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1.
Anaesth Rep ; 10(2): e12199, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36530341

RESUMO

The erector spinae plane block is a versatile regional anaesthesia technique used for a variety of truncal surgeries. A novel variation is the sacral erector spinae plane block which is gaining popularity for perineal and anorectal procedures. Local anaesthetic injected at this level blocks the sacral dermatomes and has the potential for more proximal spread to involve lumbar nerve fibres via spread to the lumbar plexus or the epidural space. The advantage of a sacral erector spinae plane block over a neuraxial block is that it is less invasive and may have a better safety profile: there is a reduced risk of epidural haematoma, epidural abscess, haemodynamic instability and motor weakness of the lower extremities. Until now, this approach has been used for midline surgical procedures when the local anaesthetic was injected bilaterally. Its application for lower limb procedures with a single unilateral injection has not been described. We report the use of a unilateral sacral erector spinae plane block at the level of the S2 median crest in two children undergoing lower limb procedures of the hip and thigh. The block was found to provide effective peri-operative analgesia with minimal need for any opioid analgesics and without any significant adverse effects.

2.
Osteoarthritis Cartilage ; 29(7): 946-955, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33895290

RESUMO

AIMS: To systematically review observational studies for the association between features detected on ultrasound (US) and magnetic resonance imaging (MRI) and, symptoms, signs and radiographic progression of hand osteoarthritis (OA). METHODS: Medline, Web of Science, EMBASE, CINAHL and AMED were searched from inception to 14th January 2020 to identify relevant studies. Quality of studies was assessed using the Newcastle-Ottawa scales and data were extracted. Odds ratios (OR) and linear regression coefficients and 95% confidence intervals (CI) were pooled using the random-effects model (METAN package, Stata v16.1). Heterogeneity and publication bias were assessed. RESULTS: Thirty-two studies using US and MRI comprising 1,350 and 638 participants respectively were included. While only grey-scale synovitis (GSS) associated with AUSCAN-pain (pooled Regression coefficient (95% CI): 0.46 (0.13-0.79); 0-20 scale for AUSCAN-pain), US-detected osteophytes, GSS and power Doppler (PD) [pooled ORs (95% CI): 2.68(2.16-3.33), 2.38(1.74-3.26) and 2.04 (1.45-2.88)] as well as MRI-detected bone marrow lesions (BMLs), synovitis, osteophytes, and central bone erosions (CBEs) associated with joint tenderness [pooled ORs (95% CI): 2.59(2.12-3.18), 2.17(1.85-2.54), 2.15(1.55-2.99), and 2.41 (1.45-4.02)] respectively. US-detected GSS and PD associated with radiographic progression of CBEs [pooled ORs 5.37, 5.08], osteophytes [pooled ORs 5.17, 6.45], and joint space narrowing (pooled ORs 4.28, 4.36) whilst MRI-detected synovitis and BMLs associated with increasing KL grades with pooled ORs 2.92, 2.54 respectively. CONCLUSIONS: US and MRI-detected structural and inflammatory changes associate with tenderness, whilst articular inflammation and subchondral bone damage associate with radiographic hand OA progression. There was inconsistent relationship between these changes and pain.


Assuntos
Medula Óssea/diagnóstico por imagem , Progressão da Doença , Articulação da Mão/diagnóstico por imagem , Osteoartrite/diagnóstico por imagem , Sinovite/diagnóstico por imagem , Articulação da Mão/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Estudos Observacionais como Assunto , Osteoartrite/fisiopatologia , Osteófito/diagnóstico por imagem , Ultrassonografia
4.
Clin Transl Oncol ; 22(9): 1472-1480, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32124242

RESUMO

BACKGROUND: The role of DNA damage response (DDR) proteins is poorly understood in uveal melanoma. ATR belongs to one of those proteins that induce DDR by arresting the cell cycle which leads to DNA repair. ATR is localized at position 23 on the same chromosome 3 where BAP1 is located at position 21.1 which is a known poor prognostic marker of UM. The aim of our study is to detect the expression of ATR at the protein and RNA levels and determine its prognostic significance. METHODS: Expression of nuclear ATR was investigated on sixty-nine UM patients. Formalin-fixed paraffin-embedded choroidal melanoma samples were taken to evaluate the expression of ATR. Fifty samples were also validated by real-time PCR. Results of both protein and mRNA were then correlated with clinicopathological parameters. To determine the prognostic significance, Kaplan-Meier and multivariate analyses were performed. RESULTS: Loss of ATR protein was seen in 72% cases which was statistically significant with epithelioid cell type (p = 0.005), tumor thickness (p = 0.016), mitotic figures (p = 0.001) and BAP1 loss (p < 0.001). At the transcriptional level loss of ATR was seen in 76% cases which were statistically significant with metastasis (p = 0.046), staging (0.044) and loss of BAP1 (p = 0.022). On multivariate analysis loss of ATR and tumor staging came out to be independent prognostic parameters. CONCLUSION: Our data suggest that ATR might serve as a potential prognostic marker in UM patients and could serve as a potential therapeutic target.


Assuntos
Dano ao DNA , Melanoma/genética , Neoplasias Uveais/genética , Adulto , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Células Epitelioides/metabolismo , Células Epitelioides/patologia , Feminino , Humanos , Masculino , Melanoma/metabolismo , Melanoma/mortalidade , Melanoma/patologia , Gradação de Tumores , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Neoplasias Uveais/metabolismo , Neoplasias Uveais/mortalidade , Neoplasias Uveais/patologia
5.
J Appl Microbiol ; 125(5): 1455-1465, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29877011

RESUMO

AIM: The present study aimed to isolate and screen endophytes from Trachyspermum ammi with the ability to inhibit alpha glucosidase enzyme and evaluate their insecticidal potential. METHODS AND RESULTS: Endophytic fungi isolated from T. ammi were screened for alpha glucosidase inhibitory activity. Maximum inhibition (96%) was observed in an isolate AZ-9, identified to be Exophiala spinifera on morphological and molecular basis. Production of fungal metabolites was carried out in malt extract broth followed by extraction with ethyl acetate. Brown coloured gummy residue obtained after evaporation of ethyl acetate was partially soluble in water yielding white precipitates. The precipitate exhibiting α-glucosidase inhibitory activity was purified by repeated washing and centrifugation. The insecticidal activity of inhibitor was evaluated on Spodoptera litura (Fab.) by feeding this pest on diet amended with inhibitor. It resulted in significant larval mortality as well as deformities in emerging adults. A reduction in vivo digestive enzyme activity was also observed. Nutritional analysis revealed the toxic effect of AZ-9 inhibitor on various food utilization parameters of S. litura. A significant reduction was recorded in relative growth and consumption rate of S. litura. CONCLUSIONS: This is the first report on production of an alpha glucosidase inhibitor from E. spinifera with insecticidal activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The study highlights the importance of endophytes in providing protection against insect pests to the host. It also suggests the insecticidal potential of alpha glucosidase inhibitor from E. spinifera against polyphagous pest S. litura.


Assuntos
Exophiala/química , Inibidores de Glicosídeo Hidrolases , Inseticidas , Spodoptera , Animais , Endófitos/química , Exophiala/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Larva , Testes de Toxicidade , alfa-Glucosidases/metabolismo
6.
Int J Tuberc Lung Dis ; 22(7): 807-812, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29914607

RESUMO

SETTING: Despite overwhelming evidence for the association between tuberculosis (TB) and tobacco use, it remains neglected in the context of policy, planning and practice. There is limited evidence about the extent of integration of TB and tobacco control programmes in South-East Asia Region (SEAR) countries. OBJECTIVE: To assess the level of TB-tobacco integration in 11 SEAR countries. DESIGN: Cross-sectional study using a structured questionnaire addressed to TB and tobacco focal points at the World Health Organization Country Offices. RESULTS: Apart from India, no country in the SEAR has a formal coordination mechanism for national TB and tobacco control programmes or a system of referral for tobacco users among TB patients for treatment of tobacco dependence. There is no joint planning, joint training or joint supervision and monitoring in any country. CONCLUSION: There is poor integration between TB and tobacco control programmes in most SEAR countries. This assessment fed into the development of a regional framework for TB-tobacco integration, which outlines three strategies: 1) integrated patient-centred care and prevention; 2) joint TB tobacco actions covering policy development, planning, training and monitoring; and 3) research and innovation. Every country in the region should adopt the TB-tobacco integration framework to improve programme performance.


Assuntos
Política de Saúde , Tabagismo/prevenção & controle , Uso de Tabaco/prevenção & controle , Tuberculose/prevenção & controle , Sudeste Asiático , Estudos Transversais , Humanos , Assistência Centrada no Paciente/organização & administração , Desenvolvimento de Programas , Inquéritos e Questionários
7.
Photochem Photobiol Sci ; 17(5): 539-551, 2018 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-29565434

RESUMO

Triple-negative breast cancer (TNBC) and malignant melanoma are highly aggressive cancers that widely express the cell surface chondroitin sulfate proteoglycan 4 (CSPG4/NG2). CSPG4 plays an important role in tumor cell growth and survival and promotes chemo- and radiotherapy resistance, suggesting that CSPG4 is an attractive target in cancer therapy. In the present work, we applied the drug delivery technology photochemical internalization (PCI) in combination with the novel CSPG4-targeting immunotoxin 225.28-saporin as an efficient and specific strategy to kill aggressive TNBC and amelanotic melanoma cells. Light-activation of the clinically relevant photosensitizer TPCS2a (fimaporfin) and 225.28-saporin was found to act in a synergistic manner, and was superior to both PCI of saporin and PCI-no-drug (TPCS2a + light only) in three TNBC cell lines (MDA-MB-231, MDA-MB-435 and SUM149) and two BRAFV600E mutated malignant melanoma cell lines (Melmet 1 and Melmet 5). The cytotoxic effect was highly dependent on the light dose and expression of CSPG4 since no enhanced cytotoxicity of PCI of 225.28-saporin compared to PCI of saporin was observed in the CSPG4-negative MCF-7 cells. The PCI of a smaller, and clinically relevant CSPG4-targeting toxin (scFvMEL-rGel) validated the CSPG4-targeting concept in vitro and induced a strong inhibition of tumor growth in the amelanotic melanoma xenograft A-375 model. In conclusion, the combination of the drug delivery technology PCI and CSPG4-targeting immunotoxins is an efficient, specific and light-controlled strategy for the elimination of aggressive cells of TNBC and malignant melanoma origin. This study lays the foundation for further preclinical evaluation of PCI in combination with CSPG4-targeting.


Assuntos
Antineoplásicos/farmacologia , Proteoglicanas de Sulfatos de Condroitina/antagonistas & inibidores , Imunotoxinas/farmacologia , Melanoma/tratamento farmacológico , Proteínas de Membrana/antagonistas & inibidores , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Imunotoxinas/química , Luz , Melanoma/metabolismo , Melanoma/patologia , Proteínas de Membrana/metabolismo , Camundongos , Processos Fotoquímicos , Relação Estrutura-Atividade , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Células Tumorais Cultivadas
8.
Clin Oral Investig ; 22(2): 633-640, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29344805

RESUMO

OBJECTIVE: The objective of the study was to conduct a systematic review of the literature assessing potential salivary biomarkers of oral cancer and pre-cancer and discuss emerging issues and challenges in relation to oral cancer and pre-cancer diagnostics. MATERIALS AND METHODS: Search for articles involved the Medline, PubMed, and EMBASE. Specific terms were used from January 1995 to March 2017 by three experts. RESULTS: This search collected 270 articles, of which 105 articles such as reviews, case reports, news, letter to editor, etc. in first round and 117 articles such as publications in other languages than English, non-human studies, etc. were excluded. The remaining 48 articles considered analyzing whole saliva as well as specific gland saliva. Thirty-one studies considered oral stimuli such as eating, drinking, and oral hygiene practices for varied periods of time prior to sample collection. The time of collection of saliva was morning in most studies, but the exact time of collection was not mentioned. Three studies showed to have evaluated the whole saliva without centrifugation. Two-dimensional gel electrophoresis and tandem mass spectrometry were the most commonly used methods. Most of the potential salivary biomarkers of oral cancer are salivary proteins. CONCLUSION: Combination approach of salivary biomarkers could be used as screening tool to improve early detection and diagnostic precision of oral pre-cancer and cancer. CLINICAL RELEVANCE: The current findings are of importance for clinicians and researchers to mitigate the challenges in salivary-based diagnosis of oral cancer and to evaluate reliable, specific, and sensitive salivary biomarkers for oral pre-cancer and cancer diagnosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Detecção Precoce de Câncer , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/metabolismo , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/metabolismo , Saliva/química , Eletroforese em Gel Bidimensional , Humanos , Espectrometria de Massas em Tandem
9.
Morphologie ; 102(337): 87-90, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28890314

RESUMO

Omohyoid muscle present in cervical region is of particular importance to anatomists as it defines anteriorly the carotid triangle and divides the posterior cervical triangle. It has superior and inferior bellies and an intermediate common tendon. Like sternohyoid, sternothyroid and thyrohyoid muscles, omohyoid is also an infrahyoid muscle, but it differs from them in its course. The infrahyoid muscles are formed from a muscle primordium occurring in the anterior cervical area. Anderson (Anderson, 1881) theorized that the superior belly of the omohyoid muscle is a true infrahyoid muscle, whereas the inferior belly most likely shares a common embryology with the subclavius muscle. In the present study, during routine dissection in the neck region of an adult male cadaver of 50 years age, an anomalous origin of inferior belly of omohyoid with absence of intermediate tendon was observed bilaterally. It was arising from clavicle on both sides. Both the muscle bellies were measured from the lateral end of fascial sling. The inferior belly of omohyoid extending from the lateral margin of sling to clavicular surface was measured 3.3cm in length on left side and 3.6cm on right side. The omohyoid is important in neck dissections because it is considered as an ideal landmark for level III and IV lymph node metastases. Knowledge of variations of this muscle is very important for surgeries in neck region because of its close relation to the internal jugular vein and brachial plexus. Its crucial relationship to vascular structures in the neck makes it an important landmark during neck surgeries.


Assuntos
Variação Anatômica , Clavícula/anatomia & histologia , Músculos do Pescoço/anormalidades , Cadáver , Humanos , Masculino , Pessoa de Meia-Idade
10.
Exp Oncol ; 39(1): 57-64, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28361856

RESUMO

Promoter hypermethylation mediates gene silencing in many neoplasms. Acute leukemia has been reported to harbor multiple genes aberrantly silenced by hypermethylation. AIM: In present study, we investigated the prevalence of hypermethylation of caspase-8 (CASP8), TMS1 and DAPK genes in correlation with clinicopathological factors in childhood acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A case-control study has been conducted based on bone marrow and peripheral blood samples from 125 ALL patients and 100 sex-age matched healthy controls. Methylation specific polymerase chain reaction (PCR) and bisulfite sequencing PCR was performed to analyze the methylation status of these genes. Reverse transcription PCR and real time PCR was carried out to determine changes in the mRNA expression level of the genes due to hypermethylation. RESULTS: Hypermethylation of the 5´CpG islands of the CASP8, TMS1 and DAPK gene promoters was found in 3.2, 6.4, and 13.6% of 125 childhood ALL samples from north Indian population, respectively. There were significant differences in pattern of hypermethylation of TMS1 (p = 0.045) and DAPK (p < 0.001) between patients and healthy controls. Down-regulation of mRNA expression was found in cases in which CASP8, TMS1 and DAPK were hypermethylated. CONCLUSIONS: The present study indicated the impact of hypermethylation-mediated inactivation of CASP8, TMS1 and DAPK genes, which is associated with risk of childhood ALL. This abnormality occurs in leukemogenesis and it may be used as a biomarker and for predicting the prognosis of ALL.


Assuntos
Apoptose/genética , Metilação de DNA , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Regiões Promotoras Genéticas/genética , Sequência de Bases , Proteínas Adaptadoras de Sinalização CARD , Estudos de Casos e Controles , Caspase 8/genética , Criança , Pré-Escolar , Proteínas do Citoesqueleto/genética , Proteínas Quinases Associadas com Morte Celular/genética , Regulação para Baixo , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Índia , Lactente , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
11.
Trends Cancer Res ; 12: 97-110, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-31213748

RESUMO

We have previously identified a single-item measure for baseline overall quality of life (QOL) as a strong prognostic factor for survival, and that fatigue was an important component of patient QOL. To explore whether patient-reported fatigue was supplemental or redundant to the prognostic information of overall QOL, we performed a patient-level pooled analysis of 43 North Central Cancer Treatment Group (NCCTG) and Mayo Clinic Cancer Center (MCCC) oncology clinical trials assessing the effect of baseline fatigue on overall survival (OS). 3,915 patients participating in 43 trials provided data at baseline for fatigue on a single-item 0-100 point scale. OS was tested for association with clinically deficient fatigue (CDF, score 0-50, n = 1,497) versus not clinically deficient fatigue (nCDF, score 51-100, n = 2,418). We explored whether fatigue contributed to overall survival in the presence of performance status and overall QOL. We used Cox proportional hazards models that adjusted for the effects of overall QOL, performance score, race, disease site, age and gender. Baseline fatigue was a strong predictor of OS for the entire patient cohort (CDF vs. nCDF: 31.5 months vs > 83.9 months, p < 0.0001). The effect sizes of fatigue on survival were more variable across different disease sites than was seen for overall QOL (GI, esophageal, head and neck, prostate, lung, breast and others). After controlling for covariates, including performance status and overall QOL, baseline fatigue remained a strong prognostic factor in multivariate models (CDF vs. nCDF: HR = 1.23, p = 0.02). Baseline fatigue is a strong and independent prognostic factor for OS over and above performance status (PS) and overall QOL in a wide variety of oncology patient populations. Single-item measures of overall QOL and fatigue can help to identify vulnerable subpopulations among cancer patients. We recommend these single-item measures for routine inclusion as a stratification factor or key covariate in the design and analysis of oncology treatment trials.

12.
Genetika ; 52(2): 255-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27215041

RESUMO

Tumor-specific genetic or epigenetic alterations have been detected in serum DNA in case of various types of cancers. In breast cancer, the detection of tumor suppressor gene hypermethylation has been reported in several body fluids. Promoter hypermethylation of some genes like MYOD1, CALCA, hTERT etc. has also been detected in serum samples from cervical cancer. The present study is the first report on the comparison of promoter hypermethylation of tumor suppressor genes likep14, p15, p16, p21, p27, p57, p53, p73, RARß2, FHIT, DAPK, STAT1 and-RB1 genes in paired biopsy and serum samples from cervical cancer patients among north Indian population. This is also the first report on the hypermethylation of these genes in serum samples from cervical cancer patients among north Indian population. According to the results of the present study, promoter hypermethylation of these genes can also be detected in serum samples of cervical cancer patients. The sensitivity of detection of promoter hypermethylation in serum samples of cervical cancer patients as compared to paired biopsy samples was found to be around 83.3%. It was observed that promoter hypermethylation was mainly observed in the serum samples in the higher stages and very rarely in the lower stages. The present study clearly showed that serum of patients with cervical cancer can also be used to study methylated genes as biomarkers.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA/genética , Proteínas de Neoplasias/genética , Neoplasias do Colo do Útero/genética , Biomarcadores Tumorais/sangue , Biópsia , Feminino , Genes Supressores de Tumor , Humanos , Índia , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Regiões Promotoras Genéticas , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/patologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-28691116

RESUMO

BACKGROUND: Significant efforts have been made to increase access and accrual to clinical trials for minority cancer patients (MP). This meta-analysis looked for differences in survival and baseline quality of life (QOL) between MP and non-minority cancer patients (NMP). MATERIALS AND METHODS: Baseline QOL and overall survival times from 47 clinical trials (6513 patients) conducted at Mayo Clinic Cancer Center/North Central Cancer Treatment Group were utilized. Assessments included Uniscale, Linear Analogue Self Assessment, Symptom Distress Scale (SDS), Profile of Mood States and Functional Assessment of Cancer Therapy - General, each transformed into a 0-100 scale with higher scores indicating better outcomes. This transformation involves subtracting the lowest possible value from the assessment, dividing by the range of the scale (the maximum minus the minimum), and multiplying by 100. Analyses included Fisher's Exact tests, linear regression, Kaplan-Meier curves, and Cox proportional hazards models. RESULTS: Eight percent of patients self-reported as MP (0.45% American Indian/Alaskan Native, 0.7% Asian, 5% Black/African American, 1.5% Hispanic, 0.1% Native Hawaiian and 0.3% Other). MP had no meaningful deficits relative to non-MP in overall QOL but were slightly worse on FACT-G total score, physical, social/family, functional, and SDS nausea severity. MP with lung, neurological or GI cancers had significantly worse mean scores in nausea (58 vs. 69), sleep problems (34 vs. 54); emotional (53 vs. 74); and social/family (60 vs. 67), respectively. Regression models confirmed these results. After adjusting for disease site, there were no significant differences in survival. CONCLUSION: MP on these clinical trials indicated small deficits in physical, social, and emotional subscales at baseline compared to NMP. Within cancer sites, MP experienced large deficits for selected QOL domains that bear further attention.

15.
Folia Biol (Praha) ; 61(2): 81-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26333125

RESUMO

Curcumin has been documented to exert anticancer effects by interacting with altered proliferative and apoptotic pathways in cancer models. In this study, we evaluated the potential of curcumin to reverse promoter methylation of the p15 gene in Raji cells and its ability to induce apoptosis and genomic instability. Anti-neoplastic action of curcumin showed an augmentation in reactive oxygen species (ROS) and cell cycle arrest in G1 phase. Subsequently, curcumin- exposed Raji cells showed structural abnormalities in chromosomes. These observations suggest that curcumin also causes ROS-mediated apoptosis and genomic instability. The treatment of Raji cell line with 10 µM curcumin caused hypomethylation of the p15 promoter after six days. Hypomethylation of p15 was further found to be favoured by downregulation of DNA methyltransferase 1 after 10 µM curcumin treatment for six days. Methylation-specific PCR suggested demethylation of the p15 promoter. Demethylation was further validated by DNA sequencing. Reverse-transcription PCR demonstrated that treatment with curcumin (10 µM) for six days led to the up-regulation of p15 and down-regulation of DNA methyltransferase 1. Furthermore, curcumin- mediated reversal of p15 promoter methylation might be potentiated by down-regulation of DNA methyltransferase 1 expression, which was supported by cell cycle analysis. Furthermore, curcumin acts as a double-pronged agent, as it caused apoptosis and promoter hypomethylation in Raji cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Inibidor de Quinase Dependente de Ciclina p15/biossíntese , DNA (Citosina-5-)-Metiltransferases/biossíntese , Metilação de DNA/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Instabilidade Genômica/efeitos dos fármacos , Proteínas de Neoplasias/biossíntese , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Regiões Promotoras Genéticas/efeitos dos fármacos , Antineoplásicos Fitogênicos/toxicidade , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Quebra Cromossômica/efeitos dos fármacos , Curcumina/toxicidade , Inibidor de Quinase Dependente de Ciclina p15/genética , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/genética , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Indução Enzimática/efeitos dos fármacos , Humanos , Proteínas de Neoplasias/genética , Espécies Reativas de Oxigênio/metabolismo
16.
J Laryngol Otol ; 129(7): 710-4, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26077504

RESUMO

BACKGROUND: Aspiration pneumonia is an important cause of death in head and neck cancer patients. This study therefore aimed to evaluate the risk factors associated with aspiration pneumonia in head and neck cancer patients. METHODS: Hospital death records from 12 years (2000-2012) were reviewed to obtain the number of deaths. Treatment details and cause of death were analysed. Statistical analysis was performed to identify the risk factors for aspiration pneumonia. RESULTS: The records revealed that aspiration pneumonia was the cause of death in 51 out of 85 patients. Primary tumour site (oropharynx and hypopharynx, odds ratio 3.3; 95 per cent confidence interval 1.17-9.4, p = 0.02) and advanced tumour stage (odds ratio 4.2, 95 per cent confidence interval 1.16-15.61, p = 0.02) had significant negative impacts on aspiration pneumonia related mortality. CONCLUSION: Advanced pharyngeal cancer patients are at an increased risk of aspiration pneumonia related death. Investigations for the early detection of this condition are recommended in these high-risk patients.


Assuntos
Neoplasias de Cabeça e Pescoço/complicações , Pneumonia Aspirativa/mortalidade , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Estudos Retrospectivos , Fatores de Risco
17.
Oncogenesis ; 4: e147, 2015 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-25893634

RESUMO

Loco-regional recurrence in 50% of oral squamous cell carcinoma (OSCC) patients poses major challenge for oncologists. Lack of biomarkers that can predict disease aggressiveness and recurrence risk makes the scenario more dismal. On the basis of our earlier global proteomic analyses we identified five differentially expressed proteins in OSCC. This study aimed to develop protein biomarkers-based prognostic risk prediction model for OSCC. Sub-cellular expression of five proteins, S100A7, heterogeneous nuclear ribonucleoproteinK (hnRNPK), prothymosin α (PTMA), 14-3-3ζ and 14-3-3σ was analyzed by immunohistochemistry in test set (282 Indian OSCCs and 209 normal tissues), correlated with clinic-pathological parameters and clinical outcome over 12 years to develop a risk model for prediction of recurrence-free survival. This risk classifier was externally validated in 135 Canadian OSCC and 96 normal tissues. Biomarker signature score based on PTMA, S100A7 and hnRNPK was associated with recurrence free survival of OSCC patients (hazard ratio=1.11; 95% confidence interval 1.08, 1.13, P<0.001, optimism-corrected c-statistic=0.69) independent of clinical parameters. Biomarker signature score stratified OSCC patients into high- and low-risk groups with significant difference for disease recurrence. The high-risk group had median survival 14 months, and 3-year survival rate of 30%, whereas low-risk group survival probability did not reach 50%, and had 3-year survival rate of 71%. As a powerful predictor of 3-year recurrence-free survival in OSCC patients, the newly developed biomarkers panel risk classifier will facilitate patient counseling for personalized treatment.

18.
Oncogene ; 34(41): 5216-28, 2015 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-25639877

RESUMO

Nanomedicine era is not far from its realization, but a major concern of targeted delivery still stands tall in its way. Herein we demonstrate the mechanism underlying the anticancer activity of an RNA aptamer (Apt) conjugated to gefitinib-loaded poly (lactic co-glycolic acid) nanoparticles (GNPs). Apt was selected through Cell-SELEX (systemic evolution of ligands by exponential enrichment) process against gefitinib-resistant H1975 lung cancer cells. The selected aptamer exhibited high specificity toward H1975 cells, both qualitatively as well as quantitatively. Software analysis using the MATCH tool predicted Ets1, a proto-oncoprotein, to be the target of the selected aptamer. Interestingly, the localization of identified aptamer varied in descending order of Ets1 expression, wherein maximum localization was observed in H1975 cells than in MDA-MB231, DU-145, H23, H460, A431, A549 and MCF-7 cells, and minimum in L132 cells. Furthermore, Apt-GNP bio-conjugate showed augmented anticancer activity specifically in Ets1-overexpressing cells. In addition, partial depletion of Ets1 in H1975 cells and overexpression of Ets1 in L132 cells reversed the targeting efficacy of the aptamer. Notably, a single intratumoral injection of the Apt-GNP bio-conjugate abrogated the growth of tumor in H1975 xenograft nude mice. Altogether, we present a pioneering platform, involving aptamers, which can be clinically used as a diagnostic marker for metastasis as well as an effective delivery system to escort the pharmaceutical cargo specifically to Ets1-overexpressing highly progressive tumors.


Assuntos
Aptâmeros de Nucleotídeos/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Proteína Proto-Oncogênica c-ets-1/metabolismo , Animais , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Portadores de Fármacos/metabolismo , Portadores de Fármacos/farmacologia , Feminino , Gefitinibe , Humanos , Ácido Láctico/metabolismo , Neoplasias Pulmonares/patologia , Camundongos Nus , Nanopartículas/metabolismo , Metástase Neoplásica , Ácido Poliglicólico/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Quinazolinas/metabolismo , Quinazolinas/farmacologia , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Andrologia ; 47(3): 333-5, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24635732

RESUMO

Malignant peripheral nerve sheath tumour (MPNST) is a rare variety of soft tissue sarcoma that originates from Schwann cells or pluripotent cells of neural crest origin. They have historically been difficult tumours to diagnose and treat. Surgery is the mainstay of treatment with a goal to achieve negative margins. Despite aggressive surgery and adjuvant therapy, the prognosis of patients with MPNST remains poor. MPNST arising from penis is a very rare entity; thus, it presents a diagnostic and therapeutic challenge. We present a case of penile MPNST in a 38-year-old man in the absence of neurofibromatosis treated with surgery followed by post-operative radiotherapy to a dose of 60 Gray in 30 fractions and adjuvant chemotherapy with ifosfamide and adriamycin.


Assuntos
Neurilemoma/patologia , Neoplasias Penianas/patologia , Adulto , Antineoplásicos/uso terapêutico , Terapia Combinada , Doxorrubicina/uso terapêutico , Humanos , Ifosfamida/uso terapêutico , Masculino , Neurilemoma/terapia , Neoplasias Penianas/terapia , Resultado do Tratamento
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