In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

BACKGROUND AND OBJECTIVES: Information about the role of the stromal cell-derived factor-1α (SDF-1α)/chemokine receptor type 4 (CXCR4) axis in ischemic postconditioning (IPOC) is currently limited. We hypothesized that the SDF-1α/CXCR4 signaling pathway is directly involved in the cardioprotective effect of IPOC. METHODS: Isolated rat hearts were divided into four groups. The control group was subjected to 30-min of regional ischemia and 2-hour of reperfusion (n=12). The IPOC group was induced with 6 cycles of 10-second reperfusion and 10-second global ischemia (n=8) in each cycle. The CXCR4 antagonist, AMD3100, was applied before reperfusion in the IPOC group (AMD+IPOC group, n=11) and control group (AMD group, n=9). Hemodynamic changes with electrocardiography were monitored and infarct size was measured. The SDF-1α, lactate dehydrogenase (LDH) and creatine kinase (CK) concentrations in perfusate were measured. We also analyzed extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation state expression. RESULTS: IPOC significantly reduced infarct size, but AMD3100 attenuated the infarct reducing effect of IPOC. IPOC significantly decreased LDH and CK, but these effects were reversed by AMD3100. ERK1/2 and Akt phosphorylation increased with IPOC and these effects were blocked by AMD3100. CONCLUSION: Based on the results of this study, SDF-1α/CXCR4 signaling may be involved in IPOC cardioprotection and this signaling pathway couples to the ERK1/2 and Akt pathways.
Animals ; Creatine Kinase ; Electrocardiography ; Family Characteristics ; Heart* ; Hemodynamics ; Ischemia ; Ischemic Postconditioning* ; L-Lactate Dehydrogenase ; Phosphorylation ; Phosphotransferases ; Rats* ; Receptors, CXCR4 ; Reperfusion ; Reperfusion Injury

BACKGROUND/AIMS: We compared the efficacy and safety of the second-generation everolimus-eluting stent (EES) and the third generation biolimus-eluting stent (BES) in patients with acute myocardial infarction (AMI). METHODS: We analyzed 629 consecutive patients (mean age 65.1 +/- 11.2 years, 426 males) with AMI undergoing percutaneous coronary intervention from February 2008 to April 2012. They were divided into two groups according to stent type (EES group, n = 426; BES group, n = 203). The primary end-point was 2-year major adverse cardiac events (MACEs), defined as the composite of all-cause death, myocardial infarction, target vessel revascularization, non-target vessel revascularization and target lesion revascularization. The secondary end-point was 2-year target lesion failure (TLF). RESULTS: There were no significant differences in baseline characteristics, except that the patients with EES had a significantly higher prevalence of diabetes mellitus (34.7 vs. 22.7%, p = 0.002) and were older (67.1 +/- 11.3 vs. 64 +/- 12.9 years, p = 0.039) compared with the patients with BES. After propensity score matching, 2-year clinical outcomes showed no differences in composite MACEs or TLF between the two groups. Multivariate Cox regression analysis showed that stent type was not a predictor of 2-year mortality or MACEs. However, older age (hazard ratio [HR] 1.037, 95% confidence interval [CI] 1.014-1.060, p = 0.001), diabetes mellitus (HR 2.247, 95% CI 1.426-3.539, p = 0.001) and a left ventricular ejection fraction < or = 45% (HR 3.007, 95% CI 1.978-4.573, p = 0.001) were independent predictors for 2-year MACEs in patients undergoing EES or BES. CONCLUSIONS: Patients with BES had similar clinical 2-year outcomes compared with EES patients with AMI.
Diabetes Mellitus ; Humans ; Mortality ; Myocardial Infarction* ; Percutaneous Coronary Intervention ; Prevalence ; Prognosis ; Propensity Score ; Stents* ; Stroke Volume

BACKGROUND/AIMS: Despite improved revascularization techniques, the clinical outcomes of patients with diffuse coronary artery lesions after percutaneous coronary intervention are unsatisfactory. However, few studies have compared the efficacy of first- and second-generation drug-eluting stents (DES) in patients with diffuse long coronary artery lesions. METHODS: Between January 2006 and July 2012, 364 patients who were treated with DES for long coronary artery stenosis (> 30 mm) were enrolled in this study and assigned to either Group I (first-generation DES, 62.3 +/- 10.4 years, 136 males, n = 183) or Group II (second-generation DES, 64.3 +/- 10.7 years, 134 males, n = 181). The incidence of major adverse cardiac events (MACE) was compared between the two groups over 2 years of follow-up, and predictive factors associated with MACE were evaluated through a multivariate analysis. RESULTS: Although several coronary angiographic characteristics were different between the two groups, most demographic and baseline clinical variables were the same. The cumulative incidence of MACE was significantly higher in Group I than in Group II (25.7 vs. 6.6%; p < 0.001), mainly due to reduced target lesion revascularization (21.9 vs. 2.2%; p < 0.001). According to the results of the multivariate analysis, the use of a paclitaxel-eluting stent (PES) (hazard ratio [HR], 5.168; 95% confidence interval [CI], 2.515-10.617; p < 0.001), decreased left ventricular function (< or = 45%; HR, 3.586; 95% CI, 1.839-6.990; p < 0.001), and diabetes mellitus (HR, 2.984; 95% CI, 1.605-5.548; p < 0.001) were independent contributors to MACE. CONCLUSIONS: For patients with diffuse long coronary artery stenosis, the use of second-generation DES improved the clinical outcome compared with first-generation DES. In addition, the use of a PES, left ventricular dysfunction, and diabetes were predictors of MACE after overlapping stenting.
Coronary Stenosis ; Coronary Vessels ; Diabetes Mellitus ; Drug-Eluting Stents* ; Follow-Up Studies ; Humans ; Incidence ; Male ; Multivariate Analysis ; Percutaneous Coronary Intervention ; Stents ; Ventricular Dysfunction, Left ; Ventricular Function, Left

BACKGROUND/AIMS: Delay in symptom-to-door time (SDT) in patients with acute ST-segment elevation myocardial infarction (STEMI) is the most important factor in the prediction of short and long-term mortality. The purpose of this study was to investigate the social and clinical factors affecting SDT in patients with STEMI. METHODS: We analyzed 784 patients (61.0 +/- 13.2 years, 603 male) diagnosed with STEMI from November 2005 to February 2012. The patients were divided into four groups according to SDT: Group I (n = 163, < or = 1 h), Group II (n = 183, 1-2 h), Group III (n = 142, 2-3 h) and Group IV (n = 296, > 3 h). RESULTS: Delay in SDT increased with age (Group I, 58.4 +/- 12.0; Group II, 59.4 +/- 13.3; Group III, 62.0 +/- 12.8; Group IV, 63.0 +/- 13.8 years, p = 0.001). In 119 patients, transportation was less frequently used as the delay in SDT (41.7% vs. 29.0% vs. 26.1% vs. 9.8%, p < 0.001). By multiple logistic regression analysis, family history [OR, 0.488; CI, 0.248-0.959; p = 0.037], previous ischemic heart disease [OR, 0.572; CI, 0.331-0.989; p = 0.045], no occupation [OR, 1.600; CI, 1.076-2.380; p = 0.020] and method of transportation [OR, 0.353; CI, 0.239-0.520; p < 0.001] were independent predictors of delay in SDT. CONCLUSIONS: Our study shows that general education about cardiovascular symptoms and a prompt emergency call could be important to reduce SDT in STEMI.
Education ; Emergencies ; Humans ; Logistic Models ; Mortality ; Myocardial Infarction* ; Myocardial Ischemia ; Occupations ; Transportation

BACKGROUND AND OBJECTIVES: We investigated the effects of commonly used contrast media (CM) on myocardial ischemia-reperfusion injury in isolated rat hearts. SUBJECTS AND METHODS: Isolated rat hearts were subjected to 30 minutes of regional ischemia and 2 hours of reperfusion. The following CM (1 mL/1 L Krebs-Henseleit buffer) were randomly perfused for 15 minutes beginning 5 minutes before reperfusion and ending 10 minutes after reperfusion: iohexol (n=8), iopromide (n=8), ioversol (n=8), iomeprol (n=8), iopamidol (n=7), ioxaglate (n=8), and iodixanol (n=7). The effects of a direct bolus injection of undiluted iohexol, iopromide, or ioxaglate (each n=6) via the aortic root immediately prior to reperfusion were also evaluated. The area of necrosis, expressed as the percentage of the area at risk (AN/AR), and cardiodynamic variables were measured. RESULTS: The AN/AR of the control and experimental groups in the order described in methods was 33.7+/-6.4%, 30.3+/-7.4%, 34.7+/-12.6%, 29.2+/-10.2%, 20.9+/-7.6%, 22.6+/-8.7%, 18.8+/-7.9%, and 19.9+/-11.4%, respectively. Groups that received iomeprol and ioxaglate exhibited significantly decreased AN/AR values compared to those of control hearts (p=0.042 and p=0.013). No significant differences in the AN/AR were observed between control hearts and the groups injected with a single bolus of CM. No significant hemodynamic changes were noted after reperfusion among the groups. CONCLUSION: The overall effects of the CM on coronary reperfusion were not deleterious, and better effects were noted in two CM groups. However, it is unclear whether this result was attributed to a specific physiochemical property of the CM.
Animals ; Contrast Media* ; Heart* ; Hemodynamics ; Iohexol ; Iopamidol ; Ioxaglic Acid ; Ischemia ; Myocardial Infarction ; Myocardial Reperfusion ; Necrosis ; Rats* ; Reperfusion ; Reperfusion Injury*

BACKGROUND: Several studies showed the relationship between serum homocysteine and pulse wave velocity, but their subjects were confined to high risk group for cardiovascular diseases and recent study revealed no relationship in young healthy adults. We hypothesized that time interval would be needed for serum homocysteine to infl uence pulse wave velocity after exposure to vascular endothelium. The purpose of this study was to determine the relationship between serum homocysteine and pulse wave velocity in middle aged women on the basis of that hypothesis and necessity for further study in general population. METHODS: The study subjects were 110 middle aged women who visited a health promotion center of a general hospital. We collected medical history by means of self-reported questionnaire and measured height, weight, blood pressure and brachial-ankle pulse wave velocity (baPWV). Blood sampling was performed after overnight fasting. We analyzed the relationship between several cardiovascular risk factors and baPWV and performed multiple regression analysis. RESULTS: BaPWV velocity was correlated significantly with age, mean blood pressure, serum homocysteine, total cholesterol and diabetes mellitus, but not with body mass index, high-density lipoprotein cholesterol, triglyceride, creatinine clearance, alcohol intake, hypertension and smoking. In multiple regression, there was a significant association between age (P = 0.04), moderate hyperhomocysteinemia (P = 0.02), mean blood pressure (P < 0.001) and baPWV. CONCLUSION: In middle aged women, there was an independently positive association between serum homocysteine and baPWV
Adult ; Blood Pressure ; Body Mass Index ; Cardiovascular Diseases ; Cholesterol ; Creatinine ; Diabetes Mellitus ; Endothelium, Vascular ; Fasting ; Female ; Health Promotion ; Homocysteine ; Hospitals, General ; Humans ; Hyperhomocysteinemia ; Hypertension ; Lipoproteins ; Middle Aged ; Pulse Wave Analysis ; Risk Factors ; Smoke ; Smoking

To investigate the emergence and prevalence of antiviral resistance, we analyzed influenza A/H3N2 viruses isolated in Korea during 2002/03 to 2003/04 season by genetic and phenotypic assay. For the genetic analysis to the amantadine, an M2 protein inhibitor, the M gene was amplified by RT-PCR and regions corresponding to the amino acid at positions 27, 30, and 31 were amplified by nested PCR with size of 154 bp, 95 bp, and 153 bp fragments, respectively. A total of 3 of 31 (9.7%) viruses were found to be mutated by restriction fragment length polymorphism (RFLP) with Sca I and sequence analysis, showing the single amino acid change (Ser to Asn) at position 31. Also it was observed that their growths in Madin-Darby Canine Kidney (MDCK) cells were unaffected by amantadine (up to 1 microgram/ml) in both plaque assay and WST-1 assay, confirming that these viruses were resistant against amantadine. We also examined the resistant pattern against zanamivir, a neuraminidase inhibitor, for 15 Korean influenza A/H3N2 viruses isolated in 2002~2003 season. Sequence analysis showed that there were no genetic changes of NA genes including R292K, K274Y, R152K, and E119V which were related to resistance against the neuraminidase inhibitor. In the NA inhibition assay to zanamivir, Korean isolates were found to be sensitive, ranging from 0.17 nM to 1.77 nM in 50% inhibitory concentration (IC(50)). These results suggest that monitoring for the antiviral resistance should be intensified and maintained to provide guideline for prophylaxis and treatment of influenza in Korea.
Amantadine ; Influenza, Human ; Kidney ; Korea ; Neuraminidase ; Orthomyxoviridae ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Prevalence ; Seasons ; Sequence Analysis ; Zanamivir

Since genetic abnormalities of human cancer are greatly geographically dependent, cultural and environmental backgrounds are thought to be closely related to the carcinogenic process. In the present study, eight human cell lines were established by culture from untreated carcinomas of the oral cancer, of which five were from primary oral squamous cell carcinomas (OSC), one from a mucoepidermoid carcinoma (MEC) and one each originating from metastatic OSC and MEC. All the studied tumor lines grew as monolayers, and showed: i) an epithelial origin by the presence of cytokeratin, and ii) tumorigenic potential in nude mice. Western blot analysis revealed i) over expression of EGFR in six of the cell lines ii) decreased expression of E- cadherin in six cell lines compared to normal human oral mucosa. A mutational analysis showed: point mutations of p53 at exon 7, with transversion, and at exon 8, with transition. These well-characterized human YD cell lines should serve as useful tools in the study of the molecular pathogenesis and biological characteristics of head and neck cancer cells, and in the future testing of new therapeutic reagents for oral cancer.
Adult ; Aged ; Animals ; Base Sequence ; Carcinoma, Mucoepidermoid/genetics/*metabolism/*pathology ; Carcinoma, Squamous Cell/genetics/*metabolism/*pathology ; *Cell Line, Tumor ; Epithelial Cells/metabolism ; Female ; Humans ; Male ; Mice ; Mice, Nude ; Middle Aged ; Mouth Neoplasms/genetics/*metabolism/*pathology ; Mutation/genetics ; Papillomavirus/physiology ; Receptor, Epidermal Growth Factor/genetics/metabolism ; Research Support, Non-U.S. Gov't ; Tumor Markers, Biological ; Tumor Suppressor Protein p53/genetics/metabolism ; Xenograft Model Antitumor Assays