Correlation analysis of cancer stem cell marker CD133 and human endogenous retrovirus (HERV)-K env in SKOV3 ovarian cancer cells.

BACKGROUND: Human endogenous retrovirus (HERV)-K is a type of retrovirus that is present in the human genome, and its expression is usually silenced in healthy tissues. The precise mechanism by which HERV-K env influences cancer stemness is not fully understood, but it has been suggested that HERV-K env may activate various signaling pathways that promote stemness traits in cancer cells. OBJECTIVE: To establish the connection between HERV-K env expression and cancer stemness in ovarian cancer cells, we carried out correlation analyses between HERV-K env and the cancer stem cell (CSC) marker known as the cluster of differentiation 133 (CD133) gene in SKOV3 ovarian cancer cells. METHOD: To perform correlation analysis between HERV-K env and CSCs, ovarian cancer cells were cultured in a medium designed for cancer stem cell induction. The expression of HERV-K env and CD133 genes was verified using quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot analyses. Additionally, the expression of stemness-related markers, such as OCT-4 and Nanog, was also confirmed using RT-qPCR. RESULTS: In the stem cell induction medium, the number of tumorsphere-type SKOV3 cells increased, and the expression of CD133 and HERV-K env genes was up-regulated. Additionally, other stemness-related markers like OCT-4 and Nanog also exhibited increased expression when cultured in the cancer stem cell induction medium. However, when HERV-K env knockout (KO) SKOV3 cells were cultured in the same cancer stem cell induction medium, there was a significant decrease in the number of tumorsphere-type cells compared to mock SKOV3 cells subjected to the same conditions. Furthermore, the expression of CD133, Nanog, and OCT-4 did not show a significant increase in HERV-K env KO SKOV3 cells compared to mock SKOV3 cells cultured in the same cancer stem cell induction medium. CONCLUSION: These findings indicate that the expression of HERV-K env increased in SKOV3 cells when cultured in cancer stem cell induction media, and cancer stem cell induction was inhibited by KO of HERV-K env in SKOV3 cells. These results suggest a strong association between HERV-K env and stemness in SKOV3 ovarian cancer cells.

Effect of human endogenous retrovirus-K env gene knockout on proliferation of ovarian cancer cells.

BACKGROUND: Among various human endogenous retroviruses (HERVs), the HERV-K (HML-2) group has been reported to be highly related to cancer. In pancreatic cancer cells, shRNA-mediated downregulation of HERV-K env RNA decreases cell proliferation and tumor growth through the RAS-ERK-RSK pathway; in colorectal cancer, CRISPR-Cas9 knockout (KO) of the HERV-K env gene affects tumorigenic characteristics through the nupr-1 gene. OBJECTIVE: The effect of HERV-K env KO has not been studied in ovarian cancer cell lines. In this study, we analyzed the tumorigenic characteristics of ovarian cancer cell lines, including cell proliferation, migration, and invasion, and the expression patterns of related proteins after CRISPR-Cas9 KO of the HERV-K env gene. METHODS: The HERV-K env gene KO was achieved using the CRISPR-Cas9 system in ovarian cancer cell lines SKOV3 and OVCAR3. Tumorigenic characteristics including cell proliferation, migration, and invasion were analyzed, and related protein expression was investigated by western blot analysis. RESULTS: The expression of the HERV-K env gene in KO cells was significantly reduced at RNA and protein levels, and tumorigenic characteristics including cell proliferation, migration, and invasion were significantly reduced. In HERV-K env KO SKOV3 cells, the expression of the RB protein was significantly up-regulated and the cyclin B1 protein level was significantly reduced. In contrast, in HERV-K env KO OVCAR3 cells, the level of phospho-RB protein was significantly reduced, but other protein levels were not changed. CONCLUSION: The results of this study showed that HERV-K env gene KO affects cell proliferation, invasion, and migration of ovarian cells through RB and Cyclin B1 proteins, but the specific regulation pattern can differ by cell line.

Effects of thymosin ß4-derived peptides on migration and invasion of ovarian cancer cells.

BACKGROUND: Thymosin ß4 (Tß4) is a highly conserved actin binding protein associated with the metastatic potential of tumor cells by stimulating cell migration. The role of Tß4 and its derived fragment peptides in migration of ovarian cancer cells has not been studied. OBJECTIVE: To analyze the effects of Tß4 and its derived fragment peptides on ovarian cancer cell migration and invasion, we applied Tß4 and three Tß4-derived synthetic peptides to SKOV3 ovarian cancer cells. METHOD: The migration and invasion of SKOV3 cells treated with Tß4(1-43), Tß4(1-15), Tß4(12-26), Tß4(23-), and untreated control were analyzed by in vitro migration and invasion assay with transwell plate. Cell proliferation assay was conducted to identify the effect of Tß4 and its derived peptide on SKOV3 cell proliferation. The expression of Tß4 related proteins related with cell proliferation was analyzed by Western blot after treatment with Tß4 and its derived peptides. RESULTS: Cell migration and invasion were significantly increased in Tß4 peptide-treated SKOV3 cells compared with untreated control. All three Tß4-derived fragment peptides including those without an actin binding site significantly stimulated migration and invasion of SKOV3 cells. Tß4 and its derived peptide significantly stimulated SKOV3 cell proliferation and up-regulated the expression of RACK-1 protein. CONCLUSIONS: The Tß4 peptide and all of its derived fragment peptides including those without an actin binding motif stimulate migration and invasion of SKOV3 ovarian cancer cells. All peptides significantly increased RACK-1 expression and cell proliferation of SKOV3 cells. These results suggest that Tß4 stimulates migration and invasion of SKOV3 cells by stimulation of cell proliferation through up-regulation of RACK-1 protein.

Analysis of KAP1 expression patterns and human endogenous retrovirus Env proteins in ovarian cancer.

BACKGROUND: Human endogenous retroviruses (HERVs) constitute around 8% of the human genome and have important roles in human health and disease, including cancers. Previous studies showed that HERV envelope (Env) proteins are highly expressed in cancer tissues and co-related with cancer progression. KAP1 has been reported to play a key role in regulating retrotransposons, including HERV-K, through epigenetic silencing. OBJECTIVE: The relationship between KAP-1 and HERV Envs expressions was analyzed only in tumor cell lines and has not yet been studied in cancer tissues. In this study, we analyzed the expression patterns and relationship between KAP1 and HERV Env proteins in ovarian cancer tissues. METHOD: The expression patterns of KAP-1 and HERV Env proteins, including HERV-K and HERV-R, were analyzed in ovarian cancer tissue microarrays that contained 80 surgical specimens, including normal ovary and malignant ovarian cancers. RESULTS: The expression of HERV-R Env and KAP1 proteins is significantly higher in ovarian cancer compared with normal ovary tissues. However, the expression of HERV-K Env did not change significantly in cancer tissues. The expression patterns of HERV-K Env and HERV-R Env significantly increased in early stages of cancer and KAP1 expression was higher in certain stage and types of cancers. However, the expression of HERV-K Env, HERV-R Env, and KAP1 did not change in different age groups. The correlation between the expression of KAP1 and HERV-Env, including HERV-K and HERV-R, was not significantly correlated. CONCLUSIONS: The results of this study showed that there was no significant correlation between the expression of KAP1 and HERV Env proteins in ovarian cancer tissues, unlike studies with cell lines in vitro. These results suggest that the actual expression of HERV Env proteins in ovarian cancer tissues may be regulated through various complex factors as well as KAP1.

Preoperative plateletcrit is a Prognostic Biomarker for Survival in Patients with Non-Small Cell Lung Cancer.

Objectives: Several factors associated with the prognosis of patients with NSCLC have been reported in the literature; however, most of these factors cannot be examined preoperatively. In this study, the clinical utility of platelet parameters in patients with NSCLC who underwent curative resection was evaluated. Materials and Methods: A retrospective study on patients with NSCLC who underwent curative resection from July 2006 to September 2016 was conducted. The Cox proportional hazard regression model was applied to evaluate the variables that demonstrated effects on disease-free and overall survival (DFS and OS). Results: A total of 116 patients with NSCLC were analyzed. There were 15 patients with plateletcrit greater than 0.2755%, and 101 patients whose plateletcrit was 0.2755% or lower. Multivariate analysis identified plateletcrit higher than 0.2755% (hazard ratio [HR] = 4.18, 95% confidence interval [CI] = 1.54-11.34, P =0.004), patient age of 65 years or more (HR = 4.02, 95% CI = 1.67-9.66, P = 0.001), and stage II or IIIA disease (HR = 2.95, 95% CI = 1.26-6.87, P = 0.012) as independent factors for OS that predicted a poor prognosis. Multivariate analysis identified plateletcrit higher than 0.2755% (HR = 4.07, 95% CI = 1.52-10.94, P = 0.005), stage II or IIIA disease (HR = 5.38, 95% CI = 2.71-10.66, P < 0.001) and non-adenocarcinoma (HR = 1.92, 95% CI = 1.02-3.59, P = 0.040) as independent prognostic factors for DFS that predicted a poor prognosis. Conclusion: Our results suggest a potential role of preoperative plateletcrit as an independent prognostic marker for patients with resectable NSCLC.

Correlation of long interspersed element-1 open reading frame 1 and c-Met proto-oncogene protein expression in ovarian cancer.

BACKGROUND: Hypomethylation of long interspersed nuclear element-1 (LINE-1) is closely related to certain cancers and concerns with aggressive tumor behavior. Previously, we reported LINE-1 open reading frame-1 (ORF1) protein level was significantly up-regulated in ovarian cancers compared with normal ovary. Hypomethylation of local LINE-1 sequence has been reported to reactivate MET proto-oncogene in colon cancers and hepatocellular carcinoma. However, the relationship between LINE-1 and c-MET expressions in ovarian cancer is not yet studied. METHOD: Here, we analyzed the expression patterns of LINE-1 ORF1 and c-Met protein in ovarian cancer tissue microarrays containing 208 surgical specimens including normal ovary and malignant ovarian cancers. RESULTS: The expressions of both LINE-1 ORF1 and c-Met protein were significantly increased in ovarian cancers and peaked in early stage of tumor. Other clinical data including age and tumor types were not significantly related with both proteins. Co-relationship between LINE-1 ORF1 and c-Met protein was significant (p = 0.03) but several patients show different expression patterns. CONCLUSIONS: These results propose that LINE-1 ORF1 significantly activates c-Met but not in all cases, suggesting other factors may be involved simultaneously.

Correlation of constitutive photomorphogenic 1 (COP1) and p27 tumor suppressor protein expression in ovarian cancer.

BACKGROUND: Constitutive photomorphogenic 1 (COP1) is an E3 ubiquitin ligase that regulates important target proteins for cell growth including p27. The tumor suppressor p27 negatively regulates the cell cycle by inhibiting cyclin-dependent kinase. COP1 negatively regulates p27 stability by mediating its nuclear export and degradation. OBJECTIVE: Even if COP1 and p27 are tightly related and have significant roles in tumor progression, the expression patterns and relationship of both proteins in cancer have not yet been studied. METHOD: We analyzed the expression patterns and relationship between COP1 and p27 using an ovarian cancer tissue microarray by dual immunofluorescence analysis. RESULTS: The expression levels of COP1 and p27 proteins were not significantly different between ovarian cancer tissue and normal control tissue. Other clinical data including age, tumor type, tumor grade, and stage were not significantly related to expression of the two proteins. The co-relationship between COP1 and p27 proteins was significantly high (Pearson correlation coefficient 0.79, p = 8.65 × 10-22). CONCLUSIONS: Our results demonstrate that while the expression levels of COP1 and p27 are highly correlated, they are not significantly related to cancer progression in ovarian cancer.

Diagnostic accuracy of inflammatory markers for distinguishing malignant and benign ovarian masses.

Objective: To evaluate the role of inflammatory markers for distinguishing malignant and benign ovarian masses. Methods: Preoperative demographic, clinicopathologic, and laboratory variables were reviewed in patients with an ovarian mass that was subsequently diagnosed as either epithelial ovarian cancer (EOC) or a benign ovarian mass on histologic analysis. The differences between variables of the two groups were further evaluated. Logistic regression analysis was applied to evaluate variables to predict the presence of EOC. Results: According to the analysis of 229 patients with EOC, 120 (52.4%) patients had serous adenocarcinoma. Of the 229 patients, 110 (48.1%) patients had stage I or II disease and 119 (52.0%) had stage III or IV disease. There was a significant difference between EOC and benign ovarian mass in median values of variables such as age, white blood cell (WBC) count, hemoglobin concentration, platelet count, cancer antigen 125 (CA125) levels, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) (all P < 0.001, except for WBC count [P = 0.009]). In addition, there was significant difference in median values of these continuous variables among early-stage EOC, advanced-stage EOC, and benign ovarian mass (P < 0.001 for all variables). On multivariate logistic regression analysis, age (odds ratio [OR] = 4.14, P < 0.001), CA125 levels (OR = 9.87, P < 0.001), NLR (OR = 1.76, P = 0.049), PLR (OR = 2.41, P = 0.004), and LMR (OR = 0.51, P = 0.024) were found to significantly predict the presence of EOC. Conclusion: The three LMR, NLR, and PLR markers were found to be predictors for the presence of EOC. Further prospective studies to assess these markers as screening tools for the presence of EOC are required.

Monocytosis as a prognostic factor for survival in stage IB and IIA cervical cancer.

Objective: To measure hematologic parameters derived from the white blood cell (WBC) count and differential count (DC) as prognostic factors for survival in patients with stage IB and IIA cervical cancer. Methods: We retrospectively examined demographic, clinicopathologic, and laboratory parameters in a cohort of 233 patients with International Federation of Gynecology and Obstetrics stage IB and IIA cervical cancer who underwent surgical resection. We further assessed the effects of the WBC count and DC-derived hematologic parameters on progression-free survival (PFS) and overall survival (OS) after controlling for other parameters. Results: Patients were followed up for a median of 46.6 months (range, 9-142 months). The Kaplan-Meier estimates of PFS and OS at 5 years were 88.5% and 92.3%, respectively. In a multivariate analysis, we identified the absolute monocyte count (AMC) (hazard ratio [HR], 11.78; P <0.001) and tumor size (HR, 5.41; P = 0.003) as the strongest prognostic factors affecting PFS. We also identified AMC (HR, 23.29; P <0.001), tumor size, (HR, 5.27; P = 0.033), and lymph node involvement (HR, 3.90; P = 0.027) as the strongest prognostic factors affecting OS. AMC remained prognostic with respect to PFS or OS in a Cox model that controlled for the neutrophil-lymphocyte ratio or lymphocyte-monocyte ratio, although neither ratio was a significant prognostic factor for survival. Conclusions: Monocytosis and an increased tumor size were found to be independent prognostic factors affecting both PFS and OS in patients with stage IB and IIA cervical cancer.

Elevated Serum Vitamin B12 Levels as a Prognostic Factor for Survival Time in Metastatic Cancer Patients: A Retrospective Study.

BACKGROUND: Serum vitamin B12 levels have been proposed as one of the survival prediction factors, although no survival analysis in metastatic cancer patients has been conducted yet. This study examined whether serum vitamin B12 levels could be a prognostic factor in metastatic cancer patients. METHODS: Data from a retrospective chart review were used to perform Kaplan-Meier and multivariate analyses of the Cox proportional hazards. Subgroup analysis was performed on patients without a liver lesion (hepatocellular carcinoma or liver metastasis). RESULTS: A total of 523 patients were included. The median survival time was 1.8 months (mo) in the high B12 group (>911 pg/mL) and 5.1 mo in the normal B12 group (211-911 pg/mL) (p < 0.001). In patients without a liver lesion, the median survival times were 2.1 and 6.1 mo in the high and normal B12 groups, respectively (p < 0.001). Multivariate analysis revealed that serum vitamin B12 level was an independent prognostic factor for overall survival (hazard ratio [HR]: 1.62; 95% confidence interval [CI]: 1.34-1.96, p < 0.001). CONCLUSION: Serum vitamin B12 level can be used to predict survival time in metastatic cancer patients. Further large-scale cohort studies are required to confirm these findings.

Detection of angiogenic factors in midtrimester amniotic fluid and the prediction of preterm birth.

OBJECTIVE: We investigated whether the level of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and soluble VEGF receptor-1 (sFlt-1) in midtrimester amniotic fluid of preterm birth have different values compared with term delivery. MATERIALS AND METHODS: Our participants were 86 pregnant women who had undergone amniocentesis from 16 to 19 weeks of gestation. Forty-three cases were women with preterm delivery, and the other 43 cases were matched women with full-term delivery. Stored amniotic fluid was investigated after the delivery. The levels of VEGF, PlGF, and sFlt-1 were measured by enzyme-linked immunosorbent assay and Western blot. RESULTS: The levels of VEGF and PlGF in the preterm group were significantly higher than in the control group (30.48 ± 8.57 pg/mL vs. 26.06 ± 8.24 pg/mL and 28.83 ± 7.83 pg/mL vs. 25.35 ± 8.26 pg/mL, respectively) (p = 0.017 and 0.048, respectively). In terms of sFlt-1, the levels were decreased in the preterm group (10,478.51 ± 4012.56 pg/mL vs. 12,544.05 ± 4140.96 pg/mL) (p = 0.021). CONCLUSION: This study explains that elevated levels of VEGF and PlGF, suggestive of angiogenesis and tendency of inflammation at midtrimester, are predictive of preterm delivery, and their availability is maximized by downregulation of sFlt-1.

The Lymphocyte-Monocyte Ratio Predicts Patient Survival and Aggressiveness of Endometrial Cancer.

OBJECTIVE: We assessed the prognostic implications of preoperative lymphocyte-monocyte ratio (LMR) in patients with endometrial cancer (EC). METHODS: We retrospectively examined the LMR as a prognostic variable in a cohort of 255 patients with EC who underwent surgical resection. Patients were categorized into two groups according to the LMR (LMR-low and LMR-high) using cutoff points determined by receiving operator characteristic (ROC) curve analysis. The primary objective was to correlate the LMR to clinicopathological factors; the secondary objective was to determine the survival significance of the LMR in patients with EC. RESULTS: Using data from the entire cohort, the most discriminative LMR cutoff value selected on the ROC curve was 3.28 for both disease-free survival (DFS) and overall survival (OS). The LMR-low and LMR-high groups included 33 (12.9%) and 222 patients (87.1%), respectively. The 5-year DFS rates in the LMR-low and LMR-high groups were 64.5 and 93.9% (P < 0.0001), respectively, and the 5-year OS rates in the two groups were 76.7 and 96.5% (P < 0.0001), respectively. On multivariate analysis, we identified histologic grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and LMR levels as the strongest prognostic factors affecting DFS (P = 0.0037, P < 0.0001, and P < 0.0001, respectively), and FIGO stage and the LMR as the strongest prognostic factors predicting OS (P < 0.0001 and P < 0.0001, respectively). CONCLUSION: The LMR is an independent prognostic factor for both DFS and OS after surgical resection, and it provides additional prognostic value beyond standard clinicopathological parameters.

The Lymphocyte-Monocyte Ratio Predicts Patient Survival and Aggressiveness of Ovarian Cancer.

OBJECTIVE: To measure the prognostic value of the lymphocyte-monocyte ratio (LMR) in patients with epithelial ovarian cancer (EOC). METHODS: We retrospectively examined the LMR as a prognosticator in a cohort of 234 patients with EOC who underwent surgical resection. Patients were categorized into two different groups based on the LMR (LMR-low and LMR-high) using cut-off values determined by receiver operating characteristic (ROC) curve analysis. The objective of the study was to assess the effect of the LMR on progression-free survival (PFS) and overall survival (OS), and to validate the LMR as an independent predictor of survival. RESULTS: Using the data collected from the whole cohort, the optimized LMR cut-off value selected on the ROC curve was 2.07 for both PFS and OS. The LMR-low and LMR-high groups included 48 (20.5%) and 186 patients (79.5%), respectively. The 5-year PFS rates in the LMR-low and LMR-high groups were 40.0 and 62.5% (P < 0.0001), respectively, and the 5-year OS rates in these two groups were 42.2 and 67.2% (P < 0.0001), respectively. On multivariate analysis, we identified age, International Federation of Gynecology and Obstetrics (FIGO) stage, and cancer antigen 125 levels to be the strongest valuable prognostic factors affecting PFS (P = 0.0421, P = 0.0012, and P = 0.0313, respectively) and age, FIGO stage, and the LMR as the most valuable prognostic factors predicting OS (P = 0.0064, P = 0.0029, and P = 0.0293, respectively). Conclusion : The LMR is an independent prognostic factor affecting the survival of patients with EOC.

The Prognostic Nutritional Index Predicts Survival and Identifies Aggressiveness of Gastric Cancer.

Nutritional status has been associated with long-term outcomes in cancer patients. The prognostic nutritional index (PNI) is calculated by serum albumin concentration and absolute lymphocyte count, and it may be a surrogate biomarker for nutritional status and possibly predicts overall survival (OS) of gastric cancer. We evaluated the value of the PNI as a predictor for disease-free survival (DFS) in addition to OS in a cohort of 314 gastric cancer patients who underwent curative surgical resection. There were 77 patients in PNI-low group (PNI ≤ 47.3) and 237 patients in PNI-high group (PNI > 47.3). With a median follow-up of 36.5 mo, 5-yr DFS rates in PNI-low group and PNI-high group were 63.5% and 83.6% and 5-yr OS rates in PNI-low group and PNI-high group were 63.5% and 88.4%, respectively (DFS, P < 0.0001; OS, P < 0.0001). In the multivariate analysis, the only predictors for DFS were PNI, tumor-node-metastasis (TNM) stage, and perineural invasion, whereas the only predictors for OS were PNI, age, TNM stage, and perineural invasion. In addition, the PNI was independent of various inflammatory markers. In conclusion, the PNI is an independent prognostic factor for both DFS and OS, and provides additional prognostic information beyond pathologic parameters.

Bone Density in Patients with Cervical Cancer or Endometrial Cancer in comparison with Healthy Control; According to the stages.

OBJECTIVE: To evaluate the bone mineral density (BMD) in the lumbar spine and femur in postmenopausal women with cervical cancer and endometrial cancer without bone metastasis in comparison with that in healthy control postmenopausal women, and to assess the loss of BMD according to the cancer stage. MATERIALS AND METHODS: We analyzed the BMD of the lumbar spine and femur using dual-energy X-ray absorptiometry (DXA) in 218 patients with cervical cancer, 85 patients with endometrial cancer, and 259 healthy controls. The serum levels of calcium (Ca), phosphorus (P), osteocalcin (OSC), and total alkaline phosphatase (ALP), and urine deoxypyridinoline(DPL) were measured in all participants. RESULTS: Age, body mass index, parity, and time since menopause were not significantly different between the three groups. Serum Ca level was higher in the cervical cancer group (p = 0.000), however, urine DPL was lower in endometrial cancer group (p = 0.000). The T-scores of basal BMD at the second and fourth lumbar vertebra (L2, L4) were significantly lower in patients with cervical cancer (p = 0.038, 0.000, respectively) compared to those in the healthy control groups. Additionally, the incidence of osteoporosis and osteopenia basal status of bone mass was significantly higher in patients with cervical cancer compared to that in controls (p = 0.016). No differences in basal BMD of the lumbar spine and femur were observed between patients with cervical cancer according to their stages. CONCLUSION: Our results suggest that postmenopausal women with cervical cancer have a lower BMD and are at increased risk of osteoporosis in the lumbar spine before receiving anticancer treatment compared with postmenopausal women with endometrial cancer.

Absolute monocyte and lymphocyte count prognostic score for patients with gastric cancer.

AIM: To measure the prognostic significance of absolute monocyte count/absolute lymphocyte count prognostic score (AMLPS) in patients with gastric cancer. METHODS: We retrospectively examined the combination of absolute monocyte count (AMC) and absolute lymphocyte count (ALC) as prognostic variables in a cohort of 299 gastric cancer patients who underwent surgical resection between 2006 and 2013 and were followed at a single institution. Both AMC and ALC were dichotomized into two groups using cut-off points determined by receiving operator characteristic curve analysis. An AMLPS was generated, which stratified patients into three risk groups: low risk (both low AMC and high ALC), intermediate risk (either high AMC or low ALC), and high risk (both high AMC and low ALC). The primary objective of the study was to validate the impact of AMLPS on both disease-free survival (DFS) and overall survival (OS), and the second objective was to assess the AMLPS as an independent prognostic factor for survival in comparison with known prognostic factors. RESULTS: Using data from the entire cohort, the most discriminative cut-off values of AMC and ALC selected on the receiver operating characteristic curve were 672.4/µL and 1734/µL for DFS and OS. AMLPS risk groups included 158 (52.8%) patients in the low-risk, 128 (42.8%) in the intermediate-risk, and 13 (4.3%) in the high-risk group. With a median follow-up of 37.2 mo (range: 1.7-91.4 mo), five-year DFS rates in the low-, intermediate-, and high-risk groups were 83.4%, 78.7%, and 19.8%, respectively. And five-year OS rates in the low-, intermediate-, and high-risk groups were 89.3%, 81.1%, and 14.4%, respectively. On multivariate analysis performed with patient- and tumor-related factors, we identified AMLPS, age, and pathologic tumor-node-metastasis stage as the most valuable prognostic factors impacting DFS and OS. CONCLUSION: AMLPS identified patients with a poor DFS and OS, and it was independent of age, pathologic stage, and various inflammatory markers.

DDX4 (DEAD box polypeptide 4) colocalizes with cancer stem cell marker CD133 in ovarian cancers.

DDX4 (DEAD box polypeptide 4), characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), is an RNA helicase which is implicated in various cellular processes involving the alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. DDX4 is known to be a germ cell-specific protein and is used as a sorting marker of germline stem cells for the production of oocytes. A recent report about DDX4 in ovarian cancer showed that DDX4 is overexpressed in epithelial ovarian cancer and disrupts a DNA damage-induced G2 checkpoint. We investigated the relationship between DDX4 and ovarian cancer stem cells by analyzing the expression patterns of DDX4 and the cancer stem cell marker CD133 in ovarian cancers via tissue microarray. Both DDX4 and CD133 were significantly increased in ovarian cancer compared to benign tumors, and showed similar patterns of expression. In addition, DDX4 and CD133 were mostly colocalized in various types of ovarian cancer tissues. Furthermore, almost all CD133 positive ovarian cancer cells also express DDX4 whereas CD133-negative cells did not possess DDX4, suggesting a strong possibility that DDX4 plays an important role in cancer stem cells, and/or can be used as an ovarian cancer stem cell marker.

Efficacy and safety of Rhus verniciflua stokes extracts in patients with previously treated advanced non-small cell lung cancer.

BACKGROUND: Systemic treatments for advanced non-small cell lung cancer (NSCLC) have modest survival benefits but high toxicity. Rhus verniciflua Stokes (RVS), the lacquer tree, is an ancient traditional medicine being used for the treatment of cancer. We investigated the efficacy and safety of allergen-removed RVS extract (aRVS) for the prolongation of survival in NSCLC after the failure of first-line or second-line chemotherapy. PATIENTS AND METHODS: We reviewed the medical records of 40 patients who were treated with aRVS for previously treated, advanced NSCLC at the M×µ Integrative Cancer Center, Korea, between June 2006 and June 2009. The primary objective of this study was to assess overall survival. Secondary objectives included assessments of disease control rates, progression-free survival, and the safety of aRVS treatment. RESULTS: The median survival time was 8.4 months with a 1-year survival of 40%. The disease control rate was 63.6%, and the median progression-free survival interval was 3.9 months. Patients who had better performance status and adenocarcinoma experienced more favorable outcomes in terms of overall survival. in aRVS treatment were negligible, with the most common drug-related adverse events being mild epigastric pain and itching skin. Hematologic toxicity was absent. CONCLUSIONS: Survival data and favorable levels of tolerability suggest the potential of aRVS treatment in previously treated patients with advanced NSCLC. Treatment with aRVS might be a viable alternative in patients for whom chemotherapy is not feasible, or who refuse chemotherapy.

A case of recurred hepatocellular carcinoma refractory to doxorubicin after liver transplantation showing response to herbal medicine product, Rhus verniciflua Stokes extract.

There is no established protocol proven to be beneficial for treatment of hepatocellular carcinoma recurrence after liver transplantation. Only a few reports have shown direct treatment by surgery or ablation to be independent predictors of survival for localized recurrence. Moreover, the necessity of immunosuppression to prevent allograft rejection makes many physicians hesitate to administer systemic chemotherapy. This case report documents a case in which the administration of an herbal product, an extract of the lacquer tree, Rhus verniciflua Stokes, was associated with a decrease in the size of lung metastases in a patient with recurrent hepatocellular carcinoma after liver transplantation refractory to doxorubicin. This patient experienced prolonged survival compared with average survival times and little toxicity.