Mitoxantrone-cytarabine-etoposide induction therapy in children with acute myeloid leukemia: a single-center study of complications and clinical outcomes / 中国当代儿科杂志

OBJECTIVE@#To investigate the complications and clinical outcome of children with acute myeloid leukemia (AML) undergoing mitoxantrone-cytarabine-etoposide (MAE) induction therapy.@*METHODS@#A total of 170 children with AML were given MAE induction therapy, and the complications and remission rate were analyzed after treatment.@*RESULTS@#The male/female ratio was 1.33:1 and the mean age was 7.4 years (range 1-15 years). Leukocyte count at diagnosis was 29.52×10/L [range (0.77-351)×10/L]. Of all children, 2 had M0-AML, 24 had M2-AML, 2 had M4-AML, 48 had M5-AML, 3 had M6-AML, 7 had M7-AML, 69 had AML with t(8;21)(q22;q22), and 15 had AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22). The most common complication was infection (158/170, 92.9%). Among these 158 patients, 22 (13.9%) had agranulocytosis with pyrexia (with no definite focus of infection), and 136 (86.1%) had definite focus of infection (including bloodstream infection). Other complications included non-infectious diarrhea, bleeding, and drug-induced hepatitis. Treatment-related mortality was observed in 10 children, among whom 8 had severe infection, 1 had multiple organ failure, and 1 had respiratory failure. Remission rate was evaluated for 156 children and the results showed a complete remission rate of 85.3%, a partial remission rate of 4.5%, and a non-remission rate of 10.3%.@*CONCLUSIONS@#Induction therapy with the MAE regimen helps to achieve a good remission rate in children with AML after one course of treatment. Infection is the main complication and a major cause of treatment-related mortality.

Trasplante de médula ósea alogénico en un paciente con fusariosis diseminada y leucemia mieloide aguda / Allogeneic hematopoietic cell transplantation in a patient with disseminated fusariosis and acute myeloid leukemia

La infección diseminada por Fusarium se ha convertido en un problema creciente en las personas con neoplasias hematológicas malignas, principalmente en pacientes con leucemias agudas; se describen cada vez más casos en aquellos sometidos a un trasplante de médula ósea. No existe un tratamiento óptimo establecido para la fusariosis diseminada. La mortalidad global comunicada de esta infección oscila entre el 50 y el 80%. Se presenta a continuación el caso de un paciente de sexo masculino de 29 años, con diagnóstico de leucemia mieloide aguda, que presenta como complicación una fusariosis diseminada, y logra sobrellevar un trasplante alogénico de médula ósea en el Hospital Italiano de San Justo (Argentina) de forma exitosa. (AU)

Disseminated fusariosis has become an increasing problem in people with hematopoietic neoplasms, mainly in patients affected by acute leukemias, and even more in those who undergo hematopoietic cell transplantation. There is not an optimal treatment for disseminated fusariosis. The global mortality described in the literature is between 50% and 80%. We introduce a case of a 29 year old patient with diagnosis of acute myeloid leukemia complicated with disseminated fusariosis, who copes with an allogeneic hematopoietic cell transplantation with a successful outcome in the "Hospital Italiano de San Justo" (Argentina). (AU)

Un caso de leucemia cutánea / A case of cutaneous leukemia

Leucemia cutánea es una manisfestación extramedular de Leucemia. La frecuencia y edad de distribución depende del subtipo de leucemia1. Usualmente se presenta después que la enfermedad sistémica se ha manifestado y sugiere recaída o resistencia al tratamiento 11,12. Los hallazgos clínicos y morfológicos tienen una amplia variedad de manifestaciones y se pueden presentar en lesiones nodulares y placas. Raras manifestaciones incluyen máculas eritomatosas, ampollas y úlceras que pueden ocurrir solas o en combinación. A partir de una manifestación solitaria o en grupo, la leucemia cutis puede presentarse con rash eritematoso en un patrón clinicamente polimórfico. Consecuentemente , la leucemia cutánea debe distinguirse de diferentes diagnósticos diferenciales como por ejemplo: metástasis cutáneas o malignidades viscerales, linfoma, erupciones por fármacos, infecciones virales, sifilis, úlceras de varios orígenes. En la mucosa oral, hiperplasia gingival es el principal diagnóstico diferencial.1 El conocimiento de la morfologia clinica es de tremenda importancia en casos en donde la Leucemia no fuera conocida.1 Se presenta el caso poco frecuente de una paciente con diagnóstico de leucemia mieloide aguda que desarrolla una leucemia cutánea durante su seguimiento en Consulta Externa...(AU)

Cutaneous leukemia is an extramedullary manifestation of Leukemia. The frequency and age distribution depends on the subtype of leukemia1. It usually occurs after the systemic disease has manifested and suggests relapse or resistance to treatment 11,12. The clinical and morphological findings have a wide variety of manifestations and can occur in nodular lesions and plaques. Rare manifestations include erythematous macules, blisters and ulcers that can occur alone or in combination. From a solitary or group manifestation, leukemia cutis can present with erythematous rash in a clinically polymorphic pattern. Consequently, cutaneous leukemia must be distinguished from different differential diagnoses such as: cutaneous metastases or visceral malignancies, lymphoma, drug eruptions, viral infections, syphilis, ulcers of various origins. In the oral mucosa, gingival hyperplasia is the main differential diagnosis.1 The knowledge of the clinical morphology is of tremendous importance in cases where the Leukemia was not known.1 The rare case of a patient diagnosed with acute myeloid leukemia is presented that develops a cutaneous leukemia during its follow-up in Outpatient Consultation ... (AU)  

The effect of MDR1 (P-gp) and ABCG2 on the drug resistance in Hep 2 cells / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the effect of MDR1 (P-gp) and ABCG2 on the drug resistance in Hep 2 cells.@*METHOD@#Flow cytometry was used to detect the variations of the antitumor drugs accumulation and discharging, and activity variations when MDR1 and ABCG2 inhibitors were used in Hep-2.@*RESULT@#The accumulation and discharging of mitoxantrone was significantly higher than the control group when ABCG2 inhibitor FTC was used in Hep-2 (P<0. 05). In contrast, P-gp did not appear similar case; To the mitoxantrone and cisplatin, there was no statistical correlation about activity of Hep-2 between P-gp or ABCG2 antagonist and the control; To the doxorubicin, combining FTC and P-gp, the activity of Hep-2 was higher than the control and difference was significant (P<. 05), In contrast, FTC and P-gp did not appear similar case when used alone; To the 5-FU, when PGP used, the activity of Hep-2 was higher than that in the control and difference was significant (P<0. 05), In con- trast, FTC and FTC+P-gp did not appear similar case; To the paclitaxel, when P-gp or FTC+P-gp used, the activity of Hep-2 was higher than that in the control and difference was significant(P<0. 05).@*CONCLUSION@#ABCG2 may lead to drug resistance mainly by changing the ability of cell in accumulating and discharging chemotherapy drugs. P-gp has other way. P-gp and ABCG2 play different roles in different drug resistance.

Clinical Analysis of 4 AML Patients Aged Over 80 Years Treated with Chemotherapy Combined with Haploidentical Hematopoietic Stem Cell Infusion / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of MA (mitoxantrone and cytarabine) regimen chemotherapy combined with granulocyte-colony stimulating factor (G-CSF)-mobilized family related HLA-haploidentical donor peripheral blood hematopoietic stem cell (G-PBHSC) infusion for the treatment of acute myeloid leukemia (AML) patients aged over 80 years.</p><p><b>METHODS</b>Four elderly patients with AML were treated in Chinese Second Artillery General Hospital from August 2008 to September 2013. The proportion of male to female was 1 : 3 and the median age 83 (80-85) years. All patients received programmed infusions of G-PBHSC after MA regimen chemotherapy without graft-versus-host disease (GVHD) prophylaxis. After complete remission (CR), patients only received G-PBHSC infusion without chemotherapy.</p><p><b>RESULTS</b>Three cases achieved CR and their disease free survival (DFS) time was 18, 8, 6 months, respectively. 1 case did not reach remission after 2 cycles chemotherapy. The median overall survival (OS) time was 10 (3-20) months. No GVHD was observed in any of the patients during treatment. Concludsion: The combination of chemotherapy and programmed haploidentical G-PBHSC infusion is an alternative approach for AML patients aged over 80 years.</p>

Cardiotoxicity of Mitoxantrone Treatment in a German Cohort of 639 Multiple Sclerosis Patients

BACKGROUND AND PURPOSE: The aim of this study was to elucidate the role of therapy-related cardiotoxicity in multiple sclerosis (MS) patients treated with mitoxantrone and to identify potential predictors for individual risk assessment. METHODS: Within a multicenter retrospective cohort design, cardiac side effects attributed to mitoxantrone were analyzed in 639 MS patients at 2 MS centers in Germany. Demographic, disease, treatment, and follow-up data were collected from hospital records. Patients regularly received cardiac monitoring during the treatment phase. RESULTS: None of the patients developed symptomatic congestive heart failure. However, the frequency of patients experiencing cardiac dysfunction of milder forms after mitoxantrone therapy was 4.1% (26 patients) among all patients. Analyses of the risk for cardiotoxicity revealed that cumulative dose exposure was the only statistically relevant risk factor associated with cardiac dysfunction. CONCLUSIONS: The number of patients developing subclinical cardiac dysfunction below the maximum recommended cumulative dose is higher than was initially assumed. Interestingly, a subgroup of patients was identified who experienced cardiac dysfunction shortly after initiation of mitoxantrone and who received a low cumulative dose. Therefore, each administration of mitoxantrone should include monitoring of cardiac function to enhance the treatment safety for patients and to allow for early detection of any side effects, especially in potential high-risk subgroups (as determined genetically).

Repeated injection of mitoxantrone containing thermosensitive liposomes in rat induced ABC phenomenon / 药学学报

To investigate whether accelerated blood clearance (ABC) phenomenon could be induced after repeated injection of mitoxantrone thermosensitive liposomes, LC-MS/MS and enzyme linked immunosorbent assay (ELISA) were used to measure the concentration of mitoxantrone and the anti-polyethylene glycol (PEG) IgM levels in rat plasma, separately. The drug was rapidly cleared away after the second administration. The anti-PEG IgM was detected after the first dose which was neutralized quickly after the second dose. It is proved that repeated administration of mitoxantrone thermosensitive liposomes in rat caused the ABC phenomenon.

Effect of mitoxantrone on proliferation and apoptosis of human multiple myeloma cell RPMI8226 / 中国实验血液学杂志

This study was aimed to investigate the effects of mitoxantrone on proliferation and apoptosis of human multiple myeloma cell line RPMI-8226 and its mechanism. The inhibitory rate of RPMI8226 cells proliferation was assayed by MTT, the morphological changes of RPMI-8226 cells were observed by inverted flurescent microscopy and transmission electron microscopy, the apoptosis rate and the cell cycle distribution of RPMI-8226 cells were detected by flow cytometry. The effects of mitoxantrone on the expression of BCL-2, BAX, caspase-3 mRNA were detected by RT-PCR, the BCL-2, BAX, caspase-3 protein expression of RPMI-8226 cells was analyzed by Western blot. The results showed that mitoxantrone could inhibit the proliferation of RPMI-8226 cells in time- and dose-dependent manners. Light microscopy showed that the cell number in mitoxantrone group was significantly less than that in control group and the cell growth arrangement was irregular, apoptotic cells could be seen. Under electron microscope, typical apoptotic morphological and ultrastructural changes could be observed, these results confirmed that the mitoxantrone could induce apoptosis of RPMI-8226 cells, the difference have statistical significance (P < 0.05). The 1.0 µg/ml low concentration of mitoxantrone mainly arrested RPMI-8226 cells in the G2/M phase(P < 0.05), and the 2.0 µg/ml high concentration of mitoxantrone mainly arrested RPMI-8226 cells in the S phase (P < 0.05). The expression of BCL-2 mRNA decreased (P < 0.05),while the expression of BAX, caspase-3 mRNA increased (P < 0.05). Western blot indicated that BCL-2 protein expression also decreased (P < 0.05) and BAX, caspase-3 protein expression increased. It is concluded that the mitoxantrone can inhibit the proliferation of RPMI-8226 cells by inducing cell apoptosis. Activation of the mitochondrial and death receptor pathways of apoptosis may be involved in the mitoxantrone-induced apoptosis, the cell cycle arrest may also play an important role in the apoptosis mechanism.

Docetaxel plus prednisone versus mitoxantrone plus prednisone as first-line chemotherapy for metastatic hormone-refractory prostate cancer: long-term effects and safety / 中华外科杂志

<p><b>OBJECTIVE</b>To compare docetaxel plus prednisone with mitoxantrone plus prednisone as first-line chemotherapy for metastatic hormone-refractory prostate cancer (mHRPC).</p><p><b>METHODS</b>From January 2007 through August 2010, 62 patients with mHRPC received 5 mg of prednisone twice daily were randomly assigned to receive mitoxantrone 12 mg/m² every three weeks (group A) or 75 mg/m² every three weeks (group B). The cycles of each regimen were less than 10 times. The primary end point was overall survival. The secondary end points were the prostate-specific antigen (PSA) response rate, the duration of PSA response and the objective tumor response rate (ORR). All the t test, χ² test and Fisher's exact test were performed between 2 groups.</p><p><b>RESULTS</b>Thirty-one patients enrolled in group A received a median 4 cycles of regimen (range 1 - 10), whereas 30 patients enrolled in group B received a median of 7 cycles of regimen (range 2 - 10). There were 45.2% patients in group A and 70.0% in group B had PSA response (χ² = 3.85, P < 0.05). The duration time of PSA response was 121 days (range 20-323 days) in group A and 168 days (range 42 - 447 days) in group B, respectively. The ORR was 15.0(3/20) in group A and 10.3% (3/29) in group B, respectively. The median survival was 511 days (95%CI: 357 - 665 days) in group A and 833 days (95%CI: 634 - 1032 days) in group B, respectively (χ² = 4.20, P = 0.040). The incidence of thrombocytopenia in group A was higher than group B (χ² = 5.60, P = 0.018); the incidences of nausea and vomiting (χ² = 4.32, P = 0.038), diarrhea (P = 0.024), fatigue (χ² = 5.90, P = 0.015), and alopecia (χ² = 5.42, P = 0.020) in group B were higher than group A.</p><p><b>CONCLUSION</b>Docetaxel plus prednisone can lead to superior overall survival and PSA response rate in patients with mHRPC.</p>

ABCG2-overexpressing S1-M1-80 cell xenografts in nude mice keep original biochemistry and cell biological properties / 癌症

S1-M1-80 cells, derived from human colon carcinoma S1 cells, are mitoxantrone-selected ABCG2-overexpressing cells and are widely used in in vitro studies of multidrug resistance(MDR). In this study, S1-M1-80 cell xenografts were established to investigate whether the MDR phenotype and cell biological properties were maintained in vivo. Our results showed that the proliferation, cell cycle, and ABCG2 expression level in S1-M1-80 cells were similar to those in cells isolated from S1-M1-80 cell xenografts (named xS1-M1-80 cells). Consistently, xS1-M1-80 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan, but remained sensitive to the non-ABCG2 substrate cisplatin. Furthermore, the specific ABCG2 inhibitor Ko143 potently sensitized xS1-M1-80 cells to mitoxantrone and topotecan. These results suggest that S1-M1-80 cell xenografts in nude mice retain their original cytological characteristics at 9 weeks. Thus, this model could serve as a good system for further investigation of ABCG2-mediated MDR.

Establishment of BCRP expressed pig kidney cell line LLC-PK1/BCRP and its biological profile / 药学学报

To establish a pig kidney cell line LLC-PK1/BCRP in which human breast cancer resistance protein was highly expressed, the expression vector pcDNA3.1(+)-BCRP which contained BCRP gene was constructed and transfected into LLC-PKI cells via liposomes. After selecting with G418, population doubling time, flow cytometry and Western blotting analysis were used to evaluate the cell line. MTT assays were employed to determine the drug resistance index of mitoxantrone and doxorubicin. Invert fluorescent microscope was used to observe the efflux of fluorescence dye Hoechst 33342 by BCRP, furthermore, the BCRP's inhibitor GF120918 was applied to reverse the efflux of Hoechst 33342. The experiment results showed that the expression of BCRP protein increased in LLC-PK1/BCRP cell. The population doubling time of LLC-PK1/BCRP cell was a little longer than that of the parental cell LLC-PK1. The resistance indexes to mitoxantrone and doxorubicin were 51.95 and 6.09 times, respectively, higher than LLC-PK1 cell. The efflux of Hoechst 33342 was significantly enhanced and could be reversed by GF120918. So a LLC-PK1/BCRP cell line was established, which highly expressed BCRP protein successfully. This cell line could be a valuable model to further investigate the biological profile of BCRP and select the substrate and inhibitor of BCRP.

Current Treatment Strategies for Castration-Resistant Prostate Cancer

Prostate cancer is the most common cancer in men in United States and the fifth most common cancer in men in Korea. Although the majority of patients with metastatic prostate cancer initially respond to androgen deprivation therapy, almost all patients will eventually progress to develop castration-resistant prostate cancer (CRPC). Treatment options for CRPC remain limited. Prostate cancer was considered unresponsive to chemotherapy until the mid-1990s, when mitoxantrone combined with prednisone was shown to play a role in the palliative treatment of patients with CRPC. In 2004, two large randomized clinical trials demonstrated for the first time a small but significant survival advantage of docetaxel-based chemotherapy compared with mitoxantrone in patients with metastatic CRPC. Recently, cabazitaxel was shown to improve survival in patients with metastatic CRPC who progressed after docetaxel-based chemotherapy. Sipuleucel-T was also demonstrated to improve overall survival in patients with asymptomatic or minimally symptomatic metastatic CRPC. Along with mitoxantrone and docetaxel, cabazitaxel and sipuleucel-T are now approved for use in metastatic CRPC by the US Food and Drug Administration. There have been multiple early-phase clinical trials of various agents for the treatment of CRPC, and some are in phase III development. This review focuses on the key clinical trials of various treatment options of CRPC currently in use and under investigation.

Fludarabine-containing chemotherapy for patients with previously untreated low-grade non-Hodgkin's lymphoma

BACKGROUND: The clinical efficacy and safety of fludarabine combination chemotherapy was investigated for the treatment of previously untreated patients with low-grade (NHL). METHODS: Twenty-five patients who were newly diagnosed as low-grade NHL were treated with fludarabine combination chemotherapy. Fludarabine combination regimens consisted of fludarabine, mitoxantrone and dexamethasone or fludarabine, cyclophosphamide and mitoxantrone with or without rituximab and repeated every 4 weeks. RESULTS: The median age was 60 years (range, 35-77 years), with 13 of 25 patients (52%) > or =60 years of age. Seven of 25 patients (28%) with an intermediate risk follicular lymphoma international prognostic index (FLIPI) and 9 of 25 patients (36%) with a high risk FLIPI were enrolled in this study. The delivered median number of chemotherapy was six (range, 2-9 cycles). The overall response rate with fludarabine-based treatment was 88%, including 52% complete remission and 36% partial remission. During the median follow-up of 19 months, the estimated 2-year event-free survival was 63+/-10% (95% CI, 43-83) and the 2-year overall survival was 78+/-9% (95% CI, 60-96). Fludarabine combination chemotherapy was frequently associated with grade 3 or 4 neutropenia in 84% patients. However, neutropenic infection was observed in only one (4%) patient. Four patients (16%) showed grade 3 or more non-hematologic toxicities, such as acute coronary syndrome, intracranial hemorrhage, anaphylaxis and gastric cancer. CONCLUSION: Fludarabine-combination treatment was a highly active regimen with well toleration in untreated low-grade NHL.

Regulation mechanism of breast cancer resistance protein by toremifene to reverse BCRP-mediated multidrug resistance in breast cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the regulation mechanism of the reversal of breast cancer resistance protein-mediated multidrug resistance by toremifene.</p><p><b>METHODS</b>Two recombinant plasmids (pcDNA3-promoter-BCRP and pcDNA3-CMV-BCRP) were designed to express the wild-type full-length BCRP cDNA enforced driven by its endogenous promoter containing a functional ERE and a CMV promoter as control, respectively. Two recombinant plasmids were transfected into ERα-positive MCF-7 and ERα-negative MDA-MB-231 breast cancer cell lines. Four kinds of BCRP expressing cell lines of MCF-7/Promoter-BCRP, MCF-7/CMV-BCRP, MDA-MB-231/Promoter-BCRP and MDA-MB-231/CMV-BCRP were established in which BCRP was promoted by the BCRP promoter and a CMV promoter as control, respectively. The drug resistant cells were treated with toremifene. Then RT-PCR, Western blot, mitoxantrone efflux assays and cytotoxicity assay were performed to detect the reversal function of BCRP by toremifene on the drug resistance cell lines.</p><p><b>RESULTS</b>Toremifene significantly downregulated BCRP mRNA levels in a dose-dependent manner in ERα-positive MCF-7/Promoter-BCRP cells than that of untreated control cells. In MCF-7/Promoter-BCRP cells, toremifene at the dose of 0.1, 1 and 10 µmol/L decreased BCRP mRNA expression by 29.5% (P < 0.05), 68.1% (P < 0.01) and 97.4% (P < 0.01), respectively. After being treated with toremifene and 17β-estradiol, the BCRP mRNA level in MCF-7/Promoter-BCRP cells was 64.2% ± 1.3%, significantly higher than that of toremifene treatment control cells (3.8% ± 0.2%,P < 0.01). Furthermore, the effect of toremifene on BCRP protein is similar in BCRP mRNA. Toremifene obviously increased the mitoxantrone fluorescence intensity and decreased the efflux activity by 47.3% (P < 0.05) in MCF-7/promoter-BCRP cells when compared with the untreated control, whereas intracellular accumulation of mitoxantrone obviously decreased and the efflux activity increased by 61.5% were observed in combination with 17β-estradiol when compared with toremifene treatment alone. The results therefore suggested that toremifene reversed mitoxantrone resistance in MCF-7/Promoter-BCRP cells. However, in MCF-7/CMV-BCRP, MDA-MB-231/Promoter-BCRP and MDA-MB-231/CMV-BCRP cells, toremifene or in combination with 17β-estradiol did not affect intracellular mitoxantrone uptake.</p><p><b>CONCLUSION</b>Taken together, our findings indicate that expression of BCRP is downregulated by toremifene, via a novel transcriptional mechanism which might be involved in the ERE of BCRP promoter through ER-mediated to inactivate the transcription of BCRP gene.</p>

Prognostic Factors in Patients with Stage II/III Breast Cancer Treated with Adjuvant Extension of Neoadjuvant Chemotherapy: A Retrospective Cohort Study with Ten-Years of Follow-Up Data / 한국유방암학회지

PURPOSE: The aim of this retrospective study was to identify the reliable long term prognostic factors in patients with stage II/III breast cancer who were treated with an adjuvant extension of neoadjuvant chemotherapy (NC). METHODS: Women under the age of 70-years, with previously untreated clinical stage II and III breast cancer, were treated with NC, which was comprised of three cycles of FEC (5-FU, epirubicin, and cyclophosphamide every 3 weeks) or MMM (methotrexate, mitoxantrone, and mitomycin-C every 3 weeks) with an adjuvant extension of three cycles of the same regimen. RESULTS: Cumulative 10-years disease-free survival (DFS) was 87.3% for patients with a good response and 55.5% for patients with no response (p=0.032); 92.9% for node negative patients, 75.0% for 1-3 positive nodes, 50.0% for 4-9 positive nodes and no survival for 10 or more positive nodes (p<0.001). Cumulative 10-years overall survival (OS) was 89.1% for patients with good response and 55.5% for patients with no response (p=0.024); 95.2% for node negative patients, 80.0% for 1-3 positive nodes, 50.0% for 4-9 positive nodes and no survival for 10 or more positive nodes (p<0.001). No significant difference was observed in DFS and OS between the FEC and MMM treated groups. CONCLUSION: Based on a review of data with a long follow-up, only the clinical response to NC and the absolute number of metastatic axillary lymph node identified at surgical staging were independent predictors of both DFS and OS in patients with stage II/III breast cancer patients treated with adjuvant extension of NC.

Validity of Estimating EuroQol (EQ5D) from a Health Assessment Questionnaire (HAQ) / 대한류마티스학회지

OBJECTIVE: Assessment of health-related quality of life in patients with rheumatoid arthritis (RA) has become important in health research. Health economists have used linear regression equations to mathematically transform changes in HAQ scores into EQ5D data, which can be used to calculate quality adjusted life years (QALYs). We aimed to examine whether a given approach is justified. METHODS: A total of 223 patients with RA were recruited from the Hospital for Rheumatic Diseases at Hanyang University. They completed the HAQ and EQ5D and a correlation analysis was performed between the two instruments. We compared HAQ and EQ5D score changes for patients who completed the EQ5D and HAQ at first and second visits (n=159). Predicted EQ5D was estimated from the HAQ using the calculating method of Bansnack et al. The mean difference between the predicted EQ5D from the HAQ and observed health utility score at the first visit and change during the study were tested by the paired t-test. RESULTS: In the cross-sectional study, EQ5D scores were moderately inversely correlated with HAQ (r=-0.716, p<0.001). However, the predicted EQ5D from the HAQ was significantly different from the observed EQ5D (p=0.001; 95% confidence interval [CI] 0.020~0.079). The change in EQ5D was also inversely correlated with the change in the HAQ (r=-0.615, p<0.001), and change in the predicted EQ5D scores corresponded well with changes in observed health utility scores (p=0.155; 95% CI (-0.0873~0.0140). CONCLUSION: Changes in predicted EQ5D corresponded with observer changes in EQ5D, suggesting that it may be better to use predicted EQ5D form HAQ to identify change in the quality of life.

Pharmacodynamics, pharmacokinetics and tissue distribution of liposomal mitoxantrone hydrochloride / 药学学报

This study is to compare the pharmacodynamics, pharmacokinetics and tissue distribution of liposomal mitoxantrone (Mit-lipo) and free mitoxantrone (Mit-free). The antineoplastic effect of Mit-lipo was evaluated on PC-3 human xenograft tumor model after repeated intravenous injection at dose levels of 1, 2 and 4 mg x kg(-1). The pharmacokinetic study of Mit-lipo and Mit-free was performed on dogs following a single intravenous injection. The tissue distribution of Mit-lipo and Mit-free was observed on S-180 bearing mice after a single intravenous injection. (1) Pharmacodynamics: Mit-lipo dose-dependently inhibited PC-3 tumor growth at a dose ranging from 1 to 4 mg x kg(-1). The antitumor effect studies showed that Mit-lipo significantly improved the therapeutic effect in comparison with free drug. (2) Pharmacokinetics: in comparison with Mit-free, the AUC and t(1/2) values of Mit-lipo at the same dose level were higher than those of Mit-free in Beagle dogs. The results showed that Mit-lipo had long circulation characteristics. (3) Tissue distribution in S-180 bearing mice: compared to Mit-free, Mit-lipo preferentially accumulated into tumor zones instead of normal tissues. Tumor AUC in Mit-lipo treated animals was 8.7 fold higher than that in mice treated with the same dose of Mit-free. The Cmax values of Mit-lipo in heart, kidney, lung, spleen and intestinal tissue in Mit-lipo were 30.2%, 161.6%, 20.2%, 27.9% and 78.3% lower than those of Mit-free, respectively. The pharmacokinetics and tissue distribution of Mit-lipo changed obviously, thus increasing therapeutic effect and improving drug therapeutic index.

Effect of physical exercise on the efficacy of mitoxantrone-loaded nanoparticles in treating early breast cancer / 生物医学工程学杂志

Physical exercise of moderate intensity is becoming readily accepted as an adjunct therapy to enhance curative effects of chemotherapy in patients with breast cancer. In this study, we investigated the putative effect of physical exercise on inhibition of breast cancer and the possible mechanism therein involoved. Balb/c female mice were transplanted with BCAP-37 breast xenografts and randomly assigned to four groups: (a) saline control, (b) exercise-only, (c) DHAQ-loaded NPs, (d) exercise + DHAQ-loaded NPs. The mice in exercise groups performed progressive wheel running up to 15 m/min for 30 minutes, 6 d/wk for 4 weeks. Tumor growth delay was significantly longer in the DHAQ-loaded NPs group and the exercise + DHAQ-loaded NPs groups compared with that in the control group (P < 0.05; P < 0.01, respectively). Tumor volume and the value of hemoglobin (HGB) showed significant difference between the DHAQ-loaded NPs and exercise + DHAQ-loaded NPs groups (P < 0.05), suggesting that physical exercise of moderate intensity can significantly induce an influence of DHAQ-loaded NPs on delay in tumor growth, and can enhance the anti-tumor efficacy of DHAQ-loaded PLA-PLL-RGD NPs. It is a contributor to adjuvant therapy for breast cancer.

Multidrug resistance in breast cancer cells during epithelial-mesenchymal transition is modulated by breast cancer resistant protein / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Epithelial-mesenchymal transition (EMT) not only initiates invasion and metastasis of tumors, but also induces multidrug resistance in tumor cells. Our experiment analyzed the dependability between breast cancer resistant protein (BCRP) and EMT in breast cancer to explore the effect of EMT on BCRP-mediated multidrug resistance.</p><p><b>METHODS</b>The expressions of BCRP and transcription inhibitor Snai1 (Snail) in breast cancer were detected by immunohistochemistry. The eukaryotic expression vector pCDNA3.1-Snail was constructed and then transfected into human breast cancer cell line MCF-7. Snail, epithelial marker gene E-cadherin, interstitial marker gene Vimentin, multidrug resistance protein BCRP, and relative drug resistance were measured by immunofluorescence, Western blot, real-time polymerase chain reaction (PCR), and MTT assay.</p><p><b>RESULTS</b>Immunohistochemistry showed that Snail was highly correlated with BCRP in breast cancer. Immunofluorescence, Western blot, real-time PCR revealed that compared with parent cell MCF-7, after transfected with Snail, the expression of E-cadherin in MCF-7 decreased, but Snail, Vimentin, and BCRP increased. MTT displayed that the relative drug resistance increased to 9.93.</p><p><b>CONCLUSION</b>After transfected with eukaryotic expression vector pCDNA3.1-Snail, breast cancer cells MCF-7 showed EMT with BCRP-mediated multidrug resistance.</p>

Esclerosis múltiple: guía clínica: serie guías clínicas MINSAL 2010 / Multiple sclerosis: clinical guide: clinical guide series MINSAL 2010

Objetivos: -Aportar recomendaciones a los profesionales de salud sobre el manejo de estos pacientes, basadas en la mejor evidencia científica disponible, el consenso de expertos, y adecuada al contexto nacional. -Mejorar la calidad del proceso diagnóstico y terapéutico de los pacientes portadores de EM. -Disminuir la variabilidad de la atención en el manejo de pacientes portadores de EM, en especial en su fase de rehabilitación. -Apoyar la identificación de estándares para la evaluación de estructuras, procesos y resultados de las instituciones involucradas en el manejo de pacientes con EM. Usuarios a los que está dirigida la guía: Esta guía es dirigida a médicos neurólogos, médicos fisiatras, médicos intensivistas, médicos de servicios de urgencia, médicos generales y de familia, kinesiólogos y otros profesionales de salud, con responsabilidad en el manejo de pacientes con EM. También se encuentra dirigida a directivos de instituciones de salud. Métodos: Se realizó una revisión sistemática de la literatura. Se priorizó la selección de revisiones sistemáticas recurriendo en los casos pertinentes a los artículos primarios. También se buscó dirigidamente guías clínicas relacionadas al manejo de EM. A su vez fueron incorporados textos de referencia y artículos aportados directamente por los integrantes del panel. Las recomendaciones fueron realizadas mediante consenso simple en sucesivas etapas de revisión. La construcción de la presente guía consideró la participación de los especialistas involucrados en el piloto de EM. Sucesivas modificaciones de actualización deberán incorporar elementos de la experiencia adquirida. Previo a su publicación, la guía fue sometida a revisión por personas ajenas al grupo que participó en su desarrollo