• The Korean Journal of Physiology and Pharmacology
• /
• v.2 no.6
• /
• pp.733-742
• /
• 1998

Background: We have previously reported that not only cGMP but also 8-Br-cGMP or 8-pCPT-cGMP, specific and potent stimulators of cGMP-dependent protein kinase (cGMP-PK), increased basal L-type calcium current $(I_{Ca})$ in rabbit ventricular myocytes. Our findings in rabbit ventricular myocytes were entirely different from the earlier findings in different species, suggesting that the activation of cGMP-PK is involved in the facilitation of $I_{Ca}}$ by cGMP. However, there is no direct evidence that cGMP-PK can stimulate $I_{Ca}}$ in rabbit ventricular myocytes. In this report, we focused on the direct effect of cGMP-PK on $I_{Ca}}$ in rabbit ventricular myocytes. Methods and Results: We isolated single ventricular myocytes of rabbit hearts by using enzymatic dissociation. Regulation of $I_{Ca}}$ by cGMP-PK was investigated in rabbit ventricular myocytes using whole-cell voltage clamp method. $I_{Ca}}$ was elicited by a depolarizing pulse to +10 mV from a holding potential of -40 mV. Extracellular 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP), potent stimulator of cGMP-dependent protein kinase (cGMP-PK), increased basal $I_{Ca}}$. cGMP-PK also increased basal $I_{Ca}}$. The stimulation of basal $I_{Ca}}$ by cGMP-PK required both 8-Br-cGMP in low concentration and intracellular ATP to be present. The stimulation of basal $I_{Ca}}$ by cGMP-PK was blocked by heat inactivation of the cGMP-PK and by bath application of 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer (Rp-pCPT-cGMP), a phosphodiesterase-resistant cGMP-PK inhibitor. When $I_{Ca}}$ was increased by internal application of cGMP-PK, IBMX resulted in an additional stimulation of $I_{Ca}}$. In the presence of cGMP-PK, already increased $I_{Ca}}$ was potentiated by bath application of isoprenaline or forskolin or intracellular application of cAMP. Conclusions: We present evidence that cGMP-PK stimulated basal $I_{Ca}}$ by a direct phosphorylation of L-type calcium channel or associated regulatory protein in rabbit ventricular myocytes.

• Genomics & Informatics
• /
• v.15 no.1
• /
• pp.2-10
• /
• 2017

Early detection and proper management of kidney rejection are crucial for the long-term health of a transplant recipient. Recipients are normally monitored by serum creatinine measurement and sometimes with graft biopsies. Donor-derived cell-free deoxyribonucleic acid (cfDNA) in the recipient's plasma and/or urine may be a better indicator of acute rejection. We evaluated digital PCR (dPCR) as a system for monitoring graft status using single nucleotide polymorphism (SNP)-based detection of donor DNA in plasma or urine. We compared the detection abilities of the QX200, RainDrop, and QuantStudio 3D dPCR systems. The QX200 was the most accurate and sensitive. Plasma and/or urine samples were isolated from 34 kidney recipients at multiple time points after transplantation, and analyzed by dPCR using the QX200. We found that donor DNA was almost undetectable in plasma DNA samples, whereas a high percentage of donor DNA was measured in urine DNA samples, indicating that urine is a good source of cfDNA for patient monitoring. We found that at least 24% of the highly polymorphic SNPs used to identify individuals could also identify donor cfDNA in transplant patient samples. Our results further showed that autosomal, sex-specific, and mitochondrial SNPs were suitable markers for identifying donor cfDNA. Finally, we found that donor-derived cfDNA measurement by dPCR was not sufficient to predict a patient's clinical condition. Our results indicate that donor-derived cfDNA is not an accurate predictor of kidney status in kidney transplant patients.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.sup3
• /
• pp.179-183
• /
• 2016

Breast cancer is the most prevalent type of cancer among women around the world, and mortality is primarily caused by micro-metastatic disease. The complex mechanisms of breast cancer invasion and metastasis are intrinsically related to the malignant cell type so that early detection of micro-metastases can help prolongation of survival for patient. The aim of the present research work was evaluation of the expression status of mammoglobin protein as a candidate molecular marker in the negative sentinel lymph node (SLN). Fifty tumor specimens, and 50 normal adjacent breast tissue samples from the same patients were selected on the basis of having more than 10% tumor content for RNA extraction from SLNs. Tumor samples and normal adjacent breast tissue were archived in the form of frozen fresh tissue in liquid nitrogen. Real-time PCR was performed on a Bioner life express gradient thermal cycler system. Mammoglobin gene overexpression in breast cancer metastasis was investigated. Single marker results were mammaglobin 66.7% and CK19 50.0%, with 58.3% for the two in combination. Due to improved outcome with at least 3 genes (83.3%), it seems, triple marker evaluation will be most likely useful for detecting micro-metastases instead of studying separate genes.

• Nuclear Medicine and Molecular Imaging
• /
• v.40 no.4
• /
• pp.205-210
• /
• 2006

Purpose: FDG uptake on positron omission tomography (PET) has been considered a prognostic indicator in non-small cell lung cancer (NSCLC). The aim of this study was to assess the clinical significance of maximum value of SUV (maxSUV) in recurrence prediction in patients with surgically resected NSCLC. Materials & methods: NSCLC patients (n=42, F:M =14:28, age $62.3{\pm}12.3$ y) who underwent curative resection after FDG-PET were enrolled. Twenty-nine patients had pathologic stage 1, and 13 had pathologic stage II. Thirty-one patients were additionally treated with adjuvant oral chemotherapy. MaxSUVs of primary tumors were analyzed for correlation with tumor recurrence and compared with pathologic or clinical prognostic indicators. The median follow-up duration was 16 mo (range, 3-26 mo). Results: Ten (23.8%) of the 42 patients experienced recurrence during a median follow-up of 7.5 mo (range, 3-13 mo). Univariate analysis revealed that disease-free survival (DFS) was significantly correlated with maxSUV (<7 vs. $\geq7$, p=0.006), tumor size (<3 cm vs. $\geq3$ cm, p=0.024), and tumor tell differentiation (well/moderate vs. poor, p=0.044). However, multivariate Cox proportional analysis identified maxSUV as the single determinant for DFS (p=0.014). Patients with a maxSUV of $\geq7$(n=10) had a significantly lower 1-year DFS rate (50.0%) than those with a maxSUV of <7 (n=32, 87.5%). Conclusion: MaxSUV is a significant independent predictor for recurrence in surgically resected NSCLC. FDG uptake can be added to other well-known factors in prognosis prediction of NSCLC.

• Journal of the Korean Orthopaedic Association
• /
• v.56 no.2
• /
• pp.142-149
• /
• 2021

Purpose: This study examined the effectiveness of tranexamic acid in reducing postoperative blood loss in total knee arthroplasty by comparing the methods of administration between an intravenous group, topical group, and non-tranexamic acid group. Materials and Methods: This was a retrospective case series study of patients who underwent primary total knee arthroplasty from March 2017 to February 2019 performed by a single surgeon. The study population was divided into three groups according to the method of tranexamic acid administration (Group I: intravenous group, Group II: topical group, Group III: non-tranexamic acid group). To evaluate the effectiveness of tranexamic acids, the total amount of postoperative blood loss, postoperative hemoglobin loss, and volume of red blood cell transfusion in the three groups were compared. Results: The total amount of postoperative blood loss was lower in the tranexamic acid administered group than in the non-tranexamic acid group (1,366±866 ml). Among the administration methods, the intravenous group (987±449 ml) was significantly lower than the topical group (1,136±339 ml) (p=0.004). Postoperative hemoglobin loss was lower in the tranexamic acid group than the non-tranexamic acid group. Among the administration methods, the intravenous group was lower than the topical group. The transfusion rate was higher in the non-tranexamic acid group (5.7%) than the tranexamic administered group. The transfusion rate of the intravenous group was 1.4%, and no patient required a transfusion postoperatively in the topical group. The number of postoperative thromboembolic events, as a complication of tranexamic acid, was similar in the three groups. Conclusion: Tranexamic acid was effective in reducing postoperative blood loss after primary total knee arthroplasty compared to the non-tranexamic acid administered group. No significant difference in the complications induced by tranexamic acid was observed among the three groups.

• The Journal of Korean Medicine
• /
• v.16 no.2 s.30
• /
• pp.177-194
• /
• 1995

The following conclusions were obtained after bibliographic investigation on the therapy of lung cancer by western, oriental, and integrated oriental and western medicine. 1. Lung cancer is classified into small cell lung cancer(SCLC) or non small cell lung cancer(NSCLC) in the treatment by western medicine, and applied with the means of surgery, radiotherapy and chemotherapy alone or combined, depending on the stage and the symptom. 2. Treatment by oriental medicine includes the means of strengthening body resistance to dispel pathogenic factors(扶正祛邪), combined approach of reinforcement and expulsion(攻補兼施), and reinforcing both qi and blood(氣血雙補), depending on the initial, middle, and terminal stage. And also treatment based on differentiation of symptom(辨證施治) is applied according to the type of symptom; deficiency of qi of both lung and spleen(肺脾氣虛), heat symptom of lung by deficiency of yin(肺熱陰虛), stagnation of damp-phlegm and blood(濕痰瘀阻), stagnation of qi and blood(氣血瘀滯), deficiency of both qi and yin(氣陰兩虛). Single or combined herb drug is used according to the symptom. 3. Treatment by integrated oriental and western medicine improved survival rate and quality of life. It promoted recovery and improved survival rate in the patients receiving surgery. Integrated radiotherapy and oriental medicine treatment reduced adverse effect by radiotherapy and improved therapeutic effect and survival rate. Integrated chemotherapy with oriental medicine treatment reduced side effect by chemotherapy and improved quality of life and survival rate. These results suggest that therapy of lung cancer should be applied with integrated oriental and western medicine from diagnosis to treatment for promoting therapeutic effect. And further study on this therapy should be ensued.

• Radiation Oncology Journal
• /
• v.27 no.3
• /
• pp.126-132
• /
• 2009

Purpose: We wanted to evaluate the prognostic factors for the pathologic N2 non-small cell lung cancer (NSCLC) patients who were treated by postoperative radiotherapy. Materials and Methods: We retrospectively reviewed 112 pN2 NSCLC patients who underwent surgery and postoperative radiotherapy (PORT) From January 1999 to February 2008. Seventy-five (67%) patients received segmentectomy or lobectomy and 37 (33%) patients received pneumonectomy. The resection margin was negative in 94 patients, and it was positive or close in 18 patients. Chemotherapy was administered to 103 (92%) patients. Nine (8%) patients received PORT alone. The median radiation dose was 54 Gy (range, 45 to 66), and the fraction size was 1.8~2 Gy. Results: The 2-year overall survival (OS) rate was 60.2% and the disease free survival (DFS) rate was 44.7% for all the patients. Univariate analysis showed that the patients with multiple-station N2 disease had significantly reduced OS and DFS (p=0.047, p=0.007) and the patients with an advanced T stage ($\geq$T3) had significantly reduced OS and DFS (p<0.001, p=0.025). A large tumor size ($\geq$5 cm) and positive lymphovascular invasion reduced the OS (p=0.035, 0.034). Using multivariate analysis, we found that multiple-station N2 disease and an advanced T stage ($\geq$T3) significantly reduced the OS and DFS. Seventy one patients (63.4%) had recurrence of disease. The patterns of failure were loco-regional in 23 (20.5%) patients, distant failure in 62 (55.4%) and combined loco-regional and distant failure in 14 (12.5%) patients. Conclusion: Multiple involvement of mediastinal nodal stations for the pN2 NSCLC patients with PORT was a poor prognostic factor in this study. A prospective study is necessary to evaluate the N2 subclassification and to optimize the adjuvant treatment.

• The Korean Journal of Physiology and Pharmacology
• /
• v.9 no.2
• /
• pp.103-108
• /
• 2005

To study the direct effect of somatostatin (SS) on calcium channel current ($I_{Ba}$) in guinea-pig gastric myocytes, $I_{Ba}$ was recorded by using whole-cell patch clamp technique in single smooth muscle cells. Nicardipine ($1{\mu}M$), a L-type $Ca^{2+}$ channel blocker, inhibited $I_{Ba}$ by $98{\pm}1.9$% (n=5), however $I_{Ba}$ was decreased in a reversible manner by application of SS. The peak $I_{Ba}$ at 0 mV were decreased to $95{\pm}1.5$, $92{\pm}1.9$, $82{\pm}4.0$, $66{\pm}5.8$, $10{\pm}2.9$% at $10^{-10}$, $10^{-9}$, $10^{-8}$, $10^{-7}$, $10^{-5}$ M of SS, respectively (n=3∼6; $mean{\pm}SEM$). The steady-state activation and inactivation curves of $I_{Ba}$ as a function of membrane potentials were well fitted by a Boltzmann equation. Voltage of half-activation ($V_{0.5}$) was $-12{\pm}0.5$ mV in control and $-11{\pm}1.9$ mV in SS treated groups (respectively, n=5). The same values of half-inactivation were $-35{\pm}1.4$ mV and $-35{\pm}1.9$ mV (respectively, n=5). There was no significant difference in activation and inactivation kinetics of $I_{Ba}$ by SS. Inhibitory effect of SS on $I_{Ba}$ was significantly reduced by either dialysis of intracellular solution with $GDP_{\beta}S$, a non-hydrolysable G protein inhibitor, or pretreatment with pertussis toxin (PTX). SS also decreased contraction of guinea-pig gastric antral smooth muscle. In conclusion, SS decreases voltage-dependent L-type calcium channel current ($VDCC_L$) via PTXsensitive signaling pathways in guinea-pig antral circular myocytes.

• Tuberculosis and Respiratory Diseases
• /
• v.46 no.1
• /
• pp.129-135
• /
• 1999

We describe unusual manifestations of congenital cystic adenomatoid malformation (C.C.A.M.) of the lung, such as movable fungal ball-like intracystic blood clots and hemoptysis, which were detected in previously healthy 23 years-old woman. We identified blood clots only after left upper lobectomy and could not distinguish from fungal ball with radiographic methods. CCAM of the lung, rare and lethal form of congenital pulmonary cystic disease, was initially introduced by Ch, in and Tang in 1949. The histogenesis of this lesion is characterized by polypoid glandular tissue proliferation and overgrowth of mesenchymal elements due to cessation of bronchiolar maturation which occurred in after 16weeks intrauterine period. In 80-95% of reported cases, the lesion was confined to a single lobe and there was no lobe and right and left lung predilection The clinical presentation may be widely variable, ranging from intrauterine fetal death to late discovery in childhood with recurrent pulmonary infection. But there,s no reports which were misdiagnosed with intracystic fungal ball. The treatment choice is lobectomy of affected lobe. There,s a few case reports with rhabdomyosarcoma, bronchiolar cell carcinoma and myxosarcoma arising in CCAM patients. Therefore, early resection is recommended even if asymtomatic cases. We experienced a rare case of CCAM of the lung in 23 years old female, and there were intracystic fungal ball-like movable blood clots in lower portion of left lung. After left upper lobectomy was performed, now she is discharged and followed up without any complications.

• Journal of Life Science
• /
• v.34 no.6
• /
• pp.434-441
• /
• 2024

Mammary gland tumors are the most common tumors detected in non-spayed female dogs and pose a significant clinical challenge. Due to the strong similarity between canine mammary tumors (CMT) and human breast cancer (HBC), biomarkers identified in HBC can also be detected in CMT. These biomarkers have been shown to offer valuable insights into early diagnosis, prognosis, and treatment strategies. The purpose of this article is to provide a concise overview of CMT biomarkers based on the current literature. Traditional treatments for CMT in dogs typically begin with surgery, followed by chemotherapy, radiotherapy, or hormonal therapy. However, these treatments alone are not always fully effective. A diagnostic biomarker can detect the presence of a disease or the characteristics of a disease and classify an individual's status. Prognostic biomarkers focus on predicting the expected progression, recurrence, or survival of the disease in patients. By utilizing advances in understanding the mechanism of canine-specific mammary gland tumors, the estimation of biomarkers offers hope for improved outcomes in cancer patients. Novel technologies, such as single-cell RNA sequencing analysis, could provide a valuable resource for deciphering intra- and inter-tumoral heterogeneity. This review paper explores current research on CMT biomarkers and suggests directions for their development.