Clinical features and treatment outcomes of resected large cell neuroendocrine carcinoma of the lung

Purpose@#Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a high-grade lung neuroendocrine tumor with a poor prognosis, similar to small cell lung cancer (SCLC). However, it remains unclear whether to treat LCNEC as non-small-cell lung cancer (NSCLC) or as SCLC. We reviewed our experiences to suggest appropriate treatment strategy for resected pulmonary LCNEC. @*Materials and Methods@#Forty-four patients were treated for pathologically diagnosed pulmonary LCNEC during 2005‒2018. We considered curative surgery first in early-stage or some locally advanced tumors, unless medically inoperable. Adjuvant treatments were decided considering patient’s clinical and pathological features. After excluding two stage I tumors with radiotherapy alone and three stage III tumors with upfront chemotherapy, we analyzed 39 patients with stage I‒III pulmonary LCNEC, who underwent curative resection first. @*Results@#Adjuvant chemotherapy (NSCLC-based 91%, SCLC-based 9%) was performed in 62%, and adjuvant radiotherapy was done in three patients for pN2 or positive margin. None received prophylactic cranial irradiation (PCI). With a median follow-up of 30 months, the 2- and 5-year overall survival (OS) rates were 68% and 51%, and the 2- and 5-year recurrence-free survival (RFS) rates were 49% and 43%, respectively. Aged ≥67 years and SCLC-mixed pathology were significant poor prognostic factors for OS or RFS (p < 0.05). Among 17 recurrences, regional failures were most common (n = 6), and there were five brain metastases. @*Conclusions@#Surgery and adjuvant treatment (without PCI) could achieve favorable outcomes in pulmonary LCNEC, which was more similar to NSCLC, although some factors worsened the prognosis. The importance of intensified adjuvant therapies with multidisciplinary approach remains high.

Treatment outcome of anaplastic ependymoma under the age of 3 treated by intensity-modulated radiotherapy

Purpose@#Intensity-modulated radiotherapy (IMRT) allows for more precise treatment, reducing unwanted radiation to nearby structures. We investigated the safety and feasibility of IMRT for anaplastic ependymoma patients below 3 years of age. @*Materials and Methods@#A total of 9 anaplastic ependymoma patients below 3 years of age, who received IMRT between October 2011 and December 2017 were retrospectively reviewed. The median equivalent dose in 2 Gy fractions was 52.0 Gy (range, 48.0 to 60.0 Gy). Treatment outcomes and neurologic morbidities were reviewed in detail. @*Results@#The median patient age was 20.9 months (range, 12.1 to 31.2 months). All patients underwent surgery. The rates of 5-year overall survival, freedom from local recurrence, and progression-free survival were 40.6%, 53.3%, and 26.7%, respectively. Of the 9 patients, 5 experienced recurrences (3 had local recurrence, 1 had both local recurrence and cerebrospinal fluid [CSF] seeding, and 1 had CSF seeding alone). Five patients died because of disease progression. Assessment of neurologic morbidity revealed motor dysfunction in 3 patients, all of whom presented with hydrocephalus at initial diagnosis because of the location of the tumor and already had neurologic deficits before radiotherapy (RT). @*Conclusion@#Neurologic morbidity is not caused by RT alone but may result from mass effects of the tumor and surgical sequelae. Administration of IMRT to anaplastic ependymoma patients below 3 years of age yielded encouraging local control and tolerable morbidities. High-precision modern RT such as IMRT can be considered for very young patients with anaplastic ependymoma.

Transaminase Changes in Korean Rheumatoid Arthritis Patients with Chronic Hepatitis C after Biologic Therapy

OBJECTIVE: Coexisting chronic hepatitis C can be problematic when treating rheumatoid arthritis (RA). This study examined the changes in the transaminase and viral load in hepatitis C virus (HCV)-infected RA patients after initiating biologic agents. METHODS: A multicenter retrospective study was conducted at 12 University Hospitals in Korea between November 2014 and November 2015, and 78 RA patients, who met the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for RA and were concomitantly infected with HCV, were identified. The baseline and longitudinal clinical data, changes in liver function, and viral RNA titers were evaluated. RESULTS: Seventeen (21.8%) patients were treated with biologic agents, including etanercept (n=8), adalimumab (n=8), infliximab (n=2), tocilizumab (n=2), abatacept (n=1), and golimumab (n=1) (median 1.5 patient-years). Four patients experienced marked increases in transaminase during treatment with adalimumab (n=2) and tocilizumab (n=2). Two patients (one using adalimumab, the other using tocilizumab) were treated with anti-viral agents and showed dramatic improvement in both the viral RNA and transaminase. One patient discontinued adalimumab due to the repeated elevated transaminase levels along with a twofold increase in the viral RNA titer, and the transaminase level subsequently normalized. No case of overt viral reactivation was identified. CONCLUSION: The data support that changes in transaminase and/or viral load associated with biologic agents in HCV-infected RA patients are possible. Therefore, the liver function and viral RNA titer should be followed regularly during biologic therapy.

Fruits extracts of Hovenia dulcis Thunb. suppresses lipopolysaccharide-stimulated inflammatory responses through nuclear factor-kappaB pathway in Raw 264.7 cells

OBJECTIVE@#To investigate the anti-inflammatory effects and the action mechanism of the fruits of Hovenia dulcis (H. dulcis) in lipopolysaccharide (LPS)-induced mouse macrophage Raw 264.7 cells.@*METHODS@#The extract of H. dulcis fruits (EHDF) were extracted with 70% ethanol. Mouse macrophages were treated with different concentrations of EHDF in the presence and absence of LPS (1 μg/mL). To demonstrate the inflammatory mediators including nitric oxide, inducible nitric oxide synthase and cyclooxygenase (COX)-2 expression levels were analyzed by using in vitro assay systems. COX-derived pro-inflammatory cytokines including interleukin-1β, tumor necrosis factor-α and prostaglandin E2 were determined using ELISA kits. Cell viability, heme oxygenase-1 expression, nuclear factor-kappaB and nuclear factor E2-related factors 2 translocation were also investigated.@*RESULTS@#EHDF potently inhibited the LPS-stimulated nitric oxide, inducible nitric oxide synthase, COX-2, interleukin-1β and tumor necrosis factor-α expression in a dose-dependent manner. EHDF suppressed the phosphorylation of inhibited kappaB-alpha and p65 nuclear translocation. Treatment of macrophage cells with EHDF alone induced the heme oxygenase-1 and nuclear translocation of nuclear factor E2-related factor 2.@*CONCLUSIONS@#These results suggest that the ethanol extract of H. dulcis fruit exerts its anti-inflammatory effects by inhibiting inhibited kappaB-alpha phorylation and nuclear translocation of nuclear factor-kappaB.

Compound K attenuates stromal cell-derived growth factor 1 (SDF-1)-induced migration of C6 glioma cells

BACKGROUND/OBJECTIVES: Stromal cell-derived growth factor 1 (SDF-1), also known as chemokine ligand 12, and chemokine receptor type 4 are involved in cancer cell migration. Compound K (CK), a metabolite of protopanaxadiol-type ginsenoside by gut microbiota, is reported to have therapeutic potential in cancer therapy. However, the inhibitory effect of CK on SDF-1 pathway-induced migration of glioma has not yet been established. MATERIALS/METHODS: Cytotoxicity of CK in C6 glioma cells was determined using an EZ-Cytox cell viability assay kit. Cell migration was tested using the wound healing and Boyden chamber assay. Phosphorylation levels of protein kinase C (PKC)α and extracellular signal-regulated kinase (ERK) were measured by western blot assay, and matrix metallopeptidases (MMP) were measured by gelatin-zymography analysis. RESULTS: CK significantly reduced the phosphorylation of PKCα and ERK1/2, expression of MMP9 and MMP2, and inhibited the migration of C6 glioma cells under SDF-1-stimulated conditions. CONCLUSIONS: CK is a cell migration inhibitor that inhibits C6 glioma cell migration by regulating its downstream signaling molecules including PKCα, ERK1/2, and MMPs.

Compound K attenuates stromal cell-derived growth factor 1 (SDF-1)-induced migration of C6 glioma cells

BACKGROUND/OBJECTIVES: Stromal cell-derived growth factor 1 (SDF-1), also known as chemokine ligand 12, and chemokine receptor type 4 are involved in cancer cell migration. Compound K (CK), a metabolite of protopanaxadiol-type ginsenoside by gut microbiota, is reported to have therapeutic potential in cancer therapy. However, the inhibitory effect of CK on SDF-1 pathway-induced migration of glioma has not yet been established. MATERIALS/METHODS: Cytotoxicity of CK in C6 glioma cells was determined using an EZ-Cytox cell viability assay kit. Cell migration was tested using the wound healing and Boyden chamber assay. Phosphorylation levels of protein kinase C (PKC)α and extracellular signal-regulated kinase (ERK) were measured by western blot assay, and matrix metallopeptidases (MMP) were measured by gelatin-zymography analysis. RESULTS: CK significantly reduced the phosphorylation of PKCα and ERK1/2, expression of MMP9 and MMP2, and inhibited the migration of C6 glioma cells under SDF-1-stimulated conditions. CONCLUSIONS: CK is a cell migration inhibitor that inhibits C6 glioma cell migration by regulating its downstream signaling molecules including PKCα, ERK1/2, and MMPs.

Fruits extracts of Hovenia dulcis Thunb. suppresses lipopolysaccharide-stimulated inflammatory responses through nuclear factor-kappaB pathway in Raw 264.7 cells

Objective: To investigate the anti-inflammatory effects and the action mechanism of the fruits of Hovenia dulcis (H. dulcis) in lipopolysaccharide (LPS)-induced mouse macrophage Raw 264.7 cells. Methods: The extract of H. dulcis fruits (EHDF) were extracted with 70% ethanol. Mouse macrophages were treated with different concentrations of EHDF in the presence and absence of LPS (1 μg/mL). To demonstrate the inflammatory mediators including nitric oxide, inducible nitric oxide synthase and cyclooxygenase (COX)-2 expression levels were analyzed by using in vitro assay systems. COX-derived pro-inflammatory cytokines including interleukin-1β, tumor necrosis factor-α and prostaglandin E

A Unique Case of Erdheim-Chester Disease with Axial Skeleton, Lymph Node, and Bone Marrow Involvement / Journal of the Korean Cancer Association, 대한암학회지

Erdheim-Chester disease is a rare non-Langerhans-cell histiocytosis with bone and organ involvement. A 76-year-old man presented with low back pain and a history of visits for exertional dyspnea. We diagnosed him with anemia of chronic disease, cytopenia related to chronic illness, chronic renal failure due to hypertension, and hypothyroidism. However, we could not determine a definite cause or explanation for the cytopenia. Multiple osteosclerotic axial skeleton lesions and axillary lymph node enlargement were detected by computed tomography. Bone marrow biopsy revealed histiocytic infiltration, which was CD68-positive and CD1a-negative. This report describes an unusual presentation of Erdheim-Chester disease involving the bone marrow, axial skeleton, and lymph nodes.

Phenotype Difference between Familial and Sporadic Ankylosing Spondylitis in Korean Patients

Clustered occurrences of ankylosing spondylitis (AS) in family have been noticed. We evaluated patients with AS confirmed by the modified New York criteria for familial history of AS (one or more first to third degree relatives). The clinical characteristics and the recurrence risks (number of AS patients/number of familial members) of the familial AS compared to sporadic AS were investigated. Out of a total of 204 AS patients, 38 patients (18.6%) reported that they had a familial history of AS. The recurrence risks in the familial AS patients for first, second and third degree family members were 14.5%, 5.2%, and 4.4% respectively. Erythrocyte sedimentation rate (ESR) (22.6+/-22.2 vs 35.4+/-34.4, P=0.029) and C-reactive protein (CRP) (1.24+/-1.7 vs 2.43+/-3.3, P=0.003) at diagnosis, body mass index (21.9+/-2.7 vs 23.7+/-3.3, P=0.002) and frequency of oligoarthritis (13.2% vs 33.7%, P=0.021) were significantly lower in the familial form. The presence of HLA-B27 (97.4% vs 83.1%, P=0.044) was significantly higher in familial AS. In conclusion, Korean familial AS patients show a lower frequency of oligoarthritis, lower BMI, lower ESR and CRP at diagnosis and higher presence of HLA-B27.

A Case of Relapsing Polychondritis Improved by Infliximab Treatment

Relapsing polychondritis is an episodic, systemic inflammation of the cartilage with unknown autoimmune etiology. It leads to the destruction of cartilaginous structures of the ear, eye, nose, respiratory tract, joints, skin, and heart valve, and its presented symptoms are diverse. It can be improved mainly by corticosteroid or immunosuppressive agents. Recently, the use of biologic agents (TNF inhibitors, rituximab, tocilizumab et al) was reported from abroad. However, there is no reported case of relapsing polychondritis, which is treated by biologic agents in Korea. We report this first case of refractory relapsing polychondritis, which was improved with a treatment of Infliximab.

Rituximab Treatment for the Patients with Refractory Inflammatory Myopathy

OBJECTIVE: To assess the efficacy and safety of rituximab (RTX) on disease activity and muscle strength in patients with inflammatory myopathies refractory to conventional therapy. METHODS: Four inflammatory myopathy patients who had been refractory to glucocorticoids, one or more immunosuppressive therapies and intravenous immunoglobulin were treated on an open-label basis. Each patient received two 500 mg doses of RTX 2 weeks apart in one cycle. In one patient who did not respond after the first cycle of RTX, the infusion schedule was modified by the physician. We measured muscle enzyme including CPK, LDH and assessed muscle strength individually to evaluate RTX response. Additionally anti-CD19 antibody was measured. RESULTS: Three patients responded to the first cycle of RTX treatment with improvements in muscle enzyme and muscle strength, and then maintained physical function over the duration of several infusion cycles. In one patient, muscle enzyme did not decrease after the first cycle of RTX, and a high dose glucocorticoid was given. After modifying the treatment schedule with monthly RTX infusion, his muscle enzyme level and muscle strength improved. Anti-CD19 antibody decreased after RTX generally, but responses were variable. Herpes zoster infection occurred in two patients. CONCLUSION: Rituximab may be a therapeutic choice in refractory inflammatory myopathy. However a further trial is needed to confirm the efficacy and prove the safety.

The Prevalence of Hepatitis G Virus by Reverse Transcription-Polymerase Chain Reaction / 대한임상미생물학회지

BACKGROUND: Hepatitis G virus(HGV) is known to be associated with non-A-E hepatitis but pathogenic relevance and mode of transmission are still unclear. In this study, we analyzed the prevalence and clinical implicati ons of HGV infection in patients on hemodialysis or being treated for hematologic disease, and healthy controls. METHODS: HGV RNA was identified in serum by reverse transcription-polymerase chain reaction(RT-PCR) with nested primers deduced from highly conserved area of the 5'-untranslated region. Other parenterally transmissible hepatitis viral markers(HBsAg and anti-HCV) and alanine aminotransferase(ALT), history of transfusion, duration of hemodialysis were assessed. RESULTS: HGV RNA was detected in 12.5%(8 of 64) of the patients on hemodialysis and in 24.1%(14 of 58) of the patients treated for hematologic disease, as compared with 0.8%(1 of 120) of healthy controls(P<0.05). HBsAg, anti-HCV, ALT level, rate of transfusion history and duration of hemodialysis were not significantly different between HGV-infected patients and non-HGV-infected patients. In patients treated for hematologic disease, sex was significantly different between HGV positive and negative groups. CONCLUSIONS: Patients on hemodialysis and being treated for hematologic disease have increased risk for HGV infection, but there was no clinical difference between HGV RNA positive and negative groups. HGV infection itself does not seem to be a frequent cause of liver disease in these patients. The clinical significance of long-term infection with HGV remains to be established.

A Case of Human Parvovirus B19 Infection with Red Cell Aplasia and Idiopathic Thrombocytopenic Purpura / 대한임상병리학회지

Human parvovirus B19 (B19V) is a small (5.5kb) single-stranded DNA virus with known tropism and cytotoxicity for erythroid progenitors. Although B19V was known to be incapable of propagating in the cells other than erythroid progenitors in vitro, leukopenia and thrombocytopenia sometimes occur in addition to erythrocytopenia in patients with B19V infection. Recently, idiopathic thrombocytopenic purpura (ITP) was reported as a rare complication in children following B19V infection. We experienced a case of B19V infection with erythroid aplasia and ITP in 10 years-old girl who presented with severe nasal bleeding and whole body petechiae. Marked thrombocytopenia (4x109/L) and reticulocytopenia (0.1%) were observed. The bone marrow aspiration smears revealed increased number of megakaryocytes and severe red cell hypoplasia with occasional giant pronormoblasts and nearly absence of mature normoblasts. Serum anti- B19V IgM and IgG antibodies were positive.

Comparison of Three Third-generation Anti-HCV Enzyme Immunoassay Tests / 영남의대학술지

The aim of this study was to evaluate domestic enzyme immunoassay(EIA) kit ?LG HCD 3.0?(LG) for the detection of antibody to hepatitis C virus(anti-HCV) in comparision with Axsym HCV version 3.0(Axsym), Cobas Core anti-HCV EIA(Cobas). Cobas kit shows better clear distinction between positive and negative by signal/cutoff ratio(S/C), but it also reveal relatively high false positive rate. The concordance rate of test results between LG and Axsym was 96.2%, between LG and Cobas was 95.5%, and total agreement between three EIA kit was 93.9%. LG were relative poor distinction between positive and negative results, but it could be applied clinically as a screening tool for hepatitis C in general population. The S/C of one false negative result by LG was 0.91, and false positive were less than 4.0, therefore we concluded it is necessary to confirm by immunoblotting assay when S/C were between 0.8 and 4.0.

Effects of Pilose Antler on Lipid Peroxidation and Antioxidative Enzymes in Cultured Liver Cells / 대한면역학회지

No abstract available.

Surface Marker Analysis in Acute Leukemias / 영남의대학술지

We studied the expression of the cell surface antigen associated with myeloid and lymphoid leukemias on bone marrow or peripheral blood blast cells from 153 leukemic patients including 61 cases of acute myelogenous leukemias(AML), 46 of acute lymphocytic leukemias(ALL) and 12 of acute leukemias. They were analyzed by direct or indirect immunofluorescence method for reactivity with the monoclonal antibodies to B cells(CD10, CD19, SmIg), T cells(CD2, CD5, CD7, CD3, CD4, CD8), myeloid antigen(CD13, CD14, CD33, CD61) and a nonspecific antigen, HLA-DR. Lymphoid associated markers detected on AML is CD7 32.8%, CD10 14.8%, CD5 13.1%, CD2 6.6% and CD19 1.6%. TdT was positive in 4.9% of AMLs. Hybrid leukemias were 8 cases out 61 AML cases and were mainly composed of monocytic lineage, M4 and M5a. Myeloid markers detected in ALL were CD13 2.2% and CD33 2.2%. In this study, immunologically classified ALLs were composed of 65.2% of CALLA (+) B precursor type, 10.9% of CALLA (-) B precursor pattern, 8.7% of T cell type, 2.2% of B cell type, 4.5% of mixed lymphoid lineage(B&T), 2.2% of undifferentiated leukemia, and 6.5% of hybrid leukemia. Twelve cases of acute leukemias ware finally diagnosed to be 5 cases of hybrid leukemia, 3 cases of B lineage, 3 case of T lineage and 1 case of mixed lymphoid(B&T) leukemia. In summary, we think the best method for typing acute leukemias is by using a combination of FAB classification and immunophenotying.

8 cases of delayed onset P. vivax malaria / 영남의대학술지

South Korea has been free from endemic malaria by P. vivax since the mid-1980s, but malaria infections, including military outbreak in 1995, have been increasing steadily in the soldiers serving near the western part of Demilitarized Zone(DMZ) since its first resurgence in 1993. We experinced 8 cases of delayed onset P. vivax malaria in young men who had never been abroad and had no history of blood transfusion or parenteral use of drug. All the patients had served near the western part of DMZ during their military life. They were admitted to Yeungnam University hospital due to cyclic fever with chills and the clinical symptoms were developed 2 months to 11months after discharge from military service. Peripheral blood smears showed typical ring forms and trophozoites of P. vivax in red blood cell. Patients were treated with hydroxychloroquine and primaquine showing rapid clinical and hematologic responses in all cases, but 2 cases were relapsed later. We presumed that theses cases were delayed onset of P. vivax infection resulted from the recent outbreak in the western part of DMZ, in 1995. Therefore, we reported theses cases to emphasize the need of active surveillance and prevention.

Effects of Panax ginseng Aqua - acupuncture on Lymphocyte Activities in Glucocorticoid Treated Mice / 대한면역학회지

Panax ginseng (PG) has been used as an important analeptic in traditional medicine. This study was purposed to investigate the effect of PG on immune responses induced by glucocorticoid in mice. PG solution was injected into CV6 and BL23, which are the classical acupuncture points, for 7 days after injection with glucocorticoid. And then B and T cell proliferation and cytolytic activity of natural killer (NK) cells were measured. B cell proliferation by 'H-thymidine incorporation was decreased by about 25% in control group as compared with normal group. However, B cell proliferation was significantly increased 1.8-fold in CV6 group and 2.5-fold in BL23 group as compared with normal group. T cell proliferation by H- thymidine incorporation was decreased by about 15% in control group as compared with normal group. On the other hand, T cell proliferation was significantly increased 1.9-fold in CV6 group and 2.3-fold in BL23 group as cornpared with normal group. Furthermore in purified T cell, the proliferation was furtherly increased rather than in non-purified T cell. The activity of NK cell was remarkably decreased in control group as compared with normal group. However, the activities of NK cells in CV6 and BL23 groups were recovered to the above levels of normal group. On the other hand, the activity of NK cell in the blank locus group was slightly increased compared with control group. However this increasement was not reached the levels of CV6 and BL23 groups. And in the case of purified NK cell, the cytolytic activity of NK cell was respectively increased 1.6-fold in normal group, 1.4-fold in control group, 2.0-fold in blank locus group and 2.0-fold in CV6 group and 1.4-fold in BL23 group as compared to the non-purifed NK cell. These results suggest that PG aqua-acupuncture at CV6 and BL23 may proliferate B and T cells that is suppressed by glucocorticoid, and activate NK cell activity.