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1.
JCO Clin Cancer Inform ; 8: e2300074, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38552191

RESUMO

Standardizing image-data preparation practices to improve accuracy/consistency of AI diagnostic tools.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Inteligência Artificial , Confiabilidade dos Dados
3.
Radiother Oncol ; 188: 109874, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37640162

RESUMO

BACKGROUND AND PURPOSE: Radiation oncology protocols for single fraction radiosurgery recommend setting dosing criteria based on assumed risk of radionecrosis, which can be predicted by the 12 Gy normal brain volume (V12). In this study, we show that tumor surface area (SA) and a simple power-law model using only preplan variables can estimate and minimize radiosurgical toxicity. MATERIALS AND METHODS: A 245-patient cohort with 1217 brain metastases treated with single or distributed Gamma Knife sessions was reviewed retrospectively. Univariate and multivariable linear regression models and power-law models determined which modeling parameters best predicted V12. The V12 power-law model, represented by a product of normalized Rx dose Rxn, and tumor longest axial dimension LAD (V12 âˆ¼ Rxn1.5*LAD2), was independently validated using a secondary 63-patient cohort with 302 brain metastases. RESULTS: Surface area was the best univariate linear predictor of V12 (adjR2 = 0.770), followed by longest axial dimension (adjR2 = 0.755) and volume (adjR2 = 0.745). The power-law model accounted for 90% variance in V12 for 1217 metastatic lesions (adjR2 = 0.906) and 245 patients (adjR2 = 0.896). The average difference ΔV12 between predicted and measured V12s was (0.28 ± 0.55) cm3 per lesion and (1.0 ± 1.2) cm3 per patient. The power-law predictive capability was validated using a secondary 63-patient dataset (adjR2 = 0.867) with 302 brain metastases (adjR2 = 0.825). CONCLUSION: Surface area was the most accurate univariate predictor of V12 for metastatic lesions. We developed a preplan model for brain metastases that can help better estimate radionecrosis risk, determine prescription doses given a target V12, and provide safe dose escalation strategies without the use of any planning software.

5.
Discov Oncol ; 13(1): 126, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380219

RESUMO

PURPOSE: Poor outcomes in IDH wild-type (IDHwt) glioblastomas indicate the need to determine which genetic alterations can indicate poor survival and guidance of patient specific treatment options. We sought to identify the genetic alterations in these patients that predict for survival when adjusting particularly for treatments and other genetic alterations. METHODS: A cohort of 167 patients with pathologically confirmed IDHwt glioblastomas treated at our institution was retrospectively reviewed. Next generation sequencing was performed for each patient to determine tumor genetic alterations. Multivariable cox proportional hazards analysis for overall survival (OS) was performed to control for patient variables. RESULTS: CDKN2A, CDKN2B, and MTAP deletion predict for worse OS independently of other genetic alterations and patient characteristics (hazard ratio [HR] 2.192, p = 0.0017). Patients with CDKN2A copy loss (HR 2.963, p = 0.0037) or TERT mutated (HR 2.815, p = 0.0008) glioblastomas exhibited significant associations between radiation dose and OS, while CDKN2A and TERT wild type patients did not. CDKN2A deleted patients with NF1 mutations had worse OS (HR 1.990, p = 0.0540), while CDKN2A wild type patients had improved OS (HR 0.229, p = 0.0723). Patients with TERT mutated glioblastomas who were treated with radiation doses < 45 Gy (HR 3.019, p = 0.0010) but not those treated with ≥ 45 Gy exhibited worse OS compared to those without TERT mutations. CONCLUSION: In IDHwt glioblastomas, CDKN2A, CDKN2B, and MTAP predict for poor prognosis. TERT and CDKN2A mutations are associated with worse survival only when treated with lower radiation doses, thus potentially providing a genetic marker that can inform clinicians on proper dose-fractionation schemes.

6.
Front Neurol ; 13: 1024138, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36438954

RESUMO

Introduction: Poor outcomes in glioblastoma patients, despite advancing treatment paradigms, indicate a need to determine non-physiologic prognostic indicators of patient outcome. The impact of specific socioeconomic and demographic patient factors on outcomes is unclear. We sought to identify socioeconomic and demographic patient characteristics associated with patient survival and tumor progression, and to characterize treatment options and healthcare utilization. Methods: A cohort of 169 patients with pathologically confirmed glioblastomas treated at our institution was retrospectively reviewed. Multivariable cox proportional hazards analysis for overall survival (OS) and cumulative incidence of progression was performed. Differences in treatment regimen, patient characteristics, and neuro-oncology office use between different age and depressive disorder history patient subgroups were calculated two-sample t-tests, Fisher's exact tests, or linear regression analysis. Results: The median age of all patients at the time of initiation of radiation therapy was 60.5 years. The median OS of the cohort was 13.1 months. Multivariable analysis identified age (Hazard Ratio 1.02, 95% CI 1.00-1.04) and total resection (Hazard Ratio 0.52, 95% CI 0.33-0.82) as significant predictors of OS. Increased number of radiation fractions (Hazard Ratio 0.90, 95% CI 0.82-0.98), depressive disorder history (Hazard Ratio 0.59, 95% CI 0.37-0.95), and total resection (Hazard Ratio 0.52, 95% CI 0.31-0.88) were associated with decreased incidence of progression. Notably, patients with depressive disorder history were observed to have more neuro-oncology physician office visits over time (median 12 vs. 16 visits, p = 0.0121). Patients older than 60 years and those with Medicare (vs. private) insurance were less likely to receive as many radiation fractions (p = 0.0014) or receive temozolomide concurrently with radiation (Odds Ratio 0.46, p = 0.0139). Conclusion: Older glioblastoma patients were less likely to receive as diverse of a treatment regimen as their younger counterparts, which may be partially driven by insurance type. Patients with depressive disorder history exhibited reduced incidence of progression, which may be due to more frequent health care contact during neuro-oncology physician office visits.

7.
Front Oncol ; 12: 1000280, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36158642

RESUMO

Introduction: Poor outcomes in glioma patients indicate a need to determine prognostic indicators of survival to better guide patient specific treatment options. While preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) have been suggested as prognostic systemic inflammation markers, the impact of post-radiation changes in these cell types is unclear. We sought to identify which hematologic cell measurements before, during, or after radiation predicted for patient survival. Methods: A cohort of 182 patients with pathologically confirmed gliomas treated at our institution was retrospectively reviewed. Patient blood samples were collected within one month before, during, or within 3 months after radiation for quantification of hematologic cell counts, for which failure patterns were evaluated. Multivariable cox proportional hazards analysis for overall survival (OS) and progression-free survival (PFS) was performed to control for patient variables. Results: Multivariable analysis identified pre-radiation NLR > 4.0 (Hazard ratio = 1.847, p = 0.0039) and neutrophilia prior to (Hazard ratio = 1.706, p = 0.0185), during (Hazard ratio = 1.641, p = 0.0277), or after (Hazard ratio = 1.517, p = 0.0879) radiation as significant predictors of worse OS, with similar results for PFS. Post-radiation PLR > 200 (Hazard ratio = 0.587, p = 0.0062) and a percent increase in platelets after radiation (Hazard ratio = 0.387, p = 0.0077) were also associated with improved OS. Patients receiving more than 15 fractions of radiation exhibited greater post-radiation decreases in neutrophil and platelet counts than those receiving fewer. Patients receiving dexamethasone during radiation exhibited greater increases in neutrophil counts than those not receiving steroids. Lymphopenia, changes in lymphocyte counts, monocytosis, MLR, and changes in monocyte counts did not impact patient survival. Conclusion: Neutrophilia at any time interval surrounding radiotherapy, pre-radiation NLR, and post-radiation thrombocytopenia, but not lymphocytes or monocytes, are predictors of poor patient survival in glioma patients.

8.
Adv Radiat Oncol ; 7(5): 100995, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36148376

RESUMO

Purpose: Five-fraction stereotactic ablative radiotherapy (SABR) regimens are frequently used to treat centrally located early-stage non-small cell lung cancer or disease in the proximity of the chest wall as a means of optimizing tumor control and reducing treatment toxicity. However, increasing these SABR regimens to 5 fractions may reduce tumor control outcomes. We sought to identify the clinical parameters predictive of treatment failures with these 5-fraction courses. Methods: Ninety patients with T1-2 non-small cell lung cancer were treated with 50 or 60 Gy in 5 fractions. Failure over time was modeled using cumulative incidences of local, regional, or distant failure, with death as a competing risk. Cox proportional hazards analysis for incidences of failure was performed to control for patient variables. Results: Of 90 patients, 24 of 53 patients with T1 tumors and 19 of 37 patients with T2 tumors received 50 Gy SABR, and the other 47 patients received 60 Gy. Two-year overall survival and progression-free survival for the whole cohort were 75.8% and 59.3%, respectively. Total SABR dose (50 vs 60 Gy) did not influence survival nor failure rates at 2 and 5 years. Within 2 years of treatment, 7.8% of all patients developed local failure. For all patient and tumor characteristics evaluated, only T stage and pretreatment positron emission tomography standardized uptake values served as predictors of local, regional, and distant failure at 2 and 5 years posttreatment on univariate and multivariable analysis. Conclusions: Five-fraction SABR provides excellent in-field control. T2 and high fluorodeoxyglucose uptake tumors have increased failure rates, suggesting the potential need for adjuvant therapies, which are being assessed in randomized phase 3 trials.

9.
3D Print Med ; 8(1): 22, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35844030

RESUMO

BACKGROUND: Malignancies of the head and neck region, encompassing cutaneous, mucosal, and sarcomatous histologies, are complex entities to manage, comprising of coordination between surgery, radiation therapy, and systemic therapy. Malignancies of the posterior scalp are particular challenging to treat with radiation therapy, given its irregular contours and anatomy as well as the superficial location of the target volume. Bolus material is commonly used in radiation therapy to ensure that the dose to the skin and subcutaneous tissue is appropriate and adequate, accounting for the buildup effect of megavoltage photon treatment. The use of commercially available bolus material on the posterior scalp potentially creates air gaps between the bolus and posterior scalp. CASE PRESENTATIONS: In this report, we created and utilized a custom 3D-printed integrated bolus and headrest for 5 patients to irradiate malignancies involving the posterior scalp, including those with cutaneous squamous cell carcinoma, melanoma, malignant peripheral nerve sheath tumor, and dermal sarcoma. Treatment setup was consistently reproducible, and patients tolerated treatment well without any unexpected adverse effects. CONCLUSIONS: We found that the use of this custom 3D-printed integrated bolus/headrest allowed for comfortable, consistent, and reproducible treatment set up while minimizing the risk of creating significant air gaps and should be considered in the radiotherapeutic management of patients with posterior scalp malignancies.

10.
Med Phys ; 49(8): 5304-5316, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35460584

RESUMO

PURPOSE: Adaptive radiotherapy (ART), especially online ART, effectively accounts for positioning errors and anatomical changes. One key component of online ART process is accurately and efficiently delineating organs at risk (OARs) and targets on online images, such as cone beam computed tomography (CBCT). Direct application of deep learning (DL)-based segmentation to CBCT images suffered from issues such as low image quality and limited available contour labels for training. To overcome these obstacles to online CBCT segmentation, we propose a registration-guided DL (RgDL) segmentation framework that integrates image registration algorithms and DL segmentation models. METHODS: The RgDL framework is composed of two components: image registration and RgDL segmentation. The image registration algorithm transforms/deforms planning contours that were subsequently used as guidance by the DL model to obtain accurate final segmentations. We had two implementations of the proposed framework-Rig-RgDL (Rig for rigid body) and Def-RgDL (Def for deformable)-with rigid body (RB) registration or deformable image registration (DIR) as the registration algorithm, respectively, and U-Net as the DL model architecture. The two implementations of RgDL framework were trained and evaluated on seven OARs in an institutional clinical head-and-neck dataset. RESULTS: Compared to the baseline approaches using the registration or the DL alone, RgDLs achieved more accurate segmentation, as measured by higher mean Dice similarity coefficients (DSCs) and other distance-based metrics. Rig-RgDL achieved a DSC of 84.5% on seven OARs on average, higher than RB or DL alone by 4.5% and 4.7%. The average DSC of Def-RgDL was 86.5%, higher than DIR or DL alone by 2.4% and 6.7%. The inference time required by the DL model component to generate final segmentations of seven OARs was less than 1 s in RgDL. By examining the contours from RgDLs and DL case by case, we found that RgDL was less susceptible to image artifacts. We also studied how the performances of RgDL and DL vary with the size of the training dataset. The DSC of DL dropped by 12.1% as the number of training data decreased from 22 to 5, whereas RgDL only dropped by 3.4%. CONCLUSION: By incorporating the patient-specific registration guidance to a population-based DL segmentation model, RgDL framework overcame the obstacles associated with online CBCT segmentation, including low image quality and insufficient training data, and achieved better segmentation accuracy than baseline methods. The resulting segmentation accuracy and efficiency show promise for applying this RgDL framework for online ART.


Assuntos
Aprendizado Profundo , Planejamento da Radioterapia Assistida por Computador , Algoritmos , Tomografia Computadorizada de Feixe Cônico/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Órgãos em Risco , Planejamento da Radioterapia Assistida por Computador/métodos
11.
Mol Cell Probes ; 59: 101760, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34364994

RESUMO

Human papillomavirus (HPV)-mediated cancers, particularly cervical and oropharyngeal cancer, lead to hundreds of thousands of deaths worldwide each year. Simple, straightforward, and cost-effective detection of HPV DNA from patients with these malignancies or at risk for developing cancer can improve outcomes for patients, serving as a tool for early detection, monitoring treatment response, and assessment of cancer recurrence. Loop-mediated isothermal amplification (LAMP) is a simple and robust method for the detection and amplification of DNA in a single tube, utilizing the Bst strand-displacing DNA polymerase. We developed a workflow utilizing LAMP for the visual detection of HPV DNA in oral rinses. We demonstrate that LAMP is able to easily discriminate between two of the high-risk HPV subtypes, HPV16 and HPV18. We then utilized LAMP to visually detect HPV DNA directly from cells in oral rinses, mimicking a clinical inspired scenario of detecting HPV DNA in clinical samples. Our results suggest that LAMP is a robust, colorimetric assay method for the detection of HPV DNA in complex cellular samples, and further development is warranted to bring LAMP into the clinic.


Assuntos
DNA Viral/isolamento & purificação , Papillomavirus Humano 16/isolamento & purificação , Infecções por Papillomavirus , Humanos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Infecções por Papillomavirus/diagnóstico , Sensibilidade e Especificidade
12.
Am J Clin Pathol ; 156(3): 356-369, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-33899092

RESUMO

OBJECTIVES: We investigated the accuracy of clinical breast carcinoma anatomic staging and the greatest tumor dimension measurements. METHODS: We compared clinical stage and greatest dimension values with the pathologic reference standard values using 57,747 cases from the 2016 US National Cancer Institute Surveillance, Epidemiology, and End Results program who were treated by surgical resection without prior neoadjuvant therapy. RESULTS: Agreement for clinical vs pathologic anatomic TNM group stage, overall, is 74.3% ± 0.4%. Lymph node N staging overall agrees very well (85.1% ± 0.4%). Based on tumor dimension and location, T staging has an agreement of only 64.2% ± 0.4%, worsening to 55% without carcinoma in situ (Tis) cases. In approximately 25% of cases, pathologic T stage is higher than clinical T stage. The mean difference in the greatest dimension is 1.36 ± 9.59 mm with pathologic values being generally larger than clinical values; pathologic and clinical measurements correlate well. T-stage disagreement is associated with histology, tumor grade, tumor size, N stage, patient age, periodic biases in tumor size measurements, and overuse of family T-stage categories. Pathologic measurement biases include rounding and specimen-slicing intervals. CONCLUSIONS: Clinical and pathologic T-staging values agree only moderately. Pathologists face challenges in increasing the precision of gross tumor measurements, with the goal of improving the accuracy of clinical T staging and measurement.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/epidemiologia , Monitoramento Epidemiológico , Feminino , Hospitais , Humanos , Linfonodos/patologia , Estadiamento de Neoplasias , Patologia Clínica , Estudos Retrospectivos , Estados Unidos
13.
Acad Radiol ; 28(6): 753-766, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32563559

RESUMO

RATIONALE AND OBJECTIVES: Examine the accuracy of clinical non-small cell lung cancer staging and tumor length measurements, which are critical to prognosis and treatment planning. MATERIALS AND METHODS: Compare clinical and pathological staging and lengths using 10,320 2016 National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) and 559 2010-2018 non-SEER single-institute surgically-treated cases, and analyze modifiable causes of disagreement. RESULTS: The SEER clinical and pathological group-stages agree only 62.3% ± 0.9% over all stage categories. The lymph node N-stage agrees much better at 83.0% ± 1.0%, but the tumor length-location T-stage agrees only 57.7% ± 0.8% with approximately 29% of the cases having a greater pathology than clinical T-stage. Individual T-stage category agreements with respect to the number of pathology cases are Tis, T1a, T1b, T2a, T2b, T3, T4: 89.9% ± 10.0%; 78.7% ± 1.7%; 51.8% ± 1.9%; 46.1% ± 1.3%; 40.5% ± 3.1%; 44.1% ± 2.2%; 56.4% ± 4.7%, respectively. Most of the single-institute results statistically agree with SEER's. Excluding Tis cases, the mean difference in SEER tumor length is ∼1.18 ± 9.26 mm (confidence interval: 0.97-1.39 mm) with pathological lengths being longer than clinical lengths except for small tumors; the two measurements correlate well (Pearson-r >0.87, confidence interval: 0.86-0.87). Reasons for disagreement include the use of family-category descriptors (e.g., T1) instead of their subcategories (e.g., T1a and T1b), which worsens the T-stage agreement by over 15%. Disagreement is also associated with higher tumor grade, larger resected specimens, higher N-stage, patient age, and periodic biases in clinical and pathological tumor size measurements. CONCLUSIONS: By including preliminary non-small cell lung cancer clinical stage values in their evaluation, diagnostic radiologists can improve the accuracy of staging and standardize tumor-size measurements, which improves patient care.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Institutos de Câncer , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Prognóstico
14.
Cancer Treat Res Commun ; 25: 100253, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33310370

RESUMO

BACKGROUND: Hospitals lack intuitive methods to monitor their accuracy of clinical cancer staging, which is critical to treatment planning, prognosis, refinements, and registering quality data. METHODS: We introduce a tabulation framework to compare clinical staging with the reference-standard pathological staging, and quantify systematic errors. As an example, we analyzed 9,644 2016 U.S. National Cancer Institute SEER surgically-treated non-small cell lung cancer (NSCLC) cases, and computed concordance with different denominators to compare with incompatible past results. RESULTS: The concordance for clinical versus pathological lymph node N-stage is very good, 83.4 ± 1.0%, but the tumor length-location T-stage is only 58.1 ± 0.9%. There are intuitive insights to the causes of discordance. Approximately 29% of the cases are pathological T-stage greater than clinical T-stage, and 12% lower than the clinical T-stage, which is due partly to the fact that surgically-treated NSCLC are typically lower-stage cancer cases, which results in a bounded higher probability for pathological upstaging. Individual T-stage categories Tis, T1a, T1b, T2a, T2b, T3, T4 invariant percent-concordances are 85.2 ± 9.7 + 10.3%; 72.7 ± 1.6 + 11.3%; 46.6 ± 1.8 + 10.9%; 54.6 ± 1.6 - 20.5%; 41.6 ± 3.3 - 0.1%; 54.7 ± 2.8 - 24.1%; 55.2 ± 4.7 + 2.6%, respectively. Each percent-concordance is referenced to an averaged number of pathological and clinical cases. The first error number quantifies statistical fluctuations; the second quantifies clinical and pathological staging biases. Lastly, comparison of over and under staging versus clinical characteristics provides further insights. CONCLUSIONS: Clinical NSCLC staging accuracy and concordance with pathological values can improve. As a first step, the framework enables standardizing comparing staging results and detecting possible problem areas. Cancer hospitals and registries can implement the efficient framework to monitor staging accuracy.


Assuntos
Neoplasias Pulmonares/fisiopatologia , Estadiamento de Neoplasias/métodos , Humanos , Prognóstico
15.
Sci Rep ; 10(1): 13399, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32753612

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

16.
Sci Rep ; 10(1): 8979, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488114

RESUMO

High-dose radiation is the main component of glioblastoma therapy. Unfortunately, radio-resistance is a common problem and a major contributor to tumor relapse. Understanding the molecular mechanisms driving response to radiation is critical for identifying regulatory routes that could be targeted to improve treatment response. We conducted an integrated analysis in the U251 and U343 glioblastoma cell lines to map early alterations in the expression of genes at three levels: transcription, splicing, and translation in response to ionizing radiation. Changes at the transcriptional level were the most prevalent response. Downregulated genes are strongly associated with cell cycle and DNA replication and linked to a coordinated module of expression. Alterations in this group are likely driven by decreased expression of the transcription factor FOXM1 and members of the E2F family. Genes involved in RNA regulatory mechanisms were affected at the mRNA, splicing, and translation levels, highlighting their importance in radiation-response. We identified a number of oncogenic factors, with an increased expression upon radiation exposure, including BCL6, RRM2B, IDO1, FTH1, APIP, and LRIG2 and lncRNAs NEAT1 and FTX. Several of these targets have been previously implicated in radio-resistance. Therefore, antagonizing their effects post-radiation could increase therapeutic efficacy. Our integrated analysis provides a comprehensive view of early response to radiation in glioblastoma. We identify new biological processes involved in altered expression of various oncogenic factors and suggest new target options to increase radiation sensitivity and prevent relapse.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Glioblastoma/genética , Glioblastoma/radioterapia , Splicing de RNA/genética , Transcrição Gênica/genética , Neoplasias Encefálicas/patologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Replicação do DNA/genética , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Expressão Gênica , Glioblastoma/patologia , Humanos , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Biossíntese de Proteínas/genética , Tolerância a Radiação , Radiação Ionizante , Dosagem Radioterapêutica
17.
Neoplasia ; 21(9): 849-862, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31325708

RESUMO

MicroRNAs (miRNAs) are short single-stranded RNAs, measuring 21 to 23 nucleotides in length and regulate gene expression at the post-transcriptional level through mRNA destabilization or repressing protein synthesis. Dysregulation of miRNAs can lead to tumorigenesis through changes in regulation of key cellular processes such as cell proliferation, cell survival, and apoptosis. miR-125a-5p has been implicated as a tumor suppressor miRNA in malignancies such as non-small cell lung cancer and colon cancer. However, the role of miR-125a-5p has not been fully investigated in head and neck squamous cell carcinoma (HNSCC). We performed microRNA microarray profiling of HNSCC tumor samples obtained from a prospective clinical trial evaluating the role of postoperative radiotherapy in head and neck cancer. We also mined through The Cancer Genome Atlas to evaluate expression and survival data. Biological experiments, including cell proliferation, flow cytometry, cell migration and invasion, clonogenic survival, and fluorescent microscopy, were conducted using HN5 and UM-SCC-22B cell lines. miR-125a-5p downregulation was associated with recurrent disease in a panel of high-risk HNSCC and then confirmed poor survival associated with low expression in HNSCC via the Cancer Genome Atlas, suggesting that miR-125a-5p acts as a tumor suppressor miRNA. We then demonstrated that miR-125a-5p regulates cell proliferation through cell cycle regulation at the G1/S transition. We also show that miR-125a-5p can alter cell migration and modulate sensitivity to ionizing radiation. Finally, we identified putative mRNA targets of miR-125a-5p, including ERBB2, EIF4EBP1, and TXNRD1, which support the tumor suppressive mechanism of miR-125a-5p. Functional validation of ERBB2 suggests that miR-125a-5p affects cell proliferation and sensitivity to ionizing radiation, in part, through ERBB2. Our data suggests that miR-125a-5p acts as a tumor suppressor miRNA, has potential as a diagnostic tool and may be a potential therapeutic target for the management and treatment of squamous cell carcinoma of the head and neck.


Assuntos
Biomarcadores Tumorais , Genes Supressores de Tumor , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/mortalidade , MicroRNAs/genética , Regiões 3' não Traduzidas , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Recidiva Local de Neoplasia , Prognóstico , Interferência de RNA , RNA Mensageiro/genética , Radiação Ionizante
18.
Cureus ; 9(7): e1501, 2017 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-28948121

RESUMO

Penetrating brain injuries from gunshot wounds can carry a poor prognosis and require an aggressive, multifaceted approach to obtain a good prognosis and outcome. An initial evaluation requires appropriate imaging studies followed by management and prophylaxis against increased intracranial pressure, infection, and seizures. Surgical management is then followed to ensure the watertight closure of any wounds, removal of any areas of hematoma, and removal of any potential areas of infection. In this paper, we report the case of a patient who presented with a self-inflicted gunshot wound to the head and then received aggressive medical and surgical management. This case presents that an image-guided stereotactic approach with suitable medical management should be used in patients with penetrating missile injuries to the head.

19.
Pract Radiat Oncol ; 7(6): e361-e367, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28666899

RESUMO

PURPOSE: The purpose of this study was to evaluate the utility of moderate deep inspiration breathhold (mDIBH) in reducing heart exposure in left breast cancer patients who have unfavorable cardiac anatomy and need internal mammary lymph node (IMLN) radiation therapy (RT). METHODS AND MATERIALS: We used maximum heart distance (MHD), defined as the maximum distance of the heart within the treatment field, >1 cm as a surrogate for unfavorable cardiac anatomy. Twenty-two left breast cancer patients with unfavorable cardiac anatomy requiring IMLN-RT underwent free-breathing (FB) and mDIBH computed tomography simulation and planning. Three-dimensional partially wide tangents (3D-PWTs) and intensity modulated RT plans were generated. Dose-volume histograms were used to compare heart and lung dosimetric parameters. Duration of treatment delivery was recorded for all fractions. RESULTS: MHD decreased significantly in mDIBH scans. mDIBH significantly reduced mean heart dose (222.7 vs 578.4 cGy; P < .0001) and percentage of left lung receiving doses ≥20 Gy (V20; 31.93 vs 38.41%; P = .0006) in both 3D-PWT and intensity modulated RT plans. The change in MHD after breathhold reliably predicted mean heart dose reduction after mDIBH. Radiation was effectively delivered in 11.31 ± 3.40 minutes with an average of 10.06 ± 2.74 breathholds per fraction. CONCLUSIONS: mDIBH is efficient and can effectively decrease mean heart dose in patients with unfavorable cardiac anatomy who need IMLN-RT, thus simplifying planning and delivery for them. The reduction in mean heart dose is proportional to the reduction in maximum heart distance.


Assuntos
Suspensão da Respiração , Dosagem Radioterapêutica , Neoplasias Unilaterais da Mama/radioterapia , Feminino , Coração/anatomia & histologia , Coração/efeitos da radiação , Humanos , Linfonodos/patologia , Linfonodos/efeitos da radiação , Tratamentos com Preservação do Órgão , Fatores de Tempo , Tomografia Computadorizada por Raios X , Neoplasias Unilaterais da Mama/diagnóstico por imagem , Neoplasias Unilaterais da Mama/cirurgia
20.
Int J Surg Case Rep ; 26: 7-11, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27424104

RESUMO

INTRODUCTION: Hemangioblastomas are benign, slow growing but highly vascularized tumors of the central nervous system, with the most common location of occurrence in the posterior fossa. Hemangioblastomas usually have an associated with patients that have Von-Hippel Lindau disease, resulting a germline mutation in the VHL tumor suppressor gene. Isolated or sporadic occurrences of hemangioblastomas are much more infrequent and typically respond well after surgery. PRESENTATION OF CASE: We present case of a 22year old female with worsening shoulder pain, decreased sensation in the hands and feet, and decreasing strength and was found to have a hemangioblastoma of the cervical spine. DISCUSSION: The patient was treated with surgery and responded well to treatment. We also present a review of the literature on isolated occurrences of hemangioblastomas of the spinal cord. CONCLUSION: Isolated hemangioblastoma are a rare tumor of the central nervous system and can be managed with surgery.

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