Objective: Signal transducer and activator of transcription 3 (STAT3) plays key roles in regulating cancer cell proliferation, survival, and metastasis. We aimed to determine the effects of YHO-1701, an oral STAT3 inhibitor, in ovarian cancer (OC). Methods: We evaluated the impact of YHO-1701 on cell growth in patient-derived cells (PDCs) and OC cell lines using standard cell proliferation assays. Spheroid models derived from PDCs were assessed using three-dimensional (3D) cell viability assays. Antitumor activity was performed in SKOV3 xenograft mice treated orally administrated YHO-1701 with 20 mg/kg.Changes in STAT3 signaling were analyzed by western blotting. The molecular mechanisms of STAT3 inhibition were investigated by sequencing RNA and analyzing pathways in the SKOV3 using a small interfering RNA targeting STAT3 (STAT3 siRNA) and YHO-1701. Results: YHO-1701 inhibited the growth of OC cell lines by preventing STAT3 dimerization and decreasing the expression of its downstream signaling molecule, survivin. The growth of PDCs and spheroids obtained from patients with primary and recurrent OCs was significantly inhibited. Antitumor effect was observed in the SKOV3 xenograft mice with YHO-1701. YHO-1701 induced apoptosis in OC cells. Additionally, p53 and/or MAPK signaling pathways were upregulated in SKOV3 cells incubated with YHO-1701 and in those with STAT3 siRNA. Conclusion Our results showed that YHO-1701 suppressed cell growth in PDCs of OC, accompanied by survivin inhibition, and a decrease in the number of peritoneal metastasis in the mice by YHO-1701, compared with those treated with control. Therefore, YHO-1701 could be a promising candidate agent for treating OC

Conventional endoscopy often misses early gastric cancers with minimal red discoloration because they cannot be distinguished from inflamed mucosa. We treated a patient with a small early gastric cancer that was difficult to diagnose using conventional endoscopy. Conventional endoscopy using a small-caliber endoscope showed only subtle red discoloration of the gastric mucosa. However, blue laser imaging showed a clearly discolored area measuring 10 mm in diameter around the red lesion, which was distinct from the surrounding inflamed mucosa. Irregular vessels on the tumor surface (suspicious for early gastric cancer) were observed even with small-caliber endoscopy. Biopsy revealed a well-moderately differentiated tubular adenocarcinoma, and endoscopic submucosal dissection was performed. Histopathological examination of the specimen confirmed well-moderately differentiated adenocarcinoma localized to the mucosa with slight depression compared to the surrounding mucosa, consistent with the endoscopic findings. This small early gastric cancer became clearly visible with blue laser imaging using small-caliber endoscopy.
Adenocarcinoma ; Biopsy ; Depression ; Endoscopes ; Endoscopy ; Gastric Mucosa ; Humans ; Mucous Membrane ; Stomach Neoplasms

White light imaging (WLI) may not reveal early upper gastrointestinal cancers. Linked color imaging (LCI) produces bright images in the distant view and is performed for the same screening indications as WLI. LCI and blue laser imaging (BLI) provide excellent visibility of gastric cancers in high color contrast with respect to the surrounding tissue. The characteristic purple and green color of metaplasias on LCI and BLI, respectively, serve to increase the contrast while visualizing gastric cancers regardless of a history of Helicobacter pylori eradication. LCI facilitates color-based recognition of early gastric cancers of all morphological types, including flat lesions or those in an H. pylori-negative normal background mucosa as well as the diagnosis of inflamed mucosae including erosions. LCI reveals changes in mucosal color before the appearance of morphological changes in various gastric lesions. BLI is superior to LCI in the detection of early esophageal cancers and abnormal findings of microstructure and microvasculature in close-up views of upper gastrointestinal cancers. Excellent images can also be obtained with transnasal endoscopy. Using a combination of these modalities allows one to obtain images useful for establishing a diagnosis. It is important to observe esophageal cancers (brown) using BLI and gastric cancers (orange) surrounded by intestinal metaplasia (purple) and duodenal cancers (orange) by LCI.
Diagnosis ; Endoscopy ; Esophageal Neoplasms ; Gastrointestinal Neoplasms ; Helicobacter pylori ; Mass Screening* ; Metaplasia ; Microvessels ; Mucous Membrane ; Stomach Neoplasms

Barrett's adenocarcinoma may occur in multiple sites, and recurrence and metachronous lesions are the major problems with endoscopic resection. Therefore, early detection of such lesions is ideal to achieve complete resection and obtain improved survival rates with minimally invasive treatment. Laser imaging systems allow multiple modalities of endoscopic imaging by using white light laser, flexible spectral imaging color enhancement (FICE), blue laser imaging (BLI), and linked color imaging even at a distant view. However, the usefulness of these modalities has not been sufficiently reported regarding Barrett's adenocarcinoma. Here, we report on a patient with three synchronous lesions followed by one metachronous lesion in a long segment with changes of Barrett's esophagus, all diagnosed with this new laser endoscopic imaging system and enhanced by using FICE and/or BLI with high contrast compared with the surrounding mucosa. Laser endoscopic imaging may facilitate the detection of malignancies in patients with early Barrett's adenocarcinoma.
Adenocarcinoma* ; Barrett Esophagus* ; Humans ; Mucous Membrane ; Recurrence ; Survival Rate