Anti-Metastatic Effects of Standardized Polysaccharide Fraction from Diospyros kaki Leaves via GSK3ß/ß-Catenin and JNK Inactivation in Human Colon Cancer Cells.

A polysaccharide fraction from Diospyros kaki (PLE0) leaves was previously reported to possess immunostimulatory, anti-osteoporotic, and TGF-ß1-induced epithelial-mesenchymal transition inhibitory activities. Although a few beneficial effects against colon cancer metastasis have been reported, we aimed to investigate the anti-metastatic activity of PLE0 and its underlying molecular mechanisms in HT-29 and HCT-116 human colon cancer cells. We conducted a wound-healing assay, invasion assay, qRT-PCR analysis, western blot analysis, gelatin zymography, luciferase assay, and small interfering RNA gene silencing in colon cancer cells. PLE0 concentration-dependently inhibited metastasis by suppressing cell migration and invasion. The suppression of N-cadherin and vimentin expression as well as upregulation of E-cadherin through the reduction of p-GSK3ß and ß-catenin levels resulted in the outcome of this effect. PLE0 also suppressed the expression and enzymatic activity of matrix metalloproteinases (MMP)-2 and MMP-9, while simultaneously increasing the protein and mRNA levels of the tissue inhibitor of metalloproteinases (TIMP-1). Furthermore, signaling data disclosed that PLE0 suppressed the transcriptional activity and phosphorylation of p65 (a subunit of NF-κB), as well as the phosphorylation of c-Jun and c-Fos (subunits of AP-1) pathway. PLE0 markedly suppressed JNK phosphorylation, and JNK knockdown significantly restored PLE0-regulated MMP-2/-9 and TIMP-1 expression. Collectively, our data indicate that PLE0 exerts an anti-metastatic effect in human colon cancer cells by inhibiting epithelial-mesenchymal transition and MMP-2/9 via downregulation of GSK3ß/ß-catenin and JNK signaling.

Efficacy of Total En Bloc Spondylectomy versus Stereotactic Ablative Radiotherapy for Single Spinal Metastasis.

To compare total en bloc spondylectomy (TES) with stereotactic ablative radiotherapy (SABR) for single spinal metastasis, we undertook a single center retrospective study. We identified patients who had undergone TES or SABR for a single spinal metastasis between 2000 and 2019. Medical records and images were reviewed for patient and tumor characteristics, and oncologic outcomes. Patients who received TES were matched to those who received SABR to compare local control and survival. A total of 89 patients were identified, of whom 20 and 69 received TES and SABR, respectively. A total of 38 matched patients were analyzed (19 TES and 19 SABR). The median follow-up period was 54.4 (TES) and 26.1 months (SABR) for matched patients. Two-year progression-free survival (PFS) and overall survival (OS) rates were 66.7% and 72.2% in the TES and 38.9% and 50.7% in the SABR group, respectively. At the final follow-up of the matched cohorts, no significant differences were noted in OS (p = 0.554), PFS (p = 0.345) or local progression (p = 0.133). The rate of major complications was higher in the TES than in the SABR group (21.1% vs. 10.5%, p = 0.660). These findings suggest that SABR leads to fewer complications compared to TES, while TES exhibits better mid-term control of metastatic tumors.

Accurate Diagnosis of COVID-19 from Self-Collectable Biospecimens Using Synthetic Apolipoprotein H Peptide-Coated Nanoparticle Assay.

A high-throughput, accurate screening is crucial for the prevention and control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current methods, which involve sampling from the nasopharyngeal (NP) area by medical staffs, constitute a fundamental bottleneck in expanding the testing capacity. To meet the scales required for population-level surveillance, self-collectable specimens can be used; however, its low viral load has hindered its clinical adoption. Here, we describe a magnetic nanoparticle functionalized with synthetic apolipoprotein H (ApoH) peptides to capture, concentrate, and purify viruses. The ApoH assay demonstrates a viral enrichment efficiency of >90% for both SARS-CoV-2 and its variants, leading to an order of magnitude improvement in analytical sensitivity. For validation, we apply the assay to a total of 84 clinical specimens including nasal, oral, and mouth gargles obtained from COVID-19 patients. As a result, a 100% positivity rate is achieved from the patient-collected nasal and gargle samples, which exceeds that of the traditional NP swab method. The simple 12 min pre-enrichment assay enabling the use of self-collectable samples will be a practical solution to overcome the overwhelming diagnostic capacity. Furthermore, the methodology can easily be built on various clinical protocols, allowing its broad applicability to various disease diagnoses.

Spatial epitranscriptomics reveals A-to-I editome specific to cancer stem cell microniches.

Epitranscriptomic features, such as single-base RNA editing, are sources of transcript diversity in cancer, but little is understood in terms of their spatial context in the tumour microenvironment. Here, we introduce spatial-histopathological examination-linked epitranscriptomics converged to transcriptomics with sequencing (Select-seq), which isolates regions of interest from immunofluorescence-stained tissue and obtains transcriptomic and epitranscriptomic data. With Select-seq, we analyse the cancer stem cell-like microniches in relation to the tumour microenvironment of triple-negative breast cancer patients. We identify alternative splice variants, perform complementarity-determining region analysis of infiltrating T cells and B cells, and assess adenosine-to-inosine base editing in tumour tissue sections. Especially, in triple-negative breast cancer microniches, adenosine-to-inosine editome specific to different microniche groups is identified.

A Real-Time Detection Device for the Rapid Quantification of Skin Casual Sebum Using the Oil Red O Staining Method.

The human skin sebum suggests that it (along with other epidermal surface lipids) plays a role in skin barrier formation, the moderation of cutaneous inflammation, and antimicrobial defense. Various methods have been developed for collecting and measuring skin sebum. We tested methods of detection using "color intensity", by staining the skin casual sebum. This process was conducted in three steps; first, the selection of materials for sebum collection; second, staining the collected sebum; third, the development of a device that can measure the level of stained sebum. A plastic film was used to effectively collect sebum that increased with the replacement time of the sebum. In addition, the collected sebum was stained with Oil Red O (ORO) and checked with RGB; as a result, the R2 value was higher than 0.9. It was also confirmed that the correlation value was higher than 0.9 in the comparison result with Sebumeter®, which is a common standard technology. Finally, it was confirmed that the R2 value was higher than 0.9 in the detection value using the sensor. In conclusion, we have proven the proof of concept (PoC) for this method, and we would like to introduce an effective sebum measurement method that differs from the existing method.

The nature of triple-negative breast cancer classification and antitumoral strategies.

Identifying the patterns of gene expression in breast cancers is essential to understanding their pathophysiology and developing anticancer drugs. Breast cancer is a heterogeneous disease with different subtypes determined by distinct biological features. Luminal breast cancer is characterized by a relatively high expression of estrogen receptor (ER) and progesterone receptor (PR) genes, which are expressed in breast luminal cells. In ~25% of invasive breast cancers, human epidermal growth factor receptor 2 (HER2) is overexpressed; these cancers are categorized as the HER2 type. Triple-negative breast cancer (TNBC), in which the cancer cells do not express ER/PR or HER2, shows highly aggressive clinical outcomes. TNBC can be further classified into specific subtypes according to genomic mutations and cancer immunogenicity. Herein, we discuss the brief history of TNBC classification and its implications for promising treatments.

Novel Discovery of LINE-1 in a Korean Individual by a Target Enrichment Method.

Long interspersed element-1 (LINE-1 or L1) is an autonomous retrotransposon, which is capable of inserting into a new region of genome. Previous studies have reported that these elements lead to genomic variations and altered functions by affecting gene expression and genetic networks. Mounting evidence strongly indicates that genetic diseases or various cancers can occur as a result of retrotransposition events that involve L1s. Therefore, the development of methodologies to study the structural variations and interpersonal insertion polymorphisms by L1 element-associated changes in an individual genome is invaluable. In this study, we applied a systematic approach to identify human-specific L1s (i.e., L1Hs) through the bioinformatics analysis of high-throughput next-generation sequencing data. We identified 525 candidates that could be inferred to carry non-reference L1Hs in a Korean individual genome (KPGP9). Among them, we randomly selected 40 candidates and validated that approximately 92.5% of non-reference L1Hs were inserted into a KPGP9 genome. In addition, unlike conventional methods, our relatively simple and expedited approach was highly reproducible in confirming the L1 insertions. Taken together, our findings strongly support that the identification of non-reference L1Hs by our novel target enrichment method demonstrates its future application to genomic variation studies on the risk of cancer and genetic disorders.

Indoor levels of volatile organic compounds and formaldehyde from emission sources at elderly care centers in Korea.

The objective of this study is to characterize indoor and outdoor levels of volatile organic compounds (VOCs) and formaldehyde (HCHO) and identify indoor emission sources in thirty elderly care centers (ECCs) located in the Seoul metropolitan city and Gyeonggi province in Korea. Air monitoring samples from indoor and outdoor environments were collected from January to December in 2007. Statistical analyses of indoor and outdoor VOCs and HCHO levels in three rooms (a bedroom, living, and dining rooms) of each ECC were performed, and these were compared to identify environmental factors associated with an increase of indoor pollution levels. Total volatile organic compounds (TVOC) levels were significantly (p<0.05) different between indoor (230.7±1.7 µg/m3) and outdoor (137.8±1.9 µg/m3) environments, with an I/O ratio of 1.67. The indoor HCHO level (20.1±1.6 µg/m3) was significantly (p<0.05) higher than the outdoor level (8.1±1.9 µg/m3), with an I/O ratio of 2.48. Indoor VOCs and HCHO levels in the bedrooms were significantly (p<0.05) higher than those in the living and dining rooms. Furthermore, indoor levels of VOCs and HCHO at ECCs were significantly (p<0.05) different depending on environmental factors such as the use of carpet, paint, and wooden furniture. In multiple regression analysis, indoor VOCs and HCHO levels at ECCs were significantly (p<0.05) correlated with two micro-environmental factors: the use of carpet and paint. This study confirmed that indoor VOCs and HCHO levels were significantly higher than those in outdoor environments. These air pollutants were mainly emitted from indoor sources, such as carpet, paint, and construction materials at the ECCs in Korea.

Immunostimulatory effects of cordycepin-enriched WIB-801CE from Cordyceps militaris in splenocytes and cyclophosphamide-induced immunosuppressed mice.

The medicinal mushroom Cordyceps militaris has been reported to possess anticancer and immunomodulatory effects. We investigated the immunostimulatory effects of culture supernatant of C. militaris (WIB-801CE) by examining its in vitro enhancing effects on cell proliferation and cytokine releases in splenocytes and its in vivo effects on cyclophosphamide-induced immunosuppressed mice. WIB-801CE enhanced normal and methotrexate-induced cell proliferation. WIB-801CE significantly ameliorated interleukin (IL)-2, interferon-γ, and tumor necrosis factor-α secretion in methotrexate-induced splenocytes. Oral administration of WIB-801CE effectively increased the cyclophosphamide-suppressed splenocyte proliferation and natural killer cytotoxic activity. WIB-801CE effectively recovered cyclophosphamide-induced decreases in IL-2, interferon-γ, tumor necrosis factor-α, and IL-10 level. The collective data implicate WIB-801CE as a therapeutic candidate in ameliorating the immunosuppression through immunostimulatory properties.

Synthesis of New Tricyclic and Tetracyclic Fused Coumarin Sulfonate Derivatives and Their Inhibitory Effects on LPS-Induced Nitric Oxide and PGE2 Productions in RAW 264.7 Macrophages: Part 2.

The synthesis of a new series of 21 fused coumarin derivatives is described, and the biological evaluation of their in vitro antiinflammatory effects as inhibitors of lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2 ) production in RAW 264.7 macrophages. The target compounds 1a-u were first tested for cytotoxicity to determine a non-toxic concentration for antiinflammatory screening, so that the inhibitory effects against NO and PGE2 production would not be caused by cytotoxicity. Compounds 1f and 1p were the most active PGE2 inhibitors with IC50 values of 0.89 and 0.95 µM, respectively. Western blot and cell-free COX-2 screening showed that their effects were due to inhibition of both COX-2 protein expression and COX-2 enzyme activity. Their IC50 values against the COX-2 enzyme were 0.67 and 0.85 µM, respectively, which is more potent than etoricoxib. The selectivity indexes of compounds 1f and 1p against COX-2 compared to COX-1 were 41.1 and 42.5, respectively. Compound 1f showed strong inhibitory effects at 5 µM concentration on COX-2 mRNA expression in LPS-induced RAW 264.7 macrophages. Moreover, the tricyclic compounds 1l and 1n as well as the tetracyclic analog 1u were the most potent NO inhibitors, with one-digit micromolar IC50 values. They showed dose-dependent inhibition of inducible nitric oxide synthase (iNOS) protein expression. The tetracyclic derivative 1u was the most potent inhibitor of NO production. It also exhibited a strong inhibitory effect on iNOS mRNA expression in LPS-induced RAW 264.7 macrophages.

Cnidilide, an alkylphthalide isolated from the roots of Cnidium officinale, suppresses LPS-induced NO, PGE2, IL-1ß, IL-6 and TNF-α production by AP-1 and NF-κB inactivation in RAW 264.7 macrophages.

Cnidilide, an alkyl phthalide isolated from the rhizome of Cnidium officinale, has been reported to possess antispasmodic and sedative effects. However, the anti-inflammatory capacity and molecular mechanism of cnidilide have not been studied to date. In the present study, we investigated the inhibitory effects of cnidilide on LPS-induced pro-inflammatory mediators and the underlying molecular mechanisms in RAW 264.7 macrophages. Our results indicated that cnidilide potently inhibits inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression at the protein and mRNA levels and their promoter activities, causing attendant decreases in the production of nitric oxide (NO) and prostaglandin E2 (PGE2). In addition, cnidilide reduced LPS-induced production and mRNA expression of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) in a dose-dependent manner. Molecular data revealed that cnidilide inhibited LPS-induced transcriptional activity of activator protein-1 (AP-1) by reducing the phosphorylation and nuclear translocation of c-Fos and c-Jun. In addition, cnidilide attenuated LPS-induced transcriptional activity of nuclear factor-κB (NF-κB), and this reduction was accompanied by parallel reduction in the phosphorylation, but not in the translocation of p65 NF-κB. In addition, cnidilide inhibited LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and mitogen- and stress-activated protein kinase 1(MSK-1), a downstream kinase. Moreover, the phosphorylation of c-Jun N-terminal kinase (JNK) was suppressed by cnidilide in a concentration-dependent manner, whereas it did not inhibit the extracellular signal-regulated kinase (ERK) phosphorylation in LPS-stimulated RAW 264.7 macrophages. Taken together, our findings suggest that cnidilide has anti-inflammatory properties by inhibiting p38 MAPK, JNK, AP-1, and the NF-κB pathway in LPS-stimulated RAW 264.7 macrophages.

Chikusetsusaponin IVa Methyl Ester Isolated from the Roots of Achyranthes japonica Suppresses LPS-Induced iNOS, TNF-α, IL-6, and IL-1ß Expression by NF-κB and AP-1 Inactivation.

We investigated the effect of chikusetsusaponin IVa (CS) and chikusetsusaponin IVa methyl ester (CS-ME) from the roots of Achyranthes japonica NAKAI on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW264.7 macrophages. CS-ME more potently inhibited LPS-induced NO and PGE2 production than CS. CS-ME concentration-dependently inhibited LPS-induced tumor necrosis factor (TNF)-α and interleukin (IL)-6 and IL-1ß production in RAW264.7 macrophages and mouse peritoneal macrophages. Consistent with these findings, CS-ME suppressed LPS-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 at protein level as well as iNOS, COX-2, TNF-α, IL-6, and IL-1ß at mRNA level. In addition, CS-ME suppressed LPS-induced transcriptional activity of nuclear factor (NF)-κB and activator protein (AP)-1. The anti-inflammatory properties of CS-ME might result from suppression of iNOS, COX-2, TNF-α, IL-6, and IL-1ß expression through downregulation of NF-κB and AP-1 in macrophages.

Biflorin, Isolated from the Flower Buds of Syzygium aromaticum L., Suppresses LPS-Induced Inflammatory Mediators via STAT1 Inactivation in Macrophages and Protects Mice from Endotoxin Shock.

Two chromone C-glucosides, biflorin (1) and isobiflorin (2), were isolated from the flower buds of Syzygium aromaticum L. (Myrtaceae). Here, inhibitory effects of 1 and 2 on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7 macrophages were evaluated, and 1 (IC50 = 51.7 and 37.1 µM, respectively) was more potent than 2 (IC50 > 60 and 46.0 µM). The suppression of NO and PGE2 production by 1 correlated with inhibition of iNOS and COX-2 protein expression. Compound 1 reduced inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expression via inhibition of their promoter activities. Compound 1 inhibited the LPS-induced production and mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6. Furthermore, 1 reduced p-STAT1 and p-p38 expression but did not affect the activity of nuclear factor κ light-chain enhancer of activated B cells (NF-κB) or activator protein 1 (AP-1). In a mouse model of LPS-induced endotoxemia, 1 reduced the mRNA levels of iNOS, COX-2, and TNF-α, and the phosphorylation-mediated activation of the signal transducer and activator of transcription 1 (STAT1), consequently improving the survival rates of mice. Compound 1 showed a significant anti-inflammatory effect on carrageenan-induced paw edema and croton-oil-induced ear edema in rats. The collective data indicate that the suppression of pro-inflammatory gene expression via p38 mitogen-activated protein kinase and STAT1 inactivation may be a mechanism for the anti-inflammatory activity of 1.

Constituents of PG201 (Layla(®)), a multi-component phytopharmaceutical, with inhibitory activity on LPS-induced nitric oxide and prostaglandin E2 productions in macrophages.

Fourteen compounds, coumarin (1), demethylsuberosin (2), xanthotoxin (3), psoralen (4), decursinol (5), decursin (6), decursinol angelate (7), chikusetsusaponin IVa (8), chikusetsusaponin IVa methyl ester (9), ethyl caffeate (10), syringaresinol (11), cnidilide (12), farnesol (13), and linoleic acid (14), were isolated from phytopharmaceutical PG201 (Layla(®)) by activity-guided fractionation utilizing inhibitory activity on nitric oxide (NO) production in vitro. The isolates 1-14 were evaluated for their inhibitory activity on LPS-induced NO and prostaglandin E2 (PGE2) productions in RAW 264.7 cells. All the compounds except 14 displayed suppressive effects on LPS-induced NO and PGE2 production with IC50 values ranging from 8 to 60 µM. Among these, compound 10 showed the most potent inhibitory effect on NO production from RAW 264.7 cells with an IC50 value of 8.25 µM. Compounds 2, 9, and 10 exhibited high inhibitory effects on PGE2 production with the IC50 values of 9.42, 7.51, and 6.49 µM, respectively. These findings suggest that compounds 2, 9, and 10 are the potential anti-inflammatory active constituents of PG201 and further study may be needed to explain their mechanism of action.

Evaluating the efficiency of an asbestos stabilizer on ceiling tiles and the characteristics of the released asbestos fibers.

The efficiency of asbestos stabilizers and their adaptability were evaluated by investigating the characteristics of asbestos fibers released from ceiling tiles. The impact of such variables as the wind speed or vibration conditions was also studied along with the asbestos stabilizers. The concentrations of the asbestos fibers released from damaged ceiling tiles treated with stabilizers decreased by 69.5-84.4% compared with those of untreated tiles for all variables, with a statistically significant difference (p<0.001). The effects of the environmental factors on the asbestos concentrations were analyzed through a multiple regression analysis. It was determined that the surface status of the ceiling tiles and stabilizers were the main factors affecting the concentration, and the reliability of these factors was estimated as 58.3%. The lengths of the chrysotile fibers released from the damaged ceiling tiles were in the range of 0.991-79.1 µm for the untreated tiles and 3.74-35.6 µm for the tiles treated with inorganic stabilizers. It was confirmed that inorganic stabilizers are more efficient for damaged ceiling tiles. The results of this study also show that the asbestos concentrations are greatly reduced after treating damaged ceiling tiles with a stabilizer.

Metformin inhibits ovarian cancer growth and increases sensitivity to paclitaxel in mouse models.

OBJECTIVE: There is increasing preclinical evidence indicating that metformin, a medication commonly used for type 2 diabetes mellitus, may protect against cancer. Motivated by this emerging evidence we asked 2 questions: (1) can metformin prevent ovarian cancer growth by altering metabolism and (2) will metformin increase sensitivity to chemotherapy. STUDY DESIGN: The effect of metformin in ovarian cancer was tested in vitro and with 2 different mouse models. In vitro, cell lines (n = 6) were treated with metformin (10-40 mmol/L) or phosphate-buffered saline solution and cellular proliferation and metabolic alterations (adenosine monophosphate-activated protein kinase activity, glycolysis, and lipid synthesis) were compared between the 2 groups. In mouse models, a prevention study was performed by treating mice with metformin (250 mg/kg/d intraperitoneally) or placebo for 2 weeks followed by intraperitoneal injection of the SKOV3ip1 human ovarian cancer cell line, and the mean number of tumor implants in each treatment group was compared. In a treatment study, the LSL-K-ras(G12D/+)/PTEN(floxP/floxP) genetic mouse model of ovarian cancer was used. Mice were treated with placebo, paclitaxel (3 mg/kg/wk intraperitoneally for 7 weeks), metformin (100 mg/kg/d in water for 7 weeks), or paclitaxel plus metformin, and tumor volume was compared among treatment groups. RESULTS: In vitro, metformin decreased proliferation of ovarian cancer cell lines and induced cell cycle arrest, but not apoptosis. Further analysis showed that metformin altered several aspects of metabolism including adenosine monophosphate-activated protein kinase activity, glycolysis, and lipid synthesis. In the prevention mouse model, mice that were pretreated with metformin had 60% fewer tumor implants compared with controls (P < .005). In the treatment study, mice that were treated with paclitaxel plus metformin had a 60% reduction in tumor weight compared with controls (P = .02), which is a level of tumor reduction greater than that resulting from either paclitaxel or metformin alone. CONCLUSION: Based on these results, we conclude that metformin alters metabolism in ovarian cancer cells, prevents tumor growth, and increases sensitivity to chemotherapy in vitro and in mouse models. These preclinical findings suggest that metformin warrants further investigation for use as an ovarian cancer therapeutic.

The effects of 17ß-estradiol and a selective estrogen receptor modulator, bazedoxifene, on ovarian carcinogenesis.

OBJECTIVE: To test if estrogen promotes carcinogenesis in vitro and in a genetic mouse model of ovarian cancer and whether its effects can be inhibited by a novel selective estrogen receptor modulator (SERM), bazedoxifene. METHODS: Bazedoxifene was synthesized and it was confirmed that the drug abrogated the uterine stimulatory effect of 17ß-estradiol in mice. To determine if hormones alter tumorigenesis in vivo LSL-K-ras(G12D/+)Pten(loxP/loxP) mice were treated with vehicle control, 17ß-estradiol or bazedoxifene. Hormone receptor status of a cell line established from LSL-K-ras(G12D/+)Pten(loxP/loxP) mouse ovarian tumors was characterized using Western blotting and immunohistochemistry. The cell line was treated with hormones and invasion assays were performed using Boyden chambers and proliferation was assessed using MTT assays. RESULTS: In vitro 17ß-estradiol increased both the invasion and proliferation of ovarian cancer cells and bazedoxifene reversed these effects. However, in the genetic mouse model neither treatment with 17ß-estradiol nor bazedoxifene changed mean tumor burden when compared to treatment with placebo. The mice in all treatment groups had similar tumor incidence, metastatic nodules and ascites. CONCLUSION: While 17ß-estradiol increases the invasion and proliferation of ovarian cancer cells, these effects do not translate into increased tumor burden in a genetic mouse model of endometrioid ovarian cancer. Likewise, while the SERM reversed the detrimental effects of estrogen in vitro, there was no change in tumor burden in mice treated with bazedoxifene. These findings demonstrate the complex interplay between hormones and ovarian carcinogenesis.

Prognostic value of the copper transporters, CTR1 and CTR2, in patients with ovarian carcinoma receiving platinum-based chemotherapy.

OBJECTIVE: CTR1 and CTR2 are copper transporters that have been associated with platinum sensitivity in several human cancers. We investigated the prognostic significance of CTR1 and CTR2 in women with ovarian carcinoma. MATERIALS AND METHODS: We evaluated the expression of CTR1 and CTR2 using real-time PCR in 40 women with ovarian carcinoma (IIb=2, IIIb=2, IIIc=30, IV=6). We compared the expression of CTR1 and CTR2 with participants' clinicopathological findings. RESULTS: We found lower expression of CTR1 and CTR2 mRNA in ovarian cancer cells against normal ovarian tissue with statistically significant differences (p=0.018 and 0.011, respectively). High CTR1 expression was a prognostic factor for improved survival after adjusting for age, tumor grade, stage, residual tumor, and CTR2 mRNA expression (HR, 0.35; 95% CI, 0.15-0.84). However, CTR2 expression did not exhibit any prognostic significance. Of the 20 women with elevated CTR1 expression, 17 (85%) were sensitive to platinum-based chemotherapy. Of the 7 women with low CTR1 expression and high CTR2 expression, 6 (85.7%) were resistant to platinum-based chemotherapy and had the shortest progression-free survival of all women in our study sample. CONCLUSION: In our sample of 40 women with ovarian carcinoma, high CTR1 expression was significantly associated with sensitivity to platinum-based chemotherapy and longer progression-free survival. Conversely, low CTR1 expression and high CTR2 expression were significantly associated with resistance to platinum-based chemotherapy and the shortest survival.

Oncologic and reproductive outcomes in patients with advanced-stage borderline ovarian tumors.

OBJECTIVE: To evaluate the oncologic safety and reproductive outcomes in patients with advanced-stage borderline ovarian tumors (BOTs). STUDY DESIGN: The medical records of patients with advanced-stage BOTs who were treated between 1997 and 2009 were reviewed retrospectively. Reproductive outcomes were assessed by telephone interviews. RESULTS: Six (24%) and 19 patients (76%) had stages II and III disease, respectively. Twenty patients (80%) were treated by radical surgery and five patients (20%) underwent fertility-sparing surgery. Five patients (20%) had invasive implants and 20 patients (80%) had non-invasive implants. The median follow-up time was 71.4 months (range, 10-135 months). Four patients relapsed after a median interval of 40 months (range, 16-77 months) following primary treatment. Of these four patients, two who initially had invasive implants relapsed in the form of invasive ovarian carcinoma. Patients with invasive implants (2 of 5 [40%]) tend to relapse more frequently than patients with non-invasive implants (2 of 20 [10%]). Among five women who underwent fertility-sparing surgery, four attempted to conceive and five singleton pregnancies occurred. CONCLUSION: Patients with advanced-stage BOTs with non-invasive implants have an excellent prognosis. Fertility-sparing surgery should be considered if there are no invasive implants. Indeed, reproductive outcomes after fertility-sparing surgery with non-invasive implants are promising.