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OBJECTIVE: To evaluate the inhibitory effect and its mechanism of celecoxib combined with capecitabine on the growth of implanted H22 hepatoma in mice. METHODS: Tumor model was established by hypodermical injection of H22 cells in BALB/c nude mice. Forty mice were equally randomly divided into 4 groups: control group, celecoxib group (receiving 100 mg/kg celecoxib), capecitabine group (receiving 755 mg/kg capecitabine), and combined treatment group (receiving 100 mg/kg of celecoxib and 755 mg/kg of capecitabine). From the third post-implantation day, each mouse was given relevant drug (or normal saline) by oral gavage. Fifteen days later, all mice were sacrificed and the tumor tissues were measured. The mRNA and protein levels of nuclear factor kappa-B (NF-ΚB) p65 and cyclooxygenase (COX)-2 in tumor tissues were detected by the quantitative polymerase chain reaction (qPCR)and Western blotting, respectively. RESULTS: The tumor inhibition rate was 30.2% in celecoxib group and 49.9% in capecitabine group, which was significantly lower than that (75.4%) in the combined treatment group (P<0.01,P<0.05, respectively). qPCR showed a significant decrease of the mRNA expression of COX-2 in celecoxib group and combined treatment group when compared with control group (P<0.001), but no significant change in NF-ΚB p65.Capecitabine had no significant effects on the mRNA expression of COX-2 and NF-ΚB p65. Western blotting showed that celecoxib and combined treatment significantly inhibited the protein expression of COX-2 and NF-ΚB p65(P<0.05), but not capecitabine. CONCLUSION: Celecoxib can enhance the antitumor effect of capecitabine by inhibiting the expressions of COX-2 and NF-ΚB p65 in mice bearing H22 implanted tumor.
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Desoxicitidina/análogos & derivados , Fluorouracilo/análogos & derivados , Neoplasias Hepáticas/tratamiento farmacológico , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Animales , Capecitabina , Celecoxib , Línea Celular Tumoral , Ciclooxigenasa 2/metabolismo , Desoxicitidina/uso terapéutico , Sinergismo Farmacológico , Fluorouracilo/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Factor de Transcripción ReIA/metabolismoRESUMEN
Endoplasmic reticulum stress (ERS) is a new pathway inducing cell apoptosis that has been discovered in recent years. This study focused on the protective effect of Liangxue Huayu recipe (LHR) on tumor necrosis factor-alpha (TNF-alpha) and D-GalN-induced hepatocyte apoptosis. It found that TNF-alpha and D-GalN could obviously inhibit hepatocyte proliferation, induce cell apoptosis, and significantly increase free calcium ions in cytoplasms, as well as protein expressions of ERS apoptosis-related signal molecules phosphorylated PERK, phosphorylated elF2alpha, cleaved Caspase-12, GRP78 and CHOP. After the administration of LHR of different concentrations, compared with the TNF-alpha/GalN injury group, LHR could significantly alleviated L02 hepatocyte proliferation, decreased cell apoptosis, inhibited growth of intracytoplasmic free calcium content, and gradually reduced the protein expressions of phosphorylated PERK, phosphorylated elF2alpha, cleaved Caspase-12, GRP78 and CHOP. These findings indicated that LHR has the inhibitory effect on TNF-alpha and D-GalN-induced hepatocyte apoptosis. Its mechanism may be related to down-regulation of ERS apoptosis-related signal molecules phosphorylated PERK, phosphorylated elF2alpha, cleaved Caspase-12, GRP78 and CHOP that maintain calcium homeostasis in endoplasmic reticulum.
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Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Chaperón BiP del Retículo Endoplásmico , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Hepatocitos/citología , Humanos , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: More and more novel anticancer drugs have been approved for patients with hematological malignancies in recent years, but HBV reactivation (HBV-R) data in this population is very scarce. This study aimed to evaluated HBV-R risk in patients with hematological malignancies receiving novel anticancer drugs. METHODS: HBV markers and serum HBV DNA levels of patients with hematological malignancies receiving novel anticancer drugs in a tertiary cancer hospital were retrospectively collected. HBV-R risk in the whole cohort and subgroups was described. The relevant literature was reviewed to make a pooled analysis. RESULTS: Of 845 patients receiving novel anticancer drugs, 258 (30.5%) were considered at risk for HBV-R. The median duration of exposure to novel drugs was 5.6 (0.1-67.6) months. The incidence of HBV-R was 2.1% in patients with past HBV infection without prophylactic antiviral treatment (PAT) and 1.2% in all patients at risk of HBV-R. In a pooled analysis of 11 studies with 464 patients, the incidence of HBV-R was 2.4% (95% CI: 1.3-4.2) in all at-risk patients receiving novel anticancer drugs and 0.6% (95% CI: 0.03-3.5) in patients with anticancer drugs plus PAT. The incidence of death due to HBV-R was 0.4% (95% CI: 0.1-1.6) in all at-risk patients and 18.2% (95% CI: 3.2-47.7) in patients with HBV-R. CONCLUSION: Most episodes of HBV-R are preventable, and most cases with HBV-R are manageable. We recommend that novel anticancer drugs should not be intentionally avoided when treating cancer patients with HBV infection.
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Antineoplásicos , Neoplasias Hematológicas , Hepatitis B , Neoplasias , Humanos , Virus de la Hepatitis B/genética , Incidencia , Estudios Retrospectivos , Antineoplásicos/efectos adversos , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , Antivirales/uso terapéutico , Antivirales/farmacología , Activación Viral , Hepatitis B/tratamiento farmacológico , Hepatitis B/epidemiología , Antígenos de Superficie de la Hepatitis BRESUMEN
The mechanical properties of loess-steel interface are of great significance for understanding the residual strength and deformation of loess. However, the undisturbed loess has significant structural properties, while the remolded loess has weak structural properties. There are few reports on the mechanical properties of loess-steel interface from the structural point of view. This paper focused on the ring shear test between undisturbed loess as well as its remolded loess and steel interface under the same physical mechanics and test conditions (water content, shear rate and vertical pressure), and explored the influence mechanism of structure on the mechanical deformation characteristics of steel-loess interface. The results show that the shear rate has little effect on the residual strength of the undisturbed and remolded loess-steel interface. However, the water content has a significant influence on the residual strength of the loess-steel interface, moreover, the residual internal friction angle is the dominant factor supporting the residual strength of the loess-steel interface. In general, the residual strength of the undisturbed loess-steel interface is greater than that of the remolded loess specimen (for example, the maximum percentage of residual strength difference between undisturbed and remolded loess specimens under the same moisture content is 6.8%), which is because that compared with the mosaic arrangement structure of the remolded loess, the overhead arrangement structure of the undisturbed loess skeleton particles makes the loess particles on the loess-steel interface re-adjust the arrangement direction earlier and reach a stable speed relatively faster. The loess particles with angular angles in the undisturbed loess make the residual internal friction between the particles greater than the smoother particles of the remolded loess (for example, the maximum percentage of residual cohesion difference between undisturbed and remolded loess specimens under the same vertical pressure is 4.29%), and the intact cement between undisturbed loess particles brings stronger cohesion than the remolded loess particles with destroyed cement (for example, the maximum difference percentage of residual cohesion between undisturbed and remolded soil specimens under the same vertical pressure is 33.80%). The test results provide experimental basis for further revealing the influence mechanism of structure, and parameter basis for similar engineering construction.
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Resistencia al Corte/fisiología , Suelo/química , Acero/química , Fenómenos Biomecánicos/fisiología , China , Fuerza Compresiva/fisiología , Industria de la Construcción , Materiales de Construcción , Geografía , Humanos , Fenómenos Mecánicos , Estrés Mecánico , Propiedades de Superficie , Agua/químicaRESUMEN
Previous studies have shown that structure has a significant influence on the mechanical deformation of unsaturated loess, but there is little published information focused on the influence mechanism of microstructure and mesostructure on the mechanical properties of loess. In this paper, the unsaturated undisturbed loess and its remolded loess under the same physical condition were taken as the research objects. The unsaturated triaxial shear tests with constant suction and net confining pressure were carried out, and the microstructure differences between the two are compared by using SEM and CT scanning to reveal the influence of structure on strength characteristics. The test results show that the cohesion and internal friction angle of undisturbed loess are greater than those of remolded loess. The angle of undisturbed soil particles is obvious, and the particles are bracket contact with good cementation. The remolded loess particles are close to round shape, and the particles are inlaid contact with destroyed cementation. The average radius of undisturbed soil is higher than that of remolded soil, indicating that there are bracket pores in undisturbed soil, but the bracket structure and macropores are deformed during shear deformation, and good structural and cementation ensure the strength of loess specimens.
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Aim: Advanced esophageal squamous cell carcinoma (ESCC) is a lethal disease with poor response to conventional chemotherapy. Immunotherapy showed better activity than chemotherapy in late-line treatment. However, the rate and duration of response are far from satisfactory. The efficacy of an anti-angiogenic agent combined with immunotherapy for ESCC is unknown. Results: A patient with ESCC experienced disease relapse after chemo-radiotherapy. The disease progressed after combined chemotherapy. A combination regimen of the PD-1 inhibitor camrelizumab and the anti-angiogenic agent apatinib was administered. The patient achieved a PET/CT-confirmed durable complete response with mild toxicity. Conclusion: The PD-1 inhibitor combined with the anti-angiogenic agent is effective and safe for the treatment of ESCC. This regimen is worth investigation in clinical trials.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Inmunoterapia/métodos , Piridinas/uso terapéutico , Quimioterapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Primary mediastinal large B-cell lymphoma (PMBCL) is relatively infrequent and generally has a good prognosis with standard immunochemotherapy. However, treatment options are limited for patients with relapsed/refractory PMBCL who are ineligible for stem cell transplantation. In this report, we treated a refractory PMBCL patient, who did not respond to salvage chemotherapy, with combined nivolumab and radiotherapy. The patient achieved a complete remission with mild adverse reactions and has survived without relapse 2 years after treatment.
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PURPOSE: Anlotinib, a newly developed oral small-molecule receptor tyrosine kinase inhibitor (TKI), has been shown to have encouraging activity against sarcoma. The purpose of this study was to retrospectively evaluate the safety and clinical efficacy of chemotherapy combined with anlotinib plus anlotinib maintenance in advanced/metastatic soft tissue sarcoma (STS) patients in a real-world setting in China. PATIENTS AND METHODS: We retrospectively collected the medical data of thirty-two patients with advanced/metastatic STS who received chemotherapy combined with anlotinib plus anlotinib maintenance therapy. The objective response rate (ORR) and disease control rate (DCR) were calculated according to the RECIST 1.1 criteria. The progression-free rates (PFRs) at three and six months, the progression-free survival (PFS) time, and adverse events were recorded. RESULTS: On the basis of investigator assessments, two patients (6%) achieved CR (complete response) and nine patients (28%) achieved PR (partial response), with an ORR of 34%. Eleven patients (34%) achieved SD (stable disease), and ten patients (31%) achieved PD (progression disease), with a DCR of 69%. The progression-free rates (PFRs) at three and six months were 81% and 69%, respectively. The median PFS time was 8.2 months. The hematologic and non-hematologic toxicities were manageable. The most common grade 3 and 4 adverse events were febrile neutropenia (9%), leukopenia (19%), thrombocytopenia (3%), anemia (6%), anorexia (6%), vomiting (3%), and hypertension (6%). The combination therapy was generally well tolerated. CONCLUSION: Our study suggests that chemotherapy combined with anlotinib plus anlotinib maintenance therapy had good efficacy and resulted in more favorable survival with good tolerance among patients with advanced/metastatic STS.
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PURPOSE: Anlotinib is a newly developed oral multitarget tyrosine kinase inhibitor. We retrospectively evaluated the toxicity and clinical efficacy of chemotherapy combined with anlotinib versus chemotherapy alone for metastatic/advanced non-small cell lung cancer (NSCLC) in patients who failed first- or second-line systemic treatment in China. PATIENTS AND METHODS: In this retrospective trial, ninety-four advanced NSCLC patients received chemotherapy combined with anlotinib (n = 41) or chemotherapy alone (n = 53) in Henan Cancer Hospital. We recorded the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and adverse events (AEs). RESULTS: In the anlotinib plus chemotherapy group, eleven patients (27%) achieved a PR (partial response), and twenty-one patients (51%) achieved SD (stable disease), with an ORR of 27% and a DCR of 78%. In the chemotherapy alone group, eight patients (15%) achieved a PR, and nineteen patients (36%) had SD, with an ORR of 15% and a DCR of 51%. The ORR in the combination arm was slightly, but not obviously, higher than that in the chemotherapy arm (27% vs 15%, p > 0.05). In addition, the DCR was significantly higher in the combination arm than in the chemotherapy alone arm (78% vs 51%, p=0.007). At the end of follow-up, patients in the combination arm had a 1.5-month longer median PFS than patients in the chemotherapy arm; this difference was statistically significant (5.0 vs 3.5, p=0.002). The median OS was not achieved at the final analysis. The hematological and nonhematological toxicities were well tolerated and controlled. In general, most toxicity was limited to grade I or II, well tolerated and controlled. CONCLUSION: Our study suggests that anlotinib combined with chemotherapy may be an effective and well-tolerated treatment for advanced NSCLC in patients who fail first- or second-line therapy.
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PURPOSE: One third of patients with diffuse large B-cell lymphoma (DLBCL) succumb to the disease partly due to rituximab resistance. Rituximab-induced calcium flux is an important inducer of apoptotic cell death, and we investigated the potential role of calcium channels in rituximab resistance. EXPERIMENTAL DESIGN: The distinctive expression of calcium channel members was compared between patients sensitive and resistant to rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone (RCHOP) regimen. The observation was further validated through mechanistic in vitro and in vivo studies using cell lines and patient-derived xenograft mouse models. RESULTS: A significant inverse correlation was observed between CACNA1C expression and RCHOP resistance in two independent DLBCL cohorts, and CACNA1C expression was an independent prognostic factor for RCHOP resistance after adjusting for International Prognostic Index, cell-of-origin classification, and MYC/BCL2 double expression. Loss of CACNA1C expression reduced rituximab-induced apoptosis and tumor shrinkage. We further demonstrated direct interaction of CACNA1C with CD20 and its role in CD20 stabilization. Functional modulators of L-type calcium channel showed expected alteration in rituximab-induced apoptosis and tumor suppression. Furthermore, we demonstrated that CACNA1C expression was directly regulated by miR-363 whose high expression is associated with worse prognosis in DLBCL. CONCLUSIONS: We identified the role of CACNA1C in rituximab resistance, and modulating its expression or activity may alter rituximab sensitivity in DLBCL.
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Antineoplásicos Inmunológicos/uso terapéutico , Canales de Calcio Tipo L/metabolismo , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/metabolismo , Rituximab/uso terapéutico , Animales , Antígenos CD20/metabolismo , Antineoplásicos Inmunológicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Apoptosis/genética , Canales de Calcio Tipo L/genética , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Modelos Animales de Enfermedad , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos , Epigénesis Genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/genética , Ratones , Tomografía Computarizada por Tomografía de Emisión de Positrones , Prednisona/efectos adversos , Prednisona/uso terapéutico , Rituximab/efectos adversos , Rituximab/farmacología , Tomografía Computarizada por Rayos X , Vincristina/efectos adversos , Vincristina/uso terapéutico , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Phytoremediation is a potential cleanup technology for the removal of heavy metals from contaminated soils. Bidens maximowicziana is a new Pb hyperaccumulator, which not only has remarkable tolerance to Pb but also extraordinary accumulation capacity for Pb. The maximum Pb concentration was 1509.3 mg/kg in roots and 2164.7 mg/kg in overground tissues. The Pb distribution order in the B. maximowicziana was: leaf > stem > root. The effect of amendments on phytoremediation was also studied. The mobility of soil Pb and the Pb concentrations in plants were both increased by EDTA application. Compared with CK (control check), EDTA application promoted translocation of Pb to overground parts of the plant. The Pb concentrations in overground parts of plants was increased from 24.23-680.56 mg/kg to 29.07-1905.57 mg/kg. This research demonstrated that B. maximowicziana appeared to be suitable for phytoremediation of Pb contaminated soil, especially, combination with EDTA.
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Bidens/metabolismo , Quelantes/farmacología , Ácido Edético/farmacología , Plomo/metabolismo , Contaminantes del Suelo/metabolismo , Bidens/efectos de los fármacos , Bidens/crecimiento & desarrollo , Biodegradación Ambiental/efectos de los fármacos , Ácido Cítrico/farmacología , Fosfatos/farmacología , Componentes Aéreos de las Plantas/efectos de los fármacos , Componentes Aéreos de las Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismoRESUMEN
BACKGROUND: In advanced esophageal squamous cell carcinoma (ESCC), paclitaxel plus cisplatin are considered as active and tolerable. The current clinical study was conducted to retrospectively compare the efficacy and safety of first-line paclitaxel/S-1(PS) and paclitaxel/cisplatin(TP) regimens in advanced ESCC. RESULTS: The overall response rate of PS was slightly, but not significantly, higher (25 patients, 46%) than that of TP (23 patients, 39%, P = 0.432). Median overall survival (OS) was similar for PS and TP (11.5 months vs. 10.4 months, p = 0.37). However PS had longer median progression-free survival than TP (PFS: 5.5 months vs5.0months, p = 0.04). When compared with PS, more grade 3 or 4 adverse events were recorded for TP, including leukopenia, neutropenia, anemia, anorexia and vomiting (P < 0.05). No treatment-related deaths were recorded in either group. PATIENTS AND METHODS: Between 2008 and 2014, all patients diagnosed with advanced ESCC and treated with paclitaxel/S-1 or paclitaxel/cisplatin at Cancer Hospital Affiliated to Zhengzhou University were analyzed retrospectively. One hundred and thirteen patients were included in this study. Disease control rates and progression-free survival (PFS) and overall survival (OS) were recorded. Survival analysis was calculated by using Kaplan-Meier method. CONCLUSIONS: The PS option improves PFS and its OS is similar to TP. Moreover, the PS regimen is an effective and safe first-line treatment for ESCC with less hematological and non-hematological toxicity.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Cisplatino/administración & dosificación , Neoplasias Esofágicas/tratamiento farmacológico , Ácido Oxónico/administración & dosificación , Paclitaxel/administración & dosificación , Tegafur/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , China , Cisplatino/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Combinación de Medicamentos , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Ácido Oxónico/efectos adversos , Paclitaxel/efectos adversos , Estudios Retrospectivos , Tegafur/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
The effects of culture conditions in vitro and biosurfactant detection were studied on bacterial strains capable of degrading gasoline from contaminated soils near gas station. The main results were summarized as follows. Three bacteria (strains Q 10, Q14 and Q18) that were considered as efficiently degrading strains were isolated and identified as Pseudomonas sp., Flavobacterium sp. and Rhodococcus sp., respectively. The optimal growth conditions of three bacteria including pH, temperature and the concentration of gasoline were similar. The reduction in surface tension was observed with all the three bacteria, indicating the production of biosurfactant compounds. The value of surface tension reduced by the three strains Q10, Q14 and Q18 was 32.6 mN x m, 12.4 mNx m and 21.9 mN x m, respectively. Strain Q10 could be considered as a potential biosurfactant producer. Gasoline, diesel oil, benzene, toluene, ethylbenzene and xylene (BTEX) could easily be degraded by the three isolates. The consortium was more effective than the individual cultures in degrading added gasoline, diesel oil, and BTEX. These results indicate that these strains have great potential for in situ remediation of soils contaminated by gas station leaking.
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Bacterias/metabolismo , Gasolina , Contaminantes del Suelo/metabolismo , Bacterias/crecimiento & desarrollo , Concentración de Iones de Hidrógeno , Tensión Superficial , Tensoactivos/metabolismo , TemperaturaRESUMEN
OBJECTIVE: More effective regimens for advanced esophageal squamous cell carcinoma (ESCC) are urgently needed. Therefore, a retrospective study concerning the efficacy and safety of nanoparticle albumin-bound paclitaxel plus cisplatin (nab-TP) versus solvent-based paclitaxel plus cisplatin (sb-TP) as a first-line therapy was conducted in Chinese patients with advanced ESCC. METHODS: From June 2009 to June 2015, 32 patients were treated with nab-paclitaxel (125 mg/m2) on the first and eighth days (30 minutes infusion) and cisplatin (75 mg/m2) on the second day every 21 days (nab-TP arm). Also, 43 patients were treated with solvent-based paclitaxel (80 mg/m2) intravenously on the first and eighth days and the same dose of cisplatin (sb-TP arm). The two groups were compared in terms of objective response rate (ORR), disease control rate, progression-free survival (PFS), overall survival (OS), and safety profile. OS and PFS were estimated using Kaplan-Meier methods to determine associations between chemotherapy regimens and survival outcomes. RESULTS: Nab-TP demonstrated a higher ORR (50% vs 30%; P=0.082) and disease control rate (81% vs 65%; P=0.124) than sb-TP. Median OS was similar for nab-TP and sb-TP (12.5 vs 10.7 months; P=0.269). However, nab-TP resulted in a longer median PFS (6.1 months [95% confidence interval: 5.3-6.9]) than sb-TP (5.0 months [95% confidence interval: 4.4-5.6]) (P=0.029). The most common adverse events included anemia, leukopenia, neutropenia, febrile neutropenia, and thrombocytopenia in both the groups and no statistically significant differences were observed between the groups. With statistically significant differences, significantly less grade ≥3 peripheral neuropathy, arthralgia, and myalgia occurred in the nab-TP arm (all P<0.05). Dose reduction, treatment delays, and second-line therapy were similar between the two regimens. There were no treatment-related deaths in either group. CONCLUSION: Nab-paclitaxel plus cisplatin is found to be an effective and tolerable option for advanced ESCC in the People's Republic of China.
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There is currently no standard first-line regimen for patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTCL). In this study, we investigated the efficacy and toxicity of gemcitabine (GEM) combined with oxaliplatin (L-OHP), L-asparaginase (L-ASP) and dexamethasone (DXM) (GOLD regimen) as a systemic treatment scheme for newly-diagnosed ENKTCL cases. A total of 55 patients were recruited at the Henan Province Cancer Hospital and the Cancer Center of Sun Yat-sen University between May, 2008 and August, 2012. The GOLD regimen included a 14-day treatment cycle with GEM (1,000 mg/m2) on day 1, L-OHP (100 mg/m2) on day 1, L-ASP (10,000 U/m2) on days 1-5 and DXM (20 mg b.i.d.) on days 1-4. The response rate, survival rate and treatment toxicity were analyzed. The overall response rate was 91% (48/55) with a complete response in 62% (34/55) and a partial response in 29% (15/55) of the patients. For all patients, the 1-, 2- and 3-year progression-free survival (PFS) rate was 86, 64 and 57% and the overall survival (OS) 91, 80 and 74%, respectively. The 1-year PFS in patients with stage I/II vs. those with III/IV disease was 87 vs. 66% (P<0.001) and the 1-year OS was 98 vs. 75%, respectively (P<0.001). No chemotherapy-related mortality or severe complications were recorded. In conclusion, the GOLD regimen was found to be highly effective and safe for the treatment of patients with newly-diagnosed ENKTCL.
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p63 is highly expressed in some malignant tumors and is associated with tumorigenesis, invasion and metastasis. The aim of our study was to evaluate the clinical significance of p63 in colorectal cancer (CRC). p63 expression was detected by immunohistochemistry in 66 CRC patients. Correlations between p63 expression and clinicopathological factors, progression-free survival (PFS) and overall survival (OS) were analyzed. Among the 66 CRC cases, 31 cases (47%) exhibited a high score of p63 expression, while 35 cases (53%) were marked with a low score. The p63 level correlated with peritumoral deposits (p=0.021). The 5-year OS rates in the low p63 score and high p63 score groups were, respectively, 49% and 74% (p<0.001). The 5-year PFS rates in the low p63 score and high p63 score groups were, respectively, 44% and 71% (p<0.001). Univariate analysis revealed that p63 expression was correlated with OS and PFS. Multivariate analysis suggested that p63 expression was an independent prognostic factor for OS (p=0.035). In conclusion, p63 was negatively correlated with peritumoral deposits and positively associated with OS and PFS in CRC. The data suggest that p63 is a potential prognostic factor for CRC.
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Biomarcadores de Tumor/biosíntesis , Neoplasias Colorrectales/metabolismo , Factores de Transcripción/biosíntesis , Proteínas Supresoras de Tumor/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Neoplasias Colorrectales/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de SupervivenciaRESUMEN
The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and P53 tumor suppressors are among the most commonly inactivated or mutated genes in human cancers, whose pathways cross-talk and interact in a complementary mode. In order to understand their roles and relationship in diffuse large B-cell lymphoma (DLBCL), we examined their expression and evaluated their prognostic significance in 62 patients with DLBCL treated with standard chemotherapy. Results showed that PTEN protein was lost in 23 (37.1%) cases, and the loss was associated with the activation of PI3K/AKT pathway, but was not associated with patient's clinical outcome. P53 mutation protein was detected in 30 (48.4%) cases and was associated with poor survival. Results of multivariate analysis showed that P53 mutation but not PTEN loss is associated with short survival in patients with DLBCL. PTEN status has no effect on P53 mutation-associated poor survival. We conclude that PTEN may play less prognostic role than P53 and that P53 mutation protein should be considered as a predictive factor of the need for a more aggressive therapy in patients with DLBCL who express P53.
Asunto(s)
Linfoma de Células B Grandes Difuso/metabolismo , Mutación/genética , Fosfohidrolasa PTEN/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Linfocitos B/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Ciclofosfamida/administración & dosificación , ADN/genética , Doxorrubicina/administración & dosificación , Elafina/genética , Elafina/metabolismo , Femenino , Genotipo , Humanos , Técnicas para Inmunoenzimas , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Fosfohidrolasa PTEN/genética , Fosforilación/efectos de los fármacos , Reacción en Cadena de la Polimerasa , Prednisona/administración & dosificación , Pronóstico , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Rituximab , Tasa de Supervivencia , Vincristina/administración & dosificación , Adulto JovenRESUMEN
The experiments were made in laboratory to analyze the characteristics and principle of benzene's biodegradation using the microorganism (G-, Flavobacterium) taken from Daqing oil fields. Results show that the maximal concentration of benzene, which microorganisms could endure is between 8.8 mg x L(-1) and 17.6 mg x L(-1); microorganisms were inhibited as benzene's concentration was beyond 17.6 mg x L(-1). Trends of benzene's concentration in and out of microorganism's cell are almost same; the biodegradation could be achieved efficiently as the pH range of 6.5 - 7.0 and benzene initial concentration range of 7.04 - 13.2 mg x L(-1). Change of - lgP (P is the distributive ratio of benzene in membrane and water) could be illustrated the trends of toxicity and degradation of benzene in and out of microorganism's cell; the biodegradation rate varied simultaneously with the change of P as initial concentration of benzene was beyond 8.8 mg x L(-1).