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Synthesis and biological evaluation of tricarbonyl technetium labeled 2-(4-chloro)phenyl-imidazo[1,2-a]pyridine analog (99mTc-CB257) as a TSPO-binding ligand

  • Choi, Ji Young;Jung, Jae Ho;Song, In Ho;Moon, Byung Seok;Lee, Byung Chul;Kim, Sang Eun
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.4 no.2
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    • pp.73-79
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    • 2018
  • In our previous study, tricarbonyl $^{99m}Tc$-labeled TSPO-binding ligand, named $^{99m}Tc$-CB256, having positively charge (+1) was investigated but did not show promising results in in vivo environment despite of a nanomolar binding affinity for TSPO. Because the overall positively charge of $^{99m}Tc$-CB256 would likely interrupt its target protein uptake, we herein designed the neutral tricarbonyl-$^{99m}Tc$ labeled TSPO-binding ligand ($^{99m}Tc$-CB257, 1). $^{99m}Tc$-CB257 was prepared by the facile incorporation of the $[^{99m}Tc(CO)_3]^+$ into a N-(hydroxycarbonylmethyl)-2-picoly moiety in CB257. The radiochemical yield of $^{99m}Tc$-CB257 after HPLC purification was $54.1{\pm}2.4%$ (decay corrected, n = 3). The authentic Re-CB257 (2) was synthesized by using $(NEt_4)_2[Re(CO)_3Br_3]$ in 69.0% yield. The binding affinity of 2 for TSPO was measured in leukocyte and showed approximately 280 times higher than that observed for the positively charged (+1) ligand, Re-CB256 ($K_i=0.57{\pm}0.06nM$ versus $159.3{\pm}8.7nM$, respectively). Our results indicated that 1 can be considered potentially as a new SPECT radiotracer for TSPO-rich cancer and provides the foundation for further in vivo evaluation related with abnormal TSPO-overexpression environments.

Detection of bone marrow involvement with FDG PET/CT in patients with newly diagnosed lymphoma

  • Ozpolat, H. Tahsin;Yilmaz, Ebru;Goksoy, Hasan Sami;Ozpolat, Sahre;Dogan, Oner;Unal, Seher Nilgun;Nalcaci, Meliha
    • BLOOD RESEARCH
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    • v.53 no.4
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    • pp.281-287
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    • 2018
  • Background Bone marrow involvement (BMI) affects the lymphoma stage, survival, and treatment. Bone marrow biopsy (BMB) and fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) are useful techniques to detect BMI. Both have advantages and disadvantages. We aimed to identify factors that could be used to predict BMI with positive and negative results on PET/CT compare them with BMB in newly diagnosed patients with lymphoma. Methods We included 22 non-Hodgkin and 16 Hodgkin lymphoma patients in this single center study. All patients had PET/CT examination and BMB before treatment. BMI in BMB was reported as negative or positive. Bone marrow was classified into 3 types by FDG uptake on PT/CT; diffuse involvement, focal involvement, and normal bone marrow. Results PET/CT and BMB results were concordant (7 positive, 15 negative) in 22 patients (57%). We evaluated concordant and discordant patient characteristics and risk-stratified patients for BMI. Our findings suggest that patients with diffuse FDG uptake on PET/CT, especially patients with advanced age and low platelet and white blood cell counts, are likely to have BMI and could potentially forego BMB. Patients with negative PET/CT findings and no significant laboratory abnormalities are very unlikely to have BMI. Conclusion Our results suggest that BMI should not be decided solely based PET/CT or BMB findings. It is reasonable to use both diagnostic assays along with clinical and laboratory findings. PET/CT result, clinical and laboratory findings could be useful for predicting BMI in patient for whom BMB is contraindicated.

Clinical presentation and treatment outcomes of primary ocular adnexal MALT lymphoma in Thailand

  • Seresirikachorn, Kasem;Norasetthada, Lalita;Ausayakhun, Sakarin;Apivatthakakul, Atitaya;Tangchittam, Sirima;Pruksakorn, Vannakorn;Wudhikarn, Kitsada;Wiwatwongwana, Damrong
    • BLOOD RESEARCH
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    • v.53 no.4
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    • pp.307-313
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    • 2018
  • Background Primary ocular adnexal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (POML) is the most common subtype of lymphoma involving the eyes in Thailand. We sought to assess the characteristics and treatment outcomes of patients with POML in Thailand. Methods We retrospectively reviewed patient data and included patients diagnosed with POML between January 2004 and December 2016 at Chiang Mai University Hospital and King Chulalongkorn Memorial Hospital, Thailand. We collected and analyzed patients' clinical characteristics and treatment outcomes. Results Among 146 patients with lymphoma involving the eyes, 121 (82%) were diagnosed with POML. Sixty-four (52.9%) were women with median age 58 (range, 22-86) years. The most common presenting symptom was orbital mass (71.1%). Common sites of origin were the orbit (46.3%) and lacrimal gland (34.7%). At presentation, 22.3% of patients had bilateral eye involvement. About half of patients had stage I disease (N=59, 56.2%) and 20% had stage IV. Most patients (73.3%) had a low-risk International Prognostic Index. Radiotherapy was the main treatment for patients with limited-stage disease (66.7% in stage I and 56.5% in stage II). The overall response rate was 100% with complete response rates 80%, 77.3%, and 64.7% for stages I, II, and IV, respectively. Five-year progression-free survival (PFS) and overall survival were 66.1% and 94.0%, respectively. For patients with limited-stage disease, radiotherapy significantly improved PFS compared with treatment not involving radiotherapy (5-year PFS 89.9% vs. 37.3%, P=0.01). Conclusion We revealed that POML has good response to treatment, especially radiotherapy, with excellent long-term outcome.

Treatment and clinical outcomes of patients relapsing after allogeneic hematopoietic cell transplantation for myelodysplastic syndrome

  • Choi, Eun-Ji;Lee, Je-Hwan;Lee, Jung-Hee;Park, Han-Seung;Ko, Sun-Hye;Seol, Miee;Lee, Young-Shin;Kang, Young-Ah;Jeon, Mijin;Lee, Kyoo-Hyung
    • BLOOD RESEARCH
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    • v.53 no.4
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    • pp.288-293
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    • 2018
  • Background Although allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment option for myelodysplastic syndrome (MDS), a substantial number of patients experience relapse. We reviewed the clinical outcomes of patients with MDS who relapsed after allogeneic HCT. Methods Thirty patients who experienced relapse or progression after allogeneic HCT for MDS between July 2000 and May 2016 were included in this retrospective analysis. Results The median time from HCT to relapse was 6.6 (range, 0.9-136.3) months. Donor lymphocyte infusions (DLIs) were administered to four patients: one achieved complete remission (CR) and survived disease free, while three did not respond to DLI and died. Hypomethylating agents were administered to seven patients: one who had stable disease continuously received decitabine, while six died without response to treatment. Six patients received AML-like intensive chemotherapy, and three achieved CR: two underwent second HCT and one DLI. One patient receiving second HCT survived without disease, but the other two relapsed and died. Three, four, and eight patients who did not respond to intensive chemotherapy, low-dose cytarabine, and best supportive care, respectively, died. One patient who underwent second HCT following cytogenetic relapse survived disease free. Median overall survival after relapse was 4.4 months, and relapse within 6 months after HCT was associated with shorter survival. Conclusion Outcomes of MDS patients relapsing after allogeneic HCT were disappointing. Some patients could be saved using DLI or second HCT.

Relationship between liver iron concentration determined by R2-MRI, serum ferritin, and liver enzymes in patients with thalassemia intermedia

  • Al-Momen, Hayder;Jasim, Shaymaa Kadhim;Hassan, Qays Ahmed;Ali, Hayder Hussein
    • BLOOD RESEARCH
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    • v.53 no.4
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    • pp.314-319
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    • 2018
  • Background Iron overload is a risk factor affecting all patients with thalassemia intermedia (TI). We aimed to determine whether there is a relationship of serum ferritin (SF) and alanine aminotransferase (ALT) with liver iron concentration (LIC) determined by R2 magnetic resonance imaging (R2-MRI), to estimate the most relevant degree of iron overload and best time to chelate in patients with TI. Methods In this cross-sectional study, 119 patients with TI (mean age years) were randomly selected and compared with 120 patients who had a diagnosis of thalassemia major (TM). Correlations of LIC, as determined by R2-MRI, with SF and ALT levels, were assessed in all participants. A P-value <0.05 was considered statistically significant. Results SF and LIC levels were lower in patients with TI than in those with TM; only ferritin values were significant. We found a statistically significant relationship between SF and LIC, with cut-off estimates of SF in patients with TI who had splenectomy and those who entered puberty spontaneously (916 and 940 ng/mL, respectively) with LIC >5 mg Fe/g dry weight (P<0.0001). A significant relationship was also found for patients with TI who had elevated ALT level (63.5 U/L), of 3.15 times the upper normal laboratory limit, using a cut-off for LIC ${\geq}5mg\;Fe/g\;dry\;weight$. Conclusion We determined the cut-off values for ALT and SF indicating the best time to start iron chelation therapy in patients with TI, and found significant correlations among iron overload, SF, and ALT.

Altered expression of MALAT1 lncRNA in chronic lymphocytic leukemia patients, correlation with cytogenetic findings

  • Ahmadi, Abdolrahim;Kaviani, Saeid;Yaghmaie, Marjan;Pashaiefar, Hossein;Ahmadvand, Mohammad;Jalili, Mahdi;Alimoghaddam, Kamran;Eslamijouybari, Mohammad;Ghavamzadeh, Ardeshir
    • BLOOD RESEARCH
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    • v.53 no.4
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    • pp.320-324
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    • 2018
  • Background Recent studies have devoted much attention to non-protein-coding transcripts in relation to a wide range of malignancies. MALAT1, a long non-coding RNA, has been reported to be associated with cancer progression and prognosis. Thus, we here determined MALAT1 gene expression in chronic lymphocytic leukemia (CLL), a genetically heterogeneous disease, and explored its possible relationships with cytogenetic abnormalities. Methods MALAT1 expression level was evaluated using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) on blood mononuclear cells from 30 non-treated CLL patients and 30 matched healthy controls. Cytogenetic abnormalities were determined in patients by fluorescence in situ hybridization (FISH). Results MALAT1 expression level was up-regulated in the CLL group compared to healthy controls (P=0.008). Del13q14, followed by Del11q22, were the most prevalent cytogenetic abnormalities. We found no association between the FISH results and MALAT1 expression in patients. Conclusion Altered expression of MALAT1 is associated with CLL development. Further investigations are required to assess the relationship between this long non-coding RNA and CLL patient survival and prognosis.

Comparison of mean platelet volume levels in coronary artery ectasia and healthy people: systematic review and meta-analysis

  • Moghadam, Reza Heidary;Shahmohammadi, Afshar;Asgari, Nader;Azizi, Koorosh;Mansour, Sahar Mehr;Roozbahani, Mohammad
    • BLOOD RESEARCH
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    • v.53 no.4
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    • pp.269-275
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    • 2018
  • Coronary artery ectasia (CAE) is defined as the dilation of a segment of a coronary vessel to at least 1.5 times the diameter of its normal adjacent segment. Mean platelet volume (MPV) plays a role in acute coronary syndromes, with high MPV correlating to poor prognosis for acute thrombotic events and CAE. Several studies investigated the relationship between MPV and CAE, resulting in conflicting results. These results led us to systematically review all studies investigating the relationship between MPV and ectatic heart diseases by performing a meta-analysis study in order to report a unified result. This meta-analysis study investigated all case-control articles examining the relationship between MPV and CAE. All studies in the following databases published until January 31, 2018, were investigated: Science Direct, Scopus, PubMed, Google Scholar, and Web of Science. Following a quality control evaluation, 14 articles, all of which were published following studies performed in Turkey from 2007 to 2016, met the criteria for study inclusion. After pooling the results from all of the articles, a total standardized mean difference (SMD) value of 0.584 (95% CI, 0.219, 0.95) was obtained using the D+L pooled SMD, indicating a significant difference (P=0.002) between the two groups, with higher MPV values in ectatic patients when comparing to healthy individuals. Therefore, increased MPV levels were significantly related to CAE, suggesting that platelets, with their inflammatory and thrombotic activities, play a role in this disease. Therefore, anti-platelet and anti-inflammatory therapies may be effective in treating CAE.

Clinicohematological parameters and outcomes in a cohort of chronic lymphocytic leukemia patients with Deletion 17p from Pakistan

  • Mahmood, Rafia;Khan, Saleem Ahmed;Altaf, Chaudhry;Malik, Hamid Saeed;Khadim, Muhammad Tahir
    • BLOOD RESEARCH
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    • v.53 no.4
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    • pp.276-280
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    • 2018
  • Background Chronic lymphocytic leukemia (CLL) exhibits profound heterogeneity in its clinical course. Its clinicohematological and cytogenetic features play a significant role in determining the clinical course and in predicting the treatment response and prognosis. In this context, 17p deletion is known to predict a poor prognosis, as these cases are refractory to conventional therapy. This study aimed to evaluate the clinicohematological characteristics, outcomes, and prognostic factors among CLL patients with and without del 17p in Pakistan. Methods This prospective observational study was conducted at the Department of Haematology, Armed Forces Institute of Pathology (Rawalpindi, Pakistan) between January 2013 and December 2017. Patients were diagnosed based on the International Workshop on Chronic Lymphocytic Leukaemia IWCLL criteria, their clinicohematological parameters were recorded, and cytogenetic analyses were performed. The time from diagnosis to treatment and the 2-year overall survival rate were also evaluated. Results We evaluated 130 CLL cases, including 24 patients (18.5%) with del 17p, who included 18 men (75%) and 6 women (25%). The median age was 68 years. Binet stage C was detected at the presentation in 16 patients (67%). Treatment was administered to 14 patients (70%) at a median interval of 11 months (range, 0-28 mo) after diagnosis. The overall response rate was 64.3%, the median event-free survival was 9 months (range, 1-23 mo), and the 2-year overall survival rate was 65%. Conclusion Del 17p is relatively common in Pakistan, and patients harboring this deletion had poor treatment response and survival outcomes.

Effects of Flexi-bar Exercise on Shoulder Pain, Disfunction, Quality of Life and Range of Motion in Women with Breast Cancer Surgery (유방암 수술을 한 여성에게 Flexi-bar 운동이 견관절 통증, 기능장애, 삶의 질, 관절가동범위에 미치는 영향)

  • Lee, Min-ji;Kwon, O-kook;Kim, Youn-jin;Shin, Eui-joo;Yu, Dal-young
    • The Journal of Korean Academy of Orthopedic Manual Physical Therapy
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    • v.27 no.2
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    • pp.45-54
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    • 2021
  • Background: The purpose of this study was to investigate the effects of flexi-bar exercise on shoulder pain, dysfunction, quality of life, and range of motion of women with breast cancer surgery. Methods: A total of 42 female patients who had breast cancer were included in this study. By drawing lots, subjects were divided into a flexi-bar exercise group (FBG, n=21) and a general breast cancer group (GBG, n=18). The effects of flexi-bar exercise on patients were evaluated in terms of the visual analogue scale (VAS), the shoulder pain and disability index (SPADI), the European organization for the research and treatment of cancer quality of life questionnaire (EORTC QLQ-C30), the breast cancer specific EORTC quality of life questionnaire (EORTC QLQ-BR23), and range of motion (ROM), all of which were measured pre- and post- intervention followed by evaluation. Results: A significant increase was pain, functional disability level, quality of life, ROM within the two groups (p<.01). There were pain, functional disability level, quality of life, ROM post test then invention were significant between the two groups(p<.01). Conclusion: The flexi-bar exercise has a positive treatment effect on breast cancer patients.

Antioxidant Activities of Eggplant (Solanum melongena) Powder with Different Drying Methods and Addition Levels to Pork Sausages

  • Sembring, Hanna Seprina br;Chin, Koo Bok
    • Food Science of Animal Resources
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    • v.41 no.4
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    • pp.715-730
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    • 2021
  • The objective of this study was to evaluate antioxidant activities of eggplant (EP) powder with different drying methods and addition levels to pork sausages to improve product quality. Antioxidant activities of EP with different drying methods, particle sizes, and solvents of extraction were determined. Freeze dried (FD) EP extracted with 100% ethanol had higher 2,2-diphenyl-1picrylhydrazyl radical-scavenging activities (DPPH-RSA) and total phenolic content (TPC) values than other drying methods. FD500 had the highest iron chelating ability (ICA) value. Oven-dried (OD) EP at 60℃ had the highest reducing power. Dried EP was added to sausages of six groups: control without EP, reference added with ascorbic acid, O1 and O2 added with 0.25% and 0.5% OD EP, respectively, and F1 and F2 added with 0.25% and 0.5% FD EP, respectively. Pork sausages added with O2 had the lowest TBARS and TPC values. These values increased during storage. Purge loss (%), lightness (L*), and redness (a*) values of F2 were lower than those of other groups, whereas sausages containing F2 had the highest yellowness (b*). pH values of sausages added with EP were increased regardless of the level of EP added. Hardness values of F2 were higher. However, there were no significant differences in other textural characteristics. Sausages added with EP had higher moisture and protein contents (%), but lower fat contents (%). These results indicate that EP powder could be used to retard lipid oxidation and inhibit microbial counts during storage time.