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ABSTRACT: We investigated the role of endogenous stromal cell-derived factor-1 (SDF-1; CXCL12) in the survival and proliferation of acute myeloid leukemia (AML) cells in vitro. CD34+ cells from the peripheral blood of five patients with AML, as well as five AML cell lines, produced and secreted SDF-1. Knock-down of endogenous SDF-1 expression using siRNA technology downregulated the constitutive phosphorylation of SDF-1-related signaling molecules and significantly inhibited spontaneous proliferation of the AML cell lines during a 3-day incubation in serum-free conditions. These results indicate that endogenous SDF-1 expression by AML cells plays a role in the autonomous growth of the cells.
Leukemia research 03/2013; · 2.36 Impact Factor
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Ik-Chan Song,
Hyo Jin Lee,
Han-Jo Kim,
Sang-Byung Bae,
Kyu-Taek Lee,
Young-Jun Yang,
Suk-Young Park,
Do-Yeun Cho,
Nae Yu Kim,
In-Sung Cho,
Deog-Yeon Jo
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ABSTRACT: To determine the approximate incidence and clinical features of pernicious anemia in a Korean population, we retrospectively analyzed clinical data for patients with pernicious anemia who were diagnosed between 1995 and 2010 at five hospitals in Chungnam province. Ninety-seven patients were enrolled, who accounted for 24% of patients with vitamin B(12) deficiency anemia. The approximate annual incidence of pernicious anemia was 0.3 per 100,000. The median age was 66 (range, 32-98) yr, and the male/female ratio was 1.25. Anemia-associated discomfort was the most common symptom (79.4%), followed by gastrointestinal and neurological symptoms (78.4% and 38.1%, respectively). Pancytopenia was found in 36 patients (37.1%), and autoimmune disorders were found in 15 patients (15.5%). Antibody to intrinsic factor was detected in 62 (77.5%) of 80 patients examined, and antibody to parietal cells was detected in 35 (43.2%) of 81 patients examined. Of the 34 patients who underwent tests for Helicobacter pylori, 7 (12.5%) were positive. The anemia-associated and gastrointestinal symptoms resolved completely in all patients after intramuscular injection of cobalamin, whereas neurological symptoms remained in some. In conclusion, pernicious anemia is less frequent in Koreans than in Western populations; however, the clinical features of this disorder in Koreans do not differ from those of Western cases.
Journal of Korean medical science 02/2013; 28(2):200-4. · 0.84 Impact Factor
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ABSTRACT: Given the important role of CXCR4 in cancer metastasis, microenvironmental factors that modulate CXCR4 may have an impact on the process of tumor expansion. Hypoxia is a common feature of solid tumors and a significant microenvironmental factor that drives aggressive behavior. CXCR4 is upregulated in several cancer cells under hypoxic conditions, suggesting a relationship between tumor hypoxia and CXCR4. However, the role of hypoxia in regulating CXCR4 in gastric cancer remains poorly understood. KATO III gastric cancer cells were exposed to hypoxia or normoxia. CXCR4 expression in cells transfected with shRNA specific for HIF-1α was investigated by western blotting and flow cytometry. Wound healing, migration and invasion assays were used to assess cell motility and the chemotactic response to CXCL12, a major CXCR4 ligand. CXCR4 expression at the protein level and in the cell membrane was significantly increased in KATO III cells following exposure to hypoxia. This upregulation of CXCR4 was implicated in increased cell motility and enhanced chemotactic responses (migration and invasion) to CXCL12 treatment in vitro. The increases in CXCR4 expression and metastatic potential in gastric cancer cells exposed to hypoxia were blocked by HIF-1α-specific shRNA. Our results indicate that hypoxia upregulates CXCR4 in gastric cancer cells in a HIF-1α-dependent manner, and that upregulation of CXCR4 plays a role in cancer cell migration and invasion. Thus, disrupting the hypoxia-HIF-1α-CXCR4 axis could be an attractive therapeutic strategy for the treatment of gastric cancer.
Oncology Reports 09/2012; 28(6):2239-46. · 1.84 Impact Factor
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The Korean journal of hematology 09/2012; 47(3):162.
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ABSTRACT: Metastatic tumors in the oral cavity are rare and usually affect the jaws more often than the oral soft tissues. In particular, metastases confined to the oral mucosa are extremely rare and originate mainly from the lung and breast. Only one case restricted to the oral mucosa and originating from urinary bladder carcinoma has previously been described. We report on a painful polypoid mass located in the oral mucosa with no bone involvement that was confirmed to be a metastatic oral tumor that originated from transitional cell carcinoma of the urinary bladder and progressed rapidly.
Oncology letters 02/2012; 3(2):343-345. · 0.11 Impact Factor
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Young-Joon Yang,
Gak-Won Yun, Ik-Chan Song,
Seung-Woo Baek,
Kyu-Seop Lee,
Hye Won Ryu,
Myung-Won Lee,
Hyo-Jin Lee,
Hwan-Jung Yun,
Samyong Kim,
Deog-Yeon Jo
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ABSTRACT: Antiphospholipid antibodies (aPL) have been detected in various proportions of patients with primary immune thrombocytopenia (ITP), but the clinical significance of this is debatable. The present study aimed to determine the frequency and clinical implications of elevated aPL in adult patients with ITP.
We prospectively studied newly diagnosed adult patients with ITP who were enrolled between January 2003 and December 2008 at Chungnam National University Hospital. They were evaluated for the presence of lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) at diagnosis and were followed for the development of thrombosis.
Seventy consecutive patients with ITP (median age, 48 years; range, 18 to 79) were enrolled. Twenty patients (28.5%) were positive for aPL at the time of diagnosis: aCL alone in 15 (75%), aCL and LA in two (10%), and LA alone in three (15%). Patients who had platelet counts < 50,000/µL were administered oral prednisolone with or without intravenous immune globulin. No difference was found between the aPL-positive and -negative groups regarding gender, initial platelet count, and response to the therapy. After a median follow-up of 20 months (range, 2 to 68), two of 20 patients who were aPL-positive (10%) developed thrombosis, whereas no thrombotic event was found among those who were aPL-negative.
Our data suggest that aPL levels should be determined at the initial presentation of ITP and that patients found to be aPL-positive should receive closer follow-up for thrombotic events.
The Korean Journal of Internal Medicine 12/2011; 26(4):449-54.
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Ik-Chan Song,
Zhe-Long Liang,
Jung-Chan Lee,
Song-Mei Huang,
Ha-Yon Kim,
Yoon-Suk Oh,
Hwan-Jung Yun,
Ji-Young Sul,
Deog-Yeon Jo,
Samyong Kim,
Jin-Man Kim,
Hyo-Jin Lee
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ABSTRACT: Lymph node metastasis is considered to be a significant prognostic factor for early gastric cancer (EGC). However, no real consensus exists on which patient and/or tumor characteristics are associated with lymph node metastasis. We investigated whether stromal cell-derived factor (SDF)-1α expression correlates with lymph node metastasis in patients with EGC by immunohistochemically examining the expression of SDF-1α in 138 archival tissue specimens of EGC. Of these specimens, 59 (42.8%) and 79 (57.2%) were grouped into SDF-1α-positive and SDF-1α-negative groups, respectively. No significant differences existed with respect to age, gender, tumor location, proportion of tumors >20 mm in size, macroscopic type, depth of invasion or histology between the SDF-1α-positive and -negative groups. However, the SDF-1α-positive group was significantly correlated with lymphovascular invasion and lymph node metastasis. Results of the univariate analyses indicated that lymphovascular invasion, undifferentiated histology and SDF-1α positivity were statistically significant risk factors affecting lymph node metastasis in patients with EGC. Multivariate analyses showed that lymphovascular invasion [hazard ratio (HR), 8.595; 95% confidence interval (CI), 1.694-43.595; P=0.009], undifferentiated histology (HR, 2.965; 95% CI, 1.037-8.471; P=0.043) and SDF-1α positivity (HR, 2.108; 95% CI, 1.316-10.135; P=0.013) were independent risk factors predicting lymph node metastasis in EGC. In conclusion, these results suggest that SDF-1α expression in tumor cells is a predictive marker of lymph node metastasis in EGC.
Oncology letters 11/2011; 2(6):1197-1202. · 0.11 Impact Factor
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ABSTRACT: There has been no report on the clinical features or natural history of autoimmune hemolytic anemia (AIHA) in the Korean adult population. This study retrospectively analyzed the clinical characteristics and long-term outcomes of AIHA in the Korean adults.
Patients newly diagnosed with AIHA between January 1994 and December 2010 at Chungnam National University Hospital were enrolled. Patient characteristics at diagnosis, response to treatment, and the natural course of the disease were documented.
Thirty-two patients (31 females and 1 male) with a median age of 48 years (range, 17-86) were enrolled. Of these, 21.9% were initially diagnosed with secondary AIHA. Thirteen patients (40.6%) were initially diagnosed with Evans' syndrome. Of the 29 patients who were placed on therapy, 27 (93.1%) showed a partial response or better. Nevertheless, 1 year after initiating treatment, 80% of the patients were still treatment-dependent. During follow-up (median length 14 months; range, 0.5-238), 14 of 25 patients (56.0%) who were initially diagnosed with primary warm antibody AIHA were found to have systemic lupus erythematosus (SLE). Median time to conversion to SLE was 8.0 months (95% CI, 4.3-11.7), and the probabilities of conversion at 12 and 24 months were 63% and 91%, respectively. Younger age (<60 years) and a positive fluorescent anti-nuclear antibody test were associated with a higher probability of SLE conversion (P=0.01 and P<0.001, respectively).
Primary AIHA is rare. Regular, vigilant testing for SLE is required in patients initially diagnosed with AIHA.
The Korean journal of hematology 06/2011; 46(2):111-7.
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ABSTRACT: Hypocellularity of bone marrow (BM), not associated with significant dyshematopoiesis, is often found in patients with isolated thrombocytopenia, but its clinical implications have not been studied. We prospectively studied the clinical features and natural history of these patients.
Adults with isolated thrombocytopenia (platelet counts <100×10(9)/L) in the absence of dyshematopoiesis, cytogenetic abnormalities, or megakaryocytic hyperplasia and who had BM hypocellularity (below 30% in patients aged less than 60 years; below 20% in patients aged 60 years or more) were enrolled at Chungnam National University Hospital between January 2002 and December 2006. They were monitored regularly for changes in platelet counts or development of additional cytopenia.
Twenty patients (17 men and 3 women) were enrolled in the study. The median age was 29 years (range, 18-70 years). At initial presentation, the platelet counts ranged from 12×10(9)/L to 99×10(9)/L (median, 63×10(9)/L) and were >50×10(9)/L in 16 patients (80%). BM cellularity ranged from 5% to 25% (median, 15%) and was ≤10% in 6 patients (30%). During the median 48-month follow-up (range, 12-90 months), platelet counts of 3 of the 20 patients recovered to normal levels (>150×10(9)/L) after 12, 56 and 66 months. Three patients developed pancytopenia after 11, 70 and 90 months. Two patients were consistent with moderate aplastic anemia, and 1 was confirmed as having refractory cytopenia with multilineage dysplasia. In the remainder of the patients, platelet counts remained unchanged.
Isolated thrombocytopenia accompanied by hypocellular marrow encompasses a group of heterogeneous conditions.
The Korean journal of hematology 06/2011; 46(2):128-34.
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ABSTRACT: Iron-deficiency anemia (IDA) is the most common nutritional deficiency worldwide. However, the information concerning various causes of IDA in adult men is still insufficient. The aim of our study was to evaluate adult men with IDA.
We prospectively studied 206 adult men with IDA. All subjects had a direct history taken and underwent a physical examination. Esophagogastroduodenoscopy was performed in most patients, and colonoscopy was conducted if no lesion causing IDA was found or the fecal occult blood test was positive.
The history of prior gastrectomy and blood-letting cupping therapy that probably had caused IDA were reported in 24 (11.7%) and 11 (5.3%) patients, respectively. In terms of potential causes of IDA, 68 (33.0%) patients were found to have upper gastrointestinal disorders (34 peptic ulcers, 17 erosive gastritis, 16 gastric cancers, and one gastrointestinal stromal tumor). Colonoscopy showed 42 (20.4%) clinically relevant lesions that probably caused IDA: colon cancer (five patients), colon polyps (14 patients), ulcerative colitis (one patient), and hemorrhoids (22 patients). One small bowel tumor was detected at small bowel series. Concerning malignant lesions that were responsible for IDA, 22 malignant lesions were found in patients of 50 years or older, accounting for 16.8% (22 of 131 patients), while only one (1.3%) early gastric cancer was found in the younger patients.
This study demonstrated that gastrointestinal blood loss is the main cause of IDA in adult men, and that there is a high rate of malignancy in men older than 50 years, emphasizing the need for a complete, rigorous gastrointestinal examination in this group of patients. Considering blood-letting cupping therapy, there is a need to consider culture-specific procedures as a possible cause of IDA.
Internal Medicine 01/2011; 50(13):1371-5. · 0.94 Impact Factor
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ABSTRACT: Sunitinib is a small molecular inhibitor of tyrosine kinases and is used to treat advanced renal cell carcinoma and gastrointestinal stromal tumour after disease progression or intolerance to imatinib therapy. Here, we describe biochemical and pathological response of prostate cancer in a patient with metastatic renal cell carcinoma during sunitinib treatment. A 62-year-old man was referred to our hospital because of a mass in the scalp. He was diagnosed with left renal cell carcinoma with right renal and scalp metastases. In addition, synchronous prostate cancer involving less than one-half of the right lobe was found with a prostate-specific antigen (PSA) value of 23.4 ng/ml. Treatment was begun with sunitinib (50 mg daily, 4 weeks on and 2 weeks off). Regarding the prostate cancer, active monitoring was planned considering the far advanced renal cell carcinoma. Surprisingly, the PSA level was 3.4 ng/ml at week 6 and 0.2 ng/ml at week 12, and it subsequently remained normal. At the time of writing (cycle 6 of sunitinib therapy), the prostate nodule significantly decreased in size. Furthermore, a 12-core re-biopsy revealed pathological evidence of regression with sunitinib treatment, with control of his renal cell carcinoma.
Japanese Journal of Clinical Oncology 09/2009; 39(12):833-6. · 1.78 Impact Factor
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ABSTRACT: The chemokine receptor CXCR4 plays a role in the metastasis and progression of a broad range of malignant tumors; however, its influence on hepatocellular carcinoma (HCC) is not well defined. Thus, we analyzed the expression of CXCR4 and its functions in HCC cell lines in vitro.
Five HCC cell lines (HepG2, Hep3B, SK-HEP-1, NCI-H630 and PLC/PRF5) were investigated. The CXCR4 expression was analyzed by RT-PCR, Western blotting, flow cytometry and immunofluorescence staining. In addition, the effects of stromal cell-derived factor-1 (SDF-1) on the migration, proliferation and survival of the cells were investigated, as well as the SDF-1-induced phosphorylation of signaling molecules.
All five cell lines had abundant CXCR4 in their cytoplasm, whereas a cell surface CXCR4 expression was only detected in a very small population of PLC/PRF5 cells. In contrast, SDF-1 bound to all the cells. SDF-1 induced the phosphorylation of AKT and ERK1/2 in the PLC/PRF5 cells and the phosphorylation of Stat3, AKT and ERK1/2 in the Hep3B cells. Nonetheless, SDF-1 did not induce migration or proliferation in any of the cells, nor did it rescue the cells from serum deprivation-induced apoptosis. Recruitment of CXCR4 from the cytoplasm to the cell surface was not elicited by dexamethasone, proinflammatory cytokines or VEGF. Hypoxia increased both the cytoplasmic and cell surface expressions of CXCR4 in only the PLC/PRF5 cells.
CXCR4 is trapped in the cytoplasm and it is not recruited to the cell surface by standard extrinsic stimuli in the majority of HCC cell lines, and the result of this is a negligible response to SDF-1.
Cancer Research and Treatment 07/2008; 40(2):53-61.
