Showing papers in "Clinical & Translational Oncology in 2016"
TL;DR: Recurrent tumors can be offered re-intervention, participation in clinical trials, anti-angiogenic agent or local electric field therapy, without an evident impact on survival, while molecular-targeted therapies, immunotherapy and gene therapy are promising tools currently under research.
Abstract: Glioblastoma (GBM) is the most common and lethal tumor of the central nervous system. The natural history of treated GBM remains very poor with 5-year survival rates of 5 %. Survival has not significantly improved over the last decades. Currently, the best that can be offered is a modest 14-month overall median survival in patients undergoing maximum safe resection plus adjuvant chemoradiotherapy. Prognostic factors involved in survival include age, performance status, grade, specific markers (MGMT methylation, mutation of IDH1, IDH2 or TERT, 1p19q codeletion, overexpression of EGFR, etc.) and, likely, the extent of resection. Certain adjuncts to surgery, especially cortical mapping and 5-ALA fluorescence, favor higher rates of gross total resection with apparent positive impact on survival. Recurrent tumors can be offered re-intervention, participation in clinical trials, anti-angiogenic agent or local electric field therapy, without an evident impact on survival. Molecular-targeted therapies, immunotherapy and gene therapy are promising tools currently under research.
434 citations
TL;DR: Tumor-associated macrophages (TAMs) are major component of leukocytic infiltrate of tumors and play important roles in progression and regression of tumors.
Abstract: Tumor-associated macrophages (TAMs) are major component of leukocytic infiltrate of tumors and play important roles in progression and regression of tumors. Tumor microenvironment determines the mutual conversion between M1 and M2 macrophages. In many kinds of tumors, M2 type macrophages are of the majority in TAMs and promote tumor progression and metastasis. The dynamic balance and interaction between TAMs and tumor cells have important effects on the occurrence and development of tumor. TAMs in malignant tumors are useful for clinical diagnosis and may provide a novel target for cancer treatment.
105 citations
TL;DR: It is indicated that high value of total TILs is not associated with breast cancer clinicopathological features, but can predict a favorable outcome for neoadjuvant chemotherapy in majority except for hormone receptor (−) subtype.
Abstract: Background
Breast cancer is the most common invasive cancer to affect women in the world. Studies showed tumor-infiltrating lymphocytes can exhibit both beneficial and harmful effects on the biology and clinical outcome of breast cancer, the conclusion still remains incomplete. Here, we conducted a meta-analysis to evaluate the relationship between tumor-infiltrating lymphocytes and breast cancer.
101 citations
TL;DR: It is proposed that HER2 positivity could be a significant risk factor for the presence of CTCs and have a significant prognostic value for MBC patients, especially those with HER2 + primary tumors.
Abstract: Metastatic breast cancer (MBC) remains the main cause of cancer-related death, and the clinical significance and prognostic role of circulating tumor cells (CTCs) in metastatic breast cancer are still controversial. Here, we conducted a meta-analysis to clarify the correlation between CTCs and the clinicopathological features and prognosis of MBC. We performed a comprehensive search of Pubmed and the ISI Web of Science through December 2014. Only articles that focused on MBC patients and detected CTCs using the CellSearch system were included. The associations between CTCs and survival rate and clinicopathological parameters, including molecular pattern, metastatic region and treatment response, were evaluated. This meta-analysis included 24 studies (3701 MBC patients), 13 prospective studies and 11 retrospective studies. We found that CTCs were more frequently detected with HER2 + primary tumors (pooled RR = 0.73, 95 % CI = 0.63–0.84). Additionally, higher CTC numbers indicated a worse treatment response (RR = 0.56, 95 % CI = 0.40–0.79), poorer PFS (RR = 0.64, 95 % CI = 0.56–0.73) and poorer OS (RR = 0.69, 95 % CI = 0.64–0.75) in MBC patients. Based on these results, we propose that HER2 positivity could be a significant risk factor for the presence of CTCs. Additionally, CTCs have a significant prognostic value for MBC patients. Therefore, CTCs should be continually monitored to guide the treatment of MBC patients, especially those with HER2 + primary tumors.
65 citations
TL;DR: 18F-FDG PET demonstrates high diagnostic accuracy for response to initial chemotherapy in patients with ES and it correlates with outcome; the role of FDG PET in predicting response and outcome should be further investigated.
Abstract: Response to chemotherapy is a prognostic factor in patients with Ewing sarcoma (ES); the role of FDG PET to predict response in these patients has not been thoroughly investigated. We evaluated the diagnostic accuracy and the potential of FDG PET to predict response to chemotherapy (CHT). We analyzed data of 50 patients with ES (median age 12.6 years). All patients were treated with neoadjuvant CHT, and underwent surgery for local control. All patients had 18F-FDG PET/CT at diagnosis and after induction CHT, prior to local control. We compared response assessed by histopathology with FDG PET using standard uptake values (SUVs). Median SUV at diagnosis (SUV I) was 5 (range 1.2–17), and median SUV after neoadjuvant chemotherapy (SUV II) was 1.8 (range 0–8.4). Median SUV II/I ratio was 0.3 (range 0–1). SUV at diagnosis was significantly lower in patients with good histological response than in patients with poor histological response (median 3.8 vs. 7.2, p 0.02). We found a significant correlation between SUV II and outcome; the positive predictive value of an SUV II ≤ 2.5 for favorable response was 84.21 %, and the median SUV II was significantly higher in patients with disease progression (2.3 vs. 1.6, p = 0.04). In multivariate analysis, necrosis and SUV II were significant predictors of outcome. 18F-FDG PET demonstrates high diagnostic accuracy for response to initial chemotherapy in patients with ES and it correlates with outcome. The role of FDG PET in predicting response and outcome should be further investigated.
54 citations
TL;DR: The evaluation of DCLK1 promoter region methylation may be useful in both early diagnosis and prediction of the course of lung cancer.
Abstract: The possibility of detection of suppressor genes methylation in circulating free DNA (cf-DNA) of cancer patients and the lack of methylation in healthy individuals makes this epigenetic alternation an ideal diagnostic marker of neoplastic processes. Moreover, hypermethylation in several genes promoter was described as a biomarker of lung cancer. Methylation in the gene encoding doublecortin-like kinase 1 (DCLK1) is observed in patients with colorectal cancer and cholangiocarcinoma. However, there are no studies concerning DCLK1 methylation in lung cancer patients. The aims of the study was to evaluate the frequency of DCLK1 promoter methylation in cf-DNA of lung cancer patients and of healthy persons as well as the usefulness of this test for predicting the lung cancer course. DCLK1 methylation status was evaluated in DNA isolated from peripheral blood plasma from 65 lung cancer patients and 95 healthy individuals. After DNA bisulfitation, DCLK1 methylation was determined using the qMSP-PCR technique. Moreover, the presence of DCLK1 methylation was correlated with the overall survival (OS) probability of lung cancer patients. DCLK1 promoter methylation was detected in 32 lung cancer patients (49.2 %) and 8 healthy individuals (8.4 %). The methylation of the region before transcription start site (TSS) and the region after TSS of DCLK1 gene was detected in 28 and 11 patients, respectively. In seven cases (10.8 %), the DCLK1 promoter methylation in both regions was reported simultaneously. The methylation was observed slightly frequently in patients with small cell lung cancer (75 % of SCLC patients). The median overall survival of patients with DCLK1 promoter methylation was lower than that of patients without DCLK1 gene modification (p = <0.001, HR = 4.235). The evaluation of DCLK1 promoter region methylation may be useful in both early diagnosis and prediction of the course of lung cancer.
53 citations
TL;DR: There is a critical need for improvements in clinical care to ensure patients are well informed about infertility risks and fertility preservation options and to support them in their reproductive decision-making prior to cancer treatment.
Abstract: Chemotherapy and radiotherapy often result in reduced fertility in cancer patients. With increasing survival rates, fertility is an important quality-of-life concern for many young cancer patients. Around 70–75% of young cancer survivors are interested in parenthood but the numbers of patients who access fertility preservation techniques prior to treatment are significantly lower. Moreover, despite existing guidelines, healthcare professionals do not address fertility preservation issues adequately. There is a critical need for improvements in clinical care to ensure patients are well informed about infertility risks and fertility preservation options and to support them in their reproductive decision-making prior to cancer treatment.
52 citations
TL;DR: ATAD2 could serve as a prognostic biomarker for gastric cancer patients by correlated with advanced clinical stage, tumor depth, lymph node metastasis, and distant metastasis and according to the survival analysis, ATAD2 protein overexpression was a poor independent prognostic factor for gastrics cancer patients.
Abstract: ATPase family, AAA domain containing 2 (ATAD2) has been found overexpressed in various cancer types and correlated with malignant status and poor prognosis. However, little is known about the clinical significance of ATAD2 in gastric cancer patients. The aim of this study was to explore the clinical and prognostic significance of ATAD2 in gastric cancer. The mRNA and protein levels expression of ATAD2 were detected in clinical tissue samples by qRT-PCR and immunohistochemistry, respectively. We examined the ATAD2 protein expression by immunohistochemistry. Furthermore, we analyzed the association between ATAD2 expression and clinicopathological features including prognosis in 166 gastric cancer samples. In our results, ATAD2 mRNA and protein were highly expressed in gastric cancer samples. ATAD2 overexpression was correlated with advanced clinical stage, tumor depth, lymph node metastasis, and distant metastasis. According to the survival analysis, ATAD2 protein overexpression was a poor independent prognostic factor for gastric cancer patients. In summary, ATAD2 could serve as a prognostic biomarker for gastric cancer patients.
49 citations
TL;DR: Evidence is presented that SOX4 is a potential prognostic biomarker in human cancers and its correlation with overall survival in patients with human cancers is correlated with poor overall survival.
Abstract: Objective
The aim of the this study was to analyze the status of sex-determining region Y-related high-mobility group box 4 (SOX4) expression in varied human cancers and its correlation with overall survival in patients with human cancers.
46 citations
TL;DR: Results indicated that EBER-1 expression is a potential prognosis factor of NPC and highly negative correlated with the progress of NPC.
Abstract: EBER-1 (a non-coding RNA transcribed by EBV) expression was detected in most of Epstein–Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) patients However, the relevance between EBER-1 expression and NPC clinical outcome has not been reported This study aims to assess the possible correlations of EBER-1 expression and clinical parameters and its potential prognostic predictive ability in NPC patient’s outcomes We examined EBER-1 mRNA expression in 301 NPC and 130 non-NPC tissues using in situ hybridization and did statistics EBER-1 expression was up-regulated in NPC tissues when compared to non-NPC tissues A receiver operating characteristic analysis revealed that EBER-1 expression could distinguish non-cancerous patients from NPC patients (p < 0001, sensitivity: 725 %, specificity: 835 %, AUC = 0815) A survival analysis revealed that patients with high levels of EBER-1 expression had a significantly good prognosis (Disease-free survival: p = 0019, overall survival: p = 0006) These results indicated that EBER-1 expression is a potential prognosis factor of NPC and highly negative correlated with the progress of NPC
45 citations
TL;DR: Fibrinogen and D-dimer levels after two cycles of chemotherapy are predictors for response on chemotherapy and prognosis in SCLC patients.
Abstract: Elevated plasma fibrinogen and D-dimer levels indicate activation of hemostasis and fibrinolysis, and this activation is required for tumor angiogenesis, metastasis, and invasion. Previous studies demonstrated that the plasma fibrinogen and D-dimer levels correlate with patient’s prognosis in several solid tumors. The aim of this study is to examine the relationship between plasma fibrinogen and D-dimer levels before and during chemotherapy and treatment response and survival in patients with small cell lung cancer (SCLC). Plasma fibrinogen and D-dimer levels before and during chemotherapy were prospectively measured in 74 SCLC patients who received first-line therapy. The results were analyzed for correlation between fibrinogen and D-dimer levels and treatment response, as well as progressive-free survival (PFS) and overall survival (OS). The levels of fibrinogen and D-dimer in SCLC patients before (C0) and after two cycles (C2) of chemotherapy were significantly higher than those in controls. Fibrinogen and D-dimer levels decreased during chemotherapy, and changes in fibrinogen and D-dimer levels between at C0 and at C2 were associated with treatment response. No matter which disease stage, patients with fibrinogen or D-dimer positivities at C0 and C2 time points had worse PFS and OS than those with fibrinogen or D-dimer negativities. Multivariate analyses revealed that fibrinogen and D-dimer positivities after two chemotherapy cycles were independently unfavorable factors for PFS and OS. Fibrinogen and D-dimer levels after two cycles of chemotherapy are predictors for response on chemotherapy and prognosis in SCLC patients.
TL;DR: First-line treatment with anthracyclines (or in combination with ifosfamide) is the treatment of choice and new drugs have shown activity in second-line therapy and in specific histological subtypes.
Abstract: Soft-tissue sarcomas are uncommon and heterogeneous tumors of mesenchymal origin. A soft-tissue mass that is increasing in size, greater than 5 cm, or located under deep fascia are criteria for suspicion of sarcoma. Diagnosis, treatment, and management should preferably be performed by a multidisciplinary team in reference centers. MRI and lung CT scan are mandatory for local and distant assessment. A biopsy indicating histological type and grade is needed previous to the treatment. Wide surgical resection with tumor-free tissue margin is the primary treatment for localized disease. Radiotherapy is indicated in large, deep, high-grade tumors, or after marginal resection not likely of being improved with reexcision. Neoadjuvant and adjuvant chemotherapy improve survival in selected cases, usually in high-grade sarcomas of the extremities. In the case of metastatic disease, patients with exclusive lung metastasis could be considered for surgery. First-line treatment with anthracyclines (or in combination with ifosfamide) is the treatment of choice. New drugs have shown activity in second-line therapy and in specific histological subtypes.
TL;DR: There is a potential role for ProGRP and NSE in both therapy monitoring and predicting survival in SCLC patients, and there was a significant correlation between ProgrP mRNA expression in peripheral blood and serum Pro GRP protein level.
Abstract: The aim of this study was (1) to evaluate and predict the value of ProGRP and NSE in therapy and survival; (2) as well as to investigate the correlation between the ProGRP mRNA expression in peripheral blood and serum ProGRP protein. The study included 122 patients with SCLC without prior therapy. The serum levels of ProGRP and NSE were detected by enzyme-linked immunosorbent assay and eletro-chemiluminescence immunoassay, respectively. The expression of ProGRP mRNA was detected by real-time reverse transcriptase-polymerase chain reaction. Distribution of serum levels of ProGRP, NSE and ProGRP mRNA differed significantly according to tumor size, disease stage and distant metastasis (all P 0.05). After two courses of chemotherapy, patients of remission and stable groups showed a marked decrease in ProGRP and NSE concentrations (P 0.05). Multiple Cox regression model analysis found that only disease stage and NSE were significant predictors (P < 0.05). This study has found that there is a potential role for ProGRP and NSE in both therapy monitoring and predicting survival in SCLC patients.
TL;DR: The potential roles of CD47 in immune system are highlighted, and the promising therapeutic application of anti-CD47 antibodies for eliminating tumor cells is discussed.
Abstract: The relationship between the immune system and cancer growth and aggravation has been discussed over a century. A number of molecules have been shown to participate in this process. CD47, a normal universally expressed member of the immunoglobulin superfamily, plays multiple functions in immune system. Researches demonstrated that CD47 was also highly expressed on the surface of tumor cells as well as cancer stem cells (CSCs). Whether the highly expressed CD47 was associated with tumor growth, metastasis, recurrence, or drug resistance has become the hotspot. Besides the roles of CD47 in tumor immunoregulation, the monoclonal antibodies targeting CD47 used in acute myelogenous leukemia (AML) and bladder CSCs were reported, which shed new light on tumor treatment. CSCs have been recognized as the root of tumor drug resistance and recurrence. Whether CD47 on CSCs could serve as a potential target for future anti-cancer treatment forms the focus of our review. Here we highlight the potential roles of CD47 in immune system, and discuss the promising therapeutic application of anti-CD47 antibodies for eliminating tumor cells.
TL;DR: Metformin use may associate with a good prognosis in lung cancer patients with type 2 diabetes but the effect was modest, however, it could achieve benefits in a selective sub-group of Lung cancer patients especially in SCLC patients from Asian.
Abstract: Background
Anti-cancer effect of metformin on different kinds of lung cancer has been studied frequently. However, the association between metformin and the prognosis of lung cancer in type 2 diabetes patients is still controversial.
TL;DR: Bone-targeted therapies include zoledronic acid, a potent biphosfonate, and denosumab, an anti-RANKL monoclonal antibody, which reduce the risk and/or delay the development of SREs in several types of tumours.
Abstract: Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease. Bone-targeted therapies include zoledronic acid, a potent biphosfonate, and denosumab, an anti-RANKL monoclonal antibody. Both reduce the risk and/or delay the development of SREs in several types of tumours. Radium 233, an alpha-particle emitter, increases overall survival in patients with bone metastases from resistant castration prostate cancer. Multidisciplinary approach is essential and bone surgery and radiotherapy should be integrated in the treatment of bone metastases when necessary. This SEOM Guideline reviews bone metastases pathogenesis, clinical presentations, lab tests, imaging techniques for diagnosis and response assessment, bone-targeted agents, and local therapies, as radiation and surgery, and establishes recommendations for the management of patients with metastases to bone.
TL;DR: Serum albumin, tumor size, hemoglobin and treatment modality affect survival in metastatic STS, with mixed results for EFS and OS.
Abstract: Data on treatment outcome and prognostic factors in patients with metastatic soft tissue sarcoma (STS) are limited in the literature. A total of 119 patients with metastatic STS treated between June 2003 and December 2012 were analyzed for treatment outcome and prognostic factors. Median age was 37 years (range 2–72 years) with a male to female ratio of 1.5:1. Most common histologic subtypes were synovial sarcoma (36 %) and leiomyosarcoma (16 %). Median tumor size was 12 cm (range 1.6–30 cm). Twenty-four (20 %) patients were treated with multimodality therapy and 80 % patients received systemic chemotherapy alone. At a median follow-up of 10 months (range 1–66 months), the 2-year EFS and OS were 10 and 19 %, respectively,
with a median EFS and OS of 6 and 10 months, respectively. Univariate analysis identified albumin ≤4 g/dl (p = 0.001), histologic subtypes other than synovial sarcoma (p = 0.02), non-extremity tumors (p = 0.03) and single modality treatment (p = 0.03) as factors predicting poor EFS; however, for OS, hemoglobin ≤10 g/dl (p = 0.02), tumor size >10 cm (p = 0.01) and single modality treatment (p = 0.04) were identified as poor prognostic factors. Multivariate analysis identified only serum albumin ≤4 g/dl (p = 0.002, HR 0.47, 95 % CI 0.29–0.75) associated with poor EFS; however, for OS, hemoglobin ≤10 g/dl (p = 0.009, HR 0.49, 95 % CI 0.29–0.83), tumor size >10 cm (p = 0.003, HR 2.11, 95 % CI 1.28–3.47) and single modality treatment (p = 0.01, HR 0.47, 95 % CI 0.25–0.86) emerged as poor prognostic factors. Serum albumin, tumor size, hemoglobin and treatment modality affect survival in metastatic STS.
TL;DR: Observations imply that the down-regulation of miR-200f in human BC is associated with an invasive phenotype, and mi R-200b may be useful to estimate the likelihood of the presence of pathologically positive lymph nodes.
Abstract: MicroRNA-200 family (miR-200f) has been consistently reported to be deregulated and modulate the metastatic process in multiple cancers. In the present study, we detected the expression of miR-200f in breast cancer (BC) tissue and explored its relationships with clinicopathological characteristics, especially with lymph node metastasis. Expression levels of miR-200a, miR-200b, miR-200c, miR-141, and miR-429 in 99 pairs of BC tissues and adjacent normal tissues were measured by real-time quantitative PCR. The correlation between miR-200f level and multiple clinicopathological factors was then examined by Mann–Whitney test, ANOVA, and operating characteristic (ROC) analysis. All members of the miR-200f were down-regulated in BC tissue compared with that in normal adjacent tissue; miR-200a, miR-200b, and miR-200c were highly decreased (p < 0.05), while the differences of miR-141 and miR-429 between patients and the control group were not statistically significant. Furthermore, all five members were found to be distinctly decreased with the incidence of lymph node metastasis (p < 0.05); When the patients were divided into three groups according to the number of lymph node metastasis (0; 1–3; ≥4), a gradual decrease of miR-200f expression was observed with the increasing number of lymph node metastasis; ROC revealed that miR-200b can differentiate patients with lymph node metastasis from those without lymph node metastasis. These observations imply that the down-regulation of miR-200f in human BC is associated with an invasive phenotype, and miR-200b may be useful to estimate the likelihood of the presence of pathologically positive lymph nodes.
TL;DR: These data suggested that such combination therapy model be effective and safe for younger metastatic TNBC exposure to previous anthracyclines and taxanes based adjuvant chemotherapy.
Abstract: Background
The recent immunotherapy treatment on triple-negative breast cancer (TNBC) leads to the breakthrough assignation. In this study, we have tried the new combinations of specific chemo with DC-CIKs immunotherapy to treat those patients.
TL;DR: The general surgeon should be aware of the governing principles of the treatment of appendiceal neoplasms with or without peritoneal dissemination, know the therapeutic frontiers in every situation and send early these patients to specialised centres in the radical management of malignant diseases of the peritoneum in the conditions and with the necessary information to facilitate a possible radical treatment.
Abstract: The epithelial appendiceal neoplasms are uncommon and are usually detected as an unexpected surgical finding. The general surgeon should be aware of the diversity of its clinical manifestations and biological behaviors along with the significance of the surgical treatment on the progression of the illness and the prognosis of the patients. The operative findings and, especially, tumor histology, determine the type of surgery. Intestinal histologic subtype behaves and should be treated similarly to the right colon neoplasms; while mucinous tumors, often discordant between histology and its aggressiveness, can be treated with a simple appendectomy or require complex oncological surgeries. Mucinous tumors are often associated with the presence of mucin or tumor implants in the abdominal cavity, being the clinical syndrome known as pseudomyxoma peritonei (PMP). PMP tends to present an indolent but deadly evolution and requires a multimodal approach as a single treatment with curative potential: complete cytoreductive surgery plus hyperthermic Intra-peritoneal chemotherapy (CCRS + HIPEC) now considered the standard of care in this pathology. The general surgeon should be aware of the governing principles of the treatment of appendiceal neoplasms with or without peritoneal dissemination, know the therapeutic frontiers in every situation (avoiding unnecessary or counterproductive surgeries) and sending early these patients to specialised centres in the radical management of malignant diseases of the peritoneum in the conditions and with the necessary information to facilitate a possible radical treatment.
TL;DR: This is the largest data on metastatic osteosarcoma treated with a uniform chemotherapy protocol without high dose methotrexate and showed prognostic factors similar to what have been observed previously such as elevated serum alkaline phosphatase and >3 metastatic lesions in lung predicting inferior outcome.
Abstract: Data on prognostic factors in patients with metastatic osteosarcoma treated with uniform chemotherapy protocol are lacking. The objective of this study was to analyze demographic data, treatment outcome and prognostic factors for patients with metastatic osteosarcoma at our center treated with a uniform chemotherapy protocol without high dose methotrexate. This is a single-institutional data review of patients treated between June 2003 and December 2012 with neoadjuvant chemotherapy, local site surgery followed by adjuvant chemotherapy and metastasectomy at completion of adjuvant chemotherapy. 102 patients of metastatic osteosarcoma were
treated with a median age of 18 years (range 8–48 years), male to female ratio of 3.3:1 and median symptom duration of 4 months. EFS and OS at 5 years were 12.7 ± 0.1 and 28.1 ± 0.1 %, respectively. On multivariate analysis, elevated serum alkaline phosphatase (p 3 (p = 0.04) were predictive of lower EFS, whereas elevated serum alkaline phosphatase (p = 0.01), number of metastasis >3 (p = 0.05), and margin positivity (p 3 metastatic lesions in lung predicting inferior outcome. Notably our survival was comparable to data from other studies despite our practice of delaying metastasectomy to completion of chemotherapy rather than performing the same along with local site surgery.
TL;DR: The level of miR-203 was an independent prognostic indicator of NSCLC using univariate analysis and may be a new target for the molecular therapy ofNSCLC patients.
Abstract: Although miR-203 has been proposed as a relevant biomarker for several cancers, the validated prognostic significance of miR-203 in lung cancer remains obscure. Thus, we aimed to identify the relationship between miR-203 expression and clinicopathological significance in non-small cell lung cancer (NSCLC) patients in the current study. The expression of miR-203 in 125 cases of NSCLC and their paired adjacent non-cancerous tissues was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Simultaneously, the correlation of miR-203 expression with a variety of clinicopathological factors and patient survival was analyzed. Functionally, in vitro effects of miR-203 on proliferation and viability were explored in lung cancer H460, A549, H1299, PC9 and H292 cells, as assessed by MTS tetrazolium assay and fluorimetric resorufin viability assay, respectively. The relative level of miR-203 was 6.12 ± 6.25 in NSCLC tissues, remarkably downregulated than that of their paired non-tumorous lung tissues (7.88 ± 5.56, P = 0.019). The area under curve (AUC) of low expression of miR-203 to diagnose NSCLC was 0.622 (95 % CI 0.552–0.692, P = 0.001). MiR-203 expression was negatively correlated to lymphatic metastasis (r = −0.334, P < 0.001), tumor size (r = −0.407, P < 0.001) and clinical TNM stages (r = −0.298, P = 0.001). Furthermore, the survival of the low miR-203 expression group was 4.88 ± 4.38 months, markedly shorter than that of the high expression group (23.35 ± 1.12 months, P < 0.001). The level of miR-203 was an independent prognostic indicator of NSCLC using univariate analysis. MiR-203 mimic could suppress the cell growth of five lung cancer cell lines tested to different degrees in vitro. MiR-203 could become a prognostic predictor in NSCLC and may be a new target for the molecular therapy of NSCLC patients.
TL;DR: This study finds that ERCC1 and RRM1 are not independent prognostic factors of recurrence in stage I NSCLC patients, and BRCA1 and SETDB1 stand out as the most significant prognostic markers in this group of patients, appearing as promising tools to predict tumor recurrence.
Abstract: Introduction
Nowadays, 40 % of early-stage NSCLC patients relapse in the 2 years following resection, suggesting a mis-staging in this group of patients who are not receiving adjuvant chemotherapy. Although different biomarkers, such as ERCC1, RRM1 and BRCA1 have been found to present prognostic value in advanced NSCLC patients, in early-stage NSCLC patients its relevance remains unclear. Moreover, SETDB1 has been recently proposed as a bona fide oncogene in lung tumourigenesis and related with metastasis. The aim of the present study was to analyze the prognostic value of ERCC1, RRM1, BRCA1 and SETDB1 expression levels in NSCLC patients at stage I.
TL;DR: Research suggests that despite the epithelial nature of Type I and Type II endometrial tumors, both are capable of undergoing an epithelial–mesenchymal transition (EMT), which may facilitate myometrial invasion and metastasis.
Abstract: Endometrial cancer (EC) prognosis is dependent on many factors such as time of diagnosis, histological type, and degree of invasion. Type I EC has a more favorable prognosis as it is less prone to myometrial invasion, which is believed to be the first step in the metastatic cascade. Type II EC displays a more aggressive and motile phenotype, and therefore has a poorer prognosis. Recent work suggests that despite the epithelial nature of Type I and Type II endometrial tumors, both are capable of undergoing an epithelial-mesenchymal transition (EMT), which may facilitate myometrial invasion and metastasis. Activation of the PI3K/Akt pathway has been shown to contribute to EMT through the upregulation of EMT-associated factors. Recent research has also linked estrogen signaling and microRNAs to the regulatory mechanisms that drive EMT in EC. Understanding the intricate relationships between these pathways will provide a better understanding of metastatic progression in EC.
TL;DR: The results suggest that ECT2 plays an important role during GC progression and it may become a new diagnostic marker and therapeutic molecular target for management of GC.
Abstract: The ECT2 (epithelial cell transforming sequence 2) oncogene acted as a guanine nucleotide exchange factor for RhoGTPases, and regulates cytokinesis; thus, it may play a role in the pathogenesis of gastric cancer. In this study, we investigated the expression ECT2 gene in tissues and serum of gastric cancer patients to explore its clinical significance. ECT2 mRNA expression levels in tissues and serum were examined by RT-PCR, and ECT2 protein expression in tissue was evaluated by Western blot, and was further validated by immunohistochemistry and enzyme-linked immunosorbent assay at serum level. ECT2 level was significantly increased in the GC tissues and serum compared to normal control. ECT2 expression was positively correlated with the histologic differentiation, stages of TNM, and lymph node metastasis in GC (P < 0.05). Our results suggest that ECT2 plays an important role during GC progression and it may become a new diagnostic marker and therapeutic molecular target for management of GC.
TL;DR: The results suggest that Pin1 plays an important role in tumorigenesis of PCa, suggesting that targeting Pin1 pathway could represent a potential modality for treating PCa.
Abstract: Recent evidence suggests that the peptidyl-prolyl isomerase Pin1 is an oncoprotein that acts as a novel therapeutic target in a variety of tumors. In this study, we investigated the clinical significance of Pin1 and its function in prostate cancer (PCa) tumor progression. Immunohistochemical and quantitative RT-PCR analyses were performed to detect the expression of Pin1 in 86 PCa tissue samples. The functional role of Pin1 was evaluated by small interfering RNA-mediated depletion in PCa cells followed by analyses of cell proliferation and migration. Furthermore, the association between expression of Pin1 and levels of β-catenin and cyclin D1 was also evaluated. Our results showed that the high expression of Pin1 staining was 66 of 86 (76.74 %) PCa samples, and in 25 of 86 (29.07 %) BPH tissues, the difference was statistically significant (P < 0.001). Pin1 was significantly elevated in all PCa cell lines when compared to the normal RWPE-1 cells. We observed that proliferation and migration of LNCaP cells were inhibited by Pin1 knockdown. The levels of β-catenin and cyclin D1 in clinical PCa specimens were positively associated with Pin1 expression. Our results suggest that Pin1 plays an important role in tumorigenesis of PCa, suggesting that targeting Pin1 pathway could represent a potential modality for treating PCa.
TL;DR: Progress in pancreatic cancer treatment will require a better knowledge of the molecular biology of this disease, focusing on personalized cancer therapies in the near future, and evidence suggests a benefit on survival with adjuvant chemotherapy after R1/R0 resection.
Abstract: Pancreatic cancer remains an aggressive disease with a 5 year survival rate of 5%. Only 15% of patients with pancreatic cancer are eligible for radical surgery. Evidence suggests a benefit on survival with adjuvant chemotherapy (gemcitabine o fluourouracil) after R1/R0 resection. Adjuvant chemoradiotherapy is also a valid option in patients with positive margins. Borderline resectable pancreatic cancer is defined as the involvement of the mesenteric vasculature with a limited extension. These tumors are technically resectable, but with a high risk of positive margins. Neoadjuvant treatment represents the best option for achieving an R0 resection. In advanced disease, two new chemotherapy treatment schemes (Folfirinox or Gemcitabine plus nab-paclitaxel) have showed improvements in overall survival compared with gemcitabine alone. Progress in pancreatic cancer treatment will require a better knowledge of the molecular biology of this disease, focusing on personalized cancer therapies in the near future.
TL;DR: The present Delphi study identified a set of recommendations to define, assess and monitor BTcP, which was considered very important to develop protocols for the management of cancer pain.
Abstract: There is no unanimous consensus on the clinical features to define breakthrough cancer pain (BTcP). The current project aimed to investigate the opinion of a panel of experts on cancer pain on how to define, diagnose, assess, treat and monitor BTcP. A two-round Spanish multi-centre exploratory Delphi study was conducted with medical experts (n = 90) previously selected from Medical Oncology Services, Radiation Oncology, Palliative Care/Home Care Teams, and Pain Units. The study intended to seek experts’ consensus and to define a set of recommendations for the management of BTcP. It was generally agreed that, definition of BTcP implies that baseline pain should be controlled (84 %), although not necessarily with opioids (only 30 %); there must be exacerbations (98.9 %); the duration of each episode should last <1 h (70 %); the intensity of pain ≥7 out of 10 (67.8 %); and the number of flares per day should not be less than four. All participants supported the use of the Davies algorithm for the diagnosis. The use of a ‘Patient Diary’ was highly recommended. The optimal treatment should have a rapid onset, a short-acting analgesic effect (1–2 h) and transmucosal nasal or oral administration. It was considered very important to develop protocols for the management of cancer pain. The present Delphi study identified a set of recommendations to define, assess and monitor BTcP.
TL;DR: miRNA-197 and miRNA-184 are overexpressed in EGFR-mutant patients with BM and they might be a new biomarker for stratifying the risk of BM in this subpopulation.
Abstract: The prognostic value of EGFR mutation in lung cancer patients with brain metastases is uncertain and therapeutic efficacy with EGFR TKI is limited. Looking for biomarkers closely related with early tumor changes and brain metastases in non-small cell lung cancer is warranted. MicroRNAs (miRNAs) are frequently deregulated in lung cancer. The objective of this study was to investigate whether some miRNAs are related with brain metastasis risk in EGFR-mutant non-small cell lung cancer patients. miRNA quantification was retrospectively performed in formalin-fixed, extracranial paraffin-embedded adenocarcinoma tumor tissue available from 17 human samples of advanced non-small cell lung cancer patients. Samples were classified as brain metastasis group (5 EGFR-mutant patients with initial BM, EGFRm-BM+; and 6 EGFR wild-type patients with initial BM) and the control group (6 EGFR-mutant NSCLC patients without BM). The RNA obtained was preamplified and retro-transcribed, and the miRNA was quantified with the TaqMan OpenArray Human MiRNA Panel in the QuantStudio™ 12 K Flex Real-Time PCR system. miRNA-197 and miRNA-184 showed a significant higher expression in EGFRm-BM+ group than in the control group (p = 0.017 and p = 0.01, for miRNA-197 and miRNA-184, respectively), with a trend toward overexpression in BM group compared with the control group (p = 0.08 and p = 0.065, for miRNA-197 and miRNA-184, respectively), without differences in expression in BM group according to EGFR mutational status (EGFR wild type vs. EGFR-mutant: p = 0.175 and p = 0.117, for miRNA-197, miRNA-184 respectively). miRNA-197 and miRNA-184 are overexpressed in EGFR-mutant patients with BM and they might be a new biomarker for stratifying the risk of BM in this subpopulation.
TL;DR: YAP expression in human hepatocellular carcinoma cell lines MHCC97H andMHCC97L is closely related with the characteristic markers of epithelial–mesenchymal transition, N-cadherin and E-c cadherin expression.
Abstract: Purpose
To investigate biological impact of the downregulation of yes-associated protein (YAP) through RNA interference in the process of epithelial–mesenchymal transition in MHCC97H and MHCC97L.