Huijuan Qiu

Involvement of autophagy inhibition in Brucea javanica oil emulsion-induced colon cancer cell death.

Brucea javanica oil emulsion (BJOE), the petroleum ether extract of B. javanica emulsified by phospholipid, is widely used in China as an anticancer agent. The extracts from B. javanica induce cancer cell death by various mechanisms; however, it is not known whether these mechanisms involve autophagy, which is an important process in cancer development and treatment. Thus, the current study aimed to investigate whether BJOE modulates autophagy in HCT116 human colon cancer cells and whether modulation of autophagy is an anticancer mechanism of BJOE. Immunoblotting was employed to analyze the protein expression levels of microtubule-associated protein light-chain 3 (LC3), a specific protein marker of autophagy, in HCT116 cancer cells following exposure to BJOE. The apoptosis rate of the HCT116 cancer cells was detected by performing an Annexin V-fluorescein isothiocyanate/propidium iodide assay. According to the effect of BJOE administration on autophagy in the HCT116 cancer cells (induction or suppression), a functionally opposite agent (autophagy suppressor or inducer) was applied to counteract this effect, and the apoptosis rate of the cancer cells was detected again. The role of autophagy (pro-survival or pro-death) was demonstrated by comparing the rates of apoptotic cancer cells prior to and following the counteraction. The results revealed that BJOE suppressed the protein expression levels of LC3, including the LC3-I and LC3-II forms, and induced apoptosis in the HCT116 cancer cells with a high level of basal LC3. The apoptosis-inducing activity of BJOE was significantly attenuated when autophagy was induced by the administration of trehalose, an autophagy inducer. The data indicates that autophagy inhibition is involved in BJOE-induced cancer cell death, and that this inhibition may be a potential anticancer mechanism of BJOE.

Initial LDH level can predict the survival benefit from bevacizumab in the first-line setting in Chinese patients with metastatic colorectal cancer

Background Markers to predict the efficacy of bevacizumab treatment have been not fully validated in most cancers, including metastatic colorectal cancer (mCRC). The aim of this study was to investigate the potential role of lactate dehydrogenase (LDH) in predicting the survival benefit from first-line bevacizumab treatment, in Chinese patients with mCRC. Methods All the patients were diagnosed with mCRC at the Sun Yat-sen University Cancer Center from 2003 to 2013. The study group and the control group were classified by receiving bevacizumab or not. The serum LDH value of all the patients had been detected before the first-line treatment. The primary end point was progression-free survival (PFS). Results The median PFS of the study and the control group (patients who received bevacizumab or not) was 11.3 and 9.1 months, respectively (P=0.004). In the control group, the median PFS of the high LDH level and the low LDH level groups was 6.9 and 10.2 months, respectively (P<0.001). However, in the study group, the corresponding median PFS was 9.9 and 11.9 months, respectively (P=0.145). In addition, for the low LDH level group, the median PFS was 11.9 and 10.2 months for patients who received bevacizumab or not, respectively (P=0.066); however, the median PFS of patients receiving bevacizumab or not was significantly different in the high LDH level group (9.9 and 6.9 months, respectively) (P=0.012). Conclusion The addition of bevacizumab in the first-line treatment setting could improve the PFS of mCRC patients notably. However, the benefit could only be potentially reflected on patients with high serum LDH level.

Gamma-glutamyl transpeptidase level is a novel adverse prognostic indicator in human metastatic colorectal cancer

Biomarkers have been utilized for prognosis in colorectal cancer; however, relatively few have been identified. We compared the prognostic value of serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma‐glutamyl transpeptidase (GGT) with carcinoembryonic antigen (CEA) and carbohydrate antigen 19‐9 (CA19‐9) in patients with metastatic colorectal cancer (mCRC).

Lymph Node Ratio and pN Staging Show Different Superiority As Prognostic Predictors Depending on the Number of Lymph Nodes Dissected in Chinese Patients With Luminal A Breast Cancer

BACKGROUND The lymph node ratio (LNR) classification has shown superiority to pN staging (the number of positive lymph nodes) in breast cancers, but it has not been examined according to whether sufficient lymph nodes have been dissected. METHODS All Chinese patients with luminal A breast cancer with positive lymph nodes seen at Sun Yat-sen University Cancer Center between 1995 and 2009 were enrolled. Disease-free survival (DFS) and overall survival (OS) were the endpoints, and the patients were further classified into 2 groups according to whether ≤ 10 or > 10 lymph nodes were dissected. RESULTS For the whole group, the OS curves of the pN stages overlapped, whereas they were separated in the LNR survival curves. LNR was an independent prognostic factor for OS and DFS, whereas the pN stage was not. In the ≤ 10 lymph nodes dissected group, both OS and DFS curves were clearly separated in the pN staging but overlapped in the LNR classification. In the > 10 lymph nodes dissected group, LNR showed no overlap in the OS curves and was an independent prognostic factor of OS and DFS when compared with pN staging. CONCLUSION In Chinese patients with luminal A breast cancer, LNR classification and the pN stage show different superiority as prognostic predictors according to whether > 10 or < 10 lymph nodes are dissected.

Prognostic Model Built on Blood-based Biomarkers in Patients with Metastatic Colorectal Cancer

BACKGROUND We had previously showed that the neutrophil lymphocyte ratio (NLR), γ-glutamyl transpeptidase (GGT) and carcinoembryonic antigen (CEA) are prognostic factors for metastatic colorectal cancer (mCRC) patients. In this study we developed a prognostic model based on these three indices. MATERIALS AND METHODS A total of 243 patients who were initially diagnosed as mCRC between 2005 and 2010 in the Sun Yat-sen University Cancer Center were studied. The endpoint was overall survival (OS). RESULTS NLR>3, elevated GGT and elevated CEA were confirmed as independent risk factors which could predict poor prognosis. Patients could be divided into three groups according to the number of risk factors they had. Those with two or three were defined as the high risk group, individuals with one risk factor as the modest risk group and patients without risk factor as the low risk group. The OS values for these three groups were 16.2 months (2.80~68.8), 24.2 months (4.07~79.0), and 37.2 months (12.6~87.8), respectively (p<0.001). CONCLUSIONS We developed a simple but useful model based on NLR, GGT and CEA to provide prognostic information to clinical practice in highly selected mCRC patients. Further prospective and multi-center studies are warranted to test our model.

Positive expression of programmed death ligand-1 correlates with superior outcomes and might be a therapeutic target in primary pulmonary lymphoepithelioma-like carcinoma.

Background Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare subtype of non-small cell lung cancer (NSCLC), and no effective treatments have been defined for advanced disease. Programmed cell death-ligand 1 (PD-L1) is expressed in a group of cancers that may be suitable targets for specific immunotherapy. Methods This study investigated the expression and clinical value of PD-L1 in pulmonary LELC. Seventy-nine patients with pulmonary LELC were investigated. Paraffin-embedded tumor sections were stained with PD-L1 antibody. Correlations of PD-L1 expression with clinicopathologic parameters and outcomes were analyzed. Results Fifty patients (63.3%) were PD-L1 positive. The 3-year and 5-year progression-free survival (PFS) rate was 76.0% and 68.0%, respectively, and the 3-year and 5-year overall survival (OS) rate was 88.0% and 79.0%, respectively. Kaplan–Meier analysis revealed that patients with positive PD-L1 expression had longer PFS and OS than those with negative PD-L1 expression (P=0.019 and P=0.042, respectively). In a multivariate Cox regression model including age, tumor size, stage, and PD-L1 expression status, the latter three factors were found to be independent predictors of PFS (P=0.023, P=0.000, and P=0.009, respectively), but only stage was found to be an independent factor for OS (P=0.007), and PD-L1 expression status showed a trend to be independently correlated with OS (P=0.080). Conclusion Our results showed that a large proportion of patients with pulmonary LELC had positive expression of PD-L1, supporting the potential use of anti-PD-1/PD-L1-targeted therapies in this distinct type of NSCLC.

A high LDL-C to HDL-C ratio predicts poor prognosis for initially metastatic colorectal cancer patients with elevations in LDL-C.

Although lipid disequilibrium has been documented for several types of cancer including colorectal cancer (CRC), it remains unknown whether lipid parameters are associated with the outcome of metastatic CRC (mCRC) patients. Here, we retrospectively examined the lipid profiles of 453 mCRC patients and investigated whether any of the lipid parameters correlated with the outcome of mCRC patients. Pretreatment serum lipids, including triglyceride, cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were collected in 453 initially mCRC patients. The LDL-C to HDL-C ratio (LHR) was calculated and divided into the first, second, and third tertiles. Univariate and multivariate analyses were performed to evaluate the impact of lipids on overall survival (OS) and progression-free survival (PFS). Nearly two-fifths of the patients (41.3%) exhibited elevations in LDL-C while most patients (88.3%) showed normal HDL-C levels. Decreased HDL-C (P=0.542) and increased LDL-C (P=0.023) were prognostic factors for poor OS, while triglyceride (P=0.542) and cholesterol (P=0.215) were not. Multivariate analysis revealed that LDL-C (P=0.031) was an independent prognostic factor. Triglyceride, cholesterol, HDL-C, and LDL-C did not correlate with PFS. Among patients with elevations in LDL-C levels, patients in the third tertile of the LHR had a markedly shorter median OS compared to those in the first or second tertile (P=0.012). Thus, increased LDL-C level is an independent prognostic factor for poor prognosis in mCRC patients, and a high LHR predicts poor prognosis for initially mCRC patients with elevations in LDL-C.

A Potential Administration-time Dependent Effect of Bevacizumab inImproving Overall Survival and Increasing Metastasis in MetastaticColorectal Cancer

Background: The effectiveness of Bevacizumab has been demonstrated for the treatment of metastatic colorectal cancer. However, the minimum number of bevacizumab cycles needed to improve overall survival is unknown. In addition, anti-angiogenic treatment has been shown in preclinical studies to accelerate metastasis. To investigate these two issues, we performed a retrospective case-control study in Chinese patients with metastatic colorectal cancer. Methods: Patients initially diagnosed as metastatic colorectal cancer at the Sun Yat-sen University Cancer Center from 2004 to 2010 were recruited. All patients treated with bevacizumab served as experimental group; patients not treated with bevacizumab were control group. The primary endpoints were overall survival and the incidence of new metastatic lesions in the liver and other organs. Results: Patients received more than 4 cycles of bevacizumab showed a significantly prolonged overall survival than patients in the control group. The median overall survival was 31.53 months (95% CI, 23.22-39.85 months) and 19.70 months (95% CI, 16.61-22.79 months; P=0.031) for the experimental and control groups, respectively. The patients receiving bevacizumab more than 3 times showed an increased risk compared to the patients in control group of developing new metastatic lesions in the liver (17/23 versus 25/55, respectively, P=0.022) and other organs (14/23 versus 19/55, respectively, P=0.032). Conclusion: More than 4 doses of bevacizumab were required to improve overall survival in metastatic colorectal cancer; a potentially accelerated metastasis rate was observed after more than 3 doses of bevacizumab. However, studies with larger patient sample sizes are urgently needed to validate our findings.

Pathologic diagnosis of pancreatic adenocarcinoma in the United States: Its status and prognostic value

Purpose: Even with the development of new biopsy methods, diagnosis of pancreatic cancer is sometimes without histological evidence. The aim of our study is to find out the status of pancreatic cancer patients who are diagnosed without pathologic confirm and the prognostic value of pathologic diagnosis. Methods: We identified 52,759 pancreatic adenocarcinoma patients from the Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression model was used to identify factors relating to no pathologic diagnosis. Multivariable Cox regression model identified potential prognostic factors. All statistical tests were two-sided. Results: There were 6206 (11.76%) patients without pathologic diagnosis. Older age, reported from nursing/convalescent home/hospice or physicians office/private medical practitioner, early year of diagnosis, larger tumor size, pancreatic head cancer, unmarried patients, uninsured and stage I disease all contributed to no pathologic diagnosis. Median cause specific-survival for patients with and without pathologic diagnosis were 7.72 and 3.52 months, respectively. The HR for pathologic diagnosis was 0.92 (95% CI: 0.89-0.95), P<0.001. Conclusions: Pathologic diagnosis was an independent prognostic factor for pancreatic adenocarcinoma patients. New diagnostic methods are needed to get the pathologic diagnosis.

Efficacy of Taxane-Based Regimens in a First-line Setting for Recurrent and/or Metastatic Chinese Patients with Esophageal Cancer

OBJECTIVE To compare the efficacy of taxane-based regimens in the first line setting retrospectively in Chinese patients with recurrent and/or metastatic esophageal cancer. METHODS We analyzed 102 recurrent and/or metastatic esophageal cancer patients who received taxanes-based regimens in a first-line setting from January 2009 to December 2013. Sixteen (15.7%) patients were administered Nab-PTX based chemotherapy and 86 patients (84.3%) received paclitaxel (PTX) or docetaxel (DTX) based chemotherapy. Patients in the PTX/DTX group could be further divided into TP (71 patients) and TPF (15 patients) groups. RESULTS The objective response rate (ORR) of all patients was 20.6%, and the disease control rate (DCR) was 67.6%. The median overall survival (OS) was 10.5 months (95% CI 10.1-16.4) and the median progression-free survival (PFS) was 6.04 months (95% CI 5.09-7.91). The DCR was higher in the TPF group than the TP group (93.3% vs. 59.1%; p = 0.015 ). There were no significant differences in ORR, OS, and PFS among Nab-PTX, TPF and TP groups. CONCLUSIONS The three regimens of Nab-PTX based, TP and TPF proved active in a first line setting of Chinese patients with recurrent and/or metastatic esophageal cancer, and should thus be regarded as alternative treatments.