Tae Jin Lee

Sickle Cell Disease (SCD) is a severe genetic disorder causing vascular occlusion and pain by upregulating the adhesion molecule P-selectin on endothelial cells and platelets. It primarily affects infants and children, causing chronic pain, circulatory problems, organ damage, and complications. Thus, effective treatment and management are crucial to reduce SCD-related risks. Anti-P-selectin antibody Crizanlizumab (Crimab) has been used to treat SCD. In this study, the heavy and light chain (HC and LC) genes of anti-P-Selectin antibody Crimab were cloned into a plant expression binary vector. The HC gene was under control of the duplicated 35S promoter and nopaline synthase (NOS) terminator, whereas the LC gene was under control of the potato proteinase inhibitor II (PIN2) promoter and PIN2 terminator. Agrobacterium tumefaciens LBA4404 was used to transfer the genes into the tobacco (Nicotiana tabacum cv. Xanthi) plant. In plants the genomic PCR and western blot confirmed gene presence and expression of HC and LC Crimab proteins in the plant, respectively. Crimab was successfully purified from transgenic plant leaf using protein A affinity chromatography. In ELISA, plant-derived Crimab (Crimab^P) had similar binding activity to P-selectin compared to mammalian-derived Crimab (Crimab^M). In surface plasmon resonance, the K_D (dissociation binding constant) and response unit values were lower and higher than Crimab^P, respectively. Taken together, these results demonstrate that the transgenic plant can be applied to produce biofunctional therapeutic monoclonal antibody.

Background: Angiolipoma is a benign neoplasm mainly composed of adipose tissue and proliferating blood vessels and is relatively rare in the gastrointestinal tract. And among them, gastric angiolipomas are extremely rare and tend to be small. Case Presentation: We report the clinical and imaging features of a patient with a huge angiolipoma in the stomach and an episode of hematemesis and melena, caused by the ulceration of the gastric mucosa overlying the gastric subepithelial angiolipoma revealed by the endoscopic evaluation. The patient was anemic, and the anemia resolved after local surgical resection of the tumor. We also reviewed the imaging and histological features of the presenting gastric angiolipoma. Conclusion: Radiologists should be aware of this rare benign gastric tumor that may present with gastrointestinal hemorrhage.

Background: Renal leiomyoma is a challenging diagnostic and therapeutic condition. Given that 90% of leiomyomas originate from the renal capsule, leiomyoma presenting as a renal parenchymal mass is extraordinarily rare. Case Presentation: Herein, we report the clinical and imaging features of a patient with renal leiomyoma occurring in the renal parenchyma and mimicking renal cell carcinoma. We also review the clinical, imaging, and histological features of renal leiomyoma. Conclusion: An initial partial, simple or radical nephrectomy according to tumor size and patient’s underlying condition is suitable for larger, heterogeneous, and non-peripherally located tumors, even if they demonstrate hypointensity on T1- and T2-weighted images, considering the possibility of other diagnoses.

오현지, et al. J Korean Soc Radiol. 2022 Nov;83:e78. https://doi.org/10.3348/jksr.2022.0042

Dickkopf-3 (DKK3), a tumor suppressor, is frequently downregulated in various cancers. However, the role of DKK3 in ovarian cancer has not been evaluated. This study aimed to assess aberrant DKK3 expression and its role in epithelial ovarian carcinoma. DKK3 expression was assessed using immunohistochemistry with tissue blocks from 82 patients with invasive carcinoma, and 15 normal, 19 benign, and 10 borderline tumors as controls. Survival data were analyzed using Kaplan–Meier and Cox regression analysis. Paclitaxel-resistant cells were established using TOV-21G and OV-90 cell lines. Protein expression was assessed using Western blotting and immunofluorescence analysis. Cell viability was assessed using the MT assay and 3D-spheroid assay. Cell migration was determined using a migration assay. DKK3 was significantly downregulated in invasive carcinoma compared to that in normal, benign, and borderline tumors. DKK3 loss occurred in 56.1% invasive carcinomas and was significantly associated with disease-free survival and chemoresistance in serous adenocarcinoma. DKK3 was lost in paclitaxel-resistant cells, while β-catenin and P-glycoprotein were upregulated. Exogenous secreted DKK3, incorporated by cells, enhanced anti-tumoral effect and paclitaxel susceptibility in paclitaxel-resistant cells, and reduced the levels of active β-catenin and its downstream P-glycoprotein, suggesting that DKK3 can be used as a therapeutic for targeting paclitaxel-resistant cancer.

Wnt1‐inducible signaling pathway protein‐1 (WISP1) is a Cyr61/CTGF/NOV (CCN) family matricellular protein involved in adipogenesis and low‐grade inflammation in obesity. However, the roles of WISP1 in hepatic steatosis and insulin resistance in skeletal muscle remain elusive. Mouse primary hepatocytes and differentiated mouse skeletal muscle cells (C2C12) were treated with various concentrations of WISP1 and the functions and signaling pathways were analyzed by Western blot analysis. In vivo transfection for WISP1 knockdown was also performed to examine the effects of WISP1 on hepatic steatosis and skeletal muscle insulin resistance. Knockdown of WISP1 in high‐fat diet‐fed C57BL/6 mice significantly reduced (0.45–0.5%; p < 0.05) inflammation and JNK phosphorylation (45–50%; P < 0.01) and attenuated hepatic steatosis (approximately 55%; p < 0.001) and skeletal muscle insulin resistance (30–40%; p < 0.05). Treatment with WISP1 significantly induced inflammation (hepatocytes: approximately 500%; p < 0.01, C2C12 cells: approximately 500%; p < 0.01) and JNK phosphorylation (hepatocytes: approximately 200%; p < 0.01, C2C12 cells: approximately 280%; p < 0.01) in mouse primary hepatocytes and C2C12 mouse skeletal muscle cells. Moreover, it increased lipogenesis‐associated gene expression (200–300%; p < 0.01) and accumulation of triglycerides (approximately 320%; p < 0.01) in hepatocytes, and suppressed insulin signaling (approximately 50%; p < 0.01) in C2C12 cells. These WISP1‐induced effects were significantly abrogated in NFκB‐, JNK‐, and TLR4‐knockdown hepatocytes (p < 0.05) and C2C12 cells (p < 0.05). These results indicate that WISP1 contributes to hepatic steatosis and skeletal muscle insulin resistance through a TLR4‐activated inflammation/JNK signaling pathway and could be a useful therapeutic target for treatment of non‐alcoholic fatty liver disease and type 2 diabetes.

Jin S, et al. J Korean Med Sci. 2017 Aug;32(8):1327-1336. https://doi.org/10.3346/jkms.2017.32.8.1327