• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4205-4208
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• 2013

Objective: The aim of this study was to explore change and significance of serum carcino-embryonic antigen (CEA) before and after gefitinib therapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods: Forty patients with advanced NSCLCs in III~IV stages were selected as study objects given gefitinib therapy combined with routine local radiotherapy until tumor progression or intolerable toxicity. After treatment, all patients were divided into control and non-control groups according to the results of evaluation based on RECIST 1.1 (Response Evaluation Criteria in Solid Tumors in 2009). Peripheral fasting blood from all patients was collected in the early morning and serum CEA was assessed by electro-chemiluminescence immunoassay (ECLIA) before and after treatment. Before treatment, patients were divided into high CEA group (CEA level > 50 ng/mL) and low CEA group (CEA level ${\leq}$ 50 ng/mL). Adverse reactions were noted and progression-free survival (PFS) in both groups was recorded after long-term follow-up that ended in December, 2012. Results: There was no difference between control and non-control groups in CEA level before treatment (P>0.05), whereas serum CEA decreased more markedly lower in the control group after treatment (P<0.01). All patients were divided into high CEA group (26) and low CEA group (14) according to serum CEA level. There was no statistically significant difference between two groups in adverse reactions (P>0.05) but the rate in former group was lower. Additionally, survival rates at 9 and 12 months in high CEA group were clearly higher than in the low CEA group (P<0.01). Conclusions: Serum CEA level can serve as a biochemical index to evaluate the prognosis with gefitinib treatment for NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4627-4634
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• 2013

Chemoprotection refers to the use of specific natural or synthetic chemical agents to suppress or prevent the progression to cancer. The purpose of this study is to assess the protective effect of aspirin, vitamin C or zinc in a dimethyl hydrazine (DMH) colon carcinoma model in rats and to investigate the effect of these supplements on changes associated with colonic zinc status. Rats were randomly divided into three groups, group 1 (aspirin), group 2 (vitamin C) and group 3 (zinc), each being subdivided into two groups and given subcutaneous injection of DMH (30 mg/kg body wt) twice a week for 3 months and sacrificed at 4 months (A-precancer model) and 6 months (B-cancer model). Groups 1, 2, 3 were simultaneously given aspirin, vitamin C, or zinc supplement respectively from the beginning till the end of the study. It was observed that 87.5% of rats co-treated with aspirin or vitamin C showed normal colonic histology, along with a significant decrease in colonic tissue zinc at both time points. Rats co-treated with zinc showed 100% reduction in tumor incidence with no significant change in colonic tissue zinc. Plasma zinc, colonic CuZnSOD (copper-zinc superoxide dismutase) and alkaline phosphatase activity showed no significant changes in all 3 cotreated groups. These results suggest that aspirin, vitamin C or zinc given separately, exert a chemoprotective effect against chemically induced DMH colonic preneoplastic progression and colonic carcinogenesis in rats. The inhibitory effects are associated with maintaining the colonic tissue zinc levels and zinc enzymes at near normal without significant changes.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2955-2958
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• 2013

Background: Mast cells can influence tumor progression via different pathways and increased mast cell density has been demonstrated in oral squamous cell carcinoma (OSCC). It has been shown that the serum tryptase level is elevated with some malignant tumours and may thus be a useful parameter. However, there are no data available about OSCC. The main aim of this study was the evaluation of mast cell tryptase (MCT) level in OSCC patient serum. Materials and Methods: In this cross-sectional, analytic study, the circulating levels of MCT were assessed in sera of 55 OSCC patients and 34 healthy individuals with ELISA technique. Results: The serum MCT level in OSCC patients was 12-14 ng/ml, which was not significantly higher than the healthy control group. While the serum level of MCT was higher with larger tumours, there was no apparent correlation with clinico-pathological features such as patient age, gender, tumor location, stage, nodal status, distant metastasis, histological grade and smoking. Conclusions: Our findings showed that despite the results obtained from studies of other malignant tumors, serum level of MCT in OSCC patients could not be a credited as a reliable indicator of the presence or progression of tumours.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5945-5950
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• 2014

Objectives: To retrospectively review the safety and clinical efficacy of bevacizumab concomitant with chemotherapy in Chinese patients with advanced non-squamous non-small cell lung cancer (NSNSCLC). Methods: Clinical data for 79 patients with NSNSCLC who received bevacizumab concomitant with chemotherapy in Chinese PLA General Hospital from April 28th 2009 to May 5th 2013 were retrospectively reviewed to analyze the clinical efficacy including disease control rate (DCR), overall response rate (ORR), progression-free survival (PFS), overall survival (OS), the Eastern Cooperative Oncology Group (ECOG) score and the safety. Results: The Eastern Cooperative Oncology Group (ECOG) score was 0-2. By the final cutoff date (June 9, 2013), 54 (68.4%) patients had disease progression and 37 (46.8%) died. The ORR was 32.9% and the DCR was 83.5%. The ORR of the first-, second-, and third- or later-line treatments were 51.4%, 25.0% and 12.5%, while the DCR were 94.3%, 80.0% and 70.8%, respectively. The median OS (mOS) and PFS (mPFS) were 13.5 and 5.83 months, respectively. The mOS of patients with the first-, second-, and third- or later- line treatments were 16.2, 10.9 and 8.30 months, while the mPFS were 7.27, 5.90 and 5.17 months, respectively. Chemotherapy-related adverse events included myelosuppression, vomiting, hepatic dysfunction and renal dysfunction, while the common serious bevacizumab-related adverse events were thromboembolic problems, gastrointestinal perforation and reversible posterior leukoencephalopathy syndrome, which could be well managed. Conclusions: Bevacizumab concomitant with chemotherapy is effective and the related toxicity can be well tolerated in Chinese patients with NSNSCLC.

• Molecules and Cells
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• v.41 no.8
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• pp.733-741
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• 2018

Mutations in spliceosome components have been implicated in carcinogenesis of various types of cancer. One of the most frequently found is U2AF1 S34F missense mutation. Functional analyses of this mutation have been largely limited to hematological malignancies although the mutation is also frequently seen in other cancer types including lung adenocarcinoma (LUAD). We examined the impact of knockdown (KD) of wild type (wt) U2AF1 and ectopic expression of two splice variant S34F mutant proteins in terms of alternative splicing (AS) pattern and cell cycle progression in A549 lung cancer cells. We demonstrate that induction of distinct AS events and disruption of mitosis at distinct sub-stages result from KD and ectopic expression of the mutant proteins. Importantly, when compared with the splicing pattern seen in LUAD patients with U2AF1 S34F mutation, ectopic expression of S34F mutants but not KD was shown to result in common AS events in several genes involved in cell cycle progression. Our study thus points to an active role of U2AF1 S34F mutant protein in inducing cell cycle dysregulation and mitotic stress. In addition, alternatively spliced genes which we describe here may represent novel potential markers of lung cancer development.

• Journal of Microbiology and Biotechnology
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• v.31 no.6
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• pp.775-783
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• 2021

Sea cucumber, Holothuria scabra, is a well-known traditional Asian medicine that has been used for suppressing inflammation, promoting wound healing, and improving immunity. Moreover, previous studies demonstrated that the extract from H. scabra contains many bioactive compounds with potent inhibitory effect on tumor cell survival and progression. However, the effect of the methanolic extract from the body wall of H. scabra (BWMT) on human prostate cancer cells has not yet been investigated. In this study, we aimed to investigate the effects and underlying mechanism of BWMT on prostate cancer cell viability and metastasis. BWMT was obtained by maceration with methanol. The effect of BWMT on cell viability was assessed by MTT and colony formation assays. The intracellular ROS accumulation was evaluated using a DCFH-DA fluorescence probe. Hoechst 33342 staining and Annexin V-FITC/PI staining were used to examine the apoptotic-inducing effect of the extract. A transwell migration assay was performed to determine the anti-metastasis effect. BWMT significantly reduced cell viability and triggered cellular apoptosis by accumulating intracellular ROS resulting in the upregulation of JNK and p38 signaling pathways. In addition, BWMT also inhibited the invasion of PC3 cells by downregulating MMP-2/-9 expression via the ERK pathway. Consequently, our study provides BWMT from H. scabra as a putative therapeutic agent that could be applicable against prostate cancer progression.

• Journal of Gastric Cancer
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• v.23 no.2
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• pp.328-339
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• 2023

Purpose: This study aimed to evaluate the efficacy and safety of neoadjuvant programmed cell death-1 (PD-1) inhibitors plus apatinib and chemotherapy (PAC) in patients with locally advanced gastric cancer (LAGC). Materials and Methods: Seventy-three patients with resectable LAGC were enrolled and named the PAC group (n=39) or apatinib plus chemotherapy (AC) group (n=34) based on the treatment they chose. Neoadjuvant therapy was administered in a 21-day cycle for 3 consecutive cycles, after which surgery was performed. Results: The PAC group exhibited a higher objective response rate than the AC group (74.4% vs. 58.8%, P=0.159). Moreover, the PAC group showed a numerically better response profile than the AC group (P=0.081). Strikingly, progression-free survival (PFS) (P=0.019) and overall survival (OS) (P=0.049) were prolonged, whereas disease-free survival (DFS) tended to be longer in the PAC group than in the AC group (P=0.056). Briefly, the 3-year PFS, DFS, and OS rates were 76.1%, 76.1%, and 86.7% in the PAC group and 46.9%, 49.9%, and 70.3% in the AC group, respectively. Furthermore, PAC (vs. AC) treatment (hazard ratio=0.286, P=0.034) was independently associated with prolonged PFS in multivariate Cox regression analyses. The incidence of adverse events did not differ between the two groups (all P>0.05), where leukopenia, anemia, hypertension, and other adverse events were commonly observed in the PAC group. Conclusions: Neoadjuvant PAC therapy may achieve a preferable pathological response, delayed progression, and prolonged survival compared to AC therapy with a similar safety profile in patients with LAGC; however, further validation is warranted.

• IMMUNE NETWORK
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• v.20 no.4
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• pp.33.1-33.19
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• 2020

We tested how adjuvants effect in a cancer vaccine model using an epitope derived from an autoactivation loop of membrane-type protease serine protease 14 (PRSS14; loop metavaccine) in mouse mammary tumor virus (MMTV)-polyoma middle tumor-antigen (PyMT) system and in 2 other orthotopic mouse systems. Earlier, we reported that loop metavaccine effectively prevented progression and metastasis regardless of adjuvant types and TH types of hosts in tail-vein injection systems. However, the loop metavaccine with Freund's complete adjuvant (CFA) reduced cancer progression and metastasis while that with alum, to our surprise, were adversely affected in 3 tumor bearing mouse models. The amounts of loop peptide specific antibodies inversely correlated with tumor burden and metastasis, meanwhile both T_H1 and T_H2 isotypes were present regardless of host type and adjuvant. Tumor infiltrating myeloid cells such as eosinophil, monocyte, and neutrophil were asymmetrically distributed among 2 adjuvant groups with loop metavaccine. Systemic expression profiling using the lymph nodes of the differentially immunized MMTV-PyMT mouse revealed that adjuvant types, as well as loop metavaccine can change the immune signatures. Specifically, loop metavaccine itself induces T_H2 and T_H17 responses but reduces T_H1 and T_reg responses regardless of adjuvant type, whereas CFA but not alum increased follicular T_H response. Among the myeloid signatures, eosinophil was most distinct between CFA and alum. Survival analysis of breast cancer patients showed that eosinophil chemokines can be useful prognostic factors in PRSS14 positive patients. Based on these observations, we concluded that multiple immune parameters are to be considered when applying a vaccine strategy to cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.633-636
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• 2012

Purpose: PRIL (proliferation-inducing ligand) is a newly identified member of the tumor necrosis factor (TNF) family and modulates death ligand-induced apoptosis. Here, we investigated the effect of PRIL on cellular characteristics relating to tumor progression in human gastric cancer. Method: Recombinant lentivirus containing PRIL siRNA was constructed and then infected MGC803 and SGC7901 gastric cancer cells. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] colony formation and cell cycle analysis were used to study the effect of PRIL knockdown on gastric cancer cell proliferation. Results: PRIL expression in lentivirus infected cells was significantly reduced as evidenced by quantitative real-time PCR. Cell viability and colony formation of MGC803 and SGC7901 cells were significantly hampered in PRIL knock-down cells. Moreover, the cell cycle was arrested at G2/M phase, elucidating the mechanism underlying the inhibitory effect of siRNA on cell proliferation. Conclusions: Our study indicated that PRIL functions in promoting cell growth, and lentivirus-mediated PRIL gene knockdown might be a promising strategy in the treatment of gastric cancer.

• Biomolecules & Therapeutics
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• v.26 no.1
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• pp.81-92
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• 2018

It is widely accepted that altered metabolism contributes to cancer growth and has been described as a hallmark of cancer. Our view and understanding of cancer metabolism has expanded at a rapid pace, however, there remains a need to study metabolic dependencies of human cancer in vivo. Recent studies have sought to utilize multi-modality imaging (MMI) techniques in order to build a more detailed and comprehensive understanding of cancer metabolism. MMI combines several in vivo techniques that can provide complementary information related to cancer metabolism. We describe several non-invasive imaging techniques that provide both anatomical and functional information related to tumor metabolism. These imaging modalities include: positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) that uses hyperpolarized probes and optical imaging utilizing bioluminescence and quantification of light emitted. We describe how these imaging modalities can be combined with mass spectrometry and quantitative immunochemistry to obtain more complete picture of cancer metabolism. In vivo studies of tumor metabolism are emerging in the field and represent an important component to our understanding of how metabolism shapes and defines cancer initiation, progression and response to treatment. In this review we describe in vivo based studies of cancer metabolism that have taken advantage of MMI in both pre-clinical and clinical studies. MMI promises to advance our understanding of cancer metabolism in both basic research and clinical settings with the ultimate goal of improving detection, diagnosis and treatment of cancer patients.