1.IFITM3-mediated activation of TRAF6/MAPK/AP-1pathways induces acquired TKI resistance in clear cell renal cell carcinoma
Se Un JEONG ; Ja-Min PARK ; Sun Young YOON ; Hee Sang HWANG ; Heounjeong GO ; Dong-Myung SHIN ; Hyein JU ; Chang Ohk SUNG ; Jae-Lyun LEE ; Gowun JEONG ; Yong Mee CHO
Investigative and Clinical Urology 2024;65(1):84-93
Purpose:
Vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been the standard of care for advanced and metastatic clear cell renal cell carcinoma (ccRCC). However, the therapeutic effect of TKI monotherapy remains unsatisfactory given the high rates of acquired resistance to TKI therapy despite favorable initial tumor response.
Materials and Methods:
To define the TKI-resistance mechanism and identify new therapeutic target for TKI-resistant ccRCC, an integrative differential gene expression analysis was performed using acquired resistant cohort and a public dataset. Sunitinib-resistant RCC cell lines were established and used to test their malignant behaviors of TKI resistance through in vitro and in vivo studies. Immunohistochemistry was conducted to compare expression between the tumor and normal kidney and verify expression of pathway-related proteins.
Results:
Integrated differential gene expression analysis revealed increased interferon-induced transmembrane protein 3 (IFITM3) expression in post-TKI samples. IFITM3 expression was increased in ccRCC compared with the normal kidney. TKI-resistant RCC cells showed high expression of IFITM3 compared with TKI-sensitive cells and displayed aggressive biologic features such as higher proliferative ability, clonogenic survival, migration, and invasion while being treated with sunitinib. These aggressive features were suppressed by the inhibition of IFITM3 expression and promoted by IFITM3 overexpression, and these findings were confirmed in a xenograft model. IFITM3-mediated TKI resistance was associated with the activation of TRAF6 and MAPK/AP-1 pathways.
Conclusions
These results demonstrate IFITM3-mediated activation of the TRAF6/MAPK/AP-1 pathways as a mechanism of acquired TKI resistance, and suggest IFITM3 as a new target for TKI-resistant ccRCC.
2.Real-World Outcomes of Adalimumab Treatment for Moderate and Severe Psoriasis in Korean Patients (RAPSODI Study)
Dong Hyun KIM ; Sang Wook SON ; Ki-Heon JEONG ; Jiyoung AHN ; Eun-So LEE ; Il-Hwan KIM ; Un Ha LEE ; Hai-Jin PARK ; Joo Yeon KO ; Byung-Soo KIM ; Jin Ju KIM ; Javed RASHID ; Kwang Joong KIM
Annals of Dermatology 2023;35(2):107-115
Background:
Psoriasis imposes a significant treatment burden on patients, particularly impacting well-being and quality of life (QoL). The psychosocial impact of psoriasis treatments remains unexplored in most patient populations.
Objective:
To assess the impact of adalimumab on health-related QoL (HRQoL) in Korean patients with psoriasis.
Methods:
This 24-week, multicenter, observational study, assessed HRQoL in Korean patients treated with adalimumab in a real-world setting. Patient-reported outcomes (PROs) including European Quality of Life-5 Dimension scale (EQ-5D), EQ-5D VAS, SF-36, and DLQI were evaluated at week 16 and 24, versus baseline. Patient satisfaction was assessed using TSQM.
Results:
Among 97 enrolled patients, 77 were assessed for treatment effectiveness. Most patients were male (52, 67.5%) and mean age was 45.4 years. Median baseline body surface area and Psoriasis Area and Severity Index (PASI) scores were 15.00 (range 4.00~80.00) and 12.40 (range 2.70~39.40), respectively. Statistically significant improvements in all PROs were observed between baseline and week 24. Mean EQ-5D score improved from 0.88 (standard deviation [SD], 0.14) at baseline to 0.91 (SD, 0.17) at week 24 (p=0.0067). The number of patients with changes in PASI 75, 90, or 100 from baseline to week 16 and 24 were 65 (84.4%), 17 (22.1%), and 1 (1.3%); and 64 (83.1%), 21 (27.3%), and 2 (2.6%), respectively. Overall treatment satisfaction was reported, including effectiveness and convenience. No unexpected safety findings were noted.
Conclusion
Adalimumab improved QoL and was well-tolerated in Korean patients with moderate to severe psoriasis, as demonstrated in a real-world setting. Clinical trial registration number (clinicaltrials.gov: NCT03099083).
3.A Case of Extramedullary Plasmacytoma in Both Maxillary Sinuses
Myeonggu SEO ; Ji-Hwan PARK ; Sung-Dong KIM ; Kyung Un CHOI ; Kyu-Sup CHO
Journal of Rhinology 2023;30(3):173-176
Plasmacytoma is a rare hematolymphoid malignancy. The three types of plasmacytoma, according to clinical features and morphological characteristics, include solitary bone plasmacytoma, extramedullary plasmacytoma (EMP), and multiple myeloma (MM). Although EMP of the head and neck region accounts for approximately 3% of all plasma cell tumors, the involvement of both paranasal sinuses is extremely rare. Herein, we describe a rare case of EMP involving both maxillary sinuses in a 73-year-old male patient who had achieved complete remission from MM following chemotherapy 2 years ago. The EMP was treated successfully with radiotherapy.
5.A simplified two-marker immunohistochemistry strategy for Lynch syndrome screening in endometrial cancer patients
Ala AIOB ; Yeo Rae KIM ; Kidong KIM ; Hyojin KIM ; Yong Beom KIM ; Duck Woo KIM ; Jae Hong NO ; Soo Hyun SEO ; Dong Hoon SUH ; Kyoung Un PARK
Obstetrics & Gynecology Science 2023;66(6):537-544
Objective:
To examine the efficacy of MSH6 and PMS2 immunohistochemistry (IHC) as a screening method for Lynch syndrome in endometrial cancer patients.
Methods:
Through multidisciplinary discussions, an institutional MSH6 and PMS2 IHC-initiated cascade test (MSH6, PMS2 IHC→microsatellite instability [MSI] assay→germline mismatch repair [MMR] gene sequencing) was developed to screen for Lynch syndrome in endometrial cancer patients. Testing was performed on a consecutive cohort of 218 newly diagnosed endometrial cancer patients who underwent surgery at a tertiary hospital in the Republic of Korea between August 2018 and December 2020. The number of MMR deficiencies (MSH6 or PMS2 loss in IHC) and results of subsequent tests (MSI assay and germline MMR gene sequencing) were examined.
Results:
MMR deficiency was detected in 52 of the 218 patients (24.0%). Among these 52 patients, 34 (65.0%) underwent MSI testing, of which 31 (91.0%) exhibited high MSI. Of the 31 patients with MSI-high status, 15 (48.0%) underwent germline MMR gene sequencing. Subsequently, Lynch syndrome was diagnosed in five patients (33.0%).
Conclusion
Lynch syndrome screening using MSH6 and PMS2 IHC-initiated cascade testing is a viable strategy in the management of endometrial cancer. A simplified strategy (MSH6 and PMS2 IHC→germline MMR gene sequencing) was proposed because most women with MMR deficiencies exhibited high MSI.
6.The Influence of Face Shields on the Quality of Colonoscopy in the Era of the COVID-19 Pandemic
Jin Wook LEE ; Hyo Jeong LEE ; Dae Sung KIM ; Jiyoung YOON ; Seung Wook HONG ; Ha Won HWANG ; Jong-Soo LEE ; Gwang-Un KIM ; Sinwon LEE ; Jaewon CHOE ; Jin Hwa PARK ; Dong-Hoon YANG ; Jeong-Sik BYEON
Gut and Liver 2022;16(3):404-413
Background/Aims:
The worldwide coronavirus disease 2019 pandemic has led endoscopists to use personal protective equipment (PPE) for infection prevention. This study aimed to investigate whether wearing a face shield as PPE affects the quality of colonoscopy.
Methods:
We reviewed the medical records and colonoscopy findings of patients who underwent colonoscopies at Asan Medical Center, Korea from March 10 to May 31, 2020. The colonoscopies in this study were performed by five gastroenterology fellows and four expert endoscopists. We compared colonoscopy quality indicators, such as withdrawal time, adenoma detection rate (ADR), mean number of adenomas per colonoscopy (APC), polypectomy time, and polypectomy adverse events, both before and after face shields were added as PPE on April 13, 2020.
Results:
Of the 1,344 colonoscopies analyzed, 715 and 629 were performed before and after the introduction of face shields, respectively. The median withdrawal time was similar between the face shield and no-face shield groups (8.72 minutes vs 8.68 minutes, p=0.816), as was the ADR (41.5% vs 39.8%, p=0.605) and APC (0.72 vs 0.77, p=0.510). Polypectomy-associated quality indicators, such as polypectomy time and polypectomy adverse events were also not different between the groups. Quality indicators were not different between the face shield and no-face shield groups of gastroenterology fellows, or of expert endoscopists.
Conclusions
Colonoscopy performance was not unfavorably affected by the use of a face shield. PPE, including face shields, can be recommended without a concern about colonoscopy quality deterioration.
7.Ileal long-segment ischemia after the unintended ligation of variant ileal branch during laparoscopic right hemicolectomy
Gyung Mo SON ; Tae Un KIM ; Dong-Hoon SHIN ; Joo-Young NA ; In Young LEE ; Shin Hoo PARK
Journal of Minimally Invasive Surgery 2022;25(3):116-119
The variant terminal trunk of the superior mesenteric artery (SMA) could be confused with the ileocolic artery (ICA) as it runs on the right side of the superior mesenteric vein. If the variant ileal branch of SMA is mistaken for the ICA, unintentional ligation could cause long-segment ischemia in the ileum. We encountered a rare case of ileal ischemia caused by unintentional ligation of the variant ileal branch of the SMA during laparoscopic right hemicolectomy, which was confirmed by indocyanine green (ICG) angiography and hyperspectral imaging (HSI). Intraoperative real-time perfusion monitoring using ICG angiography and tissue oxygen saturation monitoring using HSI could help detect segments of hypoperfusion and prevent hypoperfusion-related anastomotic complications.
8.Multidisciplinary treatment strategy for early colon cancer
Gyung Mo SON ; Su Bum PARK ; Tae Un KIM ; Byung-Soo PARK ; In Young LEE ; Joo-Young NA ; Dong Hoon SHIN ; Sang Bo OH ; Sung Hwan CHO ; Hyun Sung KIM ; Hyung Wook KIM
Journal of the Korean Medical Association 2022;65(9):558-567
Treatment for early colon cancer has progressed rapidly with endoscopic resection and minimally invasive surgery. Selection of patients without risk of lymph node metastasis is necessary before deciding on endoscopic resection for early colon cancer treatment. We aimed to review the optimal multidisciplinary treatment strategies for early colon cancer, including endoscopy and surgery.Current Concepts: Pathological risk factors include histologic grade of cancer cell differentiation, lymphovascular invasion, perineural invasion, tumor budding, and deep submucosal invasion. These risk factors for predicting lymph node metastasis are crucial for determining the treatment strategy of endoscopic excision and radical resection for early colon cancer. Prediction of the depth of invasion in early colon cancer using endoscopic optical assessments is vital to determine the appropriate treatment method for endoscopic or surgical resection. Furthermore, optical assessment of pit and vascular patterns is useful for estimating the depth of submucosal invasion using magnifying chromoendoscopy and narrow-band imaging endoscopy. Performing an endoscopic and pathologic evaluation of the risk factors for lymph node metastasis is imperative when selecting endoscopic or surgical resection. Endoscopic treatments include cold snare polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection. In addition, appropriate surgical treatment should be recommended for patients with early colon cancer with a high risk of lymph node metastasis.Discussion and Conclusion: A multidisciplinary approach should be recommended to establish an optimized treatment strategy, minimize the risk of complications, and obtain excellent oncologic outcomes via patienttailored treatment in patients with early colon cancer.
9.Three Cases of SARS-CoV-2 Infection with Cold Antibody of Undetermined Specificity in Antibody Screening in Transfusion Labs
Beom Joon KIM ; Dong Woo SHIN ; Yun Ji HONG ; Hyungsuk KIM ; Kyoung Un PARK
Korean Journal of Blood Transfusion 2022;33(2):107-113
SARS-CoV-2 infections continue to occur in this worldwide pandemic and have been associated with various symptoms, including autoimmune disorders. Of the latter, several reports of SARS-CoV-2-associated cold-agglutinin syndrome (CAS) have been published. CAS is associated with other viral infections, such as that by the Epstein–Barr virus. This paper reports a case series of SARS-CoV-2-associated cold-agglutinin syndrome presenting as an antibody of undetermined specificity mainly reactive at cold temperatures and mostly detected as C3d, but sometimes as IgM on the direct antiglobulin test.
10.Synchronous Quadruple Colon Cancer With Two Lesions Previously Obscured by Ischemic Colitis, Plus Bladder Cancer and Thymoma: A Case Report
Byung-Soo PARK ; Sung Hwan CHO ; Su Jin KIM ; Tae Un KIM ; Dong Il KIM ; Gyung Mo SON ; Hyun Sung KIM
Annals of Coloproctology 2021;37(Suppl 1):S44-S47
Synchronous quadruple colorectal cancer (CRC) is extremely rare without genetic alterations. We present a case of synchronous quadruple CRC with 2 lesions previously obscured by ischemic colitis. A 73-year-old woman was admitted to our emergency department. An abdominal computed tomography revealed ischemic colitis and irregular wall thickening of the sigmoid colon and sigmoid-descending junction, suspicious of 2 colon cancers. A colonoscopy examination revealed a fungating mass 20 cm from the anal verge, as well as ischemic colitis spanning the mucosa from the sigmoid colon to the transverse colon. The patient underwent laparoscopic Hartmann procedure. Pathologic examination confirmed both lesions as adenocarcinomas with microsatellite stable. Seven months postoperatively, instead of a laparoscopic Hartmann reversal, a laparoscopic total colectomy was performed due to the continued presence of severe ischemic colitis. The pathologic report suggested the presence of 2 distinct invasive adenocarcinomas in the descending colon without genetic alterations such as microsatellite instability.

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