Topical application of Aloe vera and vitamin E on induced ulcers on the tongue of rats subjected to radiation: clinical and histological evaluation.

OBJECTIVE: The aim of this study is to assess the effect of two types of antioxidants, vitamin E (VE) and Aloe vera (AV), on healing of induced oral lesions after radiation in a murine model by clinical and histological analysis. METHODS: The animals were randomly divided into three groups of 12 animals each (400 mg VE, 70 % AV and control) and two time periods (5 and 7 days). They were irradiated with a single dose of 30 Gy, and after 24 h, a lesion was produced on the ventral tongue of each animal. The products were applied daily in their respective group until euthanasia. RESULTS: On clinical analysis, there was a higher frequency of lesions in the animals of the control group at both periods. The area of the lesions was also greater in the control group compared with the groups AV and VE (5 days p = 0.006; 7 days p = 0.002). On microscopic analysis, the degree of inflammation differed between the study groups and experimental periods. At 5 days, the statistical difference was not significant among the groups evaluated, but at 7 days, animals in the control group showed intense inflammation, while those in groups VE and AV exhibited mild to moderate inflammation (p = 0.002). CONCLUSION: The results suggest that VE and AV contributed to the decrease in inflammatory response and healing of the lesions induced on the tongue of rats subjected to radiation.

Effect of low-level laser therapy on irradiated parotid glands--study in mice.

The objective of this study was to evaluate the effect of low-level laser therapy (LLLT) on radiotherapy-induced morphological changes and caspase-3 immunodetection in parotids of mice. Forty-one Swiss mice were divided into control, radiotherapy, 2- and 4-J laser groups. The experimental groups were exposed to ionizing radiation in a single session of 10 Gy. In the laser groups, a GaAlAs laser (830 nm, 100 mW, 0.028 cm2, 3.57 W/cm2) was used on the region corresponding to the parotid glands, with 2-J energy (20 s, 71 J/cm2) or 4 J (40 s, 135 J/cm2) per point. LLLT was performed immediately before and 24 h after radiotherapy. One point was applied in each parotid gland. The animals were euthanized 48 h or 7 days after radiotherapy and parotid glands were dissected for morphological analysis and immunodetection of caspase-3. There was no significant difference between groups in the immunodetection of caspase-3, but the laser groups had a lower percentage compared to the radiotherapy group. LLLT promoted the preservation of acinar structure, reduced the occurrence of vacuolation, and stimulated parotid gland vascularization. Of the two LLLT protocols, the one using 4 J of energy showed better results.

Effect of low-level laser therapy on radiotherapy-induced hyposalivation and xerostomia: a pilot study.

OBJECTIVE: The present pilot study aimed to assess the effect of low-level laser therapy (LLLT) on hyposalivation and xerostomia as a consequence of head and neck radiotherapy. BACKGROUND DATA: The benefits of LLLT in salivary flow have been shown; however, there are no studies investigating its effects on patients who have already undergone radiotherapy and present hyposalivation and xerostomia as a sequela. METHODS: Twenty-three patients with a history of head and neck malignancy, who were treated by fractioned teletherapy (dosimetry ranging from 45 to 70 Gy) in the cervicofacial region were selected. They all presented with xerostomia and severe hyposalivation. Patients were randomly distributed into a laser group (n=12) and a control group (n=11). A GaAlAs laser (830 nm, 100 mW, illuminated area 0.028 cm2, 3.57 W/cm2, 20 sec, 2.0 J, 71 J/cm2) was used punctually in the major salivary glands, twice a week for 6 weeks, with a 12 session total. Stimulated and unstimulated salivary flow rate (SFR) were assessed, as well as the xerostomia and quality of life related to oral health (QLROH). RESULTS: The analysis did not show any significant difference between the groups with regards to the SFR and xerostomia, and the QLROH. However, at the end of the treatment, the xerostomia and the QLROH showed significant improvement in both groups compared with assessments performed at baseline, highlighting the importance of advice given to the irradiated patients, and their follow-up. CONCLUSIONS: With the parameters used, LLLT was not able to increase SFR or decrease xerostomia. The results may be associated with the late effects of radiotherapy on glandular structure, such as fibrosis and acinar atrophy.

P2X7 receptor activation leads to increased cell death in a radiosensitive human glioma cell line.

Gliomas are the most lethal tumors of central nervous system. ATP is an important signaling molecule in CNS and it is a selective P2X7 purinergic receptor ligand at high concentrations. Herein, we investigated whether the activation of P2X7R might be implicated in death of a radiosensitive human glioma lineage. The effects of P2X7R agonists (ATP and BzATP) and irradiation (2 Gy) on glioma cells were analyzed by MTT assay and annexin-V/PI determination, whereas mRNA and protein P2X7R expression was assessed by qRT-PCR and flow cytometry, respectively. P2X7R pore formation was functionality examined by analyzing ethidium bromide uptake. The human glioma cells U-138 MG and U-251 MG were resistant to death when treated with either ATP (5 mM) or BzATP (100 µM), but the radiosensitive M059J glioma cells displayed a significant decrease of cell viability (32.4 ± 4.1 % and 25.6 ± 3.3 %, respectively). The M059J lineage expresses significantly higher mRNA P2X7R levels when compared to the U-138 MG and U-251 cell lines (0.40 ± 0.00; 0.28 ± 0.01, and 0.31 ± 0.01, respectively), and irradiation upregulated P2X7R expression (0.55 ± 0.08) in this lineage. Noteworthy, P2X7R protein doubled after irradiation on M059J lineage, and increased in 50 % and 42.6 % when comparing M059J-irradiated to irradiated U-138 MG and U-251 MG cells, respectively. Ethidium bromide uptake was significantly increased in 104 % and 77.8 % when comparing M059J to U-138 MG and U-251MG, respectively. Finally, the selective P2X7R antagonist A740003 significantly decreased the cell death caused by irradiation. We provide novel evidence indicating that M059J human glioma cell line is ATP-P2X7R sensitive, pointing out the relevance of the purinergic P2X7R on glioma radiosensitivity.

Radioresistance of human glioma spheroids and expression of HSP70, p53 and EGFr.

BACKGROUND: Radiation therapy is routinely prescribed for high-grade malignant gliomas. However, the efficacy of this therapeutic modality is often limited by the occurrence of radioresistance, reflected as a diminished susceptibility of the irradiated cells to undergo cell death. Thus, cells have evolved an elegant system in response to ionizing radiation induced DNA damage, where p53, Hsp70 and/or EGFr may play an important role in the process. In the present study, we investigated whether the content of p53, Hsp70 and EGFr are associated to glioblastoma (GBM) cell radioresistance. METHODS: Spheroids from U-87MG and MO59J cell lines as well as spheroids derived from primary culture of tumor tissue of one GBM patient (UGBM1) were irradiated (5, 10 and 20 Gy), their relative radioresistance were established and the p53, Hsp70 and EGFr contents were immunohistochemically determined. Moreover, we investigated whether EGFr-phospho-Akt and EGFr-MEK-ERK pathways can induce GBM radioresistance using inhibitors of activation of ERK (PD098059) and Akt (wortmannin). RESULTS: At 5 Gy irradiation UGBM1 and U-87MG spheroids showed growth inhibition whereas the MO59J spheroid was relatively radioresistant. Overall, no significant changes in p53 and Hsp70 expression were found following 5 Gy irradiation treatment in all spheroids studied. The only difference observed in Hsp70 content was the periphery distribution in MO59J spheroids. However, 5 Gy treatment induced a significant increase on the EGFr levels in MO59J spheroids. Furthermore, treatment with inhibitors of activation of ERK (PD098059) and Akt (wortmannin) leads to radiosensitization of MO59J spheroids. CONCLUSIONS: These results indicate that the PI3K-Akt and MEK-ERK pathways triggered by EGFr confer GBM radioresistance.

Seguimento dos 74 primeiros casos de radioterapia intra-operatória (eliot) no Hospital São Lucas da PUCPRS / Follow-up of the 74 first cases of intraoperative radiotherapy (eliot) at the Hospital São Lucas PUCPRS

Este artigo tem como objetivo descrever e analisar o uso da radioterapia intraoperatória no tratamento do câncer de mama inicial. Para isso, apresentaremos os dados obtidos com o seguimento das pacientes submetidas a essa modalidade de tratamento no Hospital São Lucas da PUCRS no período de janeiro de 2004 a abril de 2009.

Relaxation and guided imagery program in patients with breast cancer undergoing radiotherapy is not associated with neuroimmunomodulatory effects.

OBJECTIVE: Treatment of breast cancer is usually associated with significant psychological stress. In this study, we examined the effects of relaxation and visualization therapy (RVT) on psychological distress, cortisol levels, and immunological parameters of breast cancer patients undergoing radiotherapy. METHODS: Participants were randomly assigned to either the experimental (n=20) who underwent group RVT for 24 consecutive days or control group (n=14) who were on radiotherapy only. Psychological scores (stress, anxiety, and depression) were measured by structured clinical interviews. Salivary cortisol was assessed along the day. Lymphocytes were isolated and cultured to measure T-cell proliferation and sensitivity to glucocorticoids (GCs). RESULTS: RVT was effective to reduce stress, anxiety, and depression scores (all P<.05). However, cortisol levels as well as proliferation remained unchanged following RVT. Although T cells of experimental group were more sensitive to GCs than cells of controls at baseline, no changes were noted following RVT. Cortisol levels were positively correlated to anxiety and depression scores and inversely correlated to T-cell proliferation and sensitivity to GCs. CONCLUSION: We conclude that the psychological intervention was capable to attenuate the emotional distress presented during radiotherapy treatment. A longer RVT or worse psychological morbidity at baseline may be necessary to translate psychological into biological changes.

Radioresistance is associated to increased Hsp70 content in human glioblastoma cell lines.

Radiation therapy is routinely prescribed for high-grade malignant gliomas. However, the efficacy of this therapeutic modality is often limited by the occurrence of radioresistance, reflected as a diminished susceptibility of the irradiated cells to undergo apoptosis. Heat-shock proteins (Hsps) synthesis can be increased by cellular insults, such as radiation-induced damage. Inducible Hsp70 has been suggested to have multiple roles in cytoprotection against apoptosis. Accordingly, high levels of Hsp70 prevent stress-induced apoptosis. In the present study, we investigated whether the content of Hsp70 is associated to glioblastoma cell radioresistance. To this end, the U-87MG, U-251MG and MO59J human glioblastoma cell lines were irradiated at 2, 5 and 10 Gy and their relative radioresistance and Hsp70 were determined. Following 5 Gy irradiation, in MO59J and U-251MG a significant decrease in colony formation was found, whereas the U-87MG was relatively radioresistant. Three hours after the irradiation (at 5 Gy) Hsp70 contents increased 110% in the U-87 MG cells, but did not significantly change in the U-251MG and MO59J cells. Thus, our results suggest that Hsp70 protection against radiation-induced apoptosis might underlie glioblastoma radioresistance.

Protective effect of alpha-tocopherol in head and neck cancer radiation-induced mucositis: a double-blind randomized trial.

BACKGROUND: the study was designed to test whether vitamin E (VE) provides oral mucosal protection in patients with irradiated cancers of the head and neck. METHODS: Fifty-four patients with cancer of the oral cavity and oropharynx were randomly assigned to rinse the oral cavity in an oil solution containing either VE or placebo before every conventional fraction of 2 Gy and again 8 to 12 hours later during the 5 to 7 weeks of radiotherapy (RT). RESULTS: Thirty-six events/167 patient-weeks (21.6%) and 54 events/161 patient-weeks (33.5%) of symptomatic mucositis were observed in VE and placebo groups, respectively (p =.038). VE reduced the risk by 36%. Subjective data at the end of the treatment revealed that VE decreased pain grades 2 to 3 during RT (3 of 28 patients vs 14 of 26 patients, p =.0001). No significant influence was detected in survival. CONCLUSION: VE decreased the incidence of symptomatic oral radio-induced mucositis in patients with cancer of the oropharynx and oral cavity.

Modulation of oxidative stress in response to gamma-radiation in human glioma cell lines.

Radiation therapy is routinely used in the management of primary central nervous system malignancies. However, the efficacy of this therapeutic modality is limited by the occurrence of resistance. In the present study, we investigated whether modulation of oxidative stress might underlie glioma cell radioresistance. Superoxide dismutase activity in irradiated M059J cells was two-fold higher than that in untreated controls, but did not significantly change in U-87 and U-138 cells. This is accompanied by an increase in reactive oxygen species content and decreases in cells viability. Pharmacological or genetic modulation of oxidative stress could be associated with an enhancement in the susceptibility of tumor cells to radiation therapy.

Carcinoma Verrucoso: apresentação de casos / Verrucous carcinoma: case reports

Os autores apresentam quatro casos de Carcinoma Verrucoso, caracterizando esta lesão clínica e histologicamente, bem como as distintas formas de tratamento utilizado

Biologia das metástases: o que há de novo? / Biology of metastasis: what is new?

A interpretaçäo atual do comportamento diversificado das células metastáticas, com relaçäo ao seu padräo de crescimento e sensibilidade ao tratamento, deve-se aos fenômenos de heterogeneidade. É feita uma revisäo bibliográfica dos últimos anos acerca dos mecanismos pelos quais a heterogeneidade interfere no sucesso da terapêutica e, também, sobre o rumo das pesquisas que vêm se ocupando em superar este problema.

Radioterapia experimental: avanços nos anos 80 e rumos para o futuro / Experimental radiotherapy: advances in the 80' and course for the future

A radioterapia é um dos tratamentos mais efetivos para o controle local do câncer, tendo sua eficiência prejudicada algumas vezes pela açäo antagônica causada pelas baixas concentraçöes de oxigênio ao nível do tumor. Nos anos 80 houve um impulso notável no sentido de intensificar o efeito biológico da radioterapia pelo uso de novas tecnologias, e também pela síntese de modificadores químicos da resposta a radiaçäo. Nesta revisäo, comentam-se os avanços obtidos e as implicaçöes para a próxima década

Manuseio radioterápico na síndrome de compressäo da veia cava superior

A síndrome de compressäo da veia cava superior é uma situaçäo de emergência incomum nos casos de carcinoma brônquico e linfomas, surgindo mais remotamente em doenças benignas. Um atendimento rápido e efetivo pode reverter os síntomas em poucos dias. Foram analisadas características clínicas em 29 pacientes admitidos en nosso serviço de 1981 a 1986, havendo 4 exclusöes para os estudos de respostas clínica. A dose total de radioterapia foi ao redor de 6000 cGy/6 semanas, con o emprego de altas doses iniciais ou doses convencionais. As respostas foram consideradas muito satisfatórias. Alguns pacientes receberam quimioterapia prévia ou concomitante a irradiaçäo. Näo houve vantagem do tratamento combinado nesta série. O emprego de quimioterapia é considerado de primeira escolha pela literatura no manuseio da síndrome causada pelo carcinoma avenocelular e linfomas

Neoplasia de colo uterino associada à gestaçäo / Neoplasia of the uterine cervix associated with gestation

Säo apresentados dez casos de neoplasias de colo uterino associado à gestaçäo, ocorridos no Hospital Materno Infantil Presidente Vargas do INAMPS/RS, no período de 1982-1985. Observaram, na presente revisäo, a utilizaçäo de conizaçäo do colo uterino associada à cerclagem antes da 20ª semana de gestaçäo (quatro casos). Radioterapia com feto vivo antes da 25ª semana seguida de interrupçäo por micro cesária após irradiaçäo (dois casos). Operaçäo de Werthaim Meiggs com fetus in uterus com 16 semanas de gestaçäo (um caso), a ocorrência de parto normal a termo em paciente com carcinoma invasor. Finalmente dois casos de parto normal em displasia moderada e acentuada. Relatam ainda, a seqüência diagnóstica observada através da detecçäo por citopatológico (nove casos); biópsia crônica (quatro casos): biópsia dirigida (quatro casos). A distribuiçäo nos vários estágios foi: carcinoma in situ - 3 casos; carcinoma invasor estágio Ia - 1 caso; carcinoma invasor estágio IIa - 1 caso; carcinoma invasor estágio IIb - 2 casos; displasia grave - 2 casos; displasia moderada - 1 caso. É apresentado o seguimento com a observaçäo de má evoluçäo de um dos casos de estágio IIb cujo tipo histológico era anaplásico; e a boa evoluçäo nos demais casos. Concluem, pela importância de utilizar o citopatológico em mulheres grávidas principalmente em grupo de alto risco; multíparas, após os 25 anos e de baixo nível sócio-econômico. Destacam-se os problemas de instituiçäo precoce e adequada da terapêutica