A Case of Vancomycin-Induced Drug Reaction with Eosinophilia, Systemic Symptoms and Multiorgan Involvement Proven Using Lymphocyte Transformation Test

Drug-induced hypersensitivity syndrome (DiHS), also referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a rare but potentially life-threatening condition induced by drug hypersensitivity that leads to significant morbidity and mortality and often occurs in patients undergoing combination antibiotic therapy. Due to a recent increase in the incidence of methicillin-resistant Staphylococcus aureus infections, the occurrence of vancomycin-induced DiHS/DRESS has increased rapidly. However, because of insufficient pharmacogenetic data on vancomycin-induced drug eruptions in Asians coupled with the risk of re-eliciting the symptoms by provocation tests, confirmation of the culprit drug in vancomycin-induced DiHS/DRESS is often challenging. Here, we report a case of vancomycin-induced DiHS/DRESS, where the causal relationship was confirmed using a lymphocyte transformation test (LTT). A 51-year-old woman was treated with combination antibiotics, including vancomycin, for infective pericarditis. The patient subsequently developed fever, facial edema, generalized rash followed by multiple internal organ involvement, including the kidney, lung, liver, and heart. Thus, based on the International Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria, the case was diagnosed as ‘definite’ DiHS/ DRESS, although the culprit drug was obscured by combination antibiotic therapy. The LTT confirmed that vancomycin, but not other glycopeptide antibiotics, specifically induced Tcell proliferation in this case. Collectively, our case suggests that clinicians can utilize LTT to identify the causative medication of DiHS/DRESS when the clinical information is limited to defining the culprit drug.

Impact of Adjuvant Hormone Therapy on Sleep, Physical Activity, and Quality of Life in Premenopausal Breast Cancer: 12-Month Observational Study / 한국유방암학회지

Purpose@#This study aimed to investigate the differences in sleep disturbance changes between patients receiving two hormone therapies (“tamoxifen plus ovarian function suppression group [T+OFS group]” versus “tamoxifen group [T group]”) and the chronological changes in sleep disturbances in each group. @*Methods@#Premenopausal women with unilateral breast cancer who underwent surgery and were scheduled to receive hormone therapy (HT) with tamoxifen alone or with tamoxifen plus gonadotropin-releasing hormone (GnRH) agonist for ovarian function suppression were included. The enrolled patients wore an actigraphy watch for two weeks and completed questionnaires (insomnia, sleep quality, physical activity [PA], and quality of life [QOL]) at five time points: immediately before HT and 2, 5, 8, and 11 months after HT. @*Results@#Among the 39 enrolled patients (21 and 18 patients in the T+OFS group and T group, respectively), 25 (17 and 8 patients in the T+OFS group and T group, respectively) were finally analyzed. There were no differences between the two groups in time-dependent changes in insomnia, sleep quality, total sleep time, rapid eye movement sleep rate, QOL, and PA;however, the severity of hot flashes was significantly higher in the T+OFS group than in the T group. Although the interaction between group and time was not significant, insomnia and sleep quality significantly worsened at 2–5 months of HT when changes over time were analyzed within the T+OFS group. In both the groups, PA and QOL were maintained without significant changes. @*Conclusion@#Unlike tamoxifen alone, tamoxifen plus GnRH agonist initially worsened insomnia and sleep quality, but gradually improved with long-term follow-up. Patients who initially experience insomnia during tamoxifen plus GnRH agonist administration can be reassured based on the results of this study, and active supportive care may be used during this period.

Association of Moderate Hypothermia at Admission with Short-Term and Long-Term Outcomes in Extremely Low Birth Weight Infants

Purpose@#Extremely low birth weight (ELBW) infants exhibit immature thermoregulation and are easily exposed to hypothermia. We investigated the association between hypothermia on admission with short- and long-term outcomes. @*Methods@#Medical records of ELBW infants admitted to the neonatal intensive care unit of a tertiary medical center between June 2012 and February 2017 were retrospectively analyzed. Upon admission, the axillary body temperature was measured. Moderate hypothermia was defined as admission temperature below 36 ℃. @*Results@#A total of 208 infants with gestational age of 26.4±2.3 weeks and birth weight of 746.7±154.9 g were included. Admission temperature ranged from 33.5 to 36.8 ℃ (median 36.1 ℃). Univariate analyses of maternal and infant characteristics were performed for moderately hypothermic and control (normothermic to mildly hypothermic) infants. Lower gestational age, lower birth weight, and vaginal delivery correlated with moderate hypothermia. Logistic regression analyses adjusted for confounders revealed that the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) was associated with moderate hypothermia in ELBW infants. Moreover, abnormal mental developmental index scores on the Bayley Scales of Infant Development II at a corrected age of 18 to 24 months were associated with moderate hypothermia, but not with the psychomotor developmental index, incidence of blindness, deafness, or cerebral palsy. @*Conclusion@#Moderate hypothermia at admission is not only correlated with short-term neonatal morbidities such as hsPDA, but may also be associated with long-term neurodevelopmental impairment in ELBW infants. Future large-scale studies are required to clarify the long-term consequences of hypothermia upon admission.

Radiologic features of hepatocellular carcinoma related to prognosis

The cross-sectional imaging findings play a crucial role in the diagnosis of hepatocellular carcinoma (HCC). Recent studies have shown that imaging findings of HCC are not only relevant for the diagnosis of HCC, but also for identifying genetic and pathologic characteristics and determining prognosis. Imaging findings such as rim arterial phase hyperenhancement, arterial phase peritumoral hyperenhancement, hepatobiliary phase peritumoral hypointensity, non-smooth tumor margin, low apparent diffusion coefficient, and the LR-M category of the Liver Imaging-Reporting and Data System have been reported to be associated with poor prognosis. In contrast, imaging findings such as enhancing capsule appearance, hepatobiliary phase hyperintensity, and fat in mass have been reported to be associated with a favorable prognosis. Most of these imaging findings were examined in retrospective, single-center studies that were not adequately validated. However, the imaging findings can be applied for deciding the treatment strategy for HCC, if their significance can be confirmed by a large multicenter study. In this literature, we would like to review imaging findings related to the prognosis of HCC as well as their associated clinicopathological characteristics.

Atypical May-Thurner Syndrome Caused by Bone Spur of the L4∼5 Lumbar Vertebrae

May–Thurner syndrome (MTS) is a condition in which the left common iliac vein is irritated by chronic pulsatile compression between the right common iliac artery and the upper iliac or lumbar spine. It mainly causes swelling and pain in the left lower extremity, venous thrombosis, and repeated deep venous thrombosis. In patients with sudden swelling and pain in the left lower extremity and suspected lower extremity thrombosis, when no other obvious cause can be found, the possibility of MTS should be considered. We experienced a rare case of an older patient with atypical MTS caused by bone spur of the 4th and 5th lumbar vertebrae, which has been reported here along with a review of the literature.

Maternal Experiences of Anger While Raising a Child

Purpose@#This study aims to explore mothers’ experiences of anger while raising a child in South Korea based on a qualitative descriptive approach. @*Methods@#A total of ten mothers of children aged 1-3 years participated in the study. In-depth individual interviews were conducted from August to September 2019 to collect data, which were then subjected to thematic analysis. @*Results@#A total of 4 main themes and 10 subthemes were identified. The 4 themes were “individual and environmental factors that influence anger,” “a vicious cycle of anger expression and guilt,” “being a little bit more mature as a mother,” and “need for anger management.” This study described various causes, ways of expressing, and effects of anger, as well as the mother’s coping strategies. These experiences were viewed as milestones along the journey to becoming a real parent and helped mothers develop empathy for other children and mothers. The participants expressed support for expanding the social support system for child-rearing and providing psychological programs for mothers. @*Conclusion@#Mothers of children aged 1-3 years experienced anger owing to various factors, but adapted by developing coping skills. This study recommends family-based support interventions to help mothers manage their emotions and parenting roles.

Risk factors associated with death due to severe fever with thrombocytopenia syndrome in hospitalized Korean patients (2018–2022)

Objectives@#Severe fever with thrombocytopenia syndrome (SFTS) has no vaccine or treatment and an extremely high fatality rate. We aimed to analyze and evaluate the risk factors for death associated with SFTS. @*Methods@#Among reports from 2018 to 2022, we compared and analyzed 1,034 inpatients aged 18 years or older with laboratory-confirmed SFTS who underwent complete epidemiological investigations. @*Results@#Most of the inpatients with SFTS were aged 50 years or older (average age, 67.6 years). The median time from symptom onset to death was 9 days, and the average case fatality rate was 18.5%. Risk factors for death included age of 70 years or older (odds ratio [OR], 4.82); agriculture-related occupation (OR, 2.01); underlying disease (OR, 7.20); delayed diagnosis (OR, 1.28 per day); decreased level of consciousness (OR, 5.53); fever/chills (OR, 20.52); prolonged activated partial thromboplastin time (OR, 4.19); and elevated levels of aspartate aminotransferase (OR, 2.91), blood urea nitrogen (OR, 2.62), and creatine (OR, 3.21). @*Conclusion@#The risk factors for death in patients with SFTS were old age; agriculture-related occupation; underlying disease; delayed clinical suspicion; fever/chills; decreased level of consciousness; and elevated activated partial thromboplastin time, aspartate aminotransferase, blood urea nitrogen, and creatine levels.

Incidence of and Influencing Factors for Arm Lymphedema After Salvage Treatment for an Isolated Locoregional Recurrence of Breast Cancer / 한국유방암학회지

Purpose@#Data on subsequent arm lymphedema (SAL) after salvage treatment for locoregional recurrence (LRR) of breast cancer are limited. We conducted a study to evaluate the risk of SAL in patients with LRR. @*Methods@#We reviewed the data of patients with breast cancer who had LRR and were initially diagnosed between January 2003 and December 2017. Among the 214 patients who received curative salvage treatment, most had local (n = 125, 57.9%), followed by regional (n = 73, 34.1%), and locoregional (n = 16, 7.9%) recurrences. A competing risk analysis considering the factors of death and a second LRR were performed to exclude potential malignant lymphedema. We used the Fine-Gray subdistribution hazards model to estimate the hazard ratio (HR) for comparing the risk of SAL. @*Results@#With a median follow-up duration of 41.4 months (interquartile range, 25.6–65.1), 51 patients (23.8%) experienced SAL with a median interval of 9.9 months after treatment.The two-year cumulative incidence of SAL was 12.7%. Among the 18 patients with initial lymphedema, nine (50.0%) developed SAL. Multivariate analysis revealed that a history of lymphedema (HR, 4.61; p < 0.001) and taxane-based salvage chemotherapy (HR, 2.38; p = 0.009) were significantly associated with SAL development. @*Conclusion@#Salvage treatment for LRR-induced SAL was performed in 24% of the patients.A history of initial lymphedema and salvage taxane-based chemotherapy increases the risk of developing SAL. Therefore, close surveillance for the incidence of SAL is required in patients opting for salvage treatment for LRR.

Regional Comparison of Imaging Biomarkers in the Striatum between Early- and Late-onset Alzheimer’s Disease

Striatal changes in the pathogenesis of Alzheimer’s disease (AD) is not fully understood yet. We compared structural and functional image differences in the striatum between patients with early onset AD (EOAD) and late onset AD (LOAD) to investigate whether EOAD harbors autosomal dominant AD like imaging findings. The clinical, neuropsychological and neuroimaging biomarkers of 77 probable AD patients and 107 elderly subjects with normal cognition (NC) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI)-2 dataset were analyzed. Enrolled each subject completed a 3-Tesla MRI, baseline 18F-FDG-PET, and baseline 18F-AV-45 (Florbetapir) amyloid PET studies. AD patients were divided into two groups based on the onset age of clinical symptoms (EOAD <65 yrs; LOAD ≥65 yrs). A standardized uptake value ratio of the striatum and subcortical structures was obtained from both amyloid and FDG-PET scans. Structural MR imaging analysis was conducted using a parametric boundary description protocol, SPHARM-PDM. Of the 77 AD patients, 18 were EOAD and 59 were LOAD. Except for age of symptom onset, there were no statistically significant differences between the groups in demographics and detailed neuropsychological test results. 18F-AV-45 amyloid PET showed marked β-amyloid accumulation in the bilateral caudate nucleus and left pallidum in the EOAD group. Intriguingly, the caudate nucleus and putamen showed maintained glucose metabolism in the EOAD group compared to the LOAD group. Our image findings in the striatum of EOAD patients suggest that sporadic EOAD may share some pathophysiological changes noted in autosomal dominant AD.

Assessment of Sleep Quality of Infants and Their Mothers Using Actigraphy

Objectives@#The purpose of this study was to explore and evaluate the characteristics and quality of infant and maternal sleep (total sleep time, sleep efficiency, and wakefulness after sleep onset) using an actigraph. @*Methods@#The characteristics and quality of sleep were assessed in 22 dyads of mothers and infants aged 3–12 months. The quality of infant and mother sleep was collected using an actigraph for 12 consecutive days; this was repeated three times at 4-week intervals, and characteristics of infant sleep were measured using the Brief Infant Sleep Questionnaire-Revised. @*Results@#Bedsharing with infants at 7–12 months of age was higher (12.5%) than with those at 3–6 months of age (50.0%). Regarding the sleeping position, half of the infants aged 3–6 months adopted the lateral (25.0%) and prone (25.0%) positions, and the remaining half (50.0%) aged 7–12 months adopted the lateral position. It was found that 45.5% of mothers of infants used breastfeeding and pacifiers to induce sleep in infants and to help their babies go back to sleep when they woke up. The total sleep time and sleep efficiency of infants and mothers were 434.68 minutes per day and 73.1% and 379.53 minutes per day and 82.8%, respectively, indicating that both infants and mothers had low sleep quality. @*Conclusions@#To safeguard infants’ sleep, it is necessary to provide appropriate information and education to parents and necessary interventions for resolving sleep problems and improving the quality of sleep for both infants and mothers.

Effectiveness of Hepatocellular Carcinoma Surveillance and an Optimal Surveillance Interval:Nationwide Cohort of Korea

Purpose@#To assess associations between surveillance intervals in a national hepatocellular carcinoma (HCC) surveillance program and receiving curative treatment and mortality using nationwide cohort data for Korea. @*Materials and Methods@#Using the National Health Insurance Service Database of Korea, we retrospectively identified 3201852 patients, the target population of the national HCC surveillance program, between 2008 and 2017. After exclusion, a total of 64674 HCC patients were divided based on surveillance intervals: never screened, ≤6 months (6M), 7–12 months (1Y), 13–24 months (2Y), and 25–36 months (3Y). Associations for surveillance interval with the chance to receive curative therapy and all-cause mortality were analyzed. @*Results@#The 6M group (51.9%) received curative therapy more often than the other groups (1Y, 48.3%; 2Y, 43.8%; 3Y, 41.3%; never screened, 34.5%). Odds ratio for receiving curative therapy among the other surveillance interval groups (1Y, 0.87; 2Y, 0.76; 3Y, 0.77;never screened, 0.57; p<0.001) were significantly lower than that of the 6M group. The hazard ratios (HRs) of all-cause mortality were 1.07, 1.14, and 1.37 for 2Y, 3Y, and never screened groups. The HR for the 1Y group (0.96; p=0.092) was not significantly different, and it was lower (0.91; p<0.001) than that of the 6M group after adjustment for lead-time bias. Curative therapy was associated with survival benefits (HR, 0.26; p<0.001). @*Conclusion@#HCC surveillance, especially at a surveillance interval of 6 months, increases the chance to receive curative therapy.

Survival and Morbidities in Infants with Birth Weight Less than 500 g:a Nationwide Cohort Study

Background@#This study aimed to investigate the survival and morbidities of infants in the Korean Neonatal Network (KNN) with birth weight (BW) < 500 g. @*Methods@#The demographic and clinical data of 208 live-born infants with a BW < 500 g at a gestational age of ≥ 22 weeks who were treated in the neonatal intensive care units of the KNN between 2013 and 2017 were reviewed. @*Results@#The survival rate of the infants was 28%, with a median gestational age and BW of 24 3/7 weeks (range, 22 0/7 –33 6/7 ) and 440 g (range, 220–499), respectively. Multivariable Cox proportional hazards analysis demonstrated that survival to discharge was associated with longer gestation, higher BW, female sex, singleton gestation, use of any antenatal corticosteroids, and higher Apgar scores at 5 minutes. The overall survival rates were significantly different between the BW categories of < 400 g and 400–499 g. However, there was no significant difference in the incidence of any morbidity between the BW groups.Half of the deaths of infants with BW < 500 g occurred within a week of life, mainly due to cardiopulmonary and neurologic causes. The major causes of death in infants after 1 week of age were infection and gastrointestinal disease. Among the surviving infants, 79% had moderate to severe bronchopulmonary dysplasia, 21% underwent surgical ligation of patent ductus arteriosus, 12% had severe intraventricular hemorrhage (grade III–IV), 38% had sepsis, 9% had necrotizing enterocolitis (stage ≥ 2), and 47% underwent laser treatment for retinopathy of prematurity. The median length of hospital stay was 132 days (range, 69–291), and 53% required assistive devices at discharge. @*Conclusion@#Despite recent advances in neonatal intensive care, the survival and morbidity rates of infants with BW < 500 g need further improvement.

Radiologic Evaluation for Resectability of Pancreatic Adenocarcinoma

Imaging studies play an important role in the detection, diagnosis, assessment of resectability, staging, and determination of patient-tailored treatment options for pancreatic adenocarcinoma. Recently, for patients diagnosed with borderline resectable or locally advanced pancreatic cancers, it is recommended to consider curative-intent surgery following neoadjuvant or palliative therapy, if possible. This review covers how to interpret imaging tests and what to consider when assessing resectability, diagnosing distant metastasis, and re-assessing the resectability of pancreatic cancer after neoadjuvant or palliative therapy.

Effectiveness of Hepatocellular Carcinoma Surveillance and an Optimal Surveillance Interval:Nationwide Cohort of Korea

Purpose@#To assess associations between surveillance intervals in a national hepatocellular carcinoma (HCC) surveillance program and receiving curative treatment and mortality using nationwide cohort data for Korea. @*Materials and Methods@#Using the National Health Insurance Service Database of Korea, we retrospectively identified 3201852 patients, the target population of the national HCC surveillance program, between 2008 and 2017. After exclusion, a total of 64674 HCC patients were divided based on surveillance intervals: never screened, ≤6 months (6M), 7–12 months (1Y), 13–24 months (2Y), and 25–36 months (3Y). Associations for surveillance interval with the chance to receive curative therapy and all-cause mortality were analyzed. @*Results@#The 6M group (51.9%) received curative therapy more often than the other groups (1Y, 48.3%; 2Y, 43.8%; 3Y, 41.3%; never screened, 34.5%). Odds ratio for receiving curative therapy among the other surveillance interval groups (1Y, 0.87; 2Y, 0.76; 3Y, 0.77;never screened, 0.57; p<0.001) were significantly lower than that of the 6M group. The hazard ratios (HRs) of all-cause mortality were 1.07, 1.14, and 1.37 for 2Y, 3Y, and never screened groups. The HR for the 1Y group (0.96; p=0.092) was not significantly different, and it was lower (0.91; p<0.001) than that of the 6M group after adjustment for lead-time bias. Curative therapy was associated with survival benefits (HR, 0.26; p<0.001). @*Conclusion@#HCC surveillance, especially at a surveillance interval of 6 months, increases the chance to receive curative therapy.

Survival and Morbidities in Infants with Birth Weight Less than 500 g:a Nationwide Cohort Study

Background@#This study aimed to investigate the survival and morbidities of infants in the Korean Neonatal Network (KNN) with birth weight (BW) < 500 g. @*Methods@#The demographic and clinical data of 208 live-born infants with a BW < 500 g at a gestational age of ≥ 22 weeks who were treated in the neonatal intensive care units of the KNN between 2013 and 2017 were reviewed. @*Results@#The survival rate of the infants was 28%, with a median gestational age and BW of 24 3/7 weeks (range, 22 0/7 –33 6/7 ) and 440 g (range, 220–499), respectively. Multivariable Cox proportional hazards analysis demonstrated that survival to discharge was associated with longer gestation, higher BW, female sex, singleton gestation, use of any antenatal corticosteroids, and higher Apgar scores at 5 minutes. The overall survival rates were significantly different between the BW categories of < 400 g and 400–499 g. However, there was no significant difference in the incidence of any morbidity between the BW groups.Half of the deaths of infants with BW < 500 g occurred within a week of life, mainly due to cardiopulmonary and neurologic causes. The major causes of death in infants after 1 week of age were infection and gastrointestinal disease. Among the surviving infants, 79% had moderate to severe bronchopulmonary dysplasia, 21% underwent surgical ligation of patent ductus arteriosus, 12% had severe intraventricular hemorrhage (grade III–IV), 38% had sepsis, 9% had necrotizing enterocolitis (stage ≥ 2), and 47% underwent laser treatment for retinopathy of prematurity. The median length of hospital stay was 132 days (range, 69–291), and 53% required assistive devices at discharge. @*Conclusion@#Despite recent advances in neonatal intensive care, the survival and morbidity rates of infants with BW < 500 g need further improvement.

Rare Disease Entity of Dorsolateral Foot Pain:Lateral Branch of Deep Peroneal Nerve Entrapment Syndrome

When a patient represents pain in foot, physician can easily overlook compression neuropathy of peripheral nerve as it is uncommon. Among nerve entrapment syndrome encountered in the foot, selective compression in lateral branch of deep peroneal nerve (DPN) is rare. We report a case of a patient with pain and dysesthesia in dorsolateral foot which turned out as lateral branch of deep peroneal nerve entrapment syndrome caused by talonavicular joint effusion. We would like to share diagnostic work up flow and conservative treatment courses. This case manifests the importance of the deep peroneal nerve and its branches in clinical setting of pain and ankle instability.

Radiologic Evaluation for Resectability of Pancreatic Adenocarcinoma

Imaging studies play an important role in the detection, diagnosis, assessment of resectability, staging, and determination of patient-tailored treatment options for pancreatic adenocarcinoma. Recently, for patients diagnosed with borderline resectable or locally advanced pancreatic cancers, it is recommended to consider curative-intent surgery following neoadjuvant or palliative therapy, if possible. This review covers how to interpret imaging tests and what to consider when assessing resectability, diagnosing distant metastasis, and re-assessing the resectability of pancreatic cancer after neoadjuvant or palliative therapy.

A Case of Trisomy 9 Mosaicism Confirmed by Microarray Test / 고신대학교의과대학학술지

Trisomy 9 mosaicism syndrome is a rare chromosomal abnormality with a high incidence of natural abortion and perinatal death. This syndrome is characterized by intrauterine growth retardation, mental retardation, craniofacial dysmorphism including a prominent nasal bridge with a short root and a fish-shaped mouth with thin lips, skeletal abnormalities, congenital heart defects, and genital abnormalities. The incidence and severity of malformations depend on the percentage of trisomic cells in the different tissues. We report a neonate who had the characteristic features of trisomy 9 syndrome with dysmorphic features including micrognathia, microcephaly, a low-set and malformed ear, a prominent lip, and cardiac defect. No chromosomal abnormalities were detected on a routine peripheral blood chromosomal analysis; however, a chromosomal abnormality with trisomy 9 mosaicism (low-level mosaic type) was detected on genetic tests. This is thought to be due to the low proportion of trisomic cells, and for this reason, the patient in this case shows a better prognosis than four patients previously reported in Korea, they were all diagnosed by peripheral blood chromosome testing.

Tryptophanyl-tRNA Synthetase Sensitizes Hormone Receptor-Positive Breast Cancer to Docetaxel-Based Chemotherapy / 한국유방암학회지

Purpose@#A relatively low response to chemotherapy has been reported for hormone receptor (HR)-positive breast cancer. In this study, we investigated the role of tryptophanyl-transfer RNA synthetase (WARS) in the chemotherapeutic response of HR-positive breast cancer. @*Methods@#Pre-chemotherapeutic needle biopsy samples of 45 HR-positive breast cancer patients undergoing the same chemotherapeutic regimen were subjected to immunohistochemistry. To investigate the biological functions of WARS in HR-positive breast cancer, we conducted cell viability assay, flow cytometry analysis, caspase activity assay, Quantitative real-time polymerase chain reaction, and western blotting using WARS gene-modulated HR-positive breast cancer cells (T47D, ZR-75-1, and MCF7). @*Results@#WARS overexpression in HR-positive breast cancer patients showed a significant correlation with favorable chemotherapy response. Downregulation of WARS increased cell viability following docetaxel treatment in tumor cell lines. On the other hand, WARS overexpression sensitized the therapeutic response to docetaxel. Additionally, downregulation of WARS caused a decrease in the number of apoptotic cell populations by docetaxel. Poly (ADP-ribose) polymerase cleavage and caspase 3/7 activity were increased in docetaxel-treated tumor cells with WARS overexpression. @*Conclusion@#Our results suggest that WARS might be a potential predictor for chemotherapy response in patients with HR-positive breast cancer as well as a novel molecular target to improve chemosensitivity.

Ethanol extracts of Hizikia fusiforme induce apoptosis in human prostate cancer PC3 cells via modulating a ROS-dependent pathway

Objective: To investigate whether ethanol extracts of Hizikia fusiforme could induce apoptosis in human prostate cancer PC3 cells.Methods: Cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Apoptosis and mitochondrial membrane potential (MMP) were measured using flow cytometry in PC3 cells. DNA damage was assessed by nuclear staining and DNA fragmentation assay. Expressions of apoptosis-associated proteins were determined by Western blotting assays. Activities of caspase-3, -8, and -9 were determined by colorimetric assay. Moreover, intracellular reactive oxygen species (ROS) generation was detected using a flow cytometer and fluorescence microscope. Results: Treatment of PC3 cells with ethanol extracts of Hizikia fusiforme inhibited proliferation, which was associated with induction of apoptosis, and accompanied by increased expression of Fas, Fas-ligand (FasL), Bax and tBid, and decreased expression of Bcl-2. In addition, ethanol extracts of Hizikia fusiforme reduced c-Flip expression and activated caspase-8, -9 and -3, resulting in an increase in poly (ADP-ribose) polymerase (PARP)cleavage. However, in the presence of a pan-caspase inhibitor, ethanol extracts of Hizikia fusiforme-mediated growth inhibition and apoptosis were significantly attenuated. Ethanol extracts of Hizikia fusiforme also destroyed the integrity of mitochondria due to the loss of MMP, leading to cytosolic release of cytochrome c. Moreover, the levels of ROS were markedly increased by treatment with ethanol extracts of Hizikia fusiforme, which was significantly suppressed by the ROS scavenger N-acetyl-L-cysteine. Further investigation of whether ethanol extracts of Hizikia fusiforme-induced apoptosis was related to the generation of ROS was conducted and the results showed that N-acetyl-L-cysteine fully blocked ethanol extracts of Hizikia fusiforme-induced apoptotic events including loss of MMP, activation of caspase-3, the cytosolic release of cytochrome c and cytotoxicity.Conclusions: Ethanol extracts of Hizikia fusiforme have chemopreventive potential via induction of ROS-dependent apoptosis. Therefore, ethanol extracts of Hizikia fusiforme may be useful for developing effective and selective natural sources to inhibit cancer cell proliferation.