RESUMEN

This study aimed to assess the in vitro effects of re-irradiation on enamel and dentin properties, simulating head and neck cancer radiotherapy retreatment. Forty-five human permanent molars were classified into five groups: non-irradiated; irradiated 60 Gy, and re-irradiated with doses of 30, 40, and 50 Gy. Raman spectroscopy, scanning electron microscopy (SEM), and energy dispersive x-ray spectroscopy (EDS) were employed for analysis. Raman spectroscopy assessed intensity, spectral area, and specific peaks comparatively. Statistical analysis involved Kolmogorov-Smirnov and One-Way ANOVA tests, with Tukey's post-test (significance level set at 5%). Significant changes in irradiated, non-irradiated, and re-irradiated enamel peaks were observed, including phosphate (438 nm), hydroxyapatite (582 nm), phosphate (960 nm), and carbonate (1070 nm) (p < 0.05). Re-irradiation affected the entire tooth (p > 0.05), leading to interprismatic region degradation, enamel prism destruction, and hydroxyapatite crystal damage. Dentin exhibited tubule obliteration, crack formation, and progressive collagen fiber fragmentation. EDX revealed increased oxygen percentage and decreased phosphorus and calcium post-reirradiation. It is concluded that chemical and morphological changes in irradiated permanent teeth were dose-dependent, exacerbated by re-irradiation, causing substantial damage in enamel and dentin.

Asunto(s)

Esmalte Dental , Dentina , Humanos , Esmalte Dental/efectos de la radiación , Esmalte Dental/química , Dentina/efectos de la radiación , Dentina/química , Espectrometría Raman , Diente/efectos de la radiación , Diente Molar/efectos de la radiación

RESUMEN

Single Nucleotide Polymorphisms (SNPs) are the most common type of genetic variation found in an individual's DNA sequences. SNPs can occur in both coding and non-coding regions of the genome and can affect gene expression, protein function, and disease susceptibility. In this systematic review, we evaluate the potential of SNPs as biomarkers in the assessment of oral mucositis (OM) severity in head and neck cancer (HNC) patients treated with concomitant chemoradiation (CRT). The study selection process involved screening 66 articles from different platforms, and after removing duplicates and excluding articles that did not meet the eligibility criteria, 23 articles were included for full-text evaluation. Among them, genes from several pathways were analyzed. The DNA damage repair pathways had the highest number of genes studied. The most frequently analyzed gene was XRCC1. The proinflammatory cytokine pathways evaluated were TNF, with three articles, and NF-κB, with one article. Most included studies showed a potential association between certain SNPs and high-grade mucositis. We conclude that SNPs can be used as possible biomarkers for the assessment of OM intensity in HNC patients, and further research is needed to explore the potential of SNPs in personalized medicine for HNC treatment.

RESUMEN

OBJECTIVES: Radiotherapy (RT) is a kind of head and neck cancer (HNC) treatment, which is associated to the habit of smoking and can develop collateral effects in the oral cavity, such as the increase of caries prevalence. This study evaluated the color alteration, the microhardness, and the remineralizing potential of high fluoride concentration toothpastes on irradiated teeth. MATERIALS AND METHODS: Forty bovine teeth were used (6 × 6 × 2 mm) and after color (EasyShade, VITA) and microhardness initial readings were separated into two groups: exposed to cigarette smoke and non-exposed. All samples were submitted to RT (30 Gy) and to cariogenic challenge. New color and microhardness readings were done. After RT (60 Gy), the samples were submitted to simulated toothbrushing (73,000 cycles = 5 years of brushing) with two different toothpastes: conventional (1450 ppm) and high fluoride concentration (5000 ppm). Final color and microhardness readings were done after brushing. Data were analyzed with 2-way ANOVA with repeated measures and Tukey's test (p < .05). RESULTS: There was no color difference after RT, nor after brushing (p > .05). However, after brushing, microhardness values increased for the samples treated with high fluoride concentration toothpaste (p < .05). CONCLUSION: Radiotherapy did not influence the teeth color, and the high fluoride concentration toothpaste presented remineralizing potential; therefore, it could be used on the caries prevention related to HNC radiation. CLINICAL RELEVANCE: Considering its remineralizing potential, toothpastes with high fluoride concentration could be a proper alternative for caries prevention in patients undergoing radiotherapy.

Asunto(s)

Caries Dental , Pastas de Dientes , Animales , Bovinos , Caries Dental/tratamiento farmacológico , Caries Dental/prevención & control , Esmalte Dental , Fluoruros/uso terapéutico , Humanos , Remineralización Dental , Cepillado Dental , Pastas de Dientes/farmacología , Pastas de Dientes/uso terapéutico

RESUMEN

AIM: To evaluate the radiotherapy (RT) effect in the pelvic floor muscles (PFM) function in men with prostate cancer (PC). MATERIALS AND METHODS: A cross-sectional study included three groups of patients with PC and RT indication: 1) Pre-RT group: evaluated before the beginning of RT; 2) Acute group: evaluated between six months and one year after RT; 3) Late Group: evaluated between two and a half years and four years post-RT. PFM assessment was divided into: a) functional assessment through the digital anal palpation (Modified Oxford Scale) and surface electromyography (sEMG) with anal probe; b) anatomical assessment by pelvic magnetic resonance imaging (MRI) with thickness measurements of levator ani muscle and pelvic specific parameters at rest and under Valsalva maneuver. We used Student t test, considering as significant p <0.05. RESULTS: Thirty-three men were assessed: Pre-RT (n=12); Acute (n=10) and Late (n=11) groups. PFM functional assessment showed Late group with lower electromyographic activity, especially in the sustained contractions when compared to the Pre-RT (p=0.003) and Acute groups (p=0.006). There was no significant difference between groups in MRI. CONCLUSION: PFM functional assessment showed a decrease in sEMG activity in the Late group post-RT. Most of the sample (72.7%) did not know how to actively contract the PFM or had a weak voluntary contraction when assessed by digital anal palpation. Also, these patients presented higher prevalence of pelvic complaints. No changes were observed in the morpho-functional parameters evaluated by MRI, except the measurement of the membranous urethra length when comparing Pre-RT Group and Acute and Late Groups.

Asunto(s)

Diafragma Pélvico , Próstata , Estudios Transversales , Electromiografía , Humanos , Imagen por Resonancia Magnética , Masculino , Contracción Muscular , Palpación , Diafragma Pélvico/diagnóstico por imagen , Próstata/diagnóstico por imagen

RESUMEN

Purpose: To evaluate the morphological alterations in enamel and dentin of primary teeth following radiotherapy (RT) and to determine the best adhesive technique and time to carry out restorative procedures.
Methods: Enamel and dentin fragments of primary teeth were randomly assigned into four groups (n=30): G1 (control)-non-irradiated, only restorative procedure; G2- restorative procedure immediately before RT; G3-restorative procedure 24 hours after RT; and G4-restorative procedure six months after RT. Each group was divided into one of two subgroups according to the adhesive system used for restoration: (1) AdperSingle Bond 2 (SB); and (2) ClearfillSE Bond (CL). The specimens were submitted to fractionated RT until they reached the final dose of 60 Gy. They were then subjected to confocal microscopy and the shear bond strength test. Data were analyzed using two-way analysis of variance followed by Tukey's tests ( α = five percent).
Results: Morphological changes were first observed in enamel and dentin after 40 Gy of irradiation. G4 bond strength values were similar to G1 in the CL and SB groups for enamel and in the CL group for dentin (P >0.05). G2 showed the lowest values for enamel and dentin (P <0.05). In G3, CL presented the highest strength values in enamel; for G4, the highest values were found in dentin (P <0.05).
Conclusions: Radiotherapy affected the morphological surface of enamel and dentin. The restorations placed immediately after RT had the weakest shear bond strength, and the restorations placed six months after RT had similar means of bond strength compared to the nonirradiated teeth in enamel, regardless of the adhesive system used. In dentin, CL showed better performance than SB.

Asunto(s)

Recubrimiento Dental Adhesivo , Recubrimientos Dentinarios , Resinas Compuestas , Cementos Dentales , Dentina , Humanos , Ensayo de Materiales , Cementos de Resina , Resistencia al Corte , Diente Primario

RESUMEN

OBJECTIVE: To evaluate a pilocarpine spray as a treatment for xerostomia in patients treated with radiotherapy (RT) for head and neck cancer (HNC). METHODS: This was a placebo-controlled, double-blind, crossover clinical trial of patients complaining of dry mouth after RT for HNC. Forty patients were randomly assigned to either placebo or pilocarpine (1.54%) spray and instructed to use three times a day for 3 months. After 1-month washout period, patients were crossed over to receive placebo or pilocarpine. The assessments were salivary flow (Stimulated Whole Saliva Flow - SWSF), xerostomia (Xerostomia Inventory - XI), and quality of life (QoL/Oral Health Impact Profile - OHIP-14), assessed at baseline, 1 hr (only SWSF), and at 1, 2, and 3 months of treatment. RESULTS: Posttreatment SWFS was not statistically different between pilocarpine and placebo regardless of the treatment sequence (paired T test; p > .05), except for the SWFS rates at 2 months after therapy. When comparing pilocarpine with placebo in the time points, there was no significant difference (p > .05) for QoL or XI. Significant differences in improvement in QoL and xerostomia experience appeared along time for pilocarpine group. CONCLUSION: The topical application of pilocarpine spray tested was similar to placebo on SWSF assessments in patients treated with RT for HNC.

RESUMEN

OBJECTIVES: To evaluate the in vitro effects of radiotherapy (RT) on the morphological surface of the enamel and dentin and to determine the best adhesive system and most appropriate time to restore teeth in head and neck cancer patients. METHODS: Sixty third molars were cut into 120 enamel fragments and 120 dentin fragments and divided into four groups (n = 30): G1 (control): nonirradiated, only restorative procedure; G2: restorative procedure immediately before RT; G3: restorative procedure immediately after RT; and G4: restorative procedure 6 months after RT. Each group was divided into two subgroups: Adper™ Single Bond 2 (SB) and Clearfill SE Bond (CL) based on the material used. After RT and restorative procedures, the specimens were subjected to confocal microscopy and shear bond strength test. Data were analyzed using a two-way ANOVA followed by Tukey's test at a significance level of 5%. RESULTS: Morphological changes were observed in both substrates after a cumulative dose of 40 Gy, and after 60 Gy, the changes were more evident in both substrates. CL had the highest strength values in both substrates (p < 0.05), and G2 had the lowest strength values for the enamel and dentin (p < 0.05). CONCLUSIONS: Based on the in vitro study results, we can conclude that RT substantially changes the morphological surface of enamel and dentin and impairs the bond strength. The Clearfill system yielded better results than Adper Single Bond 2, and restoring teeth before RT resulted in the worst results in both substrates.

Asunto(s)

Adhesivos/efectos de la radiación , Esmalte Dental/efectos de la radiación , Recubrimientos Dentinarios/efectos de la radiación , Dentina/efectos de la radiación , Neoplasias de Cabeza y Cuello/radioterapia , Bisfenol A Glicidil Metacrilato/efectos de la radiación , Resinas Compuestas/efectos de la radiación , Recubrimiento Dental Adhesivo , Dentición Permanente , Neoplasias de Cabeza y Cuello/patología , Humanos , Ensayo de Materiales , Diente Molar/efectos de la radiación , Dosis de Radiación , Distribución Aleatoria , Cementos de Resina/efectos de la radiación , Resistencia al Corte/efectos de la radiación , Fracturas de los Dientes/etiología , Fracturas de los Dientes/patología

RESUMEN

The goal of this study was to assess the effect of intercessory prayer in the psychological, spiritual and biological scores of breast cancer patients who are undergoing radiotherapy. Double-blind RCT comprising a sample of 31 participants (15 in the Control Group and 16 in the Intervention Group). Data collection was performed in three time points (T0, T1 and T2). Significant changes have been identified in the intra-group analysis, concerning the decrease in spiritual distress score; negative religious/spiritual coping prevailed, while the total religious/spiritual coping increased between the posttest T2 to T0. Intercessory prayer was effective in religious and spiritual scores.

Asunto(s)

Adaptación Psicológica , Amilasas/metabolismo , Neoplasias de la Mama/psicología , Neoplasias de la Mama/radioterapia , Depresión/psicología , Curación por la Fe/psicología , Espiritualidad , Adulto , Ansiedad , Neoplasias de la Mama/metabolismo , Método Doble Ciego , Curación por la Fe/estadística & datos numéricos , Femenino , Humanos , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Calidad de Vida , Religión y Medicina , Terapias Espirituales/métodos , Terapias Espirituales/psicología , Resultado del Tratamiento

RESUMEN

The widely accepted resazurin-based assay can be used, prior to in vivo studies, as an inexpensive method to determine cytotoxicity. The aim of this study was to evaluate and standardize the assay conditions for oral squamous cancer cell (OSCC) and glioblastoma (U87-MG) lines by UV-vis spectroscopy. The cells were treated with 25 µgmL-1 of resazurin sodium salt and then incubated for 4 h, 6 h, and 6.5 h. All absorbance measurements were carried out at 21 ± 1 °C on a spectrophotometer with a microplate reader. After 4-hs of incubation, resazurin was completely reduced by OSCC cells, as demonstrated by the suppression of the absorbance at 380 nm. However, the U87-MG cells needed 6.5 h of incubation to demonstrate the same behavior. The Statistical analysis did not indicate significant differences between the OSCC and U87-MG cell lines' viability after 4 and 6.5 h respectively. We concluded that spectroscopic analysis is an efficient method for the standardization of the resazurin assay. In addition, without the implementation of suitable protocols, there could be an increase in the chance of errors or false positives or negatives that would reduce the usefulness of the data.

Asunto(s)

Carcinoma de Células Escamosas/metabolismo , Glioblastoma/metabolismo , Neoplasias de la Boca/metabolismo , Oxazinas/química , Xantenos/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Análisis Espectral/métodos

RESUMEN

BACKGROUND: High-grade gliomas (HGGs) are a heterogeneous disease group, with variable prognosis, inevitably causing deterioration of the quality of life. The estimated 2-year overall survival is 20%, despite the best trimodality treatment consisting of surgery, chemotherapy, and radiotherapy. AIM: To evaluate long-term survival outcomes and factors influencing the survival of patients with high-grade gliomas treated with radiotherapy. MATERIALS AND METHODS: Data from 47 patients diagnosed with high-grade gliomas between 2009 and 2014 and treated with three-dimensional radiotherapy (3DRT) or intensity-modulated radiotherapy (IMRT) were analyzed retrospectively. RESULTS: Median survival was 16.6 months; 29 patients (62%) died before the time of analysis. IMRT was employed in 68% of cases. The mean duration of radiotherapy was 56 days, and the mean delay to the start of radiotherapy was 61.7 days (range, 27-123 days). There were no statistically significant effects of duration of radiotherapy or delay to the start of radiotherapy on patient outcomes. CONCLUSIONS: Age, total amount of gross resection, histological type, and use of adjuvant temozolomide influenced survival rate (p < 0.05). The estimated overall survival was 18 months (Kaplan-Meier estimator). Our results corroborated those reported in the literature.

RESUMEN

BACKGROUND: The radiotherapy can directly affect the bond strength of the adhesive materials, interfering in the prognosis of restorative treatments, which may be caused by chemical changes in dentin structure. METHODS: Twenty inferior homologues premolars were distributed in 2 groups (in vitro study) (n = 10): nonirradiated and irradiated. The specimens were submitted to the analysis of phosphate (ν1 PO43- ;ν2 PO43- ;ν4 PO43- ), carbonate (ν3 CO32- ), amide I, CH2 , amide III, and amide I/III ratio by confocal Raman spectroscopy. Data were submitted to statistical analysis (T test, P < .05). RESULTS: In intracanal dentin, the irradiated group had lower ν4 PO43- values (1.23 ± 0.06) compared to nonirradiated group (1.40 ± 0.18) (P < .05), with no difference for ν1 PO43- and ν2 PO43 peaks (P > .05). The irradiated (1.56 ± 0.06) had lower carbonate, amide III (1.05 ± 0.19), and amide I/III ratio values (0.19 ± 0.06) compared to nonirradiated group (1.42 ± 0.10, 1.28 ± 0.24, and 0.31 ± 0.10, respectively) (P < .05). For medium dentin irradiated group (1.30 ± 0.12) had lower phosphate values compared to nonirradiated group (1.48 ± 0.22) (P < .05). In cementum, there was no statistical difference between the groups. CONCLUSION: The radiotherapy was able to cause changes in ν4 PO43- , carbonate, and amide III peaks of root dentin.

Asunto(s)

Dentina/química , Dentina/efectos de la radiación , Raíz del Diente/química , Raíz del Diente/efectos de la radiación , Amidas/análisis , Diente Premolar/química , Diente Premolar/efectos de la radiación , Carbonatos/análisis , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Fosfatos/análisis , Espectrometría Raman

RESUMEN

BACKGROUND AND PURPOSE: Glioblastoma (GBM) is the most aggressive brain tumor. Even with the advent of temozolomide, patient survival remains poor, with expected median survival around 1 year from diagnosis. Consequently, the relentless search for new therapeutic strategies able to increase patient outcome persists. 3-[(dodecylthiocarbonyl) methyl] glutarimide (DTCM-g) is a new anti-inflammatory compound that already showed antitumor effects. MATERIALS AND METHODS: Clonogenic survival, proliferation, apoptosis, cell cycle progression and invasion capacity of pediatric and adult GBM cell lines (U87MG, U251MG, SF188 and KNS-42) were evaluated under treatment with DTCM-g. The combined treatment with radiation was also evaluated in vitro and in vivo through xerographic models. RESULTS: DTCM-g is able to impair proliferation, reduce clonogenic capacity and induce cell cycle arrest in GBM cell lines. No alteration in apoptosis rates was found after treatment. DTCM-g also reduces the invasion capacity of all GBM cell lines without alterations in MMP2 and uPa expression. Moreover, the drug radiosensitized GBM in vitro and in vivo. CONCLUSION: Although additional studies are still necessary to support our findings, our results suggest that DTCM-g may be a promising drug on the adjuvant treatment of GBM exhibiting antitumor effects, especially through radiosensitization.

Asunto(s)

Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Piperidonas/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Ciclo Celular/efectos de los fármacos , Ciclo Celular/efectos de la radiación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Terapia Combinada/métodos , Glioblastoma/tratamiento farmacológico , Glioblastoma/radioterapia , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos

RESUMEN

INTRODUCTION: Multiple stages of carcinogenesis in colon cancer encompass subpopulations of cancer stem cells (CSC), responsible for tumor cell transformation, growth and proliferation. CD44 and CD166 proteins are CSC markers associated with cell signaling, adhesion, migration, metastasis and lymphocytic response. The expression of CSC may be modulated by some factors, such as the KRAS gene mutation. OBJECTIVE: Correlate the expression of CD44 and CD166 markers in metastatic colon adenocarcinoma and KRAS mutation status (wild-type/mutated) with clinical pathological features and patients' outcome. MATERIAL AND METHODS: Fifty-eight samples of tumor tissue samples of metastatic colon adenocarcinoma were collected from patients treated with CapeOx at the HCFMRP-USP Clinical Oncology Service. Clinical and survival data were collected from medical records. KRAS status was determined by the polymerase chain reaction (PCR) technique, and analysis of immunohistochemical expression of CD44 and CD166 proteins was performed by tissue microarray. RESULTS: The expression of CD44 and CD166 were positive in 41% and 43% of patients, respectively, and mutated KRAS was detected in 48% of patients. A significant association was found between CD166 and CD44 expression (p= 0.016), mainly in the wild-type KRAS group (p= 0.042) and patients over 65 years (p= 0.001). CD44-positive patients had 3.7-fold and 5.3-fold greater risk of liver metastasis and lung metastasis, respectively (p< 0.01), compared with CD44-negative patients. CD166-negative patients had 2.7 greater risk of lymph node involvement (0.03), compared with CD166-positive patients. KRAS mutation increased the risk of liver metastasis by 8 times (p< 0.01), and the risk of lung metastasis by 5 times (p= 0.04) in CD44-positive patients. KRAS mutation increased the risk of lymph node involvement by 8 times in CD166-negative patients (p= 0.0007). CONCLUSION: An association between CD44 and CD166 expression was demonstrated in this study. Analysis of KRAS mutation combined with immunohistochemical expression of CD44 and CD166 identified subgroups of patients with colon adenocarcinoma at higher risk of lymph node involvement by the tumor and development of liver and lung metastasis.

Asunto(s)

Molécula de Adhesión Celular del Leucocito Activado/metabolismo , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Receptores de Hialuranos/metabolismo , Mutación , Proteínas ras/genética , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Células Madre Neoplásicas/metabolismo , Evaluación del Resultado de la Atención al Paciente , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos

RESUMEN

PURPOSE: To evaluate the effects of radiation therapy on deciduous teeth. MATERIALS AND METHODS: The enamel and dentin microhardness (n = 12) was evaluated at 3 depths, both before (control) and after each 10 Gy of irradiation and up to a dose of 60 Gy. The morphology was evaluated via scanning electron microscopy (SEM) (n = 8). The data were analyzed using a two-way analysis of variance (ANOVA) and Tukey's test (α = 5%). RESULTS: The enamel microhardness, as a whole, increased (p < 0.05) after a dose of 60 Gy (211.4 KH), mostly in the superficial enamel. There was a significant difference between the values of nonirradiated dentin microhardness (28.9 KH) compared with dentin that was irradiated with doses of 10 Gy (23.8 KH), 20 Gy (25.6 KH), 30 Gy (24.8 KH), and 40 Gy (25.7 KH) (p < 0.05). There was no difference between nonirradiated dentin and dentin irradiated with 60 Gy (p > 0.05). The highest mean value of microhardness (29.9 KH) (p < 0.05) was found in the middle dentin. The groups that were irradiated with doses of 30 and 60 Gy exhibited greater surface changes in their enamel and dentin compared with the nonirradiated groups for all regions, exhibiting an amorphous surface upon increase of the irradiation doses. CONCLUSIONS: The enamel microhardness increased at a dose of 60 Gy, whereas the value of the dentin microhardness did not change. A progressive disruption of enamel and dentin morphology was found with the increased radiation dose.

Asunto(s)

Esmalte Dental/efectos de la radiación , Dentina/efectos de la radiación , Radioterapia/efectos adversos , Diente Primario/efectos de la radiación , Esmalte Dental/citología , Esmalte Dental/ultraestructura , Dentina/citología , Dentina/ultraestructura , Dureza/efectos de la radiación , Pruebas de Dureza , Humanos , Técnicas In Vitro , Fenómenos Mecánicos , Microscopía Electrónica de Rastreo , Dosificación Radioterapéutica , Diente Primario/citología , Diente Primario/ultraestructura

RESUMEN

The Bosniak classification for renal cysts was developed in the late 1980s in an attempt to standardize the description and management of complex cystic renal lesions. Alterations were made to such a classification in the 1990s and, the last one, in 2005. Currently, five categories of cystic renal lesions are defined - namely, I, II, II-F, III and IV -, according to their degree of complexity and likelihood of malignancy. Despite being initially described for computed tomography, this classification has been also utilized with some advantages also for magnetic resonance imaging. The present article reviews the different phases of this classification, its diagnostic efficacy and the most controversial features of its use.

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OBJETIVO: A oferta de radioterapia de alta tecnologia para população atendida pelo Sistema Único de Saúde (SUS) é limitada, por não pertencer ao rol de procedimentos e, muitas vezes, pela capacidade instalada frente à demanda e dificuldade de retenção de recursos humanos especializados. Dessa forma, o acesso à radioterapia de intensidade modulada (IMRT) é restrito a poucos serviços no Brasil. Pretendemos apresentar as características dos primeiros 508 tratamentos de IMRT durante os primeiros anos de instalação da técnica em um hospital universitário. MATERIAIS E MÉTODOS: Foram analisados 508 tratamentos de IMRT, de maio de 2011 a setembro de 2013, que completaram a radioterapia. A técnica empregada foi multilâminas estático. RESULTADOS: De um total de 4.233 pacientes tratados no período, 12,5% realizaram IMRT. As principais indicações foram para crânio, cabeça e pescoço, e próstata. Aproximadamente 30% das radioterapias de crânio e 50% das de próstata foram por IMRT. A toxicidade total foi 4%. CONCLUSÃO: Em razão das restrições de acesso à radioterapia e da não cobertura deste procedimento, as indicações de IMRT para pacientes do SUS devem ser apoiadas nos protocolos clínicos das instituições em acordo com sua realidade, com especial atenção à redução da toxicidade.

RESUMEN

PURPOSE: Glioblastoma (GBM) is a very aggressive and lethal brain tumor with poor prognosis. Despite new treatment strategies, patients' median survival is still lower than 1 year in most cases. The expression of the BUB gene family has demonstrated to be altered in a variety of solid tumors, pointing to a role as putative therapeutic target. The purpose of this study was to determine BUB1, BUB3, and BUBR1 gene expression profiles in glioblastoma and to analyze the effects of BUB1 and BUBR1 inhibition combined or not with Temozolomide and radiation in the pediatric SF188 GBM cell line. METHODS: For gene expression analysis, 8 cell lines and 18 tumor samples were used. The effect of BUB1 and BUBR1 inhibition was evaluated using siRNA. Apoptosis, cell proliferation, cell cycle kinetics, micronuclei formation, and clonogenic capacity were analyzed after BUB1 and BUBR1 inhibition. Additionally, combinatorial effects of gene inhibition and radiation or Temozolomide (TMZ) treatment were evaluated through proliferation and clonogenic capacity assays. RESULTS: We report the upregulation of BUB1 and BUBR1 expression and the downregulation of BUB3 in GBM samples and cell lines when compared to white matter samples (p < 0.05). Decreased cell proliferation and colony formation after BUB1 and BUBR1 inhibition were observed, along with increased micronuclei formation. Combinations with TMZ also caused cell cycle arrest and increased apoptosis. Moreover, our results demonstrate that BUB1 and BUBR1 inhibition sensitized SF188 cells to γ-irradiation as shown by decreased growth and abrogation of colony formation capacity. CONCLUSION: BUB1 and BUBR1 inhibition decreases proliferation and shows radiosensitizing effects on pediatric GBM cells, which could improve treatment strategies for this devastating tumor. Collectively, these findings highlight the potentials of BUB1 and BUBR1 as putative therapeutic targets for glioblastoma treatment.

Asunto(s)

Neoplasias Encefálicas/genética , Proliferación Celular , Glioblastoma/genética , Proteínas Serina-Treonina Quinasas/genética , Tolerancia a Radiación/genética , Apoptosis/efectos de los fármacos , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Glioblastoma/metabolismo , Humanos , Masculino , Proteínas Serina-Treonina Quinasas/metabolismo , Interferencia de ARN , ARN Interferente Pequeño , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transcriptoma

RESUMEN

Despite efforts to improve surgical, radiologic, and chemotherapeutic strategies, the outcome of patients with glioblastoma (GBM) is still poor. Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays key roles in cell cycle control and has been associated with tumor growth and prognosis. Here, we aimed at testing the radiosensitizing effects of the PLK1 inhibitor BI 2536 on eight GBM cell lines. For cell cycle analysis, T98G, U251, U343 MG-a, LN319, SF188, U138 MG, and U87 MG cell lines were treated with 10, 50, or 100 nM of BI 2536 for 24 hours. In addition, cell cultures exposed to BI 2536 50 nM for 24 hours were irradiated with γ-rays from (60)Cobalt source at final doses of 2, 4, and 6 Gy. Combinatorial effects were evaluated through proliferation and clonogenic capacity assays. Treatment with BI 2536 caused mitotic arrest after 24 hours, and increased apoptosis in GBM cells. Moreover, our results demonstrate that pretreatment with this drug sensitized six out of seven GBM cell lines to different doses of γ-irradiation as shown by decreased growth and abrogation of colony-formation capacity. Our data suggest that PLK1 blockage has a radiosensitizing effect on GBM, which could improve treatment strategies for this devastating tumor.

Asunto(s)

Proteínas de Ciclo Celular/antagonistas & inhibidores , Glioblastoma/tratamiento farmacológico , Glioblastoma/radioterapia , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Pteridinas/farmacología , Fármacos Sensibilizantes a Radiaciones/farmacología , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de la radiación , Proteínas de Ciclo Celular/metabolismo , Procesos de Crecimiento Celular/efectos de los fármacos , Procesos de Crecimiento Celular/efectos de la radiación , Línea Celular Tumoral , Glioblastoma/enzimología , Glioblastoma/patología , Humanos , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Quinasa Tipo Polo 1

RESUMEN

Osteosarcoma (OS) is the most common primary malignant bone tumor. Despite advances in neoadjuvant multi-agent chemotherapy, the outcome of patients has not significantly improved in the last decades, making the search for more effective therapeutic agents imperative. In the present study, we explored the possibility of using activator protein-1 inhibition by 3-[(dodecylthiocarbonyl)methyl]-glutarimide (DTCM-g) as a new therapeutic strategy in two OS cell lines, HOS and MG-63. Our results showed that low concentrations (2.5, 5, 10, and 20 µg/mL) of the drug significantly decreased cell proliferation and clonogenic capacity, albeit it did not significantly induce cell death. DTCM-g also decreased cell invasiveness, and inhibited PDPN, MMP-2, TIMP1, and TIMP2 expressions. Moreover, our results showed that DTCM-g synergized with ionizing radiation in both cell lines while chemosensitized MG-63 cells to doxorubicin treatment. Even though additional laboratorial and preclinical tests are still needed to support our data, we demonstrate that DTCM-g inhibits growth in OS cells, increases the cytotoxicity of other commonly used agents, and may possess antimetastatic activity.

Asunto(s)

Antibióticos Antineoplásicos/farmacología , Neoplasias Óseas/tratamiento farmacológico , Doxorrubicina/farmacología , Osteosarcoma/tratamiento farmacológico , Piperidonas/farmacología , Tolerancia a Radiación/efectos de los fármacos , Factor de Transcripción AP-1/antagonistas & inhibidores , Neoplasias Óseas/radioterapia , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Sinergismo Farmacológico , Humanos , Metaloproteinasa 2 de la Matriz/metabolismo , Glicoproteínas de Membrana/metabolismo , Invasividad Neoplásica/patología , Osteosarcoma/radioterapia , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Ensayo de Tumor de Célula Madre

RESUMEN

Glioblastoma (GBM), one of the most malignant human neoplasias, responds poorly to current treatment modalities, with temozolomide (TMZ) being the drug most frequently used for its treatment. Tetra-O-methyl Nordihydroguaiaretic Acid (M4N) is a global transcriptional repressor of genes dependent on the Sp1 transcription factor, such as Survivin and Cdk1. In the present study we evaluated the gene expression of Survivin, its spliced variants and Cdk1 in GBM samples and cell lines. Moreover, we investigated the effects of M4N combined or not with TMZ and/or radiation on GBM primary cultures and cell lines. qRT-PCR assays were performed to determine the Survivin-spliced variants and Cdk1 gene mRNA expression in GBM tumor samples and cell lines. Cell proliferation was measured by XTT assay and cell cycle and apoptosis were determined by flow cytometry. Drug combination analyses using different schedules of administration (simultaneous and sequential) were performed on GBM cell lines and primary cultures based on the Chou-Talalay method. For clonogenic survival, doses of 2, 4, and 6 Gy of gamma radiation. were used. All Survivin-spliced variants and the Cdk1 gene were expressed in GBM samples (n = 16) and cell lines (n = 6), except the Survivin-2B variant that was only expressed in GBM cell lines. M4N treatment down regulated the expression of Cdk1, Survivin and the Survivin-ΔEx3 variant, while the Survivin-2B variant was up-regulated. M4N decreased the cell proliferation separately and synergistically with TMZ, and enhanced the effects of radiation, mainly when associated with TMZ. M4N also induced apoptotic cell death, decreased the mitotic index and arrested the cell cycle mainly in the G2/M phase. Our results suggest a potential clinical application of M4N in combination with TMZ and radiation for GB treatment.

Asunto(s)

Apoptosis/efectos de los fármacos , Glioblastoma/tratamiento farmacológico , Glioblastoma/radioterapia , Proteínas Inhibidoras de la Apoptosis/genética , Masoprocol/análogos & derivados , Factor de Transcripción Sp1/metabolismo , Transcripción Genética/efectos de los fármacos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Apoptosis/efectos de la radiación , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/radioterapia , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Dacarbazina/análogos & derivados , Dacarbazina/farmacología , Dacarbazina/uso terapéutico , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Glioblastoma/genética , Glioblastoma/patología , Humanos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Concentración 50 Inhibidora , Masculino , Masoprocol/farmacología , Masoprocol/uso terapéutico , Índice Mitótico , Empalme del ARN/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Fármacos Sensibilizantes a Radiaciones/farmacología , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Survivin , Temozolomida

RESUMEN

BACKGROUND: KRAS gene mutations play an important role in the carcinogenesis of colorectal tumors. However, studies that have assessed the association between KRAS gene mutation status and disease characteristics report conflicting results. To assess KRAS gene status (mutated or wild-type) and its association with the clinical, epidemiological, and histopathological features of metastatic colorectal adenocarcinoma as well its association with clinical outcomes. METHODS: Cross-sectional descriptive study in which clinical and histopathological data were collected from the medical records of 65 patients diagnosed with metastatic colorectal adenocarcinoma at the Clinical Oncology Service of the Teaching Hospital of the School of Medicine of Ribeirao Preto, University of Sao Paulo (Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo -HCFMRP-USP) between 2005 and 2012 and analyzed based on their KRAS gene status. RESULTS: KRAS gene mutations were found in 49.2% of the tumors, and G/A (25.5%) and Gly12Asp (34.37%) were the most frequent mutations. Among the investigated clinical features (gender, ECOG (Eastern Cooperative Oncology Group), histology, degree of cell differentiation, lymph node ratio, primary tumor site, staging, presence of synchronous metastasis, lung metastasis, and liver metastasis), the association between age less than 65 years with KRAS mutation was statistically significant (P = 0.046). KRAS mutation status did not exhibit a significant correlation with the overall survival of the patients (P = 0.078); however, the cases with KRAS mutation exhibited shorter survival. In the multivariate analysis, synchronous metastasis (P = 0.03) and liver metastasis (P = 0.008) behaved as independent factors of poor prognosis relative to the overall survival of the patients. CONCLUSION: The KRAS mutation status did not exhibit prognostic value in the investigated sample. Among the older patients (> 65 years old), wild-type KRAS was more frequently observed compared to mutated KRAS.