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1.
Clin Chim Acta ; 562: 119893, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39068964

RESUMO

Pharmacogenomics has become integral to personalised medicine in breast cancer, utilising genetic insights to customize treatment strategies and enhance patient outcomes. Understanding how genetic variations influence drug metabolism, response, and toxicity is crucial for guiding treatment selection and dosing regimens. Genetic polymorphisms in drug-metabolizing enzymes and transporters significantly impact pharmacokinetic variability, influencing the efficacy and safety of chemotherapy agents and targeted therapies. Biomarkers associated with the hormone receptor status of breast cancer and mutations serve as key determinants of treatment response, aiding in the selection of therapies. Despite substantial progress in understanding the pharmacogenomic landscape of breast cancer, efforts to identify novel genetic markers and refine treatment optimisation strategies are required. Genome-wide association studies and advanced sequencing technologies hold promise for uncovering genetic determinants of drug response variability and elucidating complex pharmacogenomic interactions. The future of pharmacogenomics in breast cancer lies in real-time treatment monitoring, the discovery of additional predictive markers, and the seamless integration of pharmacogenomic data into clinical decision-making processes. However, translating pharmacogenomic discoveries into routine clinical practice requires collaborative efforts among stakeholders to address implementation challenges and ensure equitable access to genetic testing. By embracing pharmacogenomics, clinicians can tailor treatment approaches to individual patients, maximizing therapeutic benefits while minimizing adverse effects. This review discusses the integration of pharmacogenomics in breast cancer treatment, highlighting the significance of understanding genetic influences on treatment response and toxicity, and the potential of advanced technologies in refining treatment strategies.


Assuntos
Neoplasias da Mama , Farmacogenética , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Antineoplásicos/uso terapêutico , Medicina de Precisão
2.
Clin Transl Oncol ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971914

RESUMO

Exosomes, measuring between 30 and 150 nm in diameter, are small vesicles enclosed by a lipid bilayer membrane. They are released by various cells in the body and carry a diverse payload of molecules, including proteins, lipids, mRNA, and different RNA species such as long non-coding RNA, circular RNA, and microRNA (miRNA). With lengths of approximately 19-22 nucleotides, miRNAs constitute the predominant cargo in exosomes and serve as crucial regulators of protein biosynthesis. In cancer detection, exosomal miRNAs show promise as non-invasive biomarkers due to their stability and presence in various bodily fluids, aiding in early detection and precise diagnosis with specific miRNA signatures linked to different cancer types. Moreover, exosomal miRNAs influence treatment outcomes by affecting cellular processes like cell growth, cell death, and drug resistance, thereby impacting response to therapy. Additionally, they serve as indicators of disease progression and treatment response, providing insights that can guide treatment decisions and improve patient care. Through longitudinal studies, changes in exosomal miRNA profiles have been observed to correlate with disease progression, metastasis, and response to therapy, highlighting their potential for real-time monitoring of tumor dynamics and treatment efficacy. Understanding the intricate roles of exosomal miRNAs in cancer biology offers opportunities for developing innovative diagnostic tools and therapeutic strategies tailored to individual patients, ultimately advancing precision medicine approaches and improving outcomes for cancer patients. This review aims to provide an understanding of the role of exosomal miRNAs in cancer detection, treatment, and monitoring, shedding light on their potential for revolutionising oncology practices and patient care.

3.
J Dent Sci ; 19(3): 1320-1327, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39035313

RESUMO

Oral Lichen Planus (OLP) presents a significant challenge in diagnosis due to its varied clinical manifestations and the absence of specific biomarkers. Timely and accurate diagnosis is crucial, particularly given its association with oral squamous cell carcinoma (OSCC). This review aims to explore the potential role of exosomes, small extracellular vesicles, in the pathogenesis of OLP and their utility as diagnostic biomarkers. Exosomes facilitate the exchange of information between cells and modulate immune responses by carrying various bioactive molecules such as proteins, lipids, and nucleic acids. In the context of OLP, exosomes derived from affected tissues or immune cells are thought to contribute to disease progression by mediating the transfer of pro-inflammatory molecules, including cytokines like interleukin-6 and tumour necrosis factor-alpha and chemokines such as CCL2, CCL5 and microRNAs such as miR-155, miR-146a, miR-21, and miR-34a, etc. Additionally, the distinct molecular contents of exosomes derived from OLP lesions may accurately represent the pathological changes occurring in these tissues. This suggests the potential of exosomes to be used as non-invasive biomarkers for diagnosing and tracking the progression of the disease. Understanding the immune microenvironment of OLP and the role of exosomes within this context is critical for advancing our knowledge of OLP pathogenesis and identifying new diagnostic and therapeutic strategies. However, challenges remain in identifying and characterising exosomes and their clinical translation. Further research is warranted to address these challenges and fully exploit exosomes' diagnostic and therapeutic potential in OLP and other inflammatory oral diseases.

4.
ACS Omega ; 9(11): 12602-12610, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38524437

RESUMO

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the major types of cancer, with 900,000 cases and over 400,000 deaths annually. It constitutes 3-4% of all cancers in Europe and western countries. As early diagnosis is the key to treating the disease, reliable biomarkers play an important role in the precision medicine of HNSCC. Despite treatments, the survival rate of cancer patients remains unchanged, and this is mainly due to the failure to detect the disease early. Thus, the objective of this study is to identify reliable biomarkers for head and neck cancers for better healthcare management. Methods: In this study, all available, curated human genes were screened for their expression against HNSCC TCGA patient samples using genomic and proteomic data by various bioinformatic approaches and datamining. Docking studies were performed using AutoDock or online virtual screening tools for identifying potential ligands. Results: Sixty genes were short-listed, and most of them show a consistently higher expression in head and neck patient samples at both the mRNA and the protein level. Irrespective of human papillomavirus (HPV) status, all of them show a higher expression in cancer samples. The higher expression of 30 genes shows adverse effects on patient survival. Out of the 60 genes, 12 genes have crystal structures and druggable potential. We show that genes such as GTF2H4, HAUS7, MSN, and MNDA could be targets of Pembrolizumab and Nivolumab, which are approved monoclonal antibodies for HNSCC. Conclusion: Sixty genes are identified as potential biomarkers for head and neck cancers based on their consistent and statistically significantly higher expression in patient samples. Four proteins have been identified as potential drug targets based on their crystal structure. However, the utility of these candidate genes has to be further tested using patient samples.

5.
Clin Chim Acta ; 557: 117875, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38493944

RESUMO

Breast cancer (BC) is the most prevalent malignancy affecting women worldwide. Although conventional treatments such as chemotherapy, surgery, hormone therapy, radiation therapy, and biological therapy are commonly used, they often entail significant side effects. Therefore, there is a critical need to investigate more cost-effective and efficient treatment modalities in BC. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, play a crucial role in modulating recipient cell behaviour and driving cancer progression. Among the EVs, exosomes provide valuable insights into cellular dynamics under both healthy and diseased conditions. In cancer, exosomes play a critical role in driving tumor progression and facilitating the development of drug resistance. BC-derived exosomes (BCex) dynamically influence BC progression by regulating cell proliferation, immunosuppression, angiogenesis, metastasis, and the development of treatment resistance. Additionally, BCex serve as promising diagnostic markers in BC which are detectable in bodily fluids such as urine and saliva. Targeted manipulation of BCex holds significant therapeutic potential. This review explores the therapeutic and diagnostic implications of exosomes in BC, underscoring their relevance to the disease. Furthermore, it discusses future directions for exosome-based research in BC, emphasizing the necessity for further exploration in this area.


Assuntos
Neoplasias da Mama , Micropartículas Derivadas de Células , Exossomos , Vesículas Extracelulares , Humanos , Feminino , Exossomos/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Vesículas Extracelulares/patologia
6.
Anal Sci ; 40(1): 185-198, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37921942

RESUMO

A quick and sensitive liquid chromatography-mass spectrometry technique was designed, improved, and validated for simultaneous determination of Empagliflozin (EPG) and Linagliptin (LNG) using Empagliflozin-d4 (EPG-d4) and linagliptin-d4 (LNG-d4) as internal standards (IS) in rat plasma. Target analytes and the IS were extracted using freezing lipid precipitation (FLP) and optimized using the strong cation exchange solid phase extraction (SCX-SPE) method to achieve the maximum sample clean-up. In particular, when combined with SPE clean-up, FLP can efficiently eliminate the plasma sample's high lipid content. More than 84.14% of plasma lipids were rapidly removed during the FLP procedure, with minimal loss of EPG and LNG. We used LC-atmospheric chemical ionization (APCI)-mass spectrometry was employed to assess the efficiency of FLP in lipid removal. The SCX-SPE cartridges removed the remaining impurities from EPG and LNG, allowing for further purification. The samples were chromatographically separated using a Spherisorb RP/Cyano column by pumping a gradient mobile phase comprised of acetonitrile and 25 mM ammonium acetate buffer (pH 8.1) in positive ion mode at a flow rate of 0.8 mL/min. The selected reaction monitoring technique was performed using a Waters triple-stage quadrupole tandem mass spectrometer equipped with an electrospray ionization (ESI) source. The chromatographic separation was accomplished using a Waters Acquity® high-performance liquid chromatography (HPLC) system. Mass transition (m/z) of 451.15/71.12 for EPG, m/z 473.27/419.94 for LNG; m/z 455.19/71.12 for EPG-d4, and 477.27/423.94 for LNG-d4 was successfully achieved. This study successfully examined the concentration ranges of 25-1050 ng/mL for EPG and 0.35-15 ng/mL for LNG. The results showed that the linearity of EPG ranged from 25.14 to 985.26 ng/mL, while the linearity of LNG ranged from 0.59 to 14.86 ng/mL. The relative standard deviation (RSD) for both EPG and LNG, within and between days, were below 3.83%, indicating that they fall within acceptable limits. This novel approach demonstrated favourable outcomes in a pharmacokinetic study involving healthy rats, where EPG and LNG were co-administered. This study found that the co-administration of both drugs did not have a significant impact on their pharmacokinetic behavior, suggesting the absence of any drug-drug interactions.


Assuntos
Linagliptina , Espectrometria de Massas em Tandem , Ratos , Animais , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massa com Cromatografia Líquida , Congelamento , Lipídeos , Reprodutibilidade dos Testes
7.
J Indian Assoc Pediatr Surg ; 28(3): 218-222, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37389385

RESUMO

Introduction: Peutz-Jeghers Syndrome (PJS) is an autosomal dominant disease presenting with hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on lips and oral mucosa. The incidence of this syndrome is approximately 1 in 1,20,000 births. Materials and Methods: In this article, we are presenting 11 cases of PJS which were misdiagnosed and patients were compelled to visit hospital repeatedly. All these cases were diagnosed based on clinical suspicion, family history, and histopathological examination of specimens. Most of the cases presented with intussusception and required emergency surgical management. Results: PJS can be diagnosed by the presence of microscopically confirmed hamartomatous polyps and a minimum of two of the following clinical criteria: Family history, mucocutaneous melanotic spots, and small bowel polyps with bleeding per rectally. The diagnosis can be missed if the melanotic spots on the face are missed. Routine investigations, imaging, and endoscopy were done in all cases. PJS patients need regular follow-up due to chance of recurrence of symptoms and susceptibility to cancer. Conclusion: PJS needs a high index of suspicion for diagnosis in cases of recurrent abdominal pain with bleeding per rectum. Proper family history and meticulous clinical examination for melanosis are very important to prevent the misdiagnosis of these cases.

9.
J Indian Assoc Pediatr Surg ; 28(1): 14-17, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36910292

RESUMO

Introduction: Hernia of the umbilical cord (HUC) is an uncommon problem which is often misdiagnosed, leading to inadequate treatment and various complications which cause increased morbidity and mortality in neonates. To address this issue, we took up this study. Materials and Methods: Patients diagnosed with HUC from January 1, 2017, to December 31, 2021, were retrospectively analyzed. The following data of all these patients were collected and retrospectively analyzed: demography, radiological investigations, echocardiography, contents of hernia, type of surgery performed, and outcome. Results: Eighteen out of 19 patients included in the study were taken up for surgery after baseline investigations and echocardiography. Out of 19 patients, 15 were discharged successfully and are on regular follow-up. Of the remaining four patients, an anastomotic leak occurred in two and they went into sepsis and succumbed. One of the patients died before any intervention and one succumbed on 3rd postoperative day due to sepsis. Conclusion: Timely referral and intervention can save precious lives. We need to educate doctors and health-care providers so that proper diagnosis and timely management can be done for this anomaly which is associated with less morbidity and a lower rate of associated anomalies.

10.
BMJ Case Rep ; 15(5)2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35584855

RESUMO

A woman in her 30s presented with progressive worsening of dyspnoea for 6 months. On evaluation, she was diagnosed with severe rheumatic mitral stenosis (mitral valve area of 0.6 cm2) and a large ostium secundum atrial septal defect (21 mm) with a left to right shunt and severe pulmonary artery hypertension. She was diagnosed with Lutembacher syndrome and was evaluated for suitability of a percutaneous approach. She was subjected to a combined procedure of percutaneous transluminal mitral commissurotomy followed by device closure of the atrial septal defect. The patient tolerated the procedure, remained haemodynamically stable and was discharged after 4 days. This procedure can prevent the morbidity and mortality associated with anaesthesia and cardiac surgery and the psychological trauma of a thoracotomy scar particularly in a female patient, as well as obviate the need for prolonged hospital stay.


Assuntos
Comunicação Interatrial , Hipertensão Pulmonar , Síndrome de Lutembacher , Estenose da Valva Mitral , Cateterismo Cardíaco , Feminino , Comunicação Interatrial/terapia , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Síndrome de Lutembacher/terapia , Estenose da Valva Mitral/cirurgia
11.
Med Princ Pract ; 31(3): 284-292, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35468599

RESUMO

OBJECTIVE: Acute myeloid leukemia (AML) is a hematological malignancy that arises from the clonal proliferation of immature myeloid cells. Although the number of AML cases has dramatically increased worldwide, information on its prevalence and incidence in Kuwait is lacking. This study reports the incidence of AML and patient demographics in the country from 2014 to 2020, based on the 2016 WHO classification of AML. SUBJECTS AND METHODS: Data on patients with AML, including acute promyelocytic leukemia (APL), were collected from a clinical cohort with 281 cases analyzed in this study. RESULTS: The overall median age of the population was 47 years with a 1.1:1 male-to-female ratio. Over the study period, the incidence of AML demonstrated a general increasing trend, with the highest and lowest overall incidence occurring in 2018 and 2015, respectively. The frequency of APL in our cohort was 8.9%. Regarding the 2017 European LeukemiaNet (ELN) risk stratification of patients with AML, 37%, 46%, and 17% of patients had a favorable, intermediate, and adverse risk, respectively. A total of 57% of cases achieved complete remission post-induction, and the median overall survival was 37 months. CONCLUSION: Our study may help predict the future trends of AML in Kuwait to help improve clinical management and patient outcomes.


Assuntos
Leucemia Mieloide Aguda , Leucemia Promielocítica Aguda , Feminino , Humanos , Kuweit/epidemiologia , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/patologia , Leucemia Promielocítica Aguda/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Organização Mundial da Saúde
12.
Am J Cancer Res ; 12(1): 17-47, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35141003

RESUMO

BRCA1 mutation carriers have a greater risk of developing cancers in hormone-responsive tissues like breasts and ovaries. However, this tissue-specific incidence of BRCA1 related cancers remains elusive. The majority of the BRCA1 mutated breast cancers exhibit typical histopathological features of high-grade tumors, with basal epithelial phenotype, classified as triple-negative molecular subtype and have a higher percentage of DNA damage and chromosomal abnormality. Though there are many studies relating BRCA1 with ER-α (Estrogen receptor-α), it has not been reported whether E2 (Estrogen) -ER-α signaling can modulate the DNA repair activities of BRCA1. The present study analyzes whether deregulation of ER-α signaling, arising as a result of E2/ER-α deficiency, could impact the BRCA1 dependent DDR (DNA Damage Response) pathways, predominantly those of DNA-DSB (Double Strand break) repair and oxidative damage response. We demonstrate that E2/E2-stimulated ER-α can augment BRCA1 mediated high fidelity repairs like HRR (Homologous Recombination Repair) and BER (Base Excision Repair) in breast cancer cells. Conversely, a condition of ER-α deficiency itself or any interruption in ligand-dependent ER-α transactivation resulted in delayed DNA damage repair, leading to persistent activation of γH2AX and retention of unrepaired DNA lesions, thereby triggering tumor progression. ER-α deficiency not only limited the HRR in cells but also facilitated the DSB repair through error prone pathways like NHEJ (Non Homologous End Joining). ER-α deficiency associated persistence of DNA lesions and reduced expression of DDR proteins were validated in human mammary tumors.

13.
Curr Drug Res Rev ; 14(1): 11-19, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34365935

RESUMO

The novel SARS-CoV-2 is a new disease that has caused severe destruction to human lives across the globe, including infection, mortality and financial crises, for which, scientific researchers have been directed towards the development of treatment and controlling measures against coronavirus. Currently, there has been no approved drug for the treatment of the disease, but several antiviral drugs have shown therapeutic effects from which, remdesivir and favipiravir are two such drugs. These drugs have shown some therapeutic potential in the treatment of COVID-19 by inhibiting viral enzyme RNA-dependent RNA polymerase. The purpose of this systematic review is to provide an overview of the effectiveness of these two drugs based on the clinical trials reported in current published data.


Assuntos
Tratamento Farmacológico da COVID-19 , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Amidas , Humanos , Pirazinas , SARS-CoV-2 , Resultado do Tratamento
14.
Front Oncol ; 11: 733652, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760696

RESUMO

The lack of traditional cancer treatments has resulted in an increased need for new clinical techniques. Standard two-dimensional (2D) models used to validate drug efficacy and screening have a low in vitro-in vivo translation potential. Recreating the in vivo tumor microenvironment at the three-dimensional (3D) level is essential to resolve these limitations in the 2D culture and improve therapy results. The physical and mechanical environments of 3D culture allow cancer cells to expand in a heterogeneous manner, adopt different phenotypes, gene and protein profiles, and develop metastatic potential and drug resistance similar to human tumors. The current application of 3D scaffold culture systems based on synthetic polymers or selected extracellular matrix components promotes signalling, survival, and cancer cell proliferation. This review will focus on the recent advancement of numerous 3D-based scaffold models for cancer tissue engineering, which will increase the predictive ability of preclinical studies and significantly improve clinical translation.

15.
Clin Lymphoma Myeloma Leuk ; 21(9): e736-e743, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34154982

RESUMO

PURPOSE: Acute myeloid leukemia (AML) data from the Middle East are limited to single-center studies. We report leukemia-free survival (LFS) and overall survival (OS) of young (≤70 years) patients with AML treated in Kuwait. PATIENTS AND METHODS: This study investigated prognostic markers among 172 young and fit patients with de novo nonacute promyelocytic leukemia AML treated with intensive induction protocols from a tertiary cancer center. RESULTS: The median age was 44 years (interquartile range, 32-51) and 67% of cases were Arab. A greater proportion of males was found in the 2017 European Leukemia Net-defined unfavorable-risk group (20% vs 9%, respectively; P = .02). Most patients (94%) were treated by a standard 7 × 3 regimen; 72.5% of cases achieved complete remission. The 24-month LFS was 44% (95% confidence interval, 30-65), 36% (95% confidence interval, 26-50), and 23% (95% confidence interval, 10-53) for the favorable-, intermediate-, and adverse-risk groups, respectively (P = .018). The 24-month OS was 70% (95% confidence interval, 60-90), 65% (95% confidence interval, 53-79), and 49% (95% confidence interval, 31-78), respectively (P = .05). Multivariable factor analysis identified male gender (hazard ratio [HR], 1.66; P = .029) and older age (HR, 1.02; P = .05) with poor LFS outcome, whereas favorable-risk classification predicated better outcome (HR, 0.49; P = .03). Favorable-risk classification was the only predictor of OS (HR, 0.39; P = .029). CONCLUSION: Fit patients with AML in the favorable-risk group treated with intensive chemotherapy fare well, whereas patients in the adverse-risk group have poor survival.


Assuntos
Leucemia Mieloide Aguda/epidemiologia , Adulto , Feminino , Humanos , Kuweit , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Resultado do Tratamento
16.
Front Physiol ; 11: 566, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655401

RESUMO

RATIONALE: Precision-cut lung slices (PCLSs) are a valuable tool in studying tissue responses to an acute exposure; however, cyclic stretching may be necessary to recapitulate physiologic, tidal breathing conditions. OBJECTIVES: To develop a multi-well stretcher and characterize the PCLS response following acute exposure to cigarette smoke extract (CSE). METHODS: A 12-well stretching device was designed, built, and calibrated. PCLS were obtained from male Sprague-Dawley rats (N = 10) and assigned to one of three groups: 0% (unstretched), 5% peak-to-peak amplitude (low-stretch), and 5% peak-to-peak amplitude superimposed on 10% static stretch (high-stretch). Lung slices were cyclically stretched for 12 h with or without CSE in the media. Levels of Interleukin-1ß (IL-1ß), matrix metalloproteinase (MMP)-1 and its tissue inhibitor (TIMP1), and membrane type-MMP (MT1-MMP) were assessed via western blot from tissue homogenate. RESULTS: The stretcher system produced nearly identical normal Lagrangian strains (E xx and E yy , p > 0.999) with negligible shear strain (E xy < 0.0005) and low intra-well variability 0.127 ± 0.073%. CSE dose response curve was well characterized by a four-parameter logistic model (R 2 = 0.893), yielding an IC50 value of 0.018 cig/mL. Cyclic stretching for 12 h did not decrease PCLS viability. Two-way ANOVA detected a significant interaction between CSE and stretch pattern for IL-1ß (p = 0.017), MMP-1, TIMP1, and MT1-MMP (p < 0.001). CONCLUSION: This platform is capable of high-throughput testing of an acute exposure under tightly-regulated, cyclic stretching conditions. We conclude that the acute mechano-inflammatory response to CSE exhibits complex, stretch-dependence in the PCLS.

17.
Rev Sci Instrum ; 89(8): 085122, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30184680

RESUMO

This paper presents the development of a novel wavefront measuring camera capable of detecting both the amplitude and phase of the captured light wave simultaneously. The main objective of the present work is to develop a simple "aim and shoot" camera system for quantitative estimation of density variations in high-speed gas flow fields. The interrogating beam which is a plane wave used here gets distorted by flow induced change in refractive index gradients. Wavefront distortion is quantitatively measured by inspecting the projected pattern through the embedded mask of a modified CMOS image sensor, which samples the incoming wavefront space continuously. Post-processing of the captured images through Fourier- and windowed Fourier transform schemes reveals the change in phase and amplitude of the captured wave. The captured phase of the wavefront is used in an iterative tomography scheme to estimate the density distribution of the flow field. The utility of the developed camera is demonstrated in the quantitative visualization of the high-speed flow fields around test objects subjected to hypersonic flows at Mach numbers 8.89 and 5.82 in hypersonic shock tunnel facility (HST2) and also to visualize the flow field generated at the exit of a convergent-divergent nozzle (Mach number 2.9). It is observed that the recovered quantitative density values from the experiments match well with the results obtained through computational fluid dynamic simulations demonstrating the proficiency of the proposed wavefront measuring camera for high-speed flow diagnostics.

18.
Oncotarget ; 9(31): 22184-22193, 2018 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-29774131

RESUMO

Neuroblastoma (NB), a developmental cancer, is often fatal, emphasizing the need to understand its pathogenesis and identify new therapeutic targets. The heterogeneous pathological and clinical phenotype of NB underscores the cryptic biological and genetic features of this tumor that result in outcomes ranging from rapid progression to spontaneous regression. Despite recent genome-wide mutation analyses, most primary NBs do not harbor driver mutations, implicating epigenetically-mediated gene regulatory mechanisms in the initiation and maintenance of NB. Aberrant epigenomic mechanisms, as demonstrated by global changes in DNA methylation signatures, acetylation, re-distribution of histone marks, and change in the chromatin architecture, are hypothesized to play a role in NB oncogenesis. This paper reviews the evidence for, putative mechanisms underlying, and prospects for therapeutic targeting of NB oncogenesis related to DNA methylation.

19.
Int J Hyperthermia ; 34(1): 122-131, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28540819

RESUMO

We demonstrate a non-invasive technique, based on the modal frequency shift of a region insonified by a dual-beam ultrasound (US) transducer (region of interest, ROI), to remotely assess the temperature of the region in a tissue-mimicking object. The application is in ultrasound hyperthermia systems for controlled maintenance of tumour temperature during chemotherapy. Towards this, we have characterised the variation of the storage modulus with the temperature of two tissue-mimicking visco-elastic materials. Due to this variation in tissue storage modulus (and viscosity), we have observed a shift in the resonant modes of the ROI, vibrated remotely with a dual-beam focussed ultrasound transducer. A modal analysis of the vibrating ROI is done to identify the modes captured by the detector. A variation in this modal frequency with temperature is computed and matches reasonably well with the experimental measurements. Through this, we demonstrate that an ultrasound hyperthermia system can have a remote temperature sensor without using an additional imaging modality.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Hipertermia Induzida/métodos , Ultrassonografia/métodos , Acústica , Calefação , Humanos , Temperatura
20.
J Opt Soc Am A Opt Image Sci Vis ; 34(11): 1945-1956, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29091642

RESUMO

We obtain vibro-acoustic (VA) spectral signatures of a remotely palpated region in tissue or tissue-like objects through diffusing-wave spectroscopy (DWS) measurements. Remote application of force is through focused ultrasound, and the spectral signatures correspond to vibrational modes of the focal volume (also called the ROI) excited through ultrasound forcing. In DWS, one recovers the time evolution of mean-square displacement (MSD) of Brownian particles from the measured decay of intensity autocorrelation of light, adapted also to local particles pertaining only to the ROI. We observe that the plateau of the MSD-versus-time curve has noisy fluctuations when ultrasound is applied, which disappear when forcing is removed. It is shown that the spectrum of fluctuations contains peaks corresponding to some of the modes of vibration of the ROI. This enables us to measure the vibrational modes carried by VA waves. We also show recovery of components of the orthotropic elastic tensor pertaining to the material of the ROI from the measured vibrational modes. We first recover the elastic constants for agar slabs, which are verified to be isotropic. Thereafter, we repeat the exercise on fat recovered from pork back tissue, which, from these measurements, is seen to be orthotropic. We validate some of our present measurements through independent runs in a rheometer. The present work is the first step taken, to the best of our knowledge, to characterize biological tissue on the basis of the anisotropic elasticity property, which may potentially aid in the diagnosis and tracking of the progress of cancer in soft-tissue organs.


Assuntos
Módulo de Elasticidade , Técnicas de Imagem por Elasticidade , Imagens de Fantasmas , Carne Vermelha , Análise Espectral , Animais , Elasticidade , Suínos , Ondas Ultrassônicas
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