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Purpose@#This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). @*Materials and Methods@#Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). @*Results@#In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. @*Conclusion@#Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.
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Purpose@#We investigated the effects of economic status (classified based on insurance type and residential area) on oncological outcomes of prostate cancer using a nationwide database. We additionally investigated oncological outcomes based on economic status and residential area in patients who underwent surgical treatment. @*Materials and Methods@#The study included 75,518 men with newly diagnosed prostate cancer between 2009 and 2018 in whom oncological outcomes were investigated based on economic status and residential area. Among the 75,518 men with prostate cancer, the data of 29,973 men who underwent radical prostatectomy were further analyzed. Multivariate analysis was performed to determine the effects of economic status and residential area on postoperative oncological outcomes. @*Results@#Among the 75,518 patients with prostate cancer, 3,254 (4.31%) were medical aid beneficiaries. The 5-year overall survival rates were 81.2% and 64.8% in the health insurance and medical aid groups, respectively. Radical prostatectomy was more common in the health insurance group, and surgical intervention was significantly affected by the residential area. Among patients who underwent surgery, 5-year androgen deprivation therapy–free and overall survival were better in the health insurance group. Multivariate analysis showed that insurance type and residential area were significantly associated with the androgen deprivation therapy–free and overall survival after adjustment for other variables. @*Conclusion@#Economic status and residential area were shown to affect not only treatment patterns but also post-diagnosis and postoperative oncological outcomes. Political support for early diagnosis and appropriate treatment of prostate cancer is warranted for medically vulnerable populations.
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Purpose@#This study was conducted to investigate the clinical characteristics of patients with advanced non–small cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) mutations and to evaluate response to standard treatment and HER2-targeted agents. @*Materials and Methods@#Using tissue and/or blood next-generation sequencing, we identified 44 patients with NSCLC harboring HER2 mutations who were treated at Severance Hospital between December 2016 and February 2021. Clinical data, including patient characteristics, mutation status, incidence of metastasis for distant lesions, and response to chemotherapy, were retrospectively analyzed. @*Results@#The median age was 58 years, and 61% of the patients were female. Most patients (64%) were never-smokers. Adenocarcinoma was the most predominant subtype (98%). A total of 66% of the patients had extrathoracic metastatic lesions, and 32% had intracranial lesions at initial presentation. The median time to the development of brain metastasis was 15.6 months (range, 2.4 to 43.7). The most common type of HER2 mutation was 12 base pair in-frame insertion in exon 20, A775_G776insYVMA. Of the 44 patients, two had concomitant driver mutations, one with epidermal growth factor receptor (EGFR) mutation (V769M), and one with BRAF mutation (V600E). Patients treated with pemetrexed-based chemotherapy (75%) had an overall response rate (ORR) and progression-free survival (PFS) of 30% and 8.3 months (95% confidence interval [CI], 3.9 to 12.7), respectively. The ORR and PFS of HER2-targeted agent treated patients (14%) were 0.0% and 1.9 months (95% CI, 0.1 to 2.8), respectively. @*Conclusion@#Given its distinct characteristics and treatment responses, novel treatment strategies for HER2-mutant NSCLC should be developed promptly to improve survival outcomes of patients.
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Purpose@#We aimed to identify the risk factors for salvage procedure (SP) required for refractory adenomatous tissue resistant to morcellation during holmium laser enucleation of the prostate (HoLEP). @*Methods@#Patients who underwent HoLEP between January 2010 and April 2020 at Seoul National University Hospital were analyzed. SPs were defined as cases of conversion to resection of the prostatic tissue using an electrosurgical loop after morcellation or secondary morcellation a few days after surgery or conversion to open cystotomy. @*Results@#Among a total of 2,427 patients, 260 were identified as having SP (SP group) (transurethral resection-nodule [n = 250, 96.1%], secondary morcellation a few days after surgery [n = 9, 3.5%], and conversion to open cystotomy [n = 1, 0.4%]). Patients in the SP group were older and had higher 5-α reductase inhibitors use, higher prostate-specific antigen, larger total prostate volume, and larger transition zone volume (TZV) than those in the non-SP group. In the multivariable logistic regression analysis, only age and TZV were associated with SP. Compared to 40s and 50s, the odds ratios (ORs) were 3.84 in 60s (95% confidence interval [CI] 1.37–10.78, P = 0.011), 4.53 in 70s (95% CI, 1.62–12.62, P = 0.004), and 6.59 in 80s or older (95% CI, 2.23–19.46, P = 0.001). The ORs of the SP were analyzed per TZV quartile. Compared to TZV ≤ 20.3 mL, the OR was 3.75 in 32.0 mL 60 years or those with TZV > 32 mL. In order to more efficiently remove these resistant adenomas, it is necessary to develop more efficient morcellators in the future.
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Bovine viral diarrhea virus (BVDV), which is prevalent worldwide, is one of the most important viral pathogens and causes substantial economic loss to the livestock industry. Despite its importance, BVDV is largely unnoticed in the Republic of Korea (ROK). In this study, we report the case of a steer with BVDV that died suddenly due to severe enteritis. Two 1-year-old Korean indigenous cattle in the same herd presented severe hemorrhagic diarrhea. Case 1 had severe dehydration and died after 3 days, whereas case 2 had anorexia, depression, and severe diarrhea with mucus and blood. Only case 2 was necropsied, and BVDV2a was detected in the tissues of its alimentary tract. Gross lesions, including erosion, ulceration, and extensive hemorrhage, were observed in the digestive tract mucosa. Immunohistochemistry revealed marked positive staining for BVDV2a antigen in the large intestine. This report describes the first case of hemorrhagic disease caused by acute BVDV2a infection, which is characterized by high mortality in Korean indigenous cattle. This study will help establish vaccination and control strategies for BVDV in the ROK.
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Purpose@#Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non–small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial. @*Materials and Methods@#Key efficacy endpoints were blinded independent review committee (BIRC)–assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events. @*Results@#At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively. @*Conclusion@#Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.
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Background/Aims@#The prognostic value of a comprehensive geriatric assessment (CGA) for the management of older small cell lung cancer (SCLC) patients remains to be established. @*Methods@#A retrospective cohort enrolled 21 SCLC patients over 65 years from March 2018 to 2019 at the Yonsei Cancer Center. The CGA included the following instruments: frailty, body mass index, sarcopenia (circumference of arm and calf, Timed Up and Go test, grip strength), comorbidity, polypharmacy, activities of daily living (ADL), Instrumental ADL, nutrition, depression, and cognitive function. The correlations of oncological and geriatric variables with overall survival (OS) were determined. The log-rank test with Cox model and Kaplan-Meier method were used for the analysis. @*Results@#The median age was 75 years (range, 67 to 85). All patients had the Eastern Cooperative Oncology Group performance status 0–2. The median survival was 9.93 months (range, 1.53 to 36.30). Among CGA parameters, ADL and nutritional status had significant differences in OS in univariate analysis. In multivariate analysis, only nutritional status was independently associated with survival (hazard ratio, 0.17; 95% confidence interval, 0.05 to 0.57). Median OS for low nutritional status was 5.63 months and the normal nutrition group was 15.5 months (p = 0.004). @*Conclusions@#Pre-treatment nutritional status measured by CGA appears to be a predictor of OS in older SCLC patients. However, for further generalization of the implication of CGA in SCLC, a larger scale study with prospective design is strongly needed.
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Cancer-associated fibroblasts (CAFs) represent a major component of the tumor microenvironment and interplay with cancer cells by secreting cytokines, growth factors and extracellular matrix proteins. When estrogen receptor-negative breast cancer MDAMB-231 cells were treated with the CAF-conditioned medium (CAF-CM), Akt and STAT3 involved in cell proliferation and survival were activated through phosphorylation. CAFs secrete fibroblast growth factor 2 (FGF2), thereby stimulating breast cancer cell progression. Akt activation induced by CAF-CM in MDA-MB-231 cells was abolished when FGF2-neutralizing antibody was added.Treatment of MDA-MB-231 cells directly with FGF2 enhanced the phosphorylation of Akt and the FGF receptor (FGFR) substrate, FRS2α. These events were abrogated by siRNA-mediated silencing of FGFR1. In a xenograft mouse model, co-injection of MDAMB-231 cells with activated fibroblasts expressing FGF2 dramatically enhanced activation of Akt. Stable knockdown of FGFR1 blunted Akt phosphorylation in xenograft tumors. MDA-MB-231 cells co-cultured with CAFs or directly stimulated with FGF2 exhibited enhanced nuclear localization of FGFR1. Notably, FGF2 stimulation produced reactive oxygen species (ROS) accumulation in MDA-MB-231 cells, and FGF2-induced nuclear accumulation of FGFR1 was abrogated by the ROS scavenging agent, N-acetylcysteine.
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Spinal epidural arteriovenous fistula (SEDAVF) is a rare vascular malformation. Due to the mass effect of enlarged epidural veins and venous hypertension, progressive radiculopathy and myelopathy are likely to occur. A 33-year-old female presented with right upper extremity weakness for a month. The cause of this symptom was a SEDAVF, which was located near the C5-6-7 foramens and compressed the nerve roots. In the absence of intradural venous drainage, endovascular treatment is often difficult because of the large venous pouch. We performed endovascular trapping of the vertebral artery (VA) and loose packing of the coil material on the AVF to minimize mass effects. Immediately after embolization, the fistula was occluded, but a small new feeder vessel developed a day later. An n-butyl cyanoacrylate embolization was performed, and the fistula was successfully occluded.
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Background@#The purpose of this study was to classify the possible indications for a combined approach to distal radius fractures (DRFs) by investigating surgical outcomes of patients treated according to our treatment algorithm. @*Methods@#A combined approach was performed in 32 patients. Patients who were thought to need a combined approach were classified into three types according to the combined injuries associated with loss of volar cortical buttresses in DRFs. The classifications included the following: type 1, free intra-articular fragments; type 2, distally migrated dorsal fragments located beyond the wrist joint; and type 3, centrally impacted articular fragments and displaced dorsal fragments, not reduced by indirect methods. @*Results@#Seven patients had type 1 fractures treated with volar plates and excision of the intra-articular fragments. Fourteen patients had type 2 fractures: 12 were treated with volar plates and excision of dorsal fragments, and 2 with relatively large unstable dorsal fragments were treated with combined volar and dorsal plates. The remaining 11 patients had type 3 fractures treated with combined volar and dorsal plates. At the latest follow-up, the radiographs revealed an average of 16.9° of radial inclination, an average of 4.2° of volar tilt, and an average of 7.5 mm of radial height. According to the Garland and Werley scores, the functional results were excellent for 3 patients, good for 25, and fair for 4. @*Conclusions@#The classification system indicated when an additional dorsal approach was needed in unstable DRFs, and it may establish useful guidelines for appropriate surgical decision-making.
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Objective@#The purpose of this study was to investigate the status of bone health in women working in agriculture and analyze the associations between bone health and various vitamin D-related biomarkers. @*Methods@#This observational study enrolled women working in agriculture (n = 210) and control occupations (n = 180). The concentration of serum total 25-hydroxy vitamin D [25(OH)D] was measured using the Elecsys Vitamin D Total Kit, and serum vitamin D-binding protein (VDBP) was measured by enzyme-linked immunosorbent assay (ELISA). Along with albumin, 25(OH)D and VDBP were used to calculate the concentrations of bioavailable and free 25(OH)D. Bone mineral density (BMD) and T-score were measured at lumbar 1–4 and the femur neck using dual-energy X-ray absorptiometry. To identify factors affecting BMD, log-linear model and linear regression analysis were performed for statistical analysis. @*Results@#Agricultural women workers showed higher serum concentrations of bioavailable 25(OH)D (12.8 ± 3.7 vs. 8.7 ± 5.1 ng/mL) and lower VDBP concentrations (201.8 ± 45.0 vs. 216.0 ± 68.2 μg/ mL) than control women. The association between these two vitamin D related-biomarkers and femur neck BMD were confirmed through univariable and multivariable linear model analysis. Although lumbar BMD did not differ between groups, the agricultural group displayed a lower femur BMD and a 4.3-fold increase in the risk of osteoporosis compared with the control group. @*Conclusions@#Women working in agriculture showed lower femur BMD than the control group. Of the vitamin D-related biomarkers tested, bioavailable 25(OH)D and VDBP were associated with BMD. As bioavailable 25(OH)D levels are affected mainly by VDBP levels, VDBP may play a role in the lower femur neck BMD values observed in the agricultural group. Thus, the measurement of VDBP concentration might be considered a simple and non-invasive method for measuring bone health status.
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This study evaluated the test-retest repeatability and measurement variability of ultrasonographic shear wave elastography (SWE) for liver stiffness in a rat liver fibrosis model. Methods: In 31 Sprague-Dawley rats divided into three groups (high-dose, low-dose, and control), liver fibrosis was induced by intraperitoneal administration of thioacetamide for 8 weeks. A dedicated radiographer performed SWE to measure liver stiffness in kilopascals in two sessions at a 3-day interval. We calculated correlations between liver stiffness and histopathologic results, measurement variability in each session using coefficients of variation (CoVs) and interquartile/median (IQR/M), and test-retest repeatability between both sessions using the repeatability coefficient. Results: Different levels of liver fibrosis in each group were successfully induced in the animal model. The mean liver stiffness values were 8.88±1.48 kPa in the control group, 11.62±1.70 kPa in the low-dose group, and 11.91±1.73 kPa in the high-dose group. The correlation between collagen areas and liver stiffness values was moderate (r=0.6). In all groups, the second session yielded lower CoVs (i.e., more reliable results) for liver stiffness than the first session, suggesting a training effect for the operator. The mean IQR/M values were also lower in the second session than in the first session, which had four outliers (0.21 vs. 0.12, P<0.001). The test-retest repeatability coefficient was 3.75 kPa and decreased to 2.82 kPa after removing the four outliers. Conclusion: The use of ultrasonographic SWE was confirmed to be feasible and repeatable for evaluating liver fibrosis in preclinical trials. Operator training might reduce variability in liver stiffness measurements.
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STAT3 plays a prominent role in proliferation and survival of tumor cells. Thus, STAT3 has been considered to be a prime target for development of anti-cancer therapeutics. The electrophilic cyclopentenone prostaglandin,15-deoxy-Δ12,14-prostaglandin J2(15d-PGJ2 ) has been well recognized for its capability to modulate intracellular signaling pathways involved in cancer cell growth and progression. We previously reported that 15d-PGJ2 had potent cytotoxicity against harvey-ras transformed human mammary epithelial cells through direct interaction with STAT3. In this study, we have attempted to verify the inhibitory effects of 15d-PGJ2 on STAT3 signaling in human breast tumor cells. The triple negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468 displaying constitutive phosphorylation of STAT3 on the tyrosine 705 (Tyr705) residue, underwent apoptosis upon inhibition of STAT3 by 15d-PGJ2 . In contrast, estrogen receptor positive MCF-7 breast cancer cells that do not exhibit elevated STAT3 phosphorylation were much less susceptible to 15d-PGJ2 -induced apoptosis as assessed by PARP cleavage. Furthermore, 15d-PGJ2 inhibited interleukin-6-induced tyrosine phosphorylation of STAT3 in LNCaP cells. According to molecular docking studies, 15d-PGJ2 may preferentially bind to the cysteine 259 residue (Cys259) present in the coiled-coil domain of STAT3. Site-directed mutagenesis of STAT3 identified Cys259 to be the critical amino acid for the 15d-PGJ2 -induced apoptosis as well as epithelial-to-mesenchymal transition. Taken together, these findings suggest STAT3 inactivation through direct chemical modification of its Cys259 as a potential therapeutic approach for treatment of triple negative breast cancer treatment.
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Objective@#: To compare the anterior cervical discectomy and fusion (ACDF) and posterior cervical fusion (PCF) with wide facetectomy in the treatment of parallel-shaped bony foraminal stenosis (FS). @*Methods@#: Thirty-six patients underwent surgery due to one-or-two levels of parallel-shaped cervical FS. ACDF was performed in 16 patients, and PCF using CPS was performed in 20 patients. All patients were followed up at 1, 3, 6, and 12 months postoperatively. Standardized outcome measures such as Numeric rating scale (NRS) score for armeck pain and Neck disability index (NDI) were evaluated. Cervical radiographs were used to compare the C2–7 Cobb’s angle, segmental angle, and fusion rates. @*Results@#: There was an improvement in NRS scores after both approaches for radicular arm pain (mean change -6.78 vs. -8.14, p=0.012), neck pain (mean change -1.67 vs. -4.36, p=0.038), and NDI score (-19.69 vs. -18.15, p=0.794). The segmental angle improvement was greater in the ACDF group than in the posterior group (9.4°±2.7° vs. 3.3°±5.1°, p=0.004). However, there was no significant difference in C2–7 Cobb angle between groups (16.2°±7.9° vs. 14.8°±8.5°, p=0.142). As a complication, dysphagia was observed in one case of the ACDF group. @*Conclusion@#: In the treatment of parallel-shaped bony FS up to two surgical levels, segmental angle improvement was more favorable in patients who underwent ACDF. However, PCF with wide facetectomy using CPS should be considered as an alternative treatment option in cases where the anterior approach is burdensome.
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Objective@#: Cerebrospinal fluid leakage related complications (CLC) occasionally occur after intradural spinal surgery. We sought to investigate the effectiveness of early ambulation after intradural spinal surgery and analyze the risk factors for CLC. @*Methods@#: For this retrospective cohort study, we enrolled 314 patients who underwent intradural spinal surgery at a single institution. The early group contained 79 patients who started ambulation after 1 day of bedrest without position restrictions, while the late group consisted of 235 patients who started ambulation after at least 3 days of bed rest and were limited to the prone position after surgery. In the early group, Prolene 6–0 was used as the dura suture material, while black silk 5–0 was used as the dura suture material in the late group. @*Results@#: The overall incidence rate of CLC was 10.8%. Significant differences between the early and late groups were identified in the rate of CLC (2.5% vs. 13.6%), surgical repair required (1.3% vs. 7.7%), and length of hospital stay (2.99 vs. 9.29 days) (p<0.05). Logistic regression analysis revealed that CLC was associated with practices specific to the late group (p=0.011) and the revision surgery (p=0.022). @*Conclusion@#: Using Prolene 6–0 as a dura suture material for intradural spinal surgery resulted in lower CLC rates compared to black silk 5–0 sutures despite a shorter bed rest period. Our findings revealed that suture - needle ratio related to dura defect was the most critical factor for CLC. One-day ambulation after primary dura closure using Prolene 6–0 sutures appears to be a cost-effective and safe strategy for intradural spinal surgery.
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Objective@#: The period of mechanical ventilator (MV)-dependent respiratory failure after cervical spinal cord injury (CSCI) varies from patient to patient. This study aimed to identify predictors of MV at hospital discharge (MVDC) due to prolonged respiratory failure among patients with MV after CSCI. @*Methods@#: Two hundred forty-three patients with CSCI were admitted to our institution between May 2006 and April 2018. Their medical records and radiographic data were retrospectively reviewed. Level and completeness of injury were defined according to the American Spinal Injury Association (ASIA) standards. Respiratory failure was defined as the requirement for definitive airway and assistance of MV. We also evaluated magnetic resonance imaging characteristics of the cervical spine. These characteristics included : maximum canal compromise (MCC); intramedullary hematoma or cord transection; and integrity of the disco-ligamentous complex for assessment of the Subaxial Cervical Spine Injury Classification (SLIC) scoring. The inclusion criteria were patients with CSCI who underwent decompression surgery within 48 hours after trauma with respiratory failure during hospital stay. Patients with Glasgow coma scale 12 or lower, major fatal trauma of vital organs, or stroke caused by vertebral artery injury were excluded from the study. @*Results@#: Out of 243 patients with CSCI, 30 required MV during their hospital stay, and 27 met the inclusion criteria. Among them, 48.1% (13/27) of patients had MVDC with greater than 30 days MV or death caused by aspiration pneumonia. In total, 51.9% (14/27) of patients could be weaned from MV during 30 days or less of hospital stay (MV days : MVDC 38.23±20.79 vs. MV weaning, 13.57±8.40; p51.4% was a significant risk factor for MVDC (odds ratio, 7.574; p=0.039). @*Conclusion@#: As a method of predicting which patients would be able to undergo weaning from MV early, the MCC is a valid factor. If the MCC exceeds 51.4%, prognosis of respiratory function becomes poor and the probability of MVDC is increased.
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Aplasia cutis congenita (ACC) is a rare congenital disorder characterized by skin defects involving the epidermis, dermis, subcutaneous tissue, bone, and sometimes dura. It commonly affects the scalp in approximately 70% of cases, but the neck, trunk, and the extremities can also be affected. ACC can occur either as an isolated condition or associated with other anomalies and congenital syndromes, and it can be acquired either genetically or sporadically. Morbidity and mortality are associated with the defects of skull bone, dura, and other multiple anomalies. We herein report the case of a female infant, with a large scalp defect accompanied by a skull defect noted at birth, who developed mental retardation in the preschool years.
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STAT3 plays a prominent role in proliferation and survival of tumor cells. Thus, STAT3 has been considered to be a prime target for development of anti-cancer therapeutics. The electrophilic cyclopentenone prostaglandin,15-deoxy-Δ12,14-prostaglandin J2(15d-PGJ2 ) has been well recognized for its capability to modulate intracellular signaling pathways involved in cancer cell growth and progression. We previously reported that 15d-PGJ2 had potent cytotoxicity against harvey-ras transformed human mammary epithelial cells through direct interaction with STAT3. In this study, we have attempted to verify the inhibitory effects of 15d-PGJ2 on STAT3 signaling in human breast tumor cells. The triple negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468 displaying constitutive phosphorylation of STAT3 on the tyrosine 705 (Tyr705) residue, underwent apoptosis upon inhibition of STAT3 by 15d-PGJ2 . In contrast, estrogen receptor positive MCF-7 breast cancer cells that do not exhibit elevated STAT3 phosphorylation were much less susceptible to 15d-PGJ2 -induced apoptosis as assessed by PARP cleavage. Furthermore, 15d-PGJ2 inhibited interleukin-6-induced tyrosine phosphorylation of STAT3 in LNCaP cells. According to molecular docking studies, 15d-PGJ2 may preferentially bind to the cysteine 259 residue (Cys259) present in the coiled-coil domain of STAT3. Site-directed mutagenesis of STAT3 identified Cys259 to be the critical amino acid for the 15d-PGJ2 -induced apoptosis as well as epithelial-to-mesenchymal transition. Taken together, these findings suggest STAT3 inactivation through direct chemical modification of its Cys259 as a potential therapeutic approach for treatment of triple negative breast cancer treatment.
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Objective@#: To compare the anterior cervical discectomy and fusion (ACDF) and posterior cervical fusion (PCF) with wide facetectomy in the treatment of parallel-shaped bony foraminal stenosis (FS). @*Methods@#: Thirty-six patients underwent surgery due to one-or-two levels of parallel-shaped cervical FS. ACDF was performed in 16 patients, and PCF using CPS was performed in 20 patients. All patients were followed up at 1, 3, 6, and 12 months postoperatively. Standardized outcome measures such as Numeric rating scale (NRS) score for armeck pain and Neck disability index (NDI) were evaluated. Cervical radiographs were used to compare the C2–7 Cobb’s angle, segmental angle, and fusion rates. @*Results@#: There was an improvement in NRS scores after both approaches for radicular arm pain (mean change -6.78 vs. -8.14, p=0.012), neck pain (mean change -1.67 vs. -4.36, p=0.038), and NDI score (-19.69 vs. -18.15, p=0.794). The segmental angle improvement was greater in the ACDF group than in the posterior group (9.4°±2.7° vs. 3.3°±5.1°, p=0.004). However, there was no significant difference in C2–7 Cobb angle between groups (16.2°±7.9° vs. 14.8°±8.5°, p=0.142). As a complication, dysphagia was observed in one case of the ACDF group. @*Conclusion@#: In the treatment of parallel-shaped bony FS up to two surgical levels, segmental angle improvement was more favorable in patients who underwent ACDF. However, PCF with wide facetectomy using CPS should be considered as an alternative treatment option in cases where the anterior approach is burdensome.
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Objective@#: Cerebrospinal fluid leakage related complications (CLC) occasionally occur after intradural spinal surgery. We sought to investigate the effectiveness of early ambulation after intradural spinal surgery and analyze the risk factors for CLC. @*Methods@#: For this retrospective cohort study, we enrolled 314 patients who underwent intradural spinal surgery at a single institution. The early group contained 79 patients who started ambulation after 1 day of bedrest without position restrictions, while the late group consisted of 235 patients who started ambulation after at least 3 days of bed rest and were limited to the prone position after surgery. In the early group, Prolene 6–0 was used as the dura suture material, while black silk 5–0 was used as the dura suture material in the late group. @*Results@#: The overall incidence rate of CLC was 10.8%. Significant differences between the early and late groups were identified in the rate of CLC (2.5% vs. 13.6%), surgical repair required (1.3% vs. 7.7%), and length of hospital stay (2.99 vs. 9.29 days) (p<0.05). Logistic regression analysis revealed that CLC was associated with practices specific to the late group (p=0.011) and the revision surgery (p=0.022). @*Conclusion@#: Using Prolene 6–0 as a dura suture material for intradural spinal surgery resulted in lower CLC rates compared to black silk 5–0 sutures despite a shorter bed rest period. Our findings revealed that suture - needle ratio related to dura defect was the most critical factor for CLC. One-day ambulation after primary dura closure using Prolene 6–0 sutures appears to be a cost-effective and safe strategy for intradural spinal surgery.