Clinical significance of C-reactive protein-to-prealbumin ratio in predicting early recurrence in resectable pancreatic cancer

Purpose@#Resectable pancreatic ductal adenocarcinoma (PDAC) has a high risk of recurrence after curative resection; despite this, the preoperative risk factors for predicting early recurrence remain unclear. This study therefore aimed to identify preoperative inflammation and nutrition factors associated with early recurrence of resectable PDAC. @*Methods@#From March 2021 to November 2021, a total of 20 patients who underwent curative resection for PDAC were enrolled in this study. We evaluated the risk factors for early recurrence within 1 year by univariate and multivariate analyses using Cox hazard proportional regression. The cutoff values for predicting recurrence were examined using receiver operating characteristic (ROC) curves. @*Results@#In our univariate and multivariate analyses, C-reactive protein (CRP), CRP-albumin ratio, and CRP-prealbumin ratio, as well as sex and age, were significant independent prognostic factors for early recurrence in PDAC. However, known inflammatory factors (neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios), nutritional factors (albumin, prealbumin, ferritin, vitamin D), and inflammatory-nutritional factors (Glasgow Prognostic Score, modified Glasgow Prognostic Score, albumin-bilirubin) showed no association with early recurrence. In addition, using cutoff values by ROC curve analysis, a high preoperative CRP level of >5 mg/L, as well as high CRP-to-albumin (>5.3) and CRP-to-prealbumin (>1.3) ratios showed no prognostic value. @*Conclusion@#Our results showed that inflammatory and perioperative nutritional factors, especially CRP-to-prealbumin ratio, have significant associations with early recurrence after curative resection in resectable PDAC. Therefore, for such patients, a cautious approach is needed when inflammation and poor nutritional status are present.

Clinical impact of serum prealbumin in pancreaticobiliary disease

Purpose@#Although there are many studies on prealbumin in individual diseases such as malignant or inflammatory diseases, there are few comparative studies. This study aimed to compare the clinical differences between prealbumin levels in cholecystitis and pancreaticobiliary malignancies and investigate the clinical impact of low prealbumin levels in pancreaticobiliary malignancies. @*Methods@#From June 2021 to September 2021, 61 patients who had undergone surgery for various pancreaticobiliary diseases were enrolled in this study, and their clinicopathological data were retrospectively analyzed. @*Results@#Many elderly patients with malignant diseases had poor American Society of Anesthesiologists (ASA) scores, significantly lower albumin and prealbumin levels, and higher systemic immune inflammation indices. The low prealbumin group was older; had poorer ASA scores; and had significantly lower body mass index and hemoglobin and albumin levels and higher systemic immune inflammation indices than the normal prealbumin group. In malignant diseases, the low prealbumin group had significantly lower body mass index and hemoglobin levels and a tendency toward more advanced disease (lymph node and distant metastasis). @*Conclusion@#Preoperative low prealbumin levels had an area under the receiver operator characteristic curve of 0.69, suggesting that it may be useful for predicting pancreaticobiliary malignancies. Prealbumin levels were lower in malignant diseases, possibly related to poor nutritional status and systemic immune inflammation. Low prealbumin levels may predict the risk of more advanced disease.

Clinical Significance of Redundant Nerve Roots of the Cauda Equina in Spine MRI

Purpose@#This study aimed to evaluate the association of redundant nerve roots of the cauda equina (RNRCEs) with the degree and duration of symptoms in patients with lumbar spinal canal stenosis. @*Materials and Methods@#Between January 2017 and December 2018, 224 patients demonstrating central canal stenosis on lumbar spine MRI were included. Various imaging findings associated with spinal canal stenosis were investigated, as were the presence, level, type, and length of RNRCEs, and the presence of nerve root swelling. Clinically, the degree of symptoms and symptom changes after treatment were investigated. Multinomial logistic regression was used for statistical analysis. @*Results@#RNRCEs were present in 142 patients (63.4%). Most RNRCEs were observed above the level of stenosis (47.3%). RNRCE was associated with the number of stenoses and symptom duration (p < 0.05). The presence, level, type, and length of RNRCE and nerve root swelling significantly affected the severity of symptoms (p < 0.05). The type of treatment influenced symptom changes (p < 0.05). @*Conclusion@#The recognition and assessment of RNRCEs on spinal MRI are clinically important because the presence, level, type, and length of a RNRCE may be associated with the degree of symptoms and help predict the clinical outcome according to treatment methods.

Deep Learning-Based Assessment of Functional Liver Capacity Using Gadoxetic Acid-Enhanced Hepatobiliary Phase MRI

Objective@#We aimed to develop and test a deep learning algorithm (DLA) for fully automated measurement of the volume and signal intensity (SI) of the liver and spleen using gadoxetic acid-enhanced hepatobiliary phase (HBP)-magnetic resonance imaging (MRI) and to evaluate the clinical utility of DLA-assisted assessment of functional liver capacity. @*Materials and Methods@#The DLA was developed using HBP-MRI data from 1014 patients. Using an independent test dataset (110 internal and 90 external MRI data), the segmentation performance of the DLA was measured using the Dice similarity score (DSS), and the agreement between the DLA and the ground truth for the volume and SI measurements was assessed with a Bland-Altman 95% limit of agreement (LOA). In 276 separate patients (male:female, 191:85; mean age ± standard deviation, 40 ± 15 years) who underwent hepatic resection, we evaluated the correlations between various DLA-based MRI indices, including liver volume normalized by body surface area (LV BSA), liver-to-spleen SI ratio (LSSR), MRI parameter-adjusted LSSR (aLSSR), LSSR x LV BSA, and aLSSR x LV BSA, and the indocyanine green retention rate at 15 minutes (ICG-R15), and determined the diagnostic performance of the DLA-based MRI indices to detect ICG-R15 ≥ 20%. @*Results@#In the test dataset, the mean DSS was 0.977 for liver segmentation and 0.946 for spleen segmentation. The BlandAltman 95% LOAs were 0.08% ± 3.70% for the liver volume, 0.20% ± 7.89% for the spleen volume, -0.02% ± 1.28% for the liver SI, and -0.01% ± 1.70% for the spleen SI. Among DLA-based MRI indices, aLSSR x LV BSA showed the strongest correlation with ICG-R15 (r = -0.54, p < 0.001), with area under receiver operating characteristic curve of 0.932 (95% confidence interval, 0.895–0.959) to diagnose ICG-R15 ≥ 20%. @*Conclusion@#Our DLA can accurately measure the volume and SI of the liver and spleen and may be useful for assessing functional liver capacity using gadoxetic acid-enhanced HBP-MRI.

Use of a Cutting Balloon Dilation as a Rescue Therapy in Patients with Benign Bilioenteric Anastomotic Strictures Refractory to Conventional Balloon Dilation / 대한췌담도학회지

Percutaneous balloon dilation with or without placement of an external biliary drain is a nonoperative alternative method for treating benign bilioenteric anastomotic strictures. Although this procedure has a high technical success rate, outcomes are less optimal when attempting to dilate refractory tight strictures. For the stricture, cutting balloon can be an option. We present four patients with benign bilioenteric anastomotic strictures refractory to conventional balloon dilation. To the patients, a peripheral cutting balloon over-the-wire system was inflated, following subsequent conventional non-compliant balloon dilation. After the balloon dilation treatment, an external drainage catheter was placed through the stricture site and maintained for up to 30 days. Technical and end-treatment success was achieved in all four patients. In conclusion, the use of cutting balloon dilation may appear to be a safe and effective alternative method of treatment in patients with benign bilioenteric anastomotic strictures refractory to conventional balloon dilation.

Relationship between high bile juice amylase levels and chronic bacterial infections in patients with gallbladder cancer

Purpose@#Pancreatic enzyme reflux into the biliary tract is associated with chronic inflammation and increased cellular proliferation in the biliary epithelium, leading to biliary carcinoma. We evaluated the relationship between high bile juice amylase levels and biliary microflora in patients with malignant gallbladder lesions. @*Methods@#In this retrospective study, 25 gallbladder specimens were obtained from patients with gallbladder cancer to evaluate amylase levels and perform bacterial culture. The samples were divided into high and low amylase groups and culture-positive and negative groups for analysis. Bile juice amylase 3 times higher than the normal serum amylase level (36–128 IU/L) was considered high. @*Results@#The number of positive cultures was higher in the high amylase group than in the low amylase group, but the difference was insignificant. There were no differences in other clinicopathological factors. Sixteen patients showed positive culture results; Escherichia coli and Klebsiella spp. were the most common gram-negative bacteria, whereas Enterococcus and Streptococcus spp. were the most common gram-positive bacteria. Age and bile juice amylase levels were significantly higher in the culture-positive group than in the culture-negative group. The incidence of bacterial resistance to cephalosporins was 6.25%–35.29%, and this incidence was particularly high for lower-generation cephalosporins. @*Conclusion@#Bacteria in gallbladder were identified more frequently when the amylase level was high. High amylase levels in the gallbladder can be associated with caused chronic bacterial infections with occult pancreaticobiliary reflux, potentially triggering gallbladder cancer

Early Detection of the Internal Capsule Infarction by Intraoperative Neuromonitoring in Mesial Temporal Epilepsy Surgery

Intraoperative neurophysiological monitoring (INM) is underutilized during the anteromesial temporal resection (AMTR) in epilepsy surgery. Herein we report a case with intraoperative capsular infarction which was early detected by INM. Among the modalities of INM, left motor evoked potentials (MEP) showed suddenly decreased amplitude of compound muscle action potentials, after the electrocoagulation in left mesial temporal areas. Postoperative neurologic and MRI findings were well correlated to the intraoperative MEP features. We also discuss the usefulness of INM during the AMTR.

Risk Factors for pT3a Prostate Cancerin the Patients With cT1-2 on PreoperativeMultiparametric Magnetic Resonance Imaging

Purpose@#Our study aimed to evaluate the predictive value of multiparametric magnetic resonance imaging (mpMRI)to assess the capsular extension of prostate cancer. Risk factors for extraprostatic invasion or microscopic invasionof bladder neck (pT3a stage) in the cases showing localized disease findings on MRI scan were also identified. @*Materials and Methods@#We identified 198 patients who underwent robot-assisted or conventional laparoscopicradical prostatectomy in our institute between June, 2016 and May, 2018. Altogether, 170 patients withpreoperational mpMRI scans and complete pathologic data were included. Positive and negative predictive valuesof mpMRI to detect capsular extension were estimated. Chi-square test was performed for ratio variables. Logisticregression analysis was performed to identify capsular invasion risk factors. @*Results@#Median age and prostate-specific antigen level were 68 years and 7.5 ng/mL, respectively. Based onfindings, 16 patients (9.4%) were identified as cT3a stage (unilateral or bilateral extraprostatic extension), whereas37 patients (21.8%) as pT3a stage. Positive and negative predictive values of mpMRI to detect capsular extensionwere 75.0% and 73.9%, respectively. In the logistic regression analysis, positive biopsy core rate was the significantpredictor for pT3a disease in the patients with negative capsular invasion findings on mpMRI (p<0.001). Accordingto receiver-operating characteristic curve (area under the curve=0.691, p=0.001), the positive biopsy core rateof 0.275 was the best threshold. @*Conclusions@#Multiparametric MRI is an appropriate test to predict pT3a disease preoperatively. The patients withpositive core rate over 0.275 may have pT3a diseases despite negative image findings.

The Imaging Features of Desmoid Tumors: the Usefulness of Diffusion Weighted Imaging to Differentiate between Desmoid and Malignant Soft Tissue Tumors

PURPOSE: To evaluate the imaging findings of desmoid tumors using various imaging modalities and to evaluate whether diffusion-weighted imaging (DWI) can help differentiate between desmoid and malignant tumors. MATERIALS AND METHODS: The study included 27 patients with pathologically confirmed desmoid tumors. Two radiologists reviewed 23 computed tomography (CT), 12 magnetic resonance imaging (MRI) and 8 positron emission tomography-computed tomography (PET-CT) scans of desmoid tumors and recorded data regarding the shape, multiplicity, size, location, degree of enhancement, and presence or absence of calcification or hemorrhage. The signal intensity of masses on T1- and T2-weighted imaging and the presence or absence of whirling or band-like low signal intensity on T2-weighted imaging were recorded. The apparent diffusion coefficient (ADC) values of the desmoid tumors in nine patients with DWIs were compared with the ADC values of 32 malignant tumors. The maximum standardized uptake value (SUV(max)) on PET-CT images was measured in 8 patients who underwent a PET-CT. RESULTS: The mean size of the 27 tumors was 6.77 cm (range, 2.5-26 cm) and four tumors exhibited multiplicity. The desmoid tumors were classified by shape as either mass forming (n = 18), infiltrative (n = 4), or combined (n = 5). The location of the tumors was either intra-abdominal (n = 15), within the abdominal wall (n = 8) or extra-abdominal (n = 4). Among the 27 tumors, 21 showed moderate to marked enhancement and 22 showed homogeneous enhancement. Two tumors showed calcifications and one displayed hemorrhage. Eleven of the 12 MR T2-weighted images showed whirling or band-like low signal intensity areas in the mass. The mean ADC value of the desmoid tumors (1493 × 10⁻⁶ mm²/s) was significantly higher than the mean of the malignant soft tissue tumors (873 × 10⁻⁶ mm²/s, P < 0.001). On the PET-CT images, all tumors exhibited an intermediate SUV(max) (mean, 3.7; range, 2.3–4.5). CONCLUSION: Desmoids tumors showed homogenous, moderate to marked enhancement on CT and MRI scans and a characteristic whirling or band-like pattern on T2-weighted images. DWI can be useful for the differentiation of desmoid tumors from malignant soft tissue tumors.

Analysis of Characteristics in Children and Adolescents with Poisoning at Emergency Department

PURPOSE: This study was conducted to analyze the features of poisoning in individuals aged 0-18 years to understand the characteristics of potential victims and eventually prevent poisoning. METHODS: We retrospectively analyzed poisoned children and adolescents (0–18 years) who visited the emergency department of one tertiary hospital from January 2003 through December 2013. We collected data including their age, sex, reason for poisoning, components and dose of poison, results of treatment, and psychiatric diagnosis. RESULTS: During the study period, there were 436 cases of poisoning (male 47.2% (n=206); female 52.8% (n=230)). Subjects were classified into four groups (0–1 years, 2–5 years, 6–12 years, 13–18 years). The most common cause of poisoning in all age groups was accidental poisoning (72.9%), but intentional poisoning increased as age increased (p < 0.001). Moreover, females were more often subject to intentional poisoning than males (p < 0.001). The most common poisoning material was drugs (41.7%). Among intentional poisoning patients, 62.7% patients had consulted a psychiatrist, and their most common diagnosis was adjustment disorder (44.6%). CONCLUSION: The most common cause of poisoning in individuals aged 0–18 years was accidental poisoning, while intentional poisoning was most common among adolescents. Guardians should take care to prevent accidental poisoning, while psychiatric consultation and national moderation will be needed to prevent intentional poisoning.

The current epidemiological status of infectious coryza and efficacy of PoulShot Coryza in specific pathogen-free chickens

Infectious coryza (IC) is an infectious disease caused by Avibacterium (Av.) paragallinarum. IC is known to cause economic losses in the poultry industry via decreased egg production in layers. Between 2012 and 2013, Av. paragallinarum was isolated from seven chicken farms by Chungbuk National University. We identified Av. paragallinarum, the causative pathogen of IC by polymerase chain reaction (PCR) and serovar serotype A, by multiplex PCR. Antibiotic sensitivity tests indicated that a few field-isolated strains showed susceptibility to erythromycin, gentamicin, lincomycin, neomycin, oxytetracycline, spectinomycin, and tylosin. A serological survey was conducted to evaluate the number of flocks that were positive for Av. paragallinarum by utilizing a HI test to determine the existence of serovar A. Serological surveys revealed high positivity rates of 86.4% in 2009, 78.9% in 2010, 70.0% in 2011, and 69.6% in 2012. We also challenged specific pathogen-free chickens with isolated domestic strains, ADL121286 and ADL121500, according to the measured efficacy of the commercial IC vaccine, PoulShot Coryza. We confirmed the effectiveness of the vaccine based on relief of clinical signs and a decreased re-isolation rate of ADL121500 strain. Our results indicate IC is currently prevalent in Korea, and that the commercial vaccine is effective at protecting against field strains.

The Utility of CRP Velocity for the Prognostication in Patients with Acute Pyelonephritis

PURPOSE: C-reactive protein (CRP) velocity is value of the CRP level divided by the time after fever start. The aim of this study was to attempt to determine the usefulness of CRP velocity to predict the severity of acute pyelonephritis (APN). METHODS: We retrospectively reviewed medical records of patients who visited the emergency department (ED) and were diagnosed with APN for five years. The patients underwent computed tomography (CT) in the ED. The characteristics and laboratory findings compared with the CT group were classified from group I to group V as severity of APN. The patients were grouped according to mild and severe based on the CT groups for comparison of area under the curve. Patients who had fever within 24 hours were extracted and the same analysis was performed. RESULTS: A total of 199 patients were enrolled in our study. The CT groups were classified as follows: group 1 (N=24); group 2 (N=25); group 3 (N=80); group 4 (N=58); group 5 (N=12). Statistically significant differences in laboratory results including CRP, CRP velocity, age, and past history of hypertension were found between mild and severe group. The area under ROC curve of CRP and CRP velocity was 0.888 and 0.841 (p<0.05). For APN patients within 24 hours, AUROC of CRP and CRP velocity were 0.871 and 0.949 (p<0.05). However, AUROC comparison did not show statistically significant differences within CRP and CRP velocity (p=0.1410). CONCLUSION: In APN patients who had fever within 24 hours, CRP and CRP velocity had predictive value for severity of APN.

Eggshell apex abnormalities associated with Mycoplasma synoviae infection in layers

Eggs exhibiting eggshell apex abnormalities (EAA) were evaluated for changes in shell characteristics such as strength, thickness, and ultrastructure. Mycoplasma synoviae (MS) infection was confirmed by serological assay along with isolation of MS from the trachea and oviduct. Changes in eggshell quality were shown to be statistically significant (p < 0.01). We also identified ultrastructural changes in the mammillary knob layer by Scanning Electron Microscopy. While eggs may seem to be structurally sound, ultrastructural evaluation showed that affected eggs do not regain their former quality. In our knowledge, this is the first report describing the occurrence of EAA in Korea.

A Case Report of Spider Bite by Tarantula

A total of 631 species of spiders have been reported in Korea. However, there are no spiders with noxious venom such as Latrodectus sp. Because of this, to date, no serious medical problems due to spider bites have been reported in Korea, and only two cases of spider bite were officially reported. However, as the number of earning spiders from other countries is increased, the number of cases of spider bite has also shown a recent increase. A 17-year-old man presented with numbness of both extremities after being bitten by a spider which he had as a pet. The spider is called an Indian ornamental tree spider (Poecilotheria regalis sp.), one kind of tarantula species. Herein, we report on a case of a spider bite by a tarantula.

Sensory Axon Regeneration: A Review from an in vivo Imaging Perspective

Injured primary sensory axons fail to regenerate into the spinal cord, leading to chronic pain and permanent sensory loss. Re-entry is prevented at the dorsal root entry zone (DREZ), the CNS-PNS interface. Why axons stop or turn around at the DREZ has generally been attributed to growth-repellent molecules associated with astrocytes and oligodendrocytes/myelin. The available evidence challenges the contention that these inhibitory molecules are the critical determinant of regeneration failure. Recent imaging studies that directly monitored axons arriving at the DREZ in living animals raise the intriguing possibility that axons stop primarily because they are stabilized by forming presynaptic terminals on non-neuronal cells that are neither astrocytes nor oligodendrocytes. These observations revitalized the idea raised many years ago but virtually forgotten, that axons stop by forming synapses at the DREZ.

Acromion Morphology in Coronal and Sagittal Plane; Correlation with Rotator Cuff Syndrome

PURPOSE: We evaluated the correlation of the anatomic parameters of the acromion those represent on the magnetic resonance image (MRI) of impingement syndrome. MATERIALS AND METHODS: From June, 2004 to December, 2005, 71 cases were surgically proven to be impingement syndrome, and the anterior acromial hooking angle, the lateral acromial hooking angle (AAHA and LAHA) and the acromial hooking index (AHI: the sum of the AAHA and LAHA) were compared to 16 control cases. At the same period, 55 cases were surgically proven to be partial or full thickness rotator cuff tear, and age, gender and twelve anatomic parameters, including the acromial type, the acromial angle, the anterior covering, the acromial slope, the AAHA, the lateral acromial angle, the acromial torsional angle, the lateral acromial angulation, the LAHA, the lateral covering, the acromiohumeral distance and the AHI were assessed. RESULTS: The AAHA and AHI were increased as impingement syndrome proceeded. The acromial type and acromial angle, and the AAHA, LAHA and AHI showed significant differences between the controls and the rotator cuff tear patients on univariant analysis. On multivariant analysis, gender was most strongly correlated with rotator cuff tear. Age, AAHA and the acromial angle showed similar correlation, respectively. CONCLUSION: The coronal acromial shape is correlated with rotator cuff tear, and it is important to correct the lateral acromial shape when performing acromioplasty.

Clinical Outcomes After Arthroscopic Double-Row Rotator Cuff Repair and Evaluation of Cuff Integrity by CT Arthrography

PURPOSE: Our goal for this study was to prospectively evaluate the functional & structural outcomes, by means of CT arthroscopy, of arthroscopic double-row fixation for treating rotator cuff tear. We also attempted to determine the variants that affect the functional & structural outcomes. MATERIALS AND METHODS: Twenty seven consecutive patients underwent arthroscopic rotator cuff repair with double-row fixation. The average age at the time of the operation was fifty six years. The preoperative and postoperative examinations consisted of determining the Constant score, the score for the visual analogue scale for pain, the UCLA score, the American Shoulder and Elbow Surgeons (ASES) score, as well as a full physical examination of the shoulder. Preoperative MR arthrography was used to evaluate the integrity and atrophy of the rotator cuff. We measured the intraoperative tear size in the sagittal and coronal planes. Postoperative CT arthrography was used at one year postoperatively to evaluate the integrity and atrophy of the repaired tendons and muscles. RESULTS: Preoperative MR arthrography revealed an average 29.22 mm tear size in the sagittal plane and an average 22.72 mm tear size in the coronal plane. Twelve cases of supraspinatus muscle atrophy and two cases of infraspinatus atrophy were observed on the preoperative MR arthrography. The average clinical outcome scores all significantly improved at the time of follow-up. At a mean of one year postoperatively, CT arthrography revealed 48.1% of the shoulders had healed, 11.1% showed incomplete healing and 40.7% showed retear of the repaired tendon. CONCLUSION: Arthroscopic double-row repair can result in improved clinical outcomes and good patient satisfaction. However, the problems about how to enhance healing of the repaired tendon still remain.

Treatment of Male Infertility

The recent advancement of Assisted Reproductive Techniques (ART) has been problematic for the diagnosis and treatment of male infertility. Instead of exploring in depth the nature of the male infertility to achieve a natural pregnancy, ART concentrates mainly on obtaining a sperm for the purpose of fertilizing the ovum. This approach favors fertilization over the correction of male infertility and therefore often overlooks appropriate treatment options. In other words, ART is not consistent with bioethical practices and can lead to unfortunate outcomes for many infertile men. In particular, varicocelectomy, vasovasostomy, and epididymovasostomy result in high pregnancy rates when compared with ART. Moreover, redo-vasovasostomy has also been found to produce high pregnancy rates when the first trial proved unsuccessful. Twenty-five percent of male infertility cases diagnosed by semen analysis are deemed idiopathic. For the remaining seventy-five percent, however, the cause of infertility can be identified. Therefore, the primary approach to infertility should be to treat the underlying cause and thereby enable natural pregnancy to occur.

The mechanism of cell death in etoposide treated cervical cancer cells: apoptotic and non-apoptotic programmed cell death / 부인종양

OBJECTIVE: Etoposide is a potent and widely used antineoplastic agent. It is able to induce apoptosis in most cell types. However, very little is known about its mechanism of action. In this study, we demonstrate the cytotoxic signal that induced by etoposide and investigate how etoposide exerts antitumor activity in HPV-16 (+) CaSki cervical carcinoma cells. METHODS: Antiproliferation activity was measured in CaSki cell lines by using MTT assays, DNA fragmentation assay. Cell cycle distribution was analyzed using flow cytometry. Expression of proteins involved in the apoptotic pathway was analyzed by Western blotting (WB). Electron microscopic (EM) and biochemical studies (Western blotting, RT-PCR) revealed that non-apoptotic death was associated with autophagosomes/-autolysosomes. These parameters have also been measured in cells treated with 3-methyladenine (an autophagy inhibitor), zVAD-fmk (a pan-caspase inhibitor) and both. RESULTS: The etoposide induced apoptosis. In cell cycle analysis, etoposide-treated CaSki cells were few induced hypodiploid DNA content, suggesting that apoptotic cell death. EM study revealed that autophagic appearance in the presence of etoposide exhibited by autophagosomes/autolysosomes. It was confirmed by LysoTracker probe and WB against Beclin 1, APG 5, APG 12 and p53. When autophagy was blocked by 3-MA, not only the protein expression of Beclin 1, but also the antitumor effect of etoposide was suppressed. On the other hand, the addition of zVAD-fmk could induce a few etoposide-induced autophagy. And etoposide-treated CaSki cells were rescued by combination of 3-MA and zVAD-fmk. CONCLUSION: Our results suggest that etoposide not only initiated apoptosis but ultimately caused cell death through autophagy. In this study, we demonstrate novel features for the action of etoposide in HPV-16 (+) CaSki cervical carcinoma cells. Autophagic cell death induction by some anticancer agents underlines the potential utility of its induction as a new cancer treatment modality.

Differential protein expression of etoposide-treated CaSki cervical carcinoma cells / 부인종양

OBJECTIVE: This study was designed to examine the pharmaco-dynamic pattern of proteomic expression in cervical carcinoma cells (CaSki cell line; HPV-16 positive) after in vitro treatment by the etoposide. METHODS: We analyzed proteomic profiling in cervical carcinoma cells after etoposide treatment using two-dimensional gel electrophoresis (2-DE) with MALDI-TOF-MS used for protein identification. Then, we tested the several experimental methods for verification and functional identification, including MTT assay, PI staining, DNA fragmentation assay, FDA, FACS and Western blot analysis. RESULTS: Etoposide inhibited the CaSki cervical cancer cell growth in a dose-dependent manner and the optimal concentration of etoposide is 2micrometer(IC50) in the CaSki cervical cancer cells. The etoposide induced apoptosis, as determined by DNA fragmentation assay, FACS, and Western blot. The etoposide increased the protein expression of Fas (Apo-1/CD95), p53, pRb and caspase-3, but decreased the level of Bcl-2 and caspase-3 precursor and subsequently triggered the mitochondrial apoptotic pathway (release of cytochrome c and activation of caspase-9). To this end, we analyzed CaSki cancer cells using 2-DE. Eight proteins (XAP-5, HXC-36, serine/threonine protein phosphatase 2B catalytic subunit, G2/mitotic-specific cyclin B1, T-box transcription factor TBX20, diacylglycerol kinase, amiloride-sensitive amine oxidase, HEF-like protein, ras-related protein Rab-20) were down-regulated and nine proteins (RNA 3'-terminal phosphate cyclase-like protein, late endosomal/lysosomal Mp1 interacting protein, glia maturation factor, replication protein A 14 kDa subunit, mago sashi protein homolog, 14 kDa phosphohistidine phosphatase, protein C14 or f48, cyclin-dependent kinase 4 inhibitior A, retinoic acid-binding protein II) were up-regulated in etoposide-treated CaSki cells when compared with non-treated cells. CONCLUSION: Our results clearly indicate that etoposide induced cell death by apoptosis. These findings may provide insights into the mechanisms underlying the apparent anti-tumoral effects of etoposide.