Biomedical subjects

Jinho Shin

Publications and source records attributed to Jinho Shin.

8 recordsLinked to original sources

PubMed2026

Molecular profiling of pancreatic acinar cell carcinoma and amphicrine-like carcinoma: high frequency of homologous recombination deficiency and molecular heterogeneity.

BACKGROUND: The 6th edition of the WHO Classification of Digestive System Tumours distinguishes amphicrine-like carcinomas (ALCs) from mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). Acinar cell carcinomas (ACCs) with an intimately admixed and not separated neuroendocrine component comprising >30% of the tumour are classified as amphicrine-like ACCs (AL-ACCs). We characterised the genomic landscape of pancreatic ACCs and AL-ACCs to validate current classification and identify therapeutic targets. METHODS: Among 2,151 pancreatic biopsy and resection cases that underwent targeted next-generation sequencing using the OncoPanel AMC v4.3 or v4.5 (DNA-based hybrid capture, targeting 323 genes (v4.3) or 343 genes (v4.5)), eight ACCs, seven AL-ACCs originally diagnosed as MiNENs under the 5th edition of the WHO classification scheme, and four neuroendocrine tumours (NETs) were identified, diagnosed between 2020 and 2026. RESULTS: Homologous recombination deficiency (HRD)-associated alterations, involving BRCA1/2, ATM and FANCD2, were identified in 87.5% (7/8) of ACCs and 29% of AL-ACCs. One ACC had an ATRX nonsense mutation. Genomic heterogeneity was observed in molecular profiling of AL-ACCs; two demonstrated a 'true hybrid' signature with co-occurrence of lineage-specific drivers: MEN1 deletion and splice site mutation (neuroendocrine-associated), APC, SMAD4 and CTNNB1 alterations (exocrine-associated). Two others exhibited 'ACC-like' signatures, including missense BRCA1 and nonsense TP53 mutations and MDM4 and AKT3 amplifications, located on chromosome 1q, despite their neuroendocrine differentiation. CONCLUSIONS: Pancreatic ACCs frequently harbour HRD-related alterations, suggesting potential for PARP-inhibitor therapy. AL-ACCs comprise molecularly heterogeneous groups, including true hybrid and ACC-like patterns. Larger studies are required to elucidate the molecular distinction between true hybrid AL-ACCs and those with single-lineage alterations to refine their classification.

acinar↗

PubMed2006

WHO informal consultation on scientific basis for regulatory evaluation of candidate human vaccines from plants, Geneva, Switzerland, 24-25 January 2005.

In January 2005, WHO convened a meeting of leading experts in plant-derived vaccines and experts from regulatory authorities for an informal discussion on the state-of-the-art and to analyse whether specific guidance might be needed for plant-derived vaccines that is not yet provided by regulatory authorities. After a series of individual presentations, a general discussion was held to obtain a consensus on the need for further guidance. Both the presentations and the conclusions are presented. The meeting concluded that existing guidelines for the development, evaluation, and use of vaccines made by traditional methods can be applied to plant-derived vaccines. For plant-derived vaccines some specific issues will have to be addressed. These include, but are not restricted to, containment of the plants including disposal of waste materials. It was noted that plant-derived vaccines have been produced and clinically tested under US investigational new drug application, and all applicable regulatory and good manufacturing practice requirements are in place for this type of product. An innovator wishing to bring a plant-derived vaccine to market should consult closely with regulatory authorities to ensure that all appropriate studies are undertaken.

Guidelines as Topic↗

PubMed2006

Validation of a computer software program for statistical analysis of accelerated stability studies on biological standards.

Long-term stability is an essential requirement for biological measurement standards and it has been evaluated by applying the Arrhenius model to the data obtained from accelerated thermostability studies. A computer program DEGTEST suited to a mainframe computer has been used for evaluating the stability of biological standards for more than a decade. This paper describes the validation of a computer program executable in a personal computer Microsoft Windows XP environment for the analysis of accelerated thermostability study data.

Biological Products↗

PubMed2005

Feasibility and safety of regional myocardial hypothermia during myocardial ischemia and infarction in pigs.

OBJECTIVE: Mild systemic hypothermia has been shown to be feasible and safe in patients during acute myocardial infarction (AMI). Regional myocardial hypothermia of the ischemic myocardium only may be more effective in myocardial salvage with fewer side effects compared with systemic hypothermia. The purpose of this study was to evaluate the feasibility and safety of regional myocardial hypothermia in pigs. METHODS: Open-chest pigs with (n=5) or without (n=4) myocardial infarction underwent left anterior descending coronary artery (LAD) ligation followed by intracoronary infusion of lactated Ringer's solution (at room temperature and at 15 degrees C between 20-35 ml/min for 3 min) via the central lumen of a specially designed balloon catheter at the time of reperfusion. Intramyocardial temperatures via thermocouples at the ischemic zone (LAD territory) and non-ischemic zone (circumflex territory) as well as systemic temperature were constantly recorded, as were the hemodynamics. Each pig acted as its control regarding the myocardial temperature response to both solutions. In addition, intracoronary versus intramyocardial temperatures were compared with thermocouples in both territories during infusion. RESULTS: There was no hemodynamic compromise or arrhythmia seen during the intracoronary infusion of either temperature solution. There was a linear relationship between the infusion solution temperature and infusion rate versus intramyocardial temperature response, with the cooled solution providing 2 degrees C lower temperature and faster infusion resulting in lower intramyocardial temperature. There was no change in the non-ischemic zone or systemic temperature. On average, 6-8 degrees C reduction in tissue temperature, potential target temperature range for hypothermic therapy, was achieved in all animals. In addition, intracoronary temperature in distal LAD measured by intracoronary thermocouples correlated with the intramyocardial temperature (2 degrees C lower temperature in the coronary artery). CONCLUSION: It is feasible and safe to achieve regional myocardial hypothermia by intracoronary infusion of cooled solution in pigs.

Animals↗

PubMed2005

A potent opiate agonist protects against myocardial stunning during myocardial ischemia and reperfusion in rats.

OBJECTIVE: Opioids have a cardioprotective effect during ischemia. Previously, we showed in an ex-vivo model of myocardial ischemia and reperfusion that 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2, a highly potent and long-acting opioid peptide analgesic with fewer side effects than morphine, provides improved cardioprotection compared with morphine. The purpose of this study was to confirm, in an in-vivo model, the cardioprotective effect of 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2. METHODS: Rats (n=6/group) were randomized to 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2 therapy (intravenous 10 nmol bolus 30 min before ligation and 10 nmol/h continuous infusion), morphine (100 nmol bolus and 100 nmol/h infusion), or placebo, and underwent left anterior descending (LAD) ligation for 10 min followed by reperfusion for 30 min. Continuous transesophageal echocardiogram and electrocardiogram were monitored. Fractional shortening and systolic wall thickening of the ischemic area were calculated. Time to recovery of left ventricular function was the duration of time needed for fractional shortening to recover to 90% of baseline following reperfusion. Duration of reperfusion arrhythmia was the time to the cessation of salvo (at least three consecutive premature ventricular contractions (PVCs)) following reperfusion. RESULTS: Time to recovery of left ventricular function was significantly shorter in the 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2 (4.4+/-2.2 min) and morphine groups (6.0+/-2.5 min) than in the controls (10.5+/-2.2 min; p<0.01). The 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2 group showed significantly higher fractional shortening and systolic wall thickening of the ischemic area than the control group. Duration of reperfusion arrhythmia was also significantly shorter in the 2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH2 (2.8+/-1.7 min) and morphine groups (5.8+/-3.9 min) than in the controls (11.8+/-2.0 min; p<0.05). CONCLUSION: 2',6'-Dimethyltyrosine-D-Arg-Phe-Lys-NH2 provides a cardioprotective effect against myocardial ischemia and reperfusion in vivo.

Animals↗

PubMed2005

A novel adenoviral gutless vector encoding sphingosine kinase promotes arteriogenesis and improves perfusion in a rabbit hindlimb ischemia model.

OBJECTIVES: We previously demonstrated that sphingosine kinase (SPK) increases the level of extracellular sphingosine-1-phosphate and promotes neovascularization in a mouse matrigel model. In this study, we tested the hypothesis that SPK gene transfer using a novel adenoviral 'gutless' vector (AGV) can enhance arteriogenesis in a rabbit hindlimb ischemia model. METHODS: Thirty-five male New Zealand white rabbits were randomized to the AGV-SPK group (n=13), AGV-null group (n=13), and control group (n=9). On day 10, after the induction of unilateral hindlimb ischemia, gene vectors or buffer were introduced and the effect examined on day 30, using calf blood pressure, quantitative angiographic analysis, and histology. RESULTS: Calf systolic blood pressure ratios of the ischemic limb to the normal limb on day 30 were 0.77+/-0.13 in control groups, including the AGV-null group, and 0.91+/-0.14 in the AGV-SPK group (P<0.05). Angiographic vessel counts were significantly increased (8.0+/-2.1 at baseline and 11.8+/-3.2 on day 30, P<0.001) in the AGV-SPK group. Histologic analysis showed that microscopic total vessel counts on day 30 were 3.5+/-1.8/field in the control and AGV-null group and 5.4+/-1.0/field in the AGV-SPK group. Arterioles (AGV-SPK; 3.0+/-0.8 versus control and AGV-null; 2.1+/-1.1, P<0.05) were significantly increased in the AGV-SPK group. CONCLUSIONS: This study shows that SPK promotes arteriogenesis, as evidenced by the maximal improvement in the blood pressure restoration and collateral vessel counts. SPK may be an important angiogenic target to improve perfusion in ischemic tissues.

Adenoviridae↗

PubMed2005

A new percutaneous porcine coronary model of chronic total occlusion.

OBJECTIVE: Chronic total occlusion (CTO) of coronary arteries represents a challenge for percutaneous treatment. Although ameroid constrictors have been used to create CTOs from extrinsic compression of coronary arteries, this model is not suitable for evaluation of novel angioplasty equipment. Thus, the objective of this study was to create a new percutaneous animal model of CTO. METHODS: To create an animal model of CTO, we implanted copper-plated stents in the left circumflex coronary arteries of 18 pigs, and assigned the pigs to early group (n = 6; sacrifice at approximately 1 week), intermediate group (n = 6; sacrifice at approximately 4 weeks), and late group (n = 6; sacrifice at approximately 8 weeks). RESULTS: Follow-up angiography prior to sacrifice revealed complete occlusion in 14 of 17 animals, with the subtotal occlusive lesions (mean 60% stenosis) only in the early group. Most of the pigs with total occlusions (12 of 14) showed bridging collateral flow greater than or equal to grade 2 (grade 2: 4; grade 3: 8). Histology revealed organizing thrombus in the early group with persistent inflammation, and organized thrombus with fibrosis and calcification in the intermediate and late groups. Interestingly, there were fibrotic components in the proximal and distal edges of the occlusions with softer, organizing thrombus in the middle of the CTO in the late group, suggesting that the major areas of difficulty are at the entrance and exit segments of the CTO with percutaneous recanalization. CONCLUSION: This study shows the feasibility and reproducibility of a new porcine coronary percutaneous CTO model. This model may be useful in improving our percutaneous treatment of CTO.

Animals↗

PubMed2003

Vulnerable atherosclerotic plaque: clinical implications.

Coronary Artery Disease (CAD) remains globally the leading cause of death and long-term morbidity. Among the many manifestations of CAD, acute coronary syndrome (ACS), ranging from unstable angina to acute myocardial infarction, is the most catastrophic event due to our inability to predict its occurrence. Despite improved treatments of CAD, ACS results in sudden death or permanent disability in a substantial percentage of patients. If we could predict the timing of ACS or better yet prevent its occurrence, we could alter the otherwise unfavorable course of CAD. Several studies have convincingly demonstrated that majority of all ACS develops from previously mild to moderate stenoses. Thus, based on these and autopsy studies, sudden disruption or rupture of the non-obstructive "vulnerable" atherosclerotic lesion is currently considered the cause of ACS. Recent clinical studies have substantiated earlier autopsy observations that plaque vulnerability is a systemic process, involving multiple locations concurrently. Although the exact inciting factors of the vulnerable plaque rupture are unknown, inflammation is accepted to be a pivotal event. The possibility of stabilizing the vulnerable plaques has strongly been supported by the lipid lowering trials, in which dramatic reduction of the acute coronary events was noted despite subtle improvements in luminal diameter. Furthermore, antiplatelet therapies have become an important preventative therapy due to the essential role of platelets in the aftermath of plaque rupture. Finally, various imaging modalities to diagnose the plaque vulnerability could help prevent the acute coronary events in the future.

Clinical Trials as Topic↗