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BACKGROUND: Brain metastases significantly reduce the survival of cancer patients. However, detailed researches on the clinical manifestations and prognoses of patients with brain metastases are lacking. The aim of this study was to investigate the clinical features and prognostic factors of cancer patients with brain metastases. METHODS: A retrospective study was conducted on patients with brain metastases who were treated in our hospital between January 2014 and January 2019. Comparison of overall survival (OS) was performed by the Kaplan-Meier method. Multivariate Cox regression models was used to identify prognostic factors for OS. RESULTS: A total of 190 patients with complete data and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 were enrolled. Patients with brain metastases from different primary sites had significantly different survival time (P=0.001). Patients who had a longer survival time included female patients (47.4%) (34 vs. 19 months, P=0.002), those with age <65 years (63.7%) (29 vs. 18 months, P=0.002), with ECOG 0 or 1 (44.2%) (32 vs. 21 months, P=0.005), with ≤3 brain lesions (61.1%) (29 vs. 20 months, P=0.041), and with small molecular targeted therapy (48.4%) (21 vs. 18 months, P=0.006). Furthermore, multivariate analysis revealed that female, age <65 years, ≤3 brain lesions, small molecular targeted therapy were independent favorable prognostic factors of OS. CONCLUSIONS: Female, younger patients with ≤3 brain metastases predicted a better survival. To improve the poor outcomes of these patients, it is necessary to find clinically significant genetic abnormalities and administer the small molecular targeted therapy early in the course of treatment.
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OBJECTIVE: Cancer patients with bone marrow metastases are rare and dismal. The study was to identify the clinical features and prognostic factors in cancer patients with bone marrow metastases. PATIENTS AND METHODS: A total of 30 patients with bone marrow metastases were reviewed between September 2007 and September 2013. Bone marrow metastases were identified by bone marrow aspiration. RESULTS: The median age was 56.5 years (range, 8-85 years). The two most common primary tumor sites were the stomach (7, 23.3%), breast (5, 16.7%). Bone metastases (27, 90.0%) were the most common concurrent metastases. The most common cause for bone marrow aspiration was anemia and thrombocytopenia (10, 33.3%). The median survival time was 3 months (range, 0.5-82 months). Patients with good performance status (n = 19) had a longer median survival time than patients with poor performance status (n = 11) (8 months vs. 1 months, P = 0.041). Patients with primary unknown origin (n = 5) had a significantly shorter overall survival time than patients with known origin (n = 25) (1 month vs. 6 months = 0.010). The median survival time was 9 months in the systemic therapy group (n = 21) and 1 month in the best supportive care group (n = 9) (P = 0.000). CONCLUSION: To make primary origin clear and start systemic antitumor therapy is beneficial for patients with bone marrow metastases.
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Neoplasias de la Médula Ósea/mortalidad , Neoplasias de la Médula Ósea/secundario , Neoplasias/mortalidad , Neoplasias/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Médula Ósea/terapia , Niño , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Pronóstico , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: The role of microRNA (miRNA) in cholangiocarcinoma was not clear. The aim of this study was to find the potential diagnostic and prognostic miRNA in cholangiocarcinoma patients. METHODS: The miRNA expression profiles in cholangiocarcinoma patients from The Cancer Genome Atlas and Gene Expression Omnibus (GSE53870) were analyzed. The comparison of overall survival was performed using the Kaplan-Meier method. The targeted genes of prognostic miRNA were identified in miRanda, PicTar, or TargetScan, and their cell signaling pathways were analyzed by the Database for Annotation, Visualization and Integrated Discovery. RESULTS: In The Cancer Genome Atlas and the Gene Expression Omnibus miRNA dataset, miR-92b and miR-99a were found with concordant directionality, up-regulated and down-regulated, respectively. In The Cancer Genome Atlas survival data, patients with the high level of miR-99b had obviously shorter overall survival time ( P=0.038). However, the level of miR-99a was not found to be significant. The 17 shared target genes of miR-92b were identified, such as DAB21IP, BCL21L11, SPHK2, PER2, and TSC1. The related pathways included positive regulation of transcription, positive regulation of cellular biosynthetic process, regulation of programmed cell death, etc. Conclusion: miR-92b was up-regulated in cholangiocarcinoma compared with normal controls. The high level of miR-92b was associated with adverse outcomes in cholangiocarcinoma patients, which might be partly explained by the targeted genes of miR-92b and their signaling pathways.
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Biomarcadores de Tumor/genética , Colangiocarcinoma/genética , MicroARNs/genética , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Colangiocarcinoma/patología , Supervivencia sin Enfermedad , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Transducción de Señal/genéticaRESUMEN
OBJECTIVE: To investigate the therapeutic effectiveness and side effects of decitabine combined with or without cytarabine-based low dose regimen for acute myeloid leukemia in geratic patients. METHODS: Clinical data of 8 geratic patients (aged over 70 years) suffered from acute myeloid leukemia from September 2009 to March 2012 were analyzed retrospectively, including age, sex, peripheral blood and bone marrow characteristics and so on. These patients were treated by an 1-hour intravenous infusion of decitabine 20 mg/m2 per day for 5 consecutive days every 4 weeks combined with or without low dose regimen dominantly consisting of cytarabine 20 mg per day as subcutaneous injection for seven consecutive days. The therapeutic effectiveness and side-effects were evaluated. RESULTS: Among 8 patients, incinding 3 males and 5 females aged between 71-84 years old, their median white blood cell count was 31.2(1.38-179)× 109/L, and median bone marrow blast cell ratio was 42.7(23-94)% at the initial diagnosis.The median treatment courses was 2.5 (1-20).After treatment by this protocol,2 patients achieved complete remission(CR) (25%), 2 patients achieved partial remission (PR)(25%), 3 were not relieved, and 1 died, thus the overall response rate reached to 50% (4/8). The median overall survival time was 9.5 (2-36) months, and the overall survival time of 3 patients reached 1 year or more. The main side-effects of treatment were grade III-IV of myelosuppression (87.5%) and pneumonia (50%). CONCLUSION: Decitabine combined with or without cytarabine-based low dose regimen is promising for the treatment of geriatric acute myeloid leukemia, thus improving the overall response rate, and prolonging overall survival time.
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Leucemia Mieloide Aguda , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica , Azacitidina/análogos & derivados , Citarabina , Decitabina , Femenino , Humanos , Masculino , Inducción de Remisión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The concept of bacteria-based microrobot has been well recognized. It has shown great advantages and potentials for the early diagnosis and early treatment of malignant tumor and in reducing chemotherapy toxicities. In this article we review the concept,structure,and potential clinical applications of bacteria-based microrobot.
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Bacterias , Robótica , Humanos , Neoplasias/terapiaRESUMEN
Recent population studies provide clues that the use of curcumin may be associated with reduced incidence and improved prognosis of certain cancers. In the present study, we demonstrated that curcumin acted as a growth inhibitor for lung cancer cells. Our results found that curcumin inhibited cell proliferation, which was associated with upregulation of the cyclin-dependent kinase inhibitors, p27 and p21, and downregulation of cyclin D1. In addition, we showed that curcumin induced the expression of forkhead box protein O1 (FOXO1) through activation of extracellular signal-regulated kinase 1/2 signaling. These findings provide evidence for a mechanism that may contribute to the antineoplastic effects of curcumin and justify further work to explore potential roles for activators of FOXO1 in the prevention and treatment of lung cancer.
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Antineoplásicos/farmacología , Curcumina/farmacología , Factores de Transcripción Forkhead/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclina D1/genética , Ciclina D1/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Proteína Forkhead Box O1 , Factores de Transcripción Forkhead/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Metástasis de la NeoplasiaRESUMEN
BACKGROUND: Cancer/testis antigens (CTAs) are ideal targets for cancer immunotherapy in virtue of their restricted expression profile in normal tissues. However, CTA-targeted immunotherapy has been rather disappointing clinical setting for CTAs are downregulated by cytosine-phosphate-guanosine (CpG) methylation in their promoter regions, so that tumor cells have low immunogenicity. METHODS: We reinduced mouse CTA P1A through demethylation process and generated P1A-specific cytotoxic lymphocytes (CTLs) by immunizing BALB/c (H-2(d)) mice with dendritic cells pulsed with a P1A-specific peptide and CpG oligodeoxynucleotide (ODN) immune adjuvant. RESULTS: We found that demethylation and CpG ODN immune adjuvant stimulation facilitated DC maturation and enhanced the allogenic capacity of P1A-specific CTLs against target cells both in vitro and in vivo. CONCLUSIONS: Our results suggested that CTA induction and immune adjuvant stimulation is a feasible strategy in cancer immunotherapy.
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Antígenos de Neoplasias/inmunología , Antígenos de Neoplasias/metabolismo , Metilación de ADN/efectos de los fármacos , Células Dendríticas/inmunología , Neoplasias Mamarias Experimentales/genética , Neoplasias Mamarias Experimentales/inmunología , Oligodesoxirribonucleótidos/farmacología , Linfocitos T Citotóxicos/inmunología , Animales , Antígenos de Neoplasias/genética , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Citotoxicidad Inmunológica/efectos de los fármacos , Células Dendríticas/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Granzimas/metabolismo , Humanos , Ratones , Ratones Endogámicos BALB C , Péptidos/inmunología , Perforina/metabolismo , Fenotipo , Regiones Promotoras Genéticas/genética , Linfocitos T Citotóxicos/efectos de los fármacosRESUMEN
Impaired local cellular immunity contributes to the pathogenesis of persistent high-risk human papillomavirus (HR-HPV) infection and related cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms remain unclear. Recently, the programmed death 1/programmed death 1 ligand (PD-1/PD-L1; CD279/CD274) pathway was demonstrated to play a critical role in attenuating T-cell responses and promoting T-cell tolerance during chronic viral infections. In this study, we examined the expression of PD-1 and PD-L1 on cervical T cells and dendritic cells (DCs), respectively, from 40 women who were HR-HPV-negative (-) or HR-HPV-positive (+) with CIN grades 0, I and II-III. We also measured interferon-γ, interleukin-12 (IL-12) and IL-10 in cervical exudates. The most common HPV type was HPV 16, followed by HPV 18, 33, 51 and 58. PD-1 and PD-L1 expression on cervical T cells and DCs, respectively, was associated with HR-HPV positivity and increased in parallel with increasing CIN grade. The opposite pattern was observed for CD80 and CD86 expression on DCs, which decreased in HR-HPV+ patients in parallel with increasing CIN grade. Similarly, reduced levels of the T helper type 1 cytokines interferon-γ and IL-12 and increased levels of the T helper type 2 cytokine IL-10 in cervical exudates correlated with HR-HPV positivity and CIN grade. Our results suggest that up-regulation of the inhibitory PD-1/PD-L1 pathway may negatively regulate cervical cell-mediated immunity to HPV and contribute to the progression of HR-HPV-related CIN. These results may aid in the development of PD-1/PD-L1 pathway-based strategies for immunotherapy of HR-HPV-related CIN.
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Antígeno B7-H1/análisis , Células Dendríticas/inmunología , Inmunidad Celular , Papillomaviridae/inmunología , Infecciones por Papillomavirus/inmunología , Receptor de Muerte Celular Programada 1/análisis , Linfocitos T/inmunología , Displasia del Cuello del Útero/inmunología , Neoplasias del Cuello Uterino/inmunología , Adulto , Antígeno B7-1/análisis , Antígeno B7-2/análisis , Biopsia , Estudios de Casos y Controles , Células Dendríticas/virología , Ensayo de Inmunoadsorción Enzimática , Exudados y Transudados/inmunología , Femenino , Citometría de Flujo , Pruebas de ADN del Papillomavirus Humano , Humanos , Interferón gamma/análisis , Interleucina-10/análisis , Interleucina-12/análisis , Estadificación de Neoplasias , Papillomaviridae/genética , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Linfocitos T/virología , Regulación hacia Arriba , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virologíaRESUMEN
Radiotherapy and chemotherapy are the main therapeutic approaches for patients with malignant tumours, especially advanced tumours. However, they can cause adverse effects, one of which is gastrointestinal mucosal damage, which can greatly affect patients' quality of life. Until now, there have been no effective therapies to avoid or treat these adverse effects. In this study, we used attenuated Salmonella typhimurium (S. typhimurium) to deliver the hepatocyte growth factor (HGF) or keratinocyte growth factor (KGF) to murine gastrointestinal mucosa. We found that attenuated S. typhimurium carrying the HGF or KGF genes can effectively reduce the ratio of tumour to non-tumour carcass weight, repair damage to the gastrointestinal mucosal from chemotherapy, improve the immune response, and reduce the mortality rate of mice. Oral administration of attenuated S. typhimurium with HGF and KGF may be promising as a way of improving the quality of life of patients undergoing radiotherapy and chemotherapy.
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Antineoplásicos/efectos adversos , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Factor 7 de Crecimiento de Fibroblastos/genética , Terapia Genética/métodos , Factor de Crecimiento de Hepatocito/genética , Mucosa Intestinal/patología , Animales , Femenino , Vectores Genéticos , Humanos , Mucosa Intestinal/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Radioterapia/efectos adversos , Salmonella typhimurium , TransfecciónRESUMEN
This study aimed to develop a novel multiplex reverse transcription-nested polymerase chain reaction (RT-nPCR) assay to accurately and effectively detect 10 common gene rearrangements in adult acute lymphoblastic leukemia (ALL) and to examine the clinicopathologic characteristics and other genetic aberrations of patients with ALL expressing different fusion genes. Our RT-nPCR assay had a positive detection rate of 35.15% (90/256) for the 10 fusion genes. BCR-ABL1, FUS-ERG, MLL-AF4, ETV6-RUNX1, E2A-PBX1, dupMLL, MLL-AF10, MLL-ENL, SET-NUP214 and SIL-TAL1 were detected in 36 (14.06%), 14 (5.47%), 14 (5.47%), four (1.56%), four (1.56%), five (1.95%), four (1.56%), two (0.78%), two (0.78%) and five patients (1.95%), respectively. The RT-nPCR results were further confirmed by split-out PCR, and cytogenetic and fluorescence in situ hybridization (FISH) analysis revealed corresponding translocations and fusions in 63 and 74 cases, respectively. JAK2 and IKZF1 mutations were commonly detected in patients with BCR-ABL1 ALL, and HOX overexpression was highly correlated with MLL fusions and SET-NUP214. This study demonstrates that RT-nPCR is an effective method for identifying 10 gene rearrangements in adult ALL, and it could potentially be developed for diagnostic use and prognostic studies of ALL.
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Reordenamiento Génico , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Cariotipo Anormal , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Proteínas de Fusión Oncogénica/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Pronóstico , Translocación Genética , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: In severe sepsis, functional impairment and decreased numbers of dendritic cells (DCs) are essential reasons for immune function paralysis, secondary organ infection, and organ failure. We investigated the effects of N-acetylcysteine (NAC) administration on protecting lung DCs function in a zymosan-induced generalized inflammation (ZIGI) model. METHODS: ZIGI was initiated in 80 Balb/c mice by intraperitoneal injection of zymosan (ZYM; 900 mg/kg). Mice were divided into 4 groups: (1) SHAM+Vehicle; (2) SHAM+NAC; (3) ZYM+Vehicle; and (4) ZYM+NAC. NAC (100 mg/kg) was administered at different time after ZYM injection. After 48 h, we assessed: lung tissue pathological changes; arterial blood gas values; purified lung DCs surface expressions of MHC-II/I-A(d) and co-stimulatory molecules CD80, CD83, and CD86; lung DCs mRNA levels of chemokine receptors CCR5 and CCR7; lung DCs apoptosis; lung DCs ultrastructure by transmission electron microscopy; lung DCs NF-kB transcription factor activity; and LPS-stimulated lung DCs in vitro production of IL-12 and IL-10 were examined. RESULTS: NAC treatment resulted in: significant improvements in ZYM-induced lung tissue damage and impaired lung function; inhibited lung DCs ZYM-induced increased expression of MHC-II/I-A(d), CD83, and CD86, but not CD80; reduced lung DCs ZYM-induced CCR5 and CCR7 mRNA levels; suppressed ZYM-induced lung DCs apoptosis; ameliorated ZYM-induced lung DCs ultrastructural abnormalities; inhibited ZYM-induced lung DCs NF-κB activity; and enhanced lung DCs production of IL-12 and inhibited their production of IL-10. CONCLUSIONS: Repeated injections of NAC during the early stage of severe sepsis effectively inhibited lung DCs activation and their apoptosis, which could preserve DCs function.
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Acetilcisteína/administración & dosificación , Células Dendríticas/inmunología , Inflamación/inmunología , Inflamación/metabolismo , FN-kappa B/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/inmunología , Citocinas/biosíntesis , Células Dendríticas/efectos de los fármacos , Células Dendríticas/ultraestructura , Modelos Animales de Enfermedad , Activación Enzimática/efectos de los fármacos , Antígenos de Histocompatibilidad Clase II/inmunología , Inflamación/inducido químicamente , Inflamación/mortalidad , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Masculino , Ratones , ARN Mensajero/genética , Receptores CCR5/genética , Receptores CCR5/metabolismo , Receptores CCR7/genética , Receptores CCR7/metabolismo , Pruebas de Función Respiratoria , Zimosan/efectos adversosRESUMEN
Plasmablastic lymphoma (PBL) is a rare aggressive B-cell lymphoproliferative disorder, which has been characterized by the World Health Organization as a new entity. Although PBL is most commonly seen in the oral cavity of human immunodeficiency virus (HIV)-positive patients, it can also be seen in extra-oral sites in immunocompromised patients who are HIV-negative. Here we present a rare case of PBL of the small intestine in a 55-year-old HIV-negative male. Histopathological examination of the excisional lesion showed a large cell lymphoma with plasmacytic differentiation diffusely infiltrating the small intestine and involving the surrounding organs. The neoplastic cells were diffusely positive for CD79a, CD138 and CD10 and partly positive for CD38 and epithelial membrane antigen. Approximately 80% of the tumor cells were positive for Ki-67. A monoclonal rearrangement of the kappa light chain gene was demonstrated. The patient died approximately 1.5 mo after diagnosis in spite of receiving two courses of the CHOP chemotherapy regimen. In a review of the literature, this is the first case report of PBL with initial presentation in the small intestine without HIV and Epstein-Barr virus infection, and a history of hepatitis B virus infection and radiotherapy probably led to the iatrogenic immunocompromised state.
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Neoplasias Intestinales/terapia , Linfoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígenos CD79/metabolismo , Ciclofosfamida/uso terapéutico , Diagnóstico Diferencial , Doxorrubicina/uso terapéutico , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Neoplasias Intestinales/metabolismo , Intestino Delgado/metabolismo , Antígeno Ki-67/metabolismo , Linfoma/metabolismo , Masculino , Persona de Mediana Edad , Neprilisina/metabolismo , Prednisolona/uso terapéutico , Radioterapia , Sindecano-1/metabolismo , Vincristina/uso terapéuticoRESUMEN
This study was aimed to evaluate the prevalence of FT3-ITD mutation in patients with acute myeloid leukemia (AML) and its significance for prognosis. The bone marrow of 216 patients with AML were detected by using PCR and R-banding methods. On basis of patients' clinical data the clinical feature and prognosis were analyzed. The results showed that in 216 AML patients incidence of FLT3-ITD mutation was 20.83%. FLT3-ITD mutation was present in 24% patients with normal karyotype while in 12.5% patients with abnormal karyotype. The FLT3-ITD positive patients had more white blood cells in peripheral blood and leukemia cells in bone marrow (P < 0.01). The free-disease survival and overall survival time were shorter in FLT3-ITD positive cases than that in FLT3-ITD negative cases (P < 0.05). It is concluded that FLT3-ITD mutation positive patients have more white blood cells in peripheral blood and leukemia cells in bone marrow. The FLT3-ITD mutation may be a danger factor in the AML patients with normal karyotype. It may be helpful for evaluating prognosis and guiding individual treatment of AML.
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Leucemia Mieloide Aguda/genética , Mutación , Tirosina Quinasa 3 Similar a fms/genética , Adulto , Análisis Mutacional de ADN , Supervivencia sin Enfermedad , Femenino , Humanos , Cariotipo , Leucemia Mieloide Aguda/diagnóstico , Masculino , PronósticoRESUMEN
Intralobar sequestration (ILS) is an uncommon abnormality that accounts for 75% of all pulmonary sequestrations. Over the years there have been several reports of various presenting signs of which hemoptysis was commonly described, however, massive hemoptysis and hemothorax is extremely rare in literature. We present a case of a 45-year-old man who died of fatal complication from an ILS. This case report shows an uncommon presentation of ILS with massive hemoptysis and hemothorax resulting in a dramatic course of disease and a fatal outcome, and for this reason in the absence of trauma or other causes for massive hemoptysis, hemothorax, or lung hematoma, this possibility should be kept in mind so as to avoid misdiagnosis, and resection of the sequestered tissue should be considered in all patients.
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Secuestro Broncopulmonar/etiología , Hemoptisis/complicaciones , Hemotórax/complicaciones , Resultado Fatal , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Over-expression of P-glycoprotein (P-gp), encoded by the MDR1 gene, confers multidrug resistance (MDR) in renal cell carcinoma (RCC) and is a major reason for unsuccessful chemotherapy. This study aimed to determine the effct of RNA interference (RNAi) on the reversal of MDR in human RCC. METHODS: We designed and selected one short hairpin RNA (shRNA) targeting MDR1 gene, which is stably expressed from integrated plasmid and transfected by lentivirus fluid in human RCC A498 cell. RESULTS: The MDR1-targeted RNAi resulted in decreased MDR1 gene mRNA level (P < 0.001), almost abolished P-gp expression and reversed MDR to different chemotherapy drugs in the RCC A498 cell line. CONCLUSION: MDR could be reversed by RNAi in human RCC A498 cell line, which may be used for clinical application in future.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Carcinoma de Células Renales/metabolismo , ARN Interferente Pequeño/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Carcinoma de Células Renales/genética , Línea Celular Tumoral , Proliferación Celular , Humanos , Concentración 50 Inhibidora , Lentivirus/genética , ARN Interferente Pequeño/genéticaRESUMEN
The epidermal growth factor receptor (EGFR) family belongs to type I receptor tyrosine kinases. Overexpression or mutation of EGFR/ErbB1 gene has been detected in a large number of human solid tumours. According to some previous report, this gene is not expressed in hematological malignancies. However, two recent clinical case reports showed that erlotinib caused complete remission of acute myeloid leukaemia (AML)-M1 in patients who had both AML-M1 and non-small-cell lung cancer. These results are supported by preclinical studies in which EGFR tyrosine kinase inhibitors have anti-proliferative effects on AML. These findings prompted us to determine whether EGFR is expressed in human AML, through a large-scale screening of both leukaemic cell lines and clinical samples. Our results show that EGFR is expressed by about 33% of human AML (containing M1 to M7 subtypes) and by some human leukaemia cell lines (K562, MEG-01, CEM and SKO-007). Its expression is not limited to certain AML types but has been detected in many leukaemic cells. In addition, EGFR expression was intimately associated with the poor clinical outcomes. Finally, we find that only EGFR-positive leukaemic cells respond to antibody-dependent cellular cytotoxicity of cetuximab, the monoclonal antibodies against EGFR.
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Receptores ErbB/análisis , Leucemia Mieloide Aguda/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Citotoxicidad Celular Dependiente de Anticuerpos , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Femenino , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
ETV6 is an important hematopoietic regulatory factor and ETV6 gene rearrangement is involved in a wide variety of hematological malignancies. In this study, we sought to investigate the incidence of ETV6-associated fusion genes in B- and T-lineage acute lymphoblastic leukemia (ALL) by multiplex-nested reverse transcription-polymerase chain reaction (RT-PCR) in 176 adult ALL patients. Total RNA was extracted from bone marrow samples of ALL patients including 136 B- and 40 T-lineage ALL, and ETV6 fusion genes were detected by multiplex-nested RT-PCR. Changes of ETV6 fusion gene mRNA transcript levels were examined by real-time RT-PCR. We detected a total of 15 ETV6 gene rearrangements with a positive rate of 8.5%, involving seven ETV6-associated fusion genes in 13 B-ALL (13/136, 9.6%) and 2 T-ALL patients (2/40, 5.0%). ETV6-RUNX1 were observed in six cases (3.4%), ETV6-JAK2 in three cases (1.7%), ETV6-ABL1 in two cases (1.1%), and ETV6-ABL2, ETV6-NCOA2, ETV6-SYK, and PAX5-ETV6 each in one case (0.6%). ETV6-JAK2 was found in both B-ALL and T-ALL patients. Furthermore, real-time quantitative RT-PCR assays showed that the ETV6-RUNX1 mRNA transcript levels decreased during conventional chemotherapy or hematopoietic stem cell transplantation. This study shows that multiplex-nested RT-PCR is an effective and accurate tool to identify ETV6 rearrangements in adult ALL, which provides some clues into the diagnosis and prognosis of ALL but also molecular markers for the detection of minimal residual disease in adult ALL.
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Mutación , Proteínas de Fusión Oncogénica/análisis , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Proto-Oncogénicas c-ets/genética , Proteínas Represoras/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Análisis Mutacional de ADN/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Mutación/fisiología , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Proteínas Proto-Oncogénicas c-ets/metabolismo , Proteínas Represoras/metabolismo , Sensibilidad y Especificidad , Translocación Genética/fisiología , Adulto Joven , Proteína ETS de Variante de Translocación 6RESUMEN
BACKGROUND AIMS: Mesenchymal stromal cells (MSC) have been shown to be a promising candidate for tissue regeneration and cancer therapy. However, their therapeutic potential against chemotherapy-induced side-effects remains unclear. METHODS: We treated murine Lewis lung carcinoma (LLC) and xenograft human colon tumors with adriamycin (ADM) for 3 consecutive days followed by one intravenous (i.v.) injection of human umbilical cord (hUC) MSC for several cycles. RESULTS: MSC treatment mitigated ADM-induced cardiomyopathy, reduced the extent of ADM-induced apoptosis in intestinal crypts, suppressed body weight loss in mice treated with ADM and increased the survival rate of mice treated with a lethal dose of ADM. The examination of hematologic parameters indicated a moderate recovery in MSC-injected mice. Systemic administration of MSC did not increase the growth of murine LLC cells and human colon carcinoma in vivo while it strongly inhibited the lung metastases of LLC cells. CONCLUSIONS: We evaluated the prophylactic and therapeutic action of hUC MSC on the chemotherapy agent ADM-induced side-effects in two different tumor models. Our observations suggest that MSC can be used as auxiliary means in chemotherapy for certain tumor types.
Asunto(s)
Carcinoma Pulmonar de Lewis/terapia , Neoplasias del Colon/terapia , Células Madre Mesenquimatosas/citología , Cordón Umbilical/citología , Animales , Antibióticos Antineoplásicos/uso terapéutico , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Neoplasias del Colon/tratamiento farmacológico , Doxorrubicina/uso terapéutico , Humanos , Células Madre Mesenquimatosas/metabolismo , Ratones , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To evaluate the efficacy, side effects and toxicity of imatinib mesylate in the treatment of patients with locally advanced and/or metastatic dermatofibrosarcoma protuberans (DFSP). METHODS: Twenty-four cases of advanced DFSP diagnosed by pathology and treated in our hospital from Nov. 2004 to Oct. 2009 were included in this study. The patients were treated with imatinib mesylate (dosage: 400 mg, po, qd) and carefully observed for treatment efficacy, side effects and survival time. There were 2 patients taking the drug as second line therapy, and other 22 patients as third or more than third line therapy. RESULTS: The 24 patients were evaluable for the efficacy. There were 8 patients (33.3%) with CR, 10 pts (41.7%) PR, 2 patients (8.3%) SD, and 4 patients (16.7%) PD. The disease control rate (DCR = CR+PR+SD) was 83.3%. The median response time in 18 cases with CR and PR was 5.6 months. The median survival time in 20 cases with disease control was 30 months, however, that in nonresponse (PD) cases was only 10 months. Side reactions related to imatinib mesylate included nausea and vomiting (20.8%), neutropenia (12.5%), and edema (8.3%). CONCLUSIONS: Our results are consistent with previous reports in the literature. Imatinib is a safe and effective moleucular target drug used for Chinese. Only mild adverse reactions occur in the treated patients. It is worth using imatinib in the treatment of advanced DFSP patients.
Asunto(s)
Antineoplásicos/uso terapéutico , Dermatofibrosarcoma/tratamiento farmacológico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos/efectos adversos , Benzamidas , Dermatofibrosarcoma/metabolismo , Dermatofibrosarcoma/patología , Edema/inducido químicamente , Femenino , Estudios de Seguimiento , Humanos , Mesilato de Imatinib , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neutropenia/inducido químicamente , Piperazinas/efectos adversos , Proteínas Proto-Oncogénicas c-kit/metabolismo , Pirimidinas/efectos adversos , Receptores del Factor de Crecimiento Derivado de Plaquetas/metabolismo , Inducción de Remisión , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Tasa de Supervivencia , Vómitos/inducido químicamenteRESUMEN
Cellular immunity is an important component of human immune system and plays a crucial role in the fight against tumor cell or invasive pathogens. Researches on cell-based immunotherapy have long been focused on eliciting tumor-specific CD8+ cytotoxic T lymphocytes (CTL) because of their potent killing activity and their ability to reject transplanted organs. However, the resulting treatments have been surprisingly poor at inducing complete tumor rejection, in both the experimental models and clinical trials. The CD4+ T cells has been studied mainly for their role as helpers for CD8+ CTL, even suggesting that the tumor-specific CD4 T regulatory cells could act as suppressors of antitumor responses. Recent studies indicated that CD4+T cells are not a pure cell lineage with single function, but a cell population with complex functions. Moreover CD4+ T cells may not only be helper cells, but also act as potent effector cells or partners with NK cells that can clear a wide variety of tumors. In a word, the antitumor potential of effector CD4+ T cells might have been underestimated. In this article, the classification and differentiation of CD4+ T cells, the function and secreted cytokines of CD4+ T cells, the CD4+ T cells and tumor immune, the tumor-immuno regulatory effects of CD4+ T cells, and clinical researches of CD4+ T cells are reviewed.