Abstract
5-Fluorouracil (5-FU) remains the first-line treatment for colorectal cancer (CRC). Although 5-FU initially de-bulks the tumor mass, recurrence after chemotherapy is the barrier to effective ...clinical outcomes for CRC patients. Here, we demonstrate that p53 promotes
WNT3
transcription, leading to activation of the WNT/β-catenin pathway in
Apc
Min/+
/Lgr5
EGFP
mice, CRC patient-derived tumor organoids (PDTOs) and patient-derived tumor cells (PDCs). Through this regulation, 5-FU induces activation and enrichment of cancer stem cells (CSCs) in the residual tumors, contributing to recurrence after treatment. Combinatorial treatment of a WNT inhibitor and 5-FU effectively suppresses the CSCs and reduces tumor regrowth after discontinuation of treatment. These findings indicate p53 as a critical mediator of 5-FU-induced CSC activation via the WNT/β-catenin signaling pathway and highlight the significance of combinatorial treatment of WNT inhibitor and 5-FU as a compelling therapeutic strategy to improve the poor outcomes of current 5-FU-based therapies for CRC patients.
Membrane-less biomolecular compartmentalization is a core phenomenon involved in many physiological activities that occur ubiquitously in cells. Condensates, such as promyelocytic leukemia (PML) ...bodies, stress granules, and P-bodies (PBs), have been investigated to understand the process of membrane-less cellular compartmentalization. In budding yeast, PBs dispersed in the cytoplasm of exponentially growing cells rapidly accumulate in response to various stresses such as osmotic stress, glucose deficiency, and heat stress. In addition, cells start to accumulate PBs chronically in post-exponential phases. Specific protein-protein interactions are involved in accelerating PB accumulation in each circumstance, and discovering the regulatory mechanism for each is the key to understanding cellular condensation. Here, we demonstrate that Nst1 of budding yeast
is far more densely associated with PBs in post-exponentially growing phases from the diauxic shift to the stationary phase than during glucose deprivation of exponentially growing cells, while the PB marker Dcp2 exhibits a similar degree of condensation under these conditions. Similar to Edc3, ectopic Nst1 overexpression induces self-condensation and the condensation of other PB components, such as Dcp2 and Dhh1, which exhibit liquid-like properties. Altogether, these results suggest that Nst1 has the intrinsic potential for self-condensation and the condensation of other PB components, specifically in post-exponential phases.
A new strategy is reported to achieve high‐mobility, low‐off‐current, and operationally stable solution‐processable metal‐oxide thin‐film transistors (TFTs) using a corrugated heterojunction channel ...structure. The corrugated heterojunction channel, having alternating thin‐indium‐tin‐zinc‐oxide (ITZO)/indium‐gallium‐zinc‐oxide (IGZO) and thick‐ITZO/IGZO film regions, enables the accumulated electron concentration to be tuned in the TFT off‐ and on‐states via charge modulation at the vertical regions of the heterojunction. The ITZO/IGZO TFTs with optimized corrugated structure exhibit a maximum field‐effect mobility >50 cm2 V−1 s−1 with an on/off current ratio of >108 and good operational stability (threshold voltage shift <1 V for a positive‐gate‐bias stress of 10 ks, without passivation). To exploit the underlying conduction mechanism of the corrugated heterojunction TFTs, a physical model is implemented by using a variety of chemical, structural, and electrical characterization tools and Technology Computer‐Aided Design simulations. The physical model reveals that efficient charge manipulation is possible via the corrugated structure, by inducing an extremely high carrier concentration at the nanoscale vertical channel regions, enabling low off‐currents and high on‐currents depending on the applied gate bias.
High‐performance and controllable metal oxide semiconductors utilizing a corrugated bilayer structure are achieved, which display enhanced mobility and control of carrier concentration, corresponding to the operation states of the device. This novel strategy can be used as a general route to high‐mobility, extremely stable, and controllable semiconductor devices, offering compatibility with standard complementary metal‐oxide‐semiconductor (CMOS) processing and large‐scale on‐chip device applications.
This study aimed to determine the etiologic distribution of dizziness and vertigo in a referral-based dizziness clinic in South Korea. We analyzed the diagnoses of 21,166 consecutive dizzy patients ...(12,691 women, mean age = 57.9 ± 15.7, age range = 3–97) seen from 2003 to 2019 using a registry and medical records. Overall, dizziness and vertigo were more common in women (60.0%, CI 0.59–0.61) than in men without a difference in age (57.7 ± 15.5 vs. 58.1 ± 16.1,
p
= 0.094). Benign paroxysmal positional vertigo (BPPV, 24.1%) was the most common cause of dizziness/vertigo, followed by psychiatric or persistent postural perceptual dizziness (20.8%), vascular disorders (12.9%), vestibular migraine (10.2%), Meniere’s disease (7.2%), and vestibular neuritis (5.4%). These six disorders comprised more than 80% of all disorders. The etiology could not be determined in 5.0%, and more than one etiology was found in 14.1%. Vestibular migraine was the most common disorder in children and adolescents (< 19 years), psychiatric or persistent postural perceptual dizziness (26.3%) in the adults (19–64 years), and BPPV (28.2%) in the elderly (≥ 65 years). This etiologic distribution is similar to that reported in another country, and indicates no significant differences in the proportion of diseases causing dizziness and vertigo across different ethnic groups. This study provides valuable information to establish healthcare policy for dizziness and vertigo.
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•PHA production from biowaste is an economic and ecofriendly approach.•Microbes are able to recover resource from waste and produce PHA.•C, N, P and dissolved oxygen are the main ...factors that affect PHA production.•The downstream process has a big impact on whole cost of PHA production.•Functionalization of PHA has potential to improve their applications.
Biowaste management is a challenging job as it is high in nutrient content and its disposal in open may cause a serious environmental and health risk. Traditional technologies such as landfill, bio-composting, and incineration are used for biowaste management. To gain revenue from biowaste researchers around the world focusing on the integration of biowaste management with other commercial products such as volatile fatty acids (VFA), biohydrogen, and bioplastic (polyhydroxyalkanoates (PHA)), etc. PHA production from various biowastes such as lignocellulosic biomass, municipal waste, waste cooking oils, biodiesel industry waste, and syngas has been reported successfully. Various nutrient factors i.e., carbon and nitrogen source concentration and availability of dissolved oxygen are crucial factors for PHA production. This review is an attempt to summarize the recent advancements in PHA production from various biowaste, its downstream processing, and other challenges that need to overcome making bioplastic an alternate for synthetic plastic.
This study was conducted to evaluate the outcomes of multi-channel switching RFA using a separable cluster electrode in patients with HCC.
From November 2011 to July 2013, 79 patients with 98 HCCs < ...5 cm were enrolled and treated with RFA using a multi-channel switching radiofrequency system and a separable cluster electrode under the guidance of a real-time fusion imaging system. The primary and secondary endpoints were the 3-year local tumor progression (LTP) rate and recurrence-free survival (RFS) rate, respectively. For post hoc analyses, LTP, RFS, and major complication rates were retrospectively compared with a historical control group treated with RFA using the same radiofrequency system but with multiple internally-cooled electrodes.
The technique success rate of the 98 tumors was 100%. Cumulative 1-year, 2-year, and 3-year LTP rates were 3.4%, 6.9%, and 12.4%, respectively. For patient-level data, cumulative 1-year, 2-year, and 3-year RFS rates were 83.9%, 68.6%, and 45.4%, respectively. On post hoc analyses, none of the baseline characteristics showed a significant difference between the separable cluster electrode and multiple internally-cooled electrodes group. Cumulative LTP and RFS rates of the two groups also showed no significant difference (p = 0.401 and p = 0.881, respectively). Finally, major complication rates of the separable cluster electrode group (5.0%, 4/79) and multiple internally-cooled electrodes group (5.9%, 4/74) were also comparable (p = 1.000).
Switching monopolar RFA using a separable cluster electrode is a feasible and efficient technique for the treatment of HCCs smaller than 5 cm, providing comparable local tumor control to multiple internally-cooled electrodes.
ClinicalTrials.gov NCT02745483.
Background and purpose
The etiological distribution of oculomotor nerve palsy has varied amongst the studies. This study aimed to define the clinical features and underlying etiologies of isolated ...oculomotor nerve palsy by recruiting patients from all departments in a referral‐based university hospital.
Methods
The medical records of 672 patients who had a confirmed diagnosis of isolated oculomotor nerve palsy at all departments of Seoul National University Bundang Hospital, Seongnam, South Korea, from 2003 to 2020 were reviewed. A proportion of the etiology of isolated oculomotor nerve palsy was also compared with that of patients pooled from the previous studies that were searched on PubMed in May 2022.
Results
The most common etiology was microvascular (n = 168, 26.5%), followed by vascular anomalies (n = 110, 17.4%), neoplastic (n = 86, 13.6%), inflammatory (n = 79, 12.5%), idiopathic (n = 60, 9.5%) and traumatic (n = 53, 8.4%). Neurologists were mainly involved in the management of microvascular and inflammatory oculomotor nerve palsies whilst ophthalmologists mainly participated in the care of idiopathic, neoplastic and traumatic palsies. Neurosurgeons mostly took care of oculomotor nerve palsy due to vascular anomalies.
Conclusions
The proportion of etiologies of isolated oculomotor nerve palsy may differ according to the specialties involved in the management. The results of previous studies on the etiological distribution of isolated oculomotor nerve palsy should be interpreted with this consideration.
Background and Purpose
The etiologies of abducens nerve palsy have shown a large variability among studies. This study aimed to establish the clinical features and underlying etiologies of isolated ...abducens nerve palsy by recruiting patients from all departments in a referral‐based university hospital.
Methods
We reviewed the medical records of 807 patients with a confirmed diagnosis of isolated abducens nerve palsy at all departments of Seoul National University Bundang Hospital, Seongnam, Republic of Korea, from 2003 to 2020. We also compared the proportion of etiology with that of the patients pooled from the previous studies.
Results
The most common etiology was microvascular (n = 296, 36.7%), followed by idiopathic (n = 143, 17.7%), neoplastic (n = 115, 14.3%), vascular anomalies (n = 82, 10.2%), inflammatory (n = 76, 9.4%), and traumatic (n = 35, 4.3%). Patients were mostly managed by ophthalmologists (n = 576, 71.4%), followed by neurologists (n = 479, 59.4%), emergency physicians (n = 278, 34.4%), neurosurgeons (n = 191, 23.7%), and others (n = 72, 8.9%). The proportion of etiology significantly differed according to the age and sex of the patients and the specialties involved in the management (p < 0.001). Compared to the pooled data from the previous reports, the current study showed a higher prevalence of microvascular cause but a lower occurrence of traumatic and neoplastic causes.
Conclusions
The results of previous studies on etiologic distribution of isolated abducens nerve palsy should be interpreted with consideration of the demographic features of patients recruited and the specialties involved.
Survival outcomes for patients with recurrent or advanced cervical cancer are poor. Pembrolizumab has been approved for the treatment of recurrent or metastatic cervical cancer, with an overall ...response rate of 14·3%. GX-188E vaccination has been shown to induce human papillomavirus (HPV) E6-specific and E7-specific T-cell responses and cervical lesion regression in patients with cervical precancer. We aimed to investigate whether a combination of GX-188E therapeutic DNA vaccine plus pembrolizumab showed antitumour activity against recurrent or advanced cervical cancer.
In this open-label, single-arm, phase 2 trial, patients with recurrent or advanced, inoperable cervical cancer, who were aged 18 years or older with Eastern Cooperative Oncology Group performance status of 0 or 1 and histologically confirmed recurrent or advanced HPV-positive (HPV-16 or HPV-18) cervical cancer, and who had progressed after available standard-of-care therapy were recruited from seven hospitals in South Korea. Patients received intramuscular 2 mg GX-188E at weeks 1, 2, 4, 7, 13, and 19, with one optional dose at week 46 that was at the investigator's discretion, and intravenous pembrolizumab 200 mg every 3 weeks for up to 2 years or until disease progression. The primary endpoint was the overall response rate within 24 weeks assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1 in patients who received at least 45 days of treatment 45 days of treatment with at least one post-baseline tumour assessment, and this is the report of a planned interim analysis. This trial is registered with ClinicalTrials.gov, NCT03444376.
Between June 19, 2018, and March 20, 2020, 36 patients were enrolled and received at least one dose of the study treatment. 26 patients were evaluable for interim activity assessment, with at least one post-baseline tumour assessment at week 10. At the data cutoff date on March 30, 2020, median follow-up duration was 6·2 months (IQR 3·5–8·1). At 24 weeks, 11 (42%; 95% CI 23-63) of 26 patients achieved an overall response; four (15%) had a complete response and seven (27%) had a partial response. 16 (44%) of 36 patients had treatment-related adverse events of any grade and four (11%) had grade 3–4 treatment-related adverse events. Grade 3 increased aspartate aminotransferase, syncope, pericardial effusion, and hyperkalaemia, and grade 4 increased alanine aminotransferase were reported in one patient each. No treatment-related deaths were reported.
Treatment with GX-188E therapeutic vaccine plus pembrolizumab for patients with recurrent or advanced cervical cancer was safe and treatment-related adverse events were manageable. This combination therapy showed preliminary antitumour activity in this interim analysis, which could represent a new potential treatment option for this patient population. This trial is ongoing.
National OncoVenture.
Diagnosis of lymphoma involving the central nervous system (CNS) is challenging. This study aimed to explore the abnormal vestibular and ocular motor findings in CNS lymphoma.
A retrospective search ...of the medical records identified 30 patients with CNS lymphoma presenting ocular motor and vestibular abnormalities from four neurology clinics of university hospitals in South Korea (22 men, age range 14-81 years, mean 60.6 ± 15.2). The demographic and clinical features and the results of laboratory, radiological and pathological evaluation were analyzed.
Patients presented with diplopia (13/30, 43%), vestibular symptoms (15/30, 50%) or both (2/30, 7%). In 15 patients with diplopia, abnormal ocular motor findings included ocular motor nerve palsy (n = 10, 67%), internuclear ophthalmoplegia (n = 2, 13%), external ophthalmoplegia (n = 2, 13%) and exophoria (n = 1, 7%). The vestibular abnormalities were isolated in 14 (82%) of 17 patients with vestibular symptoms and included combined unilateral peripheral and central vestibulopathy in three from lesions involving the vestibular nuclei. CNS lymphoma involved the brainstem (53%), cerebellum (33%), leptomeninges (30%), deep gray nuclei (23%) or cranial nerves (17%). Two patients showed the "double-panda" sign by involving the midbrain.
This study expands the clinical and radiological spectra of CNS lymphoma. Neuro-ophthalmological and neuro-otological evaluation may guide the early diagnosis of CNS lymphoma.
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