• Journal of Ginseng Research
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• v.45 no.6
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• pp.734-743
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• 2021

Background: The underlying mechanisms of the potential tumor-suppressive effects of ginsenoside Rh2 are complex. N6-methyladenosine (m6A) RNA methylation is usually dysregulated in cancer. This study explored the regulatory effect of ginsenoside Rh2 on m6A RNA methylation in cancer. Methods: m6A RNA quantification and gene-specific m6A RIP-qPCR assays were applied to assess total and gene-specific m6A RNA levels. Co-immunoprecipitation, fractionation western blotting, and immunofluorescence staining were performed to detect protein interactions and distribution. QRT-PCR, dual-luciferase, and ChIP-qPCR assays were conducted to check the transcriptional regulation. Results: Ginsenoside Rh2 reduces m6A RNA methylation and KIF26B expression in a dose-dependent manner in some cancers. KIF26B interacts with ZC3H13 and CBLL1 in the cytoplasm of cancer cells and enhances their nuclear distribution. KIF26B inhibition reduces m6A RNA methylation level in cancer cells. SRF bound to the KIF26B promoter and activated its transcription. SRF mRNA m6A abundance significantly decreased upon KIF26B silencing. SRF knockdown suppressed cancer cell proliferation and growth both in vitro and in vivo, the effect of which was partly rescued by KIF26B overexpression. Conclusion: ginsenoside Rh2 reduces m6A RNA methylation via downregulating KIF26B expression in some cancer cells. KIF26B elevates m6A RNA methylation via enhancing ZC3H13/CBLL1 nuclear localization. KIF26B-SRF forms a positive feedback loop facilitating tumor growth.

• Genomics & Informatics
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• v.19 no.1
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• pp.5.1-5.11
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• 2021

Head and neck squamous cell carcinoma (HNSCC) is the most frequent type of head and neck cancer that usually arises from the mucosal surfaces of several organs including nasal cavity, paranasal sinuses, oral cavity, tongue, pharynx, and larynx. The Wnt signaling pathway is a crucial mechanism for cellular maintenance and development. It regulates cell cycle progression, apoptosis, proliferation, migration, and differentiation. Dysregulation of this pathway correlates with oncogenesis in various tissues including breast, colon, pancreatic as well as head and neck cancers. The present study aims to assess the gene alterations in the Wnt family of genes so as to derive an association with HNSCC. Computational approaches have been utilized for the identification of gene alterations in the Wnt family of genes. Several databases such as cBioportal, STRING, and UALCAN were used for the purpose. The frequency of alteration was high in case of Wnt family member 11 (5%). Gene amplification, deep deletions, missense and truncating mutations were observed in HNSCC patients. There was a marked difference in the gene expression profile of WNT11 between grades as well as normal samples. The survival probability measured using the Kaplan-Meier curve also presented with a significant difference among male and female subjects experiencing a low/medium level expression. The female patients showed less survival probability when compared to the male subjects. This provides the prognostic significance of the WNT11 gene in HNSCC. Taken together, the present study provides clues on the possible association of WNT11 gene alterations with HNSCC, which has to be further validated using experimental approaches.

• Quality Improvement in Health Care
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• v.25 no.1
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• pp.11-28
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• 2019

Purpose: The purpose of this paper is to derive implication on the adoption of PROMs (Patient-Reported Outcome Measures) to improve quality of care in South Korea. With this purpose, the paper examines the status of PROMs in South Korea and other countries including OECD's PaRIS (Patient Reported Indicators Survey) initiative, and reviews policy cases that have adopted PROMs to improve performance of healthcare system. Methods: We conducted literature review on OECD reports on PaRIS, peer-reviewed journals, and information from the websites of relevant institutions such as ICHOM, NQF and OECD. Results: To identify healthcare services of best values and support patient-centered health system, OECD has initiated PaRIS which develops, collects and analyzes patient-reported indicators for cross-countries comparison. PaRIS is implemented on two work streams: 1) collect, validate and standardize PROMs in the areas where patient-reported indicators already exist such as breast cancers, hip and knee replacement, and mental conditions, 2) develop a new international survey on multiple chronic conditions. Countries like England, U.S., Sweden and Netherlands use PROMs for measuring performance of hospitals and performance evaluation at the national level, and provide the financial incentives for reporting PROMs. Conclusions: The use of PROMs can support the current policy agenda that is the patient-centered healthcare system which has been emphasized to reinforce the primary and the community-based care. For the use of PROMs, it is recommended to actively participate in PaRIS initiative by OECD, select appropriate instruments for PROMs, and continue on standardization of them. This will assure patients' involvement in improving health system performance, systemize information generated in the process of adopting PROMs, and develop a system to evaluate performance.

• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.19-27
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• 2022

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in many cancers such as non-small cell lung cancer (NSCLC), pancreatic cancer, breast cancer, and head and neck cancer. Mutations such as L858R in exon 21, exon 19 truncation (Del19), exon 20 insertions, and others are responsible for aberrant activation of EGFR in NSCLC. First-generation EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib have clinical benefits for EGFR-sensitive (L858R and Del19) NSCLC patients. However, after 10-12 months of treatment with these inhibitors, a secondary T790M mutation at the gatekeeper position in the kinase domain of EGFR was identified, which limited the clinical benefits. Second-generation EGFR irreversible inhibitors (afatinib and dacomitinib) were developed to overcome this T790M mutation. However, their lack of selectivity toward wild-type EGFR compromised their clinical benefits due to serious adverse events. Recently developed third-generation irreversible EGFR TKIs (osimertinib and lazertinib) are selective toward driving mutations and the T790M mutation, while sparing wild-type EGFR activity. The latest studies have concluded that their efficacy was also compromised by additional acquired mutations, including C797S, the key residue cysteine that forms covalent bonds with irreversible inhibitors. Because second- and third-generation EGFR TKIs are irreversible inhibitors, they are not effective against C797S containing EGFR triple mutations (Del19/T790M/C797S and L858R/T790M/C797S). Therefore, there is an urgent unmet medical need to develop next-generation EGFR TKIs that selectively inhibit EGFR triple mutations via a non-irreversible mechanism.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.457-468
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• 2022

It has been demonstrated that APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) is involved in the regulation of several growth-related signaling pathways and thus closely associated with the development and progression of some cancers. Diallyl trisulfide (DAT), a garlic-derived bioactive compound, exerts selective cytotoxicity to various human cancer cells through interfering with pro-survival signaling pathways. However, whether and how DAT affects survival of human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we tested the hypothesis of the involvement of APPL1 in DAT-induced cytotoxicity in HCC HepG2 cells. We found that Lys 63 (K63)-linked polyubiquitination of APPL1 was significantly decreased whereas phosphorylation of APPL1 at serine residues remained unchanged in DAT-treated HepG2 cells. Compared with wild-type APPL1, overexpression of APPL1 K63R mutant dramatically increased cell apoptosis and mitigated cell survival, along with a reduction of phosphorylation of STAT3, Akt, and Erk1/2. In addition, DAT administration markedly reduced protein levels of intracellular TNF receptor-associated factor 6 (TRAF6). Genetic inhibition of TRAF6 decreased K63-linked polyubiquitination of APPL1. Moreover, the cytotoxicity impacts of DAT on HepG2 cells were greatly attenuated by overexpression of wild-type APPL1. Taken together, these results suggest that APPL1 polyubiquitination probably mediates the inhibitory effects of DAT on survival of HepG2 cells by modulating STAT3, Akt, and Erk1/2 pathways.

• Journal of Digestive Cancer Research
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• v.4 no.2
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• pp.122-126
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• 2016

Leptomeningeal carcinomatosis occurs in approximately 5% of patients with cancer. The most common cancers involving the leptomeninges are breast, lung cancer and melanoma. However, gastric adenocarcinoma has been rarely reported with leptomeningeal carcinomatosis. The presenting manifestations are usually headache, visual disturbances and seizures. We report a case of leptomeningeal metastasis that presented as a gastric cancer. A 75-year old man was transferred to our hospital for further evaluation and treatment after being diagnosed with adenocarcinoma through endoscopic biopsy during a regular health examination. An abdominal computed tomography (CT) showed AGC, stage IA (cT1N0M0), while an endoscopic examination showed AGC, Borrmann type 2. The patient is currently under observation after undergoing radical subtotal gastrectomy with gastroduodenostomy and subsequent administration of oral chemotherapeutic agents. As an abdominal CT response assessment performed after surgery revealed new metastasis to the liver, the patient received palliative chemotherapy as recurrence was suspected. After receiving chemotherapy in the order of DP (Cisplatin + Docetaxel), FOLFIRI (5-FU + Leucovorin + Irinotecan), an abdominal CT response assessment showed complete response. Since decreased mentality maintained throughout the follow up period based on outpatient clinic, brain MRI was performed and revealed multiple leptomeningeal metastasis. The Patient died 2 days after the diagnosis.

• Journal of Society of Preventive Korean Medicine
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• v.28 no.1
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• pp.119-130
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• 2024

Objectives : The objective of this review is to examine the variety of evaluation parameters utilized in clinical trials that assess the anticancer efficacy of herbal medicine, focusing on the importance of including both symptomatic management and direct anticancer effectiveness. Methods : A detailed literature review was conducted across PubMed, Embase, and the Cochrane Library to identify clinical trials investigating the antitumor efficacy of herbal medicine. The search was performed on February 22, 2024. This review specifically examined the employed outcome measures, which were then categorized and analyzed to understand their relevance and application in evaluating the anticancer properties of herbal medicine. Results : From an initial search of 900 records, 15 clinical trials were selected for in-depth analysis after deduplication and screening. These studies evaluated the efficacy of herbal medicine across various cancers, including hepatocellular carcinoma, colorectal cancer, and breast cancer, using outcome measures such as survival rates, disease control rates, and quality of life improvements. The research spanned multiple countries, primarily in East Asia and the United States, reflecting a global interest in herbal medicine as a complementary approach to cancer treatment. The present study demonstrated that herbal medicine, especially when used alongside standard treatments, potentially improved clinical outcomes and patient well-being. Conclusions : The findings of this review highlight the need for a broader focus on the full range of therapeutic capabilities of herbal medicine, including its direct anticancer effects, in the management of cancer patients. Future oncology research involving herbal medicine should integrate a wide spectrum of clinical endpoints to fully ascertain its impact on cancer treatment and patient health.

• Journal of Chest Surgery
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• v.57 no.2
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• pp.169-177
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• 2024

Background: Pericardial effusion (PE) is a serious condition in cancer patients, primarily arising from malignant dissemination. Pericardial window formation is a surgical intervention for refractory PE. However, the long-term outcomes and factors associated with postoperative survival remain unclear. Methods: We retrospectively analyzed data from 166 oncology patients who underwent pericardial window formation at Samsung Medical Center between 2011 and 2023. We analyzed survival and PE recurrence regarding surgical approach, cancer type, and cytopathological findings. To identify factors associated with survival, we utilized Cox proportional-hazards regression. Results: All patients had tumors documented in accordance with the American Joint Committee on Cancer staging manual, including lung (61.4%), breast (9.6%), gastrointestinal (9.0%), hematologic (3.6%), and other cancers (16.4%). Surgical approaches included mini-thoracotomy (67.5%) and thoracoscopy (32.5%). Postsurgical cytopathology confirmed malignancy in 94 cases (56.6%). Over a median follow-up duration of 50.0 months, 142 deaths and 16 PE recurrences occurred. The 1-year overall and PE recurrence-free survival rates were 31.4% and 28.6%, respectively. One-year survival rates were significantly higher for thoracoscopy recipients (43.7% vs. 25.6%, p=0.031) and patients with negative cytopathology results (45.1% vs. 20.6%, p<0.001). No significant survival difference was observed between lung cancer and other types (p=0.129). Multivariate analysis identified New York Heart Association class, cancer stage, and cytopathology as independent prognostic factors. Conclusion: This series is the largest to date concerning window formation among cancer patients with PE. Patients' long-term survival after surgery was generally unfavorable. However, cases with negative cytopathology or earlier tumor stage demonstrated comparatively high survival rates.

• BMB Reports
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• v.57 no.5
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• pp.244-249
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• 2024

Many types of cancer are associated with excessive angiogenesis. Anti-angiogenic treatment is an effective strategy for treating solid cancers. This study aimed to demonstrate the inhibitory effects of (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) in VEGFA-induced angiogenesis. The results indicated that MMPP effectively suppressed various angiogenic processes, such as cell migration, invasion, tube formation, and sprouting of new vessels in human umbilical vein endothelial cells (HUVECs) and mouse aortic ring. The inhibitory mechanism of MMPP on angiogenesis involves targeting VEGFR2. MMPP showed high binding affinity for the VEGFR2 ATP-binding domain. Additionally, MMPP improved VEGFR2 thermal stability and inhibited VEGFR2 kinase activity, suppressing the downstream VEGFR2/AKT/ERK pathway. MMPP attenuated the activation and nuclear translocation of NF-κB, and it downregulated NF-κB target genes such as VEGFA, VEGFR2, MMP2, and MMP9. Furthermore, conditioned medium from MMPP-treated breast cancer cells effectively inhibited angiogenesis in endothelial cells. These results suggested that MMPP had great promise as a novel VEGFR2 inhibitor with potent anti-angiogenic properties for cancer treatment via VEGFR2/AKT/ERK/NF-κB signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7509-7515
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• 2013

To assess the risk of cancers associated with sleep duration using meta-analysis of published cohort studies, we performed a comprehensive search using PubMed, Embase and Web of Science through October 2013. We combined hazard ratios (HRs) from individual studies using meta-analysis approaches. A random effect dose-response analysis was used to evaluate the relationship between sleep duration and cancer risk. Subgroup analyses and sensitivity analyses were also performed. Publication bias was evaluated using Funnel plots and Begg's test. A total of 13 cohorts from 12 studies were included in this meta-analysis, which included 723, 337 participants with 15, 156 reported cancer outcomes during a follow-up period ranging from 7.5 to 22 years. The pooled adjusted HRs were 1.06 (95% CI: 0.92, 1.23; P for heterogeneity =0.003) for short sleep duration, 0.91 (95% CI: 0.78, 1.07; P for heterogeneity <0.0001) for long sleep duration. In subgroup analyses stratified by cancer type, long duration of sleep showed an inverse relation with hormone-related cancer (HR=0.79; 95% CI: 0.65, 0.97; P for heterogeneity =0.009) and a greater risk of colorectal cancer (HR=1.29; 95% CI: 1.09, 1.52; P for heterogeneity =0.346). Further meta-analysis on dose-response relationships showed that the relative risks of cancer were 1.00 (95% CI: 0.99, 1.01; P for linear trend=0.9151) for one hour of sleep increment per day, and 1.00 (95% CI: 0.98, 1.01; P for linear trend=0.7749) for one hour of sleep increment per night. No significant dose-response relationship between sleep duration and cancer was found on non-linearity testing (P=0.5053). Our meta-analysis suggests a positive association between long sleep duration and colorectal cancer, and an inverse association with incidence of hormone related cancers like those in the breast. Studies with larger sample size, longer follow-up times, more cancer types and detailed measure of sleep duration are warranted to confirm these results.