Extension Project: Clinical impact of molecular and immunological markers in gastrointestinal cancers
State Report for Extension Project: Clinical impact of molecular ...
Our original project “The effect of cellular immune response on the establishment and progression of colon-rectal cancer-from laboratory bench to clinical practice" has been completed and the extend project "Clinical impact of molecular and immunological markers in gastrointestinal cancers" is to establish an early clinical diagnostic system for gastrointestinal tract cancers by demonstration of early molecular markers and the combination with cytological markers.
The extension project "Clinical impact of molecular and immunological markers in gastrointestinal cancers" is currently on going according to the schedule. The aim of this project is to establish an early clinical diagnostic system for gastrointestinal tract cancers by demonstration of early molecular markers and the combination with cytological markers. Since the sensitivity and specificity of EUS-A is still not perfect, false negative and “suspicious for malignancy” rates remain in relatively high when the biopsies are not sufficient, thus, additional markers are needed to combine with morphological observations to make correct diagnosis. Molecular diagnostic markers for pancreatic cancers such as mutated K-ras, mutated P53, P16 and Cyclin D2 etc are tested in our laboratory. In 2007, a core group for molecular cytology of endoscopic ultrasonography (EUS) has been established that composed by GI endoscopy specialists (Overlege JM Kvamme and overlege Knut Johnsen) from Gastroenterology Dept., cytologists (1.amanuensis Elin Mortensen from Pathology, UNN and Dr. Vitali Sviatoha from Karolinska Hospital, Sweden) and clinical molecular biologist (Dr.med Guanglin Cui, cand med Rasmus Goll, cand med Trine Olsen) from Gastroenterology Dept. In this project, the EUS-guided aspiration (EUS-A) has been introduced and become an important pathological (cytological) diagnosis tool for pancreatic cancers and esophageal cancers at our clinical Gastro Endoscopy Lab at Gastroenterology Dept., UNN. Right now, pancreatic cancers and colon cancer biopsies taken via EUS-A are collected into RNAlater and 10% formalin solution respectively. The primary results demonstrated that the alternations of these molecules might represent as early markers for early pancreatic cancers and measurement of molecular markers in EUS-A biopsies can provide useful genetic information and facility the diagnosis of early pancreatic cancers together with cytological changes.
Another part of our extension project is to investigate the immune mechanisms of pre-operative radiotherapy in patients with rectal cancer. In this subproject, cytokines and immune cell populations will be examined by molecular biological techniques pre- and post- radiotherapy. Biopsies are well collected from rectal cancer patients received pre-operative radiotherapy, and the following biopsies from colorectal cancer patients after surgery as well. The primary results showed that immunological markers are altered in these patients. The mechanisms of pre-operative radiotherapy in rectal cancer patients could be involved in the regulation of host snti-tumor immunity, particularly in adjust dendritic cell function.
Co-laboration with other projects in the research lab: PhD projects cand med Rasmus Goll (Helicobacter infection- submitted June 2007), cand med Trine Olsen (inflammattory bowel disease, to be submitted 2008) and the 3 new projects of cand med Aping Yuan (dendritcellefunction in cancer), cand med Knut Johnsen (eosinophilic oesophagitis) and cand med Jan Magnus Kvamme (enteral immune dysfunction in malnutrition). New projects for potential candidates of PhD at Gastroenterology Dept. in the near future are in preparation .
Distinct changes of dendritic cell number and IL-12 mRNA level in adjacent mucosa throughout the colorectal adenoma-carcinoma sequence.
Cancer Immunol Immunother 2007 Dec;56(12):1993-2001. Epub 2007 jun 20
Reduced expression of microenvironmental Th1 cytokines accompanies adenomas-carcinomas sequence of colorectum.
Cancer Immunol Immunother 2007 Jul;56(7):985-95. Epub 2006 des 8
The stromal cellular changes in the tumour microenvironment along colorectal adenoma-carcinoma sequence
Gut; suppl 2007
Altered dendritic cell distribution pattern and increased tissue cyclooxygenase-2 mRNA level in colorectal adenoma and carcinoma
Gut, Suppl 2007