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Funding Acknowledgements Type of funding sources: None. Background/Introduction Anticoagulant therapy has been important for stroke prevention in patients with atrial fibrillation (AF). However, it was not recommended due to its relatively higher risk of bleeding than its lower risk of stroke in patients with a CHA2DS2-VASc score of 0. Purpose This study aimed to evaluate the predictors of stroke in AF patients with very low risk of stroke. Methods Between 1990 and 2020, 542 patients with non-valvular AF (NVAF) with a CHA2DS2-VASc score of 0 followed up for at least 6 months were enrolled. Patients whose only risk factor was female were included as a CHA2DS2-VASc score of 0 in this study. The primary outcome was stroke or systemic embolism. Results The mean age at AF diagnosis was 49.9 years, and 398 (73.4%) were men. During the mean follow-up of 4.7 years, the primary outcome rate was 0.78%/year (stroke, 0.70%/year; systemic embolism, 0.08%/year), and major bleeding and all-cause death occurred in 0.31%/year and 1.02%/year, respectively. The proportions of age ≥50 years at diagnosis, left ventricular end-diastolic dimension (LVEDD) of ≥46 mm, and non-paroxysmal AF in patients with stroke or systemic embolism were significantly higher than in those without. Cox proportional hazard model, age of ≥50 years at diagnosis (hazard ratio [HR] 6.710, 95% confidence interval [CI] 1.811–24.860, P-value=0.004), LVEDD of ≥46 mm (HR 4.513, 95% CI 1.038–19.626, P-value=0.045), and non-paroxysmal AF (HR 5.575, 95% CI 1.621–19.175, P-value=0.006) were identified as independent predictors of stroke or systemic embolism. Patients with all three independent predictors had a higher risk of stroke or systemic embolism (4.21%/year), whereas those without did not have stroke or systemic embolism. Conclusion The annual stroke or systemic embolism rate in NVAF patients with CHA2DS2-VASc score of 0 was 0.78%/year. Age at AF diagnosis, LVEDD, and non-paroxysmal AF were independent predictors of stroke or systemic embolism in patients considered to be at very low risk of stroke.

Background Current treatment options for peripheral T-cell lymphomas (PTCLs) in the relapsed/refractory setting are limited and demonstrate modest response rates with rare achievement of complete response (CR). Patients and methods This phase I/II study ( NCT03052933 ) investigated the safety and efficacy of copanlisib, a phosphatidylinositol 3-kinase-α/-δ inhibitor, in combination with gemcitabine in 28 patients with relapsed/refractory PTCL. Patients received escalating doses of intravenous copanlisib on days 1, 8, and 15, administered concomitantly with fixed-dose gemcitabine (1000 mg/m2 on days 1 and 8) in 28-day cycles. Results Dose-limiting toxicity was not observed in the dose-escalation phase and 60 mg copanlisib was selected for phase II evaluation. Twenty-five patients were enrolled in phase II of the study. Frequent grade ≥3 adverse events (AEs) included transient hyperglycemia (57%), neutropenia (45%), thrombocytopenia, (37%), and transient hypertension (19%). However, AEs were manageable, and none were fatal. The overall response rate was 72% with a CR rate of 32%. Median duration of response was 8.2 months, progression-free survival was 6.9 months, and median overall survival was not reached. Combination treatment produced a greater CR rate in patients with angioimmunoblastic T-cell lymphoma than those with PTCL-not otherwise specified (55.6% versus 15.4%, respectively, P = 0.074) and progression-free survival was significantly longer (13.0 versus 5.1 months, respectively, P = 0.024). In an exploratory gene mutation analysis of 24 tumor samples, TSC2 mutation was present in 25% of patients and occurred exclusively in responders. Conclusion The combination of copanlisib and gemcitabine is a safe and effective treatment option in relapsed/refractory PTCLs and represents an important new option for therapy in this rare group of patients.

The clinical data and follow-up results of 27 paraspinoid aneurysms treated by Willis covered stent (WCS) in Department of Neurosurgery, Army Medical University from May 2014 to January 2021 were retrospectively analyzed. Among them, 17 cases (63.0%) were treated with WCS alone, and 10 cases (37.0%) were assisted with coiling embolization. During the follow-up, postoperative internal leakage occurred in 2 patients(7%), of which 1(type Ⅰ) wasself-healing and the other 1 (type Ⅲ) was cured by WCS implantation again. The remaining patients had no aneurysm recurrence, unobstructed parent artery, stent displacement and internal stenosis. 92.6% (25/27) of the improved mRS scores were good. WCS is a safe and effective method for the treatment of parabedinal aneurysms.回顾陆军特色医学中心神经外科2014年5月至2021年1月应用Willis覆膜支架（WCS）系统治疗27例床突旁动脉瘤患者的临床资料和随访结果，其中17例（63.0%）单纯应用WCS，10例（37.0%）辅助弹簧圈栓塞。随访期间2例发生术后内漏（7%），其中1例（Ⅰ型内漏）自愈，另1例（Ⅲ型内漏）再次置入WCS治愈，其余患者无动脉瘤复发，载瘤动脉通畅、无支架移位及内狭窄。改良mRS评分良好率92.6%（25/27）。应用WCS治疗床突旁动脉瘤是一种安全、有效的治疗方法。.

Background A clinical decision support tool (CDST) has been developed and validated for predicting outcomes of vedolizumab (VDZ) therapy for patients with Crohn’s disease (CD) and ulcerative colitis (UC), respectively. We aimed to validate each CDST for predicting outcomes and need for drug optimisation in patients with inflammatory bowel disease (IBD). Methods We retrospectively analysed 166 patients with IBD (71 with CD, and 95 with UC) treated with VDZ from January 2017 through November 2021 at 6 tertiary referral centres in Korea. We assessed clinical remission (CREM) and response (CRES), corticosteroid-free clinical remission (CfCREM) and response (CfCRES), biochemical response (BioRES), endoscopic healing (EH), and need for drug optimisation by CDST-defined response groups (low vs. intermediate to high probability group with a cut-off of 13 points in CD, Table 1A, and 26 points in UC, Table 2A, respectively). CDST was evaluated by area under the receiver operating characteristics curve (AUC) and test performance. Results Patients were classified as low (27 with CD, and 28 with UC) and intermediate to high probability group (44 with CD, and 67 with UC). Among CD patients, there showed no significant difference in the response rate of any outcomes between CDST-defined groups. Among UC patients, the rates of CREM (41.0 vs. 18.5%, p=0.040) and EH (56.5 vs. 33.3%, p=0.045) at week 14 were higher among intermediate to high probability group. The rate of drug optimisation during maintenance therapy was also higher in low probability group (54.2 vs. 30.2%, p=0.038). At week 26, CDST for CD discriminated CfCREM with an AUC of 0.656 (sensitivity 87.5%, specificity 43.8%) (Table 1B). Meanwhile, CDST for UC identified CREM with an AUC of 0.606 (sensitivity 83.3%, specificity 37.9%) at week 14 (Table 2B). BioRES of FC was identified with an AUC of 0.649 (sensitivity 84.6%, specificity 45.2%) at week 26. BioRES of CRP was identified with an AUC of 0.660 (sensitivity 68.8%, specificity 63.2%) at week 26, and with an AUC of 0.642 (sensitivity 70.0%, specificity 58.3%) at week 54. Drug optimisation during maintenance therapy was identified with an AUC of 0.620 (sensitivity 54.2%, specificity 69.8%). Conclusion Both CDST for CD and UC can be used to help guide VDZ therapy for Korean patients to predict BioRES with a fair discriminant function and moderate sensitivity.

Background We aimed to investigate the efficacy of oral beclomethasone dipropionate (BDP) as an add-on therapy to concomitant drugs and to clarify the predictive factors for response to oral BDP in Korean patients with ulcerative colitis (UC). Methods Patients with a stable concomitant drug regimen with exposure to oral BDP (5 mg/day) within 30 days before initiation were included. The partial Mayo score (pMS) was used to evaluate response to oral BDP. Clinical remission (CREM) was defined as a posttreatment pMS ≤1 point. Clinical response (CRES) was defined as an at least 2-points decrease in the posttreatment pMS and an at least 30% decrease from the baseline pMS. Patients without CREM or CRES were considered nonresponders (NRs). Results Of total 100 patients, 37 showed CREM, 19 showed CRES, and 44 were NRs (Table 1). The CREM group included more patients with mild disease activity (75.7% vs. 43.2%, P=0.011) than the NR group. In contrast to NR group, responders including CREM and CRES showed significant improvement of posttreatment ESR and CRP (ESR with P=0.001, CRP with P=0.004, respectively). Moreover, initial rectal bleeding subscore (RBS) was significantly different between CREM and CRES, or NR (both with P Conclusion Oral BDP is efficacious as an add-on therapy in Korean UC patients. In case of acute aggravation, patients with mild disease activity, especially low RBS, may be good candidates for oral BDP.

Hepatic vein tumour thrombus (HVTT) is a major determinant of survival outcomes for patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT model was established to predict the prognosis of patients with HCC and HVTT after liver resection, in order to identify optimal candidates for liver resection.Patients with HCC and HVTT from 15 hospitals in China were included. The EHBH-HVTT model with contour plot was developed using a non-linear model in the training cohort, and subsequently validated in internal and external cohorts.Of 850 patients who met the inclusion criteria, there were 292 patients who had liver resection and 198 who did not in the training cohort, and 124 and 236 in the internal and external validation cohorts respectively. Contour plots for the EHBH-HVTT model were established to predict overall survival (OS) rates of patients visually, based on tumour diameter, number of tumours and portal vein tumour thrombus. This differentiated patients into low- and high-risk groups with distinct long-term prognoses in the liver resection cohort (median OS 34·7 versus 12·0 months; P 0·001), internal validation cohort (32·8 versus 10·4 months; P = 0·002) and external validation cohort (15·2 versus 6·5 months; P = 0·006). On subgroup analysis, the model showed the same efficacy in differentiating patients with HVTT in peripheral and major hepatic veins, the inferior vena cava, or in patients with coexisting portal vein tumour thrombus.The EHBH-HVTT model was accurate in predicting prognosis in patients with HCC and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including tumour thrombus in the inferior vena cava, or coexisting portal vein tumour thrombus.La trombosis tumoral de la vena hepática (hepatic vein tumour thrombus, HVTT) es un determinante importante de los resultados de supervivencia en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC). Se desarrolló el modelo llamado Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT para predecir el pronóstico de los pacientes con HCC y HVTT después de la resección hepática (liver resection, LR), con el fin de identificar los candidatos óptimos para LR entre estos pacientes. MÉTODOS: Se incluyeron pacientes con HCC y HVTT de 15 hospitales en China. El modelo EHBH-HVTT con gráfico de contorno se desarrolló utilizando un modelo no lineal en la cohorte de entrenamiento, siendo posteriormente validado en cohortes internas y externas.De 850 pacientes que cumplieron con los criterios de inclusión, hubo 292 pacientes en el grupo LR y 198 pacientes en el grupo no LR en la cohorte de entrenamiento, y 124 y 236 en las cohortes de validación interna y externa. Los gráficos de contorno del modelo EHBH-HVTT se establecieron para predecir visualmente las tasas de supervivencia global (overall survival, OS) de los pacientes, en función del diámetro del tumor, número de tumores y del trombo tumoral de la vena porta (portal vein tumour thrombus, PVTT). Esto diferenciaba a los pacientes en los grupos de alto y bajo riesgo, con distinto pronóstico a largo plazo en las 3 cohortes (34,7 versus 12,0 meses, 32,8 versus 10,4 meses y 15,2 versus 6,5 meses, P 0,001). En el análisis de subgrupos, el modelo mostró la misma eficacia en la diferenciación de pacientes con HVTT, con trombo tumoral en la vena cava inferior (inferior vena cava tumour thrombus, IVCTT) o en pacientes con PVTT coexistente. CONCLUSIÓN: El modelo EHBH-HVTT fue preciso para la predicción del pronóstico en pacientes con HCC y HVTT después de la LR. Identificó candidatos óptimos para LR en pacientes con HCC y HVTT, incluyendo IVCTT o PVTT coexistente.

Background The use of imatinib combined with chemotherapy has demonstrated improved outcome in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). However, a substantial proportion of patients continue to die as a result of disease progression. Patients and methods We assessed the minimal residual disease (MRD)-based effect and long-term outcome of first-line incorporation of dasatinib (100 mg once daily) into chemotherapy alternatively for adults with Ph-positive ALL. The primary end point was the major molecular response (MMR) rate by the end of the second dasatinib cycle. Patients with a donor proceeded to allogeneic stem cell transplantation (SCT) as early as possible. MRD monitoring was centrally evaluated by real-time quantitative polymerase chain reaction (4.5-log sensitivity) using bone marrow samples. Results Fifty-one patients (median age, 46 years) were enrolled and treated with this strategy. After the first dasatinib cycle, 50 patients (98.0%) achieved complete remission (CR). By the end of the second dasatinib cycle, 46 (93.9%) of 49 assessable patients had persistent CR, and 38 (77.6%) had MMR (32.7%) or undetectable MRD (44.9%). On the basis of the MRD kinetics by this time point, the numbers of early-stable, late, and poor molecular responders were 23 (46.9%), 15 (30.7%), and 11 (22.4%), respectively. Thirty-nine patients (76.5%) underwent allogeneic SCT in CR1. After a median follow-up of 54 months, the 4-year cumulative incidence of relapse and disease-free survival (DFS) rate for all patients were 30.0% and 52.0%, respectively, and the corresponding outcomes among those receiving allogeneic SCT in CR1 were 20.5% and 64.1%, respectively. Poor molecular responders had a higher risk of relapse and DFS than those of early-stable molecular responders. Conclusion This dasatinib-based protocol was effective for achieving a good quality molecular response and durable DFS in adults with Ph-positive ALL. Trial registration clinicaltrials.gov, NCT01004497.

Background This nationwide population-based study sought to investigate the risk of spine and hip fracture in patients with inflammatory bowel diseases (IBD). Methods Using the 2007–2016 data from the Korean national health insurance claims database, we calculated incidence rate and incidence rate ratios (IRR) of spine and hip fracture in patients with IBD (n = 18,228; 64.1% male, 65.9% ulcerative colitis [UC]) compared with age- and sex- frequency matched subjects in 1:10 ratio (n = 186,871). A Cox regression model was used to evaluate risk of spine and hip fracture. Results The incidence rate and IRR of spine and hip fracture in IBD were 2.88/1000 person-years and 1.21 (95% confidence interval [CI], 1.11–1.31) during the median follow-up of 4.5 years. The risk for spine and hip fracture was significantly higher in UC (IRR 1.39, 95% CI, 1.25- 1.54), whereas it was not significantly higher in Crohn’s disease (IRR 0.85, 95% CI, 0.67- 1.06) than matched controls. In UC, the IRR of spine fracture was 1.41 (95% CI, 1.24–1.58) and the IRR of hip fracture was 1.40 (95% CI, 1.11–1.71). In multivariable analysis using the Cox regression model, the risk of spine and hip fracture increased with age (p trend < 0.001), in female patients (adjusted hazard ratio [aHR], 1.94; 95% CI, 1.50–2.51) and in patients with comorbidities including osteoporosis (aHR 2.86; 95% CI, 2.10–3.89), stroke (aHR 2.74; 95% CI, 1.78–4.21) hypertension (aHR 1.82; 95% CI, 1.38–2.41), diabetes mellitus (aHR 1.67; 95% CI, 1.25–2.24) and dyslipidaemia (aHR 1.36; 95% CI, 1.05–1.78). Conclusion In a population-based study from Korea, we found that the risk for spine and hip fracture increased in patients with IBD, especially in UC patients. Also, this risk increased in patients who are older, female, or have comorbidities.

Most types of cancers are made up of heterogeneous mixtures of genetically distinct subclones. In particular, acute myeloid leukemia (AML) has been shown to undergo substantial clonal evolution over the course of the disease. AML tends to harbor fewer mutations than solid tumors, making it challenging to infer clonal structure. Here, we present a 9-year, whole-exome sequencing study of a single case at 12 time points, from the initial diagnosis until a fourth relapse, including 6 remission samples in between. To the best of our knowledge, it covers the longest time span of any data set of its kind. We used these time series data to track the hierarchy and order of variant acquisition, and subsequently analyzed the evolution of somatic variants to infer clonal structure. From this, we postulate the development and extinction of subclones, as well as their anticorrelated expansion via varying drug responses. In particular, we show that new subclones started appearing after the first complete remission. The presence and absence of different subclones during remission and relapses implies differing drug responses among subclones. Our study shows that time series analysis contrasting remission and relapse periods provides a much more comprehensive view of clonal structure and evolution.

Background Mantle cell lymphoma (MCL) is a distinct subtype of B-cell lymphoma and comprises approximately 5-10% of all lymphomas. However, in Korea, MCL accounts for just 2% of B-cell lymphomas. In addition to the paucity of the disease, due to lack of feasibility of novel agents for this disease, clinical outcomes of the novel agents have yet to be defined in Korea. Methods We performed a retrospective study of MCL patients treated with ibrutinib in Korea. The primary endpoint of the analysis was progression free survival (PFS) out of ibrutinib treatment. Results Between 2013 to 2019, a total of 75 cases were eligible for analysis. Median age at diagnosis was 69 (range, 40 – 90) and 61 patients (81%) were male. Most patients had an advanced disease at diagnosis (II 10, III 10, IV 55). The received induction regimens were as follows, R-CHOP (N = 48); R-HyperCVAD/MA (N = 10); R-bendamustine (N = 5); VR-CAP (N = 3); others (N = 9) At time of ibrutinib treatment, median age was 71 (range, 41-92), and the median number of prior treatments was 1 (range, 1 – 6). Eleven patients (15%) had received salvage autologous stem cell transplantation. Complete and partial responses were achieved in 31 (41%) and 22 patients (29%), respectively. At a median follow-up duration of 30.5 months (95% CI 25.9 – 35.1), the estimated median PFS was 18.6 months (95% CI 11.0 – 26.2). Those who were classified as low- or intermediated-risk MIPI score at the time of ibrutinib start (24.4 vs. 9.9 months, p = 0.031) demonstrated superior PFS, and patients with tumor size Conclusions The response rate as well as the PFS data of the current study is similar to those of the Western reports. The current study provided additional evidence to support the use of ibrutinib in relapsed or refractory MCL, especially as the early salvage treatment. The compliance and safety data will be presented in the meeting. Funding Janssen, Korea. Disclosure All authors have declared no conflicts of interest.

To assess the predictive value of the albumin to globulin ratio (AGR) in evaluation of disease severity and prognosis in myasthenia gravis patients.A total of 135 myasthenia gravis (MG) patients were enrolled between February 2009 and March 2015. The AGR was detected on the first day of hospitalization and ranked from lowest to highest, and the patients were divided into three equal tertiles according to the AGR values, which were T1 (AGR1.34), T2 (1.34≤AGR≤1.53) and T3 (AGR1.53). The Kaplan-Meier curve was used to evaluate the prognostic value of AGR. Cox model analysis was used to evaluate the relevant factors. Multivariate Logistic regression analysis was used to find the predictors of myasthenia crisis during hospitalization.The median length of hospital stay for each tertile was: for the T1 21 days (15-35.5), T2 18 days (14-27.5), and T3 16 days (12-22.5) (P0.01), and Kaplan-Meier curves showed significant difference among the three groups. In the univariate model, serum albumin, creatinine, AGR and MGFA clinical classification were related to prognosis of myasthenia gravis. At the multivariate Cox regression analysis, the AGR (P0.001) and MGFA clinical classification (P0.001) were independent predictive factors of disease severity and prognosis in myasthenia gravis patients. Respectively, the hazard ratio (HR) were 4.655 (95% CI: 2.355-9.202) and 0.596 (95% CI: 0.492-0.723). Multivariate Logistic regression analysis showed the AGR (P0.001) and MGFA clinical classification were related to myasthenia crisis.The AGR may represent a simple, potentially useful predictive biomarker for evaluating the disease severity and prognosis of patients with myasthenia gravis.

Acute GVHD (aGVHD) is an important risk factor for predicting the incidence or severity of chronic GVHD (cGVHD). Transplant outcome can be influenced by the onset time of aGVHD in patients who have received allogeneic PBSC transplants (PBSCTs). The medical records of 134 patients who survived more than 3 months after myeloablative allogeneic PBSCT were retrospectively reviewed. In all, 38 patients (28.4%) developed grade II-IV aGVHD before day +28 (early aGVHD) and 25 patients (18.7%) after day +28 (late aGVHD). The 5-year cumulative incidence of cGVHD was 78.9% in the early-aGVHD group and 56.6% in the late-aGVHD group (P=0.034). The 5-year OS was 51.0% for the early-aGVHD and 80.8% for the late-aGVHD group (P=0.406). Infection was the primary cause of death for the early-aGVHD group (51.4 vs 16.7%, P=0.017), whereas relapse of the primary disease was higher among the patients with late aGVHD, although this was statistically insignificant (58.3 vs 25.7%, P=0.309). In a multivariate analysis, early aGVHD was identified as a risk factor for developing cGVHD (hazard ratio (HR) 2.278, P=0.004). The development of aGVHD early after allogeneic PBSCT increased the risk of cGVHD and infection-related death rate when compared with the late onset of aGVHD.

Adipokines omentin-1 and adiponectin have been reported to improve insulin resistance. It is known that insulin sensitizers exenatide, avandamet, or diet change from high-fat to normal chow ameliorate metabolic disorders. However, whether these treatments increase omentin-1 levels in high fat-diet animals and the relationship between omentin- 1 and adiponectin remain largely unknown. We investigated the effect of insulin sensitizers exenatide and avandamet, and of dietary change on these adipokine levels, body weight, and insulin sensitivity in diet-induced obese rats. Obesity was induced in rats by high-fat diet feeding for 8 weeks, and then the rats were given exenatide, avandamet and diet change to normal chow, respectively, for additional 8 weeks. Compared to the high-fat control group, exenatide and avandamet treatment significantly induced adipose gene expression and elevated the circulation levels of omentin-1 and adiponectin, whereas they decreased the leptin gene expression and circulation level, which is associated with improvement of systemic insulin sensitivity and the glucose and lipid profile. Notably, there was a significant positive correlation between omentin-1 and adiponectin in the above regimens, suggesting that omentin-1 and adiponectin may contribute to the insulin-sensitizing effect of exenatide and avandamet.

The current study aimed to evaluate the efficacy and toxicity of a combination of intravenous busulfan, cyclophosphamide and etoposide (i.v. Bu/Cy/E) as a conditioning regimen prior to autologous hematopoietic stem cell transplantation in patients with non-Hodgkin's lymphoma (NHL). Sixty-four patients with relapsed/refractory (n=36) or high-risk (n=28) lymphoma were enrolled. The high-dose chemotherapy consisted of i.v. Bu (0.8 mg kg(-1) i.v. q 6 h from day -7 to day -5), Cy (50 mg kg(-1) i.v. on day -3 and day -2) and E (400 mg m(-2) i.v. on day -5 and day -4). The median age was 43 (range 18-65) years, and 39 patients were male. Diffuse large B-cell lymphoma (40.6%) was the most common histological subtype. All evaluable patients achieved an engraftment of neutrophils (median, day 12) and platelets (median, day 13). Hepatic veno-occlusive disease was observed in four patients (three mild, one moderate grade), and two patients (3.1%) died from treatment-related complications. At a median follow-up of 16.4 months, 15 patients (23.4%) exhibited a relapse or progression, while 13 patients (20.3%) had died of disease. The estimated 3-year overall and progression-free survival for all patients was 72.1 and 70.1%, respectively. In conclusion, the conditioning regimen of i.v. Bu/Cy/E was well tolerated and seemed to be effective in patients with aggressive NHL.

P584 Vaccination and risk for inflammatory bowel disease: results of a meta-analysis G. Pineton de Chambrun1 *, L. Dauchet2, C. GowerRousseau2, A. Cortot1, J.-F. Colombel3, L. Peyrin-Biroulet4. 1Lille University Hospital, North of France University, Gastroenterology, Lille, France, 2Lille University Hospital, North of France University, Epidemiology, Lille, France, 3Mount Sinai Hospital, Gastroenterology, New-York, United States, 4Nancy University Hospital, Universite de Lorraine, Gastroenterology and Hepatology, Vandoeuvre-les-Nancy, France

Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3), the predominant IGF carrier protein in circulation, is posttranslationally modified in vivo by IGFBP-3 protease(s) into a number of fragments. Based on the ascertained and predicted recognition sites for known IGFBP-3 proteases, FLAG-epitope tagged intact IGFBP-3, NH2-terminal (1-97), intermediate fragment (88-148), and COOH-terminal fragments (98-264) and (184-264) were generated in a baculovirus and/or Escherichia coli expression system and examined, by Western ligand blot and affinity cross-linking assays, for their ability to bind IGF and insulin. The NH2- and COOH-terminal fragments bound both IGF and insulin specifically (albeit with significantly reduced affinity) for IGF but higher affinity for insulin, when compared with intact IGFBP-3. The effect of IGFBP-3 and the fragments on IGF-I receptor (IGFIR) signaling pathways was studied by testing IGF-I-induced receptor autophosphorylation in IGFIR-overexpressing NIH-3T3 cells. IGFBP-3 showed a dose-dependent inhibition of autophosphorylation of the beta-subunit of IGFIR. The (1-97)NH2-terminal fragment inhibited IGFIR autophosphorylation at high concentrations, and this effect seems largely attributable to sequestration of IGF-I. In contrast, no inhibition of IGF-I-induced IGFIR autophosphorylation was detectable with the (98-264) and (184-264) COOH-terminal fragments, despite their ability to bind IGF. However, unlike the (1-97)NH2-terminal fragment, the COOH-terminal fragments of IGFBP-3 retained their ability to associate with the cell surface, and this binding was competed by heparin, similar to intact IGFBP-3.

The preliminary performance of an optically pumped cesium beam frequency standard is reported. The stability is 1.2*10/sup -11// square root tau , comparable to the stability of commercial conventional cesium beam frequency standards. The bias-saturated-absorption lock technique is used to lock the probing laser and the pumping laser to the cesium D/sub 2/ line. It is a simple, low cost, and reliable locking method with more than 100 h locking time. >

Nonmyeloablative stem cell transplantation following a cytoreductive autograft in patients with non-Hodgkin's lymphoma who relapse after autologous transplantation

This phase II study evaluated the efficacy and safety of combination chemotherapy with paclitaxel, cisplatin, and 5-fluorouracil (5-FU) in advanced gastric cancer. Patients with histologically confirmed gastric adenocarcinoma were eligible for the study. Paclitaxel (175 mg/m(2)) and cisplatin (75 mg/m(2)) were given as a 1-hr intravenous infusion on day 1, followed by 5-FU (750 mg/m(2)) as a 24-hr continuous infusion for 5 days. This cycle was repeated every 3 weeks. Forty-five eligible patients (median age, 56 yr) were treated in this way. Of the 41 patients in whom efficacy was evaluable, an objective response rate (ORR) was seen in 51.2% (95% CI, 0.35-0.67), a complete response in two, and a partial response in 19 patients. The median progression free survival was 6.9 months (95% CI, 5.86-7.94 months), and the median overall survival was 12.7 months (95% CI, 9.9-15.5). The main hematological toxicity was neutropenia and greater than grade 3 neutropenia was observed in twelve patients (54%). Febrile neutropenia developed in three patients (6.8%). The major non-hematological toxicities were asthenia and peripheral neuropathy, but most of patients showed grade 1 or 2. In conclusion, combination chemotherapy with paclitaxel, cisplatin, and 5-FU is a promising regimen, and was well tolerated in patients with advanced gastric cancer.

Primary non-Hodgkin's lymphoma of bone (PLB) is rare, and generally presents as a single extensive and destructive bone lesion. Histopathologically, most cases present as diffuse large B-cell lymphoma, and T-cell lymphoma is rare. By contrast, multiple myeloma is a disease defined as the neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin. We report a case of multiple myeloma that developed during treatment of PLB in a type of T-cell. A 48-yr-old man was diagnosed as T-cell PLB, stage IE, 18 months ago. The patient received the chemoradiotherapy and salvage chemotherapy for PLB. However, the lymphoma progressed with generalized bone pain, and laboratory findings showed bicytopenia and acute renal failure. On bone marrow biopsy, the patient was diagnosed as having multiple myeloma newly developed with primary T-cell lymphoma of bone. In spite of chemotherapy, the patient died of renal failure.