RESUMO
Objective: To explore the prognostic factors of primary plasma cell leukemia (pPCL) in the era of novel agents. Methods: The clinical data of 66 patients with pPCL treated at the Department of Haematology, Beijing Chao-Yang Hospital, Capital Medical University from 2011 to 2022 were retrospectively collected to analyze their prognostic factors. Results: Among the 66 patients with pPCL, the median age was 59 (range: 29-79) years. The median overall survival (OS) duration was 19.0 (95% CI 10.4-27.6) months, and the median progression-free survival (PFS) duration was 11.0 (95% CI 6.5-15.6) months. The median OS and PFS were significantly longer in patients with the best post-treatment response of very good partial remission (VGPR) or better than in patients with a response of partial remission (PR) or worse (median OS: 33.0 months vs 6.0 months, P<0.001; median PFS: 16.0 months vs 3.0 months, P<0.001). OS was significantly longer in patients who underwent autologous hematopoietic stem cell transplantation than in those who did not undergo transplantation (49.0 months vs 6.0 months, P=0.002), and there was a trend toward a longer PFS in patients who underwent transplantation than in those who did not undergo transplantation (19.0 months vs 8.0 months, P=0.299). The median OS and PFS were significantly longer in patients who received maintenance therapy than in those who did not receive maintenance therapy (median OS: 56.0 months vs 4.0 months, P<0.001; median PFS: 20.0 months vs 2.0 months, P<0.001). Multivariate analysis showed that hypercalcemia was an independent risk factor (HR=3.204, 95% CI 1.068-9.610, P=0.038) for patients with pPCL, while receiving maintenance therapy (HR=0.075, 95% CI 0.022-0.253, P<0.001) and post-treatment response of VGPR or better (HR=0.175, 95% CI 0.048-0.638, P=0.008) were independent protective factors for patients with pPCL. Conclusions: In the era of novel agents, hypercalcemia, receiving maintenance therapy, and post-treatment response of VGPR or better are independent prognostic factors for pPCL.
Assuntos
Leucemia Plasmocitária , Humanos , Pessoa de Meia-Idade , Leucemia Plasmocitária/terapia , Leucemia Plasmocitária/diagnóstico , Adulto , Idoso , Prognóstico , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas , Masculino , Feminino , Taxa de Sobrevida , Indução de RemissãoRESUMO
Objective: The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) . Methods: Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1â¶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed. Results: â Collection results: the ETO and CTX groups [2 (1-3) d vs 2 (1-5) d; P<0.001] and CD34(+) cells [7.62×10(6) (2.26×10(6)-37.20×10(6)) /kg vs 2.73×10(6) (0.53×10(6)-9.85×10(6)) /kg; P<0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) (P<0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; P<0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. â¡Adverse reactions: granular deficiency with fever (21.5%[14/65] vs. 10.7%[6/56]; P=0.110), requiring platelet transfusion [10.7% (7/65) vs 1.8% (1/56) ; P=0.047]. â¢Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34(+) cells infused in the two groups was 4.62×10(6) (2.14×10(6)-19.89×10(6)) /kg versus 2.62×10(6) (1.12×10(6)-5.31×10(6)) /kg (P<0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d (P=0.049), and platelet implantation time was 11 (0-19) d vs. 12 (0-34) d (P=0.035). One case in the CTX group experienced delayed platelet implantation. Conclusion: The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34(+) cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.
Assuntos
Ciclofosfamida , Etoposídeo , Fator Estimulador de Colônias de Granulócitos , Mobilização de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Transplante Autólogo , Humanos , Mieloma Múltiplo/terapia , Etoposídeo/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Ciclofosfamida/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Estudos Retrospectivos , Células-Tronco de Sangue Periférico , Transplante de Células-Tronco de Sangue Periférico/métodos , Feminino , Masculino , Pessoa de Meia-IdadeRESUMO
Objective: To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China. Methods: This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival. Results: The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage â , 259 patients (64.6%) with stage â ¡, and 68 patients (17.0%) with stage â ¢. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage â , 95 patients (23.7%) in stage â ¡, 206 patients (51.4%) in stage â ¢, and 50 patients (12.5%) in stage â £. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage â ; 62.0 months for stage â ¡, 39.2 months for stage â ¢, and 30.3 months for stage â £; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages â ¢ and â £ of the R2-ISS were independent prognostic factors for PFS (HR=2.37, 95%CI 1.30-4.30; HR=4.50, 95%CI 2.35-9.01) and OS (HR=4.20, 95%CI 1.50-11.80; HR=9.53, 95%CI 3.21-28.29). Conclusions: The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Prognóstico , Estudos Retrospectivos , Transplante AutólogoRESUMO
Objective: To investigate the clinical prognostic value of dynamic minimal residual disease (MRD) after autologous hematopoietic stem cell transplantation (AHSCT) in patients with multiple myeloma (MM). Methods: Patients with MM who underwent AHSCT in Beijing Chao-Yang Hospital from February 2016 to December 2019 were enrolled in this study. All the patients in the study had complete baseline data at the diagnosis. AHSCT was performed after induction chemotherapy. Response evaluation was performed after induction therapy. All the patients were assessed at approximately 100 days after AHSCT. Bone marrow MRD by NGF was performed every three months and dynamically monitored for at least 12 months. All the patients were divided into different groups according to cytogenetics and MRD status. Survivals in different groups were analyzed by IBM SPSS 22.0 statistical software. Results: A total of 150 patients with MM were enrolled in this study at last, including 66 patients in the cytogenetic standard risk group and 84 patients in the cytogenetic high-risk group. The median age was 54 years (range 30-68 years) and 87 male patients (58.0%) was in the study. The median follow-up was 36 months (range 16-72 months). Patients in the standard-risk group had better clinical prognosis than those in the high-risk group [median PFS in the standard-risk group was not achieved, and median PFS in the high-risk group was 45 months (P<0.001); median OS of both groups was not reached, and the estimated 3-year OS rate of the standard-risk group and the high-risk group was 95.2% and 78.9%, respectively (P=0.001)]. According to MRD status of patients, patients in each group were divided into three subgroups: persistent positive (Ppos), transient negative (Tneg) and persistent negative (Pneg). The median OS and median PFS of all subgroups in the standard-risk group was not reached (P=0.324 and P=0.086). In high-risk group, the median OS of MRD Pneg subgroup was not reached, and the estimated 3-year OS rate was 100%; The median OS of MRD Ppos subgroup was 52 months, and MRD Tneg subgroup only 31 months (P=0.002); the median PFS of MRD Pneg group was not reached, and the estimated 3-year PFS rate was 85.4%; median PFS of MRD Ppos subgroup was 40 months, and MRD Tneg subgroup only 17 months (P=0.001). Conclusions: MRD Pneg might overcome the adverse prognosis of MM patients with high-risk cytogenetics. However, MRD Tneg might be a poor prognostic factor for the patients with cytogenetic high-risk MM.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Neoplasia Residual , Prognóstico , Transplante Autólogo , Resultado do TratamentoRESUMO
Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinomatose Meníngea , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Carcinomatose Meníngea/tratamento farmacológico , Pemetrexede , Resultado do TratamentoRESUMO
Objective: To evaluate the prognostic value of CD56 expression in newly diagnosed MM (NDMM). Methods: A total of 332 NDMM patients were enrolled in Beijing Chaoyang Hospital, Capital Medical University from January 1, 2011 to January 1, 2021, with a median age of 60 years and a male to female ratio of 1.2â¶1. CD56 expression on myeloma cells was detected by flow cytometry before induction therapy. Overall survival (OS) and progression-free survival (PFS) data were collected. In order to reduce the confounding factors, the propensity score matching technique was used to match CD56 positive versus negative patients at a ratio of 1â¶1. Results: Among 332 patients, CD56 positivity rate was 65.1% (216/332). Patients with CD56 expression had significantly longer median OS (58.4 vs. 43.1 months, P=0.024) and PFS (28.7 vs. 24.1 months, P=0.013) than those with negative CD56. Univariate Cox proportional hazards regression analyses showed that CD56 expression was positively correlated with OS (HR=0.644, 95%CI 0.438-0.947, P=0.025) and a favorable prognostic factor for PFS (HR=0.646, 95%CI 0.457-0.913,P=0.013). The favorable effect of CD56 expression on PFS was confirmed in multivariate analysis (HR=0.705, 95%CI 0.497-0.998, P=0.049), but OS was not affected (P>0.05).In the propensity score matching analysis, 194 patients with 97 in each group were identified. CD56 positivity consistently predicted longer PFS (34.2 vs.25.1 months, P=0.047), but not OS (63.4 vs.43.1 months, P=0.056). Conclusion: These results demonstrate that CD56 expression is a favorable prognostic factor for PFS of newly diagnosed MM patients.
Assuntos
Mieloma Múltiplo , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Prognóstico , Intervalo Livre de Progressão , Estudos RetrospectivosRESUMO
Objective: To evaluate the effect of autologous stem cell transplantation (auto-HSCT) on treatment remission and survival of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 243 new diagnosed MM patients (age ≤65 years) who had received auto-HSCT were selected, and 176 MM patients (age ≤65 years) who had not received auto-HSCT were selected as the control group to evaluate the effect of auto-HSCT on the remission and survival. To balance the distribution of prognostic factors between auto-HSCT and non-auto-HSCT patients, the propensity score matching technique was used to reduce the bias between groups in a 1â¶1 scale, 64 in each group, and correlation analysis was performed. Results: A total of 128 patients (64 cases in each group) were screened by propensity score matching analysis. 64 patients received auto-HSCT after induction therapy. After auto-HSCT, 24 patients (37.5%) obtained sCR, 16 patients (25.0%) obtained CR, 15 patients (23.4%) obtained VGPR, and 9 patients (14.1%) obtained PR. The efficacy of patients with auto-HSCT was significantly better than that of non-auto-HSCT patients (P=0.032) . Progression-free survival (PFS) and overall survival (OS) were significantly longer in auto-HSCT patients compared with non-auto-HSCT patients[PFS: 42.2 (95% CI 29.9-54.5) months vs 22.4 (95% CI 17.1-27.7) months, P=0.007; OS: 87.6 (95% CI 57.3-117.9) months vs 53.9 (95% CI 36.1-71.7) months, P=0.011]. Multivariate analysis confirmed that auto-HSCT had a favorable effect on OS (HR=0.448, 95%CI 0.260-0.771, P=0.004) and PFS (HR=0.446, 95%CI 0.280-0.778, P=0.003) . Conclusion: These results demonstrated that auto-HSCT was a favorable prognostic factor for newly diagnosed MM patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Idoso , Intervalo Livre de Doença , Humanos , Estudos Retrospectivos , Transplante Autólogo , Resultado do TratamentoRESUMO
Ultrasounds (US) are one of the most used imaging techniques in medicine for assessing the physiological and pathological state of soft tissue. Apart from therapeutic applications, most of the interaction of the acoustic beams with tissues occur passively and without substantial modification to the physiology of the latter. However, US can also be used to remotely power implantable devices with sensing capabilities. In this study, we propose small-form devices interfaced with functionalized electrochemical electrodes for the detection of pH and lactate levels, powered by ultrasounds and data transmission through a Frequency Shift Keying (FSK) modulation technique. A custom-made piezoelectric transducer is responsible for converting the acoustic waves into electrical voltage at the device with operational levels as low as 0.5 V (power consumption of 10 µW) obtained from implantation distances of 50 mm inside tissue. This conjugated with the high sensitivity of the developed electrochemical sensors allows to detect and transmit local parameter variations below 0.1 pH (4.2 mV) and 1 mM lactate (70 nA). Potential applications include real-time access to intrabody tissue monitoring post-operatively, with the view of assessing proper soft tissue healing or infection detection by bacteria, as well as tissue cancer screening in structures such as the human breast.
Assuntos
Técnicas Biossensoriais , Ultrassom , Eletrodos , Transferência de Energia , Humanos , Monitorização FisiológicaRESUMO
Objective: To explore the influence of lateral patellofemoral joint degeneration on the treatment of anteromedial osteoarthritis of knee joint by Oxford medial unicompartmental knee arthroplasty. Methods: The clinical data of 73 patients (73 knees) with knee osteoarthritis underwent unicompartmental knee arthroplasty at Department of Orthopaedic Surgery, Xuanwu Hospital, Capital Medical University from March 2016 to December 2017 were analysed respectively.There were 18 males and 55 females, aged (68.6±7.5) years(range: 53 to 89 years).The lateral patellofemoral joints of patients were evaluated by Ahlback grading system. Patients with Ahlback 0 andâ were in the non degenerative group (37 cases), and those with Ahlback â ¡ and above were in the degenerative group (36 cases). Hospital for special surgery knee score(HSS) and the Western Ontario and McMaster Universities(WOMAC) osteoarthritis index, as well as the condition of kneeling, sit to stand movement, up stair and down stair were recorded. The data before and after operation were compared by paired sample t test, and the data between groups were compared by independent sample t test. χ(2) test was used for counting data. Pearson correlation analysis was used to compare the correlation between ahlback score, HSS and WOMAC osteoarthritis index. Results: The follow-up time was (35.1±6.6) months (range: 25 to 47 months).The knee function of the patients improved significantly after operation.The HSS score increased from 57.7±11.8 preoperative to 81.8±7.8 postoperative (t=16.64, P=0.00) and WOMAC osteoarthritis index decreased from 48.9±13.4 preoperative to 15.6±8.8 postoperative (t=20.48, P=0.00). There was no statistical difference in the change of HSS between the degenerative group and the non-degenerative group before and after surgery(27.5±12.2 vs. 22.5±12.3, t=-1.65, P=0.10) as well as the change of WOMAC osteoarthritis index(31.8±14.0 vs. 36.4±13.7, t=-1.35, P=0.18), but the lateral patellofemoral joint degeneration was related to inability to complete squats (χ(2)=5.17, P=0.04) and sitting up (χ(2)=7.22, P=0.01). Conclusion: The degeneration of lateral patellofemoral joint has no effect on the early functional recovery of patients with anteromedial knee osteoarthritis after Oxford medial unicompartmental knee arthroplasty.
Assuntos
Artroplastia do Joelho/métodos , Osteoartrite do Joelho/cirurgia , Articulação Patelofemoral , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Articulação do Joelho/cirurgia , Prótese do Joelho , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Resultado do TratamentoAssuntos
Laringoscópios , Laringoscopia , Adulto , Idoso , Calibragem , Criança , Humanos , Intubação Intratraqueal , Estudos ProspectivosRESUMO
Objective: To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM). Methods: It was a prospective, multi-center, observational study. A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015. Relevant information was recorded, such as baseline clinical data, cytogenetic abnormalities, treatment regimens, and duration of treatment, safety, and survival. Results: (1)There were 126 relapsed and refractory MM (RRMM) patients, 25 newly diagnosed patients and 19 maintenance patients. The evaluable RRMM patients accounted for 120 cases, among which 74 cases(61.7%) reached the partial response (PR) or above, and a very good partial response (VGPR) in 16 patients (13.3%), a complete response (CR) in 14 cases (11.7%), a strictly complete response (sCR) in 4 cases (3.3%). Thus, a VGPR or above in 34 patients accounted for 28.3%. (2)The median follow-up was 13 months, the median time to progression 12 months. The median survival after receiving lenalidomide was 19 months, and the median overall survival (OS) was 62 months. (3) The univariate analysis in 120 RRMM patients suggested that prognostic factors for significant improvement in PFS included normal karyotype, international staging system (ISS) â -â ¡, t(4; 14) negative (detected by fluorescence in situ hybridization), non-bortezomib resistance and response to previous regimens. As to OS, non-bortezomib resistance, response to previous regimens and non-primary refractoriness were positive factors. Multivariate analysis showed that the response to previous regimens (PR or better) was an independent good prognostic factor for progress-free survival(PFS), non-bortezomib resistance and non-primary refractoriness for OS. (4) Grade 3 or 4 adverse events that occurred in more than 10% of all enrolled patients were neutropenia (12.7%), leukocytosis(11.5%) and thrombocytopenia (12.7%). Owing to intolerance of toxic side effects, 7 cases withdrew lenalidomide. Conclusions: No matter what combination, regimens containing lenalidomide are effective to RRMM patients with overall response rate 61.7%, a time to progression 12 months and an overall survival 62 months.The toxicity is quite tolerable and manageable. In addition, the response to previous treatment (reached PR or above) is the independent good prognostic factor for PFS, non-bortezomib resistance and non-primary refractoriness for OS. Clinical trail registration: Clinicaltrials.gov, NCT01947309.
Assuntos
Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Aberrações Cromossômicas , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Hibridização in Situ Fluorescente , Lenalidomida , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Neutropenia , Estudos Prospectivos , Indução de Remissão , Taxa de Sobrevida , Talidomida/uso terapêutico , Resultado do TratamentoRESUMO
Objective: To investigate the effects of berberine in combination with bortezomib on proliferation and apoptosis of multiple myeloma (MM) cell line. Methods: MM cell line U266 cells were treated with berberine and/or bortezomib. The effects of berberine and/or bortezomib on proliferation of cells were measured by methylthiazolyl tetrazolium bromide (MTT). Flow cytometric Annexin â ¤/PI double staining method was used to detect effect of either drug alone or in combination on apoptosis of MM cell line U266. ELISA was used to measure the expression of casepase-3,-8,-9 affected by the two drugs. Western blot was used to detect the expression of the apoptosis-related protein TRADD and FADD. King formula was used to determine if there was a synergistic effect of berberine in combination with bortezomib. Results: â Both berberine and bortezomib as single agent had dose- and time-dependent effects of proliferation inhibition on U266 cells. Berberine (20 µmol/L) and bortezomib (5 nmol/L) had a synergistic effect of proliferation inhibition (Q value: 1.31-1.65). â¡ The proportion of early stage apoptosis in both single agent groups and combination group significantly increased compared to control group (P< 0.05). Berberine and bortezomib had a synergistic effect on cell apoptosis (Q value after 6 h and 12 h were 0.896 and 1.197, respectively). ⢠Berberine in combination with bortezomib significantly upregulated expressions of caspase-3, -8 and -9, which were statistically significant (P<0.05). â£Berberine in combination with bortezomib significantly upregulated expressions of TRADD (0.91±0.01, 0.70±0.01) and FADD (0.98±0.01, 0.98±0.01) compared with control group (both P<0.05). Conclusion: Berberine in combination with bortezomib had synergistic effects on proliferation inhibition and apoptosis, which were mediated by up-regulated levels of TRADD and FADD.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Berberina/farmacologia , Bortezomib/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Ácidos Borônicos , Caspase 3 , Linhagem Celular Tumoral , Proliferação de Células , Humanos , PirazinasRESUMO
Hepatocellular carcinoma (HCC) is believed to arise from tumor-initiating cells (T-ICs), which are responsible for tumor relapse and metastases. Portal vein tumor thrombus (PVTT) is raised from HCC and strongly correlated to a poor prognosis. However, the mechanism underling the formation of PVTT is largely unknown. Herein, we provide evidence that RNA polymerase II subunit 5 (RPB5)-mediating protein (RMP) was progressively upregulated in PVTT and overexpressed RMP appeared to increase T-ICs self-renewal. Moreover, RMP promoted metastases of PVTT cells and HCC cells in vitro and in vivo. Knockdown of RMP attenuated T-ICs self-renewal and reversed epithelial-mesenchymal transition (EMT) in HCC and PVTT cells. The neutralizing assays suggested that interleukin-6 (IL-6) had an indispensable role in RMP regulating metastases and self-renewal of HCC cells. Furthermore, the transcription of IL-6 was verified to be modulated by RMP via interaction with p65 and RPB5, through which expanding the T-IC/cancer stem cell populations, as well as inducing EMT was promoted. These results suggested that RMP may promote PVTT formation by promoting IL-6 transcription. Thus, RMP serves as a potent factor contributed to develop PVTT and a promising therapeutic target for HCC patients.
Assuntos
Carcinoma Hepatocelular/metabolismo , Interleucina-6/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Hepáticas/metabolismo , Veia Porta/patologia , Proteínas Repressoras/metabolismo , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Técnicas de Silenciamento de Genes , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Transplante de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Veia Porta/metabolismo , Proteínas Repressoras/genéticaRESUMO
Measuring gait asymmetry is an important feature when characterizing functional imbalance between limbs. This could be due to pathologies, such as osteoarthritis, stroke, or associated with the effects of surgeries such as hip arthroplasty. Generally, the study of asymmetry or imbalance has required the use of a gait lab or force plates, which could be expensive and difficult to use in home settings. This work validates the use of a light weight ear sensor (7.4 g) with an instrumented treadmill for 64 subjects (age (60.04 (15.36)) including healthy subjects (14) as well as subjects who had been treated for hip (17), knee-replacement surgery (21) and knee osteoarthritis (12). Subjects performed treadmill walking at several speeds on flat surfaces, inclines and declines. Accelerometer data from the ear sensor were segmented into consecutive steps and temporal features were extracted. The measures of gait cycle time and step-period asymmetry obtained from the ear sensor matched well those of the treadmill for flat surfaces, inclines and declines. The key implication of the study is that the proposed method could replace expensive equipment for monitoring temporal gait features in clinics as well as free-living environments, which is important for monitoring rehabilitation after surgery and the progress of diseases affecting limb imbalance.
Assuntos
Orelha , Marcha/fisiologia , Monitorização Fisiológica/instrumentação , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/fisiopatologia , Fatores de TempoRESUMO
The feasibility of robotic surgery has been extensively explored over the past decade with a more recent shift towards defining focused clinical applications for which quantifiable patient benefits can be directly attributed to its use. The aim of this article is to review the current literature on the use of daVinci robotic surgery for the management of rectal cancer and identify the potential benefits, if any, that robotic-assisted total mesorectal excision (RTME) may provide over the current conventional approach. A comprehensive search strategy was used to identify relevant evidence in order to explore the oncological, operative and functional outcome measures for the RTME in addition to quantifying the level of evidence which describes the clinical effectiveness of the daVinci robot in oncological surgery. Both robotic assisted techniques and the primary outcomes are discussed. In total, 23 studies were reviewed across 11 institutions, including one pilot randomised control trial. When data repetition is disregarded, a total of 452 robotic assisted laparoscopic anterior resections and 60 robotic-assisted laparoscopic abdomino-perineal excision of the rectum have been published since the introduction of the daVinci into clinical practice. Feasibility of the daVinci robotic assisted total mesorectal excision is demonstrated, with comparable oncological outcomes presented for rectal cancer excision. A demonstration of a reduced open conversion rate as well as of reduced hospital stay with the use of the robot is highlighted, although further trials are required to confirm both these findings. No functional benefit in using the daVinci could be confirmed due to the lack of focused trials in this area.