%) in codon 13, and four (6%) in codon 61. There was no correlation between the presence of a ras mutation and age, sex, Dukes' stage, histology, or tumor markers. Thirty-one of 72 patients (43%) responded to therapy with 5-FU and IFN, and 10 of 31 responders (32%) and 15 of 41 nonresponders (37%) had mutations in ras. There was no difference in response rates or overall survival between the groups with and without ras mutations. CONCLUSIONS: It is unlikely that ras mutations will have significant prognostic value for either response to therapy or survival in patients with colorectal carcinomas treated with 5-FU and IFN.