• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5275-5279
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• 2013

Background: The XRCC1 (X-ray repair cross complimenting group-I) gene in BER (base excision repair) pathway is essential for DNA repair process. Polymorphisms in this gene are associated with variations in the repair efficiency which might predispose individuals to development of various cancers. Two variants of XRCC1gene (at codon 399), Gln/Gln and Arg/Gln, have been shown to be related to lowered DNA repair capacity and increased genomic instability in multiple studies. Hence our investigation focused on genotyping these variants to correlate with other multiple risk factors in lung cancer (NSCLC) patients since we hypothesized that these variants of the XRCC1 gene might influence disease susceptibility. Materials and Methods: We examined the frequency of the polymorphism in one hundred cases and an almost equal number of controls after recording their demographics with a structured questionnaire. Genomic DNA from blood samples was extracted for PCR studies, followed by RFLP to determine the variants. The significance of the data was statistically analyzed. Results: The three genotypes in cases and controls were Arg/Arg (40% and 54.45%); Gln/Gln (19% and 9.90%), and Arg/Gln (41.0% and 35.64%) respectively. Among these 3 genotypes, we found Gln/Gln and Arg/Gln to show association with lung cancer. Correlating these genotypes with several parameters, we also found that these two variants were associated with risk in males (p<0.05) and with smoking habits (p<0.05). In females Arg/Gln genotype showed association with stage of the disease (p=0.04). This is the first report in South Indian scenario where Arg399Gln genotypes were found to be associated with stage of the disease in females. Conclusions: It is concluded that XRCC1 genotypes Gln/Gln and Arg/Gln may influence cancer susceptibility in patients with smoking habits and these functional SNPs in XRCC1 gene may act as attractive candidate biomarkers in lung cancer for diagnosis and prognosis.

• Molecules and Cells
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• 제39권2호
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• pp.103-110
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• 2016

As a degenerative joint disease, osteoarthritis (OA) constitutes a major cause of disability that seriously affects the quality of life of a large population of people worldwide. However, effective treatment that can successfully reverse OA progression is lacking until now. The present study aimed to determine whether two small non-coding RNAs miR-29a and miR-140, which are significantly down-regulated in OA, can be applied together as potential therapeutic targets for OA treatment. MiRNA synergy score was used to screen the miRNA pairs that potentially synergistically regulate OA. An in vitro model of OA was established by treating murine chondrocytes with IL-$1{\beta}$. Transfection of miR-29a and miR-140 via plasmids was investigated on chondrocyte proliferation and expression of nine genes such as ADAMTS4, ADAMTS5, ACAN, COL2A1, COL10A1, MMP1, MMP3, MMP13 and TIMP metallopeptidase inhibitor 1 (TIMP1). Western blotting was used to determine the protein expression level of MMP13 and TIMP1, and ELISA was used to detect the content of type II collagen. Combined use of miR-29a and miR-140 successfully reversed the destructive effect of IL-$1{\beta}$ on chondrocyte proliferation, and notably affected the MMP13 and TIMP1 gene expression that regulates extracellular matrix. Although co-transfection of miR-29a and miR-140 did not show a synergistic effect on MMP13 protein expression and type II collagen release, but both of them can significantly suppress the protein abundance of MMP13 and restore the type II collagen release in IL-$1{\beta}$ treated chondrocytes. Compared with single miRNA transfection, cotransfection of both miRNAs exceedingly abrogated the suppressed the protein production of TIMP1 caused by IL-$1{\beta}$, thereby suggesting potent synergistic action. These results provided1novel insights into the important function of miRNAs' collaboration in OA pathological development. The reduced MMP13, and enhanced TIMP1 protein production and type II collagen release also implies that miR-29a and miR-140 combination treatment may be a possible treatment for OA.

• Journal of Chest Surgery
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• 제44권2호
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• pp.169-177
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• 2011

Background: Video-assisted thoracic surgery (VATS) lobectomy has been performed with increasing frequency over the last decade. However, there is still controversy as to its indications, safety, and feasibility. Especially regarding lung cancer surgery, it is not certain whether it can reduce local recurrences and improve overall survival. Materials and Methods: We retrospectively reviewed 1,067 cases of VATS lobectomy performed between 2003 and 2009, including the indications, postoperative morbidity, mortality, recurrence, and survival rate. Results: One thousand and sixty seven patients underwent VATS lobectomy for the following indications: non-small cell lung cancer (NSCLC) (n=832), carcinoid tumors (n=12), metastatic lung cancer (n=48), and benign or other diseases (n=175). There were 63 cases (5.9%) of conversion to open thoracotomy during VATS lobectomy. One hundred thirty one (15.7%) of the 832 NSCLC patients experienced pathologic upstaging postoperatively. The hospital mortality rate was 0.84% (9 patients), and all of them died of acute respiratory distress syndrome. One hundred forty-nine patients (14.0%) experienced postoperative complications. The median follow-up was 22.9 months for patients with NSCLC. During follow-up, 120 patients had a recurrence and 55 patients died. For patients with pathologic stage I, the overall survival rate and disease-free survival rate at 3 years was $92.2{\pm}1.5%$ and $86.2{\pm}1.9%$, respectively. For patients with pathologic stage II disease, the overall survival rate and disease-free survival rate at 3 years was $79.2{\pm}6.5%$ and $61.9{\pm}6.6%$, respectively. Conclusion: Our results suggest that VATS lobectomy is a technically feasible and safe operation, which can be applied to various lung diseases. In patients with early-stage lung cancer, excellent survival can be also achieved.

• Applied Microscopy
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• 제40권2호
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• pp.101-108
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• 2010

특정 성분 방출에 중요한 기능을 수행하는 것으로 추정되는 좀목형(Vitex negundo) 엽육 표피조직의 분비모 유형에 대한 구조적 발달양상을 전자현미경적으로 연구하였다. 엽육 표피에 발달하는 두 유형의 분비모는 peltate형(peltate glandular type, PT)과 capitate형(capitate glandular type, CT)으로 크기 및 밀도, 분비강 형성 등의 구조적 특성이 생장단계에 따라 상이하게 나타났다. 어린잎 상피에는 이미 분화된 PT형 분비모가 밀생하여 생장 초기에서부터 뚜렷한 형태구조적 차이를 나타내었다. 이 시기의 하피는 비분비성 단순모에 피복되어 전혀 외부로 노출되지 않는다. 엽신의 발달로 표피조직이 신장되면 PT 및 CT 분비모들은 성숙한 상피 및 하피조직에서 비교적 낮은 밀도로 발달하는 특성을 보이며 분화하였다. PT형 분비모는 6~8개의 분비세포(ca. 35~40 ${\mu}m$)와 하나의 병세포(ca. 5 ${\mu}m$)로 구성되어 있으나, CT형 분비모는 4개의 분비세포(ca. 10~15 ${\mu}m$)와 1~2개의 병세포(ca. 10 ${\mu}m$)로 이루어져 있다. 분비세포 내에는 분비강이 형성되나 크기, 구조 및 형성과정은 유형에 따라 매우 다르게 진행되었다. 분화초기 PT형 분비세포 외부 세포벽으로부터 분리된 층이 빠르게 팽창하면서 분비강이 형성되고, 분비강 내에는 수많은 분비소낭들이 분비물질을 축적하며 저장되었다. 이들 구획은 팽창된 분비강을 가득 채우며 생성되는 물질을 축적한 후 누출형 분비를 통해 방향성분 및 물질을 외부로 방출하였다. 반면, CT형 분비세포 내에는 분비소낭 생성 없이 비교적 작은 분비강만 형성되었다. 이와 같이 좀목형의 특정성분 방출 기작에서는 PT형 분비모가 CT형 분비모에 비해 더 중요한 기능을 수행하는 것으로 추정되었다.

• Molecules and Cells
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• 제20권3호
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• pp.315-324
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• 2005

Pain is an unpleasant sensation experienced when tissues are damaged. Thus, pain sensation in some way protects body from imminent threat or injury. Peripheral sensory nerves innervated to peripheral tissues initially respond to multiple forms of noxious or strong stimuli, such as heat, mechanical and chemical stimuli. In response to these stimuli, electrical signals for conducting the nociceptive neural signals through axons are generated. These action potentials are then conveyed to specific areas in the spinal cord and in the brain. Sensory afferent fibers are heterogeneous in many aspects. For example, sensory nerves are classified as $A{\alpha}$, $-{\beta}$, $-{\delta}$ and C-fibers according to their diameter and degree of myelination. It is widely accepted that small sensory fibers tend to respond to vigorous or noxious stimuli and related to nociception. Thus these fibers are specifically called nociceptors. Most of nociceptors respond to noxious mechanical stimuli and heat. In addition, these sensory fibers also respond to chemical stimuli [Davis et al. (1993)] such as capsaicin. Thus, nociceptors are considered polymodal. Recent advance in research on ion channels in sensory neurons reveals molecular mechanisms underlying how various types of stimuli can be transduced to neural signals transmitted to the brain for pain perception. In particular, electrophysiological studies on ion channels characterize biophysical properties of ion channels in sensory neurons. Furthermore, molecular biology leads to identification of genetic structures as well as molecular properties of ion channels in sensory neurons. These ion channels are expressed in axon terminals as well as in cell soma. When these channels are activated, inward currents or outward currents are generated, which will lead to depolarization or hyperpolarization of the membrane causing increased or decreased excitability of sensory neurons. In order to depolarize the membrane of nerve terminals, either inward currents should be generated or outward currents should be inhibited. So far, many cationic channels that are responsible for the excitation of sensory neurons are introduced recently. Activation of these channels in sensory neurons is evidently critical to the generation of nociceptive signals. The main channels responsible for inward membrane currents in nociceptors are voltage-activated sodium and calcium channels, while outward current is carried mainly by potassium ions. In addition, activation of non-selective cation channels is also responsible for the excitation of sensory neurons. Thus, excitability of neurons can be controlled by regulating expression or by modulating activity of these channels.

• Molecules and Cells
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• 제20권2호
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• pp.235-240
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• 2005

Extracts of pine needles (Pinus densiflora Sieb. et Zucc.) have diverse physiological and pharmacological actions. In this study we show that pine needle extract alters pacemaker currents in interstitial cells of Cajal (ICC) by modulating ATP-sensitive $K^+$ channels and that this effect is mediated by prostaglandins. In whole cell patches at $30^{\circ}C$, ICC generated spontaneous pacemaker potentials in the current clamp mode (I = 0), and inward currents (pacemaker currents) in the voltage clamp mode at a holding potential of -70 mV. Pine needle extract hyperpolarized the membrane potential, and in voltage clamp mode decreased both the frequency and amplitude of the pacemaker currents, and increased the resting currents in the outward direction. It also inhibited the pacemaker currents in a dose-dependent manner. Because the effects of pine needle extract on pacemaker currents were the same as those of pinacidil (an ATP-sensitive $K^+$ channel opener) we tested the effect of glibenclamide (an ATP-sensitive $K^+$ channels blocker) on ICC exposed to pine needle extract. The effects of pine needle extract on pacemaker currents were blocked by glibenclamide. To see whether production of prostaglandins (PGs) is involved in the inhibitory effect of pine needle extract on pacemaker currents, we tested the effects of naproxen, a non-selective cyclooxygenase (COX-1 and COX-2) inhibitor, and AH6809, a prostaglandin EP1 and EP2 receptor antagonist. Naproxen and AH6809 blocked the inhibitory effects of pine needle extract on ICC. These results indicate that pine needle extract inhibits the pacemaker currents of ICC by activating ATP-sensitive $K^+$ channels via the production of PGs.

• Tuberculosis and Respiratory Diseases
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• 제69권2호
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• pp.115-118
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• 2010

Paclitaxel has been widely used for treating many solid tumors. Although colonic toxicity is an unusual complication of paclitaxel-based chemotherapy, the reported toxicities include pseudomembranous colitis, neutropenic enterocolitis and on rare occasions ischemic colitis. $Genexol-PM^{(R)}$, which is a recently developed cremophor-free, polymeric micelle-formulated paclitaxel, has shown a more potent antitumor effect because it can increase the usual dose of paclitaxel due to that $Genexol-PM^{(R)}$ does not include the toxic cremophor compound. We report here on a case of a 57-year-old man with advanced non-small cell lung cancer and who developed ischemic colitis after chemotherapy with $Genexol-PM^{(R)}$ and cisplatin. He complained of hematochezia with abdominal pain on the left lower quadrant. Colonoscopy revealed diffuse mucosal hemorrhage and edema from the sigmoid colon to the splenic flexure. After bowel rest, he recovered from his symptoms and the follow-up colonoscopic findings showed that the mucosa was healing. Since then, he was treated with pemetrexed monotherapy instead of a paclitaxel compound and platinum.

• Archives of Plastic Surgery
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• 제37권4호
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• pp.469-472
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• 2010

Purpose: Aplasia Cutis Congenita (ACC) is a rare disease characterized by the focal defect of the skin at birth, frequently involving scalp, but it may affect any region of the body. There are no etiology known but some conditions such as intrauterine vascular ischemia, amniotic adherences and viral infections are associated. The ideal treatment for the ACC is not known. Superficial and relatively small sized defects (< $3{\times}5\;cm$) may heal spontaneously and large defects related with risks of infection and bleeding may require aggressive surgical treatment. Hyalomatrix$^{(R)}$ is a bilayer of an esterified hyaluronan scaffold beneath a silicone membrane. It has been used as a temporary dermal substitute to cover deep thickness skin defect and has physiological functions derive from the structural role in extracellular matrix and interaction with cell surface receptor. This material has been used for the wound bed pre-treatment for skin graft to follow and especially in uncooperative patient, like a newborn, this could be a efficient and aseptic way of promoting granulation without daily irritative wound care. For this reason, using Hyalomatrix$^{(R)}$ for the treatment of ACC was preferred in this paper. Methods: We report a case of a newborn with ACC of the vertex scalp and non-ossified partial skull defect. The large sized skin and skull defect ($6{\times}6\;cm$) was found with intact dura mater. No other complications such as bleeding or abnormal neurologic sign were accompanied. Escharectomy was performed and Hyalomatrix$^{(R)}$ was applied for the protection and the induction of acute wound healing for 3 months before the split-thickness skin graft. During the 3 months period, the dressing was renewed in aseptic technique for every 3 weeks. The skin graft was achieved on the healthy granulation bed. Results: The operative procedure was uneventful without necessity of blood transfusion. Postoperative physical examination revealed no additional abnormalities. Regular wound management was performed in out-patient clinic and the grafted skin was taken completely. No other problems developed during follow-up. Conclusion: Hyalomatrix$^{(R)}$ provides protective and favorable environment for wound healing. The combination of the use of Hyalomatrix$^{(R)}$ and the skin graft will be a good alternative for the ACC patients with relatively large defect on vertex.

• Molecules and Cells
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• 제37권3호
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• pp.213-219
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• 2014

MicroRNAs (miRNAs) represent a class of small non-coding regulatory RNAs that play important roles in normal hematopoiesis, including erythropoiesis. Although studies have identified several miRNAs that regulate erythroid commitment and differentiation, we do not understand the mechanism by which the crucial erythroid transcription factors, GATA-1and NF-E2 directly regulate and control differentiation via miRNA pathways. In this study, we identified miR-199b-5p as a key regulator of human erythropoiesis, and its expression was up-regulated during the erythroid differentiation of K562 cells. Furthermore, the increase of miR-199b-5p in erythroid cells occurred in a GATA-1- and NF-E2-dependent manner during erythrocyte maturation. Both GATA-1 and NF-E2 bound upstream of the miR-199b gene locus and activated its transcription. Forced expression of miRNA-199b-5p in K562 cells affected erythroid cell proliferation and maturation. Moreover, we identified c-Kit as a direct target of miR-199b-5p in erythroid cells. Taken together, our results establish a functional link among the erythroid transcription factors GATA-1/NF-E2, miR-199b-5p and c-Kit, and provide new insights into the coupling of transcription and post-transcription regulation in erythroid differentiation.

• Tuberculosis and Respiratory Diseases
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• 제82권3호
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• pp.227-233
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• 2019

Background: Programmed death-ligand 1 (PD-L1), a transmembrane protein, binds to the programmed death-1 (PD-1) receptor, and anti-PD-1 therapy enables immune responses against tumors. This study aimed to assess clinical characteristics of PD-L1 expression using immunohistochemistry among Korean patients with lung cancer. Methods: We retrospectively reviewed the data of patients with pathologically proven lung cancer from a single institution. PD-L1 expression determined by Tumor Proportion Score (TPS) was detected using 22C3 pharmDx (Agilent Technologies) and SP263 (Ventana Medical Systems) assays. Results: From July 2016 to July 2017, 267 patients were enrolled. The main histologic type was adenocarcinoma (69.3%). Most participants were smokers (67.4%) and had clinical stage IV disease (60.7%). In total, 116 (42%) and 58 (21%) patients had TPS ${\geq}1%$ and ${\geq}50%$, respectively. The patients were significantly older in TPS ${\geq}1%$ group than in TPS <1% group ($64.83{\pm}9.38years$ vs. $61.73{\pm}10.78years$, p=0.014), not in TPS ${\geq}50%$ cutoff value ($64.69{\pm}9.39$ vs. $62.36{\pm}10.51$, p=0.178). Regarding histologic grade, higher proportions of poorly differentiated tumor were observed in the TPS ${\geq}1%$ (40.8% vs. 25.8%, p=0.020) and TPS ${\geq}50%$ groups (53.2% vs. 27.2%, p=0.004). Among 34 patients examined with 22C3 and SP263 assays, 27 had positive results in both assays, with a cutoff of TPS ${\geq}1%$ (r=0.826; 95% confidence interval, 0.736-0.916). Conclusion: PD-L1 expression, defined as TPS ${\geq}1%$, was related to older age and poorly differentiated histology. There was a similar distribution of PD-L1 expression in both 22C3 and SP263 results.