Biology subjects

Kuo, Y.-Y.

Publications and source records attributed to Kuo, Y.-Y..

25 records · Page 2Linked to original sources

bioRxiv2022

Thermal cycling hyperthermia sensitizes non-small cell lung cancer A549 cells to EGFR-tyrosine kinase inhibitor Erlotinib

Molecular targeted therapy has emerged as a mainstream treatment for non-small cell lung cancer (NSCLC), the most common lung cancer, which has been the leading cause of cancer death in both genders. Erlotinib (Erl), a targeted therapy inhibiting epidermal growth factor receptor (EGFR) pathways, has been proved to have noticeable response rate for NSCLC cells. However, limited efficacy arises due to intrinsic and acquired resistance among most NSCLC patients. Therefore, sensitizers are required to potentiate the efficacy of Erl in NSCLC treatment. The study proposed a novel thermal therapy, thermal cycling hyperthermia (TC-HT), as a supplement to amplify the effects of Erl. We found that TC-HT remarkably reduced the half-maximal inhibitory concentration (IC50) of Erl to as little as 0.5 M and demonstrated that TC-HT could sensitize A549 NSCLC cells to Erl via the downstream of EGFR signaling cascades. Furthermore, combination treatment induced G2/M cell cycle arrest, and inhibition of cell proliferation and migration. Besides, via raising the high temperature of TC-HT slightly, TC-HT treatment alone can produce excellent antineoplastic effect without hurting the normal cells. The method is expected to be applicable to other combination therapies and may be a starter for more sophisticated, side-effect-free anticancer treatments.

cancer biology↗

bioRxiv2021

Study on the effect of a triple cancer treatment of propolis, thermal cycling-hyperthermia, and low-intensity ultrasound on PANC-1 cells

BackgroundPancreatic cancer is a deadly cancer around the world. To reduce side effects and enhance treatment efficacy, study on combination therapy for pancreatic cancer has gained much attention in recent years. MethodsIn this paper, we propose a novel triple treatment combining propolis and two physical stimuli-thermal cycling-hyperthermia (TC-HT) and low-intensity ultrasound (US) on a human pancreatic cancer cell line PANC-1. MTT assay was used to determine the viability of PANC-1 cells. Flow cytometry was used to detect apoptosis, mitochondrial membrane potential (MMP) loss, and intracellular reactive oxygen species (ROS) levels. Western blot analysis was further performed to measure protein expression and phosphorylation. ResultsThe experiments found that, after the triple treatment, the cell viability of the PANC-1 cells decreased to a level 80% less than the control, without affecting the normal pancreatic cells. Another result was excessive accumulation of ROS after the triple treatment, leading to the amplification of apoptotic pathway through the mitogen-activated protein kinase (MAPK) family and mitochondrial dysfunction. Moreover, the combination of TC-HT and US also promotes the anticancer effect of the heat-sensitive chemotherapy drug cisplatin on PANC-1 cells. ConclusionThis study, to the best of our knowledge, is the first attempt to combine TC-HT, US and a nature compound in cancer treatment. We demonstrate that physical stimuli could augment the therapeutical effect of anticancer agents. It is expected that optimized parameters for different agents and different types of cancer will expand the methodology on oncological therapy in a safe manner.

cancer biology↗

bioRxiv2019

Effect of high frequency and low intensity pulsed electric field on protecting SH-SY5Y cells against hydrogen peroxide and β-amyloid-induced cell injury via ERK pathway

As the most common type of neurodegenerative diseases (NDDs), Alzheimers disease (AD) is thought to be caused mainly by the excessive aggregation of {beta}-amyloid protein (A{beta}). However, a growing number of studies have found that reactive oxygen species (ROS) play a key role in the onset and progression of AD. The present study aimed to probe the neuroprotective effect of high-frequency low-intensity pulsed electric field (H-LIPEF) for SH-SY5Y cells against hydrogen peroxide (H2O2) and A{beta}-induced cytotoxicity. By looking in a systematic way into the frequency- and amplitude-dependent neuroprotective effect of pulsed electric field (PEF), the study finds that H-LIPEF at 200 Hz produces the optimal protective effect for SH-SY5Y cells. The underlying mechanisms were confirmed to be due to the activation of extracellular signal-regulated kinase (ERK) pathway and the downstream prosurvival and antioxidant proteins. Because the electric field can be modified to focus on specific area in a non-contact manner, the study suggests that H-LIPEF holds great potential for treating NDDs, whose effect can be further augmented with the administering of drugs or natural compounds at the same time.

neuroscience↗

bioRxiv2019

Thermal cycling protects SH-SY5Y cells against hydrogen peroxide and -amyloid-induced cell injury through stress response mechanisms involving Akt pathway

Neurodegenerative diseases (NDDs) are becoming a major threat to public health, according to the World Health Organization (WHO). The most common form of NDDs is Alzheimers disease (AD), boasting 60-70% share. Excessive aggregation of {beta}-amyloid protein (A{beta}) and neurofibrillary tangles has been deemed the major cause for the pathogenesis of AD. A growing number of evidences from studies, however, have suggested that reactive oxygen species (ROS) also play a key role in the onset and progression of AD. Although scientists have had some understanding of the pathogenesis of AD, the disease still cannot be cured, with existing treatment only capable of providing a temporary relief at best, partly due to the obstacle of blood-brain barrier (BBB). The study was aimed to ascertain the neuroprotective effect of thermal cycle hyperthermia (TC-HT) against hydrogen peroxide (H2O2) and A{beta}-induced cytotoxicity in SH-SY5Y cells. Treating cells with this physical stimulation beforehand significantly improved the cell viability and decreased the ROS content. The underlying mechanisms were confirmed to be due to the activation of Akt pathway and the downstream antioxidant and prosurvival proteins. The findings manifest significant potential of TC-HT in neuroprotection, via inhibition of oxidative stress and cell apoptosis. It is believed that coupled with the use of drugs or natural compounds, this methodology can be even more effective in treating NDDs.

neuroscience↗

bioRxiv2019

Application of non-invasive low-intensity pulsed electric field with thermal cycling-hyperthermia for synergistically enhanced anticancer effect of chlorogenic acid on PANC-1 cells

Most existing cancer treatments involve high-cost chemotherapy and radiotherapy, with major side effects, prompting effort to develop alternative treatment modalities. In this study, we propose a novel non-invasive treatment calling for exposure of cells to CGA, coupled with thermal-cycling hyperthermia (TC-HT) and low-intensity pulsed electric field (LIPEF). The study finds that this triple combination can significantly impede the proliferation of human pancreatic cancer PANC-1 cells, with only about 20% viable cells left after 24h, whereas being non-toxic to normal cells. The synergistic activity against the PANC-1 cells was achieved by inducing G2/M phase arrest and apoptosis, which were associated with up-regulation of p53 and coupled with increased expression of downstream proteins p21 and Bax. Further mechanism investigations revealed that the cytotoxic activity could be related to mitochondrial apoptosis, characterized by the reduced level of Bcl-2, mitochondrial dysfunction, and sequential activation of caspase-9 and PARP. Also, we found that the triple treatment led to the increase of intracellular reactive oxygen species (ROS) production. Notably, the triple treatment-induced cytotoxic effects and the elevated expression of p53 and p21 proteins as well as the increased Bax/Bcl-2 ratio, all could be alleviated by the ROS scavenger, N-acetyl-cysteine (NAC). These findings indicate that the combination of CGA, TC-HT, and LIPEF may be a promising modality for cancer treatment, as it can induce p53-dependent cell cycle arrest and apoptosis through accumulation of ROS in PANC-1 cells.

cancer biology↗

bioRxiv2019

Thermal cycling-hyperthermia in combination with polyphenols, epigallocatechin gallate and chlorogenic acid, exerts synergistic anticancer effect against human pancreatic cancer PANC-1 cells

Hyperthermia (HT) has shown feasibility and potency as an anticancer therapy. Administration of HT in the chemotherapy has previously enhanced the cytotoxicity of drugs against pancreatic cancer. However, the drugs used when conducting these studies are substantially conventional chemotherapeutic agents that may cause unwanted side effects. Additionally, the thermal dosage in the treatment of cancer cells could also probably harm the healthy cells. The purpose of this work was to investigate the potential of the two natural polyphenolic compounds, epigallocatechin gallate (EGCG) and chlorogenic acid (CGA), as heat synergizers in the thermal treatment of the PANC-1 cells. Furthermore, we have introduced a novel strategy entitled the thermal cycling-hyperthermia (TC-HT) that is capable of providing a maximum synergy and minimal side effect with the anticancer compounds. Our results demonstrate that the combination of the TC-HT and the CGA or EGCG markedly exerts the anticancer effect against the PANC-1 cells, while none of the single treatment induced such changes. The synergistic activity was attributed to the cell cycle arrest at the G2/M phase and the induction of the ROS-dependent mitochondria-mediated apoptosis. These findings not only represent the first thermal synergistic study of natural compounds in the treatment of pancreatic cancer, but also highlight the potential application of the TC-HT as an alternative strategy in anticancer treatment.

cancer biology↗

bioRxiv2018

Charting the emergent organotypic landscape of the mammalian gut endoderm at single-cell resolution

To comprehensively delineate the ontogeny of an organ system, we generated 112,217 singlecell transcriptomes representing all endoderm populations within the mouse embryo until midgestation. We employed graph-based approaches to model differentiating cells for spatio-temporal characterization of developmental trajectories. Our analysis reveals the detailed architecture of the emergence of the first (primitive or extra-embryonic) endodermal population and pluripotent epiblast. We uncover an unappreciated relationship between descendants of these lineages, before the onset of gastrulation, suggesting that mixing of extra-embryonic and embryonic endoderm cells occurs more than once during mammalian development. We map the trajectories of endoderm cells as they acquire embryonic versus extra-embryonic fates, and their spatial convergence within the gut endoderm; revealing them to be globally similar but retaining aspects of their lineage history. We observe the regionalized localization of cells along the forming gut tube, reflecting their extra-embryonic or embryonic origin, and their coordinate patterning into organ-specific territories along the anterior-posterior axis.

developmental biology↗