Jung Hye Choi

Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation and metastasis in gastric cancer.

Choi JH, Song YS, Yoon JS, Song KW, Lee YY. Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation and metastasis in gastric cancer. APMIS 2010; 118: 196–202.

Comparison between Matched Related and Alternative Donors of Allogeneic Hematopoietic Stem Cells Transplanted into Adult Patients with Acquired Aplastic Anemia: Multivariate and Propensity Score-Matched Analysis

We retrospectively compared the outcomes of 225 patients with adult acquired aplastic anemia (AA) who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) from matched related donors (MRDs), and those treated by alloHSCT from alternative donors (ADs). Univariate and multivariate analyses of factors associated with survival were performed. Multivariate analysis showed that age at alloHSCT of ≤ 31 years, MRD, successful engraftment, absence of acute graft-versus-host disease (aGVHD), and platelet engraftment at ≤ 21 days, were independent predictors of longer survival. In addition, time to aGVHD and cumulative nonrelapse mortality (NRM) were better in MRD than in AD recipients. Using propensity score matching (PSM), we performed a case-control study comparing 25 patients in each group who underwent alloHSCT from MRDs and ADs. Pretransplantation clinical factors were well balanced in either group. Median survival time was similar, and no statistically significant difference in transplantation outcomes was apparent when MRD and AD recipients were compared. In conclusion, our results suggest that alloHSCT from an AD should be considered earlier in adult patients with AA who do not have an MRD.

Clinical characteristics of monomorphic post-transplant lymphoproliferative disorders.

Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of lymphoproliferative disorders associated with immunosuppression and Epstein-Barr virus infection. PTLD is classified into three major categories: early lesions, polymorphic PTLD, and monomorphic PTLD. The majority of monomorphic PTLD cases are non-Hodgkins lymphoma of B-cell origin. This retrospective study was conducted to investigate the incidence, clinical manifestation, treatment, and outcomes of monomorphic PTLD among 5,817 recipients of solid organ or allogeneic hematopoietic stem cell transplantation from five institutions. Fourteen patients with monomorphic PTLD were identified (male:female 11:3; median age 42.6 yr, range 24-60). The overall incidence rate was 0.24%. The most common disease type was diffuse large B cell lymphoma (n=7). The median time between the transplant and diagnosis of PTLD was 85.8 months. However, all cases of PTLD after allogeneic hematopoietic stem cell transplantation occurred within 1 yr after transplantation. Ten of the 14 patients had EBV-positive tumor. Fourteen patients received combination systemic chemotherapy and four patients were treated with radiation therapy. Ten patients achieved a complete response (CR) and two patients a partial response (PR). The median follow-up period for surviving patients was 36.6 months. Nine patients remain alive (eight CR, one PR). Nine of 11 solid organ transplantations preserved graft function. The present study indicates a lower incidence rate and a longer median time before the development of PTLD than those of previous reports. Careful monitoring was needed after allogeneic hematopoietic stem cell transplantation for PTLD.

Inhibitory effects of eupatilin on tumor invasion of human gastric cancer MKN-1 cells

Extracts of the whole herb of Artemisia asiatica Nakai (Asteraceae) are used in traditional oriental medicine to treat inflammation. Eupatilin (5,7-dihydroxy-3′,4′,6-trimethoxyflavone) is one of the pharmacologically active components found in A. asiatica, and has been shown to possess anti-tumoral effects in some malignancies, including gastric cancer. However, its anti-metastatic effect in gastric cancer is hardly known. In this study, anti-metastatic effect of eupatilin was investigated in the human gastric cancer cell line, MKN-1. Eupatilin inhibited MKN-1 growth in a dose- and a time-dependent manner, and induced apoptosis with a concomitant increase of caspase-3 activity. ELISA demonstrated that release of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-8) was significantly reduced by eupatilin. And p-AKT and p-ERK (p44/42) was reduced. Expression level of β-catenin and integrin was reduced and p-GSKβ was increased. In transcription reporter system, the activity of the transcriptional factor, NF-κB, was reduced by eupatilin and the expression of p65 was down-regulated when MKN-1 cells were treated with eupatilin. Moreover, a zymography study revealed that this reduction in invasive potential resulted from a reduction in type IV collagenolytic (gelatinolytic) activity. The expressions of metalloproteinases (MMP-2 and MMP-9) were also reduced in MKN-1 cells treated with eupatilin. In vitro invasion assay, eupatilin inhibited MKN-1 penetrating reconstituted basement membrane barriers. These results suggest that eupatilin inhibits the MKN-1 gastric cancer cell proliferation via activation of caspase-3 and the metastatic potential of gastric cancer cells via down-regulation of NF-κB activity followed by reduction of pro-inflammatory cytokine-mediated MMPs expressions.

Allogeneic Hematopoietic Stem Cell Transplant for Adults over 40 Years Old with Acquired Aplastic Anemia

Although younger age is associated with favorable prognosis in adults undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) for aplastic anemia (AA), other pretransplantation factors may be more important than age. We retrospectively analyzed the impact of older age on transplantation outcomes and survival in a total of 225 adult patients with AA who underwent allo-HSCT: 57 patients >40 years old (older patient group [OPG]) and 168 patients ≤40 years old (younger patient group [YPG]). Age at allo-HSCT ≤40 years, time from diagnosis to allo-HSCT ≤6 months, and matched related donor (MRD) were favorable prognostic factors in all study patients. Risk analysis of survival in the OPG showed that age >50 years was the only poor prognostic factor. Survival did not differ significantly between the YPG and patients <50 years old in the OPG. In conclusion, patients between the ages of 41 and 50 years with severe AA and MRDs should undergo allo-HSCT as early as possible to optimize survival.

A case of primary plasmacytoma of lymph nodes.

Extramedullary plasmacytoma may originate in any organ, either as a primary tumor or as a facet of systemic multiple myeloma. These solid lesions most commonly affect the upper respiratory tract, gastrointestinal and urogenital tract, skin, and lung. Primary plasmacytoma of the lymph node is a rare hematologic neoplasm, which usually manifests as an enlargement of the cervical lymph nodes with no evidence of any other plasma cell dyscrasia. A 56-year-old man was admitted, due to the presence of multiple palpable masses in the right cervical and submandibular areas. Surgical resection revealed plasmacytoma of the lymph nodes. According to our full work-up, no evidence of the systemic involvement of plasma cell dyscrasia was discovered and thus, the diagnosis of primary plasmacytoma of the lymph node was made. Radiotherapy was administered, and the remnant mass was reduced substantially, to 1×2 cm in size. The patient was scheduled to be monitored by a PET CT scan, as well as by a neck CT scan.

A Case of Avascular Necrosis of the Femoral Head as Initial Presentation of Chronic Myelogenous Leukemia

Chronic myelogenous leukemia (CML) is a malignant clonal disorder of hemopoietic stem cells characterized by abnormal proliferation and accumulation of immature granulocyte. Leukostasis is one of the complications of CML and is characterized by partial or total occlusion of microcirculation by aggregation of leukemic cells and thrombi leading to respiratory, ophthalmic or neurologic symptoms. We experienced a rare case of avascular necrosis of the femoral head as the initial presentation of chronic myelogenous leukemia. A 24-year-old male patient was admitted to our hospital with pain in the right hip joint. The patient was diagnosed to be suffering from chronic myelogenous leukemia by packed marrow with granulocytic and megakaryocytic hyperplasia and the presence of Philadelphia chromosome. The right hip joint pain was attributed to avascular necrosis of the femoral head. And the avascular necrosis could be considered as the complication of chronic myelogenous leukemia due to microcirculatory obstruction of the femoral head. The avascular necrosis of the right femoral head was treated with bipolar hemiarthoplasty.

Anti-leukemic effect of sodium metaarsenite (KML001) in acute myeloid leukemia with breaking-down the resistance of cytosine arabinoside

Sodium metaarsenite (NaAs2O3: code name KML001) is an orally bioavailable arsenic compound with potential anti-cancer activity. However, the effect of KML001 has not been studied in acute myeloid leukemia (AML). We investigated the anti-leukemic effect of KML001 in AML, and determined the mode of action of KML001. KML001 inhibited the cellular proliferation in all AML cell lines and primary AML blasts as well as HL-60R (cytosine arabinoside-resistant HL-60) cells, while As2O3 was not effective in primary AML blasts and AML cell lines including HL-60R cells. KML001 induced G1 arrest and apoptosis in HL-60 and HL-60R cells. KML001 inhibited the activation of STAT (signal transducer and activator of transcription) 1, 3, 5, NF-κB, AKT and PI3K, while phosphorylated PTEN was upregulated. In addition, activation of ERK, p38 and JNK was observed in KML001-induced growth inhibition of HL-60 and HL-60R cells. Furthermore, KML001 induced telomeric terminal restriction fragment (TRF) length shortening in a time-dependent manner in HL-60 and HL-60R cells. Real‑time PCR with RNA extracted from KML001-treated HL-60 and HL-60R cells showed a significant reduction of catalytic subunit of telomerase, hTERT, in a time-dependent manner. Additionally, γ-H2AX, a sensitive molecular marker of DNA damage, in HL-60 and HL-60R cells was induced by KML001. These results suggest that KML001 inhibits the proliferation of AML cells including cytosine arabinoside-resistant AML cells via various mechanisms such as cell cycle arrest, induction of apoptosis, inhibition of JAK/STAT and PI3K pathways, activation of MAPK pathway and telomere targeting.

Clinical Prognostic Factors and Treatment Outcome of Aggressive Non-Hodgkin's Lymphoma in Elderly Patients

PURPOSE The aim of this study was to determine the prognostic factors and treatment outcome of for elderly patients (age>or=60 at time of diagnosis) with aggressive non-Hodgkins lymphoma (NHL). MATERIALS AND METHODS We analyzed 52 patients diagnosed with aggressive NHL between January 1990 and May 2000. RESULTS The patients median age was 69 years (range: 60~92). Thirty-two (61.5%) patients were male. Patients included those with diffuse large B cell (53.8%), peripheral T cell (23.1%), AILD-like T-cell (3.8%), angiocentric (3.8%), mantle cell (3.8%), Burkitts lymphoma (3.8%), and others (7.9%). International prognostic index (IPI) parameters were as follows: elevated LDH (60.8%), ECOG performance status>or=2 (32.7%), advanced stage (III/IV, 62.7%), and extranodal site>or=2 (11.5%). Twenty-six (50.0%) patients demonstrated a high and high-intermediate IPI. The median follow-up for surviving patients was 26.6 months. The overall median survival was 22.7 months and the 2-year survival rate was 46.9%. Among the 49 patientstreated with chemotherapy, 28 (57.1%) patients achieved complete remission (CR). Univariate analysis identified 8 prognostic factors for overall survival: age<70 (P=0.04), low/low-intermediate IPI (P=0.02), good performance (P= 0.04), normal WBC (P=0.008), normal Hb (P=0.02), normal LDH (P=0.04), CR on first line therapy (P<0.001), and absence of B symptom (P=0.001). In the multivariate analysis, the independent prognostic factors for improved overall survival were age <70 (P=0.03), low/low-intermediate IPI (P=0.03), normal WBC (P=0.006), and CR on first line therapy (P<0.001). CONCLUSION In our experience, even elderly patients (>or=60 years) with aggressive NHL can be successfully treated with conventional chemotherapy and the important prognostic factors for survival are age, IPI, initial WBC, and CR on first line treatment.

Diffuse Nodular Lymphoid Hyperplasia of the Intestine Caused by Common Variable Immunodeficiency and Refractory Giardiasis

Diffuse nodular lymphoid hyperplasia of the gastrointestinal tract is a rare disease characterized by numerous small polypoid nodules in the small intestine, large intestine, or both. It is associated with immunodeficiency and infection, such as Giardia lamblia and Helicobacter pylori. Although diffuse nodular lymphoid hyperplasia associated with common variable immunodeficiency (CVID) and giardiasis is already known, a few studies have reported a regression of the lymphoid nodules after the eradication of infection. We herein describe a case of diffuse nodular lymphoid hyperplasia of the intestine associated with CVID and refractory giardiasis that markedly improved after successfully treating giardiasis.