Picropodophyllotoxin Inhibits Cell Growth and Induces Apoptosis in Gefitinib-Resistant Non-Small Lung Cancer Cells by Dual-Targeting EGFR and MET

Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) amplification or sensitive muta-tions initially respond to the tyrosine kinase inhibitor gefitinib, however, the treatment becomes less effective over time by resis-tance mechanism including mesenchymal-epithelial transition (MET) overexpression. A therapeutic strategy targeting MET and EGFR may be a means to overcoming resistance to gefitinib. In the present study, we found that picropodophyllotoxin (PPT), derived from the roots of Podophyllum hexandrum, inhibited both EGFR and MET in NSCLC cells. The antitumor efficacy of PPT in gefitinib-resistant NSCLC cells (HCC827GR), was confirmed by suppression of cell proliferation and anchorage-independent colony growth. In the targeting of EGFR and MET, PPT bound with EGFR and MET, ex vivo, and blocked both kinases activity. The binding sites between PPT and EGFR or MET in the computational docking model were predicted at Gly772/Met769 and Arg1086/Tyr1230 of each ATP-binding pocket, respectively. PPT treatment of HCC827GR cells increased the number of annexin V-positive and subG1 cells. PPT also caused G2/M cell-cycle arrest together with related protein regulation. The inhibition of EGFR and MET by PPT treatment led to decreases in the phosphorylation of the downstream-proteins, AKT and ERK. In addition, PPT induced reactive oxygen species (ROS) production and GRP78, CHOP, DR5, and DR4 expression, mitochondrial dysfunc-tion, and regulated involving signal-proteins. Taken together, PPT alleviated gefitinib-resistant NSCLC cell growth and induced apoptosis by reducing EGFR and MET activity. Therefore, our results suggest that PPT can be a promising therapeutic agent for gefitinib-resistant NSCLC.

Licochalcone H Targets EGFR and AKT to Suppress the Growth of Oxaliplatin -Sensitive and -Resistant Colorectal Cancer Cells

Treatment of colorectal cancer (CRC) has always been challenged by the development of resistance. We investigated the antiproliferative activity of licochalcone H (LCH), a regioisomer of licochalcone C derived from the root of Glycyrrhiza inflata, in oxaliplatin (Ox)-sensitive and -resistant CRC cells. LCH significantly inhibited cell viability and colony growth in both Ox-sensitive and Ox-resistant CRC cells. We found that LCH decreased epidermal growth factor receptor (EGFR) and AKT kinase activities and related activating signaling proteins including pEGFR and pAKT. A computational docking model indicated that LCH may interact with EGFR, AKT1, and AKT2 at the ATP-binding sites. LCH induced ROS generation and increased the expression of the ER stress markers. LCH treatment of CRC cells induced depolarization of MMP. Multi-caspase activity was induced by LCH treatment and confirmed by Z-VAD-FMK treatment. LCH increased the number of sub-G1 cells and arrested the cell cycle at the G1 phase.Taken together LCH inhibits the growth of Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, and inducing ROS generation and ER stress-mediated apoptosis. Therefore, LCH could be a potential therapeutic agent for improving not only Ox-sensitive but also Ox-resistant CRC treatment.

Licochalcone D Inhibits Skin Epidermal Cells Transformation through the Regulation of AKT Signaling Pathways

Cell transformation induced by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) is a critical event in cancer initiation and progression, and understanding the underlying mechanisms is essential for the development of new therapeutic strategies. Licorice extract contains various bioactive compounds, which have been reported to have anticancer and anti-inflammatory effects. This study investigated the cancer preventive efficacy of licochalcone D (LicoD), a chalcone derivative in licorice extract, in EGF and TPA-induced transformed skin keratinocyte cells. LicoD effectively suppressed EGF-induced cell proliferation and anchorage-independent colony growth. EGF and TPA promoted the S phase of cell cycle, while LicoD treatment caused G1 phase arrest and down-regulated cyclin D1 and up-regulated p21 expression associated with the G1 phase. LicoD also induced apoptosis and increased apoptosis-related proteins such as cleaved-caspase-3, cleaved-caspase-7, and Bax (Bcl-2-associated X protein). We further investigated the effect of LicoD on the AKT signaling pathway involved in various cellular processes and found decreased p-AKT, p-GSK3β, and p-NFκB expression. Treatment with MK-2206, an AKT pharmacological inhibitor, suppressed EGF-induced cell proliferation and transformed colony growth. In conclusion, this study demonstrated the potential of LicoD as a preventive agent for skin carcinogenesis.

3-Deoxysappanchalcone Inhibits Cell Growth of Gefitinib-Resistant Lung Cancer Cells by Simultaneous Targeting of EGFR and MET Kinases

The mechanistic functions of 3-deoxysappanchalcone (3-DSC), a chalcone compound known to have many pharmacological effects on lung cancer, have not yet been elucidated. In this study, we identified the comprehensive anti-cancer mechanism of 3-DSC, which targets EGFR and MET kinase in drug-resistant lung cancer cells. 3-DSC directly targets both EGFR and MET, thereby inhibiting the growth of drug-resistant lung cancer cells. Mechanistically, 3-DSC induced cell cycle arrest by modulating cell cycle regulatory proteins, including cyclin B1, cdc2, and p27. In addition, concomitant EGFR downstream signaling proteins such as MET, AKT, and ERK were affected by 3-DSC and contributed to the inhibition of cancer cell growth. Furthermore, our results show that 3-DSC increased redox homeostasis disruption, ER stress, mitochondrial depolarization, and caspase activation in gefitinib-resistant lung cancer cells, thereby abrogating cancer cell growth. 3-DSC induced apoptotic cell death which is regulated by Mcl-1, Bax, Apaf-1, and PARP in gefitinib-resistant lung cancer cells. 3-DSC also initiated the activation of caspases, and the pan-caspase inhibitor, Z-VAD-FMK, abrogated 3-DSC induced-apoptosis in lung cancer cells. These data imply that 3-DSC mainly increased mitochondria-associated intrinsic apoptosis in lung cancer cells to reduce lung cancer cell growth. Overall, 3-DSC inhibited the growth of drug-resistant lung cancer cells by simultaneously targeting EGFR and MET, which exerted anti-cancer effects through cell cycle arrest, mitochondrial homeostasis collapse, and increased ROS generation, eventually triggering anticancer mechanisms. 3-DSC could potentially be used as an effective anti-cancer strategy to overcome EGFR and MET target drug-resistant lung cancer.

Licochalcone H Induces Cell Cycle Arrest and Apoptosis in Human Skin Cancer Cells by Modulating JAK2/STAT3 Signaling

Licochalcone H (LCH) is a phenolic compound synthetically derived from licochalcone C (LCC) that exerts anticancer activity. In this study, we investigated the anticancer activity of LCH in human skin cancer A375 and A431 cells. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) cell viability assay was used to evaluate the antiproliferative activity of LCH. Cell cycle distribution and the induction of apoptosis were analyzed by flow cytometry. Western blotting assays were performed to detect the levels of proteins involved in cell cycle progression, apoptosis, and the JAK2/STAT3 signaling pathway. LCH inhibited the growth of cells in dose- and time-dependent manners. The annexin V/propidium iodide double staining assay revealed that LCH induced apoptosis, and the LCH-induced apoptosis was accompanied by cell cycle arrest in the G1 phase. Western blot analysis showed that the phosphorylation of JAK2 and STAT3 was decreased by treatment with LCH. The inhibition of the JAK2/STAT3 signaling pathway by pharmacological inhibitors against JAK2/STAT3 (cryptotanshinone (CTS) and S3I-201) simulated the antiproliferative effect of LCH suggesting that LCH induced apoptosis by modulating JAK2/STAT3 signaling.

Podophyllotoxin Induces ROS-Mediated Apoptosis and Cell Cycle Arrest in Human Colorectal Cancer Cells via p38 MAPK Signaling

Podophyllotoxin (PT), a lignan compound from the roots and rhizomes of Podophyllum peltatum, has diverse pharmacological activities including anticancer effect in several types of cancer. The molecular mechanism of the anticancer effects of PT on colorectal cancer cells has not been reported yet. In this study, we sought to evaluate the anticancer effect of PT on human colorectal cancer HCT116 cells and identify the detailed molecular mechanism. PT inhibited the growth of cells and colony formation in a concentration-dependent manner and induced apoptosis as determined by the annexin V/7-aminoactinomycin D double staining assay. PT-induced apoptosis was accompanied by cell cycle arrest in the G2/M phase and an increase in the generation of reactive oxygen species (ROS). The effects of PT on the induction of ROS and apoptosis were prevented by pretreatment with N-acetyl-L-cysteine (NAC), indicating that an increase in ROS generation mediates the apoptosis of HCT116 cells induced by PT.Furthermore, Western blot analysis showed that PT upregulated the level of phospho (p)-p38 mitogen-activated protein kinase (MAPK). The treatment of SB203580, a p38 inhibitor, strongly prevented the apoptosis induced by PT, suggesting that PT-induced apoptosis involved the p38 MAPK signaling pathway. In addition, PT induced the loss of mitochondrial membrane potential and multi-caspase activation. The results suggested that PT induced cell cycle arrest in the G2/M phase and apoptosis through the p38 MAPK signaling pathway by upregulating ROS in HCT116 cells.

Cytotoxic Constituents from the Roots of Asarum sieboldii in Human Breast Cancer Cells

Bioassay-guided fractionation of the roots of Asarum sieboldii led to the isolation of the six compounds methylkakuol (1), sesamin (2), asarinin (3), xanthoxylol (4), and (2E,4E,8Z,10E/Z)-N-(2-methylpropyl) dodeca-2,4,8,10-tetraenamide (5/6). Among the isolates, xanthoxylol (4) exhibited significant cytotoxicity against human breast cancer cells MCF-7 and MDA-MB-231 in vitro with IC₅₀ values of 9.15 and 13.95 µM, respectively.

Initial Experience of Transperineal Biopsy After Multiparametric Magnetic Resonance Imaging in Korea; Comparison With Transrectal Biopsy

PURPOSE: The aim of this study is to confirm the detection rate of transperineal biopsy after multiparametric magnetic resonance imaging (mpMRI) and compared it to that of transrectal biopsy. We also examined the role of mpMRI and the rate of complications for each method. MATERIALS AND METHODS: In a retrospective study, we analyzed 147 patients who underwent mpMRI before prostate biopsy because of elevated serum prostate-specific antigen and/or abnormal digital rectal examination findings at Korea University Hospital, Seoul, Korea from March 2017 to April 2018. Regions on the mpMRI that were suggestive of prostate cancer were categorized according to the Prostate Imaging–Reporting and Data System (PI-RADS v2). For transperineal biopsy, a 20-core saturation biopsy was performed by MRI-TRUS cognitive or fusion techniques and a 12-core biopsy was performed in transrectal biopsy. RESULTS: Sixty-three and 84 patients were enrolled in transperineal group and transrectal group, respectively. The overall detection rate of prostate cancer in transperineal group was 27% higher than that in transrectal group. Classification according to PI-RADS score revealed a significant increase in detection rate in all patients, as the PI-RADS score increased. Frequency of complications using the Clavien-Dindo classifications revealed no significant differences in the total complications rate, but two patients in transrectal group received intensive care unit care due to urosepsis. CONCLUSIONS: Our results confirmed that transperineal biopsy is superior to transrectal biopsy for the detection of prostate cancer. From the complication point of view, this study confirmed that there were fewer severe complications in transperineal biopsy.

The clinical significance of a second transurethral resection for T1 high-grade bladder cancer: Results of a prospective study

PURPOSE: This study was designed to estimate the value of a second transurethral resection of bladder tumor (TURBT) procedure in patients with initially diagnosed T1 high-grade bladder cancer. MATERIALS AND METHODS: Between August 2009 and January 2013, a total of 29 patients with T1 high-grade bladder cancer prospectively underwent a second TURBT procedure. Evaluation included the presence of previously undetected residual tumor, changes to histopathological staging or grading, and tumor location. Recurrence-free and progression-free survival curves were generated to compare the prognosis between the groups with and without residual lesions by use of the Kaplan-Meier method. RESULTS: Of 29 patients, 22 patients (75.9%) had residual disease after the second TURBT. Staging was as follows: no tumor, 7 (24.1%); Ta, 5 (17.2%); T1, 6 (20.7%); Tis, 6 (20.7%); Ta+Tis, 1 (3.4%); T1+Tis, 1 (3.4%); and > or =T2, 3 (10.3%). The muscle layer was included in the surgical specimen after the initial TURBT in 24 patients (82.7%). In three patients whose cancer was upstaged to pT2 after the second TURBT, the initial surgical specimen contained the muscle layer. In the group with residual lesions, the 3-year recurrence-free survival and 3-year progression-free survival rates were 50% and 66.9%, respectively, whereas these rates were 68.6% and 68.6%, respectively, in the group without residual lesions. This difference was not statistically significant. CONCLUSIONS: Initial TURBT does not seem to be enough to control T1 high-grade bladder cancer. Therefore, a routine second TURBT procedure should be recommended in patients with T1 high-grade bladder cancer to accomplish adequate tumor resection and to identify patients who may need to undergo prompt cystectomy.

A Case of an Esophageal Stricture Due to Transesophageal Echocardiography / 대한소화기내시경학회지

Transesophageal echocardiography (TEE) is widely used to assess cardiac function and anatomical relationships. Although monitoring of the heart by the use of TEE is perceived to be safe and noninvasive, there are significant complications associated with the use of a probe in the esophagus. Oropharyngeal trauma, esophageal perforation, difficulty or pain with swallowing, and gastric mucosal injury are adverse events that can occur from TEE probe insertion. However, no reports have shown that placement of a TEE probe in the esophagus can be a cause of an esophageal stricture. We report a case of a 74-year-old woman with an esophageal stricture after intraoperative TEE. Bougie dilatation is generally considered as an effective treatment for a benign esophageal stricture. The benign stricture in the esophagus was treated safely using Savary-Gilliard bougie dilatation.

Two Cases of Successful Primary Percutaneous Coronary Intervention in Patients With an Anomalous Right Coronary Artery Arising From the Left Coronary Cusp

An anomalous origin of the right coronary artery (RCA) from the left coronary cusp is a rare congenital anomaly. Because of the unusual location and the noncircular luminal orifice of this anomaly, cannulation of this artery during coronary angiography and percutaneous coronary intervention (PCI) poses significant technical difficulties when using the currently available guiding catheters. Primary PCI should be performed as quickly as possible when a patient displays this condition. When we face the situation of an anomalous artery during primary PCI, it takes a much longer time to open the occluded artery. We report here on two cases of successful primary PCI with using manually manipulated catheters and Ikari type guiding catheters in 2 patients who both had an anomalous RCA arising from the left coronary cusp.

A Case of Terminal Ileal Ulcer of Henoch-Sch?nlein Purpura Treated with High Dose Steroid / 대한소화기학회지

Henoch-Schonlein purpura (H-S purpura) is a systemic small-vessel vasculitis involving skin, joint, gastrointestinal tract, and kidney. It is characterized by the classic tetrad of abdominal pain, arthralgia, typical rash, and renal involvement. All of these clinical findings can occur in any order and at any time over several days to weeks. Gastrointestinal manifestations such as abdominal pain, melena, or hematochezia occur in 45-85% and preceed skin lesions upto 40% in H-S purpura. However, endoscopically proven gastrointestinal lesion is rare because majority of involved sites are small intestine. We report a case of Henoch-Schonlein purpura with terminal ileal ulcer, healed after treatment with high dose steroid, proven by colonoscopy.

A Case of Vivax Malaria with Seizure and Shock

Vivax malaria reemerged in the Republic of Korea in 1993. Vivax malaria is generally a benign disease with few severe complications. Even in the worldwide literature, there is only a small number of case reports on severe complications in vivax malaria. We report a unique case of P. vivax infection complicated by seizure and shock. A 58 year-old male showed generalized tonic-clonic seizure and shock after P. vivax infection. The species of malarial parasite was identified using peripheral blood film examination and polymerase chain reaction (PCR). He successfully recovered after treatment with hydroxychloroquine.

A Case of Vivax Malaria with Seizure and Shock

Vivax malaria reemerged in the Republic of Korea in 1993. Vivax malaria is generally a benign disease with few severe complications. Even in the worldwide literature, there is only a small number of case reports on severe complications in vivax malaria. We report a unique case of P. vivax infection complicated by seizure and shock. A 58 year-old male showed generalized tonic-clonic seizure and shock after P. vivax infection. The species of malarial parasite was identified using peripheral blood film examination and polymerase chain reaction (PCR). He successfully recovered after treatment with hydroxychloroquine.

A Case of Abciximab Induced Acute Profound Thrombocytopenia Resulting in Compartment Syndrome of the Forearm from Massive Bleeding at the Brachial Artery Access Site

Abciximab is one of the glycoprotein IIb/IIIa receptor inhibitors, and it is known to be effective for preventing and treating the thrombotic complications of percutaneous coronary intervention (PCI). On the other hand, there is an increasing risk of hemorrhagic complications when using abciximab, especially in the case of abciximab-induced thrombocytopenia. Acute profound thrombocytopenia is a rare, but life threatening adverse reaction to abciximab, and it can even occur within a few hours of the first exposure. We report here on a case of 56 year-old woman who experienced massive bleeding of her brachial artery access site. This was caused by abciximab-induced acute profound thrombocytopenia after performing PCI concomitant with using abciximab.

Efficacy of N-Butyl 2-Cyanoacrylate Injection Therapy for Gastric Variceal Bleeding / 대한소화기내시경학회지

BACKGROUND/AIMS: The aim of the study was to evaluate the efficacy of n-butyl 2-cyanoacrylate injection therapy for gastric variceal bleeding and to find out the factors related to clinical outcome. METHODS: Sixty-seven patients treated with n-butyl 2-cyanoacrylate injection therapy for gastric variceal bleeding were retrospectively reviewed. RESULTS: Initial hemostasis was achieved in all 12 patients. Success of therapy was achieved in 88% of the patients. A stepwise logistic regression analysis including age, sex, cause of cirrhosis, Child-Pugh class, variceal form, bleeding site, initial hemoglobin, and presence of hepatocellular carcinoma as variables indicated that only the Child-Pugh class was an independent predictive factor of treatment failure. Rebleeding occurred in 19% of the patients during the 4 weeks after therapy. The cumulative probability of 4-week remaining free of rebleeding was significantly higher in Child-Pugh A and B than in Child-Pugh C. Mortality at 4 weeks was 15%. The Child-Pugh class and the presence of hepatocellular carcinoma were the independent predictive factors of mortality at 4 weeks. CONCLUSIONS: N-butyl 2-cyanoacrylate injection therapy is highly effective in the management of bleeding from gastric varices. Child-Pugh class is an important predictive factor of treatment failure, rebleeding, and survival after the therapy.

The pH of the Gastric Mucosal Surface and Helicobacter pylori Infection in Non-Ulcer Dyspepsia / 대한소화기내시경학회지

BACKGROUND/AIMS: The Helicobacter pylori(H. pylori) infection induces gastric mucosal injury through the various bacterial cytotoxins, the inflammatory reaction of the host and the increased gastric acid secretion. Urease is a kind of adaptive protein of H. pylori to survive in strong acid environment of the stomach, may increase the pH of the gastric mucosal surface and induces gastrin release by the feedback mechanism. This study was performed to evaluate whether 0.1% phenol red solution without urea is useful as a pH indicator of the gastric mucosa for the diagnosis of H. pylori infection in stomach and whether the pH of the gastric mucosal surface is changed by H. pylori infection. METHODS: The gastric mucosa was stained by 0.1% phenol red solution without urea during endoscopy in 89 patients with non-ulcer dyspepsia. The patterns of staining of the gastric mucosa were divided into unstained, patchy regional and diffuse staining by the area of color change from yellow to red. The pH of the gastric mucosal surface was measured directly on the stained and unstained areas of the gastric mucosa by using pH meter and antimony pH electrode through the biopsy channel. RESULTS: The pH of the stained areas after spray of phenol red solution was significantly higher(6.9) than that(1.9) of the unstained gastric mucosa(P<0.01). The patterns of the staining were different between antrum and body. The patterns of unstaining and patchy staining were more common in the body than in the antrum. But the patterns of regional and diffuse staining were more common in the antrum than in the body(P<0.05). The positive rates of H. pylori in antrum, body and total gastric biopsies were higher in stained than in unstained mucosa significantly(P<0.05). Severity of active inflammatory reactions was higher in stained mucosa than unstained mucosa in the antrum. But there was no difference in severity of active inflammatory reactions between stained mucosa and unstained mucosa in the body. CONCLUSIONS: 0.1% phenol red solution without urea is useful as a pH indicator for the diagnosis of the H. phlori infection in the stomach. H. pylori infection may increase the pH of gastric mucosal surface and induce severe active inflammation of the gastric mucosa in non-ulcer dyspepsia.

Analysis of Histological Findings and Estrogen and Progesterone Receptor Status in Luteal Phase Defect Caused by Delayed Ovulation and Clomiphen Treatment

Luteal phase defect (LPD) is an ovulatory disorder of considerable clinical importance that leads to delayed endometrial maturation and inadequate endometrium for blastocyst implantation. This disorder is implicated in infertility and recurrent spontaneous abortion. We analyzed the endometrial histological maturation, and the estrogen receptor(ER) and progesterone receptor(PR) status in patients with unexplained delayed ovulation, and in patients with ovulation induction by clomiphen citrate. The purpose of this study was to determine whether the length of the follicular phase influences the endometrial histological maturation and the hormonal receptor status, and to know the effect of clomiphen citrate on the endometrium. In the delayed ovulation group, the endometrium was characterized by an irregular outpouching and dilated lumina of the glands, a decreased secretory activity and predecidualization, and a decreased number of granulocytes in the stroma. In the clomiphen citrate-ovulation induction group, glandular proliferation was markedly diminished with poorly convoluted and narrow glands, secretory activity was decreased, stroma was undecidualized, and there was an absence of granulocytes. ER expression was increased in the glandular epithelium in the delayed ovulation group, and both ER and PR expressions were markedly decreased in the glandular epithelium and stromal cells in the ovulation induction group. Endometrial maturation and differentiation may be diminished by increased estrogenic and relatively deficient progesterone effects in patients with delayed ovulation. The hormonal receptor status might also be influenced by hormonal changes. Clomiphen citrate successfully induced ovulation in patients with delayed ovulation, however, endometrial proliferation and maturation were markedly suppressed. This might be related to the lower pregnancy rate and higher abortion rate in patients with clomiphen citrate induced ovulation.

A Case of Interstitial Pneumonitis developed by Interferon- alpha Treatment for Chronic Hepatitis C / 결핵

Interstitial pneumonitis associated with interferon alpha therapy for chronic hepatitis C was first described in 1994 by Kazuo et al in Japan. The mechanism of interstitial pneumonitis deveoped by interferon alpha was still unknown but immunologic, allergic or direct lung toxicity were suggested. We experienced a case of interstitial pneumonitis developed during interferon alpha therapy for chronic hepatitis C in a 52-year-old male patient. He was treated with 6 million units of interferon alpha intramuscularly 3 times per week for 4 weeks and noted progressive dyspnea and cough. These symptoms were subsided after 6 weeks' discontinuation of interferon alpha therapy. And so, he was retreated with 3 million units of interferon alpha 3 times per week for 8 weeks and felt dyspnea again. He was admitted to our hospital for further evaluation of progressive dyspnea. Arterial blood gas(ABG) values were PaO2 90.7 mmHg and PaCO2 31.9 mmHg, and antinuclear antibody(ANA) was negative. A chest X-ray film revealed diffuse reticulo-nodular shadows in bilateral lung fields, suggesting a diagnosis of interstitial pneumonitis. A marked increase in lymphocyte count and suppressor T cell were observed in bronchoalveolar lavage(BAL) fluid. Lymphocyte stimulation test with interferon alpha was positive. Interstitial pneumonitis was confirmed by transbronchial lung biopsy. After discontinuation of interferon alpha, we gave oral steroid in the condition that clinical symptoms were being improved gradually.

Correlation between High-Resolution CT and PulmonaryFunction Tests in Patients with Emphysema / 결핵

BACKGROUND: The diagnosis of emphysema during life is based on a combination of clinical, functional, and radiographic findings, but this combination is relatively insensitive and nonspecific. The development of rapid, high-resolution third and fourth generation CT scanners has enabled us to resolve pulmonary parenchymal abnormalities with great precision. We compared the chest HRCT findings to the pulmonary function test and arterial blood gas analysis in pulmonary emphysema patients to test the ability of HRCT to quantify the degree of pulmonary emphysema. METHODS: From October 1994 to October 1995, the study group consisted of 20 subjects in whom HRCT of the thorax and pulmonary function studies had been obtained at St. Mary's hospital. The analysis was from scans at preselected anatomic levels and incorporated both lungs. On each HRCT slice the lung parenchyma was assessed for two aspects of emphysema: severity and extent. The five levels were graded and scored separately for the left and right lung giving a total of 10 lung fields. A combination of severity and extent gave the degree of emphysema. We compared the HRCT quantitation of emphysema, pulmonary function tests, ABGA, CBC, and patients characteristics(age, sex, height, weight, smoking amounts etc.) in 20 patients. RESULTS: 1) There was a significant inverse correlation between HRCT scores for emphysema and percentage predicted values of DLco(r = -0.68, p < 0.05),DLco/VA(r = -0.49, p < 0.05),FEVl(r = -0.53, p < 0.05),, and FVC(r = -0.47, p < 0.05). 2) There was a significant correlation between the HRCT scores and percentage predicted values of TLC(r = 0.50, p < 0.05),RV(r = 0.64, p < 0.05). 3) There was a significant inverse correlation between the HRCT scores and PaO2(r = -0.48, p < 0.05) and significant correlation with D(A-a)02(r = -0.48, p < 0.05) but no significant correlation between the HRCT scores and PaCO2. 4) There was no significant correlation between the HRCT scores and age, sex, height, weight, smoking amounts in patients, hemoglobin, hematocrit, and wbc counts. CONCLUSION: High-Resolution CT provides a useful method for early detection and quantitating emphysema in life and correlates significantly with pulmonary function tests and arterial blood gas analysis.