Min Jong Song

Clinical analysis of intra-operative frozen section proven borderline tumors of the ovary

OBJECTIVE We have assessed the accuracy of frozen section diagnosis and the outcomes of misdiagnosis in borderline tumors of the ovary (BTO) according to frozen section. METHODS All pathology reports with BTO in both frozen and permanent section analyses between 1994 and 2008 at Seoul St. Marys Hospital were reviewed. Frozen section diagnosis and permanent section histology reports were compared. Logistic regression models were conducted to evaluate the correlation of patient and tumor characteristics with diagnostic accuracy. The clinical outcomes of misdiagnosis were evaluated. RESULTS Agreement between frozen section diagnosis and permanent histology was observed in 63 of 101 patients (62.4%). Among the 76 patients with frozen section proven BTO, under-diagnosis and over-diagnosis occurred in 8 of 76 (10.5%) and 5 of 76 patients (6.6%), respectively. Mean diameter of under-diagnosed tumor was larger than matched BTO (21.0+/-11.4 vs. 13.7+/-7.1; p=0.021). Tumor size 20 cm was determined as the optimal cut-off for under-diagnosis (50% sensitivity, 87.3% specificity). Among 8 under-diagnosed patients, no patient relapsed. Among 5 over-diagnosed patients, 2 patients < 35 years of age had fertility-preserving surgery. CONCLUSION Although frozen section diagnosis is an important and reliable tool in the clinical management of patients with ovarian tumors, over-diagnosis and under-diagnosis are relatively frequent in frozen proven BTO. Surgical decision-making for BTO based on frozen section diagnosis should be done carefully, especially in large tumors.

Anti-cancer effect of bee venom on colon cancer cell growth by activation of death receptors and inhibition of nuclear factor kappa B.

Bee venom (BV) has been used as a traditional medicine to treat arthritis, rheumatism, back pain, cancerous tumors, and skin diseases. However, the effects of BV on the colon cancer and their action mechanisms have not been reported yet. We used cell viability assay and soft agar colony formation assay for testing cell viability, electro mobility shift assay for detecting DNA binding activity of nuclear factor kappa B (NF-κB) and Western blotting assay for detection of apoptosis regulatory proteins. We found that BV inhibited growth of colon cancer cells through induction of apoptosis. We also found that the expression of death receptor (DR) 4, DR5, p53, p21, Bax, cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9 was increased by BV treatment in a dose dependent manner (0–5 μg/ml). Consistent with cancer cell growth inhibition, the DNA binding activity of nuclear factor kappa B (NF-κB) was also inhibited by BV treatment. Besides, we found that BV blocked NF-κB activation by directly binding to NF-κB p50 subunit. Moreover, combination treatment with BV and p50 siRNA or NF-κB inhibitor augmented BV-induced cell growth inhibition. However, p50 mutant plasmid (C62S) transfection partially abolished BV-induced cell growth inhibiton. In addition, BV significantly suppressed tumor growth in vivo. Therefore, these results suggested that BV could inhibit colon cancer cell growth, and these anti-proliferative effects may be related to the induction of apoptosis by activation of DR4 and DR5 and inhibition of NF-κB.

Incidence and clinicopathologic behavior of uterine cervical carcinoma in renal transplant recipients

BackgroundRenal allograft recipients are reported to have a higher incidence of malignancy than the general population. This single hospital-based study examined the incidence and clinicopathologic behavior of uterine cervical carcinoma in renal transplant recipients.MethodsAmong 453 women receiving renal transplantation from January 1990 to December 2008, 5 patients were diagnosed with cervical carcinoma. Medical records of these 5 patients were retrospectively reviewed, and clinicopathologic data were collected and analyzed.ResultsThe incidence of cervical carcinoma in renal transplant recipients was 58.1 out of 100,000 per year, which is 3.5 times higher than in the general Korean population. The mean interval between the time of renal transplantation and the time of cervical carcinoma diagnosis was 80.7 months. After a median follow-up of 96.2 months, there was no recurrence of the disease or death. In 4 patients who were positive from human papillomavirus in situ hybridization (HPV ISH), high or probably high risk HPV DNA was detected in all. Punctate staining of HPV ISH was detected in 3 out of 4 patients.ConclusionsHigher incidence of cervical carcinoma is expected in renal transplant recipients, so appropriate surveillance is needed to ensure early detection and treatment of cervical carcinoma.

Correlation between immunocytochemistry of human papilloma virus L1 capsid protein and behavior of low‐grade cervical cytology in Korean women

Aim:  The aim of this study was to evaluate the behavior of low‐grade squamous intraepithelial lesion (LSIL) in Korean women infected with human papillomavirus (HPV) in relation to the immunocytochemical detection of the HPV L1 capsid protein.

MMPP Attenuates Non-Small Cell Lung Cancer Growth by Inhibiting the STAT3 DNA-Binding Activity via Direct Binding to the STAT3 DNA-Binding Domain

Rationale: Signal transducer and activator of transcription-3 (STAT3) plays a pivotal role in cancer biology. Many small-molecule inhibitors that target STAT3 have been developed as potential anticancer drugs. While designing small-molecule inhibitors that target the SH2 domain of STAT3 remains the leading focus for drug discovery, there has been a growing interest in targeting the DNA-binding domain (DBD) of the protein. Methods: We demonstrated the potential antitumor activity of a novel, small-molecule (E)-2-methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol (MMPP) that directly binds to the DBD of STAT3, in patient-derived non-small cell lung cancer (NSCLC) xenograft model as well as in NCI-H460 cell xenograft model in nude mice. Results: MMPP effectively inhibited the phosphorylation of STAT3 and its DNA binding activity in vitro and in vivo. It induced G1-phase cell cycle arrest and apoptosis through the regulation of cell cycle- and apoptosis-regulating genes by directly binding to the hydroxyl residue of threonine 456 in the DBD of STAT3. Furthermore, MMPP showed a similar or better antitumor activity than that of docetaxel or cisplatin. Conclusion: MMPP is suggested to be a potential candidate for further development as an anticancer drug that targets the DBD of STAT3.

Cell-mediated immune response to human papillomavirus 16 E7 peptide pools in patients with cervical neoplasia

Objective. To identify characteristics of the cell‐mediated immune (CMI) response to human papillomavirus‐16 (HPV) E7 viral peptide pools to help the formulation of therapeutic vaccines. Design. Prospective study. Population. Korean women. Setting. University hospital. Methods. From December 2008 to August 2010, 33 HPV‐16‐positive patients, seven patients exhibiting a high‐risk HPV infection other than HPV‐16 with grade 2/3 cervical intraepithelial neoplasm (CIN2/3), and nine healthy control donors were enrolled. Main Outcome Measures. CMI response to synthetic HPV‐16 E7 overlapping peptide pools using the IFN‐γ ELISPOT assay. Results. The E7 sequence comprising amino acids 16–55 was a major immunogenic region. The CMI response to HPV‐16 E7 is highly type‐specific. The follow‐up CMI response may last longer than expected after the lesion is resected. Conclusions. We found that the E7 sequence comprising amino acids 16–55 is a major immunogenic region that is critical for the T‐cell‐mediated immune response with CIN2/3 or cervical cancer. The identification of CMI responses to HPV‐16 E7 peptide pools may provide insight into therapeutic vaccine trials for the control of HPV‐associated diseases.

Autoamputation of an ovarian mature cystic teratoma: a case report and a review of the literature

BackgroundTorsion is known to be the most frequent complication of ovarian teratomas. Torsion of the adnexa usually manifests with severe abdominal pain and is treated as an acute surgical emergency. However, it may be asymptomatic. Autoamputation of an ovary, along with other adnexal structures, due to previous torsion is extremely rare.Case presentationA parasitic ovarian teratoma that underwent torsion, autoamputation, and reimplantation was found incidentally during laparoendoscopic single-site surgery (LESS). The amputated tumor was located in the omentum of the right upper abdomen of a patient with concomitant torsion of a left ovarian teratoma. The right ovary and tube were absent even though she had no surgical history. This finding could be interpreted as an autoamputation of the adnexa due to torsion of a previous ovarian cyst arising from the right ovary. We removed all masses by LESS.ConclusionsAlthough both ultrasonography and computed tomography were performed preoperatively in our patient, the correct diagnosis of autoamputation and exact localization of the teratoma were extremely difficult. Physicians should consider the possibility of an autoamputated ovarian cyst even if preoperative radiography shows no calcification.

Loss of Parkin reduces inflammatory arthritis by inhibiting p53 degradation

Parkin is associated with various inflammatory diseases, including Parkinsons disease (PD) and rheumatoid arthritis (RA). However, the precise role of Parkin in RA is unclear. The present study addressed this issue by comparing the development of RA between non-transgenic (non-Tg) mice and PARK2 knockout (KO) mice. We found that cyclooxygenase-2 and inducible nitric oxide synthase expression and nuclear factor-κB activity were reduced but p53 activation was increased in PARK2 KO as compared to non-Tg mice. These effects were associated with reduced p53 degradation. Parkin was found to interact with p53; however, this was abolished in Parkin KO mice, which prevented p53 degradation. Treatment of PARK2 KO mice with p53 inhibitor increased Parkin expression as well as inflammation and RA development while decreasing nuclear p53 translocation, demonstrating that PARK2 deficiency inhibits inflammation in RA via suppression of p53 degradation. These results suggest that RA development may be reduced in PD patients.

KRICT-9 inhibits neuroinflammation, amyloidogenesis and memory loss in Alzheimer’s disease models

Alzheimer’s disease (AD) is one of the most common forms of dementia and is characterized by neuroinflammation and amyloidogenesis. Here we investigated the effects of KRICT-9 on neuroinflammation and amyloidogenesis in in vitro and in vivo AD models. We found that KRICT-9 decreased lipopolysaccharide (LPS)-induced inflammation in microglial BV-2 cells and astrocytes while reducing nitric oxide generation and expression of inflammatory marker proteins (iNOS and COX-2) as well as APP, BACE1, C99, Iba-1, and GFAP. KRICT-9 also inhibited β-secretase. Pull-down assays and docking model analyses indicated that KRICT-9 binds to the DNA binding domain of signal transducer and activator of transcription 3 (STAT3). KRICT-9 also decreased β-secretase activity and Aβ levels in tissues from LPS-induced mice brains, and it reversed memory impairment in mice. These experiments demonstrated that KRICT-9 protects against LPS-induced neuroinflammation and amyloidogenesis by inhibiting STAT3 activity. This suggests KRICT-9 or KRICT-9-inspired reagents could be used as therapeutic agents to treat AD.

Giant Peritoneal Loose Body Formation due to Adnexal Torsion.

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