Morishita, Masayo;Mevius, Damiaan;Shen, Yunpeng;Di Luccio, Eric
Current Research on Agriculture and Life Sciences
/
v.31
no.3
/
pp.157-164
/
2013
Chromatin remodelers that include histone methyl transferases (HMTases) are becoming a focal point in cancer drug development. The NSD family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L are bona fide oncogenes found aberrantly expressed in several cancers, suggesting their potential role for novel therapeutic strategies. Several histone modifiers including HMTase have clear roles in human carcinogenesis but the extent of their functions and regulations are not well understood, especially in pathological conditions. The extents of the NSDs biological roles in normal and pathological conditions remain unclear. In particular, the substrate specificity of the NSDs remains unsettled and discrepant data has been reported. NSD2/MMSET is a focal point for therapeutic interventions against multiple myeloma and especially for t(4;14) myeloma, which is associated with a significantly worse prognosis than other biological subgroups. Multiple myeloma is the second most common hematological malignancy in the United States, after non-Hodgkin lymphoma. Herein, as a first step before entering a pipeline for protein x-ray crystallography, we cloned, recombinantly expressed and purified the catalytic SET domain of NSD2. Next, we demonstrated the catalytic activities, in vitro, of the recombinantly expressed NSD2-SET on H3K36 and H4K20, its biological targets at the chromatin.
Objectives: Waste treatment by incineration is gradually increasing as the emission of harmful substances has decreased owing to developments in incineration technology. However, residents living near incinerators continue to express anxiety regarding the effects on their health. Therefore, we attempted to summarize the health impact of incinerators by comprehensively reviewing the recently reported literature. Methods: Sixty-two epidemiological research papers related to incineration and health effects were selected from the Google Scholar database and analyzed (from between January 2001 and December 2019). Results: When compared to older incinerators, newer incinerators established after 2000 are considered relatively safe in terms of health effects. Nevertheless, there have been some studies that have linked them to various diseases, such as malignant tumors including soft tissue cancer and non-Hodgkin's lymphoma, reproductive disorders, respiratory diseases, and more. In addition, incinerator workers and local residents are considered to be exposed to dioxins and some heavy metals from the incinerator. Since most studies included subjects exposed to older incinerators, it is difficult to apply these results to the health impact assessment of new incinerators. However, it is not appropriate to conclude that new incinerators made with state-of-the-art technology are safe, as chronic environmental diseases caused by hazardous substances tend to appear only after prolonged exposure. Conclusions: In terms of environmental health, it is necessary to continuously monitor the health effects of incinerators. Also, there is a need to develop a research methodology that can minimize various confounders in incineration-related epidemiological study.
Sooyoung Kim;Bit Na Lee;Seung Woo Kim;Ha Young Shin
Annals of Clinical Neurophysiology
/
v.25
no.2
/
pp.84-92
/
2023
Background: Clinical spectrum of immunoglobulin M (IgM) monoclonal gammopathy varies from IgM monoclonal gammopathy of unknown significance (IgM-MGUS) to hematological malignancies. We evaluated the clinical features, electrophysiological characteristics, and prognosis of patients with peripheral neuropathy associated with IgM monoclonal gammopathy (PN-IgM MG). Methods: We retrospectively evaluated 25 patients with PN-IgM MG. Peripheral neuropathy was classified as axonal, demyelinating, or undetermined, based on electrophysiological studies. We classified the enrolled patients into the IgM-MGUS and malignancy groups, and compared the clinical and electrophysiological features between the groups. Results: Fifteen patients had IgM-MGUS and 10 had hematologic malignancies (Waldenström's macroglobulinemia: two and B-cell non-Hodgkin's lymphoma: eight). In the electrophysiological evaluation, the nerve conduction study (NCS) criteria for demyelination were met in 86.7% of the IgM-MGUS group and 10.0% of the malignancy group. In particular, the distal latencies of the motor NCS in the IgM-MGUS group were significantly prolonged compared to those in the malignancy group (median, 9.1 ± 5.1 [IgM-MGUS], 4.2 ± 1.3 [malignancy], p = 0.003; ulnar, 5.4 ± 1.9 [IgM-MGUS], 2.9 ± 0.9 [malignancy], p = 0.001; fibular, 9.3 ± 5.1 [IgM-MGUS], 3.8 ± 0.3 [malignancy], p = 0.01; P-posterior tibial, 8.3 ± 5.4 [IgM-MGUS], 4.4 ± 1.0 [malignancy], p = 0.04). Overall treatment responses were significantly worse in the malignancy group than in the IgM-MGUS group (p = 0.004), and the modified Rankin Scale score at the last visit was higher in the malignancy group than in the IgM-MGUS group (2.0 ± 1.1 [IgM-MGUS], 4.2 ± 1.7 [malignancy], p = 0.001), although there was no significant difference at the initial assessment. Conclusions: The risk of hematological malignancy should be carefully assessed in patients with PN-IgM MG without electrophysiological demyelination features.
Suh Chang Ok;Chung Sang Sup;Chu Sung Sil;Kim Young Soo;Yoon Do Heum;Kim Sun Ho;Loh John Juhn Kyu;Kim Gwi Eon
Radiation Oncology Journal
/
v.10
no.1
/
pp.7-14
/
1992
Between August 1988 and December 1991, 24 patients with intracranial tumors were treated with stereotactic radiosurgery(RS) using a 10 MV linear accelerator at Severance Hospital, Yonsei University College of Medicine. There were 5 meningiomas, 3 craniopharyngiomas, 9 glial tumors, 2 solitary metastases, 2 acoustic neurinomas, 2 pineal tumors, and 1 non-Hodgkin's lymphoma. Ten patients were treated as primary treatment after diagnosis with stereotactic biopsy or neuroimaging study. Nine patients underwent RS for post-op. residual tumors and three patients as a salvage treatment for recurrence after external irradiation. Two patients received RS as a boost followed by fractionated conventional radiotherapy. Among sixteen patients who were followed more than 6 months with neuroimage, seven patients (2 meningiomas, 4 benign glial tumors, one non-Hodgkin's lymphoma) showed complete response on neuroimage after RS and nine patients showed decreased tumor size. There was no acute treatment related side reaction. Late complications include three patients with symptomatic peritumoral brain edema and one craniopharyngioma with optic chiasmal injury. Through this early experience, we conclude that stereotactically directed single high doses of irradiation to the small intracranial tumors is effective for tumor control. However, in order to define the role of radiosurgery in the management of intracraniai tumors, we should get the long-term results available to demonstrate the benefits versus potential complications of this therapeutic modality.
Lee Sang Rok;Jeong Deok Yang;Lee Byoung Koo;Kwon Young Ho
The Journal of Korean Society for Radiation Therapy
/
v.15
no.1
/
pp.19-27
/
2003
I. Purpose In special cases of Total Body Irradiation(TBI), Half Body Irradiation(HBI), Non-Hodgkin's lymphoma, E-Wing's sarcoma, lymphosarcoma and neuroblastoma a large field can be used clinically. The dose distribution of a large field can use the measurement result which gets from dose distribution of a small field (standard SSD 100cm, size of field under $40{\times}40cm2$) in the substitution which always measures in practice and it will be able to calibrate. With only the method of simple calculation, it is difficult to know the dose and its uniformity of actual body region by various factor of scatter radiation. II. Method & Materials In this study, using Multidata Water Phantom from standard SSD 100cm according to the size change of field, it measures the basic parameter (PDD,TMR,Output,Sc,Sp) From SSD 180cm (phantom is to the bottom vertically) according to increasing of a field, it measures a basic parameter. From SSD 350cm (phantom is to the surface of a wall, using small water phantom. which includes mylar capable of horizontal beam's measurement) it measured with the same method and compared with each other. III. Results & Conclusion In comparison with the standard dose data, parameter which measures between SSD 180cm and 350cm, it turned out there was little difference. The error range is not up to extent of the experimental error. In order to get the accurate data, it dose measures from anthropomorphous phantom or for this objective the dose measurement which is the possibility of getting the absolute value which uses the unlimited phantom that is devised especially is demanded. Additionally, it needs to consider ionization chamber use of small volume and stem effect of cable by a large field.
Choi, Yun Ju;Kim, Ji Eun;Lee, Su Jin;Gong, Jeong Eun;Jin, Yu Jeong;Lee, Jae Ho;Lim, Yong;Hwang, Dae Youn
Journal of Life Science
/
v.32
no.7
/
pp.532-541
/
2022
Obesity induced by high-fat diet (HFD) is verified as a strong risk factor and negative prognostic factor for prostate cancer in several genetically engineered mice although it was not examined in the normal mice. To investigate whether HFD-induced obesity can affect the development and progression of cancer in the prostate of normal mice, alterations in the weight and histological structure of the prostate as well as the expression of cancer-related proteins were analyzed in obese C57BL/6N mice fed with 60% HFD for 16 weeks. First, HFD-induced obesity, including an increase in organ weight, body weight, fat accumulation, and serum lipid profile, was successfully induced in C57BL/6N mice after HFD treatment. The total weight of the prostate significantly increased HFD-induced obesity in the model mice compared with the control group. Among the four lobes of the prostate, the weight of the ventral prostate (VP) and anterior prostate (AP) were higher in HFD-induced obesity model mice than in the control group, although the weights of the lateral prostate (DLP) and seminal vesicle (SV) were constantly maintained. In addition, the incidences of hyperplasia and non-hodgkin's lymphoma (NHL) in the histological structure were remarkably increased in HFD-induced obesity model mice, while the epithelial thickness was higher in the same group. A significant increase in the phosphorylation levels of key proteins in the AKT (protein kinase B) signaling pathway was detected in HFD-induced obesity model mice. Therefore, these results suggest that HFD-induced obesity can promote hyperplasia and NHL in the prostates of C57BL/6N mice through the activation of the AKT signaling pathway.
Background: Extra nodal lymphoma (ENL) constitutes about 33 % of all non-Hodgkin's lymphoma. 18-28% develops in the head and neck region. A multimodality treatment with multi-agent chemotherapy (CT) and radiotherapy (RT) is considered optimum. Materials and Methods: We retrieved the treatment charts of patients of HNENL treated in our institute from 2001-2012. The charts were reviewed and the demographic, treatment details and outcome of HNENL patients were retrieved using predesigned pro-forma. Results: We retrieved data of 75consecutive patients HNENL. Median age was 47years (Range: 8-76 years). Of the 75 patients 51 were male and 24 were female. 55patients were evaluable. The patient and tumor characteristics are summarized in Table 1. All patients were staged comprehensively with contrast enhanced computed tomography of head, neck, thorax, abdomen, pelvis and bone marrow aspiration and biopsy 66 patients received a combination multi-agent CT with CHOP being the commonest regimen. 42 patients received 4 or lesser number of cycles of chemotherapy whereas 24received more than 4 cycles chemotherapy. Post radiotherapy, 41 out of 42 patients had a complete response at 3 months. Only 21patients had a complete response after chemotherapy. All patients received radiation (mostly involved field radiation) as a part of the treatment. The median radiation dose was 45 Gray (Range: 36 Gray-50 Gray). The radiation was planned by 2D fluoro simulation based technique in 37cases and by 3 Dimensional conformal radiation therapy (3DCRT) in 36 cases. Two patients were planned by the intensity modulated radiation therapy (IMRT) technique. IMRT was planned for one thyroid and one nasal cavity primary. 5 patients experienced relapse after a median follow up of 19 months. The median survival was not reached. The estimated two and three year survival were 92.9% (95%CI- 68.6- 95.35) and 88% (95%CI- 60.82 - 92.66) respectively. Univariate analysis revealed higher stage and poorer baseline performance status to be significantly associated with worse progression free survival. 5 patients progressed (relapse or primary disease progression) after treatment. Of the 5 patients, two patients were primary orbital NHL, two patients had NHL nasal cavity and one was NHL thyroid. Conclusions: Combined modality treatment in HNENL confers excellent disease control with acceptable side effects.
Objectives: Thrombotic risk is increased in patients with cancer and there are important implications for those who suffer a venous thromboembolism (VTE). We undertook this study to determine the frequency, clinical patterns, and outcome of VTE in Saudi patients with cancer. Methods: Cancer (solid tumors and lymphoma) patients who developed VTE from January 2004 to January 2009 were studied retrospectively. Demographics and clinical characteristics related to thrombosis and cancer were evaluated. Results: A total of 701 patients with cancer were seen during the study period. VTE was diagnosed in 47 (6.7%) patients (median age 52, range 18-80 years). Lower limb DVT was the most common type, seen in 47% patients, followed by PE in 19%, and 19% patients had both DVT & PE. Thrombosis was symptomatic in 72% patients while it was an incidental finding on routine workup in 28%. Cancer and VTE were diagnosed at the same time in 38% of patients, and 47% patients developed VTE during the course of disease after the cancer diagnosis. The majority of VTE post cancer diagnoses occurred during the first year (median 4 months, range 1-14). Additional risk factors for VTE were present in 22 (47%) patients and 14 (30%) of these patients were receiving chemotherapy at the time of thrombosis. Only 5 (10.6%) patients were receiving thrombo-prophylaxis at the time of VTE diagnosis. Most common types of tumors associated with thrombosis were breast cancer, non-Hodgkin's lymphoma and lung cancer. The majority of the affected patients (79%) had advanced stage of cancer. After a median follow-up of 13 (range 0.5-60) months, 38 (81%) patients had died. There was no difference in the mortality of patients with symptomatic or asymptomatic thrombosis (82% vs 78.6%). Conclusions: Thrombotic complications can develop in a significant number of patients with cancer, and almost half of the patients have additional risk factors for VTE. Thrombosis is usually associated with advanced disease and can be asymptomatic in more than a quarter of cases. Thromboprophylaxis in cancer patients is under-utilized. Community based studies are needed to accurately define the extent of this problem and to develop effective prophylactic strategies.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-hodgkin lymphoma. Advances in the chemotherapeutic treatment of this disease have improved the outcomes of DLBCL; nonetheless, many patients still die of DLBCL, and therefore, a better understanding of this disease and identification of novel therapeutic targets are urgently required. In a recent gene expression profiling study, PDE (phosphodiesterase) 4B was found to be overexpressed in chemotherapy-resistant tumors. The major function of PDE4B is to inactivate the second messenger cyclic 3',5' monophosphate (cAMP) by catalyzing the hydrolysis of cAMP to 5'AMP. It is known that cAMP induces cell cycle arrest and/or apoptosis in B cells, and PDE4B abolishes cAMP's effect on B cells. However, the mechanism by which PDE4B is overexpressed remains unclear. Here, we show that the aberrant expression of miRNA may be associated with the overexpression of this gene. The PDE4B 3' untranslated region (UTR) has three functional binding sites of miR-23b, as confirmed by luciferase reporter assays. Interestingly, miR-23b-binding sites were evolutionarily conserved from humans to lizards, implying the critical role of PDE4B-miR-23b interaction in cellular physiology. The ectopic expression of miR-2 3b repressed PDE4B mRNA levels and enhanced intracellular cAMP concentrations. Additionally, miR-23b expression inhibited cell proliferation and survival of DLBCL cells only in the presence of forskolin, an activator of adenylyl cyclase, suggesting that miR-23b's effect is via the downregulation of PDE4B. These results together suggest that miR-23b could be a therapeutic target for overcoming drug resistance by repressing PDE4B in DLBCL.
Kim, Mun-Ja;Jin, Soo-He;Lee, Duk-Hee;Park, Dae-Weon;Koh, Sung-Ae;Lee, Kyung-Hee;Hyun, Myung-Soo;Kim, Min-Kyoung
Biomedical Science Letters
/
v.18
no.2
/
pp.131-138
/
2012
Autologous peripheral blood stem cell transplantation (PBSCT) has been used as a major treatment strategy for hematological malignancies. The number of CD34 positive cells in the harvested product is a very important factor for achieving successful transplantation. We studied the factors that can predict the number of CD34 positive cells in the harvested product of acute myelocytic leukemia (AML), multiple myeloma (MM) and Non-Hodgkin's lymphoma (NHL) patients after mobilizing them with chemotherapy plus G-CSF. A total of 73 patients (AML 19 patients, MM 28 patients, NHL 26 patients) with hematological malignancies had been mobilized with chemotherapy and granulocyte colony-stimulating growth factor from April, 2000 to February, 2012. Group's characteristics, checkup opinion of pre-peripheral blood on the day of harvest & outcome of PBSC were analyzed and evaluated using SPSS statistics program after grouping patients as below; group 1: CD34 cell counts < $2{\times}10^6/kg$ (n=16); group 2: $2{\times}10^6/kg{\leq}CD34$ cell counts < $6{\times}10^6/kg$ (n=32); group 3: CD34 cell counts ${\geq}6{\times}10^6/kg$ (n=25). We analyzed the clinical characteristics, the peripheral blood (PB) parameters and the number of CD34 positive cells in the PB and their correlation with the yield of CD34 positive cells collected from the mobilized patients. The total number of leukapheresis sessions was 263 (mean: 3.55 session per patient), and the mean number of harvested CD34 positive cells per patient was $7.37{\times}10^6/kg$. The number of CD34 positive cells in product was significantly correlated with the number of platelet and CD34 positive cells in peripheral blood (P<0.05). The number of PB CD34 positive cells was the best significant factor for the quantity of harvested CD34 positive cells on the linear regression analysis (P<0.05). Many factors could influence the mobilization of peripheral blood stem cells. Platelet count and PB CD34 positive cells count were the two variables which remained to be significant in multivariate analysis. Therefore, the number of platelet and CD34 positive cells in peripheral blood on the day of harvest can be used as an accurate predictor for successful peripheral blood stem cell collection.
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