1.Lymphodepletion in Chimeric Antigen Receptor T-Cell Therapy for Solid Tumors: A Focus on Brain Tumors
Anna JU ; Soyoung CHOI ; Yeongha JEON ; Kiwan KIM
Brain Tumor Research and Treatment 2024;12(4):208-220
Chimeric antigen receptor (CAR)-T cell therapy, which has demonstrated remarkable efficacy in hematologic malignancies, is being extended to the treatment of refractory solid tumors, including brain tumors. Lymphodepletion (LD) is an essential preconditioning process that enhances CAR-T efficacy by promoting CAR-T cell expansion and persistence in the body, and has become a standard regimen for hematologic cancers. Recent clinical results of CAR-T therapy for solid tumors, including brain tumors, have shown that cyclophosphamide/fludarabine-based preconditioning has potential benefits and is gradually becoming adopted in solid tumor CAR-T trials. Furthermore, some CAR-T trials for solid tumors are attempting to develop LD regimens optimized specifically for solid tumors, distinct from the standard LD regimens used in hematologic cancers. In contrast, CAR-T therapy targeting brain tumors frequently employs locoregionally repeated administration in tumors or cerebrospinal fluid, resulting in less frequent use of LD compared to other solid tumors. Nevertheless, several clinical studies suggest that LD may still provide potential benefits for CAR-T expansion and improvement in clinical responses in systemic CAR-T administration. The studies presented in this review suggest that while LD can be beneficial for enhancing CAR-T efficacy, considerations must be made regarding its compatibility with the CAR-T administration route, potential excessive activation based on CAR-T structural characteristics, and target expression in normal organs. Additionally, given the unique characteristics of brain tumors, optimized selection of LD agents, as well as dosing and regimens, may be required, highlighting the need for further research.
2.Lymphodepletion in Chimeric Antigen Receptor T-Cell Therapy for Solid Tumors: A Focus on Brain Tumors
Anna JU ; Soyoung CHOI ; Yeongha JEON ; Kiwan KIM
Brain Tumor Research and Treatment 2024;12(4):208-220
Chimeric antigen receptor (CAR)-T cell therapy, which has demonstrated remarkable efficacy in hematologic malignancies, is being extended to the treatment of refractory solid tumors, including brain tumors. Lymphodepletion (LD) is an essential preconditioning process that enhances CAR-T efficacy by promoting CAR-T cell expansion and persistence in the body, and has become a standard regimen for hematologic cancers. Recent clinical results of CAR-T therapy for solid tumors, including brain tumors, have shown that cyclophosphamide/fludarabine-based preconditioning has potential benefits and is gradually becoming adopted in solid tumor CAR-T trials. Furthermore, some CAR-T trials for solid tumors are attempting to develop LD regimens optimized specifically for solid tumors, distinct from the standard LD regimens used in hematologic cancers. In contrast, CAR-T therapy targeting brain tumors frequently employs locoregionally repeated administration in tumors or cerebrospinal fluid, resulting in less frequent use of LD compared to other solid tumors. Nevertheless, several clinical studies suggest that LD may still provide potential benefits for CAR-T expansion and improvement in clinical responses in systemic CAR-T administration. The studies presented in this review suggest that while LD can be beneficial for enhancing CAR-T efficacy, considerations must be made regarding its compatibility with the CAR-T administration route, potential excessive activation based on CAR-T structural characteristics, and target expression in normal organs. Additionally, given the unique characteristics of brain tumors, optimized selection of LD agents, as well as dosing and regimens, may be required, highlighting the need for further research.
3.Lymphodepletion in Chimeric Antigen Receptor T-Cell Therapy for Solid Tumors: A Focus on Brain Tumors
Anna JU ; Soyoung CHOI ; Yeongha JEON ; Kiwan KIM
Brain Tumor Research and Treatment 2024;12(4):208-220
Chimeric antigen receptor (CAR)-T cell therapy, which has demonstrated remarkable efficacy in hematologic malignancies, is being extended to the treatment of refractory solid tumors, including brain tumors. Lymphodepletion (LD) is an essential preconditioning process that enhances CAR-T efficacy by promoting CAR-T cell expansion and persistence in the body, and has become a standard regimen for hematologic cancers. Recent clinical results of CAR-T therapy for solid tumors, including brain tumors, have shown that cyclophosphamide/fludarabine-based preconditioning has potential benefits and is gradually becoming adopted in solid tumor CAR-T trials. Furthermore, some CAR-T trials for solid tumors are attempting to develop LD regimens optimized specifically for solid tumors, distinct from the standard LD regimens used in hematologic cancers. In contrast, CAR-T therapy targeting brain tumors frequently employs locoregionally repeated administration in tumors or cerebrospinal fluid, resulting in less frequent use of LD compared to other solid tumors. Nevertheless, several clinical studies suggest that LD may still provide potential benefits for CAR-T expansion and improvement in clinical responses in systemic CAR-T administration. The studies presented in this review suggest that while LD can be beneficial for enhancing CAR-T efficacy, considerations must be made regarding its compatibility with the CAR-T administration route, potential excessive activation based on CAR-T structural characteristics, and target expression in normal organs. Additionally, given the unique characteristics of brain tumors, optimized selection of LD agents, as well as dosing and regimens, may be required, highlighting the need for further research.
4.Exploratory Clinical Trial of a Depression Diagnostic Software That Integrates Stress Biomarkers and Composite Psychometrics
Sooah JANG ; In-Young KIM ; Sun-Woo CHOI ; Anna LEE ; Ju-Yeal LEE ; Hyunkyung SHIN ; Junwoo LEE ; Mikyeong LEE ; Kyoung-Ryul LEE ; Saeeun JUNG ; Jin Sun RYU ; Jihee OH ; Manjae KWON ; Joohan KIM ; Ryunsup AHN ; Young-Chul JUNG ; Jeong-Ho SEOK
Psychiatry Investigation 2024;21(3):230-241
Objective:
This study evaluated the clinical effectiveness of Minds.NAVI, a depression screening kit combining psychometric measures and stress hormone biomarkers, in a prospective clinical trial. The objective was to assess its potential as a depression screening tool and investigate the associations between psychological assessments, salivary hormone staging, and depression severity.
Methods:
Thirty-five participants with major depressive disorder and 12 healthy controls (HCs) were included. The Minds.NAVI software, utilizing the PROtective and Vulnerable factors battEry Test (PROVE) and salivary cortisol/dehydroepiandrosterone (DHEA) analysis, was employed. The PROVE test is a comprehensive self-report questionnaire that assesses depressive symptoms, suicide risk, attachment style, adverse childhood experiences, mentalization capacity, and resilience. In addition, salivary cortisol and DHEA levels were measured to evaluate the functional stage of the hypothalamic–pituitary–adrenal (HPA) axis.
Results:
Minds.NAVI exhibited 100% sensitivity, 91.7% specificity, and 97.9% accuracy in distinguishing depression from HCs within an exploratory small group. Salivary stress hormone phases showed changes with depression stage (p=0.030), and the proportion of patients with “adrenal exhaustion stage” was higher in the moderate/severe depression group (p=0.038). Protective/vulnerable factors differed significantly between controls and depressed groups (p<0.001). Cortisol awakening response inversely correlated with depressive symptom severity (r=-0.31, p=0.034).
Conclusion
This study suggested possible clinical effectiveness of Minds.NAVI, a depression screening tool that integrates psychometric measures and stress hormone biomarkers. The findings support the potential association between depression, chronic stress, and HPA axis hyporesponsiveness.
5.8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases.
Damijan KNEZ ; Daniel DIEZ-IRIEPA ; Mourad CHIOUA ; Andrea GOTTINGER ; Milica DENIC ; Fabien CHANTEGREIL ; Florian NACHON ; Xavier BRAZZOLOTTO ; Anna SKRZYPCZAK-WIERCIOCH ; Anže MEDEN ; Anja PIŠLAR ; Janko KOS ; Simon ŽAKELJ ; Jure STOJAN ; Kinga SAŁAT ; Julia SERRANO ; Ana Patricia FERNÁNDEZ ; Aitana SÁNCHEZ-GARCÍA ; Ricardo MARTÍNEZ-MURILLO ; Claudia BINDA ; Francisco LÓPEZ-MUÑOZ ; Stanislav GOBEC ; José MARCO-CONTELLES
Acta Pharmaceutica Sinica B 2023;13(5):2152-2175
We describe the development of quinolylnitrones (QNs) as multifunctional ligands inhibiting cholinesterases (ChEs: acetylcholinesterase and butyrylcholinesterase-hBChE) and monoamine oxidases (hMAO-A/B) for the therapy of neurodegenerative diseases. We identified QN 19, a simple, low molecular weight nitrone, that is readily synthesized from commercially available 8-hydroxyquinoline-2-carbaldehyde. Quinolylnitrone 19 has no typical pharmacophoric element to suggest ChE or MAO inhibition, yet unexpectedly showed potent inhibition of hBChE (IC50 = 1.06 ± 0.31 nmol/L) and hMAO-B (IC50 = 4.46 ± 0.18 μmol/L). The crystal structures of 19 with hBChE and hMAO-B provided the structural basis for potent binding, which was further studied by enzyme kinetics. Compound 19 acted as a free radical scavenger and biometal chelator, crossed the blood-brain barrier, was not cytotoxic, and showed neuroprotective properties in a 6-hydroxydopamine cell model of Parkinson's disease. In addition, in vivo studies showed the anti-amnesic effect of 19 in the scopolamine-induced mouse model of AD without adverse effects on motoric function and coordination. Importantly, chronic treatment of double transgenic APPswe-PS1δE9 mice with 19 reduced amyloid plaque load in the hippocampus and cortex of female mice, underscoring the disease-modifying effect of QN 19.
6.Effects of Dietary Habits on General and Abdominal Obesity in Community-dwelling Patients with Schizophrenia
Mina KIM ; Soo Jin YANG ; Hyang Hee KIM ; Anna JO ; Min JHON ; Ju-Yeon LEE ; Seung-Hyung RYU ; Jae-Min KIM ; Young-Ran KWEON ; Sung-Wan KIM
Clinical Psychopharmacology and Neuroscience 2023;21(1):68-76
Objective:
To investigate the effects of dietary habits on general and abdominal obesity in community-dwelling patients with schizophrenia spectrum disorder according to sex.
Methods:
A total of 270 patients with schizophrenia spectrum disorder registered at mental health welfare centers and rehabilitation facilities were recruited. General obesity was defined as a body mass index ≥ 30 kg/m 2 , and abdominal obesity was defined as a waist circumstance ≥ 90 cm in men and ≥ 85 cm in women. Dietary habits were evaluated using dietary guidelines published by the Korean Ministry of Health and Welfare. Demographic and clinical characteristics along with dietary habits and information related to obesity were collected. Factors related to obesity were evaluated separately by sex.
Results:
Dietary habits differed according to sex, in that scores for healthy eating habits were lower in men than in women. In men, the prevalences of general and abdominal obesity were 17.0% and 37.3%, respectively. In women, the prevalences of general and abdominal obesity were 23.1% and 38.5%, respectively. Regression analysis showed that the scores of regular eating habits were negatively associated with general and abdominal obesity in men, and the scores of healthy eating habits were negatively associated with general and abdominal obesity in women.
Conclusion
Among patients with schizophrenia, regular eating habits might reduce the risk of obesity in men, and healthy eating habits might reduce the risk of obesity in women. Nutrition education should be provided to community-dwelling patients with schizophrenia to prevent obesity in this population.
7.Effectiveness of Switching to Long-acting Injectable Aripiprazole in Patients with Recent-onset and Chronic Schizophrenia
Sung-Wan KIM ; Bong-Ju LEE ; Eun-Jin CHEON ; Seung-Hee WON ; Anna JO ; Jae-Min KIM ; Young-Chul CHUNG
Clinical Psychopharmacology and Neuroscience 2023;21(1):57-67
Objective:
This study investigated the effectiveness of switching to once-monthly long-acting injectable (LAI) aripiprazole from other second-generation antipsychotics including LAI paliperidone palmitate in both recent-onset and chronic schizophrenia patients.
Methods:
This was a 24-week prospective, open-label, flexible dose-switching study in patients with schizophrenia. Scores on the Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance (PSP) scale, Clinical Global Impression (CGI), Subjective Well-being Under Neuroleptics−Short Form (SWN-K), and a computerized emotional recognition test (ERT) were evaluated. Subjects were divided into two groups (recent onset and chronic) based on 5 years’ duration of the illness.
Results:
Among the 82 patients participating, 67 (81.7%) completed the 24-week study. The discontinuation rate after switching to LAI aripiprazole did not differ according to clinical characteristics including type of previous antipsychotics. Scores on the PANSS, PSP, SWN-K, CGI, and ERT were significantly improved after a switch to LAI aripiprazole without exacerbation of metabolic parameters and bodyweight. The improvements in the PANSS, PSP, and CGI scores were significantly greater in patients with recent-onset than in those with chronic schizophrenia; the improvement in metabolic parameters was significantly greater in the latter group.
Conclusion
High rates of successful switching to LAI aripiprazole from other antipsychotics suggest its good tolerability and effectiveness. Improvements in psychopathology and social functioning were more evident in patients with recent-onset schizophrenia, and improvements in metabolic abnormalities were more prominent in patients with chronic schizophrenia.
8.Medical Issues and Opinions of Obstetrics Regarding Abortion Law Amendment
Anna CHOI ; Yong Won PARK ; Sei Kwang KIM ; Seung Cheol KIM ; Pil Ryang LEE ; Kyoung Joo HWANG ; Jae Kwan LEE ; Kyung SEO ; Young Ju KIM ; Dong Hyun CHA ; Sunghun NA ; Dong Suk KIM ; Young Kyu LEE ; Youngseok WON ; Jae Yoo KIM ; Jaeyean KIM ; Jinhak KIM ; Woong JU ; Mi-Kyung KIM ; Jeong Yoel PARK
Journal of the Korean Society of Maternal and Child Health 2020;24(1):9-17
There have been ongoing social discussions on revision of the abortion law since the Constitutional Court ruled it nonconformity to the constitution on April 11, 2019. Thus, Korean Society of Obstetrics and Gynecology, Korean Society of Maternal Fetal Medicine, Korean College of Obstetricians and Gynecologists, and Korean Association of Obstetricians and Gynecologists organized 'special committee for abortion law' to support social discussion on the revision of the abortion law, and they prepared official opinions of obstetrics for medical issues including doctors' right to refuse abortion. In the future, the committee will continue to adapt to changes of medical environment especially after the revision of the abortion law by collecting its members' feedbacks.
9.Medical Issues and Opinions of Obstetrics Regarding Abortion Law Amendment
Anna CHOI ; Yong Won PARK ; Sei Kwang KIM ; Seung Cheol KIM ; Pil Ryang LEE ; Kyoung Joo HWANG ; Jae Kwan LEE ; Kyung SEO ; Young Ju KIM ; Dong Hyun CHA ; Sunghun NA ; Dong Suk KIM ; Young Kyu LEE ; Youngseok WON ; Jae Yoo KIM ; Jaeyean KIM ; Jinhak KIM ; Woong JU ; Mi-Kyung KIM ; Jeong Yoel PARK
Journal of the Korean Society of Maternal and Child Health 2020;24(1):9-17
There have been ongoing social discussions on revision of the abortion law since the Constitutional Court ruled it nonconformity to the constitution on April 11, 2019. Thus, Korean Society of Obstetrics and Gynecology, Korean Society of Maternal Fetal Medicine, Korean College of Obstetricians and Gynecologists, and Korean Association of Obstetricians and Gynecologists organized 'special committee for abortion law' to support social discussion on the revision of the abortion law, and they prepared official opinions of obstetrics for medical issues including doctors' right to refuse abortion. In the future, the committee will continue to adapt to changes of medical environment especially after the revision of the abortion law by collecting its members' feedbacks.
10.Hepatitis B Screening and Vaccination Practices in Asian American Primary Care.
Danny CHU ; Ju Dong YANG ; Anna S LOK ; Tram TRAN ; Eduardo Bruno MARTINS ; Elizabeth FAGAN ; Franck ROUSSEAU ; W Ray KIM
Gut and Liver 2013;7(4):450-457
BACKGROUND/AIMS: Screening for hepatitis B virus (HBV) is recommended in populations with anticipated prevalence > or =2%. This study surveyed HBV screening and vaccination practices of Asian American primary care providers (PCPs). METHODS: Approximately 15,000 PCPs with Asian surnames in the New York, Los Angeles, San Francisco, Houston, and Chicago areas were invited to participate in a web-based survey. Asian American PCPs with > or =25% Asian patients in their practice were eligible. RESULTS: Of 430 (2.9%) survey respondents, 217 completed the survey. Greater than 50% followed > or =200 Asian patients. Although 95% of PCPs claimed to have screened patients for HBV, 41% estimated that < or =25% of their adult Asian patients had ever been screened, and 50% did not routinely screen all Asian patients. In a multivariable analysis, the proportion of Asian patients in the practice, provider geographic origin and the number of liver cancers diagnosed in the preceding 12 months were significantly associated with a higher likelihood of screening for HBV. Over 80% of respondents reported that < or =50% of their adult Asian patients had received the HBV vaccine. CONCLUSIONS: Screening and vaccination for HBV in Asian American patients is inadequate. Measures to improve HBV knowledge and care by primary-care physicians are critically needed.
Adult
;
Asian Americans
;
Asian Continental Ancestry Group
;
Chicago
;
Data Collection
;
Hepatitis
;
Hepatitis B
;
Hepatitis B virus
;
Hepatitis B, Chronic
;
Humans
;
Liver Neoplasms
;
Los Angeles
;
Mass Screening
;
New York
;
Prevalence
;
Primary Health Care
;
San Francisco
;
Vaccination

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