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1.
J Immunother Cancer ; 12(3)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38508656

RESUMO

BACKGROUND: The effectiveness of somatic neoantigen-based immunotherapy is often hindered by the limited number of mutations in tumors with low to moderate mutation burden. Focusing on microsatellite-stable colorectal cancer (CRC), this study investigates the potential of tumor-associated circular RNAs (circRNAs) as an alternative source of neoepitopes in CRC. METHODS: Tumor-associated circRNAs in CRC were identified using the MiOncoCirc database and ribo-depletion RNA sequencing of paired clinical normal and tumor samples. Candidate circRNA expression was validated by quantitative real-time PCR (RT-qPCR) using divergent primers. TransCirc database was used for translation prediction. Human leukocyte antigen binding affinity of open reading frames from potentially translatable circRNA was predicted using pVACtools. Strong binders from messenger RNA-encoded proteins were excluded using BlastP. The immunogenicity of the candidate antigens was functionally validated through stimulation of naïve CD8+ T cells against the predicted neoepitopes and subsequent analysis of the T cells through enzyme-linked immunospot (ELISpot) assay, intracellular cytokine staining (ICS) and granzyme B (GZMB) reporter. The cytotoxicity of T cells trained with antigen peptides was further tested using patient-derived organoids. RESULTS: We identified a neoepitope from circRAPGEF5 that is upregulated in CRC tumor samples from MiOncoCirc database, and two neoepitopes from circMYH9, which is upregulated across various tumor samples from our matched clinical samples. The translation potential of candidate peptides was supported by Clinical Proteomic Tumor Analysis Consortium database using PepQuery. The candidate peptides elicited antigen-specific T cells response and expansion, evidenced by various assays including ELISpot, ICS and GZMB reporter. Furthermore, T cells trained with circMYH9 peptides were able to specifically target and eliminate tumor-derived organoids but not match normal organoids. This observation underscores the potential of circRNAs as a source of immunogenic neoantigens. Lastly, circMYH9 was enriched in the liquid biopsies of patients with CRC, thus enabling a detection-to-vaccination treatment strategy for patients with CRC. CONCLUSIONS: Our findings underscore the feasibility of tumor-associated circRNAs as an alternative source of neoantigens for cancer vaccines targeting tumors with moderate mutation levels.


Assuntos
Vacinas Anticâncer , Neoplasias Colorretais , Humanos , RNA Circular/genética , Linfócitos T CD8-Positivos , Antígenos de Neoplasias/genética , Proteômica , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Neoplasias Colorretais/patologia , Peptídeos
2.
Medicina (Kaunas) ; 59(6)2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37374333

RESUMO

Background and Objectives: It remains unclear which domains of preoperative health-related quality of life (HRQOL) and mental health are predictive of postoperative clinical and patient-reported outcomes in colorectal cancer (CRC) patients. Materials and Methods: A prospective cohort of 78 CRC patients undergoing elective curative surgery was recruited. The EORTC QLQ-C30 and HADS questionnaires were administered preoperatively and one month after surgery. Results: Preoperative cognitive functioning scores (95% CI 0.131-1.158, p = 0.015) and low anterior resection (95% CI 14.861-63.260, p = 0.002) independently predicted poorer 1-month postoperative global QOL. When postoperative complications were represented using the comprehensive complication index (CCI), poorer preoperative physical function scores were associated with higher CCI scores (B = -0.277, p = 0.014). Preoperative social function score (OR = 0.925, 95% CI 0.87 to 0.99; p = 0.019) was an independent predictor for 30-day readmission, while physical functioning score (OR = -0.620, 95% CI -1.073--0.167, p = 0.008) was inversely related to the length of hospitalization. The overall regressions for 1-month postoperative global QOL (R2: 0.546, F: 1.961, p = 0.023) and 30-day readmission (R2: 0.322, χ2: 13.129, p < 0.001) were statistically significant. Conclusions: Various QLQ-C30 domains were found to be predictive of postoperative outcomes, including complications, readmission, and length of hospitalization. Preoperative cognitive dysfunction and low AR were independent predictors of poorer postoperative global QOL. Future research should seek to examine the efficacy of targeting specific baseline QOL domains in improving clinical as well as patient-reported outcomes after CRC surgery.


Assuntos
Neoplasias Colorretais , Protectomia , Humanos , Qualidade de Vida/psicologia , Estudos Prospectivos , Saúde Mental , Neoplasias Colorretais/complicações , Inquéritos e Questionários
3.
Nat Commun ; 14(1): 1726, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36977662

RESUMO

Mis-sense mutations affecting TP53 promote carcinogenesis both by inactivating tumor suppression, and by conferring pro-carcinogenic activities. We report here that p53 DNA-binding domain (DBD) and transactivation domain (TAD) mis-sense mutants unexpectedly activate pro-carcinogenic epidermal growth factor receptor (EGFR) signaling via distinct, previously unrecognized molecular mechanisms. DBD- and TAD-specific TP53 mutants exhibited different cellular localization and induced distinct gene expression profiles. In multiple tissues, EGFR is stabilized by TAD and DBD mutants in the cytosolic and nuclear compartments respectively. TAD mutants promote EGFR-mediated signaling by enhancing EGFR interaction with AKT via DDX31 in the cytosol. Conversely, DBD mutants maintain EGFR activity in the nucleus, by blocking EGFR interaction with the phosphatase SHP1, triggering c-Myc and Cyclin D1 upregulation. Our findings suggest that p53 mutants carrying gain-of-function, mis-sense mutations affecting two different domains form new protein complexes that promote carcinogenesis by enhancing EGFR signaling via distinctive mechanisms, exposing clinically relevant therapeutic vulnerabilities.


Assuntos
Receptores ErbB , Proteína Supressora de Tumor p53 , Proteína Supressora de Tumor p53/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Transdução de Sinais , Ativação Transcricional , Fosforilação
4.
Skinmed ; 20(6): 414-419, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36537673

RESUMO

Sensitive skin exposed to external insults (i.e., allergens, chemicals, and radiation) becomes erythematosus, and with repeated aggravations may become chronically dry. This is often observed in atopic dermatitis and allergic contact dermatitis, two skin conditions that display key pathogenic components: barrier dysfunction, skewed inflammatory immune response, and pruritus. Recent studies have evidenced that oxidative stress is a possible fourth component of the pathogenesis of sensitive skin. In patients with persistent disease, new agents and combination therapies that target oxidative stress along with other hallmarks of dry and sensitive skin have depicted positive effects on clinical outcomes in infants with dry and sensitive skin. In this paper, we reviewed clinical registration studies of products that have been observed to reduce skin dryness with cosmetically acceptable effects. Overall, similar approaches may be explored to improve the management of dry skin across all age groups for better consistency in achieving treatment goals. (SKINmed. 2022;20:414-419).


Assuntos
Prestação Integrada de Cuidados de Saúde , Dermatite Alérgica de Contato , Dermatite Atópica , Eczema , Dermatopatias , Humanos , Dermatite Atópica/tratamento farmacológico
5.
Nat Cell Biol ; 24(6): 928-939, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35618746

RESUMO

Most mammalian genes generate messenger RNAs with variable untranslated regions (UTRs) that are important post-transcriptional regulators. In cancer, shortening at 3' UTR ends via alternative polyadenylation can activate oncogenes. However, internal 3' UTR splicing remains poorly understood as splicing studies have traditionally focused on protein-coding alterations. Here we systematically map the pan-cancer landscape of 3' UTR splicing and present this in SpUR ( http://www.cbrc.kaust.edu.sa/spur/home/ ). 3' UTR splicing is widespread, upregulated in cancers, correlated with poor prognosis and more prevalent in oncogenes. We show that antisense oligonucleotide-mediated inhibition of 3' UTR splicing efficiently reduces oncogene expression and impedes tumour progression. Notably, CTNNB1 3' UTR splicing is the most consistently dysregulated event across cancers. We validate its upregulation in hepatocellular carcinoma and colon adenocarcinoma, and show that the spliced 3' UTR variant is the predominant contributor to its oncogenic functions. Overall, our study highlights the importance of 3' UTR splicing in cancer and may launch new avenues for RNA-based anti-cancer therapeutics.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Regiões 3' não Traduzidas/genética , Adenocarcinoma/genética , Processamento Alternativo/genética , Animais , Carcinogênese/genética , Neoplasias do Colo/genética , Mamíferos , Regulação para Cima
6.
Ann Acad Med Singap ; 51(1): 24-39, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35091728

RESUMO

INTRODUCTION: In Singapore, non-anaesthesiologists generally administer sedation during gastrointestinal endoscopy. The drugs used for sedation in hospital endoscopy centres now include propofol in addition to benzodiazepines and opiates. The requirements for peri-procedural monitoring and discharge protocols have also evolved. There is a need to develop an evidence-based clinical guideline on the safe and effective use of sedation by non-anaesthesiologists during gastrointestinal endoscopy in the hospital setting. METHODS: The Academy of Medicine, Singapore appointed an expert workgroup comprising 18 gastroenterologists, general surgeons and anaesthesiologists to develop guidelines on the use of sedation during gastrointestinal endoscopy. The workgroup formulated clinical questions related to different aspects of endoscopic sedation, conducted a relevant literature search, adopted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology and developed recommendations by consensus using a modified Delphi process. RESULTS: The workgroup made 16 recommendations encompassing 7 areas: (1) purpose of sedation, benefits and disadvantages of sedation during gastrointestinal endoscopy; (2) pre-procedural assessment, preparation and consent taking for sedation; (3) Efficacy and safety of drugs used in sedation; (4) the role of anaesthesiologist administered sedation during gastrointestinal endoscopy; (5) performance of sedation; (6) post-sedation care and discharge after sedation; and (7) training in sedation for gastrointestinal endoscopy for non-anaesthesiologists. CONCLUSION: These recommendations serve to guide clinical practice during sedation for gastrointestinal endoscopy by non-anaesthesiologists in the hospital setting.


Assuntos
Sedação Consciente , Hipnóticos e Sedativos , Endoscopia Gastrointestinal , Hospitais , Humanos , Singapura
7.
Oncogene ; 41(8): 1178-1189, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34937878

RESUMO

3'UTR shortening in cancer has been shown to activate oncogenes, partly through the loss of microRNA-mediated repression. This suggests that many reported microRNA-oncogene target interactions may not be present in cancer cells. One of the most well-studied oncogenes is the transcription factor MYC, which is overexpressed in more than half of all cancers. MYC overexpression is not always accompanied by underlying genetic aberrations. In this study, we demonstrate that the MYC 3'UTR is shortened in colorectal cancer (CRC). Using unbiased computational and experimental approaches, we identify and validate microRNAs that target the MYC coding region. In particular, we show that miR-138 inhibits MYC expression and suppresses tumor growth of CRC and hepatocellular carcinoma (HCC) cell lines. Critically, the intravenous administration of miR-138 significantly impedes MYC-driven tumor growth in vivo. Taken together, our results highlight the previously uncharacterized shortening of the MYC 3'UTR in cancer, and identify miR-138 as a potent regulator of the heterogenous MYC transcript population.


Assuntos
Carcinoma Hepatocelular
8.
Biosens Bioelectron ; 186: 113283, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33979719

RESUMO

We reported a proof-of-concept study of developing an electrochemical biosensor for prolonged continuous monitoring free flap failure caused by vascular occlusion after reconstructive surgery. Ferrocene (Fc)-containing Chitosan-cografted-Branched Polyethylenimine redox conjugates (CHIT-Fc-co-BPEI-Fc) were used as pH-tuneable matrix to attach the target enzymes (glucose oxidase ≡ GOD and lactate oxidase ≡ LOD, respectively) to build up the corresponding GOD-sensor and LOD-sensor. The sensitivity of GOD-/LOD-sensor was found to be 2.89(±0.06)µA/mM and 2.95(±0.19)µA/mM with a limit of detection (LOD) of 0.047 mM and 0.172 mM, respectively. The sensor performance was further pre-clinically validated via rabbit study, which confirmed that the designed biosensors could electrochemically detect the changes of metabolite levels caused by flap failure within minutes. This sensor protocol is able to be fabricated as embedded biosensor for prolong continuous detection for clinical application/research.

9.
Ann Acad Med Singap ; 50(12): 892-902, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34985101

RESUMO

INTRODUCTION: Prehabilitation may benefit older patients undergoing major surgeries. Currently, its efficacy has not been conclusively proven. This is a retrospective review of a multimodal prehabilitation programme. METHODS: Patients aged 65 years and above undergoing major abdominal surgery between May 2015 and December 2019 in the National University Hospital were included in our institutional programme that incorporated aspects of multimodal prehabilitation and Enhanced Recovery After Surgery concepts as 1 holistic perioperative pathway to deal with issues specific to older patients. Physical therapy, nutritional advice and psychosocial support were provided as part of prehabilitation. RESULTS: There were 335 patients in the prehabilitation cohort and 256 patients whose records were reviewed as control. No difference in postoperative length of stay (P=0.150) or major complications (P=0.690) were noted. Patients in the prehabilitation group were observed to ambulate a longer distance and participate more actively with their physiotherapists from postoperative day 1 until 4. In the subgroup of patients with cancer, more patients had undergone neoadjuvant therapy in the prehabilitation group compared to the control group (21.7% versus 12.6%, P=0.009). Prehabilitation patients were more likely to proceed to adjuvant chemotherapy (prehabilitation 87.2% vs control 65.6%, P<0.001) if it had been recommended. CONCLUSION: The current study found no differences in traditional surgical outcome measures with and without prehabilitation. An increase in patient mobility in the immediate postoperative period was noted with prehabilitation, as well as an association between prehabilitation and increased adherence to postoperative adjuvant therapy. Larger prospective studies will be needed to validate the findings of this retrospective review.


Assuntos
Cuidados Pré-Operatórios , Exercício Pré-Operatório , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Estudos Retrospectivos
10.
Sci Adv ; 6(15): eaaz5443, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32300659

RESUMO

Ocean warming increases the incidence of coral bleaching, which reduces or eliminates the nutrition corals receive from their algal symbionts, often resulting in widespread mortality. In contrast to extensive knowledge on the thermal tolerance of coral-associated symbionts, the role of the coral host in bleaching patterns across species is poorly understood. Here, we applied a Bayesian analysis of carbon and nitrogen stable isotope data to determine the trophic niche overlap between corals and their symbionts and propose benchmark values that define autotrophy, heterotrophy, and mixotrophy. The amount of overlap between coral and symbiont niche was negatively correlated with polyp size and bleaching resistance. Our results indicated that as oceans warm, autotrophic corals lose their competitive advantage and thus are the first to disappear from coral reefs.


Assuntos
Antozoários , Recifes de Corais , Animais , Carbono , Ecossistema , Meio Ambiente , Nitrogênio , Oceanos e Mares , Simbiose
11.
Int J Colorectal Dis ; 34(6): 1043-1046, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30953142

RESUMO

OBJECTIVE: Our study seeks to describe our surgical technique of the use of a tissue expander and a pelvic sling in order to perform high-dose pelvic irradiation without incurring radiation toxicity to the small bowel. High-dose radiation therapy for pelvic tumours comes at a risk of radiation toxicity to the small bowel. Our study discusses our novel surgical technique of compartmentalising the abdomen and the pelvis through the use of a tissue expander and pelvic sling to avoid small bowel radiation toxicity. METHODS: We present a patient with an unresectable sacral chordoma. We describe our surgical technique incorporating both a tissue expander and an absorbable pelvic mesh sling to successfully compartmentalise the abdomen from the pelvis. RESULTS: The patient underwent an uneventful surgical procedure to place the tissue expander within the pelvis and deploy the pelvic mesh sling. Following surgery, a separation of at least 8 cm was achieved between bowel loops and the tumour. A dose of 70 Gy delivered over 35 fractions using intensity modulated radiotherapy (IMRT) was administered to the sacral chordoma, whilst managing to constrain the maximum bowel dose to 35.7 Gy. Surgery to remove the tissue expander was uneventful. The patient has not suffered any small bowel irradiation toxicity. CONCLUSIONS: Our technique to exclude small bowel from the pelvis is effective and safe. This technique not only can be applied in the setting of unresectable sacral chordomas but also may be applicable to other pelvic cancers which require radiation therapy.


Assuntos
Intestino Delgado/patologia , Pelve/patologia , Pelve/efeitos da radiação , Dosagem Radioterapêutica , Dispositivos para Expansão de Tecidos , Idoso , Relação Dose-Resposta à Radiação , Feminino , Humanos , Telas Cirúrgicas , Resultado do Tratamento
13.
Cancer Lett ; 423: 1-8, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29518480

RESUMO

We evaluated the changes in CTC count and CTC-associated miRNAs during the course of chemotherapy in patients with metastatic colorectal cancer. Blood samples were collected from 9 metastatic colorectal cancer patients prior to chemotherapy and at every other chemotherapy session during the course of treatment. CTCs were isolated and enumerated using a size-exclusion method (CellSievo, Singapore). CTC-associated miRNAs were isolated using a paper-based, partitioning method, and analyzed using reverse transcription quantitative real-time PCR (MiRXES, Singapore). CTC count trends generally correlated with disease progression defined by radiological measurements and trends in carcinoembryonic antigen (CEA) levels; hence CTC counts may be useful in cases where CEA is not elevated. CTC-associated miRNAs identified were miR-15b, miR-16, miR-19a, miR-21, miR-25, miR-30d, miR-126, miR-185, miR-221, miR-222, and miR-324-5p. The expression of CTC-associated miRNAs did not appear to correlate with CTC count and exhibited inter-individual heterogeneity. This pilot study suggests that analysis of CTC changes during the course of treatment may be useful in monitoring response to therapy in metastatic colorectal cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , MicroRNAs/genética , Células Neoplásicas Circulantes/efeitos dos fármacos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Contagem de Células , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Estudos Longitudinais , Masculino , MicroRNAs/isolamento & purificação , Pessoa de Meia-Idade , Metástase Neoplásica , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento
14.
Singapore Med J ; 59(6): 305-310, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29167909

RESUMO

INTRODUCTION: Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) surgery for locally advanced rectal cancer has been shown to improve local control and reduce toxicity, as compared to adjuvant CRT. We reported the outcomes of our patients with locally advanced rectal cancer treated at National University Hospital, Singapore. METHODS: From April 2002 to December 2014, 117 patients with T3/4, N0/+, M0 rectal cancer received neoadjuvant CRT followed by TME surgery. The treatment regimen comprised a total radiotherapy dose of 50.4 Gy in 28 daily fractions delivered concurrently with 5-fluorouracil or capecitabine chemotherapy over 5.5 weeks. All patients were planned for TME surgery. Local control, disease-free survival, overall survival and treatment toxicities were analysed. RESULTS: Median follow-up was 34 (range 2-122) months. 11.5% (13/113) of patients achieved a pathological complete response (pCR) and 72.6% (85/117) had either tumour or nodal downstaging following neoadjuvant CRT. 5.2% (5/96) of patients had Grade 3 acute toxicities (dermatitis and diarrhoea) and 3.1% (3/96) had Grade 3 late toxicities (fistula and stricture). There was no Grade 4 toxicity noted. The five-year local recurrence, disease-free survival and overall survival rates were 4.5%, 65.7% and 80.6%, respectively. Multivariate analysis showed that nodal positivity was a predictor of poor disease-free survival and poor overall survival. Tumour downstaging and pCR did not improve outcomes. CONCLUSION: Our outcomes were comparable to internationally published data, and this treatment regimen remains the standard of care for locally advanced rectal cancer in our local population.


Assuntos
Adenocarcinoma/cirurgia , Adenocarcinoma/terapia , Quimiorradioterapia Adjuvante , Terapia Neoadjuvante , Neoplasias Retais/cirurgia , Neoplasias Retais/terapia , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais , Procedimentos Cirúrgicos do Sistema Digestório , Intervalo Livre de Doença , Feminino , Fluoruracila/farmacologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Neoplasias Retais/mortalidade , Reto/patologia , Reto/cirurgia , Singapura , Resultado do Tratamento
15.
J Cancer ; 8(16): 3114-3121, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29158782

RESUMO

Objectives: To determine the pathological response rates and toxicity and in patients with locally advanced rectal cancer treated with concurrent capecitabine and dose escalated intensity modulated radiotherapy (IMRT) Methods: Patients with stage II or III adenocarcinoma of the rectum were treated with preoperative concurrent capecitabine and IMRT. Dose of capecitabine was 825mg/m2, 5 days a week for 5 weeks. IMRT was used to deliver a dose of 45Gy in 25 fractions (1.8Gy per fraction daily, 5 days a week over 5 weeks) to the regional lymphatics and areas at risk of harbouring microscopic disease. A concomitant synchronous integrated boost (SIB) to the gross tumour with a margin to a total dose of 55Gy in 25 fractions was also delivered in the same period. TME surgery was performed 8 weeks after preoperative therapy. The primary endpoint is pathological complete response rate (pCR) and the secondary endpoint was downstaging rates, Sphincter preservation rates (SPR), disease free survival (DFS) at 2 years and toxicity graded using the CTCAE v3.0. Results: Twenty three patients were enrolled. Three were not evaluable; one did not complete treatment due to logistic issues and two declined surgery. The remaining 20 patients completed preoperative chemoIMRT followed by TME surgery. At a median follow-up of 38.2 months (17.5-53.2 months), 90% (18 of 20) patients were alive. The 2 year overall survival and DFS were 90% and 90% respectively. 35%(7/20) of patients had a pCR. 65% (13 of 20) patients had successful downstaging of their rectal tumours. There was no local recurrence. Sphincter preservation rate was 85%. Treatment was well tolerated with only one patient (5%) having Grade 3 radiation proctitis. Conclusions: Preoperative concurrent capecitabine and dose escalated IMRT is well tolerated and results in high rates of pCR. A randomized trial comparing this regimen with standard 3D conformal chemoradiotherapy is warranted.

16.
Clin Chem ; 63(3): 731-741, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28073899

RESUMO

BACKGROUND: Molecular characterization of circulating tumor cells (CTCs) holds great promise for monitoring metastatic progression and characterizing metastatic disease. However, leukocyte and red blood cell contamination of routinely isolated CTCs makes CTC-specific molecular characterization extremely challenging. METHODS: Here we report the use of a paper-based medium for efficient extraction of microRNAs (miRNAs) from limited amounts of biological samples such as rare CTCs harvested from cancer patient blood. Specifically, we devised a workflow involving the use of Flinders Technology Associates (FTA)® Elute Card with a digital PCR-inspired "partitioning" method to extract and purify miRNAs from plasma and CTCs. RESULTS: We demonstrated the sensitivity of this method to detect miRNA expression from as few as 3 cancer cells spiked into human blood. Using this method, background miRNA expression was excluded from contaminating blood cells, and CTC-specific miRNA expression profiles were derived from breast and colorectal cancer patients. Plasma separated out during purification of CTCs could likewise be processed using the same paper-based method for miRNA detection, thereby maximizing the amount of patient-specific information that can be derived from a single blood draw. CONCLUSIONS: Overall, this paper-based extraction method enables an efficient, cost-effective workflow for maximized recovery of small RNAs from limited biological samples for downstream molecular analyses.


Assuntos
Perfilação da Expressão Gênica/métodos , MicroRNAs/sangue , MicroRNAs/genética , Células Neoplásicas Circulantes/metabolismo , Papel , Humanos , MicroRNAs/análise , MicroRNAs/isolamento & purificação , Células Neoplásicas Circulantes/patologia , Células Tumorais Cultivadas
17.
J Cutan Aesthet Surg ; 9(2): 85-92, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27398008

RESUMO

Conventional acne treatment presents several challenges such as intolerable side effects and antibiotic resistance. Dermocosmetic products may be used to reduce these unwanted effects. Dermocosmetics include skin cleansers, topical sebum-controllers, skin antimicrobial/anti-inflammatory agents, moisturizers, sunscreens, and camouflage products. Appropriate use of these products may help augment the benefit of acne treatment, minimize side effects, and reduce the need for topical antibiotics. In Asia, there is currently limited scientific data on the application and recommendations for dermocosmetic use in acne vulgaris (AV). This article reviews the evidence on dermocosmetics for AV and provides practice recommendations as discussed during the 4(th) Asia-Pacific Acne Leaders' Summit held in Bangkok, Thailand, on 7 and 8 February 2015. Through a premeeting survey, a series of plenary lectures, a stepwise program of discussion sessions, and Medline article review, the Expert Panel set forth relevant recommendations on the role of dermocosmetics as adjunct for treating AV in Asian patients.

18.
Proteomics ; 15(22): 3905-20, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26359947

RESUMO

The high mortality rate in colorectal cancer is mostly ascribed to metastasis, but the only clinical biomarker available for disease monitoring and prognosis is the carcinoembryonic antigen (CEA). However, the prognostic utility of CEA remains controversial. In an effort to identify novel biomarkers that could be potentially translated for clinical use, we collected the secretomes from the colon adenocarcinoma cell line HCT-116 and its metastatic derivative, E1, using the hollow fiber culture system, and utilized the multilectin affinity chromatography approach to enrich for the secreted glycoproteins (glyco-secretome). The HCT-116 and E1 glyco-secretomes were compared using the label-free quantitative SWATH-MS technology, and a total of 149 glycoproteins were differentially secreted in E1 cells. Among these glycoproteins, laminin ß-1 (LAMB1), a glycoprotein not previously known to be secreted in colorectal cancer cells, was observed to be oversecreted in E1 cells. In addition, we showed that LAMB1 levels were significantly higher in colorectal cancer patient serum samples as compared to healthy controls when measured using ELISA. ROC analyses indicated that LAMB1 performed better than CEA at discriminating between colorectal cancer patients from controls. Moreover, the diagnostic performance was further improved when LAMB1 was used in combination with CEA.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Laminina/sangue , Proteoma/metabolismo , Biomarcadores Tumorais/metabolismo , Antígeno Carcinoembrionário/sangue , Estudos de Casos e Controles , Linhagem Celular Tumoral , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Humanos , Laminina/metabolismo , Metástase Neoplásica
19.
Eur Heart J ; 36(47): 3332-42, 2015 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-26330419

RESUMO

AIMS: Theoretically, bioresorbable vascular scaffolds (BVSs) may provide superior long-term results compared with permanent metallic drug-eluting stents (DESs). However, whether BVSs are as safe and effective as metallic DESs prior to complete bioresorption is unknown. METHODS AND RESULTS: ABSORB Japan was a single-blind, multicentre, active-controlled, randomized trial designed to support regulatory approval of the Absorb BVS in Japan. Eligible patients with one or two de novo lesions in different epicardial vessels were randomized at 38 Japanese sites in a 2:1 ratio to Absorb BVS vs. cobalt-chromium everolimus-eluting stents (CoCr-EESs). The primary endpoint was target lesion failure [TLF: a composite of cardiac death, myocardial infarction attributable to target vessel, or ischaemia-driven target lesion revascularization (ID-TLR)] at 12 months, powered for non-inferiority. The major secondary endpoint was angiographic in-segment late lumen loss (LLL) at 13 months. A total of 400 patients were randomized to BVSs (266 patients and 275 lesions) or CoCr-EESs (134 patients and 137 lesions). TLF through 12 months was 4.2% with BVSs and 3.8% with CoCr-EESs [difference (upper one-sided 95% confidence limit) = 0.39% (3.95%); Pnon-inferiority < 0.0001]. Definite/probable stent/scaffold thrombosis at 12 months occurred in 1.5% of the patients with both devices (P = 1.0), and ID-TLR for restenosis was infrequent (1.1% with BVSs and 1.5% with CoCr-EESs, P = 1.0). With 96.0% angiographic follow-up, in-segment LLL at 13 months was 0.13 ± 0.30 mm with BVSs and 0.12 ± 0.32 mm with CoCr-EESs [difference (upper one-sided 95% confidence limit) = 0.01 (0.07); Pnon-inferiority < 0.0001). CONCLUSION: In the ABSORB Japan randomized trial, 12-month clinical and 13-month angiographic outcomes of BVSs were comparable to CoCr-EESs. CLINICAL REGISTRATION: ClinicalTrials.gov, number NCT01844284.


Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Stents Farmacológicos , Everolimo/administração & dosagem , Imunossupressores/administração & dosagem , Alicerces Teciduais , Implantes Absorvíveis , Idoso , Doença da Artéria Coronariana/cirurgia , Feminino , Oclusão de Enxerto Vascular/etiologia , Humanos , Masculino , Infarto do Miocárdio/etiologia , Revascularização Miocárdica/métodos , Duração da Cirurgia , Intervenção Coronária Percutânea/métodos , Desenho de Prótese , Método Simples-Cego , Resultado do Tratamento
20.
Int J Colorectal Dis ; 30(7): 963-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26003115

RESUMO

PURPOSE: Increased physiological stress from laparoscopic surgery and the lower physiological reserves in the elderly are causes for concern. This study aims to compare the outcomes between laparoscopic and open colorectal surgery in octogenarians. METHODS: Octogenarians who underwent elective colorectal resections from 2000 to 2011 were reviewed. Patients who underwent laparoscopic surgery were matched for comorbidities, T-staging and type of resection performed to patients with open surgery. RESULTS: Each group had 36 patients. Both groups were comparable for median age (85 vs 83, p = 0.43), gender (21 vs 18 males, p = 0.64) and the American Society of Anaesthesiologists (ASA) score (p = 0.486). Both groups had comparable median maximal tumour dimensions (4.75 vs 4.25 cm, p = 0.38) and median number of lymph nodes harvested (15 vs 14, p = 0.94). The laparoscopic group had, however, a longer median operative time (167.5 vs 124.5 min, p < 0.001). Both groups had comparable median length of hospitalisation (8 vs 7, p = 0.83), number of complications with a grade of complication (GOC) of ≥3 (5 vs 7, p = 0.75) and 30-day mortality rates (8.3 vs 5.6%, p = 1.00). One-year survival rate for the open group was lower (75.0 vs 94.4%, p = 0.09). CONCLUSIONS: Despite a longer operating time, laparoscopic surgery had comparable short-term outcomes and might have a long-term survival benefit.


Assuntos
Neoplasias Colorretais/cirurgia , Cirurgia Colorretal , Laparoscopia , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Demografia , Feminino , Humanos , Masculino , Cuidados Pós-Operatórios
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