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1.
Rev. colomb. cancerol ; 24(2): 88-91, abr.-jun. 2020. graf
Article in Spanish | LILACS | ID: biblio-1144325

ABSTRACT

Resumen El carcinoma de célula pequeña (CPCP) o microcítico de pulmón es un subtipo de cáncer de pulmón que típicamente se ha asociado al tabaquismo y que se caracteriza por su agresividad y mal pronóstico a corto plazo. Como entidad, puede metastatizar en cualquier órgano, siendo las metástasis pancreáticas raras y la mayoría de las veces asintomáticas. Por ello, la presencia de una pancreatitis neoplásica, como en el caso presentado, es excepcional, y aún más cuando presenta refractariedad al tratamiento médico convencional y responde al tratamiento citotóxico sistémico. Por todo ello, se expone esta experiencia clínica y se debate la presencia de esta rara entidad y su manejo.


Abstract Small-cell lung carcinoma is a subtype of neoplasm that has been typically associated with smoking; it is characterized by its aggressiveness and poor prognosis in the short term. As an entity, it can metastasize in any organ, but pancreatic metastases are rare and most of the time asymptomatic. Therefore, the presence of neoplastic pancreatitis as in our case is exceptional; even more when it presents refractoriness to conventional medical treatment, responding instead to systemic cytotoxic treatment. Therefore, we expose our clinical experience and discuss the presence of this rare entity and its management.


Subject(s)
Humans , Male , Middle Aged , Pancreatic Neoplasms/secondary , Pancreatitis/etiology , Small Cell Lung Carcinoma/pathology , Lung Neoplasms/pathology , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/diagnostic imaging , Tobacco Use Disorder/complications , Acute Disease , Cisplatin/therapeutic use , Etoposide/therapeutic use , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/diagnostic imaging , Lung Neoplasms/drug therapy , Lung Neoplasms/diagnostic imaging , Antineoplastic Agents/therapeutic use
2.
Int. arch. otorhinolaryngol. (Impr.) ; 24(1): 47-52, Jan.-Mar. 2020. graf
Article in English | LILACS | ID: biblio-1090559

ABSTRACT

Abstract Introduction Cisplatin damages the auditory system and is related to the generation of free radicals. Glutathione peroxidase is an endogenous free radicals remover. Objective To investigate the mechanisms involved in otoprotection by N-acetylcys- teine through the expression of glutathione peroxidase in outer hair cells from rats treated with cisplatin. Methods Male Wistar rats were intraperitoneally injected with cisplatin (8 mg/Kg) and/or received oral administration by gavage of N-acetylcysteine (300 mg/Kg) for 3 consecutive days. On the 4th day, the animals were euthanized and beheaded. The tympanic bullae were removed and prepared for scanning electron microscopy and Results Among the groups exposed to ototoxic doses of cisplatin, there was an increase in glutathione peroxidase immunostaining in two groups, the one exposed to cisplatin alone, and the group exposed to both cisplatin and N-acetylcysteine. Conclusion The expression of glutathione peroxidase in the outer hair cells of rats exposed to cisplatin showed the synthesis of this enzyme under cellular toxicity conditions.


Subject(s)
Animals , Male , Acetylcysteine/therapeutic use , Free Radical Scavengers/therapeutic use , Cisplatin/toxicity , Oxidative Stress/drug effects , Antineoplastic Agents/toxicity , Acetylcysteine/metabolism , Acetylcysteine/pharmacology , Microscopy, Electron, Scanning , Evoked Potentials, Auditory, Brain Stem , Free Radical Scavengers/metabolism , Free Radical Scavengers/pharmacology , Fluorescent Antibody Technique , Cisplatin/therapeutic use , Rats, Wistar , Cochlea/anatomy & histology , Cochlea/drug effects , Free Radicals , Glutathione Peroxidase/metabolism , Hearing Loss, Sensorineural/prevention & control
3.
Article in English | WPRIM | ID: wpr-880600

ABSTRACT

OBJECTIVES@#To observe the efficacy and adverse reactions of the combination of endostar with chemotherapy in the treatment of advanced (IVb) and recurrent metastatic cervical cancer.@*METHODS@#Forty-four patients with recurrent and metastatic cervical cancer, who were admitted to the Second Xiangya Hospital, Central South University from December 2016 to December 2018 were randomly divided into an experimental group and a control group (22 cases in each group). The control group was given gemcitabine plus cisplatin (GP) or docetaxel plus cisplatin (DP) treatment, the experimental group was treated with endostar on the basis of the control group.@*RESULTS@#The objective response rate (ORR) was 42.9% in the experimental group and 22.7% in the control group. There was no significant difference between the 2 groups (@*CONCLUSIONS@#Compared with chemotherapy alone, endostar combined with chemotherapy can prolong the median progression-free survival, with higher ORR and similar adverse reactions.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/therapeutic use , Endostatins , Female , Humans , Lung Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Recombinant Proteins , Uterine Cervical Neoplasms
4.
Lima; IETSI; 2019.
Non-conventional in Spanish | LILACS, BRISA | ID: biblio-1116900

ABSTRACT

INTRODUCCIÓN: El cáncer de pulmón (CP) es uno de los tumores más frecuentes en el mundo. Se clasifica en dos grupos, siendo el subgrupo de CP de células no pequeñas (CPCNP) el más frecuente (80 %). A su vez, el CPCNP se subdivide en el subtipo escamoso y el no escamoso. El adenocarcinoma de pulmón es el subtipo histológico de CPCNP no escamoso más frecuente (40 % de todos los casos de CP) y tiene como tratamiento sistémico de elección a la quimioterapia en doblete basado en platino (QT-P), cuando las células tumorales no cuentan con las mutaciones EGFR y ALK (EGFR- y ALK-). El Petitorio Farmacológico de EsSalud cuenta con diferentes esquemas de QT-P (combinación de un agente quimioterapéutico, tales como docetaxel, gemcitabina, paclitaxel o pemetrexed, con un platino [cisplatino o carboplatino]) como tratamiento de primera línea de los pacientes con adenocarcinoma de pulmón metastásico, EGFR- y ALK-. Como alternativa terapéutica, los especialistas han sugerido la evaluación del uso combinado de pembrolizumab y QT-P, sustentado que dicha combinación podría ofrecer un beneficio adicional al uso de la QT-P sola. OBJETIVO: Evaluar la mejor evidencia científica disponible a la fecha sobre la eficacia y seguridad del uso combinado de pembrolizumab + QT-P, en comparación con el placebo + QT-P, para los pacientes adultos con adenocarcinoma de pulmón metastásico, EGFR- y ALK-. TECNOLOGÍA SANITARIA DE INTERÉS: Pembrolizumab: Pembrolizumab ha sido descrito ampliamente en dos dictámenes previos (Dictamen Preliminar de Evaluación de Tecnología Sanitaria Nº 025-SDEPFyOTS-DETS-IETSI-2017 y N° 059-SDEPFyOTS-DETS-IETSI-2017). En breve, pembrolizumab es un anticuerpo monoclonal tipo IgG que se une al receptor de muerte programada PD-1, lo cual bloquea la interacción de dicho receptor con sus ligandos PD-L1 y PD-L2, y, así, promueve la actividad antitumoral de los linfocitos T. METODOLOGÍA: Se llevó a cabo una búsqueda bibliográfica exhaustiva y jerárquica de la literatura con respecto a la eficacia y seguridad del pembrolizumab asociado a la QT-P, comparado con QT-P asociado a placebo, en pacientes con adenocarcinoma de pulmón metastásico, con EGFR negativo y ALK negativo. La búsqueda se inició revisando la información sobre el uso del medicamento de acuerdo con entidades reguladoras como FDA, EMA, y DIGEMID en el Perú. RESULTADOS: Se llevó a cabo una búsqueda de evidencia científica relacionada al uso de pembrolizumab + QT-P, comparado con placebo + QT-P, como tratamiento de primera línea de pacientes con adenocarcinoma de pulmón metastásico, EGFR- y ALK-. En la presente sinopsis se describe la evidencia disponible según el tipo de publicación, siguiendo lo indicado en los criterios de elegibilidad (GPC, ETS, RS, MA y ECA fase III). CONCLUSIONES: La evidencia principal que responde a la pregunta PICO establecida en el presente dictamen proviene del ECA de fase III KEYNOTE-189, el cual es un estudio doble ciego, multicéntrico, y financiado por el fabricante de pembrolizumab, Merck & Co., Inc., que evaluó la eficacia y seguridad de pembrolizumab + pemetrexed/platino (QT-P) comparado con placebo + pemetrexed/platino, en pacientes con CPCNP no escamoso, EGFR- y ALK-, que no hayan recibido ninguna terapia sistémica para la enfermedad metastásica. Con la evidencia disponible a la fecha procedente del ECA KEYNOTE-189, la cual corresponde a un análisis preliminar, luego de una mediana de 10.5 meses de seguimiento, con una madurez de la data de mortalidad al 55 %, no es posible determinar un beneficio neto con pembrolizumab + QT-P, en comparación con placebo + QT-P, con respecto a desenlaces clínicamente relevantes como la calidad de vida o la SG. Esto debido a que, luego de la corrección por sobrestimación, no se detectaron diferencias estadísticamente significativas en la SG ni en la SLP entre los grupos de tratamiento. Asimismo, hubo confusores fuertes en el análisis de SG, como consecuencia de desbalances en la aleatorización que se tradujo en diferencias en las características basales entre los grupos de tratamiento. También hubo un alto cruzamiento entre los grupos de tratamiento, con diferencias considerables en la elección de los esquemas de terapia subsecuente luego de progresión tumoral. Los resultados de seguridad del ECA KEYNOTE-189 no mostraron diferencias estadísticamente significativas entre los grupos de tratamiento en las tasas de EA totales, EA serios, EA fatales y EA severos. Sin embargo, se encontraron diferencias estadísticamente significativas en la tasa de descontinuación del tratamiento por EA y en la proporción de pacientes que presentaron el EA serio neutropenia febril, con resultados desfavorables para el grupo pembrolizumab + QT-P. Por lo tanto, la evidencia disponible a la fecha indicaría que el uso de pembrolizumab + QT-P tendría un perfil de seguridad desfavorable en comparación con el uso de placebo + QT-P en la población de la pregunta PICO. Con todo ello, existe incertidumbre respecto al balance riesgo beneficio entre el uso combinado de pembrolizumab + QT-P, en comparación con placebo + QT-P, en el tratamiento de pacientes de la población PICO de interés para el presente dictamen. A ello se le suma el alto costo del medicamento (aproximadamente, S/ 378,436.80 anuales por paciente), por lo que su aprobación no sería una decisión costooportuna para un sistema público de salud como es EsSalud. Asimismo, actualmente se encuentra disponible en la institución la QT-P como alternativa de tratamiento, la cual también es recomendada en las GPC internacionales. Por lo expuesto, el Instituto de Evaluaciones de Tecnologías en Salud e Investigación ­ IETSI no aprueba el uso de pembrolizumab + QT-P para el tratamiento de primera línea de los pacientes adultos con adenocarcinoma de pulmón metastásico, EGFR- y ALK-.


Subject(s)
Humans , Immunoglobulin G/therapeutic use , Cisplatin/therapeutic use , Adenocarcinoma of Lung/drug therapy , Technology Assessment, Biomedical , Health Evaluation , Cost-Benefit Analysis
5.
Braz. arch. biol. technol ; 62: e19180716, 2019. tab, graf
Article in English | LILACS | ID: biblio-1055372

ABSTRACT

Abstract In a recent study, the treatment of different human cancer cell lines in vitro with ethylene diamine tetra-acetic acid (EDTA) showed a promising anticancer activity which could be a novel promising approach for cancer treatment. The aim of this study is to address the ability of EDTA to enhance the antitumor efficacy of the low dose of cisplatin (Cis) treatment in Ehrlich ascetic carcinoma (EAC) bearing mice. Sixty female albino mice were divided into six groups. The 1st group of mice was served as a negative control. 2nd - 6th groups were inoculated intraperitoneal (i.p) with 2×106 EAC cells/mouse. After one day of inoculation, the 2nd, 3rd and 4th groups were injected daily for 6 days (early treatment) with phosphate buffer saline, low dose of Cis and Cis/EDTA, respectively. After six days, the 5th and 6th groups were injected with the low dose of Cis and Cis/EDTA for 6 consecutive days (late treatment), respectively. At day 14, all groups of mice were sacrificed, sera were collected for biochemical assessment, then tumor volumes, counts, live and dead cells were determined from all groups. The results showed that EDTA co-treatment enhanced the efficacy of low dose of Cis at early and late time points. In addition, EDTA co-treatment potentially ameliorated the Cis-induced side effects on liver and kidney functions. In summary, co-therapy with EDTA could enhance the chemotherapeutic efficacy of low dose of Cis.


Subject(s)
Carcinoma, Ehrlich Tumor/drug therapy , Cisplatin/therapeutic use , Edetic Acid/administration & dosage , Treatment Outcome , Models, Animal , Mice , Antineoplastic Agents
7.
Clinics ; 73(supl.1): e478s, 2018. tab, graf
Article in English | LILACS | ID: biblio-952835

ABSTRACT

The main goal of chemotherapeutic drugs is to induce massive cell death in tumors. Cisplatin is an antitumor drug widely used to treat several types of cancer. Despite its remarkable efficiency, most tumors show intrinsic or acquired drug resistance. The primary biological target of cisplatin is genomic DNA, and it causes a plethora of DNA lesions that block transcription and replication. These cisplatin-induced DNA lesions strongly induce cell death if they are not properly repaired or processed. To counteract cisplatin-induced DNA damage, cells use an intricate network of mechanisms, including DNA damage repair and translesion synthesis. In this review, we describe how cisplatin-induced DNA lesions are repaired or tolerated by cells and focus on the pivotal role of DNA repair and tolerance mechanisms in tumor resistance to cisplatin. In fact, several recent clinical findings have correlated the tumor cell status of DNA repair/translesion synthesis with patient response to cisplatin treatment. Furthermore, these mechanisms provide interesting targets for pharmacological modulation that can increase the efficiency of cisplatin chemotherapy.


Subject(s)
Humans , DNA Damage/genetics , Cisplatin/therapeutic use , Drug Resistance, Neoplasm/genetics , DNA Repair/genetics , Antineoplastic Agents/therapeutic use , DNA Damage/drug effects
8.
ABCD arq. bras. cir. dig ; 31(4): e1405, 2018. tab, graf
Article in English | LILACS | ID: biblio-973362

ABSTRACT

ABSTRACT Background: Esophageal squamous cell carcinoma is an aggressive neoplasia that requires a multidisciplinary treatment in which survival and prognosis are still not satisfactory. The complete pathologic response to neoadjuvant chemotherapy and radiotherapy is considered a good prognosis factor, and esophagectomy is indicated. Aim: Survival analysis of cases with pathologic complete response (ypT0 ypN0) to neoadjuvant chemotherapy and/or radiotherapy, submmitted to esophagectomy. Methods: Between 1983-2014, 222 esophagectomies were performed, and 177 were conducted to neoadjuvant treatment. In 34 patients the pathologic response was considered complete. Medical records of the patients were retrospectively reviewed regarding type of chemotherapy applied, amount of radiotherapy, interval between the neoadjuvant therapy and the surgery, body mass index; postoperative complications; hospital admission time and survival. Results: The average age was 55.8 years. Twenty-five patients were subjected to chemotherapy and radiotherapy, and nine to neoadjuvant radiotherapy. The total radiation dose ranged from 4400 until 5400 cGy. The chemotherapy was performed with 5FU, cisplatin, and carbotaxol, concomitantly with the radiotherapy. The esophagectomy was transmediastinal, followed by the cervical esophagogastroplasty performed on a average of 49.4 days after the neoadjuvant therapy. The hospital admission time was an average of 14.8 days. During the follow-up period, 52% of the patients submitted to radiotherapy and chemotherapy were disease-free, with 23.6% of them presenting more than five years survival. Conclusions: The neoadjuvant treatment followed by esophagectomy in patients with pathologic complete response is beneficial for the survival of patients with esophageal squamous cell carcinoma.


RESUMO Racional: O carcinoma epidermoide do esôfago é neoplasia de natureza agressiva, que requer tratamento multidisciplinar e tem taxas de sobrevida e prognóstico ainda não satisfatórios. A resposta patológica completa à neoadjuvância com quimioterapia e radioterapia é considerada fator de bom prognóstico e a esofagectomia está indicada. Objetivo: Análise de sobrevida dos casos com resposta patológica completa (ypT0 ypN0) à neoadjuvância com quimioterapia e/ou radioterapia, submetidos à esofagectomia. Métodos: Entre 1983-2014, 222 esofagectomias foram realizadas e 177 foram submetidas ao tratamento neoadjuvante. Em 34 pacientes, a resposta patológica foi considerada completa. Os prontuários dos pacientes foram revisados retrospectivamente quanto ao tipo de quimioterapia aplicada, quantidade de radioterapia, intervalo entre a terapia neoadjuvante e a operação, índice de massa corporal (IMC), complicações pós-operatórias, tempo de internação hospitalar e sobrevida. Resultados: A idade média foi de 55,8 anos. Vinte e cinco pacientes foram submetidos a quimioterapia e radioterapia e nove à radioterapia neoadjuvante. A dose total de radiação variou de 4400 até 5400 cGy. A quimioterapia foi realizada com 5FU, cisplatina e carbotaxol, concomitantemente à radioterapia. A esofagectomia foi transmediastinal, seguida da esofagogastroplastia cervical realizada em média 49,4 dias após a terapia neoadjuvante. O tempo de internação hospitalar foi em média de 14,8 dias. Durante o período de seguimento, 52% dos pacientes submetidos a radioterapia e quimioterapia estavam livres de doença, com 23,6% apresentando sobrevida maior que cinco anos. Conclusão: O tratamento neoadjuvante seguido de esofagectomia, nos pacientes com resposta patológica completa, oferece benefícios na sobrevida de portadores de carcinoma epidermoide do esôfago.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Esophageal Neoplasms/mortality , Esophageal Neoplasms/therapy , Esophagectomy/mortality , Esophageal Squamous Cell Carcinoma/mortality , Esophageal Squamous Cell Carcinoma/therapy , Time Factors , Esophageal Neoplasms/pathology , Retrospective Studies , Analysis of Variance , Cisplatin/therapeutic use , Treatment Outcome , Disease-Free Survival , Neoadjuvant Therapy/mortality , Chemoradiotherapy/mortality , Esophageal Squamous Cell Carcinoma/pathology , Antineoplastic Agents/therapeutic use
9.
Yonsei Medical Journal ; : 51-56, 2018.
Article in English | WPRIM | ID: wpr-742505

ABSTRACT

PURPOSE: 14-3-3ζ regulates cell signaling, cell cycle progression, and apoptosis, and its overexpression is associated with disease recurrence and poor clinical outcomes in some solid tumors. However, its clinicopathological role in ovarian cancer is unknown. Our goal was to investigate whether 14-3-3ζ is associated with ovarian cancer prognosis. MATERIALS AND METHODS: We examined 14-3-3ζ expression by immunohistochemistry in ovarian cancer tissues obtained from 88 ovarian cancer patients. The examined tissues were of various histologies and stages. 14-3-3ζ expression was also analyzed by western blot in seven ovarian cancer cell lines and a primary ovary epithelial cell line. Cell viability was measured using an MTS-based assay following cisplatin treatment. RESULTS: Among the ovarian cancer samples, 53.4% (47/88) showed high 14-3-3ζ expression, and 14-3-3ζ overexpression was positively correlated with more advanced pathologic stages and grades. 14-3-3ζ overexpression was also significantly associated with poor disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients. Median DFS and OS were 1088 and 3905 days, respectively, in the high 14-3-3ζ expression group, but not reached in the low 14-3-3ζ expression group (p=0.004 and p=0.033, log-rank test, respectively). Downregulating 14-3-3ζ by RNA interference in ovarian cancer cells led to enhanced sensitivity to cisplatin-induced cell death. CONCLUSION: 14-3-3ζ overexpression might be a potential prognostic biomarker for ovarian cancer, and the inhibition of 14-3-3ζ could be a therapeutic option that enhances the antitumor activity of cisplatin.


Subject(s)
14-3-3 Proteins/metabolism , Adult , Aged , Cell Line, Tumor , Cisplatin/therapeutic use , Disease-Free Survival , Down-Regulation , Female , Gene Knockdown Techniques , Gene Silencing , Humans , Immunohistochemistry , Middle Aged , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Prognosis , Young Adult
10.
Rev. ciênc. méd., (Campinas) ; 26(1): 37-40, 9 nov. 2017. ilus
Article in English | LILACS | ID: biblio-875994

ABSTRACT

The aim of the present report is to alert health care workers about a 64­year­old patient diagnosed with adenocarcinoma in the right lung treated with pemetrexed disodium, cisplatin and dexamethasone. He evolved with prolonged neutropenia, symptoms of lower airways infection, and recent pulmonary infiltrate in the radiographic image. The cultures for bacteria and mycobacteria in the blood and sputum were negative. Because of the lack of response to treatment with broad spectrum antibiotics and maintenance of neutropenia, a transbronchial biopsy was performed, which demonstrated infection by Aspergillus fumigatus. The patient was treated.


O objetivo do presente relato é alertar os profissionais de saúde sobre o caso de um paciente de 64 anos de idade com diagnóstico de adenocarcinoma no pulmão direito tratado com pemetrexede dissódico, cisplatina e dexametasona. Ele evoluiu com neutropenia prolongada, sintomas de infecção de vias aéreas inferiores e infiltrado pulmonar recente na imagem radiográfica. As culturas para bactérias e micobactérias no sangue e escarro foram negativas. Por falha na resposta ao tratamento com antibióticos de largo espectro e manutenção da neutropenia, foi realizada biópsia transbrônquica que demonstrou infecção por Aspergillus fumigatus e o paciente foi tratado.


Subject(s)
Humans , Male , Middle Aged , Aspergillus , Immunosuppression , Pulmonary Aspergillosis , Neutropenia , Pneumonia , Dexamethasone/therapeutic use , Adenocarcinoma , Cisplatin/therapeutic use , Pemetrexed/therapeutic use , Lung Neoplasms
11.
Int. braz. j. urol ; 42(5): 942-954, Sept.-Oct. 2016. tab, graf
Article in English | LILACS | ID: lil-796874

ABSTRACT

ABSTRACT The present study describes the histopathological and molecular effects of P-MAPA (Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride) intravesical immunotherapy combined with systemic doxorubicin or cisplatin for treatment of non-muscle invasive bladder cancer (NMIBC) in an appropriate animal model. Our results showed an undifferentiated tumor, characterizing a tumor invading mucosa or submucosa of the bladder wall (pT1) and papillary carcinoma in situ (pTa) in the Cancer group. The histopathological changes were similar between the combined treatment with intravesical P-MAPA plus systemic Cisplatin and P-MAPA immunotherapy alone, showing decrease of urothelial neoplastic lesions progression and histopathological recovery in 80% of the animals. The animals treated systemically with cisplatin or doxorubicin singly, showed 100% of malignant lesions in the urinary bladder. Furthemore, the combined treatment with P-MAPA and Doxorubicin showed no decrease of urothelial neoplastic lesions progression and histopathological recovery. Furthermore, Akt, PI3K, NF-kB and VEGF protein levels were significantly lower in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments than other groups. In contrast, PTEN protein levels were significantly higher in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments. Thus, it could be concluded that combination of intravesical P-MAPA immunotherapy and systemic cisplatin in the NMIBC animal model was effective, well tolerated and showed no apparent signs of antagonism between the drugs. In addition, intravesical P-MAPA immunotherapy may be considered as a valuable option for treatment of BCG unresponsive patients that unmet the criteria for early cystectomy.


Subject(s)
Animals , Female , Urinary Bladder Neoplasms/therapy , Carcinoma/therapy , Doxorubicin/therapeutic use , Cisplatin/therapeutic use , Immunotherapy/methods , Membrane Proteins/therapeutic use , Antineoplastic Agents/therapeutic use , Rats, Inbred F344 , Urinary Bladder Neoplasms/pathology , Administration, Intravesical , BCG Vaccine , Carcinoma/pathology , Blotting, Western , Reproducibility of Results , NF-kappa B/analysis , Treatment Outcome , Combined Modality Therapy , Disease Progression , Phosphatidylinositol 3-Kinases/analysis , Models, Animal , Vascular Endothelial Growth Factor A/analysis , PTEN Phosphohydrolase/analysis , Proto-Oncogene Proteins c-akt/analysis
12.
Rev. chil. cir ; 68(5): 355-362, oct. 2016. graf, tab
Article in Spanish | LILACS | ID: lil-797352

ABSTRACT

Objetivo: Reportar resultados de nuestro protocolo de radioquimioterapia concomitante exclusiva en el cáncer de orofaringe avanzado. Materiales y métodos: Estudio retrospectivo que incluyó 87 pacientes. Se realizó radioterapia concomitante con cisplatino semanal. Se aceptó la realización de fraccionamiento convencional (FC), hiperfraccionamiento (Hfx) o fraccionamiento acelerado tipo boost concomitante (FABC). Se revisó la sobrevida global (SG), sobrevida libre de enfermedad (SLE), sobrevida libre de recidiva local (SLRL) y regional (SLRR) según subsitio y fraccionamiento. Resultados: Ingresaron 87 pacientes. Mediana de seguimiento: 120 meses. El 53, 30 y 17% recibieron FC, FABC y Hfx respectivamente. La SG a 2, 5 y 10 años fue de un 73, 61 y 43% respectivamente. La SG a 5 años según subsitio anatómico fue: amígdala 74%, paladar blando 33%, base de lengua 33%, y pared faríngea posterior 33%. Al comparar la SG de amígdala versus otros subsitios se alcanza una diferencia estadísticamente significativa (p < 0,001). La mediana de SG para amígdala no fue alcanzada, mientras que en otros subsitios fue de 22 meses. La SLE fue diferente en los distintos subsitios, superior en amígdala y diferente entre los distintos fraccionamientos, a favor de Hfx, alcanzando diferencias significativas. Las mismas tendencias se demostraron en SLRL y SLRR. Observamos un 23% de segundos primarios, siendo el pulmón el sitio más frecuente. Conclusión: La radioterapia concomitante con cisplatino semanal es un tratamiento adecuado para el cáncer de orofaringe. Ofrece excelentes resultados en cáncer de amígdala, especialmente con fraccionamiento modificado. Para los otros subsitios nos parece recomendable explorar nuevas estrategias de tratamiento.


Objective: To report results of our concomitant radiochemotherapy protocol for advanced oropharyngeal cancer. Materials and methods: Retrospective study. Concomitant radiochemotherapy was performed with weekly cisplatin. Conventional fractionation (CF), hyperfractionation (Hfx) or accelerated fractionation with concomitant boost (FABC) were accepted. Overall survival (OS), Disease-free survival (RFS), Local relapse-free survival (LRFS) and Regional relapse-free survival (RRFS) were calculated, according subsite and radiotherapy fractionation. Results: We found 87 patients. Median follow-up: 120 months. 53%, 30% and 17% received FC, FABC, Hfx respectively. OS at 2, 5 and 10 years was 73%, 61% and 43% respectively. The 5-year OS was, by anatomic subsite: Tonsillar 74%, 33% soft palate, base of tongue 33%, and 33% for posterior pharyngeal wall. By comparing the OS in tonsil versus other subsites we found statistically significant difference in favor of tonsillar cancer (P < .001). Median OS for tonsillar cancer was not achieved, while in other subsites was 22 months. DFS was different in different subsites, better for amygdala and different among different fractionations, better for Hfx, reaching significant differences. The same trends were demonstrated in LRFS and RRFS. We observed a 23% of second cancers, being lung the most common site. Conclusion: Concomitant radiotherapy with weekly cisplatin is an appropriate treatment for oropharyngeal cancer. It provides excellent outcomes in tonsillar cancer, especially with modified fractionation and Hfx type. For other subsites it seems advisable to explore a new treatment approach.


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/radiotherapy , Oropharyngeal Neoplasms/radiotherapy , Dose Fractionation, Radiation , Radiotherapy/adverse effects , Carcinoma, Squamous Cell/drug therapy , Oropharyngeal Neoplasms/drug therapy , Survival Analysis , Retrospective Studies , Follow-Up Studies , Cisplatin/therapeutic use , Treatment Outcome , Radiotherapy, Intensity-Modulated/methods
13.
Yonsei Medical Journal ; : 1276-1281, 2016.
Article in English | WPRIM | ID: wpr-79763

ABSTRACT

Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3-12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10-22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis.


Subject(s)
Adult , Carcinoma, Hepatocellular/complications , Chemoradiotherapy , Cisplatin/therapeutic use , Disease-Free Survival , Female , Fluorouracil/therapeutic use , Humans , Liver Neoplasms/complications , Liver Transplantation , Living Donors , Male , Middle Aged , Neoplasm Recurrence, Local , Portal Vein , Venous Thrombosis/complications
14.
Oncol. clín ; 21(3): 65-70, 2016. tab
Article in Spanish | LILACS | ID: biblio-882193

ABSTRACT

El objetivo fue analizar retrospectivamente, en pacientes con cáncer de cuello uterino localmente avanzado tratados en nuestro centro, el perfil de toxicidad de la radioterapia concurrente con platinos mono droga o combinados con gemcitabine y su impacto en el tratamiento. Estudio descriptivo, retrospectivo y observacional de pacientes con cáncer de cuello uterino localmente avanzado (estadios IIa/IVa) desde marzo de 2011 a febrero de 2016. Se analizaron características patológicas, dosis de tratamiento radiante y quimioterápico, así como toxicidades graves (GIII/IV) y su impacto en el tratamiento, observado como reducción o suspensión de dosis y/o split de radioterapia (RT). Se evaluaron 60 pacientes, edad mediana 47 años (17-75), 93% PS0-1. Histología: escamoso (89%) y adenocarcinoma (8%). Estadio IIb 24 (40%) y IIIb 16 (27%). Dosis de RT utilizada 5040cGy; 35 (58%) realizaron boost y 47 (78%) braquiterapia posterior. Cuarenta y cinco realizaron tratamiento concurrente con PLA y 15 con platinos/gemcitabine (PLA/GEM). En el grupo que recibió PLA, uno requirió reducción de dosis de quimioterapia (QT), dos suspendieron algún ciclo por toxicidad y tres realizaron split de RT. El 100% completó el tratamiento de quimioradioterapia (QRT) concurrente. En el grupo que recibió PLA/GEM: 9 requirieron reducción de dosis de QT, 11 suspendieron algún ciclo y 4 no completaron el esquema por toxicidad; 4 hicieron split de RT, y 87% completó el tratamiento de RT. En este estudio, el esquema concurrente con quimioterapia combinada muestra mayor toxicidad que impacta en el cumplimiento del tratamiento, 15% no lo completó por toxicidades graves. No obstante, un correcto manejo institucional de toxicidades, permite utilizar la combinación de tratamiento para obtener potenciales beneficios (AU)


This is a retrospective analysis of profile toxicity and treatment impact of gemcitabine plus platinum radiotherapy in patients with locally advanced cervix cancer, treated at our Centre. Descriptive, retrospective and observational study of patients with locally advanced cervix cancer (Ila/IVa stages), since March 2011 until February 2016. The analysis included the pathological characteristics, chemo radiotherapy doses, as well as severs toxicity (GIII/V) and it impact in treatment observed as reduction or suspension of doses and/or radiotherapy (RT) split. There were evaluated 60 patients of 47 median age (17-75), 93-5 PS0-1. Histology: 89% of squamous cell carcinoma and 8% of adenocarcinoma. 40% of IIb 24 and 27% of IIIB 16 stages. RT doses used 5040cGy; 35 pts (58%) did boost and 47 pts (78%) followed with brachytherapy. 45pts took PLA concurrent treatment, 15pts gemcitabine plus platinum (PLA/GEM). Regarding PLA group, one required a doses reduction of chemotherapy (QT), 2pts suspended a cycle due to toxicity and 3pts did RT split. 100% pts completed chemo radiotherapy (QRT) concurrent treatment. Regarding PLA/GEM group: 9pts required QT doses reduction, 11pts suspended a cycle due to toxicity and 4 didn´t complete the cycle due to toxicity; 4 did RT split and 87% completed RT. The study shown that the scheme of concurrent combined chemotherapy presents higher toxicity that impacts in the fulfillment of treatment, 66 ONCOLOGÍA CLÍNICA - Vol. 21 Nº 3 - Diciembre 2016 15% couldn´t complete due to sever toxicity. However, a correct institutional manage of toxicities allows to use treatment combination to obtain potential benefits (AU)


Subject(s)
Cisplatin/therapeutic use , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/drug therapy , Magnetic Resonance Imaging , Radiotherapy
15.
Int. braz. j. urol ; 41(6): 1067-1079, Nov.-Dec. 2015. tab, graf
Article in English | LILACS | ID: lil-769747

ABSTRACT

Objectives: The objective of this study was to update the long-term outcome in the treatment of locally advanced upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU) regarding the role of adjuvant chemotherapy. Materials and methods: Clinical data from 138 patients who underwent RNU for locally advanced UTUC (pT3/4 or pN+) were analyzed. Results: The adjuvant chemotherapy group comprised 66 patients, and other 72 patients did not receive adjuvant chemotherapy. Cisplatin-based chemotherapy was the most common regimen, depending on the patient's eligibility and renal function. The median follow-up period was 48.7 months (interquartile range: 29.2-96.9 months). The 3-and 5-year disease-specific survival (DSS) rates were 76.0% and 69.9% for the non-adjuvant chemotherapy group versus 74.6% and 54.5% for the adjuvant chemotherapy group (p=0.301, log-rank test). Overall survival (OS) rates for the same time period were 70.1% and 62.9% for the non-adjuvant chemotherapy group versus 73.8% and 53.2% for the adjuvant chemotherapy group (p=0.931, log-rank test). On multivariate analysis, adjuvant chemotherapy could not predict DSS and OS after surgery. When patients who received cisplatin-based adjuvant chemotherapy (n=59) were compared to those who did not receive adjuvant chemotherapy, similar results were found. Conclusions: There does not appear to be a significant DSS or OS benefit associated with adjuvant chemotherapy. Prospective randomized clinical trials are necessary to verify the effect of adjuvant chemotherapy on locally advanced UTUC.


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Antineoplastic Agents/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Cisplatin/therapeutic use , Ureteral Neoplasms/drug therapy , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/surgery , Chemotherapy, Adjuvant/methods , Disease-Free Survival , Hospitals, University , Kaplan-Meier Estimate , Multivariate Analysis , Nephrectomy/methods , Prognosis , Retrospective Studies , Seoul , Time Factors , Ureteral Neoplasms/pathology , Ureteral Neoplasms/surgery
16.
Article in English | WPRIM | ID: wpr-55049

ABSTRACT

Proliferation activity has already been established as a prognostic marker or as a marker for anticancer drug sensitivity. In gastric cancer, however, the prognostic significance of proliferation activity is still being debated. Several studies evaluating proliferation activity using Ki-67 have shown controversial results in terms of the relationship between proliferation activity and overall survival (OS) or drug sensitivity in gastric cancer patients. Because cytoskeleton-associated protein 2 (CKAP2) staining has recently been introduced as a marker of proliferation activity, we analyzed 437 gastric cancer tissues through CKAP2 immunohistochemistry, and we evaluated the chromatin CKAP2-positive cell count (CPCC) for proliferation activity. Although the CPCC did not show any significant correlation with OS in the male, female or total number of cases, it did show a significant correlation in the T1 or T2 male patient subgroup, according to log-rank tests (P=0.001) and univariate analysis (P=0.045). Additionally, multivariate analysis with the Cox proportional hazard regression model showed a significant correlation between the CPCC and OS (P=0.039) for the co-variables of age, gender, T stage, N stage, histology, tumor location, tumor size and adjuvant chemotherapy. In male gastric cancer cell lines, faster-growing cancer cells showed higher sensitivity to cisplatin than slow-growing cells. Thus our study indicates that CPCC-measured proliferation activity demonstrates a significantly worse prognosis in T1 or T2 male gastric cancer patients. The CPCC will help to more precisely classify gastric cancer patients and to select excellent candidates for adjuvant chemotherapy, which in turn will facilitate further clinical chemotherapeutic trials.


Subject(s)
Aged , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/analysis , Cell Proliferation , Cisplatin/therapeutic use , Cytoskeletal Proteins/analysis , Female , Humans , Immunohistochemistry , Male , Middle Aged , Multivariate Analysis , Prognosis , Proportional Hazards Models , Stomach/drug effects , Stomach Neoplasms/diagnosis , Survival Analysis
17.
Article in English | WPRIM | ID: wpr-157197

ABSTRACT

Hepatoblastoma usually occurs in children under the age of 2 years, with very few cases reported in adults. We experienced a case of adult hepatoblastoma in a 36-year-old female with chronic hepatitis B . She had experienced sudden onset abdominal pain. Her serum alpha-fetoprotein level was markedly elevated, and abdominal CT showed a 9-cm mass with internal hemorrhage in the right hepatic lobe with hemoperitoneum, so an emergency hepatic central bisectionectomy was performed. The initial histologic examination revealed that the mass mimicked combined hepatocellular carcinoma and cholangiocarcinoma with spindle-cell metaplasia of the cholangiocarcinoma element. Follow-up abdominal CT performed 3 months later showed a 5.5-cm metastatic mass in the left subphrenic area. Laparoscopic splenectomy with mass excision was performed, and hepatoblastoma was confirmed histologically. A histologic re-examination of previously obtained surgical specimens also confirmed the presence of hepatoblastoma. Metastatic hepatoblastoma was found at multiple sites of the abdomen during follow-up, and so chemotherapy with cisplatin, 5-fluorouracil (5-FU), and vincristine was applied, followed by carboplatin and doxorubicin . Despite surgery and postoperative chemotherapy, she died 12 months after symptom onset.


Subject(s)
Adult , Carcinoma, Hepatocellular/pathology , Cholangiocarcinoma/pathology , Cisplatin/therapeutic use , Diagnostic Errors , Doxorubicin/therapeutic use , Drug Therapy, Combination , Female , Fluorouracil/therapeutic use , Hepatitis B, Chronic/complications , Hepatoblastoma/drug therapy , Humans , Liver Neoplasms/drug therapy , Tomography, X-Ray Computed , Vincristine/therapeutic use
18.
Article in English | WPRIM | ID: wpr-142449

ABSTRACT

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.


Subject(s)
Animals , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/blood , Carcinoma, Non-Small-Cell Lung/blood , Cell Line, Tumor , Cisplatin/therapeutic use , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Lung/drug effects , Lung Neoplasms/blood , Male , Mice , Mice, Nude , MicroRNAs/blood , Middle Aged , Prognosis , Survival Analysis , Treatment Outcome
19.
Article in English | WPRIM | ID: wpr-142448

ABSTRACT

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.


Subject(s)
Animals , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/blood , Carcinoma, Non-Small-Cell Lung/blood , Cell Line, Tumor , Cisplatin/therapeutic use , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Lung/drug effects , Lung Neoplasms/blood , Male , Mice , Mice, Nude , MicroRNAs/blood , Middle Aged , Prognosis , Survival Analysis , Treatment Outcome
20.
Rev. cuba. farm ; 48(4)oct.-dic. 2014. ilus, tab
Article in Spanish | LILACS, CUMED | ID: lil-748781

ABSTRACT

INTRODUCCIÓN: la mangiferina posee diferentes propiedades farmacológicas, y otras están por ser investigadas, tal como su actividad antitumoral como agente adyuvante a la quimioterapia antineoplásica convencional en la terapia combinada. OBJETIVO: evaluar el efecto antiproliferativo de la mangiferina sola y combinada con concentraciones bajas de agentes quimioterapéuticos. MÉTODOS: las líneas celulares de carcinoma de colon de ratón CT26.WT y normal de ovario de hámster chino CHO-K1, se trataron con mangiferina en combinación con cisplatino y 5-fluorouracilo bajo diferentes esquemas de tratamiento (secuencial y simultáneo), a diferentes concentraciones y tiempos de incubación. La viabilidad celular se determinó por el ensayo de MTT. RESULTADOS: la mangiferina (1-200 µg/mL) no fue citotóxica para ambas líneas celulares. El cotratamiento secuencial con mangiferina (1-200 µg/mL) por 3 h y cisplatino a concentraciones no citotóxicas (1 µM y 5 µM) durante 72 h, mostró un incremento significativo de la muerte celular en CT26.WT, sin inducir incremento significativo de la muerte en células CHO-K1, a concentraciones bajas de ambos compuestos. En el caso de los cotratamientos con mangiferina y 5-fluorouracilo (0,1 µM y 0,5 µM), se incrementó significativamente la muerte celular en los cotratamientos simultáneo por 72 h y secuencial 5-fluorouracilo 72 h y mangiferina 24 h en células CT26.WT; pero solo en este último, no se incrementó significativamente la muerte celular en CHO-K1. CONCLUSIONES: la mangiferina en combinación con concentraciones bajas no citotóxicas de cisplatino y 5-fluorouracilo, promueve la muerte celular e incrementa la citotoxicidad de estos agentes quimioterapéuticos en las condiciones de experimentación realizadas(AU)


INTRODUCTION: mangiferin has several pharmacological properties, but others remain to be deeply explored, such as antitumor activity since it may serve as adjuvant agent in conventional antitumoral chemotherapy in a combined treatment. OBJECTIVE: to evaluate the antiproliferative effect of the use of mangiferin alone and in combination with low concentrations of chemotherapeutic agents. METHODS: the CT26.WT mouse colon carcinoma and the CHO-K1 hamster ovary normal cell lines were treated with mangiferin in combination with cisplatin and 5-fluorouracil in several treatment schedules (sequential and simultaneous), at different concentrations and incubation times. The cell viability was evaluated by MTT assay. RESULTS: mangiferin (1-200 µg/mL) was not cytotoxic in both cell lines. Mangiferin (1-200 µg/mL) for 3h plus cisplatin at not citotoxic concentrations (1 µM and 5 µM) for 72 h in sequential combined treatment showed a significant increase of cell death in CT26.WT, without inducing significant increase of cell death in CHO-K1 cells at low concentrations of both compounds. In the case of combined mangiferina and 5-fluorouracil (0,1 µM and 0,5 µM) treatments, cell death rose in a significant way in simultaneous combined treatments for 72 h whereas sequential combined therapy with 5-fluorouracil for 72 h plus mangiferin for 24 h in CT26.WT cells, a significant rise was not induced in the cell line death of CHO-K1 hamster CONCLUSIONS: mangiferin in combination with low non cytotoxic concentrations of cisplatin and 5-fluorouracil promotes cell death and increases the cytotoxicity of these chemotherapeutic agents in experimental conditions of this study(AU)


Subject(s)
Rats , Antineoplastic Combined Chemotherapy Protocols , /therapeutic use , Cisplatin/therapeutic use , Fluorouracil/therapeutic use
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