[Show abstract][Hide abstract] ABSTRACT: hBMSCs are multipotent cells that are useful for tissue regeneration to treat degenerative diseases and others for their differentiation ability into chondrocytes, osteoblasts, adipocytes, hepatocytes and neuronal cells. In this study, biodegradable elastic hydrogels consisting of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(ε-caprolactone) (PCL) scaffolds were evaluated for tissue engineering because of its biocompatibility and the ability to control the release of bioactive peptides. The primary cultured cells from human bone marrow are confirmed as hBMSC by immunohistochemical analysis. Mesenchymal stem cell markers (collagen type I, fibronectin, CD54, integrin1b, and Hu protein) were shown to be positive, while hematopoietic stem cell markers (CD14 and CD45) were shown to be negative. Three different hydrogel scaffolds with different block compositions (PEG:PCL=6:14 and 14:6 by weight) were fabricated using the salt leaching method. The hBMSCs were expanded, seeded on the scaffolds, and cultured up to 8 days under static conditions in Iscove's Modified Dulbecco's Media (IMDM). The growth of MSCs cultured on the hydrogel with PEG/PCL= 6/14 was faster than that of the others. In addition, the morphology of MSCs seemed to be normal and no cytotoxicity was found. The coating of the vascular endothelial growth factor (VEGF) containing scaffold with Matrigel slowed down the release of VEGF in vitro and promoted the angiogenesis when transplanted into BALB/c nude mice. These re- sults suggest that hBMSCs can be supported by a biode gradable hydrogel scaffold for effective cell growth, and enhance the angiogenesis by Matrigel coating.
[Show abstract][Hide abstract] ABSTRACT: Bortezomib is widely used for the treatment of multiple myeloma. Bone marrow stromal cells (BMSCs) endow myeloma cells with survival and growth advantages. However, the influence of bortezomib on BMSCs is not well elucidated. We examined the effects of bortezomib on the survival and growth of BMSCs in vitro.
The effects of bortezomib on the survival and proliferation of the BMSC MS-5 cell line and on BMSCs obtained from healthy individuals (N=4) and newly diagnosed myeloma patients (N=5) were investigated in vitro. Transmembrane cell migration was evaluated using the Transwell system. A short interfering RNA strategy was used to knock down the expression of chemokine (CXC motif) ligand 12 (CXCL12) mRNA. To examine the effects of bortezomib-exposed BMSCs on the migration and localization of myeloma cells, MS-5 monolayers were treated with bortezomib for 24 hr, washed, and then overlaid with human RPMI8226 myeloma cells.
Bortezomib inhibited BMSC proliferation in a concentration-dependent manner, and induced cellular apoptosis. Bortezomib decreased CXCL12 production by BMSCs. Knockdown of CXCL12 mRNA in BMSCs revealed that CXCL12 served as an autocrine growth factor. Short-term bortezomib treatment of BMSC monolayers reduced the tendency of myeloma cells to locate to positions under the monolayers.
Bortezomib inhibits the survival and growth of BMSCs via downregulation of CXCL12, which may contribute to the clinical effects of this agent.
Blood Research 06/2015; 50(2):87-96. DOI:10.5045/br.2015.50.2.87
[Show abstract][Hide abstract] ABSTRACT: There is no regimen that is strongly recommended for more than second-line treatment. We investigated the efficacy and safety of platinum/vinorelbine as more than second-line treatment.
We selected patients with advanced NSCLC who received treatment with platinum/vinorelbine at Chungnam National University Hospital from August 2001 to December 2013. The primary end point was the response rate, and secondary end points were progression-free survival (PFS), overall survival (OS), and toxicity.
Thirty-five patients were enrolled. Response rate was 22.9% (complete response 0 patients (0.0%); partial response eight patients (22.9%); stable disease 10 patients (28.6%); progressive disease 14 patients (40.0%)). A significantly higher response rate was observed for patients who had responded to previous chemotherapy than for those who did not (34.8% [8/23] vs. 0% [0/12], p=0.020). The median progression-free survival was 4 (range 1-21) months. Patients with adenocarcinoma and non-smokers had a significantly longer PFS than patients with non-adenocarcinoma and smokers (5 vs. 2 months, p=0.007; 4.5 vs. 2 months, p=0.046, respectively). The median overall survival was 10 (range 1-41) months. Patients with good performance status and non-smokers had a significantly longer OS than patients with poor performance status and smokers (14 vs. 4 months, p=0.02; 18.5 vs. 6 months, p=0.049, respectively). The main serious adverse event (grade 3 or 4) was neutropenia (15 events, 13.3%) in a total of 113 cycles.
Platinum/vinorelbine was effective as more than second-line chemotherapy, and the toxicity was tolerable, in patients with advanced NSCLC.
Cancer Research and Treatment 03/2015; DOI:10.4143/crt.2014.316 · 2.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Screening for second primary cancer (SPC) is one of the key components to survivorship care. We aim to evaluate the oncologists' experience with SPCs and assess the current practice, perceived barriers, and recommendations related to SPC screening.
A nationwide survey was conducted with a representative sample of 496 Korean oncologists. A questionnaire based on the findings from our previous qualitative study was administered.
More than three-fourths of oncologists (76.3%), who participated in the study, had experience with SPC patients. Over half of them (51.9%) stated that it was an embarrassing experience. While the current management practice for SPC varies, most oncologists (80.2%) agreed on the necessity in proactively providing information on SPC screening. A short consultation time (52.3%), lack of guidelines and evidence on SPC screening (47.7%), and patients' lack of knowledge about SPCs (45.1%) or SPC screening (41.4%) were most frequently reported as barriers to providing appropriate care for managing SPC. Oncologists recommended the development of specific screening programs or guidelines in accordance to the type of primary cancer (65.9%), the development of an internal system for SPC screening within the hospital (59.7%) or systematic connection with the national cancer screening program (44.3%), and education of oncologists (41.4%) as well as patients (48.9%) regarding SPC screening.
Many oncologists reported the occurrence of SPC as an embarrassing experience. Given the variations in current practice and the lack of consensus, further studies are warranted to develop the optimal clinical strategy to provide SPC screening for cancer survivors.
Cancer Research and Treatment 02/2015; DOI:10.4143/crt.2014.162 · 2.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The first edition of the Korean treatment guidelines for chronic myelogenous leukemia (CML) was published in 2006. We intend to update those guidelines to include the use of next-generation tyrosine kinase inhibitors (TKIs).
[Show abstract][Hide abstract] ABSTRACT: Plasmacytoma in patients with multiple myeloma usually develops in the advanced stage of the disease. We report herein an atypical case of extramedullary relapse of multiple myeloma that presented as mechanical obstruction of the small bowel in a patient who had achieved complete remission after chemotherapy. A 75-year-old man was diagnosed with multiple myeloma 25 months previously and treated with a bortezomib-containing chemotherapy regimen. He presented for evaluation of abdominal pain. A circumferential mass resulting in mechanical ileus was observed by abdominal computed tomography. Biopsy after surgical resection confirmed the diagnosis of plasmacytoma. The patient was subsequently treated with thalidomide-containing chemotherapy, but he died of disease progression after 6 months. We suggest careful observation of unusual relapses of multiple myeloma in patients who have achieved complete remission after antimyeloma therapy.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study is to determine the diagnostic and prognostic role of baseline spinal magnetic resonance imaging (MRI) in patients with multiple myeloma.
We enrolled patients newly diagnosed with multiple myeloma from 2004-2011 at a single center. Abnormal MRI findings that were not detected in radiographs have been analyzed and categorized as malignant compression fractures or extramedullary plasmacytoma. The bone marrow (BM) infiltration patterns on MRI have been classified into five categories.
A total of 113 patients with a median age of 65 years (range, 40 to 89 years) were enrolled in the study. Malignant compression fractures not detected in the bone survey were found in 26 patients (23.0%), including three patients (2.6%) with no related symptoms or signs. Extramedullary plasmacytoma was detected in 22 patients (19.5%), including 15 (13.3%) with epidural extension of the tumor. Of these 22 patients, 11 (50.0%) had no relevant symptoms or signs. The presence of malignant compression fractures did not influence overall survival; whereas non-epidural extramedullary plasmacytoma was associated with poor overall survival in the multivariate analysis (hazard ratio, 3.205; 95% confidence interval [CI], 1.430 to 9.845; p=0.042). During the follow-up for a median of 21 months (range, 1 to 91 months), overall survival with the mixed BM infiltrative pattern (median, 24.0 months; 95% CI, 22.9 to 25.1 months) was shorter than those with other patterns (median 56 months; 95% CI, 48.9 to 63.1 months; p=0.030).
These results indicate that spine MRI at the time of diagnosis is useful for detecting skeletal lesions and predicting the prognosis in patients with multiple myeloma.
Cancer Research and Treatment 11/2014; DOI:10.4143/crt.2014.010 · 2.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present study sought to elucidate the role of induction and consolidation therapy in elderly patients. We retrospectively collected data of 477 patients who were aged over 60 years at the time of acute myeloid leukemia (AML) diagnosis. The median overall survival (OS) was 339 days in the induction group (n = 266) and 86 days in the best supportive care group (n = 211) (P < 0.001). In the induction group, the complete remission (CR) rate was 58.3 %, and treatment-related death was 15.4 %. Successful induction was related to good performance [Eastern Cooperative Oncology Group (ECOG <2)] [hazard ratio (HR) 3.215; P = 0.002]. Mortality correlated with failure to achieve CR (HR 4.059; P < 0.001) and poor performance status (ECOG >2) (HR 2.731; P = 0.035). In CR patients, poor karyotype and absence of consolidation (HR 2.313; P = 0.003) correlated with mortality. More than one cycle of consolidation was associated with better OS (P < 0.001). Lack of salvage therapy was associated with mortality in patients who did not achieve CR (HR 3.223; P = 0.005). Intensive induction in patients with good performance and >1 cycle of consolidation after CR may be the best strategy for improving OS in elderly AML patients.
International Journal of Hematology 07/2014; 100(2). DOI:10.1007/s12185-014-1617-8 · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was designed to evaluate the prevalence of chromosomal abnormalities and to identify the specific abnormalities associated with poor prognosis. A total of 2,474 patients whose conventional cytogenetics were available at the time of diagnosis were evaluated via a nationwide registry. Normal metaphase cytogenetics was observed in 2,012 patients (81.3%). Among the 462 patients with chromosomal abnormalities, there were 161 (34.8%) patients with hyperdiploidy, 197 (42.6%) with pseudodiploidy, 79 (17.1%) with hypodiploidy, and 25 (5.5%) with near-tetraploidy. Deletion 13 (Δ13) in metaphase was observed in 167 patients (6.8%). Fluorescent in situ hybridization (FISH) was carried out in 967 patients (39.1%), and 66 (13.7%) out of 482 and 63 (10.3%) out of 611 patients were positive for t(4;14) and del(17p), respectively. With a median follow-up duration of 25.1 months, the median overall survival (OS) was 51.2 months (95% confidence interval, 46.5-55.9 months). In univariate analysis, the following four chromosomal abnormalities were significantly associated with a poor survival outcome: Δ13, hypodiploidy, del(13q) in FISH, and del(17p) in FISH. In the subsequent multivariate analysis, in which del(13q) and del(17p) in FISH were excluded due to a relatively low number of patients, Δ13 and hypodiploid status were independently associated with a poor survival outcome after adjusting for important clinical factors, including age, sex, performance, beta2-microglobulin, albumin, and lactate dehydrogenase (LDH). Using conventional metaphase cytogenetics, we confirmed that both Δ13 and hypodiploid status were robust poor prognostic factors. The metaphase karyotyping should remain the primary cytogenetic tool and an essential investigation for risk stratification in newly diagnosed multiple myeloma patients.
Annals of Hematology 03/2014; 93(8). DOI:10.1007/s00277-014-2057-5 · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gastric cancer is the fourth most common cancer, and the second-highest cause of cancer-related deaths worldwide. Despite extensive research to identify novel diagnostic and therapeutic agents, patients with advanced gastric cancer suffer from a poor quality of life and poor prognosis, and treatment is dependent mainly on conventional cytotoxic chemotherapy. To improve the quality of life and survival of gastric cancer patients, a better understanding of the underlying molecular pathologies, and their application towards the development of novel targeted therapies, is urgently needed. Chemokines are a group of small proteins associated with cytoskeletal rearrangements, the directional migration of several cell types during development and physiology, and the host immune response via interactions with G-protein coupled receptors. There is also growing evidence to suggest that chemokines not only play a role in the immune system, but are also involved in the development and progression of tumors. In gastric cancer, CXC chemokines and chemokine receptors regulate the trafficking of cells in and out of the tumor microenvironment. CXC chemokines and their receptors can also directly influence tumorigenesis by modulating tumor transformation, survival, growth, invasion and metastasis, as well as indirectly by regulating angiogenesis, and tumor-leukocyte interactions. In this review, we will focus on the roles of CXC chemokines and their receptors in the development, progression, and metastasis of gastric tumors, and discuss their therapeutic potential for gastric cancer.
World Journal of Gastroenterology 02/2014; 20(7):1681-1693. DOI:10.3748/wjg.v20.i7.1681 · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462).
Journal of Korean medical science 01/2014; 29(1):61-8. DOI:10.3346/jkms.2014.29.1.61 · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dermatomyositis (DM) is an autoimmune disease characterized by subacute-onset proximal symmetric muscle weakness, skin abnormalities, and muscle inflammation. Descriptions of DM as a complication of chronic graft-versus-host disease (cGVHD) are very rare. We report a 50-year-old woman who developed DM associated with cGVHD after allogeneic stem cell transplantation.
[Show abstract][Hide abstract] ABSTRACT: We assessed health-related quality of life in cancer survivors treated in designated cancer centers when compared with the general population in Korea.
A multicenter survey was conducted from July through August 2008 using the quota-sampling approach. A general population sample was drawn from the Fourth Korean National Health and Nutrition Examination Survey, second year. We compared the multivariate-adjusted least square means of cancer patients with those of the general population to examine relationships between EuroQol five-dimensional questionnaire components and cancer sites, cancer stage and time since diagnosis. The independent variables of responses to the EuroQol five-dimensional questionnaire were evaluated using logistic regression analysis.
Cancer patients scored significantly poorer on measures of self-care (means: stomach 1.25; lung 1.40; liver 1.27; colon 1.26; breast 1.27; cervical 1.29 vs. general 1.18), engagement in usual activities (means: stomach 1.47; lung 1.63; liver 1.45; colon 1.44; breast 1.46; cervical 1.47 vs. general 1.33) and anxiety/depression (means: stomach 1.41; lung 1.50; liver 1.41; colon 1.42; breast 1.50; cervical 1.47 vs. general 1.28). Those in the local stage scored significantly better on mobility (mean = 1.35) than the general population (mean = 1.40). Cancer patients, especially those with lung cancer, in the advanced stage and more than 5 years since diagnosis had poorer health-related quality of life than the general population. Some factors such as medical insurance and healthcare services were related to health-related quality of life among cancer patients.
Health-related quality of life of cancer survivors with lung cancer at advanced stages, <1 year earlier and more than 5 years since diagnosis was poorer than that for the non-cancer control group, and these differences were statistically significant. Cancer survivors should be continuously observed and offered support.
Japanese Journal of Clinical Oncology 12/2013; 44(2). DOI:10.1093/jjco/hyt184 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Transfusional iron overload and its consequences are challenges in chronically transfused patients with myelodysplastic syndromes (MDSs) or aplastic anemia (AA).
This was a prospective, multicenter, open-label study to investigate the efficacy of deferasirox (DFX) by serial measurement of serum ferritin (S-ferritin) level, liver iron concentration (LIC) level using relaxation rates magnetic resonance imaging, and other laboratory variables in patients with MDS or AA.
A total of 96 patients showing S-ferritin level of at least 1000 ng/mL received daily DFX for up to 1 year. At the end of the study, S-ferritin level was significantly decreased in MDS (p = 0.02366) and AA (p = 0.0009). LIC level was also significantly reduced by more than 6.7 mg Fe/g dry weight from baseline. Hemoglobin level and platelet counts were significantly increased from baseline (p = 0.002 and p = 0.025, respectively) for patients showing significant anemia or thrombocytopenia. Elevated alanine aminotransferase was also significantly decreased from baseline.
This study shows that DFX is effective in reducing S-ferritin and LIC level in transfusional iron overload patients with MDS or AA and is well tolerated. In addition, positive effects in hematologic and hepatic function can be expected with DFX. Iron chelation treatment should be considered in transfused patients with MDS and AA when transfusion-related iron overload is documented.
[Show abstract][Hide abstract] ABSTRACT: Many Korean patients with transfusion-induced iron overload experience serious clinical sequelae, including organ damage, and require lifelong chelation therapy. However, due to a lack of compliance and/or unavailability of an appropriate chelator, most patients have not been treated effectively. Deferasirox (DFX), a once-daily oral iron chelator for both adult and pediatric patients with transfusion-induced iron overload, is now available in Korea. The effectiveness of deferasirox in reducing or maintaining body iron has been demonstrated in many studies of patients with a variety of transfusion-induced anemias such as myelodysplastic syndromes, aplastic anemia, and other chronic anemias. The recommended initial daily dose of DFX is 20 mg/kg body weight, taken on an empty stomach at least 30 min before food and serum ferritin levels should be maintained below 1000 ng/mL. To optimize the management of transfusion-induced iron overload, the Korean Society of Hematology Aplastic Anemia Working Party (KSHAAWP) reviewed the general consensus on iron overload and the Korean data on the clinical benefits of iron chelation therapy, and developed a Korean guideline for the treatment of iron overload.
Journal of Korean medical science 11/2013; 28(11):1563-1572. DOI:10.3346/jkms.2013.28.11.1563 · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We conducted a retrospective analysis of lenalidomide with dexamethasone for patients with relapsed/refractory multiple myeloma (RRMM) who were treated within the Korean patient access program. Lenalidomide has been approved for RRMM for several years in Europe and North America, but has not been accessible to Asian patients in the past. Between 2008 and 2012, 110 patients from 20 hospitals were enrolled. The overall response rate (ORR) was 43.6 % with 15.4 % of very good partial response (VGPR) or better. The median time to progression (TTP) in this heavily pretreated patient population was 8.0 months, and median overall survival (OS) was 23 months. Hematologic toxicities, fatigue, anorexia, and constipation were the most common adverse events. The number of previous treatment lines, previous exposure to thalidomide, refractoriness to thalidomide and bortezomib, pretreatment white blood cell count (WBC), platelet count, t(14;16), and 17p deletion were significant prognostic factors for TTP, and creatinine clearance, refractoriness to thalidomide and bortezomib, performance status, platelet count, and 17p deletion were significant for OS in univariate analysis. In multivariate analysis, WBC and platelet count were significant prognostic factors for TTP and performance status for OS. For Korean myeloma patients, lenalidomide showed considerable efficacy, and toxicities were comparable to the data published in Europe and North America.
Annals of Hematology 09/2013; 93(1). DOI:10.1007/s00277-013-1893-z · 2.40 Impact Factor