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At least 487 records · Page 27Linked to original sources
PubMed2001

Adenovirus-mediated transfer of the p53 family genes, p73 and p51/p63 induces cell cycle arrest and apoptosis in colorectal cancer cell lines: potential application to gene therapy of colorectal cancer.

p53 gene therapy is being tested clinically for the treatment of human cancer, however, some cancer models (in vivo and in vitro) are resistant to p53. To explore the potential use of two p53 homologues, p73 and p51/p63, in cancer gene therapy, we introduced p53, p73 and p51/p63 into colorectal cancer cell lines via adenoviral vectors, and compared their effects on cell growth. Among 10 cell lines tested, six cell lines displayed a similar response following transduction of p53, p73beta or p51A/p63gamma; two lines underwent cell-cycle arrest, three lines exhibited apoptosis and one line showed no-effect following transduction. The effect on cell-cycle progression was variable in the other four cell lines. Interestingly, three cell lines were resistant to p53-mediated apoptosis, including two lines having endogenous wild-type p53 alleles, but underwent apoptosis after transduction of p73beta or p51A/p63gamma. Similar to p53, transduction of p51A/p63gamma induced extensive apoptosis when combined with adriamycin or X-radiation in SW480 cells, which are normally resistant to apoptosis. Transduction of p73beta and p51A/p63gamma also reduced the tumorigenicity of two colorectal cancer cells in vivo. These results suggest that adenovirus-mediated p73beta and p51A/p63gamma transfer are potential novel approaches for the treatment of human cancers, particularly for tumors that are resistant to p53 gene therapy.

Adenoviridae↗
PubMed1994

Are women with breast, endometrial, or ovarian cancer at increased risk for colorectal cancer?

OBJECTIVES: Evidence is accumulating supporting the use of screening for colorectal cancer. Patients at higher risk for colorectal cancer are more likely to benefit from screening. Women with breast, endometrial, or ovarian cancer are often classified as at high risk for subsequent colorectal cancer, and are urged to undergo screening, but the basis for this is uncertain. METHODS: We performed a meta-analysis of published data to assess the risk of colorectal cancer after these cancers. RESULTS: Based on 154,270 women and 779,251 person-yr of observation (PYO) after breast cancer, 37,266 women and 229,498 PYO after endometrial cancer, and 41,366 women and 126,688 PYO after ovarian cancer, the age-adjusted relative risk (95% CI) for colorectal cancer after breast cancer was 1.1 (1.07, 1.19), after endometrial cancer 1.4 (1.32, 1.55), and after ovarian cancer 1.6 (1.40, 1.80). CONCLUSIONS: 1) Women with a history of breast, endometrial, or ovarian cancer are at a statistically significant increased risk for subsequent colorectal cancer. 2) Women with a history of endometrial or ovarian cancer are at higher risk than are women with breast cancer, but ascertainment bias from heightened medical surveillance after the diagnosis of a gynecologic malignancy may contribute to this observed increase in risk. 3) The association between these cancers and colorectal cancer suggests common etiologic factors, either environmental or genetic, but the degree of increased risk is small.

Aged↗
PubMed2002

Specific localisation of human cytomegalovirus nucleic acids and proteins in human colorectal cancer.

BACKGROUND: Colorectal cancer is the second most frequent cause of death from cancer in the USA, and most tumours arise sporadically with no clear cause or genetic predisposition. Human cytomegalovirus is a beta-herpesvirus that is endemic in the human population and can cause life-threatening disease in immunosuppressed adults. In vitro, human cytomegalovirus can transform cells and dysregulate many cellular pathways relevant to colon adenocarcinoma pathogenesis, especially those affecting the cell cycle, mutagenesis, apoptosis, angiogenesis, and cyclo-oxygenase-2 (COX-2) expression. We aimed to assess whether gene products of human cytomegalovirus could be detected in colorectal cancers. METHODS: We obtained formalin-fixed, paraffin-embedded pathological specimens of colorectal polyps, adenocarcinomas, and adjacent normal mucosa from 29 patients. To detect human cytomegalovirus proteins and nucleic acids, we used immunohistochemistry with two different monoclonal antibodies, in-situ hybridisation, and PCR with DNA sequencing. FINDINGS: Human cytomegalovirus proteins IE1-72 and pp65 were detected in a tumour cell-specific pattern in 14 (82%) of 17 and seven (78%) of nine colorectal polyps, respectively, and 12 (80%) of 15 and 11 (92%) of 12 adenocarcinomas, respectively, but not in adjacent non-neoplastic colon biopsy samples from the same patients (none of seven and none of two, respectively). Human cytomegalovirus infection of colon-cancer cells (Caco-2) in vitro resulted in specific induction of Bcl-2 and cyclo-oxygenase-2 proteins, both of which are thought to contribute to progression of colon cancer. INTERPRETATION: Human cytomegalovirus nucleic acids and proteins can be found that specifically localise to neoplastic cells in human colorectal polyps and adenocarcinomas, and virus infection can induce important oncogenic pathways in colon-cancer cells.

Adenocarcinoma↗
PubMed2003

Allelic imbalance in colorectal cancer at the CRAC1 locus in early-onset colorectal cancer.

A susceptibility gene to colorectal adenomas and carcinoma (CRAC1) on chromosome region 15q14 approximately q22 has been proposed on the basis of linkage in a single family. Allele-specific loss of heterozygosity (LOH) in tumors of affected family members suggests that the causative gene functions as a tumor-suppressor gene. The genes that are mutated in inherited cancer syndromes are often involved in the pathogenesis of sporadic cancer. To determine whether CRAC1 plays a role in colorectal carcinogenesis in general, we have studied 277 cases of early-onset colorectal cancers for allele loss at 15q14 approximately q22 using four microsatellite markers (D15S970, D15S117, D15S971, and D15S1028) that define the region of maximal linkage. The frequency of LOH detected was between 14% and 22%, but there was no significant association between LOH at each adjacent marker. Most cancers caused by loss of expression of a tumor suppressor involve large-scale deletion of one allele. On this basis, our findings suggest that CRAC1 is unlikely to be implicated in the development of colorectal cancer in general or, if involved, it is through small somatic mutations or other loss of function mechanisms rather than allele loss.

Allelic Imbalance↗
PubMed1996

The prognostic significance of immune changes in patients with renal cancer, melanoma and colorectal cancer, treated with interferon alpha 2b.

In the present study we evaluated the response rate and the immunorestorative properties of interferon alpha 2b (IFn alpha 2b) administered to patients with advanced renal cell carcinoma (RCC), melanoma (MEL) or colorectal cancer (CC). We studied the immune status and correlated it with clinical responses. Thirty-five patients with advanced RCC, and 14 with MEL were treated with recombinant INF alpha 2b. The dose was increased progressively from 5 x 10(6) IU/day in the first week (three times every week) to 10 x 10(6) IU/day in the second week and thereafter to 15 x 10(6) IU/day subcutaneously. In patients with CC INF alpha 2b was given at 5 x 10(6) IU/day every other day (three times every week); these patients also received (together with INF) leucovorin 200 mg m-2 day-1 in a 1-h i.v. infusion every week, and mid-infusion 400 mg/m2 5-FU was administered as an intravenous bolus every week. The response rate was as follows: for RCC, 6 patients achieved partial response (PR), 10 stable disease (SD), and 21 progressed (PD); for MEL, 5 patients achieved PR and 9 PD; for CC, 6 achieved PR, 5 SD, and 9 PD. In all patients blood was withdrawn prior to INF alpha 2b treatment and then monthly. T lymphocytes, after isolation from peripheral blood, were tested for proliferation in the autologous mixed-lymphocyte reaction and allogeneic mixed-lymphocyte reaction, interleukin-2 (IL-2) production, expression of IL-2 receptors during the allogeneic-mixed-lymphocyte reaction, and the production of IL-1 by peripheral blood monocytes. Striking increases were demonstrated in all parameters 2 months after treatment with INF alpha 2b. In comparison to normal controls, all patients with the malignant neoplasms presented decreased (> 45%) mean values of the immunological parameters under investigation (P 0.0001). Responders (patients with RCC, MEL, and PR) presented lower mean values of all the parameters studied than did non-responders (P 0.0001). Patients with CC presented the lowest mean values of the parameters than did the other patients (RCC, MEL) (P 0.0001). After therapy with INF alpha 2b, patients with RCC experiencing PR showed a mean increase of more than 30% (P 0.0001). Patients with SD showed a mean increase of about 20% (P 0.0001), and those with PD showed a 6% increase in the immunological parameters under investigation. Patients with MEL experiencing PR showed a mean increase of more than 30% and patients with PD a decrease of more than 10% (P 0.0001). All patients, regardless of the clinical response, achieved an increase of more than 60% (P 0.0001). Administration of IFN alpha 2b resulted in a marked potentiation of a deficient cellular immune response in vitro in those patients with RCC and MEL who responded to the treatment. On the other hand, non-responders demonstrated a decrease in the examined parameters and, in some, deterioration of the already depressed immunological functions was observed. This observation can have prognostic significance regarding clinical response of INF. In contrast, our findings show that the immune stimulation associated with INF alpha treatment in all our CC patients did not predict an improved clinical outcome. There are several theoretical explanations for this discrepancy.

Adult↗
PubMed2005

Regional and systemic chemotherapy for primary hepatobiliary cancers and for colorectal cancer metastatic to the liver.

Hepatic arterial infusional (HAI) chemotherapy is based on the premise that primary and metastatic tumors derive their blood supply from the hepatic artery, whereas normal liver derives its blood supply from the portal vein. This approach has been extensively studied in liver-only colorectal metastasis patients, with 10 published prospective randomized clinical trials comparing fluoropyrimidine-based HAI therapy with systemic chemotherapy. Most of these studies showed a statistically significant superior response rate and improved disease-free survival with HAI chemotherapy compared with systemic fluoropyrimidine-based chemotherapy alone. More advanced chemotherapeutic regimens including biologically targeted agents have clearly impacted survival in metastatic colorectal cancer patients and are currently under investigation with HAI-based trials. In contrast, hepatobiliary tumors remain difficult to treat with overall poor response and survival with systemic chemotherapy. Few clinical trials have attempted to address the role of HAI-based therapy for these regional tumors, although encouraging response rates up to 60% have been reported. Therefore, the regional approach for hepatobiliary tumors deserves further investigation as well as randomized trials for adequate comparison to new systemic chemotherapies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Novel therapeutic strategies for colorectal cancer.

Advanced colorectal cancer is a significant cause of cancer mortality in industrialized countries. 5-fluorouracil has remained the principal drug used in treating this disease, and although it has tangibly improved patient outcome, further gains can potentially be made. This review focuses on the current development of novel therapeutic agents which have potential in the treatment of colorectal cancer.

Colorectal Neoplasms↗
PubMed2006

Colorectal cancer screening.

Colorectal cancer is a major public health burden worldwide. There is clear-cut evidence that screening will reduce colorectal cancer mortality and the only contentious issue is which screening tool to use. Most evidence points towards screening with fecal occult blood testing. The immunochemical fecal occult blood tests have a higher sensitivity than the guaiac-based tests. In addition, their automation and haemoglobin quantification allows a threshold for colonoscopy to be selected that can be accommodated within individual health care systems.

Aged↗
PubMed1983

Pesticides and breast cancer, popcorn and colorectal cancer: innovation versus fashion in dietary epidemiology.

Organochlorine insecticides and polychlorinated biphenyls (PCBs) have been found to be carcinogenic in animal studies. Eight of these insecticides and PCBs have been detected in human milk samples. Their possible contribution to breast cancer has never been seriously studied. Substances which cause scarring or provide anchorage when embedded in tissue can contribute to carcinogenesis. Sharp outer fragments of popcorn kernels may contribute to the type of tissue fibrosis associated with colorectal cancer. Lack of innovation in dietary cancer epidemiology is discussed.

Breast Neoplasms↗
PubMed2003

Cyclooxygenase inhibition and mechanisms of colorectal cancer prevention.

Colorectal cancer is a leading cause of cancer death throughout the world. The high prevalence and mortality associated with colon cancer make effective prevention and treatment an important public health and economic concern. Among the few agents known to inhibit colorectal tumorigenesis are the nonsteroidal anti-inflammatory drugs or NSAIDs, as well as newer agents such as celecoxib and rofecoxib. Both epidemiologic studies and investigations with animals show that these compounds possess marked anti-colorectal cancer properties. NSAIDS are widely known to be inhibitors of the cyclooxygenase (COX) enzymes, and it is thought that the chemopreventive effects of NSAIDs are at least in part due to this ability to inhibit COX. More recent studies, however, have suggested that NSAIDs may also exert anti-cancer effects through mechanisms independent of COX inhibition. COX-dependent and COX-independent mechanisms are not mutually exclusive and it is likely that both are involved in the biological activity of NSAIDs.

Animals↗
PubMed1999

Genetic susceptibility to non-polyposis colorectal cancer.

Familial colorectal cancer (CRC) is a major public health problem by virtue of its relatively high frequency. Some 15-20% of all CRCs are familial. Among these, familial adenomatous polyposis (FAP), caused by germline mutations in the APC gene, accounts for less than 1%. Hereditary non-polyposis colorectal cancer (HNPCC), also called Lynch syndrome, accounts for approximately 5-8% of all CRC patients. Among these, some 3% are mutation positive, that is, caused by germline mutations in the DNA mismatch repair genes that have so far been implicated (MLH1, MSH2, MSH6, PMS1, and PMS2). Most of the remaining patients belonging to HNPCC or HNPCC-like families are still molecularly unexplained. Among the remaining familial CRCs, a large proportion is probably caused by gene mutations and polymorphisms of low penetrance, of which the I1307K polymorphism in the APC gene is a prime example. Molecular genetic findings have enabled hereditary CRC to be divided into two groups: (1) tumours that show microsatellite instability (MSI), occur more frequently in the right colon, have diploid DNA, harbour characteristic mutations such as transforming growth factor beta type II receptor and BAX, and behave indolently, of which HNPCC is an example; and (2) tumours with chromosomal instability (CIN), which tend to be left sided, show aneuploid DNA, harbour characteristic mutations such as K-ras, APC, and p53, and behave aggressively, of which FAP is an example. This review focuses most heavily on the clinical features, pathology, molecular genetics, surveillance, and management including prophylactic surgery in HNPCC. Because of the difficulty in diagnosing HNPCC, a detailed differential diagnosis of the several hereditary CRC variants is provided. The extant genetic and phenotypic heterogeneity in CRC leads to the conclusion that it is no longer appropriate to discuss the genetics of CRC without defining the specific hereditary CRC syndrome of concern. Therefore, it is important to ascertain cancer of all anatomical sites, as well as non-cancer phenotypic stigmata (such as the perioral and mucosal pigmentations in Peutz-Jeghers syndrome), when taking a family cancer history.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed2005

Claudins upregulation in human colorectal cancer.

In colorectal cancer tight junction molecular and morphological alterations are poorly understood. In this study, adenocarcinoma tissues and their paired normal mucosa (n = 12) were analyzed for tight junction alterations molecular. The expression of claudin-1, -3 and -4 was upregulated 5.7-, 1.5- and 2.4-fold, respectively, in colorectal tumor tissues in comparison to the normal ones. Although tight junction remains in the cancerous epithelium, its barrier function was altered. Despite claudins overexpression, paracellular permeability to ruthenium red was increased and a significant disorganization of tight junction strands was observed in freeze fracture replicas. Whereas the functional significance of claudin overexpression in colorectal cancer is unclear, these proteins can become potential markers and targets in colorectal cancer.

Adenocarcinoma↗
PubMed2000

Genetic testing and surgical decision making in hereditary colorectal cancer.

Hereditary colorectal cancer results from specific genetic alterations. The causative genes for familial adenomatous polyposis, juvenile polyposis, Peutz-Jeghers syndrome, and hereditary nonpolyposis colorectal cancer have been cloned and characterized within the past decade. Genetic testing has therefore become more widely used to confirm the clinical diagnosis of each of those syndromes, to provide adequate surveillance, to allow screening of at-risk family members, and to help the surgeon in surgical decision making. The aim of this review is to analyze the importance of genetic testing in view of the clinical and surgical management of those gene-carriers individuals, and to discuss how should the surgeon integrate genetic testing in the evaluation of such patients.

Adenomatous Polyposis Coli↗
PubMedDate not supplied

Progression rates of colorectal cancer by Dukes' stage in a high-risk group: analysis of selective colorectal cancer screening.

PURPOSE: The progression rates of colorectal cancer by Dukes' stage in a high-risk group were estimated and applied to evaluate the efficacy of different screening regimens. PATIENTS AND METHODS: Of 6303 high-risk subjects invited to a colorectal cancer screening project with colonoscopy, 39 screen-detected cases and 16 postscreening cases were diagnosed with information available on Dukes' stage. A five-state Markov process was applied to estimate parameters pertaining to the disease natural history of colorectal cancer by Dukes' stage. RESULTS: The estimates of the mean sojourn time in years were 3.10 for preclinical Dukes' A and B and 1.92 for preclinical Dukes' stages C and D. The predicted reductions of Dukes' stages C and D achieved by annual, biennial, 3-yearly, and 6-yearly screening regimens against the control group were 60%, 49%, 40%, and 25%, respectively. These, in turn, yield the corresponding predicted mortality reductions of 39%, 33%, 28%, and 18%. CONCLUSIONS: These findings suggest that to achieve a 30% mortality reduction, as observed in annual fecal occult blood testing, a prudent interscreening interval with colonoscopy for this high-risk group should not be longer than 3 years.

Aged↗
PubMed2004

Plasma prolactin in patients with colorectal cancer.

BACKGROUND: Colorectal cancer is a common malignancy of the gastrointestinal tract. It is the second cancer cause of death in females and third in males. Production of prolactin has been reported with several tumours. However, elevated prolactin plasma levels in colorectal cancer patients remained unclear. METHODS: In this cross sectional study serum prolactin and carcinoembryonic antigen (CEA) concentrations were assayed using immunoradiometric assay kits, preoperatively in 47 patients, and the results were compared with 51 age and sex matched controls. RESULTS: Prolactin and CEA concentration in patients were significantly more as compared with controls. Hyperprolactinemia was found in 36 (76.6%) patients, while 28 (59.6%) had high level of CEA. CONCLUSIONS: Prolactin may be a better tumour marker than CEA in patients with colorectal malignancy.

Adult↗
PubMed2003

Laparoscopic colorectal cancer surgery.

Colorectal cancer remains the second most common cause of cancer death in the USA and western Europe, with more than 34,000 new cases per year in the UK alone. Annual expenditure is in excess of pounds sterling 300 million, required for surgical, adjuvant and palliative treatment. Laparoscopic colorectal surgery has yet to gain the widespread support observed with gallbladder surgery. Randomized controlled trials are ongoing, evaluating the short- and long-term risks and benefits of laparoscopic versus conventional open surgery. Although long-term results are awaited, there is evidence of short-term benefits and no obvious evidence of laparoscopic techniques conferring any additional harm in terms of tumor recurrence or disease-free survival. This review explores the likely benefits and areas of continued concern. Information resources provide a background to colorectal cancer for nonclinicians and new strategies and a 5-year view are presented.

Colorectal Neoplasms↗
PubMed2005

Brachytherapy of prostate cancer after colectomy for colorectal cancer: pilot experience.

PURPOSE: We present a method of brachytherapy for prostate cancer using a 3-dimensional stereotactic system and computerized tomography guidance in patients without a rectum due to previous treatment for colorectal cancer. MATERIALS AND METHODS: From June 1994 to November 2003 a cohort of 800 patients were treated with brachytherapy for prostate cancer. Four patients had previously been treated for colorectal cancer with 4,500 cGy external beam radiation therapy, abdominoperineal resection and chemotherapy, while 1 underwent abdominoperineal resection alone for ulcerative colitis. Because of previous radiation therapy, these patients were not candidates for salvage external beam radiation therapy or radical prostatectomy and they had no rectum for transrectal ultrasound guided transperineal brachytherapy or cryotherapy. A previously described, 3-dimensional stereotactic system was used for brachytherapy in these patients. The prescribed radiation dose was 120 to 144 Gy with iodine seeds in rapid strand format. Patient followup included clinical examination and serum prostate specific antigen measurement. RESULTS: Average followup was 18.6 months. Four patients had excellent biochemical control, while 1 had biochemical failure. Patients did not experience any gastrointestinal morbidity. One patient had a stricture of the distal ureter, requiring a stent. CONCLUSIONS: Three-dimensional computerized tomography guided brachytherapy for prostate cancer in patients with a history of colorectal cancer who have no rectum is a feasible method of treatment.

Adenocarcinoma↗
PubMed1999

The treatment of metastatic colorectal cancer.

Metastatic colorectal cancer represents an incurable condition, with the exception of a very select group of patients in whom surgical excision of recurrent disease is possible. Chemotherapy offers a significant palliative benefit and may prolong patient survival. The preferred cytotoxic agent is 5-fluorouracil, through the optimal administration schedule is unknown. Recent evidence also supports the use of second-line chemotherapy for patients who develop progressive disease following 5-fluorouracil treatment. Promising results have been obtained with new drugs, in particular oxaliplatin and irinotecan. Novel therapeutic approaches, including immunotherapy and liver directed strategies, are undergoing clinical evaluation. Comprehensive supportive care, with appropriate community and hospital based palliative care, is essential in the management of patients with advanced colorectal cancer.

Antineoplastic Agents↗