Phase I dose escalation and expansion study of golidocitinib, a highly selective JAK1 inhibitor, in relapsed or refractory peripheral T-cell lymphomas.

BACKGROUND: Relapsed or refractory peripheral T-cell lymphomas (r/r PTCLs) are a group of rare and aggressive diseases that lack effective therapies. Constitutive activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is reported to be associated with PTCLs. Golidocitinib is an oral, potent JAK1 selective inhibitor evaluated in a phase I/II multinational study in patients with r/r PTCLs. PATIENTS AND METHODS: Patients with r/r PTCLs were eligible. The primary objectives were to assess safety and tolerability of golidocitinib and to define its recommended phase II dose (RP2D). The secondary objectives were to evaluate its antitumor activity and pharmacokinetics (PK). RESULTS: A total of 51 patients were enrolled and received golidocitinib treatment at 150 or 250 mg once daily (QD). The median prior lines of therapies were 2 (range: 1-8). Golidocitinib was tolerated at both doses tested, while a higher incidence of serious adverse events and dose modifications at 250 mg were observed. The most common grade ≥3 drug-related treatment-emergent adverse events were neutropenia (27.5%) and thrombocytopenia (11.8%). An objective response rate of 39.2% and a complete response rate of 21.6% were observed. With median follow-up time of 14.7 and 15.9 months, the median duration of response (DoR) and progression-free survival were 8.0 and 3.3 months, respectively. Based on these data, 150 mg QD was defined as the RP2D. Golidocitinib demonstrated a favorable PK profile as an oral agent. Biomarker analysis suggested a potential correlation between JAK/STAT pathway aberrations and clinical activity of golidocitinib. CONCLUSIONS: In this phase I study, golidocitinib demonstrated an acceptable safety profile and encouraging antitumor efficacy in heavily pretreated patients with r/r PTCLs. These results support the initiation of the multinational pivotal study in patients with r/r PTCLs.

Beyond first-line non-anthracycline-based chemotherapy for extranodal NK/T-cell lymphoma: clinical outcome and current perspectives on salvage therapy for patients after first relapse and progression of disease.

BACKGROUND: Current standard treatment, including non-anthracycline-based chemotherapy and optimal combining of radiotherapy, has dramatically improved outcomes of patients with extranodal natural killer/T-cell lymphoma (ENKTL) during the last decade. This study was conducted to investigate the clinical outcome of ENKTL patients with relapsed or progressive disease after initial current standard therapy. PATIENTS AND METHODS: We retrospectively reviewed patients diagnosed with ENKTL at six centers in four countries (China, France, Singapore, and South Korea) from 1997 to 2015 and analyzed 179 patients who had relapsed or progressed after initial current standard therapy. RESULTS: After a median follow-up of 58.6 months (range 27.9-89.2), the median second progression-free survival (PFS) was 4.1 months [95% confidence interval (CI) 3.04-5.16] and overall survival (OS) was 6.4 months (95% CI 4.36-8.51). Multivariate Cox-regression analysis revealed that elevated lactate dehydrogenase, multiple extranodal sites (≥2), and presence of B symptoms were associated with inferior OS (P < 0.05). OS and PFS were significantly different according to both prognostic index of natural killer lymphoma (PINK) and PINK-E (Epstein-Barr virus) models. Salvage chemotherapy with l-asparaginase (l-Asp)-based regimens showed a significantly better clinical benefit to response rate and PFS, although it did not lead to OS improvement. First use of l-Asp in the salvage setting and l-Asp rechallenge at least 6 months after initial treatment were the best candidates for salvage l-Asp containing chemotherapy. CONCLUSIONS: Most patients with relapsed or refractory ENKTL had poor prognosis with short survival. Further studies are warranted to determine the optimal treatment of patients with relapsed or refractory ENKTL.

A phase II study of everolimus (RAD001), an mTOR inhibitor plus CHOP for newly diagnosed peripheral T-cell lymphomas.

BACKGROUND: Everolimus, an oral mTOR inhibitor, has single-agent activity against relapsed lymphomas. Thus, we carried out a phase II study of everolimus in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) as a first-line treatment for patients with peripheral T-cell lymphoma (PTCL) based on our phase I study results. PATIENTS AND METHODS: Participants (n = 30) received CHOP with 5 mg everolimus per day from day 1 to 14 every 21 days for a total of six cycles. The primary end point was the overall response rate (ORR), which included complete response (CR) and partial response (PR) to this regimen. Immunohistochemistry was used to evaluate the expression of phosphatase and tensin homology (PTEN) and phosphorylated S6 kinase (pS6K) as a response. RESULTS: The objective response rate was 90% with CR (n = 17) and PR (n = 10). The CR rate was different among subtypes; angioimmunoblastic T-cell lymphoma (AITL, n = 3) had a CR whereas PTCL-not-otherwise specified and ALK-negative anaplastic large-cell lymphoma (ALCL) patients showed 63% (12/19) and 29% (2/7) of CR rate, respectively. This difference in CR rate among subtypes was associated with PTEN loss because PTEN loss was not seen in AITL but 33% of ALCL patients. The most common toxicity was hematological, with 80% of patients experiencing at least one event of grade 3/4 neutropenia, and 60% of patients had grade 3/4 thrombocytopenia. CONCLUSION: The everolimus plus CHOP was effective for PTCL patients, and its efficacy might be related with the preservation of PTEN.

EBV-positive diffuse large B-cell lymphoma in young adults: is this a distinct disease entity?

BACKGROUND: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is defined only in adults older than 50 years. However, EBV-positive DLBCL can affect younger patients. We investigated the prevalence, clinical characteristics and survival outcomes of EBV-positive DLBCL in young adults. PATIENTS AND METHODS: We analyzed patients with de novo DLBCL who were registered in the Samsung Medical Center (SMC) retrospective lymphoma cohort and prospective SMC Lymphoma Cohort Study I (ClinicalTrials.gov: NCT00822731). RESULTS: A total of 571 cases were included in the analysis. The prevalence of EBV positivity was 6.7% (13/195) and 9.3% (35/376) in the young group (≤50 years) and in the elderly group (>50 years), respectively. EBV status was closely associated with unique unfavorable clinical characteristics [older age, more advanced stage, two or more sites of extranodal involvement, higher International Prognostic Index (IPI), and age-adjusted IPI risk] only in the elderly group. Poor prognostic impact of EBV positivity on overall survival was observed only in the elderly group [hazard ratio (HR) 2.86; 95% confidence interval (CI) 1.83-4.47; P < 0.001], but not in the young group (HR 1.17; 95% CI 0.35-3.89; P = 0.801). CONCLUSION: A substantial proportion of EBV-positive DLBCL of the elderly can occur in young adults. EBV positivity of DLBCL in young adults was not associated with unfavorable clinical characteristics or worse outcomes. We suggest that EBV-positive DLBCL should not be confined only in the elderly and 'EBV-positive DLBCL in young adults' needs to be considered as a clinically distinct disease entity. ClinicalTrials.gov: NCT02060435.

The highest prognostic impact of LDH among International Prognostic Indices (IPIs): an explorative study of five IPI factors among patients with DLBCL in the era of rituximab.

Although the International Prognostic Index (IPI) is considered as the current standard prognostication system for diffuse large B-cell lymphoma (DLBCL), prognostic heterogeneity is suggested to exist among the patients within the same IPI risk group. Hence, we investigated the pattern of distribution and prognostic impact of five IPI factors within the same IPI score. We retrospectively reviewed the medical records of 387 patients newly diagnosed as pathologically proven DLBCL between February 2002 and February 2010. We classified patients to IPI risk scores and categorized them according to the combinations of IPI. Then, we explored the frequency of five IPI factors and analyzed the correlation between these subgroups and efficacy outcomes: complete response (CR), event-free survival (EFS), and overall survival (OS). Survival estimates by IPI score in this cohort corresponded to the classic IPI. Elevated serum level of lactate dehydrogenase (LDH) was the most prevalently distributed factor throughout the scores, and patients with elevated serum level of LDH tended to have lower CR, inferior EFS, and/or OS irrespective of IPI scores. Particularly, among the subgroups of IPI score of 2, elevated serum level of LDH was significantly associated with inferior CR (73.1 vs 95.2 %), 3-year EFS (57 vs 87 %), and 3-year OS (58 vs 82 %). In addition, the higher serum level of LDH, particularly above 2,000 IU/L, was significantly correlated with the inferior survival outcomes (3-year EFS 78.0 vs 58.5 vs 45.5 vs 20.0 %, 3-year OS 86.0 vs 66.2 vs 58.2 vs 40.0 %). In conclusion, among five factors of IPI, elevated serum level of LDH seems to be the most frequently distributed and, more importantly, the most relevant IPI factor with the highest prognostic impact. These findings still warrant further validation in larger cohorts.

Thermochromic properties of Sn, W co-doped VO2 nanostructured thin film deposited by pulsed laser deposition.

Tin (Sn) and tungsten (W) co-doped vanadium dioxide (VO2) nanostructured thin films with 50-nm thickness were deposited by pulsed laser deposition (PLD) to reduce the transition temperature and improve the IR transmittance. The crystal structure of the nanostructured thin films and the presence of elements were evaluated by XRD and XPS analysis. The transition temperature (T(c)) of 1 at% Sn-1 at% W co-doped VO2 nanostructured thin film was decreased to about 22 degrees C (from 70.3 to 48.5 degrees C) compared with the undoped VO2 nanostructured thin film. The transmittance width in the IR range of the co-doped nanostructured thin film decreased from 37.5% to 27% compared with the undoped VO2 nanostructured thin film. Also, the width of hysteresis was narrowed by Sn doping.

Comparison of the QuantiFERON-TB Gold In-Tube test with the tuberculin skin test for detecting latent tuberculosis infection prior to hematopoietic stem cell transplantation.

A total of 244 patients including 100 (41%) autologous hematopoietic stem cell transplant (HCT) recipients and 144 (59%) allogeneic HCT recipients were enrolled over a 28-month period. During the study period, no prophylaxis for latent tuberculosis (TB) infection was administrated. Of these, 201 (82%) had Bacillus Calmette-Guérin (BCG) scars or prior histories of BCG vaccination. The tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-GIT) test were performed simultaneously in all 244 patients. TST indurations were ≥ 5 mm in 39 of these patients (15%), and in 25 (10%) indurations were ≥ 10 mm. In addition, 40 (16%) had positive QFT-GIT outcomes, and 34 (14%) indeterminate outcomes. If the 34 patients with indeterminate QFT-GIT results were excluded from the overall agreement analysis, the agreement between the TST results (induration size ≥ 5 mm) and the QFT-GIT results in the 210 patients with clear QFT results was poor (κ = 0.08, 95% confidence interval [CI] -0.06 to 0.24), as it was for the patients with indurations ≥ 10 mm (κ = 0.15, 95% CI -0.004 to 0.31). During follow up, 2 patients developed TB after HCT. The incidence of TB in the patients with positive QFT-GIT outcomes was 2.80 per 100 person-years (95% CI 0.07-15.81), whereas among those with positive TST (≥ 5 mm) results, it was 0 per 100 person-years (95% CI 0-8.00). However, this finding should be cautiously interpreted because of the relatively short follow up and the fact that the sample size of the study cohort did not have adequate power. In conclusion, our data show that, although the frequencies of positive outcomes in the 2 TB screening tests were similar, the overall agreement between the TST and the QFT-GIT test was poor, regardless of BCG vaccination history.

Stage IE/IIE extranodal NK/T-cell lymphoma arising in the nasal cavity: analysis of CT findings and their prognostic value.

AIM: To investigate the computed tomography (CT) findings in patients with stage IE/IIE extranodal natural killer/T-cell lymphoma (ENKTL) arising in the nasal cavity and to evaluate whether imaging findings revealed by CT have prognostic value. MATERIALS AND METHODS: The CT findings of 62 patients diagnosed with IE/IIE ENKTL arising in the nasal cavity were retrospectively reviewed. Imaging findings were investigated, and evaluated imaging findings were analysed for the prognostic value of overall survival (OS) and disease-free survival (DFS). RESULTS: Of the 62 patients, 21 (34%) presented with a superficial infiltrative, 38 (61%) with a mass forming, and three (5%) with a combined pattern. Of all imaging findings, local invasiveness (n = 26, 42%), including bony destruction, erosion, or soft-tissue involvement, was the only independent prognostic factor for OS [p = 0.008; hazard ratio (HR): 3.85; 95% confidence intervals (CI): 1.42-10.44] and DFS (p = 0.001; HR: 4.25; 95% CI: 1.72-10.47). In a subgroup analysis of 36 cases with no local invasiveness, a superficial infiltrative pattern in one nasal cavity was a positive prognostic factor for OS (p = 0.028) and DFS (p = 0.008). CONCLUSION: Imaging findings at CT provided clinically useful predictions for treatment outcomes. Local invasiveness revealed by CT findings was a strong prognostic factor for poor OS and DFS. In addition, in patients with no local invasiveness, a superficial infiltrative pattern in one nasal cavity predicted favourable OS and DFS.

Genetic Polymorphisms of the Bovine NOV Gene Are Significantly Associated with Carcass Traits in Korean Cattle.

The objective of this study was to investigate single nucleotide polymorphisms (SNPs) in the bovine nephroblastoma overexpressed (NOV) gene and to evaluate whether these polymorphisms affect carcass traits in the Korean cattle population. We resequenced to detect SNPs from 24 unrelated individuals and identified 19 SNPs within the full 8.4-kb gene, including the 1.5-kb promoter region. Of these 19 SNPs, four were selected for genotyping based on linkage disequilibrium (LD). We genotyped 429 steers to assess the associations of these four SNPs with carcass traits. Statistical analysis revealed that g.7801T>C and g.8379A>C polymorphisms in the NOV gene were associated with carcass weight (p = 0.012 and 0.008, respectively), and the g.2005A>G polymorphism was associated with the back fat thickness (BF) trait (p = 0.0001). One haplotype of the four SNPs (GGTA) was significantly associated with BF (p = 0.0005). Our findings suggest that polymorphisms in the NOV gene may be among the important genetic factors affecting carcass yield in beef cattle.

Hypoxia-specific GM-CSF-overexpressing neural stem cells improve graft survival and functional recovery in spinal cord injury.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine that stimulates the differentiation and function of hematopoietic cells. GM-CSF has been implicated in nervous system function. The goal of the present study was to understand the effects of hypoxia-induced GM-CSF on neural stem cells (NSCs) in a model of spinal cord injury (SCI). GM-CSF-overexpressing NSCs were engineered utilizing a hypoxia-inducible gene expression plasmid, including an Epo enhancer ahead of an SV promoter (EpoSV-GM-CSF). Cells were then subjected to hypoxia (pO(2), 1%) or a hypoxia-mimicking reagent (CoCl(2)) in vitro. The progression of time of GM-CSF expression was tracked in EpoSV-GM-CSF-transfected NSCs. Overexpression of GM-CSF in undifferentiated and differentiated NSCs created resistance to H(2)O(2)-induced apoptosis in hypoxia. NSCs transfected with EpoSV-GM-CSF or SV-GM-CSF were transplanted into rats after SCI to assess the effect of GM-CSF on NSC survival and restoration of function. Moreover, a significantly higher amount of surviving NSCs and neuronal differentiation was observed in the EpoSV-GM-CSF-treated group. Significant improvement in locomotor function was also found in this group. Thus, GM-CSF overexpression by the Epo enhancer in hypoxia was beneficial to transplanted NSC survival and to behavioral improvement, pointing toward a possible role for GM-CSF in the treatment of SCI.

Phase II study of everolimus with biomarker exploration in patients with advanced gastric cancer refractory to chemotherapy including fluoropyrimidine and platinum.

BACKGROUND: To evaluate the activity and safety of everolimus and identify potential biomarkers for efficacy of everolimus in patients with advanced gastric cancer (AGC), who failed both fluoropyrimidine and platinum. METHODS: Fifty-four patients received everolimus (10 mg day(-1)). The primary objective was to determine the 4-month progression-free survival (PFS) rate, assumed to be 30%. We additionally investigated the potential biomarkers for everolimus as an exploratory endpoint in those who underwent tumour biopsies. RESULTS: Two patients (3.7%) achieved partial response and the disease control rate (DCR) was 38.9%. At a median follow-up duration of 8.7 months, the 4-month PFS rate was 18.4%, not fulfilling the primary hypothesis, with a median PFS of 1.7 months and a median overall survival of 8.3 months. The high expression of pS6(Ser240/4) at baseline was significantly associated with higher DCR (P=0.043) and prolonged PFS (P=0.001). Grade 1/2 asthenia (96.3%) recorded as the leading toxicity and hyperglycaemia (20.4%) was the most common non-hematological grade 3/4 toxicity. Three patients experienced grade 3/4 pneumonitis. Notably, two experienced treatment-related deaths. CONCLUSION: Everolimus is active against a limited number of patients with AGC. pS6(Ser240/4) may be a potential predictive biomarker for everolimus, which requires validation. Careful monitoring is necessary despite generally favourable toxicity profile.

Extranodal natural killer/T-cell lymphoma from skin or soft tissue: suggestion of treatment from multinational retrospective analysis.

BACKGROUND: Clinical features and outcomes of extranodal natural killer/T-cell lymphoma (ENKL) arising from extranasal sites are not fully understood. The purpose of this study was to study the prognosis and treatment outcome of skin/soft tissue primary ENKL. PATIENTS AND METHODS: This multicenter retrospective study included 48 patients with skin/soft tissue primary ENKL diagnosed from 1993 to 2010. RESULTS: Patients with Ann Arbor stage I, T1-2N0M0 by International Society for Cutaneous Lymphomas-European Organization of Research and Treatment of Cancer TNM (tumour-node-metastasis) stage, International prognostic index score of 0-1, and a Korean prognostic index (KPI) score of 0-1 were associated with better survival. Four of five patients with T1-2N0M0 disease achieved complete response with radiation alone. In disseminated disease, only 6 of 13 patients responded to anthracycline-containing chemotherapy, and all the two patients receiving SMILE showed response. CONCLUSION: In conclusion, we identified the prognostic value of KPI, and we suggest a treatment recommendation according to the TNM (tumour-node-metastasis) stage. Radiotherapy with/without chemotherapy seemed to be optimal in localized disease. In advanced stages, a more aggressive treatment regimen with newer agents should be sought.

The role of prophylactic antimicrobials during autologous stem cell transplantation: a single-center experience.

The aim of this study was to investigate the efficacy of antibiotic prophylaxis in patients undergoing autologous stem cell transplantation (ASCT) for multiple myeloma and non-Hodgkin lymphoma. Among 232 ASCT cases performed at the Asan Medical Center, 114 cases underwent treatment with ciprofloxacin, fluconazole, and acyclovir (between January 2001 and August 2005), while 118 cases were performed without antimicrobial prophylaxis (between February 2004 and June 2008). The two-rate χ2 test was applied to accommodate the differences in neutropenia duration. The incidence of febrile episodes was 9.8 cases per 100 person-days in the prophylactic group, while it was 16.2 cases in the no-prophylactic group (p<0.001). The rate of unexplained fever was 8.0 cases per 100 person-days in the prophylactic group, while it was 13.8 cases in the no-prophylactic group (p<0.001). The rate of clinically and microbiologically documented infection was 1.7 cases per 100 person-days in the prophylactic group, while it was 2.3 cases in the no-prophylactic group (p=0.404). There were fewer cases of methicillin-susceptible Staphylococcus aureus infection and a greater number of quinolone-resistant Escherichia coli in the prophylactic group compared with the no-prophylactic group (p=0.056 and p=0.040, respectively). The prophylactic antimicrobials reduced the incidence rate of febrile episodes, especially unexplained fever, despite there being no difference in the incidence of documented infection. Resistant microbe infection occurred more frequently in the prophylactic group.

Characterization of the MgO nano powder synthesized by using a liquid phase precursor method for plasma display panels protecting layer.

The characterization of MgO nano powders that were synthesized using a conventional firing liquid phase precursor, rapid firing liquid phase precursor and rapid cooling firing liquid phase precursor were investigated as a function of the heating and cooling rates and the concentration of the impregnated Mg(NO3)2 x 6H2O solution from 1 to 20%. The relative intensity of diffraction peak in the MgO nano powder increased with increasing firing temperature from 800 to 1200 degrees C, indicating a higher crystalline MgO nano powder. In addition, the relative intensities of the MgO nano powder synthesized at the designated temperature showed similar behavior regardless of the impregnated Mg(NO3)2 x 6H2O solution concentration from the XRD analysis. The field emission scanning electron microscope and high resolution transmission electron microscope analysis showed that the size and shape of the MgO nano powder can be controlled by the temperature, the firing and cooling processes, and the impregnated Mg(NO3)2 x 6H2O solution concentration. Moreover, the CL spectra of the synthesized MgO nano powders showed a higher luminance efficiency than commercial MgO nano powder.

Proteome Analysis of Bovine Longissimus dorsi Muscle Associated with the Marbling Score.

The breeding value of marbling score in skeletal muscle is an important factor for evaluating beef quality. In the present study, we investigated proteins associated with the breeding value of the marbling score for bovine sirloin to select potential biomarkers to improve meat quality through comparative proteomic analysis. Proteins isolated from muscle were separated by two-dimensional gel electrophoresis. After analyzing images of the stained gel, seven protein spots for the high marbling score group were identified corresponding to changes in expression that were at least two-fold compared to the low marbling score group. Four spots with increased intensities in the high marbling score group were identified as phosphoglycerate kinase 1, triosephophate isomerase, acidic ribosomal phosphoprotein PO, and capping protein (actin filament) Z-line alpha 2. Spots with decreased intensities in the high marbling score group compared to the low score group were identified as 14-3-3 epsilon, carbonic anhydrase II, and myosin light chain 1. Expression of myosin light chain 1 and carbonic anhydrase 2 was confirmed by Western blotting. Taken together, these data could help improve the economic performance of cattle and provide useful information about the underlying the function of bovine skeletal muscle.

Determination of Genetic Diversity among Korean Hanwoo Cattle Based on Physical Characteristics.

This study was conducted to establish genetic criteria for phenotypic characteristics of Hanwoo cattle based on allele frequencies and genetic variance analysis using microsatellite markers. Analysis of the genetic diversity among 399 Hanwoo cattle classified according to nose pigmentation and coat color was carried out using 22 microsatellite markers. The results revealed that the INRA035 locus was associated with the highest Fis (0.536). Given that the Fis value for the Hanwoo INRA035 population ranged from 0.533 (white) to 1.000 (white spotted), this finding was consistent with the loci being fixed in Hanwoo cattle. Expected heterozygosities of the Hanwoo groups classified by coat colors and degree of nose pigmentation ranged from 0.689±0.023 (Holstein) to 0.743±0.021 (nose pigmentation level of d). Normal Hanwoo and animals with a mixed white coat showed the closest relationship because the lowest DA value was observed between these groups. However, a pair-wise differentiation test of Fst showed no significant difference among the Hanwoo groups classified by coat color and degree of nose pigmentation (p<0.01). Moreover, results of the neighbor-joining tree based on a DA genetic distance matrix within 399 Hanwoo individuals and principal component analyses confirmed that different groups of cattle with mixed coat color and nose pigmentation formed other specific groups representing Hanwoo genetic and phenotypic characteristics. The results of this study support a relaxation of policies regulating bull selection or animal registration in an effort to minimize financial loss, and could provide basic information that can be used for establishing criteria to classify Hanwoo phenotypes.

Effects of High-Speed Power Training on Neuromuscular and Gait Functions in Frail Elderly with Mild Cognitive Impairment Despite Blunted Executive Functions: A Randomized Controlled Trial.

BACKGROUND: Physical frailty and impaired executive function of the brain show similar pathophysiology. Both of these factors lead to dysfunction of neuromuscular and abilities in elderly. High-speed power training (HSPT) has been determined to have positive effects on neuromuscular function and gait performance, as well as executive function in the elderly. OBJECTIVES: The purpose of this study was to investigate the effects of 8-week HSPT on neuromuscular, gait and executive functions in frail elderly with mild cognitive impairment (MCI). DESIGN, SETTING AND PARTICIPANTS: We performed a randomized controlled trial of frail elderly from community and medical center in republic of Korea. Forty-two physically frail elderly with MCI were randomly allocated to control (n=22, age=74.22±4.46) and intervention groups (n=18, age=73.77±4.64). The intervention group was subjected to HSPT, 3 times weekly for 8 weeks. MEASUREMENTS: Isometric contraction of knee extension and flexion with electromyography (EMG) was measured to determine the neuromuscular function such as knee extensor strength, rate of torque development, movement time, pre-motor time, motor time, rate of EMG rise, and hamstrings antagonist co-activation. Additionally, the 4.44-meter gait and timed up-and-go (TUG) test were administered to assess gait performance. A frontal assessment battery was measured in this study. RESULTS: The 8-week HSPT regimen improved the knee extensor strength from 1.13±0.08 to 1.25±0.07 (p<0.05), the 200-ms RTD from 3.01±0.3 to 3.55±0.24 (p<0.05) and the rate of EMG rise from 166.48±13.31 to 197.94±11.51 (p<0.05), whereas the movement time and motor time were statistically decreased from 921.69±40.10 to 799.51±72.84, and 271.40±19.29 to 181.15±38.08 (p<0.05), respectively. The 4.44-m gait speed and TUG significantly decreased from 6.39±0.25 to 5.5±0.24, and 11.05±0.53 to 9.17±0.43 respectively (p<0.05). CONCLUSION: The findings of this study suggest the favorable effects of 8-week HSPT on the neuromuscular function and the gait performance in the frail elderly with MCI without increase in the executive function.

Single crystal growth of nanoporous C12A7:e- by controlling melt state.

It has been known that electron doped 12CaO x 7Al2O3 (C12A7:e-, electride) single crystals, which are composed of a closed-packed periodic quantum dot structure, may be prepared by strong reduction of the precursor C12A7:O2-, but direct single crystal growth of the C12A7:e- from the melt state has never been achieved to date. We report the melt state of polycrystalline electride in pure dry Ar atmosphere at temperatures of 1290 approximately 1500 degrees C, which leads to the direct single crystal growth of the C12A7:e- from the melt. The electride single crystals with a diameter of 7 mm and a length of 43 mm have been grown by a floating zone method, where a polycrystalline electride feed and an electride single crystal seed rod were employed. The electron concentration in the crystal increased up to approximately 1.0 x 10(20) cm(-3) as the growth proceeded. The present findings suggest that electron-entrapped local structure may exist in the melt and the electrons may act as a template for the formation of C12A7 electride in the solidification process of the C12A7 lattice.

Phase II study of erlotinib as a salvage treatment for non-small-cell lung cancer patients after failure of gefitinib treatment.

BACKGROUND: Both gefitinib and erlotinib are reversible epidermal growth factor receptor tyrosine kinase inhibitors, but they have somewhat different pharmacological properties. We conducted a phase II study of erlotinib after failure of gefitinib treatment in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced/metastatic NSCLC who had shown disease progression on gefitinib treatment were treated with erlotinib 150 mg/day until disease progression or intolerable toxicity. RESULTS: Between September 2006 and January 2008, a total of 23 patients were enrolled and all were assessable for response and toxicity. All patients were never smokers and all but one had adenocarcinoma. Of these 23 patients, one had a partial response and one stable disease, resulting in an objective response rate of 4.3% and a disease control rate of 8.7%. These two patients benefited from erlotinib for 6.2 months and 7.8 months, respectively; both had also benefited from prior gefitinib therapy. The most common toxic effects were skin rash and diarrhea. CONCLUSION: Erlotinib should not be given routinely after failure of gefitinib treatment, but can be an option for more highly selected subsets, especially those who had benefited from prior gefitinib treatment. Identification of molecular markers in tumors is important to understand and overcome acquired resistance to gefitinib.