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1.
Medicine (Baltimore) ; 98(34): e16916, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441872

RESUMO

BACKGROUND: Colorectal Cancer (CRC) is a highly heterogeneous disease. RNA profiles of bulk tumors have enabled transcriptional classification of CRC. However, such ways of sequencing can only target a cell colony and obscure the signatures of distinct cell populations. Alternatively, single-cell RNA sequencing (scRNA-seq), which can provide unbiased analysis of all cell types, opens the possibility to map cellular heterogeneity of CRC unbiasedly. METHODS: In this study, we utilized scRNA-seq to profile cells from cancer tissue of a CRC patient. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to understand the roles of genes within the clusters. RESULTS AND CONCLUSION: The 2824 cells were analyzed and categorized into 5 distinct clusters by scRNA-seq. For every cluster, specific cell markers can be applied, indicating each 1 of them different from another. We discovered that the tumor of CRC displayed a clear sign of heterogenicity, while genes within each cluster serve different functions. GO term analysis also stated that different cluster's relatedness towards the tumor of CRC differs. Three clusters participate in peripheral works in cells, including, energy transport, extracellular matrix generation, etc; Genes in other 2 clusters participate more in immunology processes. Lastly, trajectory plot analysis also supports the viewpoint, in that some clusters present in different states and pseudo-time, while others present in a single state or pseudo time. Our analysis provides more insight into the heterogeneity of CRC, which can provide assistance to further researches on this topic.


Assuntos
Neoplasias Colorretais/genética , Perfilação da Expressão Gênica/métodos , Heterogeneidade Genética , Análise de Sequência de RNA/métodos , Idoso , Biomarcadores Tumorais/genética , Feminino , Humanos
2.
Cancer Manag Res ; 10: 4333-4347, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30349367

RESUMO

Neoadjuvant therapy (NAT) has been used increasingly in patients with locally advanced or early-stage breast cancer. However, the accurate evaluation and prediction of response to NAT remain the great challenge. Biomarkers could prove useful to identify responders or nonresponders, or even to distinguish between early and delayed responses. These biomarkers could include markers from the tumor itself, such as versatile proteins, genes, and ribonucleic acids, various biological factors or peripheral blood cells, and clinical and pathological features. Possible predictive markers could also include multiple features from functional imaging, such as standard uptake values in positron emission tomography, apparent diffusion coefficient in magnetic resonance, or radiomics imaging biomarkers. In addition, cells that indirectly present the immune status of tumor cells and/or their host could also potentially be used as biomarkers, eg, tumor-infiltrating lymphocytes, tumor-associated macrophages, and myeloid-derived suppressor cells. Though numerous biomarkers have been widely investigated, only estrogen and/or progesterone receptors and human epidermal growth factor receptor have been proven to be reliable biomarkers to predict the response to NAT. They are the only biomarkers recommended in several international guidelines. The other aforementioned biomarkers warrant further validation studies. Some multigene profiling assays that are commercially available, eg, Oncotype DX and MammaPrint, should be used with caution when extrapolated to NAT settings. A panel of combined multilevel biomarkers might be able to predict the response to NAT more robustly than individual biomarkers. To establish such a panel and its prediction model, reliable methods and extensive clinical validation are warranted.

3.
Quant Imaging Med Surg ; 8(7): 637-647, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30211031

RESUMO

Background: To quantify the geometrical changes of each neck nodal level (NNL) and estimate the geometric planning target volume (PTV) margin during image-guided radiotherapy (IGRT) for nasopharyngeal cancer (NPC). Methods: Twenty patients with locally advanced NPC underwent one planning computed tomography (CTplan) and 6 weekly repeat CT (CTrep) scans during chemoradiotherapy. Each CTrep was rigidly registered to the CTplan. All the NNLs were manually delineated in each transverse CT section. When comparing the NNL in CTrep with CTplan, their volumes, displacement of the center of the mass, and the shortest perpendicular distance (SPD) were automatically calculated. This was followed by calculation of the systematic and random errors, overlapping index (OI), and dice similarity coefficient (DSC). With PTVs isotropically expanded from NNL by 1, 2, 3, 4, and 5 mm, they were compared with NNL itself; OI >0.95 was defined as the acceptable geometrical coverage. The Mann-Whitney test was used for statistical analysis. Results: All volumes, OI, and DSC of the NNLs (not including level IA) showed a linear decrease over time throughout the treatment course. The volume of NNLs decreased by 1-6% in the first week and 10-21% in the sixth week. The mean SPD was 1.3-1.7 and 1.9-3.5 mm in the first and sixth week respectively. The DSCs for nodal level IB, II, III, and IV were >0.7 and that of level V was <0.7 throughout the treatment course. For level IA and VI, DSC was <0.7 after the 2nd week. To maintain the OI >0.95, 2-5 mm was needed to expand the different NNLs. Conclusions: The geometrical changes of each NNL are substantial and the necessary margin of 2-5 mm depended on individual NNL is needed to maintain geometrical coverage throughout the course of IGRT for NPC.

4.
Chem Commun (Camb) ; 54(47): 6060-6063, 2018 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-29808876

RESUMO

Black phosphorus quantum dots are incorporated into liposomal bilayers to produce a drug delivery system with excellent near-infrared (NIR) photothermal properties and drug release capability controlled by light. In vitro experiments demonstrate its good biocompatibility and NIR-light-induced chemo-photothermal antitumor efficiency.


Assuntos
Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Bicamadas Lipídicas/química , Lipossomos/química , Fósforo/química , Pontos Quânticos/efeitos da radiação , Animais , Colesterol/química , Colesterol/toxicidade , Liberação Controlada de Fármacos , Calefação , Humanos , Raios Infravermelhos , Bicamadas Lipídicas/toxicidade , Lipossomos/toxicidade , Células MCF-7 , Camundongos , Microscopia Confocal , Tamanho da Partícula , Fosfatidilcolinas/química , Fosfatidilcolinas/toxicidade , Fósforo/toxicidade , Pontos Quânticos/química , Pontos Quânticos/toxicidade
5.
Cancer Manag Res ; 10: 447-464, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29563835

RESUMO

Background: Circulating endothelial cells (CECs) and their subpopulations could be potential novel biomarkers for various malignancies. However, reliable enumerable methods are warranted to further improve their clinical utility. This study aimed to optimize a flow cytometric method (FCM) assay for CECs and subpopulations in peripheral blood for patients with solid cancers. Patients and methods: An FCM assay was used to detect and identify CECs. A panel of 60 blood samples, including 44 metastatic cancer patients and 16 healthy controls, were used in this study. Some key issues of CEC enumeration, including sample material and anticoagulant selection, optimal titration of antibodies, lysis/wash procedures of blood sample preparation, conditions of sample storage, sufficient cell events to enhance the signal, fluorescence-minus-one controls instead of isotype controls to reduce background noise, optimal selection of cell surface markers, and evaluating the reproducibility of our method, were integrated and investigated. Wilcoxon and Mann-Whitney U tests were used to determine statistically significant differences. Results: In this validation study, we refined a five-color FCM method to detect CECs and their subpopulations in peripheral blood of patients with solid tumors. Several key technical issues regarding preanalytical elements, FCM data acquisition, and analysis were addressed. Furthermore, we clinically validated the utility of our method. The baseline levels of mature CECs, endothelial progenitor cells, and activated CECs were higher in cancer patients than healthy subjects (P<0.01). However, there was no significant difference in resting CEC levels between healthy subjects and cancer patients (P=0.193). Conclusion: We integrated and comprehensively addressed significant technical issues found in previously published assays and validated the reproducibility and sensitivity of our proposed method. Future work is required to explore the potential of our optimized method in clinical oncologic applications.

6.
Biomark Med ; 11(8): 665-676, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28597689

RESUMO

Angiogenesis contributes to the growth of solid tumors. Antiangiogenic agents are widely used in various cancers and considerable efforts have been made in the development of novel biomarkers that can predict the outcome of an anticancer treatment. Of those, circulating endothelial cells (CECs) and their subsets constitute a surrogate tool for monitoring disease activity. However, owing to the lack of standardization on the phenotypes and detection of CECs and their subsets, results have always been inconsistent and uninterpretable. In this review, we focus on the biological characteristics in terms of physiology, phenotypes and detection of CECs along with their subsets; review the current scenario of CEC enumeration as a surrogate biomarker in clinical oncology; and explore their future potential applications.

7.
Onco Targets Ther ; 10: 67-72, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28053541

RESUMO

Patients with stage IV nasopharyngeal carcinoma (NPC) have a poor prognosis, even with effective chemotherapy. Target agents combined with chemotherapy may improve NPC patients' outcome. The case of a patient with NPC, who was treated by adding bevacizumab to chemotherapy after disease progression using first-line chemotherapy, is reported. Recently published literature about effects of combining bevacizumab with standard chemotherapy in NPC cell lines or patients are also reviewed and discussed. Consistent with a few preclinical trials and Phase II clinical trials, bevacizumab may reverse the drug resistance to chemotherapy, and its toxic side effects are well tolerated.

8.
Oncotarget ; 7(35): 56998-57010, 2016 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-27486770

RESUMO

Lung adenocarcinomas are more commonly associated with brain metastases (BM). Epidermal growth factor receptor (EGFR) mutations have been demonstrated to be both predictive and prognostic for patients with lung adenocarcinoma. We aimed to explore the potential association between EGFR mutation and the risk of BM in pulmonary adenocarcinoma patients. Data of 234 patients from 2007 to 2014 were retrospectively reviewed. A total of 108 patients had EGFR mutations in the entire cohort. Among them, 76 patients developed BM during their disease course. The incidence of BM was statistically higher in patients with EGFR mutations both at initial diagnosis (P=0.014) and at last follow-up (P<0.001). Multivariate logistic regression analysis revealed that EGFR mutation significantly increased the risk of BM at initial diagnosis (OR=2.515, P=0.022). In patients without BM at initial diagnosis, the accumulative rate of subsequent BM was significantly higher with EGFR mutations (P=0.001). Multivariate Cox regression analysis identified EGFR mutation as the only independent risk factor for subsequent BM (HR=3.036, P=0.001). Patients with EGFR mutations demonstrated longer overall survival (OS) after BM diagnosis than patients with wild-type EGFR (P=0.028). Our data suggest that EGFR mutation is an independent predictive and prognostic risk factor for BM and a positive predictive factor for OS in patients with BM.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias Encefálicas/metabolismo , Receptores ErbB/genética , Neoplasias Pulmonares/metabolismo , Mutação , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/secundário , Análise Mutacional de DNA , Receptores ErbB/metabolismo , Éxons , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
9.
Quant Imaging Med Surg ; 6(2): 115-24, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27190763

RESUMO

BACKGROUND: Considerable geometrical change occurs during chemoradiotherapy (CRT) course of nasopharyngeal carcinoma (NPC). This aim of this study was to quantify the volumetric and surface variability of the target volumes (TV) and to estimate the expanded margin to maintain acceptable geometrical coverage. METHODS: Twenty patients with locally advanced nasopharyngeal cancer underwent one planning CT (pCT) and six weekly repeated CT (rCT) scans during the treatment course of definitive CRT. The TV included the gross tumor volume (GTV) of the primary tumor, large (shortest diameter >3.0 cm) and small (diameter >1 cm and ≤3 cm) positive neck lymph nodes, and low-risk clinical target volume (CTV_Lr) that were delineated manually on the pCT and each rCT. When comparing TV in pCT (V_pCT) and TV in rCT (V_rCT), the overlapping index (OI), Dice similarity coefficient (DSC), shortest perpendicular distance (SPD), and overall standard deviation (overall SD) were calculated to present the geometric changes. An isotropical margin was expanded outward around CTV_Lr in pCT to establish the mimic planning target volume (PTV). An OI ≥0.95 was defined as acceptable geometrical coverage. RESULTS: For all TV, DSCs decreased, and the SPDs and overall SD increased with the increasing number of fractions delivered. The DSCs of all gross TV were <70% after the third week. The mean SPDs were 1.5-2.5 mm in the first week and 5.2-6.2 mm in the last week. The OI and DSC in concurrent CRT were smaller than those in the sequential therapy; and similarly the SPD and overall SD in the concurrent therapy were larger than those in the sequential one. To maintain >95% geometrical coverage, a 2-mm additional margin could maintain the coverage throughout the treatment course and a 1-mm margin could maintain the desired coverage if there is an adaptive re-planning no later than the third week of the treatment course. CONCLUSIONS: Both volumetric coverage and surface of the tumour underwent the progressive changes during the treatment course of CRT. One to two mm as the expanded margin to establish the PTV is required to maintain >95% geometrical coverage.

10.
World J Microbiol Biotechnol ; 31(3): 477-85, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25595731

RESUMO

Microsclerotia (MS) formation was successfully induced in Nomuraea rileyi in liquid amended medium (AM) culture. To investigate how N. rileyi senses growth stress and regulates MS differentiation, based on transcriptome library, sho1 and sln1 genes were cloned. The transcription levels of sho1 and sln1 were upregulated in response to the changing culture conditions. To determine the functions of sho1 and sln1, gene-silencing mutants (sholi, sln1i and shol&sln1i) were generated using RNA silencing technology. The significant phenotypic changes in the mutants included reduced conidial yields by 22.72, 40.27, and 63.67 % and virulence by 24.53, 25.74, and 59.04 %, respectively. Furthermore, the mutants presented decreased MS yields by approximately 96 % under changing culture conditions. Our results confirmed the crucial role of Sho1p and Sln1p in sensing growth stress due to changing culture conditions and regulating MS differentiation.


Assuntos
Adaptação Fisiológica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Metarhizium/fisiologia , Proteínas Quinases/metabolismo , Estresse Fisiológico , Clonagem Molecular , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Metarhizium/crescimento & desenvolvimento , Proteínas Quinases/genética , Esporos Fúngicos/crescimento & desenvolvimento , Transcrição Genética
11.
Onco Targets Ther ; 7: 1361-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25114574

RESUMO

Paclitaxel (PTX) and/or cisplatin (CDDP), as important cytotoxic anti-cancer agents, are widely used to treat various solid tumors. Both may cause moderate or severe neurotoxicity, but ocular neurotoxicity is also occasionally reported. A patient diagnosed with nasopharyngeal cancer suffering acute ocular neurotoxicity 10 days after paclitaxel and CDDP administration at the recommended dose is described in the present case report, and PTX- and/or CDDP-induced ocular neurotoxicity are summarized according to previous reports. Possible mechanisms and the potential diagnostic, therapeutic and predictive strategies of PTX- and/or CDDP-induced ocular neurotoxicity are reviewed, to help the oncologist to take the infrequent toxicity of cytotoxic drugs into account and improve patient safety during anti-cancer therapy.

12.
Radiother Oncol ; 112(3): 413-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25104017

RESUMO

BACKGROUND AND PURPOSE: Compressed sensing (CS) based cone-beam computed tomography (CBCT) reconstruction techniques have been shown to improve image quality. This study was to investigate possible improvements of CBCTCS on manual delineation uncertainties of targets and organs-at-risk. PATIENTS AND METHODS: Eight H&N and eight breast cancer patients were selected. Each H&N or breast cancer patient had planning-CT (pCT), repeat-CT (rCT), and CBCT reconstructed by both Feldkamp (CBCTFDK) and compressed sensing methods. On each scan, targets and organs-at-risk were delineated by a radiation oncologist. The impact of reconstruction technique was quantitatively assessed by dice similarity coefficient (DSC) and the shortest perpendicular distance (SPD) between contours of two corresponding scans. RESULTS: The mean CBCTCS-to-rCT DSC was 7.2% and 8.0% bigger than the CBCTFDK-to-rCT for H&N and breast cancer patients respectively. The mean CBCTCS-to-rCT SPD was 16.6% and 25.4% smaller than CBCTFDK-to-rCT SPD. Due to anatomical changes, delineation accuracy reduced in reference to pCT, but no time trend was observed in CBCT based delineation accuracy in reference to rCT. CONCLUSION: This study demonstrated that CBCTCS has the potential to improve delineation accuracy in H&N and breast cancer patients over CBCTFDK, and CBCTCS thus has potential for adaptive radiotherapy.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico/métodos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Órgãos em Risco/diagnóstico por imagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
13.
PLoS One ; 9(2): e90007, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24587184

RESUMO

PURPOSE: The objective of this study was to evaluate the dosimetric feasibility of using hippocampus (HPC) sparing intensity-modulated radiotherapy (IMRT) in patients with locally advanced nasopharyngeal carcinoma (NPC). MATERIALS/METHODS: Eight cases of either T3 or T4 NPC were selected for this study. Standard IMRT treatment plans were constructed using the volume and dose constraints for the targets and organs at risk (OAR) per Radiation Therapy Oncology Group (RTOG) 0615 protocol. Experimental plans were constructed using the same criteria, with the addition of the HPC as an OAR. The two dose-volume histograms for each case were compared for the targets and OARs. RESULTS: All plans achieved the protocol dose criteria. The homogeneity index, conformity index, and coverage index for the planning target volumes (PTVs) were not significantly compromised by the avoidance of the HPC. The doses to all OARs, excluding the HPC, were similar. Both the dose (Dmax, D2%, D40%, D mean, D median, D98% and D min) and volume (V5, V10, V15, V20, V30, V40 and V50) parameters for the HPC were significantly lower in the HPC sparing plans (p<0.05), except for D min (P = 0.06) and V5 (P = 0.12). CONCLUSIONS: IMRT for patients with locally advanced NPC exposes the HPC to a significant radiation dose. HPC sparing IMRT planning significantly decreases this dose, with minimal impact on the therapeutic targets and other OARs.


Assuntos
Neoplasias Nasofaríngeas/radioterapia , Tratamentos com Preservação do Órgão/métodos , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/métodos , Carcinoma , Hipocampo , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Órgãos em Risco , Radiometria , Dosagem Radioterapêutica
14.
Future Oncol ; 10(11): 1863-72, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23987920

RESUMO

During intensity-modulated radiotherapy, an organ is usually assumed to be functionally homogeneous and, generally, its anatomical and spatial heterogeneity with respect to radiation response are not taken into consideration. However, advances in imaging and radiation techniques as well as an improved understanding of the radiobiological response of organs have raised the possibility of sparing the critical functional structures within various organs at risk during intensity-modulated radiotherapy. Here, we discuss these structures, which include the critical brain structure, or neural nuclei, and the nerve fiber tracts in the CNS, head and neck structures related to radiation-induced salivary and swallowing dysfunction, and functional structures in the heart and lung. We suggest that these structures can be used as potential surrogate organs at risk in order to minimize their radiation dose and/or irradiated volume without compromising the dose coverage of the target volume during radiation treatment.


Assuntos
Neoplasias/patologia , Neoplasias/radioterapia , Tratamentos com Preservação do Órgão , Radioterapia de Intensidade Modulada , Fracionamento da Dose de Radiação , Humanos , Doses de Radiação , Planejamento da Radioterapia Assistida por Computador
15.
Onco Targets Ther ; 6: 1719-28, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24311943

RESUMO

PURPOSE: Considerable anatomical changes occur during intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). This study aimed to quantify volumetric and positional variations of the target volume during IMRT. MATERIALS AND METHODS: Twenty patients with locally advanced NPC who received concurrent (13 patients) or sequential (seven patients) chemoradiotherapy were prospectively recruited and underwent planning computed tomography (CT) and six repeat CTs (every five fractions). Each repeat CT was rigidly registered to the planning CT. Gross tumor volume (GTV) and elective clinical target volume (CTV) were manually delineated on each axial CT image. CTVs of the primary tumor and lymph nodes were expanded with 5 mm margins to corresponding GTVs, with necessary modifications. Volume loss, system and random errors, and the mean and three-dimensional vector displacements were calculated and compared statistically. RESULTS: Volumes of the primary tumor and small (>1 cm, ≤3 cm) and large (>3 cm) positive neck lymph nodes decreased at a rate of 2.6%, 3.7%, and 3.9% per treatment day, respectively. CTVs of the primary tumor, lymph nodes, and elective region decreased 1.5%, 2.3%, and 0.3% per treatment day, respectively. Average displacements of the GTVs and CTVs were <1.3 mm in all directions. GTVs and CTVs of the large and small lymph nodes shifted medially by 0.8-1.3 and 0.6-1.2 mm, respectively, on average. Average three-dimensional displacements of the GTVs and CTVs were 3.4-4.3 mm and 2.5-3.7 mm, respectively. Volume loss and displacements in most directions were significantly larger in patients receiving concurrent chemoradiotherapy than in those receiving sequential therapy. Volume loss and displacements of the GTV of large nodes and elective CTV were significantly larger in male than in female patients. CONCLUSION: Volumetric and positional changes of the target volume were considerable, and volume loss increased as treatment time elapsed during IMRT for NPC.

16.
Onco Targets Ther ; 6: 1325-32, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24098082

RESUMO

PURPOSE: The aim of this study was to quantify the displacement of cardiac substructures, including the anterior myocardial territory (AMT), left ventricle, and coronary arteries during a normal cardiac cycle. MATERIALS AND METHODS: Computed tomography (CT) images with retrospective electrocardiographic gating of 17 eligible patients were obtained. All images were reconstructed automatically for the end-diastolic and end-systolic phases. CT scanning without contrast at a random phase and a selected vertebral body were used as references to measure three-dimensionaldisplacements of the cardiac substructures. RESULTS: The displacement between the end-diastolic and end-systolic phases (Dd-s) was greater than that between the end-systolic and random phases and between the end-diastolic and random cardiac phases. The largest displacements for the heart were in the left, posterior, and inferior directions with an average Dd-s of approximately 4-6 mm. The average Dd-s for the AMT and left ventricle was 1.2-2.7 mm in the anterior and right directions, 4.3-7.8 mm in left and posterior directions, and 4.9-6.3 mm in superior and inferior directions. For the coronary arteries, the average Dd-s was 2.8-5.9 mm in the anterior-posterior direction, 3.5-6.6 mm in left-right direction, and 3.8-5.3 mm in the superior-inferior direction. Inter-observer agreement was excellent for the heart, AMT, and left ventricle (kappa coefficient, >0.75 for all) and good for most coronary arteries in three dimensions (kappa coefficient, 0.511-0.687). The Dd-s did not differ significantly between men and women. CONCLUSION: Most average displacements of the cardiac substructures and coronary arteries were 3-8 mm in three dimensions. These findings will be useful to accurately estimate the radiation dose to cardiac substructures during thoracic radiation and to evaluate the risk of radiation-related heart disease.

17.
Int J Radiat Oncol Biol Phys ; 82(5): 1689-97, 2012 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-21621342

RESUMO

PURPOSE: We investigated whether the heart could be replaced by the anterior myocardial territory (AMT) as the organ at risk (OAR) in intensity-modulated radiotherapy (IMRT) of the breast for patients with left-sided breast cancer. METHODS AND MATERIALS: Twenty-three patients with left-sided breast cancer who received postoperative radiation after breast-conserving surgery were studied. For each patient, we generated five IMRT plans including heart (H), left ventricle (LV), AMT, LV+AMT, and H+LV as the primary OARs, respectively, except both lungs and right breast, which corresponded to IMRT(H), IMRT(LV), IMRT(AMT), IMRT(LV+AMT), and IMRT(H+LV). For the planning target volumes and OARs, the parameters of dose-volume histograms were compared. RESULTS: The homogeneity index, conformity index, and coverage index were not compromised significantly in IMRT(AMT), IMRT(LV) and IMRT(LV+ AMT), respectively, when compared with IMRT(H). The mean dose to the heart, LV, and AMT decreased 5.3-21.5% (p < 0.05), 19.9-29.5% (p < 0.05), and 13.3-24.5% (p < 0.05), respectively. Similarly, the low (e.g., V5%), middle (e.g., V20%), and high (e.g., V30%) dose-volume of the heart, LV, and AMT decreased with different levels. The mean dose and V10% of the right lung increased by 9.2% (p < 0.05) and 27.6% (p < 0.05), respectively, in IMRT(LV), and the mean dose and V5% of the right breast decreased significantly in IMRT(AMT) and IMRT(LV+AMT). IMRT(AMT) was the preferred plan and was then compared with IMRT(H+LV); the majority of dose-volume histogram parameters of OARs including the heart, LV, AMT, both lungs, and the right breast were not statistically different. However, the low dose-volume of LV increased and the middle dose-volume decreased significantly (p < 0.05) in IMRT(AMT). Also, those of the right lung (V10%, V15%) and right breast (V5%, V10%) decreased significantly (p < 0.05). CONCLUSIONS: The AMT may replace the heart as the OAR in left-sided breast IMRT after breast-conserving surgery to decrease the radiation dose to the heart.


Assuntos
Neoplasias da Mama/radioterapia , Coração/efeitos da radiação , Miocárdio , Órgãos em Risco/efeitos da radiação , Lesões por Radiação/prevenção & controle , Radioterapia de Intensidade Modulada/métodos , Mama/efeitos da radiação , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Coração/anatomia & histologia , Coração/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/efeitos da radiação , Humanos , Pulmão/diagnóstico por imagem , Pulmão/efeitos da radiação , Mastectomia Segmentar , Radiografia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/efeitos adversos
18.
Int J Radiat Oncol Biol Phys ; 81(5): 1544-51, 2011 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-21470785

RESUMO

PURPOSE: We evaluated heart sparing using an intensity-modulated radiotherapy (IMRT) plan with the left ventricle (LV) and/or the anterior myocardial territory (AMT) as additional organs at risk (OARs). METHODS AND MATERIALS: A total of 10 patients with left-sided breast cancer were selected for dosimetric planning. Both lungs, the right breast, heart, LV, and AMT were defined as OARs. We generated one tangential field plan and four IMRT plans for each patient. We examined the dose-volume histogram parameters of the planning target volume and OARs. RESULTS: Compared with the tangential field plan, the mean dose to the heart in the IMRT plans did not show significant differences; however, the dose to the AMT and LV decreased by 18.7-45.4% and 10.8-37.4%, respectively. The maximal dose to the heart decreased by 18.6-35.3%, to the AMT by 22.0-45.1%, and to the LV by 23.5-45.0%, And the relative volumes of the heart (V≥12), AMT (V>11) and LV (V>10) decreased significantly with different levels, respectively. The volume of the heart, AMT, LV, both lungs, and right breast receiving≥5 Gy showed a significant increase. Compared with the IMRT (H) plan, the mean dose to the heart, AMT, and LV decreased by 17.5-21.5%, 25.2-29.8%, and 22.8-29.8% and the maximal dose by 13.6-20.6%, 23.1-29.6%, and 17.3-29.1%, respectively. The IMRT plans for both lungs and the right breast showed no significant differences. CONCLUSIONS: The IMRT plans with the addition of the AMT and/or LV as OARs considerably increased heart sparing. We recommend including the LV as an additional OAR in such plans.


Assuntos
Neoplasias da Mama/radioterapia , Coração/efeitos da radiação , Órgãos em Risco/efeitos da radiação , Lesões por Radiação/prevenção & controle , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Mama/efeitos da radiação , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Angiografia Coronária/métodos , Feminino , Coração/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/efeitos da radiação , Humanos , Pulmão/diagnóstico por imagem , Pulmão/efeitos da radiação , Miocárdio , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/diagnóstico por imagem , Dosagem Radioterapêutica , Radioterapia Conformacional/métodos , Tomografia Computadorizada por Raios X , Carga Tumoral/efeitos da radiação
19.
Cancer Sci ; 99(5): 952-7, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18341653

RESUMO

Recent research indicates that inflammatory factors play important roles in the initiation and progression of cancers, including breast cancer. Daintain/allograft inflammatory factor-1 (AIF-1) is a crucial mediator in the inflammatory response, but it has not yet been reported whether daintain/AIF-1 is involved in the development of breast cancers. In this study, immunohistochemical analysis found strong positive expression of daintain/AIF-1 in breast ductal tumor epithelia, but only weakly positive or negative expression in the adjacent histologically normal ductal epithelia. Then, the effect of daintian/AIF-1 on the proliferation of the breast cancer cell line MDA-MB-231 was explored via transduction of the daintian/AIF-1 gene into the cells, and via inhibition of the expression of daintain/AIF-1 through short interference RNA. The results demonstrated that up-regulation and down-regulation of daintain/AIF-1 expressions promoted and inhibited the proliferation of MDA-MB-231, respectively. More interestingly, daintain/AIF-1 overexpression facilitated tumor growth in female nude mice. Furthermore, we found that daintain/AIF-1 overexpression up-regulated the expression of cyclin D1 and enhanced the transcriptional activity of nuclear factor-kappa B (NF-kappaB), a regulator of cyclin D1 expression. In contrast, the down-regulation of daintain/AIF-1 expression decreased cyclin D1 expression and inhibited the transcriptional activity of NF-kappaB. These results strongly suggest that daintain/AIF-1 can promote the growth of breast tumors via activating NF-kappaB signaling, which consequently up-regulates the expression of cyclin D1, implying that daintain/AIF-1 may be a novel target molecule for the prognosis and therapy of breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Ciclina D1/metabolismo , Proteínas de Ligação a DNA/metabolismo , NF-kappa B/metabolismo , Animais , Proteínas de Ligação ao Cálcio , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/genética , Humanos , Camundongos , Camundongos Nus , Proteínas dos Microfilamentos , NF-kappa B/genética , Transdução de Sinais , Transcrição Genética , Transfecção , Regulação para Cima
20.
Ai Zheng ; 26(12): 1360-4, 2007 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-18076802

RESUMO

BACKGROUND & OBJECTIVE: The treatment strategies of Hodgkin's lymphoma (HL) are different according to clinical stage and risk factors, yet the optimal treatment strategy remains unclear. This study was to analyze the treatment results and prognostic factors of stage IA HL. METHODS: According to prognosis, 97 patients with stage IA HL were divided into 3 groups: 7 (7.2%) in very favorable (VF) group, 72 (74.2%) in favorable (F) group, and 18 (18.6%) in unfavorable (UF) group. Short-term treatment outcome and long-term survival were analyzed. The prognosis was analyzed with Cox regression model. RESULTS: Median follow-up time was 65 months. After radiotherapy or radiochemotherapy, 90 patients (92.8%) achieved complete remission (CR). The 5-and 10-year overall survival (OS) rates were 87.7% and 76.3%; the 5-and 10-year disease-free survival (DFS) rates were 79.4% and 74.5%. The 5-and 10-year OS rates were 100% and 100% in VF group, 88.9% and 88.4% in F group, 78.1% and 39.1% in UF group (P=0.292). The 5-and 10-year DFS rates were 100% and 87.2% in VF group, 86.3% and 71.8% in F group, 73.6% and 34.5% in UF group (P=0.032). Cox analysis showed that pathologic type (P=0.056) and tumor relapse (P=0.011) influenced OS, and the response to primary treatment (P=0.024) influenced DFS. The relapse rate was 18.6%û there was no significant difference between the patients received radiotherapy alone and those received radiochemotherapy (Chi(2)=0.072, P=0.788). The occurrence rate of secondary malignancies was 5.2%, including 2 cases of non-Hodgkin's lymphoma. All the 12 patients who died had received radiotherapy alone. CONCLUSIONS: More than 90% of stage IA HL patients can achieve CR with radiotherapy alone or chemoradiotherapy. The long-term OS and DFS of the patients who received radiochemotherapy are better than those of the patients who received radiotherapy alone. The pathologic type, response to primary treatment and tumor relapse may be independent prognostic factors of stage IA HL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Radioterapia de Alta Energia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Terapia Combinada , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Doença de Hodgkin/patologia , Humanos , Metástase Linfática , Masculino , Mecloretamina/uso terapêutico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Prednisona/uso terapêutico , Procarbazina/uso terapêutico , Radioterapia de Alta Energia/efeitos adversos , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Vincristina/uso terapêutico , Adulto Jovem
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