Ki Hyung Kim

Loss of Zonula Occludens-1 (ZO-1) Enhances Angiogenic Signaling in Ovarian Cancer Cells

Zonula occludens-1 (ZO-1), encoded by the TJP1 gene, is a crucial scaffolding protein within tight junctions that maintains epithelial and endothelial barrier integrity. In addition to its structural role, ZO-1 participates in signal transduction pathways that influence various cellular processes such as proliferation, differentiation, and apoptosis. Increasing evidence suggests that tight junction proteins, including ZO-1, play important regulatory roles in tumor progression, particularly by modulating metastasis, cell polarity, and vascular remodeling. Ovarian cancer, the most lethal gynecologic malignancy, is characterized by rapid growth, peritoneal dissemination, and a strong reliance on tumor angiogenesis. However, the specific role of ZO-1 in regulating angiogenesis within ovarian cancer remains poorly defined. In this study, we used CRISPR-Cas9-mediated gene editing to generate TJP1 knockout (KO) ovarian cancer cell lines and investigated the impact of ZO-1 loss on the expression of angiogenesis-related genes. Transcriptomic and qRT-PCR analyses revealed upregulation of KLF5 and IL-8, both of which are well-established pro-angiogenic factors. Furthermore, functional assessment using a Matrigel™ tube formation assay demonstrated that conditioned media from ZO-1-deficient cells significantly enhanced endothelial tube formation. These findings indicate that ZO-1 loss promotes a pro-angiogenic tumor microenvironment, likely through modulation of key signaling molecules such as KLF5 and IL-8. Therefore, ZO-1 may serve as a potential suppressor of angiogenesis and a therapeutic target in ovarian cancer.

Clinical Outcomes of Poly(ADP–Ribose) Polymerase Inhibitors as Maintenance Therapy in Patients with Ovarian Cancer in the Southeastern Region of Korea

Purpose: In this study, we aimed to retrospectively investigate the real-world clinical efficacy and adverse events of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors in real-world clinical practice among patients with newly diagnosed epithelial ovarian cancer. Methods: We retrospectively reviewed the medical records from hospitals. Patients with epithelial ovarian cancer treated with olaparib or niraparib as frontline maintenance treatment between 1 January 2014 and 31 December 2022 were included. Progression-free survival (PFS) was analyzed using the Kaplan–Meier method, and adverse events associated with PARP inhibitor treatment were investigated. Results: Ninety-six patients treated with PARP inhibitors were identified. The median follow-up period was 21.8 months (95% confidence interval [CI] 19.4–24.0). Twenty (20.1%) patients experienced disease progression, and two patients died. The median PFS was 45.3 months (95% CI 39.4–NA). BRCA1 or BRCA2 gene mutations and primary cytoreductive surgery were associated with better PFS. Adverse events of any grade occurred in 74 (77.1%) patients. Nineteen (19.8%) patients experienced PARP inhibitor therapy interruptions, and 35 (36.5%) patients experienced dose reductions. Only three patients discontinued the drug due to adverse events. Conclusions: In a real-world setting, PARP inhibitors showed efficacy comparable to that reported in published randomized controlled trials and had acceptable safety profiles.

Pulmonary cryptococcosis masquerading as lung metastasis in gynecologic cancers: Two case reports

Rationale: Pulmonary cryptococcal infections occur mainly in immunocompromised individuals, such as those with malignancies. Preoperative diagnosis of pulmonary cryptococcosis (PC) can be challenging for both clinicians and radiologists because of nonspecific clinical manifestations and variable radiologic features, as it is easily misdiagnosed as metastatic lung cancer. Patient concerns: In case 1, a 76-year-old woman with a history of cervical cancer presented with lung nodules detected on chest computed tomography (CT) 13 months after completing concurrent chemoradiotherapy. In case 2, a 56-year-old woman with a history of ovarian cancer presented with pulmonary nodules on chest CT 19 months after completing chemotherapy. Both patients were clinically asymptomatic, and tumor markers were not elevated. Diagnoses: In case 1, chest CT revealed multiple enhanced nodules with lobulated margins in the left lower lobe, and positron emission tomography (PET)-CT showed uptake in the nodule with a standardized uptake value of 3.7. In case 2, chest CT revealed several nodules in the right upper lobe abutting the right major fissure, and PET-CT revealed fluorodeoxyglucose uptake in the nodules. Pathology revealed granulomatous inflammation with cryptococcal infection, and mucicarmine and periodic acid-Schiff staining confirmed cryptococcal infection in both cases. Interventions: Presumptive diagnoses of lung metastases were made in both cases and thoracoscopic lobectomy was performed. Postoperatively, the patients received antifungal therapy with fluconazole. Outcomes: PC was differentially diagnosed and effectively managed. The patients remained disease-free for both PC and gynecological cancers during subsequent follow-ups. Lessons: Recognition that PC can mimic lung metastasis is important for managing gynecological cancers. PC should be considered in the differential diagnosis when single or multiple nodules are detected on chest radiography without elevation of tumor markers in patients with gynecological cancer.

Clinical Usefulness of Cancer Antigen (CA) 125, Human Epididymis 4, and CA72-4 Levels and Risk of Ovarian Malignancy Algorithm Values for Diagnosing Ovarian Tumors in Korean Patients With and Without Endometriosis

Tumor markers are useful for detection and preoperative evaluation of ovarian tumors. We evaluated the clinical usefulness of cancer antigen (CA) 125, human epididymis 4 (HE4), and CA72-4 levels and Risk of Ovarian Malignancy Algorithm (ROMA) values for differential diagnosis of malignant and borderline tumors among suspected ovarian tumors, and the effects of endometriosis on these tumor markers. In a total of 266 patients (213, 14, and 39 with benign, borderline and malignant tumors, respectively), CA125, HE4, and CA72-4 levels were measured, and ROMA values were calculated. Medians of each marker were compared among the three groups. The area under the ROC curve (AUC), sensitivity, and specificity were calculated to analyze the diagnostic performance of each marker. All markers were significantly higher in the malignant group than in the benign group. HE4 levels and ROMA values were significantly higher in the malignant group than in the borderline group. ROMA value had the highest AUC for distinguishing the malignant and borderline groups from the benign group in premenopausal (0.773) and postmenopausal (0.927) patients. CA125 level was significantly higher in patients with endometriosis than in those without ( ROMA value is the best marker to distinguish malignant and borderline tumors from benign tumors in pre- and postmenopausal patients. HE4 and CA72-4 levels provide information on possible CA125 elevation due to endometriosis.

Spontaneous reduction of transvaginal small bowel evisceration after abdominal hysterectomy for cervical cancer

Abstract Rationale: Transvaginal evisceration of the small bowel is an extremely rare condition after hysterectomy, which requires urgent surgical intervention to prevent serious bowel morbidity and mortality. Patient concerns: A 65-year-old woman presented with sudden-onset severe abdominal pain and a mass protruding through the vagina. The past surgical history was significant, with an abdominal hysterectomy for cervical cancer performed 11 weeks prior to presentation. Diagnosis: Pelvic examination revealed prolapsed small-bowel loops (18-20 cm in length). Pelvic computed tomography scan confirmed the presence of transvaginal evisceration of the small bowel. Interventions: Bowel reduction and urgent laparotomy were the selected treatment approaches for a detailed inspection and thorough washing of the intrα-abdominal cavity. A Foley catheter was inserted in the emergency room, with the subject in the lithotomy position. The prolapsed bowel loops spontaneously reduced without manual reduction, and the vault defect was repaired transvaginally. Outcomes: The patient experienced no postoperative complications and remained disease-free for 9months postoperatively. Lessons: Transvaginal evisceration of the small bowel should be considered a surgical emergency. A multidisciplinary approach to prompt case management involving clinicians in gynecology, general surgery, and emergency medicine is vital for preventing serious consequences. Hysterectomy is the most frequently performed gynecological surgical procedure, and evisceration occurs most often after hysterectomy. Therefore, patients should be informed about this rare but possible hysterectomy complication.

Successful treatment of locally advanced bulky cervical cancer complicated by irreducible complete uterine prolapse

Abstract Rationale: Cervical cancer complicated by irreducible complete uterine prolapse in elderly patients is extremely rare. No standard treatment has been established for these conditions. Patient concerns: A 74-year-old woman with a 30-year history of pelvic organ prolapse presented with irreducible complete uterine prolapse and a large exophytic mass involving the cervix and vaginal wall. Diagnosis: Biopsy of the mass was performed at the referring institution and showed invasive verrucous-type squamous cell carcinoma. Interventions: A prolapsed uterus with a tumor mass could not be manually reduced. After completion of concurrent chemoradiotherapy, the tumor mass in the prolapsed uterus decreased and could be reduced manually. Subsequently, the patient underwent hysterectomy and intra-abdominal uterosacral ligament suspension. Outcomes: At 19 months of postoperative follow-up, the patient remained disease-free and had no evidence of vault prolapse. Lessons: This study has important clinical implications and may provide a therapeutic strategy to address unmet medical needs in combination with locally advanced cervical cancer complicated by irreducible complete uterine prolapse. These conditions were successfully treated using a multidisciplinary approach of chemoradiotherapy followed by radical hysterectomy and uterosacral ligament suspension.