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1.
Ann Hepatobiliary Pancreat Surg ; 28(2): 161-202, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38679456

RESUMO

Backgrounds/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions: The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

2.
Biomol Ther (Seoul) ; 32(3): 379-389, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38586913

RESUMO

This study was aimed to evaluate endogenous metabolic changes before and after cisplatin and radiation therapy in patients with cervical cancer via untargeted metabolomic analysis using plasma samples. A total of 13 cervical cancer patients were enrolled in this study. Plasma samples were collected from each patient on two occasions: approximately one week before therapy (P1) and after completion of cisplatin and radiation therapy (P2). Of the 13 patients, 12 patients received both cisplatin and radiation therapy, whereas one patient received radiation therapy alone. The samples were analyzed using the Ultimate 3000 coupled with Q ExactiveTM Focus Hybrid Quadrupole-OrbitrapTM mass spectrometry (Thermo Fisher Scientific, Waltham, MA, USA). Chromatographic separation utilized a Kinetex C18 column 2.1×100 mm (2.6 µm) (Phenomenex, Torrance, CA, USA), and the temperature was maintained at 40°C. Following P2, there were statistically significant increases in the concentrations of indoxyl sulfate, phenylacetylglutamine, Lysophosphatidyethanolamine (LysoPE) (18:1), and indole-3-acetic acid compared with the concentrations observed at P1. Specifically, in the human papillomavirus (HPV) noninfection group, indoxyl sulfate, LysoPE (18:1), and phenylacetylglutamine showed statistically significant increases at P2 compared with P1. No significant changes in metabolite concentrations were observed in the HPV infection group. Indoxyl sulfate, LysoPE (18:1), phenylacetylglutamine, and indole-3-acetic acid were significantly increased following cisplatin and radiation therapy.

3.
J Magn Reson Imaging ; 57(3): 930-938, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35833798

RESUMO

BACKGROUND: The Liver Imaging Reporting and Data System (LI-RADS) is a comprehensive system for standardizing the terminology and interpretation of liver imaging. The association between the LI-RADS category and tumor recurrence in patients with intrahepatic cholangiocarcinomas (iCCAs) has not yet been evaluated in a multicenter study. PURPOSE: To retrospectively investigate the preoperative clinical and imaging features associated with recurrence-free survival (RFS) after curative resection of iCCAs and to identify the role of the LI-RADS category in at-risk patients. STUDY TYPE: Retrospective, multicenter. SUBJECTS: A total of 113 patients (mean age: 61.1 years; 74 men, 39 women) who underwent preoperative contrast-enhanced MRI and curative surgical resection for a single treatment-naive iCCA between 2008 and 2021. FILED STRENGTH/SEQUENCE: A 3 T dual gradient-echo T1 WI with in- and opposed-phase, turbo spin-echo T2 WI, diffusion-weighted echo-planar images, and three-dimensional gradient-echo T1 WI before and after administration of contrast agent. ASSESSMENT: MR imaging features were evaluated and assigned for each lesion using LI-RADS version 2018. RFS was calculated from the date of surgery to tumor recurrence or the last imaging date without evidence of recurrence. Factors affecting RFS were evaluated using clinical and imaging features. STATISTICAL TESTS: Cox proportional hazards model, Kaplan-Meier method, and log-rank test. A P-value of <0.05 was considered statistically significant. RESULTS: A total of 93 (82.3%) were categorized as LR-M and 20 (17.7%) were categorized as LR-4 or 5. In the multivariable analysis, LR-M category (hazard ratio [HR], 8.035; 95% confidence interval [CI], 1.096-58.931) and a tumor size >3 cm on MRI (HR, 2.690; 95% CI, 1.319-5.487) were independent factors for poor RFS. The 5-year RFS rate was significantly higher in patients with iCCA categorized as LR-4 or 5 than in those categorized as LR-M (94.4% vs. 51.9%, respectively). DATA CONCLUSION: Patients with iCCA categorized as LR-4 or 5 may have a better RFS than those categorized as LR-M. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Recidiva Local de Neoplasia/diagnóstico por imagem , Meios de Contraste , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Imageamento por Ressonância Magnética/métodos , Ductos Biliares Intra-Hepáticos , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia
4.
Cell Death Dis ; 13(9): 791, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109513

RESUMO

Immune checkpoint molecule programmed death-ligand 1 (PD-L1) is overexpressed in cancer cells and imparts resistance to cancer therapy. Although membrane PD-L1 has been targeted for cancer immune therapy, nuclear PD-L1 was reported to confer cancer resistance. Therefore, it is important to regulate the nuclear PD-L1. The mechanisms underlying the therapeutic efficacy of PD-L1 targeting have not been well-established. Cellular senescence has been considered a pivotal mechanism to prevent cancer progression, and recently, PD-L1 inhibition was shown to be involved in cancer cell senescence. However, the relevance of PD-L1 targeting-induced senescence and the role of stimulator of interferon genes (STING) has not been reported. Therefore, we aimed to identify the role of PD-L1 in cancer progression and how it regulates cancer prevention. In this study, we found that PD-L1 depletion-induced senescence via strong induction of STING expression in mouse melanoma B16-F10 and colon cancer CT26 cells, and in human melanoma A375 and lung cancer A549 cells. Interestingly, nuclear PD-L1 silencing increased STING promoter activity, implying that PD-L1 negatively regulates STING expression via transcriptional modulation. Furthermore, we showed that PD-L1 binds to the STING promoter region, indicating that PD-L1 directly controls STING expression to promote cancer growth. In addition, when we combined PD-L1 silencing with the senescence-inducing chemotherapeutic agent doxorubicin, the effect of PD-L1-targeting was even more powerful. Overall, our findings can contribute to the understanding of the role of PD-L1 in cancer therapy by elucidating a novel mechanism for PD-L1 targeting in cancer cells.


Assuntos
Antígeno B7-H1 , Melanoma , Proteínas de Membrana/metabolismo , Animais , Antígeno B7-H1/metabolismo , Doxorrubicina , Humanos , Proteínas de Checkpoint Imunológico , Interferons , Melanoma/metabolismo , Camundongos
5.
Mol Med ; 27(1): 125, 2021 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-34602056

RESUMO

BACKGROUND: C1q has been reported to reveal complement-independent roles in immune and non-immune cells. C1q binds to its specific receptors to regulate distinct functions that rely on the environment and cell types. Discoidin domain receptor 2 (DDR2) is activated by collagen and functions in wound healing by controlling matrix metalloproteinase (MMP) expression. Since C1q exhibits a collagen-like structure, we hypothesized that C1q might engage DDR2 to regulate wound healing and extracellular matrix (ECM) remodeling. METHODS: Cell-based assay, proximity ligation assay, ELISA, and surface plasmon analysis were utilized to investigate DDR2 and C1q binding. We also investigate the C1q-mediated in vitro wound healing ability using the human fibrosarcoma cell line, HT1080. RESULTS: C1q induced the phosphorylation of DDR2, p38 kinase, and ERK1/2. C1q and DDR2 binding improved cell migration and induced MMP2 and MMP9 expression. DDR2-specific shRNA reduced C1q-mediated cell migration for wound healing. CONCLUSIONS: C1q is a new DDR2 ligand that promotes wound healing. These findings have therapeutic implications in wound healing-related diseases.


Assuntos
Movimento Celular/fisiologia , Colágeno/metabolismo , Complemento C1q/metabolismo , Receptor com Domínio Discoidina 2/metabolismo , Sequência de Aminoácidos , Linhagem Celular Tumoral , Colágeno/química , Complemento C1q/química , Receptor com Domínio Discoidina 1/genética , Receptor com Domínio Discoidina 1/metabolismo , Receptor com Domínio Discoidina 2/genética , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Microscopia Confocal , Peptídeos/metabolismo , Fosforilação , Ligação Proteica , Transdução de Sinais , Cicatrização/fisiologia
6.
PLoS One ; 11(8): e0160557, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27552165

RESUMO

We investigated potential protein markers of post-mortem interval (PMI) using rat kidney and psoas muscle. Tissue samples were taken at 12 h intervals for up to 96 h after death by suffocation. Expression levels of eight soluble proteins were analyzed by Western blotting. Degradation patterns of selected proteins were clearly divided into three groups: short-term, mid-term, and long-term PMI markers based on the half maximum intensity of intact protein expression. In kidney, glycogen synthase (GS) and glycogen synthase kinase-3ß were degraded completely within 48 h making them short-term PMI markers. AMP-activated protein kinase α, caspase 3 and GS were short-term PMI markers in psoas muscle. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was a mid-term PMI marker in both tissues. Expression levels of the typical long-term PMI markers, p53 and ß-catenin, were constant for at least 96 h post-mortem in both tissues. The degradation patterns of GS and caspase-3 were verified by immunohistochemistry in both tissues. GAPDH was chosen as a test PMI protein to perform a lateral flow assay (LFA). The presence of recombinant GAPDH was clearly detected in LFA and quantified in a concentration-dependent manner. These results suggest that LFA might be used to estimate PMI at a crime scene.


Assuntos
Rim/metabolismo , Mudanças Depois da Morte , Músculos Psoas/metabolismo , Animais , Autopsia , Patologia Legal , Expressão Gênica , Gliceraldeído 3-Fosfato Desidrogenase (NADP+)/metabolismo , Glicogênio Sintase/metabolismo , Humanos , Rim/patologia , Masculino , Músculos Psoas/patologia , Ratos , Proteína Supressora de Tumor p53/metabolismo , beta Catenina/metabolismo
7.
Cell Cycle ; 7(10): 1315-20, 2008 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-18418081

RESUMO

Relapse following initial chemotherapy remains a barrier to survival in approximately 20% of children suffering from acute lymphoblastic leukemia (ALL). Recently, to investigate the mechanism of relapse, we analysed clonal populations in 27 pairs of matched diagnosis and relapse ALL samples using PCR-based detection of multiple antigen receptor gene rearrangements. These clonal markers revealed the emergence of apparently new populations at relapse in 13 patients. In those cases where the new 'relapse clone' could be detected in the diagnosis population, there was a close correlation between length of first remission and quantity of the relapse clone in the diagnosis sample. A shorter length of time to first relapse correlated with a higher quantity of the relapsing clone at diagnosis. This observation, together with demonstrated differential chemosensitivity between sub-clones at diagnosis, indicates that relapse in ALL patients may commonly involve selection of a minor intrinsically resistant sub-clone that is undetectable by routine PCR-based methods. From a clinical perspective, relapse prediction may be improved with strategies to detect minor potentially resistant sub-clones early during treatment, hence allowing intensification of therapy. Together with the availability of relevant in vivo experimental models and powerful technology for detailed analysis of patient specimens, this new information will help shape future experimentation towards targeted therapy for high-risk ALL.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Rearranjo Gênico/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/prevenção & controle , Criança , Marcadores Genéticos/genética , Humanos , Modelos Biológicos , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Receptores de Antígenos/genética , Recidiva , Fatores de Tempo
9.
Blood ; 110(2): 632-9, 2007 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-17371950

RESUMO

Relapse following remission induction chemotherapy remains a barrier to survival in approximately 20% of children suffering from acute lymphoblastic leukemia (ALL). To investigate the mechanism of relapse, 27 matched diagnosis and relapse ALL samples were analyzed for clonal populations using polymerase chain reaction (PCR)-based detection of multiple antigen receptor gene rearrangements. These clonal markers revealed the emergence of apparently new populations at relapse in 13 patients. More sensitive clone-specific PCR revealed that, in 8 cases, these "relapse clones" were present at diagnosis and a significant relationship existed between presence of the relapse clone at diagnosis and time to first relapse (P < .007). Furthermore, in cases where the relapse clone could be quantified, time to first relapse was dependent on the amount of the relapse clone at diagnosis (r = -0.84; P = .018). This observation, together with demonstrated differential chemosensitivity between subclones at diagnosis, argues against therapy-induced acquired resistance as the mechanism of relapse in the informative patients. Instead these data indicate that relapse in ALL patients may commonly involve selection of a minor intrinsically resistant subclone that is undetectable by routine PCR-based methods. Relapse prediction may be improved with strategies to detect minor potentially resistant subclones early during treatment, hence allowing intensification of therapy.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Idade de Início , Linfócitos B/imunologia , Pré-Escolar , Células Clonais , Feminino , Rearranjo Gênico , Humanos , Imunoglobulinas/sangue , Imunofenotipagem , Lactente , Masculino , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Receptores de Antígenos/genética , Recidiva
10.
Blood ; 103(10): 3905-14, 2004 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-14764536

RESUMO

Continuous xenografts from 10 children with acute lymphoblastic leukemia (ALL) were established in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Relative to primary engrafted cells, negligible changes in growth rates and immunophenotype were observed at second and third passage. Analysis of clonal antigen receptor gene rearrangements in 2 xenografts from patients at diagnosis showed that the pattern of clonal variation observed following tertiary transplantation in mice exactly reflected that in bone marrow samples at the time of clinical relapse. Patients experienced diverse treatment outcomes, including 5 who died of disease (median, 13 months; range, 11-76 months, from date of diagnosis), and 5 who remain alive (median, 103 months; range, 56-131 months, following diagnosis). When stratified according to patient outcome, the in vivo sensitivity of xenografts to vincristine and dexamethasone, but not methotrexate, differed significantly (P =.028, P =.029, and P =.56, respectively). The in vitro sensitivity of xenografts to dexamethasone, but not vincristine, correlated significantly with in vivo responses and patient outcome. This study shows, for the first time, that the biologic and genetic characteristics, and patterns of chemosensitivity, of childhood ALL xenografts accurately reflect the clinical disease. As such, they provide powerful experimental models to prioritize new therapeutic strategies for future clinical trials.


Assuntos
Antineoplásicos/farmacologia , Modelos Animais de Doenças , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Transplante Heterólogo , Adolescente , Animais , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Feminino , Rearranjo Gênico do Linfócito T , Genes de Imunoglobulinas , Humanos , Imunofenotipagem , Masculino , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Camundongos , Camundongos SCID , Transplante de Neoplasias , Neoplasias Experimentais/tratamento farmacológico , Resultado do Tratamento , Vincristina/farmacologia , Vincristina/uso terapêutico
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