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Chinese Journal of Oncology ; (12): 416-424, 2022.
Article in Chinese | WPRIM | ID: wpr-935230


Objective: To describe the actual efficacy of programmed death-1 (PD-1)/ programmed-death ligand 1 (PD-L1) inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) and explore potential prognostic predictive biomarkers. Methods: Patients with metastatic NSCLC who were treated with PD-1/PD-L1 inhibitors at Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2019, either as monotherapy or in combination with other agents, were consecutively enrolled into this study. We retrospectively collected the data of demographics, clinical information and pathologic assessment to evaluate the therapeutic efficacy and conduct the survival analysis. Major endpoint of our study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: The ORR of 174 patients who underwent PD-1/PD-L1 inhibitor was 28.7%, and the DCR was 79.3%. Immune-related adverse events (irAEs) occurred in 23 patients (13.2%). Brain metastasis, line of treatment, and treatment patterns were associated with the ORR of metastatic NSCLC patients who underwent immunotherapy (P<0.05). After a median follow-up duration of 18.8 months, the median PFS was 10.5 months (ranged from 1.5 to 40.8 months) while the median OS was not reached. The 2-year survival rate was estimated to be 63.0%. The pathologic type was related with the PFS of metastatic NSCLC patients who underwent immunotherapy (P=0.028). Sex, age, brain metastasis and autoimmune diseases were associated with OS (P<0.05). Analysis of the receptor characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) predicting ORR of immunotherapy in metastatic NSCLC showed that the areas under the curve of NLR before immunotherapy (NLR(C0)), NLR after one cycle of immunotherapy (NLR(C1)) and ΔNLR were 0.600, 0.706 and 0.628, respectively. Multivariate logistic regression analysis showed that NLR(C1) was an independent factor of the ORR of metastatic NSCLC patients who underwent immunotherapy (OR=0.161, 95% CI: 0.062-0.422), and the efficacy of combination therapy was better than that of single agent (OR=0.395, 95% CI: 0.174-0.896). The immunotherapy efficacy in patients without brain metastasis was better than those with metastasis (OR=0.291, 95% CI: 0.095-0.887). Multivariate Cox regression analysis showed that NLR(C1) was an independent influencing factor of PFS of metastatic NSCLC patients after immunotherapy (HR=0.480, 95% CI: 0.303-0.759). Sex (HR=0.399, 95% CI: 0.161-0.991, P=0.048), age (HR=0.356, 95% CI: 0.170-0.745, P=0.006) were independent influencing factors of OS of metastatic NSCLC patients after immunotherapy. Conclusions: PD-1/PD-L1 inhibitors are proved to be efficacious and have tolerable toxicities for patients with metastatic NSCLC. Patients at advanced age could still benefit from immunotherapy. Brain metastasis is related to compromised response. Earlier application of immunotherapy in combination with other modalities enhances the efficacy without elevating risk of irAEs. NLR(C1) is an early predictor of clinical outcome. The OS of patients younger than 75 years may be improved when treated with immunotherapy.

B7-H1 Antigen/metabolism , Brain Neoplasms/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Immune Checkpoint Inhibitors , Lung Neoplasms/pathology , Prognosis , Programmed Cell Death 1 Receptor , Retrospective Studies
Article in Chinese | WPRIM | ID: wpr-880829


OBJECTIVE@#To establish a mouse model bearing orthotopic temozolomide (TMZ)-resistant glioma that mimics the development of drug resistance in gliomas @*METHODS@#Seventy-eight adult C57BL/6 mice were randomly divided into 6 groups (@*RESULTS@#The mouse models bearing TMZresistant glioma was successfully established. The cells from the high-dose induced group showed a significantly higher colony-forming rate than those from the high-dose control group (@*CONCLUSIONS@#Progressive increase of TMZ doses in mice bearing orthotopic gliomas can effectively induce TMZ resistance of the gliomas.

Animals , Antineoplastic Agents, Alkylating/pharmacology , Brain Neoplasms/drug therapy , Cell Line, Tumor , Disease Models, Animal , Drug Resistance, Neoplasm , Glioma/drug therapy , Mice , Mice, Inbred C57BL , Temozolomide/therapeutic use
Rev. Hosp. Ital. B. Aires (2004) ; 39(4): 146-148, dic. 2019. ilus
Article in Spanish | LILACS | ID: biblio-1099838


Los anticuerpos monoclonales que inhiben los puntos de control PD-1 y CTLA-4 se usan actualmente en el tratamiento del melanoma y cáncer metastásico de pulmón de células no pequeñas, entre otros. Se refiere el caso de una paciente con cáncer de pulmón en tratamiento con pembrolizumab. La paciente se presentó con edema facial y parálisis facial periférica. En el laboratorio se observó la hormona tirotrofina (TSH) elevada y se llegó al diagnóstico de hipotiroidismo por pembrolizumab. Inició tratamiento con levotiroxina con mejoría clínica. Se presenta este caso por el importante papel del dermatólogo en el manejo multidisciplinario del paciente oncológico. (AU)

Monoclonal antibodies that inhibit PD-1 and CTLA-4 control points are currently used in the treatment of melanoma and metastatic non-small cell lung cancer, among others. The case of a patient, with lung cancer being treated with Pembrolizumab. The patient was presented with facial edema and peripheral facial paralysis and in the laboratory the elevated hormone Tyrotrophin (TSH) was observed, the diagnosis of pembrolizumab hypothyroidism was reached. She started treatment with levothyroxine with clinical improvement. This case is presented by the important role of the dermatologist in the multidisciplinary management of the cancer patient. (AU)

Humans , Female , Middle Aged , M Phase Cell Cycle Checkpoints/drug effects , Immunotherapy/adverse effects , Antibodies, Monoclonal/adverse effects , Thyroxine/therapeutic use , Brain Neoplasms/complications , Brain Neoplasms/drug therapy , Thyrotropin/analysis , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/drug therapy , Tumor Suppressor Proteins/drug effects , Dermatology , Facial Injuries , Facial Paralysis , CTLA-4 Antigen/drug effects , CTLA-4 Antigen/physiology , Programmed Cell Death 1 Receptor/drug effects , Programmed Cell Death 1 Receptor/physiology , Pemetrexed/administration & dosage , Melanoma/complications , Melanoma/drug therapy , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/therapeutic use , Neoplasm Metastasis/drug therapy
An. bras. dermatol ; 94(2): 218-220, Mar.-Apr. 2019. tab, graf
Article in English | LILACS | ID: biblio-1001152


Abstract Toxic epidermal necrolysis is a condition with massive keratinocyte apoptosis, and it is associated with high mortality rates. Fulvestrant, an estrogen receptor antagonist, is indicated in the treatment of estrogen receptor-positive metastatic breast cancer in postmenopausal women. To our knowledge, this is the first described case of toxic epidermal necrolysis due to fulvestrant. A 56-year-old woman received 500 mg of intramuscular fulvestrant monthly for metastatic ductal carcinoma of the breast. Five days after the first dose, the patient presented with a maculopapular rash that evolved to blisters, and a detachment of the epidermis in over 30% of the total body surface area. Histological analysis was compatible with toxic epidermal necrolysis. Fulvestrant was discontinued, topical management and supportive care were initiated.

Humans , Female , Middle Aged , Skin/pathology , Stevens-Johnson Syndrome/etiology , Estrogen Receptor Antagonists/adverse effects , /adverse effects , Brain Neoplasms/drug therapy , Brain Neoplasms/secondary , Stevens-Johnson Syndrome/pathology , Estrogen Receptor Antagonists/therapeutic use , /therapeutic use , Necrosis
Rev. Assoc. Med. Bras. (1992) ; 65(2): 136-140, Feb. 2019. graf
Article in English | LILACS | ID: biblio-990325


SUMMARY We describe the case of a female patient, 52 years old, with dizziness and left motor incoordination for 2 weeks. Brain MRI magnetic resonance imaging) revealed a hyperintense lesion on T2-weighted images, without restricted diffusion, in the left middle cerebellar peduncle. Spectroscopy demonstrated peak of lipids and perfusion did not show any elevation in relative cerebral blood volume (rCBV). The patient underwent an open biopsy and resection, and the diagnosis of diffuse large B-cell lymphoma (DLBCL) was established. The patient received intravenous dexamethasone with symptoms remission, followed by four cycles of methotrexate plus cytarabine. After 3 months, the patient returned with decreased consciences level and a new MRI revealed a right superior frontal gyrus lesion with features suggesting a lymphomatous lesion. The patient died five days after her relapse.

RESUMO Descrevemos o caso de uma paciente do sexo feminino, de 52 anos, apresentando história de tontura e perda da coordenação motora do lado esquerdo há duas semanas. A RM (ressonância magnética) de crânio revelou uma lesão hiperintensa nas imagens ponderadas em T2, sem restrição à difusão, localizada no pedúnculo cerebelar médio esquerdo. A espectroscopia demonstrou pico de lipídeos, sem elevação do volume sanguíneo cerebral relativo (rCBV) à perfusão. A paciente foi submetida à biópsia a céu aberto, estabelecendo o diagnóstico de linfoma difuso de grandes células B (DLBCL). Houve remissão dos sintomas após o início do tratamento com dexametasona endovenosa, seguida de quatro ciclos de metotrexato associado à citarabina. Após três meses, a paciente retornou apresentando rebaixamento do nível de consciência, e a RM de crânio revelou uma nova lesão de origem linfomatosa no giro frontal superior direito. A paciente faleceu após cinco dias.

Humans , Female , Brain Neoplasms/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Brain Neoplasms/drug therapy , Magnetic Resonance Imaging , Lymphoma, Large B-Cell, Diffuse/drug therapy , Fatal Outcome , Immunocompetence , Middle Aged , Neoplasm Recurrence, Local
Braz. j. med. biol. res ; 51(1): e6073, 2018. tab, graf
Article in English | LILACS | ID: biblio-889009


Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinib-WBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (P<0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (P<0.05). Although bevacizumab-gefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC.

Humans , Male , Female , Adult , Middle Aged , Aged , Quinazolines/therapeutic use , Brain Neoplasms/drug therapy , Cranial Irradiation/methods , Carcinoma, Non-Small-Cell Lung/drug therapy , Bevacizumab/therapeutic use , Lung Neoplasms/pathology , Antineoplastic Agents/therapeutic use , Time Factors , Analysis of Variance , Treatment Outcome , Gefitinib , Mutation
Rev. Hosp. Clin. Univ. Chile ; 29(2): 154-165, 2018. Tab., Ilus.
Article in Spanish | LILACS | ID: biblio-986697


Brain metastases represent a critical stage of oncological disease and its frequency is increasing over the recent years. The treatment of brain metastases has moved from a conservative approach to an active management that should be individualized for each patient: in case of single brain metastasis, surgery or radiosurgery should be considered as first option of treatment; in case of multiple lesions, whole-brain radiotherapy is the standard of care. The aim of this review is to present general aspects including new approaches in management of patients with brain metastases.(AU)

Humans , Male , Female , Brain Neoplasms/surgery , Brain Neoplasms/radiotherapy , Brain Neoplasms/therapy , Brain Neoplasms/diagnosis , Brain Neoplasms/drug therapy , Brain Neoplasms/epidemiology , Brain Neoplasms/diagnostic imaging
Korean Journal of Radiology ; : 1341-1348, 2015.
Article in English | WPRIM | ID: wpr-172970


OBJECTIVE: To determine whether histogram values of the normalized apparent diffusion coefficient (nADC) and normalized cerebral blood volume (nCBV) maps obtained in contrast-enhancing lesions detected on immediate post-operative MR imaging can be used to predict the patient response to concurrent chemoradiotherapy (CCRT) with temozolomide (TMZ). MATERIALS AND METHODS: Twenty-four patients with GBM who had shown measurable contrast enhancement on immediate post-operative MR imaging and had subsequently undergone CCRT with TMZ were retrospectively analyzed. The corresponding histogram parameters of nCBV and nADC maps for measurable contrast-enhancing lesions were calculated. Patient groups with progression (n = 11) and non-progression (n = 13) at one year after the operation were identified, and the histogram parameters were compared between the two groups. Receiver operating characteristic (ROC) analysis was used to determine the best cutoff value for predicting progression. Progression-free survival (PFS) was determined with the Kaplan-Meier method and the log-rank test. RESULTS: The 99th percentile of the cumulative nCBV histogram (nCBV C99) on immediate post-operative MR imaging was a significant predictor of one-year progression (p = 0.033). ROC analysis showed that the best cutoff value for predicting progression after CCRT was 5.537 (sensitivity and specificity were 72.7% and 76.9%, respectively). The patients with an nCBV C99 of < 5.537 had a significantly longer PFS than those with an nCBV C99 of ≥ 5.537 (p = 0.026). CONCLUSION: The nCBV C99 from the cumulative histogram analysis of the nCBV from immediate post-operative MR imaging may be feasible for predicting glioblastoma response to CCRT with TMZ.

Adult , Aged , Antineoplastic Agents, Alkylating/therapeutic use , Brain/pathology , Brain Neoplasms/drug therapy , Chemoradiotherapy , Dacarbazine/analogs & derivatives , Diffusion Magnetic Resonance Imaging , Disease Progression , Disease-Free Survival , Female , Glioblastoma/drug therapy , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , ROC Curve , Retrospective Studies
Article in English | WPRIM | ID: wpr-215492


Although methyltransferase has been recognized as a major element that governs the epigenetic regulation of the genome during temozolomide (TMZ) chemotherapy in glioblastoma multiforme (GBM) patients, its regulatory effect on glioblastoma chemoresistance has not been well defined. This study investigated whether DNA methyltransferase (DNMT) expression was associated with TMZ sensitivity in glioma cells and elucidated the underlying mechanism. DNMT expression was analyzed by western blotting. miR-20a promoter methylation was evaluated by methylation-specific PCR. Cell viability and apoptosis were assessed using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and TdT-mediated dUTP-biotin nick end labeling assays, respectively. The results showed that compared with parental U251 cells, DNMT1 expression was downregulated, miR-20a promoter methylation was attenuated and miR-20a levels were elevated in TMZ-resistant U251 cells. Methyltransferase inhibition by 5-aza-2\'-deoxycytidine treatment reduced TMZ sensitivity in U251 cells. In U251/TM cells, DNMT1 expression was negatively correlated with miR-20a expression and positively correlated with TMZ sensitivity and leucine-rich repeats and immunoglobulin-like domains 1 expression; these effects were reversed by changes in miR-20a expression. DNMT1 overexpression induced an increase in U251/TM cell apoptosis that was inhibited by the miR-20a mimic, whereas DNMT1 silencing attenuated U251/TM cell apoptosis in a manner that was abrogated by miR-20a inhibitor treatment. Tumor growth of the U251/TM xenograft was inhibited by pcDNA-DNMT1 pretreatment and boosted by DNMT1-small hairpin RNA pretreatment. In summary, DNMT1 mediated chemosensitivity by reducing methylation of the microRNA-20a promoter in glioma cells.

Animals , Antineoplastic Agents, Alkylating/pharmacology , Apoptosis/drug effects , Brain/drug effects , Brain Neoplasms/drug therapy , DNA (Cytosine-5-)-Methyltransferases/antagonists & inhibitors , DNA Methylation , Dacarbazine/analogs & derivatives , Drug Resistance, Neoplasm , Female , Gene Expression Regulation, Neoplastic , Glioma/drug therapy , Humans , Mice, Inbred C57BL , MicroRNAs/genetics , Promoter Regions, Genetic
Rev. chil. neurocir ; 40(2): 133-135, 2014. ilus
Article in English | LILACS | ID: biblio-997480


Los tumores cerebrales metastásicos son el tipo más frecuente de cáncer que afecta el sistema nervioso central (SNC). Muchos sitios pueden generar implantes para todo el cerebro, pero hay órganos que raramente generan metastasis para el SNC. Carcinoma peritoneal primario es un cáncer raro, y su patología no es bien conocida, así como sus vías metastásicas. Se presenta un caso de una paciente que se presentó con lesiones cerebrales difusas debido a un carcinoma peritoneal primario diagnosticado previamente. También realizamos una breve revisión sobre el tema.

Brain metastatic tumors are the most frequent type of cancer affecting central nervous system. Many sites can generates implants for the entire brain, but there are organs that rarely generate metastasis. Primary peritoneal carcinoma is a rare cancer, and its pathology is not well known as well as its metastatic pathways. It is reported a case of a female patient who presented with diffuse brain lesions due to a primary peritoneal carcinoma previously diagnosed. We also perform a brief review about the theme.

Humans , Brain Neoplasms/surgery , Brain Neoplasms/complications , Brain Neoplasms/diagnosis , Brain Neoplasms/drug therapy , Neoplasm Metastasis , Magnetic Resonance Imaging
Article in English | WPRIM | ID: wpr-70747


This study evaluated the toxicity profiles of temozolomide in the treatment of malignant glioma as either concurrent or adjuvant chemotherapy. We retrospectively reviewed the medical records of 300 malignant glioma patients treated with temozolomide in two medical institutions in Korea between 2004 and 2010. Two hundred nine patients experienced a total of 618 toxicities during temozolomide therapy. A total of 84.8% of the 618 toxicities were Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or 2, while 15.2% were grade 3 or 4. Among the hematologic toxicities, thrombocytopenia (13.7%), anemia (11.0%), and AST/ALT increases (7.0%) were common. Among the non-hematologic toxicities, nausea (44.3%), vomiting (37.0%), and anorexia (14.3%) were the three most common toxicities. There was no mortality due to temozolomide. Although temozolomide showed many types of toxicities, the majority of the toxicities were tolerable and of lower grade. Gastrointestinal troubles are the most common toxicities in Korean patients treated with temozolomide.

Adolescent , Adult , Aged , Aged, 80 and over , Anorexia/etiology , Antineoplastic Agents, Alkylating/adverse effects , Brain Neoplasms/drug therapy , Dacarbazine/adverse effects , Female , Glioma/drug therapy , Hematologic Diseases/etiology , Humans , Male , Middle Aged , Nausea/drug therapy , Neoplasm Staging , Republic of Korea , Retrospective Studies , Severity of Illness Index , Sex Factors , Vomiting/drug therapy , Young Adult
Rev. venez. oncol ; 25(2): 85-97, abr.-jun. 2013. ilus, tab, graf
Article in Spanish | LILACS | ID: lil-718947


Estimar la sobrevida de pacientes pediátricos con tumores cerebrales tratados en la Unidad de Radioterapia Oncológica GURVE del Instituto Médico la Floresta. Análisis de 137 pacientes pediátricos con tumores primarios del sistema nervioso central vistos entre enero de 2000 a diciembre de 2010. Los pacientes recibieron tratamiento posoperatorio con radioterapia y quimioterapia. La dosis total de radioterapia se administró de acuerdo al tipo histológico oscilando entre 5 040 cGy-6 000 cGy. Dosis fracción fue 180 cGy y (150 cGy diario casos tratados con irradiación craneoespinal). El tiempo medio de seguimiento fue 44,2 meses con un rango 2,2 a137,4 meses. La edad osciló de 2-18 años media 12 años. En 77 (52,2%) fueron masculinos y 60 (47,7%) femenino. El sitio anatómico más frecuente fue la región infratentorial 85 (62%) seguidas 49 (35,7%) en la región supratentorial y 1 en región espinal. Los tumores más frecuentes resultaron ser gliomas con 74 (54,7%) y PNET´s 23(16,1%). La sobrevida global para los gliomas de bajo grado fue 87,5% a los 5 y 10 años respectivamente. En los gliomas de alto grado se encontró una sobrevida global 30,2% a los 5 años. En los tumores de tallo cerebral la sobrevida a los 5 años fue 9,4%. La sobrevida global obtenida en los pacientes pediátricos tratados con radioterapia y en algunos casos con quimioterapia es similar a los publicados en la literatura internacional.

To estimated super life in pediatric patients treated in the Department of Radiation Oncology, GURVE, the Floresta Medical Institute. A retrospective analysis of survival of 137 pediatric patients with primary tumors of the central nervous system from January 2000 to December 2010 was done. Patients received postoperative radiotherapy and chemotherapy. The total dose of radiotherapy ranged from 5 040 cGy to 6 000 cGy, using a daily dose of 180 cGy, (and 150 cGy per day in cases treated with craneo spinal irradiation) depending on the histological type. Mean follow-up time was 44.2 months, with a range of 2.2-137.4 month. Age ranged from 2 to 18 years average of 12 years. As for the sex distribution 77 (52.2%) were males and 60 (47.7%) were females. The most common anatomic site was the infratentorial region in 85 patients (62%), followed by 49 (35.7%) in the supratentorial region and 1 in spinal region. The most common histological type found were gliomas in 74 patients (54.7%) and PNET´s in 23 (16.1%). Overall survival for low-grade gliomas was 87.5% at 5 and 10 years respectively. In high-grade gliomas overall survival was 30.2% at 5 years. In tumors of the brain stem survival at 5 years was 9.4%. Overall survival in pediatric patients with brain tumors treated with radiation therapy and in some cases chemotherapy was similar to those found in international literature.

Humans , Male , Female , Child, Preschool , Child , Adolescent , Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Brain Neoplasms/therapy , Survival , Brain Injuries, Traumatic/pathology , Medical Oncology , Pediatrics
Arq. neuropsiquiatr ; 70(1): 52-58, Jan. 2012. ilus, tab
Article in English | LILACS | ID: lil-612664


Brain cancer is the second neurological cause of death. A simplified animal brain tumor model using W256 (carcinoma 256, Walker) cell line was developed to permit the testing of novel treatment modalities. Wistar rats had a cell tumor solution inoculated stereotactically in the basal ganglia (right subfrontal caudate). This model yielded tumor growth in 95 percent of the animals, and showed absence of extracranial metastasis and systemic infection. Survival median was 10 days. Estimated tumor volume was 17.08±6.7 mm³ on the 7th day and 67.25±19.8 mm³ on 9th day post-inoculation. Doubling time was 24.25 h. Tumor growth induced cachexia, but no hematological or biochemical alterations. This model behaved as an undifferentiated tumor and can be promising for studying tumor cell migration in the central nervous system. Dexamethasone 3.0 mg/kg/day diminished significantly survival in this model. Cyclosporine 10 mg/kg/day administration was safely tolerated.

Neoplasias encefálicas constituem a segunda causa neurológica de morte. Foi desenvolvido um modelo animal simplificado de tumor cerebral em ratos utilizando a linhagem celular W256 (carcinoma 256 de Walker) para permitir teste de novos tratamentos. Ratos Wistar foram inoculados nos gânglios da base (caudato subfrontal direito) com uma solução celular tumoral, por via estereotáxica. Este modelo demonstrou crescimento tumoral em 95 por cento dos animais inoculados com sucesso, além de mostrar ausência de metástases extracranianas e infecção sistêmica. A mediana de sobrevida dos animais foi de 10 dias. O volume tumoral estimado foi de 17,08±6,7 mm³ no sétimo dia e de 67,25±19,8 mm³ no nono dia após a inoculação. O tempo de duplicação foi estimado em 24,25 h. O crescimento tumoral induziu a caquexia, mas não houve alterações bioquímicas ou hematológicas. Esse modelo permite fácil reprodução e comporta-se como um tumor indiferenciado, mostrando potencial para estudar migração celular tumoral no sistema nervoso central. Dexametasona 3,0 mg/kg/dia reduziu significantemente a sobrevida dos animais inoculados com tumor nesse modelo. Ciclosporina 10 mg/kg/dia não teve efeito na sobrevida, sendo sua administração bem tolerada.

Animals , Male , Rats , Brain Neoplasms/drug therapy , /drug therapy , Cyclosporine/administration & dosage , Immunosuppressive Agents/administration & dosage , Analysis of Variance , Cell Line, Tumor , Disease Models, Animal , Drug Evaluation, Preclinical , Dexamethasone/administration & dosage , Neoplasm Transplantation/methods , Rats, Wistar , Stereotaxic Techniques
Braz. j. med. biol. res ; 44(5): 489-490, May 2011. ilus
Article in English | LILACS | ID: lil-586517


We investigated the effect of photodynamic therapy (PDT) and of an anti-vascular cell adhesion molecule-1 (VCAM-1) monoclonal antibody on the in vivo growth of C6 glioma. Seven days after inoculation with C6 cells, adult male Wistar rats weighing 280-300 g with MRI-confirmed glioma were randomly assigned to 4 groups (N = 15 per group): PDT + VCAM-1 antibody group; PDT group; VCAM-1 antibody group; control group. Eight days after inoculation, hematoporphyrin monomethyl ether (HMME) was administered as a photosensitizer and PDT was performed at 630 nm (illumination intensity: 360 J/cm²) for 10 min. VCAM-1 antibody (50 µg/mL) was then administered (0.5 mL) through the tail vein every other day from day 8 to day 16. At day 21, 5 rats in each group were sacrificed and cancers were harvested for immunohistochemistry and Western blot assay for the detection of VCAM-1, and TUNEL assay was used to detect apoptosis. Survival and tumor volume were recorded in the remaining 10 rats in each group. In the PDT group, tumor growth was significantly suppressed (67.2 percent) and survival prolonged (89.3 percent), accompanied by an increase in apoptosis (369.5 percent), when compared to control. Furthermore, these changes were more pronounced in the PDT + VCAM-1 antibody group. After PDT, VCAM-1 expression was markedly increased (121.8 percent) and after VCAM-1 monoclonal antibody treatment, VCAM-1 expression was significantly reduced (58.2 percent). PDT in combination with VCAM-1 antibody can significantly inhibit the growth of C6 glioma and prolong survival. This approach may represent a promising strategy in the treatment of glioma.

Animals , Male , Rats , Antibodies, Monoclonal/therapeutic use , Brain Neoplasms/drug therapy , Glioma/drug therapy , Photochemotherapy/methods , Vascular Cell Adhesion Molecule-1/immunology , Brain Neoplasms/pathology , Cell Line, Tumor , Combined Modality Therapy , Glioma/pathology , Immunohistochemistry , Magnetic Resonance Imaging , Rats, Wistar , Xenograft Model Antitumor Assays
Rev. méd. Chile ; 139(4): 415-424, abr. 2011. ilus
Article in Spanish | LILACS | ID: lil-597635


Background: Mortality rate is dramatically high in high grade brain tumors. The presence of multiple drug resistance transporters in glioblastoma multiforme, has contributed largely to the poor effcacy of targeted therapy against cancer in the central nervous system. Aim: To analyze the percentage of survival and mortality of patients with glioblastoma multiforme in a cohort of patients in Chile and to co-rrelate the chemo-resistance of these cells with the expression level of multiple drug resistance transporters. Materials and Methods: Eighteen biopsies of glioblastoma multiforme were obtained from patients at the Institute of Neurosurgery Dr. Asenjo (INCA). The tumor cells were obtained from primary cultures and the expression and activity of multiple drug resistance transporters was assessed by RT-PCR and immunohistochemistry. Population-based study was performed using the databases of the Department of Neurosurgery of INCA. Results: The number of patients with glioblastoma multiforme increased between 2007 and 2009, from 3.5 percent to 7.9 percent of total brain tumors. Mortality of these tumors is 90 percent at three years. A high expression and activity of the multiple drugs resistance associated protein 1 (Mrp1) transporter was observed in primary cultures of biopsies. Conclusions: We propose that Mrp1 activity is responsible for the chemo-resistance of the glioblastoma multiforme and inhibition of this transporter could represent a plausible strategy for the treatment.

Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , ATP-Binding Cassette Transporters/metabolism , Brain Neoplasms/drug therapy , Drug Resistance, Neoplasm , Glioblastoma/drug therapy , Neoplasm Proteins/metabolism , Brain Neoplasms/metabolism , Brain Neoplasms/mortality , Cohort Studies , Follow-Up Studies , Glioblastoma/metabolism , Glioblastoma/mortality , Immunohistochemistry , Reverse Transcriptase Polymerase Chain Reaction , Survival Analysis , Tumor Cells, Cultured
Medicina (B.Aires) ; 71(1): 73-77, ene.-feb. 2011. ilus
Article in Spanish | LILACS | ID: lil-633824


El uso profiláctico de drogas antiepilépticas en enfermedades neurológicas como el accidente cerebrovascular isquémico y hemorrágico, la hemorragia subaracnoidea, el traumatismo de cráneo y los tumores cerebrales ha sido motivo de controversia durante muchos años. Estas drogas son indicadas con el fin de disminuir el daño neurológico secundario a las crisis epilépticas. Sin embargo, la escasa evidencia científica disponible para avalar esta hipótesis, las potenciales interacciones farmacológicas, los efectos adversos y algunos informes sobre neurotoxicidad generan dudas en cuanto a esta conducta terapéutica. En esta revisión, analizamos la evidencia acerca del uso profiláctico de drogas epilépticas en las enfermedades neurológicas arriba mencionadas.

Prophylactic use of antiepileptic drugs in neurological conditions such as ischemic and hemorrhagic stroke, subarachnoid hemorrhage, head injury, and brain tumors has been matter of debate for many years. These drugs are used for reducing secondary neurological damage caused by epileptic seizures. However, the evidence supporting this indication is scarce. Potential drug interactions, side effects, and even neurotoxicity related to these drugs have raised concern about this therapeutic approach. In this review, we examine the evidence on the prophylactic use of antiepileptic drugs in the neurological disorders above mentioned.

Humans , Anticonvulsants/therapeutic use , Brain Diseases/drug therapy , Anticonvulsants/adverse effects , Brain Injuries/drug therapy , Brain Neoplasms/drug therapy , Stroke/drug therapy , Subarachnoid Hemorrhage/drug therapy
Indian J Cancer ; 2011 Jan-Mar; 48(1): 11-17
Article in English | IMSEAR | ID: sea-144405


Glioblastoma is a rapidly progressive and extremely fatal form of brain tumor with poor prognosis. It is the most common type of primary brain tumor. Even with the most aggressive conventional treatment that comprises surgery followed by radiotherapy and chemotherapy, most patients die within a year of diagnosis. Developments in molecular and cell biology have led to better understanding of tumor development, leading to novel treatment strategies including biological therapy and immunotherapy to combat the deadly disease. Targeted drug delivery strategies to circumvent the blood-brain barrier have shown efficiency in clinical trials. Gliadel wafer is a new approach to the treatment of glioblastoma, which involves controlled release delivery of carmustine from biodegradable polymer wafers. It has shown promising results and provides a silver lining for glioblastoma patients.

Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/drug therapy , Carmustine/therapeutic use , Delayed-Action Preparations , Humans
Rev. imagem ; 30(3): 85-89, jul.-set. 2008.
Article in Portuguese | LILACS | ID: lil-542290


OBJETIVO: Analisar o impacto da adição da temozolamida à radioterapia em tumores de tronco cerebral em crianças. MATERIAL E MÉTODO: Entre 2000 e 2005 foram analisadas, retrospectivamente, 64 crianças com tumor do tronco cerebral. Dessas crianças, 32 receberam temozolamida(grupo 1) e 32 não a receberam (grupo 2). RESULTADOS: A idade mediana no grupo 1 foi de 8,2 anos e no grupo 2 foi de 7,5 anos. A localização tumoral era predominantemente difusa (53%) emambos os grupos. Todos os pacientes receberam radioterapia com doses superiores a 50 Gy. No grupo1 foram ministrados nove ciclos, em média, de quimioterapia (3û14 ciclos). O tempo de progressão de doença foi de 7,9 meses no grupo 2 versus 13,8 meses no grupo 1. A sobrevida global foi de 8,8 meses (0,3û30,9 meses) no grupo 1 e de 14,6 meses (4,3û33 meses) no grupo 2. CONCLUSÃO: A utilização da temozolamida após a radioterapia proporcionou aumento da sobrevida, deseis meses em média, nos pacientes pediátricos com tumor do tronco cerebral.

OBJECTIVE: To analyze the impact of adding temozolomide to radiotherapyin pediatric brain stem tumors. MATERIAL AND METHOD: Between 2000 and 2005, 64 children with brain stem tumor were analyzed: 32 received temozolomide (group 1) and 32 did not(group 2). RESULTS: The median age of patients in group 1 was 8.2 year-old and in group 2 was 7.5 year-old. The predominant tumoral localization was diffuse (53%) in both groups. All of the patients were submitted to radiotherapy. In group 1, the median number of temozolomide cycles was 9 (3û14 cycles). Time of disease progression was 7.9 months in group 2 versus 13.8 months in group 1. Overall survival was 8.8 months (0.3û30.9 months) in group 1 and 14.6 months (4.3û33 months) in group 2. CONCLUSION: In our institution,adding temozolomide to radiotherapy increased the overall survival in approximately six months in brain stem pediatric tumors.

Humans , Child , Alkylating Agents/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Survival , Brain Stem/pathology , Retrospective Studies