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1.
J Gynecol Oncol ; 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38330380

ABSTRACT

BACKGROUND: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.

2.
Sci Rep ; 14(1): 1957, 2024 01 23.
Article in English | MEDLINE | ID: mdl-38263154

ABSTRACT

Cervical cancer, the fourth most common cancer among women worldwide, often proves fatal and stems from precursor lesions caused by high-risk human papillomavirus (HR-HPV) infection. Accurate and early diagnosis is crucial for effective treatment. Current screening methods, such as the Pap test, liquid-based cytology (LBC), visual inspection with acetic acid (VIA), and HPV DNA testing, have limitations, requiring confirmation through colposcopy. This study introduces CerviCARE AI, an artificial intelligence (AI) analysis software, to address colposcopy challenges. It automatically analyzes Tele-cervicography images, distinguishing between low-grade and high-grade lesions. In a multicenter retrospective study, CerviCARE AI achieved a remarkable sensitivity of 98% for high-risk groups (P2, P3, HSIL or higher, CIN2 or higher) and a specificity of 95.5%. These findings underscore CerviCARE AI's potential as a valuable diagnostic tool for highly accurate identification of cervical precancerous lesions. While further prospective research is needed to validate its clinical utility, this AI system holds promise for improving cervical cancer screening and lessening the burden of this deadly disease.


Subject(s)
Papillomavirus Infections , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Female , Humans , Artificial Intelligence , Early Detection of Cancer , Retrospective Studies , Software
3.
Eur J Med Chem ; 265: 116050, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38128233

ABSTRACT

Poor intracellular uptake of therapeutics in the tumor parenchyma is a key issue in cancer therapy. We describe a novel approach to enhance tumor targeting and achieve targeted delivery of camptothecin (CPT) based on a tumor-homing internalizing RGD peptide (iRGD). We synthesized an iRGD-camptothecin conjugate (iRGD-CPT) covalently coupled by a heterobifunctional linker and evaluated its in vitro and in vivo activity in human colon cancer cells. In vitro studies revealed that iRGD-CPT penetrated cells efficiently and reduced colon cancer cell viability to a significantly greater extent at micromolar concentrations than did the parent drug. Furthermore, iRGD-CPT showed high distribution toward tumor tissue, effectively suppressed tumor progression, and showed enhanced antitumor effects relative to the parent drug in a mouse model, demonstrating that iRGD-CPT is effective in vivo cancer treatment. These results suggest that intracellular delivery of CPT via the iRGD peptide is a promising drug delivery strategy that will facilitate the development of CPT derivatives and prodrugs with improved efficacy.


Subject(s)
Antineoplastic Agents , Colonic Neoplasms , Animals , Mice , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Colonic Neoplasms/drug therapy , Drug Delivery Systems , Camptothecin/pharmacology , Camptothecin/therapeutic use
4.
Biosensors (Basel) ; 13(7)2023 Jul 03.
Article in English | MEDLINE | ID: mdl-37504103

ABSTRACT

We developed a transparent and flexible electrochemical sensor using a platform based on a network of single-walled carbon nanotubes (SWCNTs) for the non-enzymatic detection of hydrogen peroxide (H2O2) released from living cells. We decorated the SWCNT network on a poly(ethylene terephthalate) (PET) substrate with platinum nanoparticles (PtNPs) using a potentiodynamic method. The PtNP/SWCNT/PET sensor synergized the advantages of a flexible PET substrate, a conducting SWCNT network, and a catalytic PtNP and demonstrated good biocompatibility and flexibility, enabling cell adhesion. The PtNP/SWCNT/PET-based sensor demonstrated enhanced electrocatalytic activity towards H2O2, as well as excellent selectivity, stability, and reproducibility. The sensor exhibited a wide dynamic range of 500 nM to 1 M, with a low detection limit of 228 nM. Furthermore, the PtNP/SWCNT/PET sensor remained operationally stable, even after bending at various angles (15°, 30°, 60°, and 90°), with no noticeable loss of current signal. These outstanding characteristics enabled the PtNP/SWCNT/PET sensor to be practically applied for the direct culture of HeLa cells and the real-time monitoring of H2O2 release by the HeLa cells under drug stimulation.


Subject(s)
Metal Nanoparticles , Nanotubes, Carbon , Humans , Hydrogen Peroxide , HeLa Cells , Reproducibility of Results , Platinum , Electrochemical Techniques/methods , Electrodes
5.
PLoS One ; 18(2): e0277285, 2023.
Article in English | MEDLINE | ID: mdl-36757936

ABSTRACT

To better understand the mechanism of chemoresistance in ovarian cancer cells, we aimed to investigate the influence of macrophages on the tumor cell response to carboplatin and identify the genes associated with chemoresistance. We mimicked the tumor microenvironment (TME) using a co-culture technique and compared the proliferation of ovarian cells with and without macrophages. We also examined M1 and M2 marker expression and the expression of key TME genes. Post the co-culture, we treated ovarian cancer cells with carboplatin and elucidated the function of programmed death-ligand 1 (PD-L1) in carboplatin chemoresistance. We investigated CD68 and PD-L1 expression in normal and cancerous ovarian tissues using immunohistochemistry (IHC). Finally, we analyzed the association between CD68 or PD-L1 expression and survival outcomes. Inducible nitric oxide synthase (iNOS) was downregulated, while the gene expression of M2 macrophage markers was increased in ovarian cancer cells. PD-L1, vascular endothelial growth factor (VEGF), Interleukin (IL)-6, IL-10, IL-12, signal transducer and activator of transcription 3 (STAT3), B-cell lymphoma 2 (BCL2), multidrug resistance 1 (MDR1), and colony stimulating factor 1 (CSF-1) were upregulated. Notably, PD-L1 was upregulated in both the ovarian cancer cells and macrophages. Ovarian cancer cells co-cultured with macrophages exhibited statistically significant carboplatin resistance compared to single-cultured ovarian cancer cells. PD-L1 silencing induced chemosensitivity in both types of co-cultured ovarian cancer cells. However, IHC results revealed no correlation between PD-L1 expression and patient survival or cancer stage. CD68 expression was significantly increased in cancer cells compared to normal or benign ovarian tumor cells, but it was not associated with the survival outcomes of ovarian cancer patients. Our study demonstrated that ovarian cancer cells interact with macrophages to induce the M2 phenotype. We also established that PD-L1 upregulation in both ovarian cancer cells and macrophages is a key factor for carboplatin chemoresistance.


Subject(s)
B7-H1 Antigen , Ovarian Neoplasms , Humans , Female , B7-H1 Antigen/metabolism , Tumor-Associated Macrophages/metabolism , Up-Regulation , Carboplatin/pharmacology , Carboplatin/therapeutic use , Vascular Endothelial Growth Factor A/metabolism , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Interleukin-6/metabolism , Tumor Microenvironment
6.
Curr Issues Mol Biol ; 44(1): 288-300, 2022 Jan 09.
Article in English | MEDLINE | ID: mdl-35723400

ABSTRACT

The aim of the study was to develop a new diagnostic biomarker for identifying serum exosomal miRNAs specific to epithelial ovarian cancer (EOC) and to find out target gene of the miRNA for exploring the molecular mechanisms in EOC. A total of 84 cases of ovarian masses and sera were enrolled, comprising EOC (n = 71), benign ovarian neoplasms (n = 13). We detected expression of candidate miRNAs in the serum and tissue of both benign ovarian neoplasm group and EOC group using real-time polymerase chain reaction. Immunohistochemistry were constructed using formalin fixed paraffin embedded (FFPE) tissue to detect expression level of suppressor of cytokine signaling 4 (SOCS4). In the EOC group, miRNA-1290 was significantly overexpressed in serum exosomes and tissues as compared to benign ovarian neoplasm group (fold change ≥ 2, p < 0.05). We observed area under the receiver operating characteristic curve (AUC) for miR-1290, using a cut-off of 0.73, the exosomal miR-1290 from serum had AUC, sensitivity, and specificity values of 0.794, 69.2 and 87.3, respectively. In immunohistochemical study, expression of SOCS4 in EOC was lower than that in benign ovarian neoplasm. Serum exosomal miR-1290 could be considered as a biomarker for differential diagnosis of EOC from benign ovarian neoplasm and SOCS4 might be potential target gene of miR-1290 in EOC.

7.
Bioinorg Chem Appl ; 2022: 8453159, 2022.
Article in English | MEDLINE | ID: mdl-35464734

ABSTRACT

Phenalenyl (PLY)-based metal complexes are a new addition to the metal complex family. Various applications of metal-based phenalenyl complexes (metal-PLY) have been reported, such as catalyst, quantum spin simulators, spin electronic devices, and molecular conductors, but the biological significance of metal-PLY (metal = Co(II), Mn(III), Ni(II), Fe(III), and Al(III)) systems has yet to be explored. In this study, the anticancer properties of such complexes were investigated in ovarian cancer cells (SKOV3 and HEY A8), and the cytotoxicity was comparable to that of other platinum-based drugs. Antibacterial activity of the metal-PLY complexes against both gram-negative (E. coli) and gram-positive (S. aureus) bacteria was studied using a disk diffusion test and minimum inhibitory concentration (MIC) methods. All five metal-PLY complexes showed significant antibacterial activity against both bacterial strains. The antioxidant properties of metal-PLY complexes were evaluated following the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging method and were acceptable. The DNA-binding properties of these metal-PLY complexes were investigated using absorption spectroscopy, fluorescence spectroscopy, viscosity measurements, and thermal denaturation methods. Experimental evidence revealed that the complexes bind to DNA through intercalation, and the molecular docking study supported this conclusion.

8.
Drug Deliv ; 29(1): 270-283, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35014934

ABSTRACT

As mitochondria are potential therapeutic targeting sites for the treatment of human diseases, delivering cytotoxic drugs, antioxidants, and imaging molecules to mitochondria can provide new therapeutic opportunities. In an attempt to develop a new mitochondria-targeting vector, we synthesized sorbitol-based molecular transporters with multiple guanidines, measured their partition coefficients, compared their targeting efficiency using fluorescent images and Pearson's correlation coefficients, and studied cellular uptake mechanisms. To increase the targeting ability of these molecular transporters to mitochondria, alanine-naphthalene as a lipophilic group was attached to the molecular transporter, which improved translocation across cellular membranes and led to higher accumulation in mitochondria. The molecular transporter was able to form an ionic complex with antibiotics, resulting in low cell viability. These data demonstrate that the molecular transporter with a lipophilic group could be utilized as a potential drug delivery vector for treating mitochondrial dysfunction.


Subject(s)
Biological Transport/physiology , Drug Carriers/chemistry , Mitochondria/metabolism , Alanine/chemistry , Cell Line, Tumor , Cell Membrane , Cell Survival , Guanidines/chemistry , Humans , Naphthalenes/chemistry , Sorbitol/chemistry
9.
Doc Ophthalmol ; 144(2): 153-162, 2022 04.
Article in English | MEDLINE | ID: mdl-34997406

ABSTRACT

PURPOSE: To report a case of Vogt-Koyanagi-Harada (VKH) syndrome-like posterior uveitis after nivolumab administration to treat an ovarian cancer with an electrophysiological finding. A 61-year-old woman with ovarian cancer (stage 3A) and salpingo-oophorectomy surgery history visited the clinic complaining of blurred vision in both eyes. She had been enrolled a clinical trial using nivolumab in patients with ovarian cancer. She received four cycles of nivolumab administration and experienced blurred vision one week before the initial visit. There was no remarkable finding in the anterior segment and the vitreous body. Multiple subretinal fluid accumulations and serous retinal detachment were identified on the posterior pole. Subretinal fluid with choroidal folding was noted in optical coherence tomography, and multiple leakage points were also observed in wide-field fundus fluorescein angiography. Therefore, intravenous high-dose steroid pulse therapy was applied under the diagnosis of VKH syndrome-like posterior uveitis induced by an immunotherapy agent. After steroid therapy, the subretinal fluid was absorbed completely, and the patient's visual acuity was recovered to the normal range. The amplitudes in the multifocal electroretinogram were also restored after the treatment. CONCLUSION: Nivolumab is a human IgG4 monoclonal antibody and an immune checkpoint inhibitor. It is associated with the upregulation of T-cell activity by interfering with the interaction between the programmed death-1 (PD-1) receptor and the PD-ligand. Targeted therapy using immunotherapy agents has been widely used for malignant melanoma, lung cancer, renal cell carcinoma, and other cancers. However, immunotherapy agents such as nivolumab can induce autoimmune-related adverse events including uveitis. This report suggests that VKH syndrome-like posterior uveitis could be induced by nivolumab administration for an ovarian cancer treatment, which was resolved by steroid pulse therapy.


Subject(s)
Ovarian Neoplasms , Uveitis, Posterior , Uveitis , Uveomeningoencephalitic Syndrome , Electroretinography , Female , Fluorescein Angiography , Humans , Middle Aged , Nivolumab/adverse effects , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/drug therapy , Tomography, Optical Coherence , Uveomeningoencephalitic Syndrome/chemically induced , Uveomeningoencephalitic Syndrome/diagnosis , Uveomeningoencephalitic Syndrome/drug therapy
10.
Int J Pharm ; 606: 120904, 2021 Sep 05.
Article in English | MEDLINE | ID: mdl-34293467

ABSTRACT

Pt-based drugs are one of the main active agents in colorectal cancer treatment. However, drug resistance and dose-dependent side effects are the main barriers that restrict their clinical applications. As an alternative approach to these issues, we designed and synthesized a cell penetrating peptide (CPP) octaarginine-oxaliplatin conjugate that quickly and successfully delivered oxaliplatin into colon cancer cells. The CPP octaarginine is a well-studied cationic peptide that can play a role as a drug delivery vector. In this work, an octaarginine CPP (RRRRRRRR) was conjugated with oxaliplatin via a specific heterobifunctional linker. The in vitro studies showed the conjugate had affinity toward mitochondria inside cells and the MTT assay confirmed that conjugate is active in low micromolar range against colon cancer cells, requiring much lower concentrations than the oxaliplatin alone to reach IC50. More importantly, in the in vivo mouse study, the conjugate effectively inhibited tumor growth and showed considerably high antitumor activity, demonstrating the conjugate can perform well in vivo. This strategy may offer a new approach for designing oxaliplatin derivatives or prodrugs with remarkable therapeutic capabilities.


Subject(s)
Antineoplastic Agents , Cell-Penetrating Peptides , Colorectal Neoplasms , Animals , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Cell-Penetrating Peptides/therapeutic use , Colorectal Neoplasms/drug therapy , Drug Delivery Systems , Mice , Oxaliplatin
11.
Cancers (Basel) ; 12(11)2020 Oct 29.
Article in English | MEDLINE | ID: mdl-33138190

ABSTRACT

This study investigated the antitumor activity and safety of pembrolizumab in patients with recurrent cervical cancer in real-world practice. We conducted a multi-center retrospective study of patients with recurrent or persistent cervical cancer treated with pembrolizumab at sixteen institutions in Korea between January 2016 and March 2020. The primary endpoints were the objective response rate (ORR) and safety. Data were available for 117 patients. The median age was 53 years (range, 28-79). Sixty-four (54.7%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥2. Forty-nine (41.9%) patients were stage ≥III at diagnosis. Eighty-eight (75.2%) patients had squamous cell carcinoma. The median number of prior chemotherapy lines was two (range, 1-6). During the median follow-up of 4.9 months (range, 0.2-35.3), the ORR was 9.4%, with three complete responses and eight partial responses. The median time to response was 2.8 months (range 1.3-13.1), and the median duration of response (DOR) was not reached. In the population of patients with favorable performance status (ECOG ≤1) (n = 53), the ORR was 18.9%, and the median DOR was 8.9 months (range, 7.3-10.4). Adverse events occurred in 55 (47.0%) patients, including eight (6.8%) patients who experienced grade ≥3 events, and two of them were suspicious treatment-related deaths. Pembrolizumab had modest antitumor activity in patients with recurrent cervical cancer comparable to that found in previously reported clinical trials. However, in patients with favorable performance status, pembrolizumab showed effective antitumor activity. Some safety profiles should be carefully monitored during treatment.

12.
Int J Clin Exp Pathol ; 13(9): 2401-2406, 2020.
Article in English | MEDLINE | ID: mdl-33042351

ABSTRACT

Ovarian yolk sac tumors are common germ cell tumors usually arising in young women. Yolk sac tumors in elderly women are infrequently encountered and most of them are combined with other epithelial tumor components including endometrioid carcinoma or serous carcinoma. Here, we report an extremely rare case of a yolk sac tumor with mucinous tumor and large cell neuroendocrine carcinoma components in a postmenopausal woman, which is the third yolk sac tumor case with a neuroendocrine tumor element in an elderly woman. An 82-year-old female visited our hospital due to abdominal distention. Abdominal computed tomography (CT) demonstrated a solid and cystic mass, measuring about 9.0 cm in the largest diameter. A total hysterectomy with bilateral salpingo-oophorectomy and excisional biopsy of the peritoneal metastatic lesions was performed. Histologic evaluation revealed a malignant ovarian tumor composed of a variety of tumor components, including a yolk sac tumor, a mucinous tumor with multifocal mucinous carcinomatous areas, and a large-cell neuroendocrine carcinoma. After surgery, the patient refused further treatment and the disease recurred in the pelvic peritoneum and a left supraclavicular lymph node nine months later.

13.
Nanomaterials (Basel) ; 10(8)2020 Aug 18.
Article in English | MEDLINE | ID: mdl-32824673

ABSTRACT

Adsorption of organic pollutants, toxic metal ions, and removal of harmful bacteria can give us clean and pure drinkable water from wastewater resources. Respective magnetite nanoparticles (MNPs) were synthesized using a cheaper and greener way in an open-air environment with the use of crude latex of Jatropha curcas (JC) and leaf extract of Cinnamomum tamala (CT). Characterization of MNPs had been performed by dynamic light scattering (DLS), Ultraviolet-visible (UV-vis) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, powdered X-ray diffraction (XRD), and field emission scanning electron microscope (FE-SEM). The size ranges of the synthesized MNPs were observed in between 20-42 nm for JC-Fe3O4 and within 26-35 nm for CT-Fe3O4 by FE-SEM images. The effect of synthesized magnetic nanoparticles in wastewater treatment (bacterial portion), dye adsorption, toxic metal removal as well as antibacterial, antioxidant, and cytotoxic activities were studied. This purification will lead to an increase in the resources of pure drinking water in the future.

14.
Cancers (Basel) ; 12(3)2020 Mar 09.
Article in English | MEDLINE | ID: mdl-32182954

ABSTRACT

In this study, we have determined the anticancer activity of doxorubicin (Dox)-loaded DNA/gold nanoparticle (AuNP) nanocarrier (Dox-DNA-AuNP) for the treatment of ovarian cancer. The anticancer effect of Dox-DNA-AuNP was evaluated in vitro using the EZ-Cytox cell viability assay on three human ovarian cancer cell lines, SK-OV-3, HEY A8, and A2780. Dox-DNA-AuNP exhibited outstanding activity with good IC50 values of 4.8, 7.4, and 7.6 nM for SK-OV-3, HEY A8, and A2780, respectively. In vivo evaluation further demonstrated the superior anticancer effects of Dox-DNA-AuNP by inhibiting tumor growth compared to free Dox in an established SK-OV-3 xenograft mice model. Dox-DNA-AuNP showed about a 2.5 times higher tumor growth inhibition rate than free Dox. Furthermore, the immunohistochemical analysis of Ki67 antigen expression showed the lowest number of proliferative cells in the ovarian tumor tissue treated with Dox-DNA-AuNP. These results suggest Dox-DNA-AuNP might be a potential effective agent in ovarian cancer chemotherapy.

15.
J Gynecol Oncol ; 30(2): e39, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30740961

ABSTRACT

The Asian Society of Gynecologic Oncology International Workshop 2018 on gynecologic oncology was held in the Ajou University Hospital, Suwon, Korea on the 24th to 25th August 2018. The workshop was an opportunity for Asian doctors to discuss the latest findings of gynecologic cancer, including cervical, ovarian, and endometrial cancers, as well as the future of fertility-sparing treatments, minimally invasive/radical/debulking surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Clinical guidelines and position statement of Asian countries were presented by experts. Asian clinical trials for gynecologic cancers were reviewed and experts emphasized the point that original Asian study is beneficial for Asian patients. In Junior session, young gynecologic oncologists presented their latest research on gynecologic cancers.


Subject(s)
Genital Neoplasms, Female/therapy , Antineoplastic Agents/therapeutic use , Asia , Clinical Trials as Topic , Female , Genital Neoplasms, Female/diagnosis , Genital Neoplasms, Female/genetics , Humans , Hyperthermia, Induced , Immunotherapy , Laparoscopy/methods , Papillomavirus Vaccines , Practice Guidelines as Topic , Societies, Medical
16.
Mol Med Rep ; 17(6): 8173-8179, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29693143

ABSTRACT

Loss of runt­related transcription factor 3 (RUNX3) has been reported in various cancers, and one of the mechanisms mediating loss of RUNX3 expression is DNA methylation. However, the role of RUNX3 expression and its DNA methylation status as prognostic factors in endometrial cancer remain unclear. In the present study, the expression and promoter methylation of RUNX3 was examined in endometrial cancer tissues and cell lines, as well as their association with endometrial cancer prognosis. Fifty­five endometrial cancer tissues and two endometrial cancer cell lines (HEC1­α and Ishikawa) were studied. RUNX3 expression and promoter methylation were examined using reverse transcription­polymerase chain reaction (RT­PCR), methylation specific PCR (MS­PCR), and immunohistochemical staining. The demethylating agent 5­aza­2'­deoxycytidine (ADC) was used to reverse the methylation of the RUNX3 promoter. Loss of RUNX3 expression was observed in 50.9% (27/53) of endometrial cancer tissues and in the HEC1­α cell line by immunohistochemistry and RT­PCR, respectively. Methylation of the RUNX3 promoter was observed in 62.2% (33/53) of endometrial cancer tissues, 12.5% (1/8) of normal endometrial tissues, and the HEC1­α cell line by MS­PCR. Tumor grade and stage were significantly correlated with loss of RUNX3 expression. The expression of RUNX3 was restored by treatment with ADC and resulted in growth inhibition in HEC1­α cells. The present results suggested that methylation may serve a critical role in the silencing of RUNX3 and loss of RUNX3 expression may serve as a prognostic marker in endometrial cancer.


Subject(s)
Core Binding Factor Alpha 3 Subunit/genetics , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Adult , Aged , Antimetabolites, Antineoplastic/pharmacology , Azacitidine/analogs & derivatives , Azacitidine/pharmacology , Cell Line, Tumor , Core Binding Factor Alpha 3 Subunit/metabolism , DNA Methylation , Decitabine , Endometrial Neoplasms/metabolism , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Immunohistochemistry , Middle Aged , Neoplasm Grading , Neoplasm Metastasis , Neoplasm Staging , Promoter Regions, Genetic , RNA, Messenger/genetics
18.
Ann Surg Treat Res ; 94(1): 19-25, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29333422

ABSTRACT

PURPOSE: Emerging evidence indicates that runt-related transcription factor 3 (RUNX3) is an important tumor suppressor gene in several cancer types, including colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation in CRC remains unclear. The aim of this study was to examine the correlation between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC. METHODS: Sixty-two CRC patients who were treated at the Soonchunhyang University College of Medicine were recruited in this study. The hypermethylation of CpG islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by methylation-specific polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively. The expression of RUNX3 was determined by immunohistochemical staining. RESULTS: Of the 62 CRC tissue samples, 20 (32.3%) presented hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion. Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038). However, expression of RUNX3 was not a prognostic factor (P = 0.363). CONCLUSION: Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.

19.
Int J Gynecol Cancer ; 27(4): 776-783, 2017 05.
Article in English | MEDLINE | ID: mdl-28333846

ABSTRACT

OBJECTIVE: This study aimed to evaluate the prognostic value of fluorine-18 fluorodeoxyglucose (FDG) uptake of bone marrow (BM) on positron emission tomography (PET)/computed tomography in patients with uterine cervical cancer. METHODS: One hundred forty-five patients with cervical cancer who underwent staging FDG PET/computed tomography and subsequent surgical resection or chemoradiotherapy were retrospectively enrolled in the study. Mean BM FDG uptake (BM standardized uptake value [SUV]) and BM-to-liver uptake ratio of FDG uptake (BLR) were measured. Relationships of BM SUV and BLR with hematologic and inflammatory markers were evaluated. Prognostic values of PET parameters for predicting disease progression-free survival and distant recurrence-free survival (DRFS) were assessed with a Cox proportional hazards regression model. RESULTS: Bone marrow SUV and BLR were significantly correlated with white blood cell count and neutrophil-to-lymphocyte ratio. In the multivariate Cox regression analysis, International Federation of Gynecology and Obstetrics stage (P = 0.048), neutrophil-to-lymphocyte ratio (P = 0.028), platelet-to-lymphocyte ratio (PLR; P = 0.004), maximum SUV of cervical cancer (P = 0.030), and BLR (P = 0.031) were significantly associated with progression-free survival, whereas lymph node metastasis (P = 0.041), PLR (P = 0.002), and BLR (P = 0.025) were significantly associated with DRFS. In a patient subgroup with chemoradiotherapy, BLR (P = 0.044) was still an independent prognostic factor for predicting DRFS in multivariate analysis along with PLR (P = 0.004). CONCLUSIONS: In patients with cervical cancer, BLR is associated with an increased risk of disease progression and distant recurrence.


Subject(s)
Bone Marrow/metabolism , Fluorodeoxyglucose F18/pharmacokinetics , Radiopharmaceuticals/pharmacokinetics , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/metabolism , Adult , Aged , Bone Marrow/diagnostic imaging , Chemoradiotherapy , Cytoreduction Surgical Procedures , Disease Progression , Female , Humans , Inflammation Mediators/blood , Lymph Node Excision , Middle Aged , Neoplasm Staging , Positron Emission Tomography Computed Tomography/methods , Prognosis , Retrospective Studies , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/therapy
20.
J Gynecol Oncol ; 28(1): e6, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27670260

ABSTRACT

The Surgery Treatment Modality Committee of the Korean Gynecologic Oncology Group has determined to develop a surgical manual to facilitate clinical trials and to improve communication between investigators by standardizing and precisely describing operating procedures. The literature on anatomic terminology, identification of surgical components, and surgical techniques were reviewed and discussed in depth to develop a surgical manual for gynecologic oncology. The surgical procedures provided here represent the minimum requirements for participating in a clinical trial. These procedures should be described in the operation record form, and the pathologic findings obtained from the procedures should be recorded in the pathologic report form. Here, we describe surgical procedure for ovarian, fallopian tubal, and peritoneal cancers.


Subject(s)
Fallopian Tube Neoplasms/surgery , Gynecologic Surgical Procedures/methods , Manuals as Topic , Ovarian Neoplasms/surgery , Peritoneal Neoplasms/surgery , Female , Humans , Republic of Korea
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