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1.
J Craniofac Surg ; 35(4): 1157-1159, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38284877

RESUMO

The aim of this study was to evaluate the quality of the information on YouTube regarding night guards (NGs). YouTube was systematically searched using the keyword "night guards." Two independent reviewers examined the first 100 videos and exclusion criteria were applied. Descriptive characteristics of the remaining 60 videos were recorded. In addition, the purpose, target audience, and source of the included videos were collected. A 12-point content scale (CS) was used to evaluate video content, and the Global Quality Scale (GQS) was used to determine video quality. Statistical analyses were performed using the Kruskal-Wallis and Mann-Whitney tests, and the correlation between scores was evaluated using Spearman rho. Of the included videos, 50% were uploaded by dentists/health institutions, 26% by commercial sources and 24% by laypersons. The aim of 80% of the videos was to inform laypeople and 14% to inform professionals only. The content discussed the most (59.3%) was the production stages of NGs. The mean CS and GQS score of the videos were 2.06 ± 1.35 (poor) and 1.71 ± 0.88 (generally poor), respectively. A positive correlation was found between the CS and GQS scores ( r = 0.447). YouTube videos were found to be poor in terms of both content and quality. Since NGs for treating bruxism will always be a trending topic for patients on social media, the content of YouTube videos should be checked and enriched by professionals so that patients can access accurate information, especially about NGs obtained over the counter.


Assuntos
Mídias Sociais , Gravação em Vídeo , Humanos , Informação de Saúde ao Consumidor/normas , Dispositivos para o Cuidado Bucal Domiciliar , Educação de Pacientes como Assunto , Bruxismo do Sono
2.
Comput Inform Nurs ; 42(4): 305-312, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38478918

RESUMO

Knee arthroplasty surgery, which is increasingly performed due to increased life expectancy, has positive outcomes, although it can also cause serious health problems following surgery. This study was conducted to evaluate the impact of patient-related education via a QR code on total knee arthroplasty problems and emergency department referral rates. Participants were randomly assigned to intervention (n = 51) and control (n = 51) groups. The intervention group received QR code-supported training. The outcomes were assessed at baseline (preoperative), discharge, and postoperative sixth week. In the intervention group, significantly fewer problems related to total knee arthroplasty occurred at discharge and in week 6, and a higher level of functionality was noted ( P < .05). In week 6, the rate of emergency department admissions was lower, and mean scores for satisfaction with patient training were higher in the intervention group ( P < .05). In conclusion, QR code-supported patient training was effective in reducing the physiological and psychosocial problems related to total knee arthroplasty and the emergency department referral rates. In addition, it provided functional improvement and increased satisfaction with patient training.


Assuntos
Artroplastia do Joelho , Procedimentos Ortopédicos , Humanos , Satisfação do Paciente , Alta do Paciente , Serviço Hospitalar de Emergência
3.
Ann Surg Oncol ; 30(3): 1795-1807, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36528743

RESUMO

BACKGROUND: Gastric adenocarcinoma (GAC) is the fifth most common cancer in the world, and the presence of germline pathogenic variants has been linked with approximately 5% of gastric cancer diagnoses. Multiple GAC susceptibility genes have been identified, but information regarding the risk associated with pathogenic variants in these genes remains obscure. We conducted a systematic review of existing studies reporting the penetrance of GAC susceptibility genes. METHODS: A structured search query was devised to identify GAC-related papers indexed in MEDLINE/PubMed. A semi-automated natural language processing algorithm was applied to identify penetrance papers for inclusion. Original studies reporting the penetrance of GAC were included and the full-text articles were independently reviewed. Summary statistics, effect estimates, and precision parameters from these studies were compiled into a table using a predetermined format to ensure consistency. RESULTS: Forty-five studies were identified reporting the penetrance of GAC among patients harboring mutations in 13 different genes: APC, ATM, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, PMS2, MUTYH-Monoallelic, NBN, and STK11. CONCLUSION: Our systematic review highlights the importance of testing for germline pathogenic variants in patients before the development of GAC. Management of patients who harbor a pathogenic mutation is multifactorial, and clinicians should consider cancer risk for each applicable gene-cancer association throughout the screening and management process. The scarcity of studies we found investigating the risk of GAC among patients with pathogenic variants in GAC susceptibility genes highlights the need for more investigations that focus on producing robust risk estimates for gene-cancer associations.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Penetrância , Neoplasias Gástricas/genética , Predisposição Genética para Doença , Mutação , Mutação em Linhagem Germinativa , Adenocarcinoma/genética
4.
J Craniofac Surg ; 33(7): 2100-2103, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35258014

RESUMO

ABSTRACT: The aim of this study is to investigate the quality of the information YouTube TM offers to patients concerning dental implant failure. YouTube TM was searched systematically using the keyword 'dental implant failure'. The first 100 videos were viewed by two independent researchers. For each video, its purpose, target audience and source were also recorded. A 10 point content scale (CS) was used to evaluate the video content. The Global Quality Scale (GQS) was also used to determine the quality of videos. Statistical analyses were performed using the Kruskal Wallis and Mann Whitney test and correlation coefficient analyses were performed using Spearman's Rho. While 92.2% of the videos included in the study were uploaded by dentists/health institutions, only 3.1% were uploaded by laypersons. Of the videos, 40.6% were aimed at informing laypersons and 56.3% targetted professionals. The content which was discussed most (71.9%) was 'definition of a dental implant' followed by 'reasons for failure' (65.6%). The mean CS and GQS score of the videos were 3.75 ± 2.35 (moderate) and 2.07 ± 1.05 (generally poor), respectively. There was a positive correlation between the CS and GQS score (r = 0.620). The quality of information on YouTube TM regarding dental implant failure was found inadequate. Thus, the information currently available online needs to be constantly checked and improved by professionals. In addition, clinicians should improve the ways in which they use YouTube TM to better inform patients about the causes, risks and treatment choices involved with failed dental implants.


Assuntos
Implantes Dentários , Mídias Sociais , Humanos , Disseminação de Informação , Reprodutibilidade dos Testes , Gravação em Vídeo
5.
Breast J ; 24(4): 592-598, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29316072

RESUMO

BACKGROUND: The impact of age on breast cancer risk model calculations at the population level has not been well documented. METHODS: Retrospective analysis of formal breast cancer risk assessment in 36 542 females ages 40-84 at a single institution from 02/2007 to 12/2009. Five-year and lifetime breast cancer risks were calculated using Gail, Tyrer-Cuzick version 6 (TC6), Tyrer-Cuzick version 7 (TC7), BRCAPRO, and Claus models. Risk of BRCA mutation was calculated using BRCAPRO, TC6, TC7, and Myriad. Eligibility for BRCA testing was assessed using NCCN guidelines. Descriptive analyses were performed and trends in risk were assessed by age. RESULTS: The lifetime risk of breast cancer trended down with increasing age in all risk models. TC7 calculated the highest estimates for lifetime risk for all age ranges and had the highest proportion of patients with a calculated lifetime risk >20%. Five-year risk increased with age in all models. By age 60-64, every risk model predicted a mean 5-year risk ≥1.7%. Myriad estimated >5% risk of BRCA mutation more often than other models for all ages. Risk of BRCA mutation stayed constant with age with Myriad, but trended down with increasing age with TC6, TC7, and BRCAPRO. CONCLUSIONS: More patients have an estimated lifetime risk of breast cancer >20% and qualify for MRI screening with the Tyrer-Cuzick model. All models predict an increased 5-year risk with age, which could impact chemoprevention recommendations. To maximize access to genetic testing, the Myriad model and NCCN guidelines should be used.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Estudos Transversais , Feminino , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença/etnologia , Testes Genéticos/métodos , Humanos , Judeus/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Inquéritos e Questionários
6.
J Oral Maxillofac Surg ; 76(9): 1983-1990, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29625030

RESUMO

PURPOSE: To evaluate the long-term postsurgical stability of counterclockwise rotation of the occlusal plane (OP) in double-jaw orthognathic surgery in patients with hyperdivergent Class III malocclusion. MATERIALS AND METHODS: This retrospective cohort study evaluated the postsurgical stability of orthognathic surgery in patients with skeletal Class III malocclusion and counterclockwise rotation of the maxillomandibular complex with an OP change of at least -2°. Patients were evaluated with lateral cephalometric analysis before surgery, immediately after surgery, and at longest follow-up. The primary predictor variable was the change in angle of the OP and the Frankfort horizontal (FH) after surgery. The primary outcome variable was stability of the OP at longest follow-up. Other study variables were age, gender, and the following cephalometric measurements: mandibular plane angle; gonial angle; angle formed by the sella, nasion, and B point; maxillary height; angle of the palatal plane to the line connecting the sella and nasion; and distances of the posterior nasal spine and A point to the FH and of the A point to the vertical line passing from the nasion. The Mann-Whitney U test was used to compare stability between groups because the variables were not normally distributed. Bonferroni correction was used to evaluate P values. The χ2 test and Fisher exact test, where appropriate, were used to compare the proportions of groups. A P value less than .05 was accepted as statistically significant. RESULTS: The sample was composed of 15 adult patients (mean age at surgery, 23.5 yr; 40% men). The median duration of follow-up was 48 months (interquartile range, 36 to 60 months). The groups had similar demographic properties and similar surgical changes. Ten patients showed very stable results with an OP-FH change no greater than 1°. Four patients showed unstable results with an OP-FH change of 2.25 ± 0.5° during the follow-up period. The change in the mandibular plane angle was notable between patients with stability and those with instability, which was the variable most affected by relapse of the OP. CONCLUSION: This study found long-term postsurgical skeletal stability of counterclockwise rotation of the OP during double-jaw orthognathic surgery in patients with high angle Class III malocclusion after a median follow-up of 48 months.


Assuntos
Má Oclusão Classe III de Angle/cirurgia , Procedimentos Cirúrgicos Ortognáticos/métodos , Cefalometria , Feminino , Humanos , Masculino , Mandíbula/cirurgia , Maxila/cirurgia , Estudos Retrospectivos , Rotação , Resultado do Tratamento , Adulto Jovem
7.
Breast Cancer Res Treat ; 164(2): 263-284, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28444533

RESUMO

Numerous models have been developed to quantify the combined effect of various risk factors to predict either risk of developing breast cancer, risk of carrying a high-risk germline genetic mutation, specifically in the BRCA1 and BRCA2 genes, or the risk of both. These breast cancer risk models can be separated into those that utilize mainly hormonal and environmental factors and those that focus more on hereditary risk. Given the wide range of models from which to choose, understanding what each model predicts, the populations for which each is best suited to provide risk estimations, the current validation and comparative studies that have been performed for each model, and how to apply them practically is important for clinicians and researchers seeking to utilize risk models in their practice. This review provides a comprehensive guide for those seeking to understand and apply breast cancer risk models by summarizing the majority of existing breast cancer risk prediction models including the risk factors they incorporate, the basic methodology in their development, the information each provides, their strengths and limitations, relevant validation studies, and how to access each for clinical or investigative purposes.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Fatores de Confusão Epidemiológicos , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Modelos Estatísticos , Medição de Risco , Fatores de Risco
8.
Lasers Med Sci ; 32(3): 673-677, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28190112

RESUMO

Oral mucositis (OM) induces severe pain and limits fundamental life behaviors such as eating, drinking, and talking for patients receiving chemotherapy or radiotherapy. In addition, through opportunistic microorganisms, OM frequently leads to systemic infection which then leads to prolonged hospitalization. Severe lesions often adversely affect curative effects in cancer cases. Therefore, the control of OM is important for oral health quality of life and prognosis. Low-level laser therapy (LLLT) and ozone may be useful to accelerate wound healing. In this study, 24 Sprague-Dawley rats were divided into three groups as control, ozone, and laser groups. All groups received 5-fluorouracil intraperitoneally and trauma to the mouth pouch with a needle. After the formation of OM in the mouth, the control group had no treatment; the ozone group was administered ozone, and the laser group, LLLT. Then, all groups were sacrificed and basic fibroblast growth factor (bFGF), transforming growth factor (TGF-ß), and platelet-derived growth factor (PDGF) were evaluated in all groups. LLLT was determined to be statistically significantly more effective than ozone on FGF and PDGF. However, in respect of TGF-ß, no statistically significant difference was observed between the groups. In conclusion, within the limitations of this study, LLLT is more effective than ozone. However, further studies on this subject are required.


Assuntos
Lasers , Ozônio/uso terapêutico , Estomatite/tratamento farmacológico , Estomatite/radioterapia , Animais , Modelos Animais de Doenças , Terapia com Luz de Baixa Intensidade , Masculino , Ratos Sprague-Dawley , Cicatrização/efeitos da radiação
9.
J Craniofac Surg ; 28(7): e657-e661, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28857982

RESUMO

The aim of this clinical study was to compare the influence of 2 different suturing techniques on postoperative complications and wound healing after surgical extractions of impacted mandibular third molars. In this randomized split mouth study, 30 patients were examined in whom 60 consecutive surgical extractions of symmetrically positioned impacted mandibular third molars were performed. After the extractions, the surgical flaps were sutured with either the simple interrupted or horizontal mattress suturing technique. Postoperative swelling and trismus were recorded on the 2nd, 7th, and 10th days. Pain was recorded in a 7-day diary and wound dehiscence was recorded on the10th postoperative day. Statistical evaluation of data was made using Mann-Whitney U test and Pearson correlation. There were no statistical differences between the 2 suturing techniques in terms of postoperative pain, trismus, and swelling (P > 0.05). There was significantly less wound dehiscence in the horizontal mattress suturing group than in the simple interrupted suturing group (P: 0017). According to the results of this study, the horizontal mattress suturing technique is more effective than the simple interrupted suturing technique on wound healing after impacted mandibular third molar surgery, although it does not decrease the levels of pain, trismus, and swelling.


Assuntos
Complicações Pós-Operatórias/epidemiologia , Técnicas de Sutura , Extração Dentária/efeitos adversos , Dente Impactado/cirurgia , Cicatrização/fisiologia , Humanos , Dente Serotino/cirurgia , Retalhos Cirúrgicos/cirurgia , Técnicas de Sutura/efeitos adversos , Técnicas de Sutura/estatística & dados numéricos , Suturas , Resultado do Tratamento
10.
J Craniofac Surg ; 27(7): 1879-1883, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27763979

RESUMO

This study aims to evaluate the possible effect of more cortical bone decortication (CBD) on guided bone augmentation. A total of 16 New Zealand rabbits and 32 titanium domes were used. No cortical bone decortication was applied to the control group and in the study groups, the cortical bones were decorticated with a round burr (Group A: 1 hole with bleeding, Group B: 5 holes with bleeding, Group C: a thin layer of compact bone was completely removed with no bleeding). Then 2 titanium domes were placed on the calvarium of each rabbit with hydroxyapatite/beta-tricalcium phosphate. After 3 months, the animals were sacrificed and specimens were sent for histological and histomorphometric analysis. Histological and histomorphometric analysis showed that bone decortication with burr significantly increased new bone regeneration in all the experimental groups compared with the control group (P <0.05). No statistically significant difference was determined between the study groups. In conclusion, CBD, which has no negative impact on surgery, has a positive effect on guided bone augmentation. However, a greater amount of CBD does not have a greater effect.


Assuntos
Regeneração Óssea , Osso Cortical/cirurgia , Implantes Experimentais , Osteogênese/fisiologia , Crânio/cirurgia , Titânio , Animais , Fosfatos de Cálcio , Modelos Animais de Doenças , Coelhos
11.
Implant Dent ; 25(2): 214-21, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26579850

RESUMO

INTRODUCTION: The aim of this study was to evaluate retrospectively the 3-year outcome of implants placed in augmented maxillary sinuses with minimal residual alveolar bone heights (≤3 mm). MATERIALS AND METHOD: A total of 28 sinus floors were augmented with xenograft, and 58 implants were placed. The outcome measures were implant success based on implant stability and the absence of periimplantitis, and marginal and apical bone resorption on periapical radiograph and prosthesis survival. RESULTS: Fifty-seven of 58 implants with their prostheses remained functional with a success rate of 98.28%. None of the implants showed any signs of mobility or periimplantitis. Both apical and cervical bone resorption around the implants were highest by the end of the first year. CONCLUSIONS: The success rate of the implants placed with staged approach in augmented maxillary sinuses with the residual alveolar bone height of ≤3 mm was high in a 3-year term. Bio-Oss is an acceptable substitute autogenous bone and can be used as an augmentation material during the maxillary sinus lift procedure.


Assuntos
Implantação Dentária Endóssea/métodos , Levantamento do Assoalho do Seio Maxilar/métodos , Adulto , Idoso , Implantes Dentários , Seguimentos , Humanos , Maxila/diagnóstico por imagem , Pessoa de Meia-Idade , Osseointegração , Radiografia Dentária , Adulto Jovem
12.
Development ; 139(23): 4405-15, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-23132247

RESUMO

Notch and Wnt are highly conserved signalling pathways that are used repeatedly throughout animal development to generate a diverse array of cell types. However, they often have opposing effects on cell-fate decisions with each pathway promoting an alternate outcome. Commonly, a cell receiving both signals exhibits only Wnt pathway activity. This suggests that Wnt inhibits Notch activity to promote a Wnt-ON/Notch-OFF output; but what might underpin this Notch regulation is not understood. Here, we show that Wnt acts via Dishevelled to inhibit Notch signalling, and that this crosstalk regulates cell-fate specification in vivo during Xenopus development. Mechanistically, Dishevelled binds and directly inhibits CSL transcription factors downstream of Notch receptors, reducing their activity. Furthermore, our data suggest that this crosstalk mechanism is conserved between vertebrate and invertebrate homologues. Thus, we identify a dual function for Dishevelled as an inhibitor of Notch signalling and an activator of the Wnt pathway that sharpens the distinction between opposing Wnt and Notch responses, allowing for robust cell-fate decisions.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Fosfoproteínas/metabolismo , Receptores Notch/metabolismo , Proteínas Wnt/metabolismo , Proteínas de Xenopus/metabolismo , Xenopus/embriologia , Animais , Células CHO , Linhagem Celular , Cricetinae , Proteínas Desgrenhadas , Epiderme/embriologia , Células HEK293 , Humanos , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/antagonistas & inibidores , Receptores Notch/antagonistas & inibidores , Via de Sinalização Wnt , Proteínas de Xenopus/antagonistas & inibidores
13.
J Craniofac Surg ; 26(4): e297-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26080238

RESUMO

Ameloblastoma, a benign neoplasm derived from odontogenic epithelium, is an aggressive and locally invasive tumor. It represents 11% of all odontogenic tumors and 1% of all oral odontogenic epithelial tumors. In this case report, a 20-month-old boy was referred to our clinic with complaint of collapse in his symphysis region of the mandible. Radiographic examination revealed unilocular radiolucency in this region. The lesion was enucleated with 1 tooth germ under general anesthesia and diagnosed as mural unicystic ameloblastoma by histopathologic examination. After the surgery, complete healing was obtained clinically and radiographically. No sign of recurrence has been seen during the follow-up period of 4.5 years. To our knowledge, this was the second youngest case of ameloblastoma in the English literature. However, it is the youngest case of ameloblastoma that occurred in an infant boy.


Assuntos
Ameloblastoma/cirurgia , Mandíbula/cirurgia , Neoplasias Mandibulares/cirurgia , Ameloblastoma/diagnóstico por imagem , Humanos , Lactente , Masculino , Mandíbula/diagnóstico por imagem , Neoplasias Mandibulares/diagnóstico por imagem , Radiografia Panorâmica
14.
J Craniofac Surg ; 26(5): e396-400, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26167994

RESUMO

This study aims to compare the effect of low-level laser therapy (LLLT) and ozone therapy on the bone healing. Thirty-six adult male Wistar albino rats were used for this study. Monocortical defects were shaped in right femur of all rats. Defects were filled with nano-hydroxyapatite graft. The animals were divided into 3 groups and each group was than divided into 2 subgroups. Then, LLLT with a diode laser was applied to the first group (G1), ozone therapy was applied to the second group (G2), and no treatment was applied to the third group as a control group (G3). Animals were sacrificed after 4th and 8th weeks and the sections were examined to evaluate the density of the inflammation, the formation of connective tissue, the osteogenic potential, and osteocalcin activity. As a result, there were no significant differences among the groups of 4 weeks in terms of new bone formation. In the immunohistochemical assessment, the number of osteocalcin-positive cells was higher in the laser group compared to the other group of 4 weeks; this difference was statistically significant in the LLLT and ozone groups (P < 0.05). Histomorphometric assessment showed that the new bone areas were higher in the LLLT and ozone groups; furthermore, there was a statistically significant difference in the LLLT in comparison with the control group at 8th week (P < 0.05). At the same time immunohistochemical assessment showed that osteocalcin-positive cells were considerably higher in G2 than G1 at 8th week (P < 0.05). The findings of this study may be the result of differences in the number of treatment sessions. Further studies are therefore needed to determine the optimal treatment modality.


Assuntos
Lasers Semicondutores/uso terapêutico , Terapia com Luz de Baixa Intensidade/métodos , Ozônio/uso terapêutico , Animais , Doenças Ósseas/tratamento farmacológico , Doenças Ósseas/radioterapia , Doenças Ósseas/cirurgia , Substitutos Ósseos/uso terapêutico , Terapia Combinada , Tecido Conjuntivo/efeitos dos fármacos , Tecido Conjuntivo/efeitos da radiação , Durapatita/uso terapêutico , Fêmur/efeitos dos fármacos , Fêmur/efeitos da radiação , Fêmur/cirurgia , Inflamação , Terapia com Luz de Baixa Intensidade/instrumentação , Masculino , Osteoblastos/efeitos dos fármacos , Osteoblastos/efeitos da radiação , Osteocalcina/efeitos dos fármacos , Osteocalcina/efeitos da radiação , Osteogênese/efeitos dos fármacos , Osteogênese/efeitos da radiação , Ratos , Ratos Wistar , Fatores de Tempo , Cicatrização/efeitos dos fármacos , Cicatrização/efeitos da radiação
15.
Sci Rep ; 14(1): 286, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167959

RESUMO

Drug insensitivity is arguably one of the biggest challenges in cancer therapeutics. Although effective therapeutic solutions in cancer are limited due to the emergence of drug insensitivity, exploiting evolutionary understanding in this context can provide potential second-line therapeutics sensitizing the drug insensitive populations. Targeted therapeutic agent dabrafenib is used to treat CRC patients with BRAF V600E genotype and insensitivity to dabrafenib is often observed. Understanding underlying clonal architecture of dabrafenib-induced drug insensitivity and identification of potential second-line therapeutics that could sensitize dabrafenib insensitive populations remain to be elucidated. For this purpose, we utilized cellular barcoding technology to decipher dabrafenib-induced clonal evolution in BRAF V600E mutant HT-29 cells. This approach revealed the detection of both pre-existing and de novo barcodes with increased frequencies as a result of dabrafenib insensitivity. Furthermore, our longitudinal monitoring of drug insensitivity based on barcode detection from floating DNA within used medium enabled to identify temporal dynamics of pre-existing and de novo barcodes in relation to dabrafenib insensitivity in HT-29 cells. Moreover, whole-exome sequencing analysis exhibited possible somatic CNVs and SNVs contributing to dabrafenib insensitivity in HT-29 cells. Last, collateral drug sensitivity testing demonstrated oxaliplatin and capecitabine, alone or in combination, as successful second-like therapeutics in inducing collateral sensitivity in dabrafenib-insensitive HT-29 cells. Overall, our findings demonstrate clonal dynamics of dabrafenib-insensitivity in HT-29 cells. In addition, oxaliplatin and capecitabine, alone or in combination, were successful second-line therapeutics in inducing collateral sensitivity in dabrafenib-insensitive HT-29 cells.


Assuntos
Sensibilidade Colateral a Medicamentos , Proteínas Proto-Oncogênicas B-raf , Humanos , Oxaliplatina , Capecitabina , Proteínas Proto-Oncogênicas B-raf/genética , Oximas/farmacologia , Oximas/uso terapêutico , Mutação
16.
ACS Biomater Sci Eng ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967485

RESUMO

Drug resistance is arguably one of the biggest challenges facing cancer research today. Understanding the underlying mechanisms of drug resistance in tumor progression and metastasis are essential in developing better treatment modalities. Given the matrix stiffness affecting the mechanotransduction capabilities of cancer cells, characterization of the related signal transduction pathways can provide a better understanding for developing novel therapeutic strategies. In this review, we aimed to summarize the recent advancements in tumor matrix biology in parallel to therapeutic approaches targeting matrix stiffness and its consequences in cellular processes in tumor progression and metastasis. The cellular processes governed by signal transduction pathways and their aberrant activation may result in activating the epithelial-to-mesenchymal transition, cancer stemness, and autophagy, which can be attributed to drug resistance. Developing therapeutic strategies to target these cellular processes in cancer biology will offer novel therapeutic approaches to tailor better personalized treatment modalities for clinical studies.

17.
Methods Mol Biol ; 2764: 265-278, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38393600

RESUMO

Microphysiological systems involving microfluidic 3D culture of cancer cells have emerged as a versatile toolkit to study tumor biological problems and evaluate potential treatment strategies. Incorporation of microfluidic technologies in 3D tissue culture offers opportunities for realistic simulation of tumor microenvironment in vitro by facilitating a dynamic culture environment mimicking features of human physiology such as reconstituted ECM, interstitial flow, and gradients of drugs and biomacromolecules. This protocol describes development of 3D microfluidic cell culture based on Tumor-Microenvironment-on-Chip (T-MOC) platform modeling tumor blood and lymphatic capillary vessels and the interstitial space in between. Based on earlier applications of T-MOC for transport characteristics, drug response, and tumor-stroma interactions in mammary carcinoma and pancreatic adenocarcinoma, this protocol provides detailed description of device fabrication, on-chip 3D culture, and drug treatment assays. This protocol can easily be adapted for applications involving other cancer types.


Assuntos
Adenocarcinoma , Neoplasias da Mama , Neoplasias Pancreáticas , Humanos , Feminino , Microambiente Tumoral , Microfluídica/métodos , Dispositivos Lab-On-A-Chip
18.
Front Cell Dev Biol ; 12: 1369597, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38813084

RESUMO

Metronomic chemotherapy (MCT), characterized by the continuous administration of chemotherapeutics at a lower dose without prolonged drug-free periods, has garnered significant attention over the last 2 decades. Extensive evidence from both pre-clinical and clinical settings indicates that MCT induces distinct biological effects than the standard Maximum Tolerated Dose (MTD) chemotherapy. The low toxicity profile, reduced likelihood of inducing acquired therapeutic resistance, and low cost of MCT render it an attractive chemotherapeutic regimen option. One of the most prominent aspects of MCT is its anti-angiogenesis effects. It has been shown to stimulate the expression of anti-angiogenic molecules, thereby inhibiting angiogenesis. In addition, MCT has been shown to decrease the regulatory T-cell population and promote anti-tumor immune response through inducing dendritic cell maturation and increasing the number of cytotoxic T-cells. Combination therapies utilizing MCT along with oncolytic virotherapy, radiotherapy or other chemotherapeutic regimens have been studied extensively. This review provides an overview of the current status of MCT research and the established mechanisms of action of MCT treatment and also offers insights into potential avenues of development for MCT in the future.

19.
Biomedicines ; 12(1)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38255322

RESUMO

Immunotherapy is now established as a potent therapeutic paradigm engendering antitumor immune response against a wide range of malignancies and other diseases by modulating the immune system either through the stimulation or suppression of immune components such as CD4+ T cells, CD8+ T cells, B cells, monocytes, macrophages, dendritic cells, and natural killer cells. By targeting several immune checkpoint inhibitors or blockers (e.g., PD-1, PD-L1, PD-L2, CTLA-4, LAG3, and TIM-3) expressed on the surface of immune cells, several monoclonal antibodies and polyclonal antibodies have been developed and already translated clinically. In addition, natural killer cell-based, dendritic cell-based, and CAR T cell therapies have been also shown to be promising and effective immunotherapeutic approaches. In particular, CAR T cell therapy has benefited from advancements in CRISPR-Cas9 genome editing technology, allowing the generation of several modified CAR T cells with enhanced antitumor immunity. However, the emerging SARS-CoV-2 infection could hijack a patient's immune system by releasing pro-inflammatory interleukins and cytokines such as IL-1ß, IL-2, IL-6, and IL-10, and IFN-γ and TNF-α, respectively, which can further promote neutrophil extravasation and the vasodilation of blood vessels. Despite the significant development of advanced immunotherapeutic technologies, after a certain period of treatment, cancer relapses due to the development of resistance to immunotherapy. Resistance may be primary (where tumor cells do not respond to the treatment), or secondary or acquired immune resistance (where tumor cells develop resistance gradually to ICIs therapy). In this context, this review aims to address the existing immunotherapeutic technologies against cancer and the resistance mechanisms against immunotherapeutic drugs, and explain the impact of COVID-19 on cancer treatment. In addition, we will discuss what will be the future implementation of these strategies against cancer drug resistance. Finally, we will emphasize the practical steps to lay the groundwork for enlightened policy for intervention and resource allocation to care for cancer patients.

20.
Nat Cancer ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997466

RESUMO

Cancer evolution lays the groundwork for predictive oncology. Testing evolutionary metrics requires quantitative measurements in controlled clinical trials. We mapped genomic intratumor heterogeneity in locally advanced prostate cancer using 642 samples from 114 individuals enrolled in clinical trials with a 12-year median follow-up. We concomitantly assessed morphological heterogeneity using deep learning in 1,923 histological sections from 250 individuals. Genetic and morphological (Gleason) diversity were independent predictors of recurrence (hazard ratio (HR) = 3.12 and 95% confidence interval (95% CI) = 1.34-7.3; HR = 2.24 and 95% CI = 1.28-3.92). Combined, they identified a group with half the median time to recurrence. Spatial segregation of clones was also an independent marker of recurrence (HR = 2.3 and 95% CI = 1.11-4.8). We identified copy number changes associated with Gleason grade and found that chromosome 6p loss correlated with reduced immune infiltration. Matched profiling of relapse, decades after diagnosis, confirmed that genomic instability is a driving force in prostate cancer progression. This study shows that combining genomics with artificial intelligence-aided histopathology leads to the identification of clinical biomarkers of evolution.

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