Direct ionizing radiation and bystander effect in mouse mesenchymal stem cells.

Purpose: This study aimed to evaluate the radiation-induced direct and bystander (BYS) responses of mesenchymal stem cells (MSCs) and to characterize these cells radiobiologically.Methods and materials: MSCs were irradiated (IR) and parameters related to DNA damage and cellular signaling were verified in a dose range from 0.5 to 15 Gy; also a transwell insert co-culture system was used to study medium-mediated BYS effects.Results: The main effects on directly IR cells were seen at doses higher than 6 Gy: induction of cell death, cell cycle arrest, upregulation of p21, and alteration of redox status. Irrespective of a specific dose, induction of micronuclei formation, H2AX phosphorylation, and decreased Akt expression also occurred. Thus, mTOR expression, cell senescence, nitric oxide generation, and calcium levels, in general were not significantly modulated by radiation. Data from the linear-quadratic model showed a high alpha/beta ratio, which is consistent with a more exponential survival curve. BYS effects from the unirradiated MSCs placed into companion wells with the directly IR cells, were not observed.Conclusions: The results can be interpreted as a positive outcome, meaning that the radiation damage is restricted to the directed IR MSCs not leading to off-target cell responses.

The Role of Low-Dose Radiation in Association with TNF-α on Immunomodulatory Properties of Mesenchymal Stem Cells.

Ionizing radiation (IR) is an important medical tool. Despite the effects associated with high-dose radiation during or after treatment, as well as in accidental exposures, the direct or indirect effect of low-dose IR in cells remain poorly documented. IR can affect the tissue microenvironment, including mesenchymal stem cells (MSCs), which have high regenerative and immunomodulatory capacities. This study aimed to investigate the effect of low-dose IR in association with the inflammatory stimuli of TNF-α on the immunomodulatory capacity of MSCs. MSCs were irradiated with a low-dose IR, stimulated with TNF-α, and cultivated in a bystander system with murine spleen cells. The results showed that TNF-R1 is expressed in MSCs and is not affected, even in irradiated MSCs. However, irradiated MSCs produced reduced amounts of IL-6 and increased amounts of IL-10. The levels of PGE2 and NO• in MSCs were also increased when stimulated with TNF-α. Furthermore, conditioned media from irradiated MSCs reduced the proliferation of bystander lymphocytes and reduced the metabolic activity of macrophages. In addition, conditioned media from irradiated MSCs modulated the profile of cytokines in bystander spleen cells (lymphocytes and macrophages), reducing inflammatory and increasing anti-inflammatory cytokines, also increasing Treg cells. In conclusion, low-dose IR in association with an inflammatory stimulus affects the immunomodulatory properties of MSCs. In this way, the immunosuppressive capability of MSCs can be explored for several disease treatments where IR usually part of the context of the treatment. However, a complete understanding of the mechanisms underlying these interactions need further investigation. Graphical Abstract.

A novel method to evaluate salivary flow rates of head and neck cancer patients after radiotherapy: a pilot study / Um novo método para avaliar as taxas de fluxo salivar em pacientes com câncer de cabeça e pescoço após radioterapia: estudo piloto

Abstract Introduction The procedure used to evaluate salivary flow rate is called sialometry. It can be performed through several techniques, but none appears to be really efficient for post-radiotherapy patients. Objective To adequate sialometry tests for head and neck cancer patients submitted to radiotherapy. Methods 22 xerostomic patients post-radiotherapy (total radiation dose ranging from 60 to 70 Gy) were included in this study. Ten patients were evaluated using sialometries originally proposed by the Radiation Therapy Oncology Group and twelve were assessed by our modified methods. Unstimulated and stimulated sialometries were performed and the results were classified according a grading scale and compared between both groups. Results There was no statistically significant difference between the salivary evaluations of both groups (p = 0.4487 and p = 0.5615). Also, most of these rates were classified as very low and low. Conclusion This novel method seems to be suitable for patients submitted to radiotherapy.

Resumo Introdução O procedimento utilizado para avaliar a taxa de fluxo salivar é denominado sialometria. Pode ser realizado por meio de várias técnicas, mas nenhuma parece ser realmente eficiente para pacientes pós-radioterapia. Objetivo Adaptar sialometrias para pacientes com câncer de cabeça e pescoço submetidos à radioterapia. Método 22 pacientes xerostômicos pós-radioterapia (dose de radiação total variando de 60-70 Gy) foram incluídos neste estudo. Dez pacientes foram avaliados utilizando sialometrias originalmente propostas pelo Radiation Therapy Oncology Group e doze foram avaliados por nossos métodos modificados. Sialometrias não estimuladas e estimuladas foram conduzidas e os resultados foram classificados de acordo com uma escala de graduação e comparados entre os dois grupos. Resultados Não houve diferença estatisticamente significante entre as avaliações salivares de ambos os grupos (p = 0,4487 e p = 0,5615). Além disso, a maioria dessas taxas foi classificada como muito baixa e baixa. Conclusão Esse novo método parece ser adequado para pacientes submetidos à radioterapia.

A novel method to evaluate salivary flow rates of head and neck cancer patients after radiotherapy: a pilot study.

INTRODUCTION: The procedure used to evaluate salivary flow rate is called sialometry. It can be performed through several techniques, but none appears to be really efficient for post-radiotherapy patients. OBJECTIVE: To adequate sialometry tests for head and neck cancer patients submitted to radiotherapy. METHODS: 22 xerostomic patients post-radiotherapy (total radiation dose ranging from 60 to 70Gy) were included in this study. Ten patients were evaluated using sialometries originally proposed by the Radiation Therapy Oncology Group and twelve were assessed by our modified methods. Unstimulated and stimulated sialometries were performed and the results were classified according a grading scale and compared between both groups. RESULTS: There was no statistically significant difference between the salivary evaluations of both groups (p=0.4487 and p=0.5615). Also, most of these rates were classified as very low and low. CONCLUSION: This novel method seems to be suitable for patients submitted to radiotherapy.

Impact of low-level laser therapy on hyposalivation, salivary pH, and quality of life in head and neck cancer patients post-radiotherapy.

Late effects of radiotherapy for head and neck cancer treatment have been increasingly investigated due to its impact on patients' quality of life. The purpose of this study was to evaluate the effect of low-level laser therapy on hyposalivation, low salivary pH, and quality of life in head and neck cancer patients post-radiotherapy. Twenty-nine patients with radiation-induced xerostomia received laser sessions twice a week, during 3 months (24 sessions). For this, a continuous wave Indium-Gallium-Aluminium-Phosphorus diode laser device was used punctually on the major salivary glands (808 nm, 0.75 W/cm2, 30 mW, illuminated area 0.04 cm2, 7.5 J/cm2, 10 s, 0.3 J). Six extraoral points were illuminated on each parotid gland and three on each submandibular gland, as well as two intraoral points on each sublingual gland. Stimulated and unstimulated salivary flow rate, pH (two scales with different gradations), and quality of life (University Of Washington Quality of Life Questionnaire for Patients with Head and Neck Cancer) were assessed at baseline and at the end of the treatment. There were significant increases in both mean salivary flow rates (unstimulated: p = 0.0012; stimulated: p < 0.0001), mean pH values (p = 0.0002 and p = 0.0004), and mean score from the quality of life questionnaire (p < 0.0001). Low-level laser therapy seems to be effective to mitigate salivary hypofunction and increase salivary pH of patients submitted to radiotherapy for head and neck cancer, thereby leading to an improvement in quality of life.

Low-level laser therapy for the prevention of low salivary flow rate after radiotherapy and chemotherapy in patients with head and neck cancer.

OBJECTIVE: To determine whether low-level laser therapy can prevent salivary hypofunction after radiotherapy and chemotherapy in head and neck cancer patients. MATERIALS AND METHODS: We evaluated 23 head and neck cancer patients, of whom 13 received laser therapy and 10 received clinical care only. An InGaAlP laser was used intra-orally (at 660 nm and 40 mW) at a mean dose of 10.0 J/cm(2) and extra-orally (at 780 nm and 15 mW) at a mean dose of 3.7 J/cm(2), three times per week, on alternate days. Stimulated and unstimulated sialometry tests were performed before the first radiotherapy and chemotherapy sessions (N0) and at 30 days after the end of treatment (N30). RESULTS: At N30, the mean salivary flow rates were significantly higher among the laser therapy patients than among the patients who received clinical care only, in the stimulated and unstimulated sialometry tests (p = 0.0131 and p = 0.0143, respectively). CONCLUSION: Low-level laser therapy, administered concomitantly with radiotherapy and chemotherapy, appears to mitigate treatment-induced salivary hypofunction in patients with head and neck cancer.

OBJETIVO: Avaliar o impacto do laser de baixa potência na prevenção de hipofluxo salivar em pacientes portadores de câncer de cabeça e pescoço após radioterapia e quimioterapia. MATERIAIS E MÉTODOS: Treze pacientes receberam laserterapia e dez receberam cuidados clínicos. Utilizou-se um InGaAlP laser diodo para aplicação intraoral (comprimento de onda de 660 nm, 40 mW de potência e dose média de 10 J/cm2) e extraoral (comprimento de onda de 780 nm, 15 mW de potência e dose média de 3,7 J/cm2), três vezes por semana, em dias alternados. Sialometrias estimulada e não estimulada foram realizadas antes da primeira sessão de radioterapia e quimioterapia (N0) e 30 dias após o final do tratamento (N30). RESULTADOS: Em N30, os pacientes submetidos à laserterapia apresentaram médias estatisticamente maiores de fluxo salivar estimulado (p = 0,0131) e não estimulado (p = 0,0143), em comparação com os pacientes que receberam apenas cuidados clínicos. CONCLUSÃO: A laserterapia de baixa potência realizada concomitantemente a radioterapia e quimioterapia foi capaz de mitigar a hipofunção das glândulas salivares em pacientes portadores de câncer de cabeça e pescoço após o tratamento oncológico.

Low-Level Laser for Mitigation of Low Salivary Flow Rate in Head and Neck Cancer Patients Undergoing Radiochemotherapy: A Prospective Longitudinal Study.

OBJECTIVE: The present study aimed to assess the impact of low-level laser (LLL) on low salivary flow rate in patients undergoing radiochemotherapy (RT-CT) for head and neck cancer. BACKGROUND DATA: LLL has shown efficiency in preventing hyposalivation in patients under different pathological conditions, including those undergoing RT-CT. METHODS: During all RT-CT, 17 patients received laser therapy and 10 received clinical care only. An Indium-Gallium-Aluminum-Phosphorus diode laser was punctually used for intraoral (660 nm, 40 mW, 10 J/cm(2), illuminated area 0.04 cm(2), 10 sec) and extraoral irradiation (780 nm, 15 mW, 3.8 J/cm(2), illuminated area 0.04 cm(2), 10 sec), three times a week and on alternate days, for a total of 21 sessions. Unstimulated salivary flow rate was assessed before the first RT session (N0), at the 15th RT session (N15), at the last RT session (Nf), and at 30 (N30) and 90 days after the end of the oncologic treatment (N90). RESULTS: At N15, Nf, and N30, patients treated with LLL showed significantly higher averages of salivary flow rate when compared with patients receiving clinical care only. CONCLUSIONS: LLL seems to be an efficient tool for mitigation of salivary hypofunction in patients undergoing RT for head and neck cancer.

Low-level laser therapy for the prevention of low salivary flow rate after radiotherapy and chemotherapy in patients with head and neck cancer / Laser de baixa potência para prevenção de hipofluxo salivar em pacientes portadores de câncer de cabeça e pescoço após radioterapia e quimioterapia

Abstract Objective: To determine whether low-level laser therapy can prevent salivary hypofunction after radiotherapy and chemotherapy in head and neck cancer patients. Materials and Methods: We evaluated 23 head and neck cancer patients, of whom 13 received laser therapy and 10 received clinical care only. An InGaAlP laser was used intra-orally (at 660 nm and 40 mW) at a mean dose of 10.0 J/cm2 and extra-orally (at 780 nm and 15 mW) at a mean dose of 3.7 J/cm2, three times per week, on alternate days. Stimulated and unstimulated sialometry tests were performed before the first radiotherapy and chemotherapy sessions (N0) and at 30 days after the end of treatment (N30). Results: At N30, the mean salivary flow rates were significantly higher among the laser therapy patients than among the patients who received clinical care only, in the stimulated and unstimulated sialometry tests (p = 0.0131 and p = 0.0143, respectively). Conclusion: Low-level laser therapy, administered concomitantly with radiotherapy and chemotherapy, appears to mitigate treatment-induced salivary hypofunction in patients with head and neck cancer.

Resumo Objetivo: Avaliar o impacto do laser de baixa potência na prevenção de hipofluxo salivar em pacientes portadores de câncer de cabeça e pescoço após radioterapia e quimioterapia. Materiais e Métodos: Treze pacientes receberam laserterapia e dez receberam cuidados clínicos. Utilizou-se um InGaAlP laser diodo para aplicação intraoral (comprimento de onda de 660 nm, 40 mW de potência e dose média de 10 J/cm2) e extraoral (comprimento de onda de 780 nm, 15 mW de potência e dose média de 3,7 J/cm2), três vezes por semana, em dias alternados. Sialometrias estimulada e não estimulada foram realizadas antes da primeira sessão de radioterapia e quimioterapia (N0) e 30 dias após o final do tratamento (N30). Resultados: Em N30, os pacientes submetidos à laserterapia apresentaram médias estatisticamente maiores de fluxo salivar estimulado (p = 0,0131) e não estimulado (p = 0,0143), em comparação com os pacientes que receberam apenas cuidados clínicos. Conclusão: A laserterapia de baixa potência realizada concomitantemente a radioterapia e quimioterapia foi capaz de mitigar a hipofunção das glândulas salivares em pacientes portadores de câncer de cabeça e pescoço após o tratamento oncológico.

Strategies to evaluate the impact of rectal volume on prostate motion during three-dimensional conformal radiotherapy for prostate cancer.

OBJECTIVE: To evaluate the rectal volume influence on prostate motion during three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. MATERIALS AND METHODS: Fifty-one patients with prostate cancer underwent a series of three computed tomography scans including an initial planning scan and two subsequent scans during 3D-CRT. The organs of interest were outlined. The prostate contour was compared with the initial CT images considering the anterior, posterior, superior, inferior and lateral edges of the organ. Variations in the anterior limits and volume of the rectum were assessed and correlated with prostate motion in the anteroposterior direction. RESULTS: The maximum range of prostate motion was observed in the superoinferior direction, followed by the anteroposterior direction. A significant correlation was observed between prostate motion and rectal volume variation (p = 0.037). A baseline rectal volume superior to 70 cm(3) had a significant influence on the prostate motion in the anteroposterior direction (p = 0.045). CONCLUSION: The present study showed a significant interfraction motion of the prostate during 3D-CRT with greatest variations in the superoinferior and anteroposterior directions, and that a large rectal volume influences the prostate motion with a cutoff value of 70 cm(3). Therefore, the treatment of patients with a rectal volume > 70 cm(3) should be re-planned with appropriate rectal preparation.

Strategies to evaluate the impact of rectal volume on prostate motion during three-dimensional conformal radiotherapy for prostate cancer / Avaliação do impacto do volume retal na movimentação da próstata durante radioterapia conformacional para câncer de próstata

Abstract Objective: To evaluate the rectal volume influence on prostate motion during three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. Materials and Methods: Fifty-one patients with prostate cancer underwent a series of three computed tomography scans including an initial planning scan and two subsequent scans during 3D-CRT. The organs of interest were outlined. The prostate contour was compared with the initial CT images considering the anterior, posterior, superior, inferior and lateral edges of the organ. Variations in the anterior limits and volume of the rectum were assessed and correlated with prostate motion in the anteroposterior direction. Results: The maximum range of prostate motion was observed in the superoinferior direction, followed by the anteroposterior direction. A significant correlation was observed between prostate motion and rectal volume variation ( p = 0.037). A baseline rectal volume superior to 70 cm3 had a significant influence on the prostate motion in the anteroposterior direction ( p = 0.045). Conclusion: The present study showed a significant interfraction motion of the prostate during 3D-CRT with greatest variations in the superoinferior and anteroposterior directions, and that a large rectal volume influences the prostate motion with a cutoff value of 70 cm3. Therefore, the treatment of patients with a rectal volume > 70 cm3 should be re-planned with appropriate rectal preparation.

Resumo Objetivo: Avaliar a influência do volume retal na movimentação da próstata durante a radioterapia tridimensional conformacional (3D-CRT) para câncer de próstata. Materiais e Métodos: Cinquenta e um pacientes com câncer de próstata foram submetidos a três tomografias seriadas, sendo a primeira de planejamento e duas durante a 3D-CRT. Os órgãos de interesse foram delineados. O contorno da próstata foi comparado ao exame inicial em relação aos seus limites anterior, posterior, superior, inferior e laterais. As variações dos limites anterior do reto e de seu volume foram avaliadas e correlacionadas à movimentação da próstata no sentido anteroposterior. Resultados: As maiores variações na próstata foram observadas no sentido superoinferior, seguido pelo anteroposterior. Observou-se correlação significante da movimentação da próstata com a variação do volume do reto ( p = 0,037). O volume retal inicial superior a 70 cm3 influenciou significativamente na maior movimentação da próstata no sentido anteroposterior ( p = 0,045). Conclusão: Este estudo mostrou que a próstata apresenta significativa movimentação interfração durante a 3D-CRT, apresentando maiores variações nos sentidos superoinferior e anteroposterior, e que um volume retal inicial superior a 70 cm3 influencia na movimentação da próstata. Desta forma, os pacientes com volume retal superior a 70 cm3 devem ser replanejados com preparo retal adequado.

A synthetic fragment of leptin increase hematopoietic stem cell population and improve its engraftment ability.

Several studies have shown the important actions of cytokine leptin that regulates food intake and energy expenditure. Additionally, the ability to modulate hematopoiesis has also been demonstrated. Previous reports have shown that some synthetic sequences of leptin molecules can activate leptin receptor. Herein, decapeptides encompassing amino acids from positions 98 to 122 of the leptin molecule were constructed to evaluate their effects on hematopoiesis. Among them, the synthetic peptide Lep(110-119)-NH2 (LEP F) was the only peptide that possessed the ability to increase the percentage of hematopoietic stem cells (HSC). Moreover, LEP F also produced an increase of granulocyte/macrophage colony-forming units and activated leptin receptor. Furthermore, LEP F also improves the grafting of HSC in bone marrow, but did not accelerate the recovery of bone marrow after ablation with 5-fluorouracil. These results show that LEP F is a positive modulator of the in vivo expansion of HSC and could be useful in bone marrow transplantation.

Long-term oral effects in patients treated with radiochemotherapy for head and neck cancer.

PURPOSE: The purpose of this study is to assess the late oral complications and the role of salivary gland hypofunction in the severity of mucosal reaction in nonsurgical head and neck cancer patients, submitted to radiotherapy with or without chemotherapy. METHODS AND MATERIALS: Five hundred fifteen charts from patients treated between 2005 and 2009 were reviewed, and 41 patients met the inclusion criteria. Salivary gland function was assessed using a simplified grading system (GSX) and sialometry. Late effects were assessed using the Common Toxicity Criteria (CTC Version 2.0). RESULTS: The average follow-up was 17.1 (4-51) months. A statistical correlation was found for whole salivary flow rates and the average CTC grades for the mucous membrane. Both unstimulated/stimulated whole salivary flow rates (<0.09 mL/min) were identified as potential risk factors (p < 0.05) and an independent predictor for late mucous membrane toxicity (≥ grade 2). A significant correlation was also found between unstimulated salivary flow rates-GSX scores (p = 0.001) and CTC grades for salivary glands. Eighty-five percent of the patients were classified as suffering from salivary gland hypofunction, as well as 58.2 % considered dryness of the mouth the most debilitating complication. CONCLUSIONS: Considering the late effects assessed, the salivary gland hypofunction was the most significant and received the highest morbidity graduation (grade 2/grade 3); xerostomia was also considered the most debilitating complication after treatment. Data show the role of salivary gland hypofunction in the severity of late mucous membrane complication.

Protracted hypofractionated radiotherapy for Graves' ophthalmopathy: a pilot study of clinical and radiologic response.

PURPOSE: To evaluate the clinical and radiologic response of patients with Graves' ophthalmopathy given low-dose orbital radiotherapy (RT) with a protracted fractionation. METHODS AND MATERIALS: Eighteen patients (36 orbits) received orbital RT with a total dose of 10 Gy, fractionated in 1 Gy once a week over 10 weeks. Of these, 9 patients received steroid therapy as well. Patients were evaluated clinically and radiologically at 6 months after treatment. Clinical response assessment was carried out using three criteria: by physical examination, by a modified clinical activity score, and by a verbal questionnaire considering the 10 most common signs and symptoms of the disease. Radiologic response was assessed by magnetic resonance imaging. RESULTS: Improvement in ocular pain, palpebral edema, visual acuity, and ocular motility was observed in all patients. Significant decrease in symptoms such as tearing (p < 0.001) diplopia (p = 0.008), conjunctival hyperemia (p = 0.002), and ocular grittiness (p = 0.031) also occurred. Magnetic resonance imaging showed decrease in ocular muscle thickness and in the intensity of the T2 sequence signal in the majority of patients. Treatments were well tolerated, and to date no complications from treatment have been observed. There was no statistical difference in clinical and radiologic response between patients receiving RT alone and those receiving RT plus steroid therapy. CONCLUSION: RT delivered in at a low dose and in a protracted scheme should be considered as a useful therapeutic option for patients with Graves' ophthalmopathy.

Effects of ionizing radiation on bone neoformation: histometric study in Wistar rats tibiae / Efeitos da radiação ionizante na neoformação óssea: estudo histométrico em tíbias de ratos

PURPOSE: Comparing the ionizing radiation effects on bone neoformation of rats tibiae previously submitted to radiotherapy with a single dosage of 30Gy with the contralateral tibiae that have received secondary radiation. METHODS: In thirty male Wistar rats, 30 days before surgical procedure when round defects would be created on the bone, the right tibia was irradiated with 30Gy and the left tibia received a calculated secondary radiation dose of 7Gy. Sacrifices were performed after 4, 7, 14, 21, 56 and 84 postoperative days and both tibiae were removed for histological processing. RESULTS: The left tibiae that received the dose of 7Gy has shown more bone neoformation from 14th postoperative days, giving evidences of less damage to cellular population responsible by bone neoformation. On the other hand, the dose of 30Gyon right tibiae did not exhibit significant differences among the periods, suggesting damage of long-lasting or even permanent duration. CONCLUSION: Tibiae submitted to radiation dose of 30Gy have shown more damage to bone cells than tibiae that received secondary radiation dose of 7Gy, especially observed on 14th, 56th and 84th postoperative days.

OBJETIVO: Comparar os efeitos da radiação ionizante na reparação óssea em tíbias de ratos, submetidas à radioterapia prévia com doses 30Gy, com as tíbias contralaterais que receberam radiação secundária. MÉTODOS: No total, 30 ratos Wistar machos foram submetidos à cirurgia para realização de defeitos circulares em ambas as tíbias de cada rato, com radioterapia prévia de 30 dias, sendo que a tíbia direita recebeu a dose de 30Gy e tíbia esquerda a dose de radiação secundária calculada em 7Gy. Os sacrifícios ocorreram em 4, 7, 14, 21, 56 e 84 dias da realização do defeito ósseo e as tíbias foram removidas para processamento histológico. RESULTADOS: O grupo de 7Gy apresentou maior neoformação a partir do período de 14 dias, indicando pouco dano aos elementos celulares responsáveis pela reparação óssea, enquanto que o grupo de 30Gy não apresentou diferenças significantes entre os períodos, sugerindo um dano de efeito prolongado ou até mesmo permanente. CONCLUSÃO: As tíbias irradiadas com 30Gy apresentaram maior dano às células ósseas do que as tíbias que receberam radiação secundária de 7Gy, principalmente observadas nos períodos de 14, 56 e 84 dias.

Mucosite em pacientes portadores de câncer de cabeça e pescoço submetidos à radioquimioterapia / Mucositis in head and neck cancer patients undergoing radiochemotherapy / Mucositis en pacientes portadores de cáncer de cabeza y cuello sometidos a radioquimioterapia

O objetivo do presente trabalho é classificar o grau de mucosite oral de acordo com os parâmetros internacionais do Common Toxicity Criterion (CTC) em pacientes portadores de tumor de cabeça e pescoço submetidos à radioterapia e quimioterapia concomitantes, e caracterizar um perfil dos pacientes em nosso meio, verificando os hábitos dos indivíduos, as características do tumor, o protocolo de tratamento e a intensidade desta reação aguda. Neste estudo foram avaliados 50 pacientes, submetidos à radioterapia em megavoltagem com doses entre 66 a 70 Gy e quimioterapia com cisplatina ou carboplatina concomitante. Semanalmente foi avaliado o grau de mucosite de acordo com o CTC, uma escala ordinal que apresenta 4 graus. Observou-se interrupção do tratamento por mucosite em 36 por cento do total de pacientes e em 100 por cento dos pacientes diabéticos, o que nos permitiu verificar que esta patologia contribui para a gravidade da mucosite.

The objective of present study was to classify oral mucositis according to the Common Toxicity Criterion (CTC) international parameters in head and neck tumor patients simultaneously treated with radio and chemotherapy, and characterize a patient profile in our area, observing the individuals' habits, tumor characteristics, treatment protocol and acute reaction intensity. Fifty patients undergoing simultaneous 66 to 70 Gy megavoltage radiotherapy and cisplatin/carboplatin chemotherapy were evaluated in this study. Weekly evaluations of the degree of mucositis were perfoemed according to CTC, a four-degree ordinal scale; 36 percent of all patients and 100 percent of those with diabetes discontinued treatment due to mucositis, showing that this pathology contributes to the severity of mucositis.

El trabajo objetivó clasificar el grado de Mucositis oral de acuerdo a parámetros internacionales del CTC en pacientes portadores de tumores de cabeza y cuello sometidos a radioterapia y quimioterapia concomitantes, y caracterizar un perfil de pacientes en nuestro medio, verificando hábitos de los individuos, características del tumor, protocolo de tratamiento e intensidad de esta reacción aguda. Fueron evaluados 50 pacientes sometidos a radioterapia en megavoltaje con dosis entre 66 y 70 G y quimioterapia con cisplatino o carboplatino concomitante. Se evaluó semanalmente el grado de Mucositis según el Common Toxicity Criterio - CTC, una escala ordinal que presenta cuatro grados. Se observó interrupción del tratamiento por Mucositis en 36 por ciento del total de pacientes y en 100 por ciento de los pacientes diabéticos, lo que nos permite verificar que dicha patología potencia la gravedad de la mucositis.

Effects of ionizing radiation on bone neoformation: histometric study in Wistar rats tibiae.

PURPOSE: Comparing the ionizing radiation effects on bone neoformation of rats tibiae previously submitted to radiotherapy with a single dosage of 30Gy with the contralateral tibiae that have received secondary radiation. METHODS: In thirty male Wistar rats, 30 days before surgical procedure when round defects would be created on the bone, the right tibia was irradiated with 30Gy and the left tibia received a calculated secondary radiation dose of 7Gy. Sacrifices were performed after 4, 7, 14, 21, 56 and 84 postoperative days and both tibiae were removed for histological processing. RESULTS: The left tibiae that received the dose of 7Gy has shown more bone neoformation from 14(th) postoperative days, giving evidences of less damage to cellular population responsible by bone neoformation. On the other hand, the dose of 30Gyon right tibiae did not exhibit significant differences among the periods, suggesting damage of long-lasting or even permanent duration. CONCLUSION: Tibiae submitted to radiation dose of 30Gy have shown more damage to bone cells than tibiae that received secondary radiation dose of 7Gy, especially observed on 14(th), 56(th) and 84(th) postoperative days.

α-Tocopherol induces hematopoietic stem/progenitor cell expansion and ERK1/2-mediated differentiation.

Tocopherols promote or inhibit growth in different cell types. In the hematopoietic system, the radioprotective property of tocopherols is thought to act through the expansion of primitive hematopoietic cells. However, the mechanisms activated by tocopherols and which HPs are affected remain poorly understood. To better address these questions, mice were treated with α-tocopherol, and its effects were investigated in the BM microenvironment. α-Tocopherol induced increased proliferation in HSC/HP cells, leading to BM hyperplasia. In addition, differentiation to the granulocytic/monocytic lineage was enhanced by α-tocopherol treatment. α-Tocopherol treatment resulted in decreased basal phosphorylation of ERK1/2, PKC, and STAT-5 in HSC/HP cells. In contrast, α-tocopherol enhanced ERK1/2 activation in response to IL-3 stimulation in HSC/HP cells without altering the expression of IL-3Rs. Moreover, α-tocopherol-induced differentiation and ERK1/2 activation were abolished in mice pretreated with a MEK inhibitor (PD98059); however, pretreatment with PD98059 did not reduce the α-tocopherol-mediated increase in HSC/HP cells but instead, further enhanced their proliferation. Therefore, α-tocopherol induces expansion of HSC/HP cells by a nonidentified intracellular pathway and granulocytic/monocytic differentiation through ERK1/2 activation.

[Mucositis in head and neck cancer patients undergoing radiochemotherapy]. / Mucosite em pacientes portadores de câncer de cabeça e pescoço submetidos à radioquimioterapia.

The objective of present study was to classify oral mucositis according to the Common Toxicity Criterion (CTC) international parameters in head and neck tumor patients simultaneously treated with radio and chemotherapy, and characterize a patient profile in our area, observing the individuals' habits, tumor characteristics, treatment protocol and acute reaction intensity. Fifty patients undergoing simultaneous 66 to 70 Gy megavoltage radiotherapy and cisplatin/carboplatin chemotherapy were evaluated in this study. Weekly evaluations of the degree of mucositis were perfoemed according to CTC, a four-degree ordinal scale; 36% of all patients and 100% of those with diabetes discontinued treatment due to mucositis, showing that this pathology contributes to the severity of mucositis.

Acurácia na reprodutibilidade do posicionamento diário de pacientes submetidos a radioterapia conformada (RT3D) para câncer de próstata / Accuracy in the reproducibility of daily patients' setup in 3D conformal radiotherapy for prostate cancer

OBJETIVO: Avaliar a reprodutibilidade do posicionamento de pacientes com diagnóstico de câncer de próstata submetidos a radioterapia conformada. MATERIAIS E MÉTODOS: Foram avaliados 960 (posições anterior e lateral) filmes radiológicos, de um total de 120 pacientes que receberam radioterapia conformada na próstata com técnica isocêntrica. As imagens foram obtidas em acelerador linear de partículas 6 MV. Aplicou-se protocolo específico para planejamento e tratamento da próstata, com o paciente em posição supina, mãos colocadas sobre o tórax, pés apoiados em suporte apropriado. Diariamente, os pacientes foram posicionados conforme demarcações na pele, coincidentes com os lasers da sala. Os filmes radiológicos foram comparados com as radiografias reconstruídas digitalmente (digitally reconstructed radiography - DRR) em sistema de planejamento computadorizado Eclipse, a partir das tomografias. As radiografias de posicionamento foram realizadas no primeiro dia e após, semanalmente, até o término do tratamento. RESULTADOS: As médias dos deslocamentos observados foram de 1,99 ± 1,25 mm no sentido crânio-caudal, 1,37 ± 0,84 mm no látero-lateral e 1,94 ± 1,10 mm no ântero-posterior. CONCLUSÃO: O uso de protocolos específicos para posicionamento dos pacientes é possível na prática clínica, possibilita reprodutibilidade adequada e rápida correção dos possíveis erros.

OBJECTIVE: To evaluate the reproducibility of daily patients' setup in 3D conformal radiotherapy for prostate cancer. MATERIALS AND METHODS: The present study evaluated a total of 960 radiological images (anterior and lateral views) of 120 patients submitted to conformal radiotherapy for prostate cancer with the isocentric technique. A 6 MV particle accelerator was utilized in the process. A specific protocol for prostate radiotherapy planning and treatment was applied, with the patients placed in supine position, hands on the chest and legs placed on and appropriate support. Daily, the patients were positioned according to previously made skin markings in alignment with the in-room laser. The portal images were compared with digitally reconstructed radiographies (DRR) in the Eclipse treatment planning system based on the tomographic images. Radiography was performed at the first day, and weekly afterwards until the treatment was completed. RESULTS: The following average position shifts were observed: 1.99 ± 1.25 mm craniocaudally, 1.37 ± 0.84 mm laterally, and 1.94 ± 1.10 mm anteroposteriorly. CONCLUSION: The use of specific protocols for patients' setup is feasible in the clinical practice, allowing appropriate reproducibility and quick correction of possible errors in conformal radiotherapy for prostate cancer.

Ressonância magnética para avaliação dos limites dos campos clássicos de radioterapia em pacientes portadoras de neoplasia maligna de colo uterino / Magnetic resonance imaging in the evaluation of standard radiotherapy field borders in patients with uterine cervix cancer

OBJETIVO: Avaliar os limites de campo padronizados para radioterapia de neoplasia maligna de colo uterino com o uso de ressonância magnética e verificar a importância deste exame na redução de possíveis erros de planejamento com técnica convencional. MATERIAIS E MÉTODOS: Foram analisados, retrospectivamente, exames de ressonância magnética do planejamento de 51 pacientes tratadas devido a neoplasia de colo uterino. Os parâmetros estudados foram limites anterior e posterior no corte sagital. RESULTADOS: Observou-se, no corte sagital das ressonâncias magnéticas, que o limite de campo anterior apresentou-se inadequado em 20 (39,2 por cento) pacientes e que houve perda geográfica em 37,3 por cento dos casos no limite posterior. A inadequação de ambos os limites de campo não se relacionou com parâmetros clínicos como idade das pacientes, estadiamento, tipo e grau histológico. CONCLUSÃO: A avaliação dos limites de campo padronizados pela literatura com o uso de ressonância magnética mostrou altos índices de inadequação dos limites do campo lateral, assim como a importância do uso deste exame no planejamento radioterápico de pacientes portadoras de câncer de colo uterino com a finalidade de reduzir a perda geográfica no volume alvo de tratamento.

OBJECTIVE: To evaluate, by means of magnetic resonance imaging, the standardized field borders in radiotherapy for malignant neoplasm of uterine cervix, and to determine the role of this method in the reduction of possible planning errors related to the conventional technique. MATERIALS AND METHODS: Magnetic resonance imaging studies for planning of treatment of 51 patients with uterine cervix cancer were retrospectively analyzed. The parameters assessed were the anterior and posterior field borders on sagittal section. RESULTS: The anterior field border was inappropriate in 20 (39.2 percent) patients and geographic miss was observed in 37.3 percent of cases in the posterior border. The inappropriateness of both field borders did not correlate with clinical parameters such as patients' age, tumor staging, histological type and degree. CONCLUSION: The evaluation of standardized field borders with the use of magnetic resonance imaging has demonstrated high indices of inappropriateness of the lateral field borders, as well as the relevant role of magnetic resonance imaging in the radiotherapy planning for patients with uterine cervix cancer with a view to reduce the occurrence of geographic miss of the target volume.