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INTRODUCTION: Intraoperative electron radiotherapy (IOERT) is a technique aiming to deliver radiotherapy during oncological surgery. In breast IOERT, the applicator and shielding disc placement are correlated with organs at risk (OAR) irradiation, in vivo verification of these parameters is scarcely reported. The aim of our study is to report and analyze possible causes of the misalignment using radiochromic films and compare our results to others reported in the bibliography. METHODS: From November 2019 to April 2023, in vivo verifications were performed for 33 patients. IOERT was performed using a LIAC 10 MeV (Sordina, Italy) electron accelerator. We attached a radiochromic film to the upper side of the polytetrafluoroethylene cover of the shielding disc. The percentage of the irradiation area outside the disc was recorded and various parameters (applicator angulations, prescription depth, tumor location and breast size) were analyzed to find possible correlations. RESULTS: For 29 patients, 20 Gy were prescribed while 10 Gy were prescribed to 4 patients. The average irradiated area outside the disc was 19% (0-56%) corresponding to a surface of 4.5 cm2 (0-17.4 cm2). The applicator of 5 cm was used for most of the patients. The mean prescription depth was 1.4 cm (0.5-2.5 cm). We found no correlation between the analyzed parameters and misalignment. CONCLUSION: This study confirms the presence and magnitude of the misalignments. We strongly recommend in vivo verifications as a quality check during IOERT procedures. The misalignment has no correlation with tumor localization parameters, so the solution could be based on technical improvements of the applicator.
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Neoplasias da Mama , Elétrons , Humanos , Feminino , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Elétrons/uso terapêutico , Controle de Qualidade , Órgãos em Risco/efeitos da radiação , Dosagem Radioterapêutica , Cuidados Intraoperatórios/métodos , Pessoa de Meia-Idade , Aceleradores de Partículas , Idoso , Planejamento da Radioterapia Assistida por Computador/métodos , AdultoRESUMO
PURPOSE: Brachytherapy (BT) has been used for many years for disease control in tumours of the head and neck area (H&N). It is currently performed with high dose rate (HDR) or pulsed dose rate (PDR), but its use has been reduced due to the implementation of new non-invasive external beam radiotherapy techniques such as intensity modulation (IMRT) and volumetric modulated arc therapy (VMAT) and the improvement of surgical techniques. METHODS: The Spanish Brachytherapy Group (GEB) has carried out a survey to find out the number of centres in Spain that continue to use BT in H&N and its indications and expectations for the future. RESULTS: The results were presented at the XX GEB Consensus Meeting held on October 21, 2022, in Valencia (Spain) and it was confirmed that, although there are fewer and fewer centres that use BT in H&N, there are still units with extensive experience in this technique that should be positioned as referral centres. CONCLUSION: It is necessary to carry out continuous work with other specialities involved, such as H&N surgeons, and other radiation oncologists, to improve the training of residents, both oncologists and medical physicists.
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Braquiterapia , Radioterapia de Intensidade Modulada , Humanos , Braquiterapia/métodos , Espanha , Radioterapia de Intensidade Modulada/métodos , Pescoço , Planejamento da Radioterapia Assistida por Computador/métodos , Dosagem RadioterapêuticaRESUMO
PURPOSE: Analyse the impact of different prognostic factors on G2-late vaginal complications after vaginal brachytherapy (VBT) ± external beam radiotherapy (EBRT) in postoperative endometrial cancer (PEC). METHODS: One hundred and twenty-six PEC patients treated with VBT ± EBRT were retrospectively analysed considering age, body mass index, applicator diameter, clinical target volume (CTV), use of dilators, chemotherapy and EQD2(α/ß=3) at the most exposed 2 cm3 of the CTV as prognostic factors for vaginal complications. Late vaginal complications were evaluated using objective LENT-SOMA criteria. STATISTICS: descriptive analysis, Chi-square, Fisher and Student tests were applied. Univariate and multivariate analyses were performed with the Baptista-Pike exact method and multiple logistic regression. RESULTS: Mean age was 65 years (SD ± 10), and median follow-up was 66 months (8-104). 19/126 patients (15%) showed G2-late vaginal complications, and 107/126 (85%) G0-G1. Univariate analysis showed: CTV ≤ 9 cm3 (p = 0.036), use of dilators < 9 months (p = 0.015), and total ≥ 68 Gy EQD2 received by 2 cm3 of CTV (p = 0.039) were associated with G2-late vaginal toxicity. Multivariate analysis showed the use of dilators < 9 months as an independent prognostic factor for G2-late vaginal toxicity (p = 0.043, OR 8.59, CI 1.59-159.9). CONCLUSION: The use of dilators < 9 months in VBT ± EBRT for PEC was an independent prognostic factor for G2-late vaginal toxicity. The use of vaginal dilators ≥ 9 months requires further analysis in studies evaluating late vaginal toxicity.
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Braquiterapia , Neoplasias do Endométrio , Feminino , Humanos , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Estudos Retrospectivos , Prognóstico , Vagina/patologia , Neoplasias do Endométrio/radioterapia , Neoplasias do Endométrio/cirurgia , Neoplasias do Endométrio/patologia , Estadiamento de NeoplasiasRESUMO
Endothelin-converting enzyme-1 (ECE1) activates the endothelin-1 peptide, which upregulates pathways that are related to diverse hallmarks of cancer. ECE1 is expressed as four isoforms differing in their N-terminal domains. Protein kinase CK2 phosphorylates the N-terminus of isoform ECE1c, enhancing its stability and promoting invasiveness of colorectal cancer cells. However, the specific residues in ECE1c that are phosphorylated by CK2 and how this phosphorylation promotes invasiveness was unknown. Here we demonstrate that Ser-18 and Ser-20 are the bona fide residues phosphorylated by CK2 in ECE1c. Thus, biphospho-mimetic ECE1cDD and biphospho-resistant ECE1cAA mutants were constructed and stably expressed in different colorectal cancer cells through lentiviral transduction. Biphospho-mimetic ECE1cDD displayed the highest stability in cells, even in the presence of the specific CK2 inhibitor silmitasertib. Concordantly, ECE1cDD-expressing cells showed enhanced hallmarks of cancer, such as proliferation, migration, invasiveness, and self-renewal capacities. Conversely, cells expressing the less-stable biphospho-resistant ECE1cAA showed a reduction in these features, but also displayed an important sensitization to 5-fluorouracil, an antineoplastic agent traditionally used as therapy in colorectal cancer patients. Altogether, these findings suggest that phosphorylation of ECE1c at Ser-18 and Ser-20 by CK2 promotes aggressiveness in colorectal cancer cells. Therefore, phospho-ECE1c may constitute a novel biomarker of poor prognosis and CK2 inhibition may be envisioned as a potential therapy for colorectal cancer patients.
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Zinc finger protein SNAI1 (SNAIL) and zinc finger protein SNAI2 (SLUG) transcription factors promote epithelialmesenchymal transition, a process through which epithelial cells acquire a mesenchymal phenotype, increasing their migratory and invasive properties. In prostate cancer (PCa) progression, increased expression levels of SNAIL and SLUG have been described. In advanced PCa, a decrease in the cell surface proteoglycan syndecan1 (SDC1), which has a role in celltoextracellular matrix adhesion, has been observed. Notably, SDC1 nuclear location has been observed in mesenchymal cancers. The present study aimed to determine if SNAIL and SLUG may be associated with the nuclear location of SDC1 in PCa. To determine the location of SDC1, antibodies against its intracellular domain (ID) or extracellular domain (ED) were used in benign prostatic hyperplasia (BPH) and PCa samples with high Gleason scores. Only IDSDC1 was located in the cell nuclei in advanced PCa samples, but not in the BPH samples. EDSDC1 was located in the cell membrane and cytoplasm, exhibiting decreased levels in PCa in comparison with those in BPH. Furthermore, LNCaP and PC3 PCa cell lines with ectopic SNAIL expression exhibited nuclear IDSDC1. No change was observed in the EDSDC1 levels, and maintained its location in the cell membrane and cytoplasm. SLUG induced no change in IDSDC1 location. At the protein level, an association between SNAIL and nuclear IDSDC1 was observed. In conclusion, the results of the present study demonstrated that nuclear IDSDC1 localization was associated with SNAIL expression in PCa cell lines.
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Núcleo Celular/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/metabolismo , Neoplasias da Próstata/metabolismo , Fatores de Transcrição da Família Snail/biossíntese , Sindecana-1/metabolismo , Transporte Ativo do Núcleo Celular , Núcleo Celular/genética , Núcleo Celular/patologia , Humanos , Masculino , Proteínas de Neoplasias/genética , Células PC-3 , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Fatores de Transcrição da Família Snail/genética , Sindecana-1/genéticaRESUMO
Syndecan 1 (SDC-1) is a cell surface proteoglycan with a significant role in cell adhesion, maintaining epithelial integrity. SDC1 expression is inversely related to aggressiveness in prostate cancer (PCa). During epithelial to mesenchymal transition (EMT), loss of epithelial markers is mediated by transcriptional repressors such as SNAIL, SLUG, or ZEB1/2 that bind to E-box promoter sequences of specific genes. The effect of these repressors on SDC-1 expression remains unknown. Here, we demonstrated that SNAIL, SLUG and ZEB1 expressions are increased in advanced PCa, contrarily to SDC-1. SNAIL, SLUG and ZEB1 also showed an inversion to SDC-1 in prostate cell lines. ZEB1, but not SNAIL or SLUG, represses SDC-1 as demonstrated by experiments of ectopic expression in epithelial prostate cell lines. Inversely, expression of ZEB1 shRNA in PCa cell line increased SDC-1 expression. The effect of ZEB1 is transcriptional since ectopic expression of this gene represses SDC-1 promoter activity and ZEB1 binds to the SDC-1 promoter as detected by ChIP assays. An epigenetic mark associated to transcription repression H3K27me3 was bound to the same sites that ZEB1. In conclusion, this study identifies ZEB1 as a key repressor of SDC-1 during PCa progression and point to ZEB1 as a potentially diagnostic marker for PCa.
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Neoplasias da Próstata/genética , Sindecana-1/genética , Fatores de Transcrição/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Adesão Celular/genética , Linhagem Celular Tumoral , Epigênese Genética/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Células PC-3 , Regiões Promotoras Genéticas/genética , Fatores de Transcrição da Família Snail/genética , Transcrição Gênica/genéticaRESUMO
PURPOSE: To analyze the results of daily high-dose-rate brachytherapy (HDRBT) on local control and toxicity in the postoperative treatment of endometrial carcinoma (EC). MATERIALS AND METHODS: From January 2007 to September 2010, 112 patients were treated with HDRBT after surgery for EC. FIGO staging: 24-IA, 48-IB, 14-II, 12-IIIA, 2-IIIB, 8-IIIC1 and 4-IIIC2. Pathology 99/112 endometrioid and 23/112 other types. Radiotherapy patients were divided into two groups-Group 1 (70/112) consists of external beam irradiation (EBI) plus HDRBT (2 fractions of 5-6 Gy) and Group 2 (42/112) consists of HDRBT alone (4 fractions of 5-6 Gy). Toxicity evaluation RTOG scores for bladder and rectum, and the objective criteria of LENT-SOMA for vagina. Statistics bivariate analysis of Chi-square and Fisher exact tests. RESULTS: With a mean follow-up of 29.52 months (range 9.60-53.57) no patient developed vaginal-cuff relapse. In Group 1 early toxicity appeared in 9 % in rectum, 8.5 % in bladder (G1-G2) and 1.4 % in vagina (G1); late toxicity was present in 8.5 % in rectum (all G1-G2 but 1 G3) and in 25 % in vagina (all G1-G2 but one G4). In Group 2, 9.4 % developed G1-G2 bladder and 6.9 % acute vagina (G1-G2) toxicity. Only 2.3 % had a G1 rectal score and 6.9 % had G1-G2 as vaginal scores for late problems. CONCLUSIONS: (1) Daily HDRBT using two fractions of 5-6 Gy after EBI and four fractions of 5-6 Gy as exclusive treatment was a safe regime. (2) Group 1 showed a higher incidence of late vaginal toxicity.