Primary colorectal cancer

Aschele C, Debernardis D, Tunesi G et al. Thymidylate synthase protein expression in primary colorectal cancer compared with the corresponding distant... 

Tomonaga T, Matsushita K, Yamaguchi S, Oohashi T, Shimada H, Ochiai T, Yoda K, Nomura F (2003) Overexpression and mistargeting of centromere protein-A in human primary colorectal cancer. Cancer Res 63 3511-3516... 

D. K., Kyu Park, S., Chun, H.K., Song, S.Y, Park, J. and Kim, D.H. (2007) Association of the SUV39H1 histone methyltransferase with the DNA methyltransferase 1 at mRNA expression level in primary colorectal cancer. International Journal of Cancer, 121, 2192-2197. 

Initial detection of primary colorectal cancer is a domain of endoscopy. Additional imaging for therapy planning is discussed controversially, especially due to the lack of a single comprehensive imaging method [8]. Conventional imaging modalities, comprising endoluminal ultrasound, CT and MRI are limited to give... 

M. Mukai, S. Sadahiro, S. Yasuda, H. Ishida, N. Tokunaga, T. Tajima, H. Makuuchi, Preoperative evaluation by whole-body F-fluorodeoxyglucose positron emission tomography in patients with primary colorectal cancer, Oncol. Rep. 7(1) (2000) 85-87. 

Monoclonal antibodies to mutated p53 proteins have been developed. The wild type of p53 is normally present in very small amounts that are not detected by immunohisto-chemistry, whereas the mutant protein accumulates to easily detectable levels. Overexpression of the mutant proteins has been detected in up to 70% of primary colorectal cancers. Overexpression of p53 in breast cancers is associated with poor prognosis, but this association is not as strong as the association with c-erhB-2. Up to 75% of small cell lung carcinomas appear to overexpress a mutant (missense mutation) protein. Finally, circulating antibodies to mutant p53 proteins have been found in sera from patients with breast and lung cancer and B-cell lymphomas. Tills antibody response may be useful in this subset of patients for monitoring for relapse. ... 

According to Binkert et al. (1998) cost savings of up to 29% can be achieved in preoperative stent placement for colonic carcinoma. However, no completed randomised prospective study has compared preoperative stenting with standard surgery in patients with potentially resectable primary colorectal cancer and obstruction. Currently such a study is under way in the United States (Baron 2001). 

Wincewicz, A., Sulkowska, M., Koda, M., Sulkowski, S. (2007). Clinicopathological significance and linkage of the distribution of HIF-1 alpha and GLUT-1 in human primary colorectal cancer. Pathol. Oncol. Res. 75(1), 15-20. 

Symptom reduction is the primary goal of radiation for patients with advanced or metastatic disease colorectal cancer. 

Primary prevention is aimed at preventing colorectal cancer in an at-risk population. To date, the only strategy shown to reduce the risk is chemoprevention with celecoxib in people with familial adenomatous polyposis. 

Stage of colorectal cancer should be determined at diagnosis to predict prognosis and to develop treatment options. Stage is based on the size of the primary tumor (T ), presence and extent of lymph node involvement (N0-2) and presence or absence of distant metastases (M). 

Chemotherapy is the primary treatment modality for metastatic colorectal cancer (MCRC). Treatment options are generally similar for metastatic cancer of the colon and rectum. 

Celecoxib has been approved for the treatment of osteoarthritis and rheumatoid arthritis, and rofecoxib has been approved for the treatment of osteoarthritis, acute pain and primary dysmenorrhea. Celecoxib and rofecoxib do not appear to differ in efficacy for the treatment of osteoarthritis. However, neither drug has efficacy greater than that of the non-selective NSAIDs. Since the COX-2 enzyme appears to play an important role in colon cancer the COX-2 inhibitors may find future uses in the treatment or prevention of colorectal cancer. 

Adjuvant chemotherapy involves the use of antineoplastic drugs when surgery or radiation therapy has eradicated the primary tumor but historical experience with similar patients indicates a high risk of relapse due to micrometastases. Adjuvant chemotherapy should employ drugs that are known to be effective in the treatment of advanced stages of the particular tumor being treated. Adjuvant chemotherapy has played a major role in the cure of several types of childhood cancers as well as breast cancer, colorectal cancer, and osteosarcoma in adults. 

Carmustine and lomustine can produce remissions that last from 3 to 6 months in 40 to 50% of patients with primary brain tumors. Both drugs also are used as secondary treatment of Hodgkin s disease and in experimental combination chemotherapy for various types of lung cancer. Other tumors in which remission rates of 10 to 30% have been obtained are non-Hodgkin s lymphomas, multiple myeloma, melanoma, renal cell carcinoma, and colorectal cancer. 

Takahashi K, Kohno T, Matsumoto S et al. Clonal and parallel evolution of primary lung cancers and their metastases revealed by molecular dissection of cancer cells. Clin Cancer Res 2001 3 - 20. Findlay MP, Cunningham D, Morgan G et al. Lack of correlation between thymidylate synthase levels in primary colorectal tumours and subsequent response to chemotherapy. Br J Cancer 1997 75 903-909. 

Colorectal cancer (CRC) is the third most common cause of cancer-related death in women and men in the United States (4). Although surgical resection is the primary therapy for CRC, prognosis remains poor and not all patients are candidates for surgery. The current therapeutic options for patients with metastatic CRC (mCRC) are 5-fluorouracil (5-FU) based therapy regimens in combination with irinotecan (CPT-11) or oxaliplatin (5,6). 

Ichikawa W, Uetake H, Shirota Y et al. Combination of dihydropyrimidine dehydrogenase and thymidylate synthase gene expressions in primary tumors as predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy for metastatic colorectal cancer. Clin Cancer Res 2003 9 786-791. 

Drug(s) Oxaliplatin Primary Antineoplastic Indication(s) Colorectal cancer Common Adverse Effects Blood disorders (anemia, leukopenia, neutropenia, thrombocytopenia) joint pain, chest pain... 

Clinical Use. Levamisole (Ergamisol) is primarily used to treat colorectal carcinoma. Specifically, this drug is administered with fluorouracil (see Chapter 36) to prevent recurrence of colorectal cancer after surgical removal of the primary tumor.1... 

Formation of regional lymph node metastasis can be an important step in dissemination of cancer cells. In colorectal cancer, lymph node metastasis frequently occurs in patients (7, 8) and is an important factor in staging the disease. In particular, the metastatic lymph node ratio (LNR number of metastatic lymph nodes/number of examined lymph nodes) is predictive of overall survival (OS) and disease-free survival (DFS) in colorectal cancer patients (9, 10). Hence, an animal model of colorectal cancer with measurable lymphatic metastasis that allows for rapid evaluation of the effects of candidate treatment regimens on primary tumor growth and lymph node metastasis would be of great value. 

We have developed a firefly luciferase-expressing HT-29 colorectal cancer cell line, HT-29LP, to realize the benefits of BLI with an orthotopic colorectal cancer model. Primary tumors were established by implantation of HT-29LP cells into the submucosal layer of the rectum of mice, and tumor growth and lymph node metastasis were evaluated. A positive control treatment... 

Anti-tumor activity of bevacizumab has been reported in various preclinical animal models (primary and metastatic) with a broad array of tumor types [106, 107]. Clinical studies have further validated the focal role of VEGF in cancer. A single infusion of bevacizumab at 5 mg/kg in patients with primary and locally advanced adenocarcinoma of the rectum demonstrated direct and rapid antivascular effect in human tumors, with decreases in tumor perfusion, vascular volume, microvascular density, and interstitial pressure [108]. Clinical efficacy of bevacizumab in combination with 5-FU- and irinotecan-based regimens has been demonstrated in patients with metastatic colorectal cancer a significant improvement in overall survival time was observed compared with chemotherapy alone (20.3 versus 15.6 months for chemotherapy plus bevacizumab versus chemotherapy alone) [109]. 

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