Clinical Study of Gastric Cancer, Colorectal Cancer and Bladder Cancer Based on Liquid Biopsy
Gastric CancerColorectal Cancer1 moreGastric cancer and colorectal cancer are common gastrointestinal malignancies in the world.Early cancer generally has no obvious symptoms. Endoscopy is the "gold standard"for the diagnosis of gastric cancer and colorectal cancer.gastric cancer and colorectal cancer treatment mainly includes surgery and medication.Compared with traditional diagnosis and treatment methods, the application of gene detection technology, especially high-throughput sequencing technology (NGS) in tumor diagnosis and treatment, performs multi-dimensional and multi-target detection of cancer-related genes, which can quickly and accurately determine the target gene mutations Morphology and expression differences, so as to provide personalized guidance to patients in terms of medication, treatment or prognosis evaluation, which can save a lot of time and treatment costs, and improve the overall treatment effect and patient quality of life. Cystoscopy and biopsy sampling pathological testing are the gold standard for bladder cancer diagnosis, and have been widely used in clinical diagnosis and prognosis judgment. However, cystoscopy is cumbersome, expensive, and often causes pain to the patients under test. At present, the main clinical non-invasive detection technique for bladder cancer is still the cytological examination of urinary tract bladder cells in urine, and its sensitivity and specificity are not good, especially for the diagnosis of early lower grade bladder cancer.For bladder cancer, tumor tissue (puncture biopsy or surgical resection) DNA, urine ctDNA, urinary tract exfoliated cell DNA and peripheral blood ctDNA can be used for genetic testing, but the consistency of the genetic testing results of these four types of samples has not been verified, especially There is no systematic evaluation of the guidance effect of non-invasive gene detection of free tumor DNA and urinary tract shed cell DNA in the diagnosis and treatment of bladder cancer.The corresponding relationship between the significant mutation genes contained in the DNA derived from bladder urinary tract cancer and the various types and stages of bladder cancer is not clear.
ctDNA for Prediction of Relapse in Gastric Cancer
Stomach NeoplasmsGastric cancer is one of the common malignant tumors in China, with relatively high incident rate and mortality among the population. Surgery is the conventional treatment option for early and intermediate-stage stage gastric cancer, but postoperative relapse is the major issue. Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA with an average size of 166 bp, mixed with cell free DNA (cfDNA) of other sources in blood circulation.ctDNA is reflecting the most up-to-date status of tumor genome. Hence, it is considered as a new biomarker for tumor, which can be qualitative, quantitative and used for disease monitoring. The present clinical trial aims to elucidate the correlation between the serum ctDNA status and the prognosis of patients with early and intermediate-stage gastric cancer upon surgical treatment, and explore the possibility of clinical utility of serum ctDNA as a clinical index to predict postoperative relapse.
Enhanced Recovery After Surgery(ERAS) for Gastric Cancer and Perioperative Nutritional Status
Nutrition DisordersThis study is a prospective, single-center, randomized controlled trial. The study protocol was approved by the Ethics Committee at the First Hospital of Jilin University.The perioperation nutritional status will be assessed in gastric cancer patients within ERAS protocols.The ERAS patients were randomly divided into perioperational nutrition support group and conventional pathway group . Inter-group differences were evaluated for nutritional index,clinical recovery index, complications etc.
Gastric Cancer Registry for Epidemiology and Molecular Risk Factor
Gastric CancerThis study is a multi-center, prospective cohort study which are planned to enroll the 2,500 patients who diagnosed the primary gastric cancer and 5,000 healthy normal cohort participants for 5 years. All participants who enrolled in this registry, the participants were questioned by the gastric cancer survey and the serum and tissue of these participants were analyzed. The main aim of this study is To evaluate the optimal interval of endoscopic screening for early detection of gastric cancer and risk factors in Korean. To evaluate the diagnostic validity of serum biomarker (combining pepsinogen, H pylori IgG Antibody, and TFF3) as a screening test for detection of GC in Korean.
Circulating Exosomes As Potential Prognostic And Predictive Biomarkers In Advanced Gastric Cancer...
Gastric CancerExosomes are formed by inward budding of late endosomes, producing multivesicular bodies (MVBs), and are released into the environment by fusion of the MVBs with the plasma membrane. It has been demonstrated that the content and function of exosomes depends on the originating cell and the conditions under which they are produced. Tumor exosome production, transfer and education of bone marrow cells supports tumor growth and metastasis. In this prospective translational study, preclinical and clinical phases have been designed. On the first step, the main goal is to characterize the molecular profile of gastric cancer derived exosomes. This exosome biosignature may provide a useful diagnostic tool. As a second step, the study will evaluate the prognostic and predictive value of gastric cancer exosomes levels in plasma and kinetics in a prospectively recruited cohort of advanced gastric cancer patients during first-line chemotherapy.
Detection of Methylated Reprimo in Plasma for Asymptomatic Gastric Cancer
Early Gastric CancerIn this proposal the investigators aim to develop a commercial kit to be used in primary screening and non-invasive triage for early detection of gastric cancer. This kit will be cost-effective and more accessible to the general population. In addition, the investigators would like to expand our current patent already submitted to INAPI (National Institute for Intellectual Property) and propose royalties to biomedical diagnostic companies for the use of our product at international level.
Lauren Classifications and HER2 Status in Gastric Cancer Patients
Gastric CancerBy literature review, there is a clear trend towards a potential role for human epidermal growth factor receptor 2 (HER2) as a negative prognostic factor in gastric cancer was shown, but only in half of the analyses used multivariate statistics. Besides, For the studies in the current review that have looked at the Lauren classification in relation to HER2, a higher level of overexpression or amplification was found in the intestinal phenotype compared to the diffuse or mixed types. As lauren classification was reported as an independent prognostic factor result in favored outcomes in gastric cancer (GC), there may probably be histologic bias exists when compare overall survival (OS) between HER2 statuses without controlling this confounding. Similarly, patients with different disease settings (early stage and advanced stage; resectable and metastatic) affect outcomes either. In this study, the investigators will retrospectively analyze HER2 status and lauren classification in 800 gastric patients who received gastrectomy in the Cancer Center of Sun Yat-Sen University between January 1996 and December 2006 with formalin-fixed and paraffin- embedded tumor tissue samples. To avoid potential influence by histologic classifications and disease settings, the investigators assess difference in OS between HER2 positive and HER2 negative groups in resectable Lauren classification of GCs, and further evaluate the prognostic value of HER2 status according to tumor-node-metastasis (TNM) stages.
Compare Different Response Evaluations to Neoadjuvant Chemotherapy for Gastric Cancer
Gastric CancerRATIONALE: Neoadjuvant chemotherapy has been proved effective for locally advanced gastric cancer, yet the best pattern of response evaluation remain unknown. PURPOSE: Compare different pattern of response evaluation for Gastric Cancer.
The Functional and Clinicopathological Roles and Therapeutic Implication of Connective Tissue Growth...
Gastric CancerFor the past 50 years, gastric cancer has been one of the ten most frequent cancers and the second leading cause of cancer-related death in the world. In Taiwan, it is the fifth most common cause of cancer-related deaths, accounting for 6.3% of all cancer deaths. The poor prognosis of gastric cancer is mostly caused by the extensive metastasis to the lymph nodes, liver, and peritoneal dissemination even if curative resection was performed. The main cause of recurrence after curative or noncurative resection of advanced tumors is peritoneal metastasis because of possible direct spillage and dissemination of tumor cells as a result of surgical manipulation, and it is associated with a poor prognosis. As yet, no effective treatment has been developed for this condition. The development of peritoneal metastasis is a multistep process, beginning with attachment to peritoneal mesothelial cells, retraction of the mesothelial cells and exposure of the basement membrane, attachment to the basement membrane, degradation in the extracellular matrix, proliferation by the cancer cells, and angiogenesis, and it is clear that many types of agents are involved at the various stages of this process. Developing a new therapeutic method for this mode of metastasis is very important for improvement of gastric cancer treatment. CTGF is a secretory protein belonging to the CCN family (one among the three originally discovered members: cysteine-rich61, CTGF, and nephroblastoma-overexpressed gene). It is a multifunctional growth factor involved in wound healing, inflammation, cell adhesion, chemotaxis, apoptosis, tumor growth, and fibrosis. Recent studies showed that overexpression of CTGF in human oral squamous cell carcinoma reduces cell growth and tumorigenecity. Similar tumor growth inhibitory effects were observed in lung cancer cells in which CTGF overexpression was less angiogenic and metastatic due to blocking of the VEGF A signaling pathway. CTGF was also reported to be a key regulator of colorectal cancer invasion and metastasis, and it appears to be a better prognostic factor. These studies suggest that CTGF may involve the processes of peritoneal metastasis which includes cancer cell adhesion in peritoneum, proliferation and angiogenesis. Peritoneal mesothelium is the first surface encountered by disseminated tumor cells and successful adhesion is, therefore, of paramount importance in metastasis formation. Therefore, we hypothesized that CTGF is a potential molecule target, which may be related to cell adhesion to peritoneum, the first step of peritoneal metastasis, and its exact mechanism may includes proliferation and angiogenesis. In order to answer these important questions, first, we have performed the preliminary studies to prove CTGF did express in different gastric cancer cell lines including AGS, N87, TSGH, and MKN-45 by using RT-PCR and Western blotting, and gastric cancer tissues by using immunohistochemical method. Second, we demonstrated different levels of CTGF expression in different cell lines pose different adhesion ability in in-vitro adhesion assay. Third, we conducted a transient CTGF-overexpressed MKN45 gastric cancer cell line, and CTGF-overexpressed cell line had lower adhesive ability compared to the control. Next step in this project, we will be studying the roles of CTGF plays in cellular and molecular biology in vitro and in vivo and clinical significance associated with therapeutic potential of peritoneal metastasis from gastric cancer. We will generate stable clones of MKN45 cells harboring CTGF and its control cell line to elucidate the roles of CTGF in cancer cell adhesion, proliferation and angiogenesis in peritoneum.
Cyclooxygenase-2-Associated Factors and Gastric Carcinogenesis Mechanisms-Clinical Association and...
Gastric CancerBackground: Gastric carcinoma (GC) remains among the most frequent malignancies in Taiwan as well as in the world and also one of leading causes of cancer-related death. Accumulating evidence shows that chronic inflammation leads to the occurrence of cancers, including GC, via multiple mechanisms. Cyclooxygenase-2 (COX-2) is a crucial enzyme in inflammatory process and is shown to be up-regulated in a variety of cancers. Therefore, COX-2 may play an important role in carcinogenesis. The hallmarks of cancer include continuing proliferation, evading apoptosis, prohibiting immunity, promoting angiogenesis, enhancing invasion and metastasis. We hypothesize that COX-2 induces carcinogenesis through multiple mechanistic strategies and interactions of multiple genes simultaneously. Laser capture microdissection (LCM) for obtaining pure cancer cells and microarray technology and analysis are now generally accepted as powerful tools in genomic research, providing reliable microdissection of cancer cells and simultaneous analysis of whole genome. Aim: Use microarray technology to investigate patterns of genomic change related to differential COX-2 expression and their clinicopathological association in GC. Materials: GC cell lines are transfected with COX-2-expressing vector to establish cell lines with differential levels of COX-2 expression. Clinical specimens are obtained from surgical resection of GC proved by pathology at the Surgical Department of National Taiwan University Hospital, which COX-2 expression is evaluated by Western blotting and immunohistochemical staining. Methods: The present project will use microarray for analysis of genome clustering patterns of surgical tissue (GC cells procured by LCM) and GC cell lines based on differential COX-2 expression levels, to discover significantly positively or negatively associated gene clusterings which contain candidate genes for studies of carcinogenesis mechanisms and establishment of animal experiment models in another component project. Execution: In the first year of this 3-year project, we will establish GC cell lines expressing differential COX-2 levels by transfection of COX-2-expressing vector and focus on analyzing their genomes by microarray. We also start to collect surgical specimens of GC, record clinicopathological characteristics, procure cells by LCM and assess RNA quality, perform microarray experiments. In the second year, we will continue LCM, RNA extraction, and microarray experiments. In the third year, microarray experiment of a total of 60 pairs, including 30 high-COX-2 cases and 30 low-COX-2 cases, of tumor and non-tumoral tissues are completed. Final analysis is carried out to identify clustering, to select candidate genes, and investigate their relationship to clinicopathological characteristics, according to COX-2 expression. These genes are to be subjected to mechanism and animal studies. We expect a better understanding of patterns of gene clustering in differential COX-2 gene expression.