Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOPinduced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects.

Purpose: The purpose of this study was to investigate the concordance rate of PIK3CA mutations between primary and matched distant metastatic sites in patients with breast cancer and to verify whether there are differences in the frequency of PIK3CA hotspot mutations depending on the metastatic sites involved. Materials and Methods: Archived formalin-fixed paraffin-embedded (FFPE) specimens of primary breast and matched distant metastatic tumors were retrospectively obtained for 49 patients. Additionally, 40 archived FFPE specimens were independently collected from different breast cancer metastatic sites, which were limited to three common sites: the liver, brain, and lung. PIK3CA mutations were analyzed using droplet digital PCR, including hotspots involving exons 9 and 20. Results: After analysis of 49 breast tumors with matched metastasis sites, 87.8% showed concordance in PIK3CA mutation status. According to PIK3CA hotspot mutation testing in 89 cases of breast cancer metastatic sites, the proportion of PIK3CA mutations at sites of metastasis involving the liver, brain, and lung was 37.5%, 28.6%, and 42.9%, respectively, which did not result in statistical significance. Conclusion The high concordance of PIK3CA mutation status between primary and matched metastasis sites suggests that metastatic sites, regardless of the metastatic organ, could be considered sample sources for PIK3CA mutation testing for improved therapeutic strategies in patients with metastatic breast cancer.

The number of migrant workers is increasing worldwide every year, and their number and role in Korean society is also increasing. However, the poor conditions faced by migrant workers often become a social issue, and it is not uncommon for them to be the subject of forensic autopsies. This study aimed to investigate the current status of medicolegal autopsy on migrant workers in Korea. We collected data of medicolegal autopsies on migrant workers conducted in Korea from 2016 to 2020 by requesting data from the institutions performing medicolegal autopsy. We calculated the autopsy rate and analyzed manner of death and cause of death. The medicolegal autopsy rate for foreign deaths was 16.4%, which was more than five times higher than the autopsy rate for Korean deaths. By manner of death, 43.7% were natural death, 6.4% were homicides, 8.5% were suicides, 23.6% were accidental deaths, 2.7% were undetermined unnatural deaths and 15.0% were unknown. These results showed a high rate of homicide, accidental death, and unknown death compared to Korean. And the proportion of industrial accident deaths and sudden manhood death syndrome were high. Through this study, it was confirmed that medicolegal autopsies are performed at a relatively high frequency when migrant workers die, and the characteristics related to the deaths of migrant workers were identified.

Sudden death during or after percutaneous coronary intervention (PCI) could be led to potential medicolegal disputes. This study aimed to investigate the clinical and postmortem findings in PCI-related deaths-focusing on the current statusto inform preventive strategies against these fatalities. Forty-three cases were retrieved from the National Forensic Service's postmortem records between 2015 and 2021, and the corresponding postmortem findings and clinical information were analyzed. The analyses revealed a relatively consistent annual incidence of PCI-related deaths. Immediate deaths during or shortly after PCI occurred in 17 cases (39.5%), and delayed PCI-related deaths after discharge from the hospital occurred in 26 cases (60.5%). The causes of PCI-related deaths in the postmortem cases were categorized into four groups: PCI complications (11 cases, 26%), acute myocardial infarction (23 cases, 53%), ischemic heart disease (8 cases, 19%), and others (1 case, 2%). Postmortem examinations played a critical role in determining the cause of death and obtaining medical evidence, including pathological findings of the heart as well as those of coronary artery and stent insertion. Our findings suggest that a detailed examination of the heart, coronary arteries, stent status, and atherosclerosis in PCI-related deaths could help provide more accurate information as medical evidence and prevent/resolve potential medicolegal issues. Further, this could advance our understanding of PCI-related deaths and inform future preventive strategies.

Colorectal strictures are uncommon in patients with ulcerative colitis (UC). An extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is rarely involved in the colon but may be associated with inflammatory bowel diseases. A 41-year-old female with a six-year history of UC presented with a severe stricture of the sigmoid colon that prevented the passage of a colonoscope. A histological examination revealed non-specific inflammation and fibrosis without dysplasia or cancer.Despite conventional treatment, including mesalazine and azathioprine for one year after that visit, the stricture persisted. In addition, diffuse, edematous exudative inflammation and multiple shallow ulcers were observed in the distal rectum, revealing a MALT lymphoma testing positive for CD20, CD43, CD5, and Bcl-2, but negative for CD3, CD10, CD23, and cyclin-D1. Four weekly doses of rituximab were administered. Follow-up colonoscopy performed one month after treatment revealed slight improvement in the rectal lesion without remnant histological evidence of a MALT lymphoma. In addition, the stricture showed marked improvement, and the colonoscope could pass easily through the stricture site. This is the first case report on an improvement of a severe sigmoid colon stricture in a patient with UC after rituximab treatment for a concomitant rectal MALT lymphoma.

Purpose: NUT carcinoma (NC) is a solid tumor caused by the rearrangement of NUTM1 that usually develops in midline structures, such as the thorax. No standard treatment has been established despite high lethality. Thus, we investigated whether targeting the junction region of NUTM1 fusion breakpoints could serve as a potential treatment option for NC. Materials and Methods: We designed and evaluated a series of small interfering RNAs (siRNAs) targeting the junction region of BRD4-NUTM1 fusion (B4N), the most common form of NUTM1 fusion. Droplet digital polymerase chain reaction using the blood of patients was also tested to evaluate the treatment responses by the junction sequence of the B4N fusion transcripts. Results: As expected, the majority of NC fusion types were B4N (12 of 18, 67%). B4N fusion-specific siRNA treatment on NC cells showed specific inhibitory effects on the B4N fusion transcript and fusion protein without affecting the endogenous expression of the parent genes, resulting in decreased relative cell growth and attenuation of tumor size. In addition, the fusion transcript levels in platelet-rich-plasma samples of the NC patients with systemic metastasis showed a negative correlation with therapeutic effect, suggesting its potential as a measure of treatment responsiveness. Conclusion This study suggests that tumor-specific sequences could be used to treat patients with fusion genes as part of precision medicine for a rare but deadly disease.

Mucinous carcinoma is a rare histologic type of breast cancer that, when classified with favorable histology, can be treated with different therapeutic options. This study reviews the histologic findings of mucinous carcinoma that support or exclude favorable histology and emphasizes the necessity of an appropriate gross examination with radiologic findings for an accurate diagnosis. In addition, unusual findings such as micropapillary arrangements and lobular differentiation in mucinous carcinoma and their implications for prognosis and treatment are reviewed. Mucinous carcinoma involves upregulation of MUC2, a mucus-associated gene common in mucinous carcinoma of the breast as well as various other organs. In mucinous carcinoma, the fraction of genome altered and tumor mutation burden are lower than those of invasive carcinoma of no special type, the most common histology of breast cancer. In addition, the genetic alterations found in mucinous carcinoma are diverse, unlike the pathognomonic genetic alterations observed in other histologic types of breast cancer. These genetic features support the importance of conventional microscopic evaluations for the pathologic differential diagnosis of mucinous carcinoma of the breast in routine practice. A variety of breast lesions, including mucinous cystadenocarcinoma and mucocele-like lesions, as well as mucinous carcinoma from other organs, can mimic mucinous carcinoma of the breast. In order to obtain an accurate pathologic diagnosis, careful evaluation of the overall histopathologic characteristics and ancillary testing are required to provide information on appropriate treatment and prognosis.

Objectives: This study aimed to analyze the outcomes of the Comprehensive Health and Social Need Assessment (CHSNA) system, which identifies community residents’ health and social needs, and to link these needs with the International Classification of Functioning, Disability, and Health (ICF). Methods: Adult community residents in a metropolitan city in Korea were recruited. They were asked to assess their health and social needs via the CHSNA system, which was integrated into an online community-care platform. Three assessment steps (basic health assessment, needs for activities of daily living, and in-depth health assessment) associated with five ICF components were used to evaluate physical health impairment, difficulties in activities and participation, and environmental problems. The final list of health and social needs was systematically linked to the domains and categories of the ICF. Only data from participants who completed all three assessment steps were included. Results: Wide ranges of impairments and difficulties regarding the daily living activities, physical health, and environmental status of the community were recorded from 190 people who completed assessments of their health and social needs by the CHSNA system. These participants reported various health and social needs for their community life; common needs corresponded to the ICF components of body functions and activities/participation. Conclusions The ICF may be suitable for determining the health-related problems and needs of the general population. Possible improvements to the present system include providing support for completing all assessment steps and developing an ICF core set for an enhanced understanding of health and social needs.

Purpose: To find biomarkers for disease, there have been constant attempts to investigate the genes that differ from those in the disease groups. However, the values that lie outside the overall pattern of a distribution, the outliers, are frequently excluded in traditional analytical methods as they are considered to be ‘some sort of problem.’ Such outliers may have a biologic role in the disease group. Thus, this study explored new biomarker using outlier analysis, and verified the suitability of therapeutic potential of two genes (TM4SF4 and LRRK2). Materials and Methods: Modified Tukey’s fences outlier analysis was carried out to identify new biomarkers using the public gene expression datasets. And we verified the presence of the selected biomarkers in other clinical samples via customized gene expression panels and tissue microarrays. Moreover, a siRNA-based knockdown test was performed to evaluate the impact of the biomarkers on oncogenic phenotypes. Results: TM4SF4 in lung cancer and LRRK2 in breast cancer were chosen as candidates among the genes derived from the analysis. TM4SF4 and LRRK2 were overexpressed in the small number of samples with lung cancer (4.20%) and breast cancer (2.42%), respectively. Knockdown of TM4SF4 and LRRK2 suppressed the growth of lung and breast cancer cell lines. The LRRK2 overexpressing cell lines were more sensitive to LRRK2-IN-1 than the LRRK2 under-expressing cell lines Conclusion Our modified outlier-based analysis method has proved to rescue biomarkers previously missed or unnoticed by traditional analysis showing TM4SF4 and LRRK2 are novel target candidates for lung and breast cancer, respectively.

Fascioliasis is a zoonotic disease caused by Fasciola Hepatica that infects mainly cattle, sheep, and goats. Humans can be infected by water or aquatic plants contaminated with metacercariae. The authors encountered two cases of F. hepatica infection. One patient reported abdominal discomfort with marked eosinophilia. The other patient had chest discomfort with marked eosinophilia. The abdominal CT images revealed hypodense lesions in the liver. The ultrasonography-guided liver biopsy findings in both patients were indicative of parasitic infections. Serological tests confirmed the definite diagnoses. Both patients were treated with a single dose of triclabendazole, which is the treatment of choice for fascioliasis. These findings suggest that a diagnosis of fascioliasis, particularly in the acute phase, should be considered in patients with abdominal pain, marked eosinophilia, and hypodense hepatic lesions on CT.