Esophageal cancer has a poor prognosis, because the progression rate is faster compared to that of other cancers, Up to 30-40% of cases are inoperable at diagnosis, and most cases occur in the elderly. By this time, surgery has been regarded as the treatment of choice in patients suffering esophageal cancer and recent improvements in surgical techniques and perioperative management have significantly increased the resection rate and reduced the operative mortality. And Although the combination of chemotherapy and radiation therapy has been reported to be an effective treatment for esophageal cancer, most cases show only partial remission. Moreover, radiation therapy alone or chemotherapy alone has limited efficacy. We report a rare case of an 80-year-old man who presented with a chief complaint of dysphasia and was diagnosed with advanced esophageal cancer, with a review of the literature. Considering his advanced age, generally poor performance status, and the risk of fistula development after radiation therapy due to indentation of esophageal cancer into the main bronchus, palliative, rather than therapeutic, chemotherapy was performed, and complete remission was obtained.
Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (Emax) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.
The Wnt/β-catenin pathway plays essential roles in regulating various cellular behaviors, including proliferation, survival, and differentiation [1-3]. The intracellular β-catenin level, which is regulated by a proteasomal degradation pathway, is critical to Wnt/β-catenin pathway control [4]. Normally, casein kinase 1 (CK1) and glycogen synthase kinase-3β (GSK-3β), which form a complex with the scaffolding protein Axin and the tumor suppressor protein adenomatous polyposis coli (APC), phosphorylate β-catenin at Ser45, Thr41, Ser37, and Ser33 [5, 6]. Phosphorylated β-catenin is ubiquitinated by the β-transducin repeat-containing protein (β-TrCP), an F-box E3 ubiquitin ligase complex, and ubiquitinated β-catenin is degraded via a proteasome pathway [7, 8]. Colorectal cancer is a significant cause of cancer-related deaths worldwide. Abnormal up-regulation of the Wnt/β-catenin pathway is a major pathological event in intestinal epithelial cells during human colorectal cancer oncogenesis [9]. Genetic mutations in the APC gene are observed in familial adenomatous polyposis coli (FAP) and sporadic colorectal cancers [10]. In addition, mutations in the N-terminal phosphorylation motif of the β-catenin gene were found in patients with colorectal cancer [11]. These mutations cause β-catenin to accumulate in the nucleus, where it forms complexes with transcription factors of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family to stimulate the expression of β-catenin responsive genes, such as c-Myc and cyclin D1, which leads to colorectal tumorigenesis [12-14]. Therefore, downregulating β-catenin response transcription (CRT) is a potential strategy for preventing and treating colorectal cancer. Plant cytokinins are N6-substituted purine derivatives; they promote cell division in plants and regulate developmental pathways. Natural cytokinins are classified as isoprenoid (isopentenyladenine, zeatin, and dihydrozeatin), aromatic (benzyladenine, topolin, and methoxytopolin), or furfural (kinetin and kinetin riboside), depending on their structure [15, 16]. Kinetin riboside was identified in coconut water and is a naturally produced cytokinin that induces apoptosis and exhibits antiproliferative activity in several human cancer cell lines [17]. However, little attention has been paid to kinetin riboside's mode of action. In this study, we show that kinetin riboside exerts its cytotoxic activity against colon cancer cells by suppressing the Wnt/β-catenin pathway and promoting intracellular β-catenin degradation.
Ji Min Jung;Su Hui Seong;Bo-Ram Kim;Jin-Ho Kim;Ha-Nul Lee;Chan Seo;Jung Eun Kim;Sua Im;Kyung-Min Choi;Jin-Woo Jeong
Proceedings of the Plant Resources Society of Korea Conference
/
2023.04a
/
pp.51-51
/
2023
The world-wide rate of obesity is increasing continuously, representing a serious medical threat since it is associated with a variety of diseases including type 2 diabetes, cardiovascular disease, and numerous cancers. Sophora japonicais used as a traditional herb for medicinal purposes in eastern Asia. However, the anti-obesity effects of S. japonicafruit have not been explored. The aim of this study is to investigate the inhibition of adipocyte differentiation and adipogenesis by an ethanol extract of S. japonicafruit (EESF) in 3T3-L1 pre-adipocytes. Our results demonstrate that EESF suppressed the terminal differentiation of 3T3-L1 pre-adipocytes in a dose-dependent manner, as confirmed by a decrease in lipid droplet number and lipid content through Oil Red O staining. EESF significantly reduced the accumulation of cellular triglyceride, which was associated with a significant inhibition of the levels of pro-adipogenic transcription factors, including PPARγ, C/EBPα and C/EBPβ. In addition, EESF potentially down regulated the expression levels of adipocyte-specific proteins, including aP2 and leptin. In particular, EESF treatment effectively enhanced the activation of the AMPK signaling pathway; however, the co-treatment with compound C, an inhibitor of AMPK, significantly restored the EESF-induced inhibition of pro-adipogenic transcription factors and adipocyte-specific genes. These results indicate that EESF may exert an anti-obesity effect by controlling the AMPK signaling pathway, suggesting that the fruit extract of S. japonica may be a potential anti-obesity agent.
Do Kyung Han;Jee Won Shon;Eui Suk Sung;Youn Sook Kim;Won G. An
Journal of Life Science
/
v.33
no.11
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pp.876-886
/
2023
In some cases of head and neck cancers (HNC), surgical interventions may result in the loss of organs and/or changes to their functions, thereby significantly affecting the patient's quality of life. As a result, the surgical treatment of HNC patients is often limited to specific cases, and alternative treatment modalities, such as chemotherapy, are considered. However, serious adverse effects caused by chemotherapy, such as severe nausea and vomiting, necessitate the need for the development of adjunctive methods to minimize patient suffering. Chuanxiong, Ligusticum chuanxiong (L. chuanxiong), is a natural herb used in Eastern medicine to treat cerebrovascular disorders and headaches. This study aimed to predict the effect and potential of L. chuanxiong as an auxiliary anticancer drug through network-based pharmacology and molecular docking analysis. The study results showed that 40 out of 41 genes of L. chuanxiong shared common targets of HNC and their proteins could be used to target HNC cells to prevent cancer progression. The results of the functional enrichment analysis confirmed that L. chuanxiong is associated with the neuroactive-ligand metabolism and neurotransmitter pathways, indicating its potential medicinal value as an adjuvant in HNC treatment. Lastly, our findings demonstrated that the active ingredient of L. chuanxiong, (Z)-Ligustilide, has the ATP binding site of heat shock protein 90, a protein known to promote the activation of cancer cells. These results suggest that L. chuanxiong is a promising candidate for developing auxiliary anticancer drugs, and further research could potentially lead to the discovery of newer and safer anti-cancer agents.
Breast cancer is one of the top three most common cancers in modern women, and the incidence rate is increasing rapidly. Breast cancer has a high family history and a mortality rate of about 15%, making it a high-risk group. Therefore, breast cancer needs constant management after an early examination. Among the various equipment that can diagnose cancer, ultrasound has the advantage of low risk and being able to diagnose in real time. In addition, breast ultrasound will be more useful because Asian women's breasts are denser and less sensitive. However, the results of ultrasound examinations vary greatly depending on the technology of the examiner. To compensate for this, we intend to incorporate motion tracking technology. Motion tracking is a technology that specifies and analyzes a location according to the movement of an object in a three-dimensional space. Therefore, real-time control is possible, and complex and fast movements can be recorded in real time. We would like to present the production of an ultrasound examination guide using these advantages.
Moonki Hong;Mingee Choi;JiHyun Lee;Kyoo Hyun Kim;Hyunwook Kim;Choong-Kun Lee;Hyo Song Kim;Sun Young Rha;Gyu Young Pih;Yoon Jin Choi;Da Hyun Jung;Jun Chul Park;Sung Kwan Shin;Sang Kil Lee;Yong Chan Lee;Minah Cho;Yoo Min Kim;Hyoung-Il Kim;Jae-Ho Cheong;Woo Jin Hyung;Jaeyong Shin;Minkyu Jung
Journal of Gastric Cancer
/
v.23
no.4
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pp.574-583
/
2023
Purpose: Gastric cancer (GC) is among the most prevalent and fatal cancers worldwide. National cancer screening programs in countries with high incidences of this disease provide medical aid beneficiaries with free-of-charge screening involving upper endoscopy to detect early-stage GC. However, the coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions to routine healthcare access. Thus, this study aimed to assess the impact of COVID-19 on the diagnosis, overall incidence, and stage distribution of GC. Materials and Methods: We identified patients in our hospital cancer registry who were diagnosed with GC between January 2018 and December 2021 and compared the cancer stage at diagnosis before and during the COVID-19 pandemic. Subgroup analyses were conducted according to age and sex. The years 2018 and 2019 were defined as the "before COVID" period, and the years 2020 and 2021 as the "during COVID" period. Results: Overall, 10,875 patients were evaluated; 6,535 and 4,340 patients were diagnosed before and during the COVID-19 period, respectively. The number of diagnoses was lower during the COVID-19 pandemic (189 patients/month vs. 264 patients/month) than before it. Notably, the proportion of patients with stages 3 or 4 GC in 2021 was higher among men and patients aged ≥40 years. Conclusions: During the COVID-19 pandemic, the overall number of GC diagnoses decreased significantly in a single institute. Moreover, GCs were in more advanced stages at the time of diagnosis. Further studies are required to elucidate the relationship between the COVID-19 pandemic and the delay in the detection of GC worldwide.
Jee-Hyung Lee;Jin Ho Choi;Kyung-Min Lee;Min Woo Lee;Ja-Lok Ku;Dong-Chan Oh;Yern-Hyerk Shin;Dae Hyun Kim;In Rae Cho;Woo Hyun Paik;Ji Kon Ryu;Yong-Tae Kim;Sang Hyub Lee;Sang Kook Lee
Biomolecules & Therapeutics
/
v.32
no.1
/
pp.123-135
/
2024
Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin also inhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.
Bo Hwa Choi;Hye Jin Baek;Ji Young Ha;Kyeong Hwa Ryu;Jin Il Moon;Sung Eun Park;Kyungsoo Bae;Kyung Nyeo Jeon;Eun Jung Jung
Korean Journal of Radiology
/
v.21
no.9
/
pp.1036-1044
/
2020
Objective: To investigate the clinical feasibility of synthetic diffusion-weighted imaging (sDWI) at different b-values in patients with breast cancer by assessing the diagnostic image quality and the quantitative measurements compared with conventional diffusion-weighted imaging (cDWI). Materials and Methods: Fifty patients with breast cancer were assessed using cDWI at b-values of 800 and 1500 s/mm2 (cDWI800 and cDWI1500) and sDWI at b-values of 1000 and 1500 s/mm2 (sDWI1000 and sDWI1500). Qualitative analysis (normal glandular tissue suppression, overall image quality, and lesion conspicuity) was performed using a 4-point Likert-scale for all DWI sets and the cancer detection rate (CDR) was calculated. We also evaluated cancer-to-parenchyma contrast ratios for each DWI set in 45 patients with the lesion identified on any of the DWI sets. Statistical comparisons were performed using Friedman test, one-way analysis of variance, and Cochran's Q test. Results: All parameters of qualitative analysis, cancer-to-parenchyma contrast ratios, and CDR increased with increasing b-values, regardless of the type of imaging (synthetic or conventional) (p < 0.001). Additionally, sDWI1500 provided better lesion conspicuity than cDWI1500 (3.52 ± 0.92 vs. 3.39 ± 0.90, p < 0.05). Although cDWI1500 showed better normal glandular tissue suppression and overall image quality than sDWI1500 (3.66 ± 0.78 and 3.73 ± 0.62 vs. 3.32 ± 0.90 and 3.35 ± 0.81, respectively; p < 0.05), there was no significant difference in their CDR (90.0%). Cancer-to-parenchyma contrast ratios were greater in sDWI1500 than in cDWI1500 (0.63 ± 0.17 vs. 0.55 ± 0.18, p < 0.001). Conclusion: sDWI1500 can be feasible for evaluating breast cancers in clinical practice. It provides higher tumor conspicuity, better cancer-to-parenchyma contrast ratio, and comparable CDR when compared with cDWI1500.
Sae Rom Chung;Jung Hwan Baek;Young Jun Choi;Tae-Yon Sung;Dong Eun Song;Tae Yong Kim;Jeong Hyun Lee
Korean Journal of Radiology
/
v.21
no.10
/
pp.1187-1195
/
2020
Objective: This study aimed to determine the sonographic features suggestive of extrathyroidal extension (ETE) of thyroid cancers. Materials and Methods: We retrospectively reviewed the sonographic images of 1656 consecutive patients who had undergone thyroidectomy in 2017. The diagnostic performance of sonographic features suggestive of ETE was evaluated using operation and histopathologic reports. Sonographic features for gross ETE to the strap muscle and minor ETE were assessed for thyroid cancer abutting the anterolateral thyroid capsule. Sonographic features for tracheal invasion were assessed according to whether the angle between the tumor and the trachea was an acute, right, or obtuse angle. Sonographic features for recurrent laryngeal nerve (RLN) invasion were assessed based on the association between the tumor and tracheoesophageal groove (TEG) as preserved normal tissue, abutting or protruding into the TEG. Results: ETE was observed in 783 patients (47.3%), including 123 patients with gross ETE (7.4% [strap muscle, n = 97; RLN, n = 24; and trachea, n = 14]) and 660 patients with minor ETE (39.9%). Regarding the diagnosis of gross and minor ETE to the strap muscle, sonographic features of replacement of the strap muscle and capsular disruption showed the highest positive predictive value (75.9% and 58.5%, respectively). Thyroid cancer forming an obtuse angle with the trachea had the highest sensitivity for the diagnosis of tracheal invasion (85.7%), and thyroid cancer protrusion into the TEG showed the highest sensitivity for the diagnosis of RLN (83.3%). Conclusion: Sonography is considered beneficial in the diagnosis of ETE to the strap muscle, trachea, and RLN. Assessment of ETE is important for the accurate staging of thyroid cancer, which in turn determines the extent of surgery or whether active surveillance is appropriate or not.
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