Showing papers in "Molecular and Clinical Oncology in 2015"
TL;DR: Using a logistic regression analysis, metastasis to the adrenal glands and the presence of pleural and/or pericardial fluid effusion were correlated with a poor performance status and when planning the treatment of NSCLC patients, particularly those with liver and adrenal gland metastases, should take into consideration information regarding these unfavorable organ metastases.
Abstract: The present retrospective study was performed to evaluate the clinicopathological characteristics associated with distant metastasis from non-small-cell lung cancer (NSCLC) The records of NSCLC patients with metastasis at the time of diagnosis between 1999 and 2012 were reviewed Of the consecutive 1,542 NSCLC patients diagnosed during the study period, 729 (473%) patients presented with distant metastasis Among those 729 metastatic NSCLC patients, 250 (343%), 234 (321%), 207 (284%), 122 (167%), 98 (134%) and 69 (95%) had bone, lung, brain, adrenal gland, liver and extrathoracic lymph node metastasis, respectively In a multivariate analysis using the Cox proportional hazards model, liver and adrenal gland metastases were unfavorable prognostic factors However, brain and bone metastases were not statistically significant prognostic factors Using a logistic regression analysis, metastasis to the adrenal glands and the presence of pleural and/or pericardial fluid effusion were correlated with a poor performance status Therefore, when planning the treatment of NSCLC patients, particularly those with liver and adrenal gland metastases, we should take into consideration information regarding these unfavorable organ metastases
198 citations
TL;DR: It is demonstrated that a low MPV predicted an unfavorable prognosis in patients with NSCLC following curative resection, and was an independent unfavorable prognostic factor for DFS and OS.
Abstract: An increased mean platelet volume (MPV) is an early marker of platelet activation. MPV was also shown to be associated with the pathophysiological characteristics of various types of cancer. A previous study demonstrated that MPV was significantly associated with the overall survival (OS) of patients with advanced non-small-cell lung cancer (NSCLC). However, there has been no analysis of the prognostic effect of MPV on patients with resected NSCLC. The aim of this study was to evaluate the contribution of MPV to the survival of patients with completely resected NSCLC. We retrospectively analyzed 308 consecutive patients with NSCLC who underwent curative resection at Kitano Hospital. The associations between MPV and clinicopathological factors were assessed. We also evaluated the effect of MPV on survival, using the two-tailed log-rank test and the Cox proportional hazards model. A MPV value of 8.50 fl was considered to be the optimal cut-off value for prognosis. A low MPV was not associated with any other clinicopathological factors. The two-tailed log-rank test demonstrated that patients with a low MPV experienced a shorter disease-free survival (DFS) and overall survival (OS) (P=0.011 and 0.001, respectively), compared to those with a high MPV. The multivariate analysis demonstrated that a low MPV was an independent unfavorable prognostic factor for DFS and OS [hazard ratio (HR)=1.713; 95% confidence interval (CI): 1.070-2.742, P=0.025; and HR=2.835; 95% CI: 1.304-6.163, P=0.009, respectively)]. Therefore, we demonstrated that a low MPV predicted an unfavorable prognosis in patients with NSCLC following curative resection.
85 citations
TL;DR: Gastric cancers treated with high-frequency microsatellite instability (MSI-H) have an improved prognosis, accompanied with reduced risk of LN metastasis, tumor invasion and mortality, and the main outcome was the overall survival rate.
Abstract: Microsatellite instability (MSI) is associated with the prognosis in several cancers and is used for determination of the chemotherapy regimen in stage II colon cancer in the National Comprehensive Cancer Network guideline. However, the association between MSI and the prognosis of gastric cancer remains unclear. PubMed database was searched until January 2014 using MeSH terms and key words to identify the studies evaluating MSI and prognosis of gastric cancer and the references were manually searched. The main outcome was the overall survival rate and the subordinate outcome was the association between high-frequency MSI (MSI-H) and clinicopathological characteristics. Eight studies met the inclusion criteria and the majority of data were collected retrospectively. There were 1,976 patients, 431 of which were MSI-H patients, with a range of 11.68-33.82%. Four studies used the National Cancer Institute panel to define MSI-H, the other four had microsatellite markers ranging 2-11. Significant associations were found in three studies and the overall summary estimate was hazard ratio, 0.63 (95% confidence interval, 0.52-0.77), with no evidence of inter-study heterogeneity (I2=0.0%). MSI-H patients were identified to have a tendency to have less lymph node (LN) metastasis, superficial tumor invasion and to be intestinal type. In conclusion, MSI-H gastric cancers have an improved prognosis, accompanied with reduced risk of LN metastasis, tumor invasion and mortality.
81 citations
TL;DR: A 5-miRNA signature identified from genome-wide serum miRNA expression profiling may serve as a fingerprint for cervical cancer diagnosis.
Abstract: Sensitive and specific biomarkers for the early detection of cervical cancer are urgently required to reduce the high morbidity and mortality of this disease. We previously demonstrated that circulating microRNAs (miRNAs) are correlated with certain types of human cancer. The aim of this study was to investigate the altered profile of serum miRNAs in cervical cancer patients in order to predict cervical cancer at a relative early stage. Serum samples were collected from 213 cervical cancer patients and 158 age- and ethnicity-matched controls. An initial screening of miRNA expression was performed by Solexa sequencing. Differential expression was validated using the stem-loop miRNA quantitative polymerase chain reaction (qPCR) assay in individual samples and the samples were arranged by two-phase selection and validation. The Solexa sequencing results revealed 12 markedly upregulated serum miRNAs in cervical cancer patients compared with controls. The reverse transcription-qPCR analysis identified a profile of 5 serum miRNAs (miR-21, -29a, -25, -200a and -486-5p) as a cervical cancer biomarker. The receiver operating characteristic curves indicated that a panel of 5 miRNAs constitutes a more sensitive and specific diagnostic test compared with any single miRNA-based assay, the squamous cell carcinoma antigen or the carbohydrate antigen 125. More importantly, miR-29a and miR-200a may indicate tumor histological grade and progression stage. Therefore, a 5-miRNA signature identified from genome-wide serum miRNA expression profiling may serve as a fingerprint for cervical cancer diagnosis.
65 citations
TL;DR: The expression of hk2 and pkm2, particularly their combination, in surgical specimens obtained during curative resection, may predict an unfavorable clinical outcome in patients with pancreatic cancer.
Abstract: Metabolism may determine the biologically malignant behavior of pancreatic cancer. To investigate the significance and prognostic value of cancer metabolism in cancer patients, we investigated the expression of two key enzymes in anaerobic glycolysis, hexokinase 2 (HK2) and pyruvate kinase isoenzyme type M2 (PKM2), in surgical specimens obtained from 36 patients who underwent curative resection of pancreatic ductal carcinoma. The hk2-glycolysis axis is a key system in the clinical imaging of tumors via positron emission tomography. Immunohistochemical staining for hk2 and pkm2 was performed and the data were statistically analyzed to evaluate their prognostic power. The expression of hk2 and pkm2 was associated with clinicopathological variables and patient prognosis, including overall survival, local recurrence-free survival and distant metastasis-free survival. Staining for hk2 was negative and positive in 42 and 58% of the patients, respectively, whereas staining for pkm2 was negative and positive in 56 and 44%, respectively; hk2-positive staining was correlated with progressive pathological tumor stage (pT3 vs. pT1 and pT2; P=0.017). In the univariate analysis, the positive expression of hk2 and pkm2, pathological stage (pT3 vs. pT1 and pT2) and nodal metastasis were significantly correlated with poor prognosis (P<0.03). In the multivariate analysis, pathological nodal metastasis was an independent prognostic factor for overall survival, whereas the positive expression of hk2 and pkm2 exhibited borderline significance (P=0.08 and 0.12, hazard ratio = 2.57 and 2.16, respectively). In addition, the combination of high expression of hk2 as well as pkm2 was found to be significant (P<0.05). These results suggested that the expression of hk2 and pkm2, particularly their combination, in surgical specimens obtained during curative resection, may predict an unfavorable clinical outcome in patients with pancreatic cancer.
56 citations
TL;DR: It is suggested that adjuvant RT for borderline and malignant phyllodes tumors decreased the LR rate in patients undergoing BCS, however, adjUvant RT was not found to exert an effect on OS or DFS.
Abstract: The standard treatment for borderline and malignant phyllodes tumors is wide local excision (margins ≥1 cm), in the context of either breast-conserving surgery (BCS) or total mastectomy (TM). Due to the high risk of local recurrence (LR) following surgical intervention alone, the addition of adjuvant radiotherapy (RT) has been previously investigated; however, the conclusions have been inconsistent. This systematic review and meta-analysis was designed to assess the efficacy of adjuvant RT for borderline and malignant phyllodes tumors. Pubmed and Web of Science were systematically searched to identify relevant studies assessing the effect of adjuvant RT on borderline and malignant phyllodes tumors from the inception of this technique through May, 2014. A total of 8 studies were identified among 332 citations. In this meta-analysis, patients who received adjuvant RT had a lower relative risk of LR [hazard ratio (HR) = 0.43, 95% confidence interval (CI): 0.23–0.64]. The absolute risk difference was 10.1% (95% CI: 4.9–17.6), corresponding to a number needed to treat of 10. Our pooled meta-analysis clearly demonstrated a decreased risk of LR in patients with borderline and malignant phyllodes tumors who received RT following BCS (HR=0.31, 95% CI: −0.10–0.72). However, the combined HR for LR in the TM group did not demonstrate that adjuvant RT was superior to no RT (HR=0.68, 95% CI: −0.28–1.64). No significant differences were observed in overall survival (OS) or disease-free survival (DFS) between the two groups. Our analysis suggested that adjuvant RT for borderline and malignant phyllodes tumors decreased the LR rate in patients undergoing BCS. However, adjuvant RT was not found to exert an effect on OS or DFS.
55 citations
TL;DR: The objective of this review was to discuss the possible role of NSAIDs in the modulation of antitumour drug cytotoxicity and the use of COX-2 inhibitors in combination with chemotherapy and the molecular and cellular mechanisms underlying the alterations in outcome that occur in response to this combination therapy.
Abstract: Cancer cell resistance, particularly multidrug resistance (MDR), is the leading cause of chemotherapy failure. A number of mechanisms involved in the development of MDR have been described, including the overexpression of ATP-dependent membrane-bound transport proteins. The enhanced expression of these proteins, referred to as ATP-binding cassette (ABC) transporters, results in an increased cellular efflux of the cytotoxic drug, thereby reducing its intracellular concentration to an ineffective level. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently consumed drugs worldwide. NSAIDs are mainly used to treat pain, fever and inflammation. Numerous studies suggest that NSAIDs also show promise as anticancer drugs. NSAIDs have been shown to reduce cancer cell proliferation, motility, angiogenesis and invasiveness. In addition to these effects, NSAIDs have been shown to induce apoptosis in a wide variety of cancer types. Moreover, several studies have indicated that NSAIDs may sensitise cancer cells to the antiproliferative effects of cytotoxic drugs by modulating ABC transporter activity. Therefore, combining specific NSAIDs with chemotherapeutic drugs may have clinical applications. Such treatments may allow for the use of a lower dose of cytotoxic drugs and may also enhance the effectiveness of therapy. The objective of this review was to discuss the possible role of NSAIDs in the modulation of antitumour drug cytotoxicity. We particularly emphasised on the use of COX-2 inhibitors in combination with chemotherapy and the molecular and cellular mechanisms underlying the alterations in outcome that occur in response to this combination therapy.
55 citations
TL;DR: Early identification and differentiation of these tumors may enable patients to benefit from surgical resection, radiation and combination chemotherapy prior to developing other comorbidities from metastatic disease, which may translate into prolonged survival with an acceptable quality of life.
Abstract: Glioblastoma (GBM) is the most common and the most malignant primary brain tumor in adults, accounting for ~12–15% of all intracranial neoplasms. Despite advances in surgical, medical and radiation therapies, the mortality of GBM remains high, with a median survival ranging between 40 and 70 weeks. Similar to other primary brain tumors, the extracranial metastasis of GBM is extremely rare, occurring in <2% of patients. To demonstrate the clinical characteristics of this rare tumor, we herein present three cases of extracranial GBM metastasis: One to the lungs, which represents the longest reported survival of lung metastases from GBM to date; the second to the soft tissue of the posterior neck; and the third to the lumbar intradural space. Unlike tumors elsewhere, there are unique barriers in the brain that prevent the hematogenous and lymphatic spread of intracranial tumors, such as the dura mater and the thickened basement membrane of the blood vessels. In addition, central nervous system tumor cells lack extracellular matrix proteins required to invade surrounding connective tissue, a prerequisite for tumor dissemination. In this study, we aimed to investigate the different possible mechanisms underlying the extracranial metastasis of GBM and determine the biomolecular and genetic characteristics differentiating GBMs that metastasize from those that do not. We also reviewed the role of systemic chemotherapy and bevacizumab in the treatment of disseminated GBMs. Early identification and differentiation of these tumors may enable patients to benefit from surgical resection, radiation and combination chemotherapy prior to developing other comorbidities from metastatic disease, which may translate into prolonged survival with an acceptable quality of life.
52 citations
TL;DR: It was suggested that the prognosis of Krukenberg tumor is dismal and ovarian metastasectomy may prove beneficial andequate treatment planning is required for this group of patients.
Abstract: Krukenberg tumor is a rare metastastic tumor of the ovary, characterized by poor prognosis. In order to analyze the clinical characteristics and prognostic factors, we retrospectively investigated 128 patients who were diagnosed with Krukenberg tumor between January, 1990 and December, 2010. The median patient age was 48 years. The median overall survival (OS) of Krukenberg tumor for all patients was 16 months (95% CI: 15-19 months). The median OS among patients with Krukenberg tumors of gastric, colorectal, breast and other origins (including appendix, gallbladder, small intestine and unknown primary) was 11, 21.5, 31 and 19.5 months, respectively (P<0.0001). In the univariate analysis, synchronous metastasis, no chemotherapy, ovarian metastasis beyond the pelvis, ascites and no metastasectomy were identified as significant poor prognostic factors. The multivariate analysis suggested that synchronous metastasis (P=0.0080), pelvic invasion (P=0.0138), ascites (P<0.0001) and no metastasectomy (P=0.0060) were independent factors for predicting unfavorable OS. It was suggested that the prognosis of Krukenberg tumor is dismal and ovarian metastasectomy may prove beneficial. Adequate treatment planning is required for this group of patients.
48 citations
TL;DR: The use of ARBs prolonged survival in mCRC patients and was independently associated with prolongation of OS and PFS in the multivariate analysis.
Abstract: The local renin-angiotensin system promotes angiogenesis and vascular proliferation via expression of vascular endothelial growth factor or epidermal growth factor receptor. We hypothesized that angiotensin II type-1 receptor blockers (ARBs) in combination with bevacizumab (Bev) may improve clinical outcomes in patients with metastatic colorectal cancer (mCRC). A total of 181 patients with histopathologically confirmed mCRC treated with first-line oxaliplatin-based chemotherapy in combination with Bev were enrolled between June, 2007 and September, 2010. The patients were divided into two groups based on the presence or absence of treatment with ARBs prior to the initiation of second-line chemotherapy. Kaplan-Meier analysis and Cox proportional hazard modeling were used in the statistical analysis. The median progression-free survival (PFS) in patients undergoing second-line chemotherapy in combination with Bev and ARBs (n=56) vs. those treated in the absence of ARBs (n=33) was 8.3 vs. 5.7 months, respectively [hazard ratio (HR)=0.57, 95% confidence interval (CI): 0.35-0.94, P=0.028]. The median overall survival (OS) was 26.5 vs. 15.2 months, respectively (HR=0.47, 95% CI: 0.25-0.88, P=0.019). In the multivariate analysis, the use of ARBs was independently associated with prolongation of OS and PFS. In conclusion, the use of ARBs prolonged survival in mCRC patients.
40 citations
TL;DR: Evaluated medical records of 284 patients diagnosed with metastatic breast cancer and elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtypes, whereas an elevated CA15-3 level was significantly correlated with bone metastasis and an elevated CEA level was observed regardless of metastatic site.
Abstract: The objective of this study was to investigate the association of serum cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels with clinicopathological parameters in patients diagnosed with metastatic breast cancer (MBC). We retrospectively evaluated the medical records of 284 patients diagnosed with MBC between January, 2007 and December, 2012 who fulfilled the specified criteria and the association between the levels of the two tumor marker and clinicopathological parameters was analyzed. Of the 284 patients, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were identified in 163 (57.4%) and 97 (34.2%) patients, respectively. Elevated CA 15-3 and CEA levels were significantly associated with breast cancer molecular subtypes (P<0.001 and P=0.032, respectively). Cases with luminal subtypes exhibited a higher percentage of elevated CA 15-3 and CEA levels compared to non-luminal subtypes. Elevated CA 15-3 level was correlated with bone metastasis (P=0.017). However, elevation of CEA was observed regardless of the site of metastasis. Elevation of CA 15-3 was significantly more common in MBC with multiple metastatic sites compared to MBC with a single metastasis (P=0.001). However, the incidence of elevated CEA levels did not differ between patients with a single and those with multiple metastatic sites. In conclusion, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtypes, whereas an elevated CA 15-3 level was significantly correlated with bone metastasis and an elevated CEA level was observed regardless of metastatic site. The proportion of MBC cases with elevated CA 15-3 levels differed according to the number of metastatic sites.
TL;DR: This study focused on the most extensively investigated lncRNAs in hepatocellular carcinoma (HCC), which may help identify lnc RNAs that may be used as novel prognostic markers and therapeutic targets.
Abstract: Recent advances in next-generation sequencing technology in transcriptome analysis have helped identify numerous non-coding RNAs. The long non-coding RNA (lncRNA) is commonly defined as an RNA molecule with a length of 200 bp-100 kbp that lacks protein-coding potential. LncRNAs play a critical role in the regulation of gene expression, including chromatin modification, transcription and post-transcriptional processing. It has been confirmed that dysregulation of lncRNAs is associated with a number of human diseases, particularly tumors. In this study, we focused on the most extensively investigated lncRNAs in hepatocellular carcinoma (HCC). The biological functions and molecular mechanisms of the majority of lncRNAs have yet to be investigated. The improved knowledge on lncRNAs in HCC may help identify lncRNAs that may be used as novel prognostic markers and therapeutic targets.
TL;DR: The neutrophil to lymphocyte ratio (NLR) was identified as an independent prognostic factor for OS in patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC) and recurrence or metastasis site were found to beindependent prognostic factors for OS.
Abstract: The neutrophil to lymphocyte ratio (NLR) has been widely investigated for its prognostic significance in cancer In the present study, we aimed to determine whether NLR is a prognostic factor in patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC) A total of 79 patients from the Akdeniz University database were retrospectively analyzed The cut-off NLR was set at 293; patients with NLR >293 had a median overall survival (OS) of 121 months, whereas the median OS was not reached for patients with NLR ≤293 (P=0027) On multivariate analysis, NLR and recurrence or metastatic site were found to be independent prognostic factors for OS (P=0014 and P=0002, respectively) Therefore, NLR was identified as an independent prognostic factor for OS in patients with recurrent or metastatic HNSCC
TL;DR: It is concluded that OPN overexpression in the tumor is a candidate positive prognostic biomarker for breast cancer patients.
Abstract: Osteopontin (OPN) has been implicated in tumor development and progression over the last few years. However, the prognostic value of OPN overexpression in patients with breast cancer remains controversial. We performed a meta-analysis to investigate the association of OPN expression in the tumor with the clinicopathological characteristics and survival of breast cancer patients. A total of 8 studies met the inclusion criteria and were entered in the meta-analysis. The data analysis demonstrated that OPN expression was positively associated with lymph node metastasis [pooled odds ratio = 2.026, 95% confidence interval (CI): 1.199-3.425, P=0.008, random-effects model]. We also found that OPN expression was positively associated with overall survival [hazard ratio (HR) = 3. 69, 95% CI: 1. 45-9.42, P=0.000, random-effects model) and disease -free survival (pooled HR=2.40, 95% CI: 1.27-4.55, P=0.007, fix ed -effects model). Based on the results of this study, we concluded that OPN overexpression in the tumor is a candidate positive prognostic biomarker for breast cancer patients.
TL;DR: VPS remains a valid option for cancer patients with low KPS, as it improves the quality of life in such patients, even in the setting of previous infection, hemorrhage, or leptomeningeal disease, since shunt patency outlasts the overall survival of nearly all patients.
Abstract: Approximately 1-5% of patients with cerebral metastasis and ~40% of patients with primary brain tumors suffer from hydrocephalus. These patients often exhibit a poor prognosis. The aim of the present study was to reassess the validity of ventriculoperitoneal shunting (VPS) with the assistance of the general surgeon in oncological patients. A total of 59 patients underwent first-time VPS at the Beth Israel Deaconess Medical Center (Boston, USA) between 2004 and 2012; 40 patients had hydrocephalus from brain metastasis and 19 from primary tumors. The analyzed independent variables included demographics, body mass index, past medical history, clinical presentation, indication for surgery, Karnofsky performance status (KPS) score and surgical technique; the dependent variables were postoperative symptoms and occurrence, cause and time of shunt failure. The outcomes were analyzed with the t-test and Kaplan-Meier estimates for shunt survival. The mean age of the patients was 57.2 years and the mean operative time was 50.4 min. Symptomatic palliation was achieved in 93% of the cases; patients with severe symptoms, such as debilitating headaches, nausea and vomiting, benefited significantly from VPS. The mean follow-up time was 6.3 months; complications occurred in only 7 patients (11.8%) during follow-up: 2 in the proximal shunt (1 infection and 1 obstruction), both requiring revision, 1 infection in the distal catheter requiring shunt removal, 2 cases of intracerebral bleeding that were monitored with computed tomography scans, 1 wound infection treated with antibiotics and 1 valve complication that required temporary revision. The initial and 3-month KPS scores were 65±16.4 and 75±16.0, respectively. The mean overall shunt survival was 6.4 months (range, 1.0 day-76.0 months) from the placement of the VP shunt. At 3 months after VPS, 93.5% of the patients remained alive with functioning shunts and at 1 year 87% of the shunts were still functioning. In conclusion, VPS remains a valid option for cancer patients with low KPS, as it improves the quality of life in such patients, even in the setting of previous infection, hemorrhage, or leptomeningeal disease, since shunt patency outlasts the overall survival of nearly all patients.
TL;DR: Findings suggested infection was likely to have positive effects on survival in osteosarcoma patients, however, underlying mechanisms remain to be elucidated.
Abstract: There is controversy regarding the impact of infection on long-term prognosis in osteosarcoma patients. Clinical trials and experiments relating to this field could bring reconsideration of immunotherapy for osteosarcoma. The clinical records were reviewed of 125 osteosarcoma patients with a mean follow-up of 5.1±3.9 years (range, 0.5–19.8 years), and a review of the literature was also carried out. Chronic localized infections (but not systemic infection) were determined in 6 patients (4.8%). Similar chemotherapeutic regimens (P=1.00) and histological reactions (P=0.65) were observed in patients with or without infection. Tumor location of proximal tibia (P=0.04) was more common in infected patients. More amputations (P<0.001) were necessitated in infected patients due to uncontrolled infection. The 5-year overall survival rate and event-free survival rate in infected patients were 100%, which were significantly higher than that of the non-infected patients, of whom the rates were 54 and 43% respectively (log-rank test: total survival, P=0.01; tumor-free survival, P=0.01). Distant metastasis was an independent risk factor for survival determined by Cox regression analysis (P<0.001, 95 confidence interval, 1.59–3.98). These findings suggested infection was likely to have positive effects on survival in osteosarcoma patients, however, underlying mechanisms remain to be elucidated. Reconsideration of the association of infection and survival in osteosarcoma patients will help to explore novel therapeutic routes and targets in these patients.
TL;DR: This is the first study to investigate the clinicopathological significance of miR-29b in breast cancer cases and miR -29b is shown to act as a tumor suppressive microRNA in breast Cancer and as a potential marker for recurrence and metastasis in Breast cancer patients.
Abstract: MicroRNA-29b (miR-29b) targets numerous important genes that mediate carcinogenesis and tumor development in breast cancer in vitro and in vivo. The aim of the present study was to determine the clinical significance of miR-29b expression in primary breast cancer patients. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) of miR-29b and certain target genes of miR-29b, such as DNA methyltransferase 3A (DNMT3A), ten-eleven translocation 1 (TET1) and thymine DNA glycosylase (TDG), was performed in 94 primary breast cancer samples. Low expression of miR-29b in primary tumors was significantly associated with poorer disease-free survival (DFS) (P=0.0075) and overall survival (OS) (p=0.0012). Multivariate analysis indicated that miR-29b expression was an independent prognostic factor for OS [relative risk=15.6 (2.33–348), P=0.0026]. In addition, a significant inverse correlation was identified between the expression levels of DNMT3A and miR-29b in estrogen receptor-positive breast cancer patients (P=0.027). To the best of our knowledge, this is the first study to investigate the clinicopathological significance of miR-29b in breast cancer cases and miR-29b is shown to act as a tumor suppressive microRNA in breast cancer and as a potential marker for recurrence and metastasis in breast cancer patients.
TL;DR: A high R R to bevacizumab combination therapy for the MPE associated with non-squamous NSCLC is demonstrated, therefore, bevicizumAB therapy may be considered a therapeutic option for patients withNon-SquamousNSCLC who develop MPE.
Abstract: Malignant pleural effusion (MPE) is a common complication of lung cancer with devastating consequences. Since vascular endothelial growth factor (VEGF) has been implicated in MPE, we hypothesized that bevacizumab, an anti-VEGF antibody, may be effective against MPE in patients with non-small-cell lung cancer (NSCLC). We analysed the records of 21 patients treated for NSCLC-associated MPE between February, 2010 and August, 2013 who consequently underwent bevacizumab combination chemotherapy at the Institute of Biomedical Research and Innovation Hospital. The results were retrospectively analysed using case records and radiographic imaging records. Three patients exhibited complete response of the pleural effusion to bevacizumab treatment, 8 patients achieved a partial response (PR) and 6 patients showed no response. When efficacy was assessed by the response of the measurable primary or metastatic lesions to the treatment, 5 patients achieved a PR, 13 patients had stable disease and 3 patients exhibited progressive disease. The response rate (RR) of the pleural effusion to the antibody treatment was 71.4% and the overall RR of measurable lesions was 23.8%. The median time-to-response for pleural effusion was 132 days. In conclusion, this study demonstrated a high R R to bevacizumab combination therapy for the MPE associated with non-squamous NSCLC. Therefore, bevacizumab therapy may be considered a therapeutic option for patients with non-squamous NSCLC who develop MPE.
TL;DR: The meta-analysis revealed that the presence of β-catenin mutation, compared with the control group, was correlated with a longer overall survival rate and may predict a favorable prognosis in patients with HCC.
Abstract: The β-catenin gene is frequently mutated in patients with hepatocellular carcinoma (HCC) and has long been thought to be one of the major oncogenes involved in the hepatocarcinogenesis. The prognostic role of β-catenin mutation in HCC remains unclear. To address this issue, a search for relevant studies was performed in the PubMed, Embase and Web of Science databases. The pooled effect was calculated from the available data to evaluate the correlation of β-catenin mutation with overall survival rate and tumor clinicopathological features in patients with HCC. The pooled odds ratio (OR) was calculated using the Mantel-Haenszel model for fixed effects. Three studies met the inclusion criteria. A total of 618 cases were included, and β-catenin mutation was identified in 104 of them. The meta-analysis revealed that the presence of β-catenin mutation (n=104), compared with the control group (n=514), was correlated with a longer overall survival rate [OR, 0.33; 95% confidence interval (CI), 0.21–0.53; P<0.00001] in patients with HCC. No significant heterogeneity was found among the eligible studies (I2=0%; P=0.72). β-catenin mutation was correlated with a relatively lower rate of hepatitis B virus infection (OR, 0.36; 95% CI, 0.21–0.61; P=0.0002), improved tumor differentiation (OR, 0.32; 95% CI, 0.19–0.56; P<0.0001) and a lower tumor-node-metastasis stage (I+II) (OR, 0.23; 95% CI, 0.14–0.38; P<0.00001). These findings suggest that β-catenin mutation may predict a favorable prognosis in patients with HCC.
TL;DR: Findings indicate that pretreatment PLR is an important predictor of prognosis in patients with recurrent cervical cancer following CCRT.
Abstract: The aim of the present study was to identify the correlations between inflammation markers such as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and C-reactive protein (CRP) and the prognosis in patients with recurrent cervical cancer. The associations among NLR, PLR and CRP and clinical characteristics and prognosis were examined in 32 patients receiving chemotherapy with recurrent cervical cancer following concurrent chemoradiation therapy (CCRT). The patient median survival time was 198 days (range, 42-1,022 days). Pretreatment NLR and PLR were significantly correlated with the recurrence of cervical cancer following CCRT (R=-0.538, P=0.002; and R=-0.542, P=0.001, respectively). Pretreatment PLR >322.0 was significantly associated with a poor prognosis for recurrent cervical cancer following CCRT by univariate and multivariate analyses (P=0.015 and P=0.029). These findings indicate that pretreatment PLR is an important predictor of prognosis in patients with recurrent cervical cancer following CCRT.
TL;DR: CKS2 is commonly elevated in cancer, most likely due to its ability to promote cancer cell growth, invasion and migration through regulating certain significant genes.
Abstract: Cyclin-dependent kinase subunit 2 (CKS2) is indicated in the processes of cell cycle and cell proliferation. Through these processes, CKS2 is identified as a cancer gene, but its role has not been well reviewed. The aim of the present study was to summarize the clinicopathological significance and the molecular mechanisms of CKS2 in human cancers. Its expression was upregulated in the majority of the types of cancer studied. CKS2 was shown to have a function in cancers of the digestive tract, genital tract, thyroid, nerve and certain other types of cancer. CKS2 can promote progression of certain cancers via positive control of proliferation, invasion and migration. Downregulation of CKS2 induces cancer cell apoptosis. CKS2 can change a multitude of cellular mechanisms in cancer pathogenesis by regulating the gene translation of numerous validated targets, such as p53, CDK1, cyclin A, cyclin B1, caspase-3 and Bax. In addition, the molecular mechanism that causes aberrant expression of CKS2 was epigenetic modification of miR-26a and the Y-box-binding protein 1 (YB-1) gene. In conclusion, CKS2 is commonly elevated in cancer, most likely due to its ability to promote cancer cell growth, invasion and migration through regulating certain significant genes. Understanding the mechanisms by which CKS2 is involved with cancer pathogenesis will be useful in the development of tumor therapy for patients with cancer.
TL;DR: Investigating the sites of mutation of the miR-7 promoter in lung cancer tissues using DNA sequencing identified a G→C change and an A→G change at the -604 site, found to be closely associated with poor prognosis of lung cancer patients, may provide novel insight on the altered expression of specific miRNA molecules in Lung cancer.
Abstract: The significance of promoter mutations of microRNAs (miRNAs) in lung cancer is poorly understood. Recent evidence demonstrated that miRNA-7 (miR-7), a unique member of the miRNA family, exhibited decreased expression and has emerged as an important regulator in lung tumorigenesis. However, the mechanism underlying the downregulation of miR-7 in lung cancer remains largely unknown. In this study, we investigated the sites of mutation of the miR-7 promoter in lung cancer tissues using DNA sequencing. We identified a G→C change at the -617 site (25/39, 64.1%) and an A→G change at the -604 site (20/39, 51.3%) in the miR-7 promoter region in lung cancer tissues. Moreover, the expression of miR-7 in cancer tissue with promoter site mutations was lower compared with that in cancer tissue without mutations (P<0.05). Furthermore, we demonstrated that mutations at these sites may decrease the activity of the miR-7 promoter and alter the expression of miR-7. Notably, mutations at these sites of the miR-7 promoter were found to be closely associated with poor prognosis of lung cancer patients (P=0.037). These data may provide novel insight on the altered expression of specific miRNA molecules in lung cancer and ultimately prove to be helpful in the development of prognostic and therapeutic strategies against lung cancer.
TL;DR: Based on the multivariate analysis, postoperative pathological vascular invasion remained an independent predictor of adverse long-term outcome and vascular invasion was significantly associated with intrahepatic metastasis, emphasizing the need for effective adjuvant therapy in selected high-risk patients with early HCC.
Abstract: Hepatocellular carcinoma (HCC) is an aggressive malignant tumor with a high mortality rate. The optimal therapeutic choice for early HCC is surgical resection. However, the rate of intrahepatic recurrence is high. The objective of this study was to evaluate the effect of various factors on the survival of patients with early HCC. Between January 1st, 2006 and December 31st, 2013, a total of 89 patients who underwent surgery for HCC were retrospectively enrolled. The analysis was conducted using the Student's t-test, Chi-square test, Kaplan-Meier method and Cox proportional hazard regression model to assess potential confounding and predictive variables. The 3-year overall survival (OS) rate was 71%. The 3-year OS rates in patients with and those without vascular invasion were 62.1 and 92.8%, respectively (P<0.003). Based on the multivariate analysis, postoperative pathological vascular invasion (hazard ratio = 4.96; 95% confidence interval: 1.55–15.9) remained an independent predictor of adverse long-term outcome. Furthermore, vascular invasion was significantly associated with intrahepatic metastasis. These data emphasize the need for effective adjuvant therapy in selected high-risk patients with early HCC. Further studies are required to determine the optimal approach to further improving the prognosis of early HCC.
TL;DR: EBV positivity was found to exert no effect on survival, despite its association with aggressive BC phenotypes, and EBV was not associated with DFS or OS, in contrast to BC phenotype, tumour size or nodal status.
Abstract: The presence of the Epstein-Barr-virus (EBV) has been reported to be a pathogenic factor in breast cancer (BC). We previously demonstrated the aggressiveness of EBV-positive BC. The purpose of the present study was to evaluate the effect of EBV on the prognosis of BC according to the BC phenotype. A total of 117 patients with primary BC previously tested for the presence of EBV were evaluated. The presence of the virus was evaluated in breast specimens using quantitative PCR (qPCR). Disease-free survival (DFS) and overall survival (OS) were evaluated for 4 molecular subtypes, namely luminal A and B (lumA and lumB, respectively), human epidermal growth factor receptor 2 (HER2) and triple-negative (TN) subtypes and according to the EBV status. EBV positivity was observed in 32.5% of the cases. TN, HER2 and lumB tumours were more frequent among EBV-BC cases (P=0.02). The DFS rates were different between BC subtypes (P=0.002), but the differences were not statistically significant when the cases were stratified according to the EBV status (P=0.08 for EBV-negative and 0.06 for EBV-positive cases). The OS rates were similar for BC subtypes (P= 0.50) and when the cases were stratified according to the EBV status (P=0.16 and P=0.67 for EBV-positive and -negative cases, respectively). EBV was not associated with DFS or OS, in contrast to BC phenotypes, tumour size or nodal status. Therefore, EBV positivity was found to exert no effect on survival, despite its association with aggressive BC phenotypes.
TL;DR: Standard RT with concurrent TMZ was associated with improved survival, even in patients aged >75 years, and HRT with and without concurrent TMZ and TMZ alone improved survival compared to the no treatment group.
Abstract: The Surveillance, Epidemiology and End Results (SEER) database was used to determine the treatment patterns, outcomes and cost of therapy in elderly patients with glioblastoma multiforme (GBM). The SEER-Medicare linked database was used to identify patients aged >66 years with GBM diagnosed between 1997 and 2009. The patients were stratified by initial treatment following diagnostic surgery (resection or biopsy) into 6 groups as follows: No treatment, standard radiation therapy (SRT) with and without concurrent temozolomide (TMZ), hypofractionated RT (HRT) with and without concurrent TMZ, or TMZ alone. The 3,759 patients identified had a median age of 74 years (range, 66-97 years). A total of ~48% of the patients received SRT without TMZ; ~10% received SRT with concurrent TMZ; ~29% received no treatment; ~10% received HRT without TMZ; ~1% received HRT with TMZ; and 75 years. HRT with and without concurrent TMZ and TMZ alone improved survival compared to the no treatment group. Therefore, in certain cases, HRT or TMZ alone may be more cost-effective, with similar survival outcomes. The various treatment options highlight the need for geriatric assessment tools to aid in therapeutic decision making.
TL;DR: It is demonstrated that higher NLR and PLR values may help identify ovarian cancer in patients with adnexal masses and predicted ovarian cancer at the cut-off value of 3.35, sensitivity and specificity of 81% and 0.38% respectively.
Abstract: The aim of this study was to evaluate the association between preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and the pathological diagnosis of adnexal masses. The predictive effect of inflammatory markers on epithelial ovarian cancer was also investigated. The present study included a total of 306 patients with adnexal masses who underwent surgical resection and the diagnosis was based on pathological investigation. The patients were divided into six groups based on their pathological findings and compared with respect to their NLR and PLR values. We used receiver-operating characteristic curves to calculate optimal cut-off values for NLR and PLR to predict ovarian cancer preoperatively. Patients with ovarian cancer exhibited significantly higher NLR and PLR values (P<0.05 and P<0.001, respectively). The multivariate analysis demonstrated that higher NLR and PLR values predicted ovarian cancer at the cut-off value of 3.35, sensitivity of 55% and specificity of 81% for NLR [95% confidence interval (CI): 0.544-0.752, P<0.05] and at the cut-off value of 572.9, sensitivity of 100% and specificity of 0.38% for PLR (95% CI: 0.192-0. 381, P=0.001). Therefore, preoperative NLR and PLR values may help identify ovarian cancer in patients with adnexal masses.
TL;DR: Although the survival outcomes were worse in Child-Pugh B patients treated with sorafenib, the toxicity profile was manageable and there remains the question of whether to treat this subgroup of patients.
Abstract: Sorafenib demonstrated a survival benefit in the treatment of advanced hepatocellular carcinoma (HCC) in phase III trials. However, almost all the patients included in those trials exhibited well-preserved liver function (Child-Pugh A). The aim of this study was to describe our experience with sorafenib in Child-Pugh B HCC patients. A database of patients with advanced HCC treated with sorafenib was retrospectively evaluated. The median overall survival of Child-Pugh B patients (n=20) was 2.53 months [95% confidence interval (CI): 0.33–5.92 months] and of Child-Pugh A patients (n=100) 9.71 months (95% CI: 6.22–13.04). Child-Pugh B patients had a significantly poorer survival compared to Child-Pugh A patients (P=0.002). The toxicities were similar between the two groups. Metastasis, vascular invasion and α-fetoprotein level >1,030 ng/ml were not associated with survival among Child-Pugh B patients (P=0.281, 0.189 and 0.996, respectively). Although the survival outcomes were worse in Child-Pugh B patients treated with sorafenib, the toxicity profile was manageable. Therefore, there remains the question of whether to treat this subgroup of patients and more data are required to define the role of sorafenib in the context of liver dysfunction.
TL;DR: Evidence is provided that honey and bee pollen may improve the menopausal symptoms of breast cancer patients on antihormonal treatment and both exceeded the extent of a placebo effect in this setting.
Abstract: Hot flushes, night sweats, pain during sexual intercourse, hair loss, forgetfulness, depression and sleeping disturbances are common problems among breast cancer patients undergoing antihormonal treatment. The aim of this study was to investigate whether bee pollen can alleviate menopausal symptoms in patients receiving tamoxifen and aromatase inhibitors/inactivators. We compared a pollen-honey mixture with pure honey (placebo) in a prospective, randomized crossover trial in breast cancer patients receiving antihormonal treatment. The menopausal complaints were assessed using the Menopause Rating Scale (MRS). A total of 46 patients were recruited; 68.3% (28/41) of the patients reported an improvement in their symptoms while taking honey, compared with 70.9% (22/31) who reported an improvement with pollen (the difference was non-significant). The results were confirmed by significant improvements in the postmenopausal complaints in the two groups in a pre-post analysis in the MRS and its 3 subscales. This study provided evidence that honey and bee pollen may improve the menopausal symptoms of breast cancer patients on antihormonal treatment. Of note, honey, which was intended to be used as a placebo, produced similar effects as pollen and they both exceeded the extent of a placebo effect in this setting (~25%).
TL;DR: General anesthesia with TEA more efficiently inhibited the onset of the Th2-dominant status and decreased the plasma levels of Cor and IL-6 compared to general anesthesia alone and PCEA inhibited the Th1/Th2 status more efficiently compared to PCIA.
Abstract: Thoracic epidural anesthesia (TEA) has been demonstrated to significantly reduce stress and immune dysfunction in trauma patients. In esophageal carcinoma patients undergoing thoracic surgery, TEA combined with general anesthesia during surgery and subsequent postoperative patient-controlled epidural analgesia (PCEA) may improve plasma cortisol (Cor), interleukin (IL)-6 and IL-17 levels and helper T-cell differentiation. A total of 60 esophageal carcinoma patients undergoing thoracic surgery were randomly allocated into groups I, II, III and I (n=15 per group). During surgery, groups I and II received total intravenous general anesthesia (TIVA), whereas groups III and IV received combined TEA and TIVA. Postoperatively, groups I and III received postoperative patient-controlled intravenous analgesia (PCIA), while groups II and IV received PCEA. The Cor, IL-6, IFN-γ, IL-4 and IL-17 levels were measured in peripheral blood samples collected prior to anesthesia (T0), at 2 h after incision (T1), at 4 h postoperatively (T2), at 24 h postoperatively (T3) and at 48 h postoperatively (T4). The plasma Cor, IL-17 and IL-6 levels increased significantly at the beginning of the operation in groups I, II and III, while in group IV there were no significant differences during the entire period, concurrent with enhanced Th0 to Th2 shift, contributing to a Th2-dominant Th1/Th2 ratio. General anesthesia with TEA more efficiently inhibited the onset of the Th2-dominant status and decreased the plasma levels of Cor and IL-6 compared to general anesthesia alone and PCEA inhibited the Th2-dominant status more efficiently compared to PCIA. Therefore, general anesthesia combined with TEA and sole administration of PCEA were demonstrated to inhibit the stress response and minimize immune dysfunction, generating most pronounced results upon combination TEA/PCEA treatment.
TL;DR: KRAS point mutations in colorectal cancer exhibited a heterogeneous distribution in terms of tumor localization and the p.G13D point mutation was found to differ from other mutations in several aspects.
Abstract: The aim of this study was to investigate the clinicopathological characteristics and distribution by tumor localization of KRAS point mutations in metastatic colorectal cancer. A total of 189 patients diagnosed with colorectal cancer between 2007 and 2014, who were either metastatic at the time of diagnosis or developed metastasis subsequently, were included in this study. KRAS mutation analysis was performed in the primary tumor tissues and KRAS mutations were identified in 47.6% of the patients. There was a high frequency of the p.G13D point mutation in left-colon tumors (P=0.011), while the p.G12D point mutation was more frequent in right-colon tumors (P=0.004). KRAS wild-type frequency (P=0.02) was higher among patients aged 50-year-old group (P=0.03) and codon 13 mutations were more common in the <70-year-old group (P=0.04). KRAS wild-type tumors were localized in the right colon (P=0.005) and tumors with the p.G13D point mutation (P=0.018) were diagnosed at non-metastatic stages. In conclusion, KRAS point mutations in colorectal cancer exhibited a heterogeneous distribution in terms of tumor localization. In addition, the p.G13D point mutation was found to differ from other mutations in several aspects.