DFIQ, a Novel Quinoline Derivative, Shows Anticancer Potential by Inducing Apoptosis and Autophagy in NSCLC Cell and In Vivo Zebrafish Xenograft Models.

Lung cancer is one of the deadliest cancers worldwide due to chemoresistance in patients with late-stage disease. Quinoline derivatives show biological activity against HIV, malaria, bacteriuria, and cancer. DFIQ is a novel synthetic quinoline derivative that induces cell death in both in vitro and in vivo zebrafish xenograft models. DFIQ induced cell death, including apoptosis, and the IC50 values were 4.16 and 2.31 µM at 24 and 48 h, respectively. DFIQ was also found to induce apoptotic protein cleavage and DNA damage, reduce cell cycle-associated protein expression, and disrupt reactive oxygen species (ROS) reduction, thus resulting in the accumulation of superoxide radicals. Autophagy is also a necessary process associated with chemotherapy-induced cell death. Lysosome accumulation and lysosome-associated membrane protein-2 (LAMP2) depletion were observed after DFIQ treatment, and cell death induction was restored upon treatment with the autophagy inhibitor 3-methyladenine (3-MA). Nevertheless, ROS production was found to be involved in DFIQ-induced autophagy activation and LAMP2 depletion. Our data provide the first evidence for developing DFIQ for clinical usage and show the regulatory mechanism by which DFIQ affects ROS, autophagy, and apoptosis.

Changing Indications for Corneal Transplantations in Southern Taiwan From 2008 to 2018.

OBJECTIVES: To investigate the changing indications for corneal transplantations in southern Taiwan from 2008 to 2018 and compare the results with those of other previous studies. METHODS: We retrospectively reviewed the records of patients who underwent corneal transplantations from January 2008 to December 2018 at Kaohsiung Veterans General Hospital. The patients' age, sex, indication for corneal transplantation, and the surgical technique were recorded and analyzed. RESULTS: In total, 336 patients (421 eyes) were included in our study from January 1, 2008, to December 31, 2018. The mean age was 63.6±15.3 years; 371 penetrating keratoplasty (88.1%), 35 deep anterior lamellar keratoplasty (8.3%), and 15 Descemet-stripping automated endothelial keratoplasty (3.6%) were performed. The leading indication for corneal transplantation was regraft (n=103, 24.5%), followed by bullous keratopathy (n=82, 19.5%), corneal scar and opacity (n=79, 18.8%), keratitis (n=59, 14.0%), corneal dystrophy (n=58, 13.8%), other indications (n=26, 6.2%), and keratoconus (n=14, 3.3%). CONCLUSION: The indications for corneal transplantations changed with time in Taiwan. Regraft was the leading indication, but there was a decreasing trend over time. The proportion of bullous keratopathy increased significantly over the past decade and is the second most common indication, similar to the most developed countries. Both corneal scar and opacity, and keratitis showed a decreasing trend of occurrence compared with a previous study in Taiwan. The proportion of keratoconus remained low, making it the least common indication for corneal transplantation.

Distant metastasis in choroidal melanoma with spontaneous corneal perforation and intratumoral calcification: A case report.

BACKGROUND: Uveal melanoma is the most common primary intraocular malignancy in adults, but its incidence is low in Asian populations. Spontaneous corneal perforation and intratumoral calcification are rare presentations of choroidal melanoma (CM) , and reports regarding these presentations have been limited. Even after complete surgical treatment, the prognosis of CM patients is usually poor if distant metastasis is present. We here present a case of CM with unique presentations and early distant metastasis to the liver. CASE SUMMARY: A 63-year-old Asian woman presented to our hospital with complaint of pain and brownish discharge from her left eye for 3 d. Imaging studies revealed intratumoral calcification within the left eye with eyeball rupture. Enucleation of the left eye was performed and pathological examination confirmed the diagnosis of CM. Systemic surveillance revealed no metastatic diseases. However, the patient was lost to follow-up 3 mo after surgery. At 1.5 years after the operation, she presented to our emergency department with complaint of dull epigastric pain that radiated to the back for 1 d. Imaging studies revealed a large mass at the upper abdomen abutting the pancreatic neck and body as well as several nodular lesions in the liver. Fine needle biopsy was performed and findings confirmed liver and pancreatic metastases. CONCLUSION: This case highlights the importance of continued follow-up of patients with CM.

Hepatoma-derived growth factor supports the antiapoptosis and profibrosis of pancreatic stellate cells.

Pancreatic cancer is refractory and is characterized by extensively surrounding and intratumor fibrotic reactions that are contributed by activated pancreatic stellate cells (PSCs). Herein, we show that CCAAT/enhancer-binding protein δ (CEBPD) responds to transforming growth factor-ß1 (TGF-ß1) through reciprocal loop regulation and that activated hypoxia inducible factor-1α (HIF-1α) further contributes to the upregulation of the hepatoma-derived growth factor (HDGF) gene. Secreted HDGF contributes to the antiapoptosis of PSCs and consequently leads to the synthesis and deposition of extracellular matrix proteins for stabilizing PSC/pancreatic cancer cell (PCC) tumor foci. This result agrees with the observation that severe stromal growth positively correlated with stromal HDGF and CEBPD expression in pancreatic cancer specimens. Collectively, the identification of the TGF-ß1-activated CEBPD/HIF-1α/HDGF axis provides new insights into novel discoveries of HDGF in the antiapoptosis and profibrosis of PSCs and the outgrowth of PCCs.