Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma.

An effective blood-based method for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has not yet been developed. Circulating tumour DNA (ctDNA) carrying cancer-specific genetic and epigenetic aberrations may enable a noninvasive 'liquid biopsy' for diagnosis and monitoring of cancer. Here, we identified an HCC-specific methylation marker panel by comparing HCC tissue and normal blood leukocytes and showed that methylation profiles of HCC tumour DNA and matched plasma ctDNA are highly correlated.

Pathologic response after preoperative therapy predicts prognosis of Chinese colorectal cancer patients with liver metastases.

Background: Pathologic response is evaluated according to the extent of tumor regression and is used to estimate the efficacy of preoperative treatment. Several studies have reported the association between the pathologic response and clinical outcomes of colorectal cancer patients with liver metastases who underwent hepatectomy. However, to date, no data from Chinese patients have been reported.

SPP1 rs4754 and its epistatic interactions with SPARC polymorphisms in gastric cancer susceptibility.

The matricellular glycoprotein products of the SPP1 and SPARC genes play critical roles in many aggressive tumor phenotypes including gastric cancer. We sought to test whether the polymorphisms of these two genes, individually or jointly, influence gastric cancer susceptibility. Nine potentially functional, tagging single nucleotide polymorphisms (tagSNPs) of SPP1 and SPARC were selected and detected using the Kompetitive Allele Specific PCR method in 301 gastric cancer cases and 1441 healthy control subjects.

Long noncoding RNA XIST expedites metastasis and modulates epithelial-mesenchymal transition in colorectal cancer.

Tumor progression and metastasis is the main cause of death in colorectal cancer (CRC). Long noncoding RNAs (lncRNAs) are critical regulators in various diseases including human cancer. In this study, we found that lncRNA XIST was overexpressed in CRC cell lines and tissues.

Fibrinogen promotes malignant biological tumor behavior involving epithelial-mesenchymal transition via the p-AKT/p-mTOR pathway in esophageal squamous cell carcinoma.

Purpose: Hyperfibrinogenemia is associated with unfavorable prognosis and advanced tumor behavior in various malignancies, including esophageal squamous cell carcinoma (ESCC). However, its biological function in ESCC is unknown. The present study was designed to further validate the prognostic value of preoperative plasma hyperfibrinogenemia and evaluate the biological role of fibrinogen, as well as the underlying mechanism in ESCC.

DNA methylation markers for diagnosis and prognosis of common cancers.

The ability to identify a specific cancer using minimally invasive biopsy holds great promise for improving the diagnosis, treatment selection, and prediction of prognosis in cancer. Using whole-genome methylation data from The Cancer Genome Atlas (TCGA) and machine learning methods, we evaluated the utility of DNA methylation for differentiating tumor tissue and normal tissue for four common cancers (breast, colon, liver, and lung). We identified cancer markers in a training cohort of 1,619 tumor samples and 173 matched adjacent normal tissue samples.

The Role of Adjuvant Chemotherapy for Colorectal Liver Metastasectomy after Pre-Operative Chemotherapy: Is the Treatment Worthwhile?

Peri-operative chemotherapy has been proposed to improve the survival of patients with colorectal cancer hepatic metastases (CRCHM). However, the role of the adjuvant chemotherapy post-metastasectomy for CRCHM patients who have undergone pre-operative chemotherapy is still undetermined. We retrospectively analyzed the role of adjuvant chemotherapy post-metastasectomy on relapse-free survival (RFS) and overall survival (OS) in 163 CRCHM patients who received pre-operative chemotherapy using a Kaplan-Meier curve and univariate/multiple Cox model.

HELOISE: Phase IIIb Randomized Multicenter Study Comparing Standard-of-Care and Higher-Dose Trastuzumab Regimens Combined With Chemotherapy as First-Line Therapy in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma.

Purpose To compare standard-of-care (SoC) trastuzumab plus chemotherapy with higher-dose (HD) trastuzumab plus chemotherapy to investigate whether HD trastuzumab increases trastuzumab serum trough concentration (C) levels and increases overall survival (OS) in first-line human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. Patients and Methods Patients with Eastern Cooperative Oncology Group performance status 2, no prior gastrectomy, and ≥ two metastatic sites were randomly assigned at a one-to-one ratio to loading-dose trastuzumab 8 mg/kg followed by SoC trastuzumab maintenance 6 mg/kg every 3 weeks or loading-dose trastuzumab 8 mg/kg followed by HD trastuzumab maintenance 10 mg/kg every 3 weeks until progression; treatment in each arm was combined with cisplatin 80 mg/m plus capecitabine 800 mg/m twice per day in cycles 1 to 6. The primary objective was HD trastuzumab OS superiority (all randomly assigned patients [full-analysis set]).

Comparison of prognostic nomograms based on different nodal staging systems in patients with resected gastric cancer.

Previous studies addressing the optimal nodal staging system in patients with resected gastric cancer have shown inconsistent results, and the optimal system for development of prognostic nomograms remains unclear. In this study, we compared prognostic nomograms based on the metastatic lymph node (MLN) count, lymph node ratio (LNR), and log odds of metastatic lymph nodes (LODDS) to predict the 5-year overall survival in patients with resected gastric cancer. We analysed 15,320 patients with resected gastric cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 1988 and 2010.

Hepatitis B virus screening and reactivation and management of patients with nasopharyngeal carcinoma: A large-scale, big-data intelligence platform-based analysis from an endemic area.

Background: Chemotherapy, target therapy, and immunotherapy are increasingly being used in the systematic treatment of nasopharyngeal carcinoma (NPC), during which the occurrence of hepatitis B virus (HBV) reactivation might increase. However, data regarding HBV screening and reactivation and the clinical management of NPC patients with HBV infections are lacking. This study was aimed at clarifying the risk of reactivation for NPC patients on different regimens while providing evidence concerning HBV screening and management in an endemic area.

Hepatitis B virus infection is associated with younger median age at diagnosis and death in cancers.

Several non-hepatocellular cancers were linked with hepatitis B virus (HBV) infection. This study was aimed to quantify the potential associations between HBV infection and multiple non-hepatocellular cancers. Continuous cases, including 5,715 non-cancer and 40,963 cancer cases diagnosed from 2008 to 2014 in Sun Yat-sen University Cancer Center were analyzed.

Mutant Kras- and p16-regulated NOX4 activation overcomes metabolic checkpoints in development of pancreatic ductal adenocarcinoma.

Kras activation and p16 inactivation are required to develop pancreatic ductal adenocarcinoma (PDAC). However, the biochemical mechanisms underlying these double alterations remain unclear. Here we discover that NAD(P)H oxidase 4 (NOX4), an enzyme known to catalyse the oxidation of NAD(P)H, is upregulated when p16 is inactivated by looking at gene expression profiling studies.

YAP-IL-6ST autoregulatory loop activated on APC loss controls colonic tumorigenesis.

Loss of tumor suppressor adenomatous polyposis coli (APC) activates β-catenin to initiate colorectal tumorigenesis. However, β-catenin () activating mutations rarely occur in human colorectal cancer (CRC). We found that APC loss also results in up-regulation of IL-6 signal transducer (IL-6ST/gp130), thereby activating Src family kinases (SFKs), YAP, and STAT3, which are simultaneously up-regulated in the majority of human CRC.

Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study.

Background: To assess the efficacy and safety of fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, in metastatic colorectal cancer (mCRC) patients.

Methods: A phase Ib open-label study and phase II randomized, placebo-controlled trial compared the efficacy of fruquintinib plus best supportive care (BSC) with placebo plus BSC in mCRC patients with ≥2 lines of prior therapies. The primary endpoint was progression-free survival (PFS).

Chemotherapy plus bevacizumab versus chemotherapy plus cetuximab as first-line treatment for patients with metastatic colorectal cancer: Results of a registry-based cohort analysis.

The present observational cohort study was designed to elucidate the efficacy and safety profile of bevacizumab or cetuximab with chemotherapy as the first-line treatment in Chinese patients with metastatic colorectal cancer (mCRC). Clinical data were collected from a single-center registry study where mCRC patients received first-line fluoropyrimidine-based chemotherapy combined with either bevacizumab (188 patients with KRAS wild-type or mutated tumors) or cetuximab (101 patients with KRAS wild-type tumors) between January 2009 and December 2013. The Kaplan-Meier method was used for survival analysis.

Phase II trial of S-1 plus leucovorin in patients with advanced gastric cancer and clinical prediction by S-1 pharmacogenetic pathway.

Background: The first one-arm phase II trial aimed to evaluate and predict efficacy and safety of S-1 plus oral leucovorin (S-1/LV) as first-line chemotherapy for patients with advanced gastric cancer (AGC), using S-1 pharmacogenetic pathway approach.

Patients And Methods: A total of 39 patients orally took S-1 at conventional dose and LV simultaneously at a dose of 25 mg twice daily for a week, within a 2-week cycle. The primary endpoint was overall response rate (ORR), while the secondary endpoints were progression-free survival (PFS), time to failure (TTF), overall survival (OS), disease control rate (DCR), and adverse events (AEs).

Efficacy and safety of cisplatin-based versus nedaplatin-based regimens for the treatment of metastatic/recurrent and advanced esophageal squamous cell carcinoma: a systematic review and meta-analysis.

Cisplatin and nedaplatin show significant antitumor activity and have been widely used for esophageal squamous cell carcinoma (ESCC). However, it is still unclear whether the efficacy and safety of nedaplatin-based regimens are comparable to those of cisplatin-based regimens in patients with metastatic/recurrent or advanced ESCC. Therefore, we conducted a systematic review and meta-analysis to compare the efficacy and safety of these two regimens for the treatment of metastatic/recurrent and advanced ESCC.

CBX4 Suppresses Metastasis via Recruitment of HDAC3 to the Runx2 Promoter in Colorectal Carcinoma.

Polycomb chromobox (CBX) proteins participate in the polycomb repressive complex (PRC1) that mediates epigenetic gene silencing and endows PRC1 with distinct oncogenic or tumor suppressor functions in a cell-type-dependent manner. In this study, we report that inhibition of cell migration, invasion, and metastasis in colorectal carcinoma requires CBX4-mediated repression of Runx2, a key transcription factor that promotes colorectal carcinoma metastasis. CBX4 inversely correlated with Runx2 expression in colorectal carcinoma tissues, and the combination of high CBX4 expression and low Runx2 expression significantly correlated with overall survival, more so than either CBX4 or Runx2 expression alone.

Melatonin enhances sensitivity to fluorouracil in oesophageal squamous cell carcinoma through inhibition of Erk and Akt pathway.

Oesophageal squamous cell carcinoma (ESCC) is the sixth most common cause of cancer-associated death in the world and novel therapeutic alternatives are urgently warranted. In this study, we investigated the anti-tumour activity and underlying mechanisms of melatonin, an indoleamine compound secreted by the pineal gland as well as naturally occurring plant products, in ESCC cells and revealed that melatonin inhibited proliferation, migration, invasion and induced mitochondria-dependent apoptosis of ESCC cells in vitro and suppressed tumour growth in the subcutaneous mice model in vivo. Furthermore, after treatment with melatonin, the expressions of pMEK, pErk, pGSK3β and pAkt were significantly suppressed.

Prognostic value of preoperative serum lactate dehydrogenase levels for resectable gastric cancer and prognostic nomograms.

The present study aimed to evaluate the prognostic significance of preoperative serum lactate dehydrogenase (SLDH) levels for resected gastric cancer and construct prognostic nomograms for risk prediction. The study cohort consisted of 619 patients with D2-resected gastric cancer. The relationship of SLDH levels with clinicopathological features and clinical outcomes was evaluated.

The clinicopathologic relevance and prognostic value of tumor deposits and the applicability of N1c category in rectal cancer with preoperative radiotherapy.

The clinicopathologic relevance and prognostic value of tumor deposits in colorectal cancer has been widely demonstrated. However, there are still debates in the prognostic value of tumor deposits and the applicability of N1c category in rectal cancer with preoperative radiotherapy. In this study, rectal cancer with preoperative radiotherapy followed by resection of primary tumors registered in Surveillance, Epidemiology and End Results (SEER) database from 2010-2012 were analyzed.

Long non-coding RNA XIST regulates gastric cancer progression by acting as a molecular sponge of miR-101 to modulate EZH2 expression.

Background: Long non-coding RNAs (lncRNAs) have emerged as critical regulators of tumor progression. However, the role and molecular mechanism of lncRNA XIST in gastric cancer is still unknown.

Methods: Real-time PCR analysis was performed to measure the expression levels of lncRNA XIST in gastric cancer tissues and cell lines, the correlation between lncRNA XIST expression and clinicopathological characteristics and prognosis was analyzed in gastric cancer patients.

Outcomes of preoperative chemoradiotherapy followed by surgery in patients with unresectable locally advanced sigmoid colon cancer.

Background: Complete resection of locally advanced sigmoid colon cancer (LASCC) is sometimes difficult. Patients with LASCC have a dismal prognosis and poor quality of life, which has encouraged the evaluation of alternative multimodality treatments. This prospective study aimed to assess the feasibility and efficacy of neoadjuvant chemoradiotherapy (neoCRT) followed by surgery as treatment of selected patients with unresectable LASCC.

Predictive value of chemotherapy-related high-density lipoprotein cholesterol (HDL) elevation in patients with colorectal cancer receiving adjuvant chemotherapy: an exploratory analysis of 851 cases.

Background: The phenomenon of chemotherapy-related lipid alterations has been reported based on a small number of patients and varies among different cancers. However, little is known about these alterations in colorectal cancer (CRC) patients.

Results: Patients in cohort 1, but not in cohort 2, exhibited significantly increased cholesterol, triglyceride, HDL-C, and ApoA-I levels, and decreased LDL-C and ApoB levels after adjuvant chemotherapy.