Colon Cancer Patients (colon + cancer_patient)

Distribution by Scientific Domains

Selected Abstracts

Antitumor activity of chimeric immunoreceptor gene-modified Tc1 and Th1 cells against autologous carcinoembryonic antigen-expressing colon cancer cells

CANCER SCIENCE, Issue 9 2006
Takeshi Sasaki
To generate tumor-specific and interferon (IFN)-,-producing Tc1 and Th1 cells applicable for many cancer patients, we previously developed a protocol for generating carcinoembryonic antigen (CEA)-specific Tc1 and Th1 cells from healthy human T cells by transduction with a lentivirus containing a chimeric immunoglobulin T-cell receptor (cIgTCR) gene composed of single-chain variable fragments from an anti-CEA-specific monoclonal antibody fused to an intracellular signaling domain of CD28 and CD3,. These cells, designated Tc1-T and Th1-T bodies, respectively, showed strong antitumor activity against CEA-expressing tumor cells in RAG2,/, mice when both of them were transferred. However, it remains unclear whether it is possible to generate Tc1-T and Th1-T bodies from cancer patients with defective T-cell function because of significant immunosuppression. Here, we prepared Tc1-T and Th1-T bodies from T cells of a colon cancer patient, and asked whether these T bodies can exert effective T-cell function against autologous tumor cells. These T bodies showed high cytotoxicity and produced IFN-, in response to CEA-expressing autologous tumor cells, even in the presence of soluble CEA. It was also demonstrated that Th1-T bodies supported the survival of Tc1-T bodies through cell-to-cell interactions. Furthermore, our protocol utilized retrovirus for cIgTCR transduction to achieve better induction efficiency compared to lentivirus-mediated transduction. Taken together, our findings here indicate that retrovirally transduced Tc1-T and Th1-T bodies will become a promising strategy for adoptive immunotherapy of human cancer. (Cancer Sci 2006; 97: 920,927) [source]

Classifying MLH1 and MSH2 variants using bioinformatic prediction, splicing assays, segregation, and tumor characteristics

HUMAN MUTATION, Issue 5 2009
Sven Arnold
Abstract Reliable methods for predicting functional consequences of variants in disease genes would be beneficial in the clinical setting. This study was undertaken to predict, and confirm in vitro, splicing aberrations associated with mismatch repair (MMR) variants identified in familial colon cancer patients. Six programs were used to predict the effect of 13 MLH1 and 6 MSH2 gene variants on pre-mRNA splicing. mRNA from cycloheximide-treated lymphoblastoid cell lines of variant carriers was screened for splicing aberrations. Tumors of variant carriers were tested for microsatellite instability and MMR protein expression. Variant segregation in families was assessed using Bayes factor causality analysis. Amino acid alterations were examined for evolutionary conservation and physicochemical properties. Splicing aberrations were detected for 10 variants, including a frameshift as a minor cDNA product, and altered ratio of known alternate splice products. Loss of splice sites was well predicted by splice-site prediction programs SpliceSiteFinder (90%) and NNSPLICE (90%), but consequence of splice site loss was less accurately predicted. No aberrations correlated with ESE predictions for the nine exonic variants studied. Seven of eight missense variants had normal splicing (88%), but only one was a substitution considered neutral from evolutionary/physicochemical analysis. Combined with information from tumor and segregation analysis, and literature review, 16 of 19 variants were considered clinically relevant. Bioinformatic tools for prediction of splicing aberrations need improvement before use without supporting studies to assess variant pathogenicity. Classification of mismatch repair gene variants is assisted by a comprehensive approach that includes in vitro, tumor pathology, clinical, and evolutionary conservation data. Hum Mutat 0, 1,14, 2009. 2009 Wiley-Liss, Inc. [source]

Patterns of Presentation, Diagnosis, and Treatment in Older Patients with Colon Cancer and Comorbid Dementia

Supriya K. Gupta MD
Objectives: To estimate patterns of colon cancer presentation, diagnosis, and treatment according to history of dementia using National Cancer Institute (NCI) Surveillance, Epidemiology, and End-Result (SEER) Medicare data. Design: Population-level cohort study. Setting: NCI's SEER-Medicare database. Participants: A total of 17,507 individuals aged 67 and older with invasive colon cancer (Stage I-IV) were identified from the 1993,1996 SEER file. Medicare files were evaluated to determine which patients had an antecedent diagnosis of dementia. Measurements: Parameters relating to the cohort's patterns of presentation and care were estimated using logistic regressions. Results: The prevalence of dementia in the cohort of newly diagnosed colon cancer patients was 6.8% (1,184/17,507). Adjusting for possible confounders, dementia patients were twice as likely to have colon cancer reported after death (i.e., autopsy or death certificate) (adjusted odds ratio (AOR)=2.31, 95% confidence interval (CI)=1.79,3.00). Of those diagnosed before death (n=17,049), dementia patients were twice as likely to be diagnosed noninvasively than with tissue evaluation (i.e., positive histology) (AOR=2.02 95% CI=1.63,2.51). Of patients with Stage I -III disease (n=12,728), patients with dementia were half as likely to receive surgical resection (AOR=0.48, 95% CI=0.33,0.70). Furthermore, of those with resected Stage III colon cancer (n=3,386), dementia patients were 78% less likely to receive adjuvant 5-fluorouracil (AOR=0.22, 95% CI=0.13,0.36). Conclusion: Although the incidences of dementia and cancer rise with age, little is known about the effect of dementia on cancer presentation and treatment. Elderly colon cancer patients are less likely to receive invasive diagnostic methods or curative-intent therapies. The utility of anticancer therapies in patients with dementia merits further study. [source]

Clinical and pathological evaluation of patients with early and late recurrence of colorectal cancer

Abstract Aim: To compare the characteristics of primary cancer between patients with early recurrence and those with late recurrence of colorectal cancer. Methods: Overall 535 patients with primary colorectal cancer were reviewed and of these 130 patients with demonstrated recurrence were evaluated. Of the 130 patients, 91 had early recurrence (less than 2 years after surgery) and 39 had late recurrence (2 years or more after surgery). The clinical and pathological characteristics of primary cancer in these two groups were compared. Results: The rate of late recurrence was 30% of total recurrences (39/130). On average, patients with early recurrence were younger than patients with late recurrence (mean age 48 vs 54 years, p = 0.027). Adjacent organ involvement and Dukes stage C was more prevalent in the early recurrence group than in the late group. The liver was the main site of distant recurrence in the early recurrence group (64% of distant recurrences), whereas bone and peritoneum were the most frequent sites of metastases in the late recurrence group (58%). In Dukes C colon cancer patients the disease-free interval was significantly longer in those who received both adjuvant therapies than in those who received either radiotherapy or chemotherapy or neither of them. Conclusion: This study showed that factors such as primary clinical signs, stage of primary tumor, and adjacent organ involvement are significant with respect to the time for recurrence of colorectal cancer. It is important to take these characteristics into account in patient care management after curative resection for colorectal cancer. [source]

Safety and tolerability of FOLFOX4 in the adjuvant treatment of colon cancer in Asian patients: The MASCOT study

Po-Huang LEE
Abstract Aims: The MOSAIC trial showed that FOLFOX4 improves overall survival as compared to 5-FU/LV and is feasible and safe in early stage colon cancer patients worldwide. Based on these positive results, the present study MASCOT (Multicenter Asia Study in adjuvant treatment of Colon cancer with Oxalipla Tin/5-FU/LV), aimed to evaluate the safety and tolerability of FOLFOX4 in postoperative adjuvant treatment of colon cancer in Asian patients. Methods: In this open-label, non-randomized, single arm feasibility study, stage II/III colon cancer patients who had undergone complete resection of a primary tumor were treated using the FOLFOX4 regimen (2 weeks/cycle, 12 cycles) and followed up for 12 months. Results: A total of 159 patients (28.3% stage II and 71.7% stage III) from 17 hospitals in five Asian countries were included in the study. Overall 130 (81.8%) patients completed all 12 planned treatment cycles. There were 60% and 11% patients who experienced , grade 3 pre-listed and non pre-listed toxicities, respectively. The incidences of grade 3 and 4 neuropathy were 5.7% and 0%, respectively. A total of 25 serious adverse events (SAE) were experienced by 21 (13%) patients, with one life-threatening SAE. At 12 months follow-up two patients were known to be dead due to disease relapse or recurrence. Conclusion: The MASCOT study demonstrates a favorable safety profile of FOLFOX4 in Asian patients. Based on these results and the safety and efficacy results from MOSAIC, FOLFOX4 may be considered a standard for the adjuvant treatment of colon cancer in the Asian population. [source]

Making use of the primary tumour

BIOESSAYS, Issue 1 2003
Arnold Baars
Surgical resection of a primary tumour is often not sufficient to cure a patient. Even when no residual cancer can be detected at time of surgery, metastases may appear in the following years, which indicates that the primary tumour had apparently spread before surgery. Following surgery, systemic chemotherapy may be used to eradicate micro-metastatic disease. Here we present two unconventional strategies that implement new insights into tumour biology and tumour immunology in the treatment of patients with cancer. Both experimental strategies use the individual characteristics of the patient's primary tumour to optimise the control of life-threatening micro-metastases. We aim to modulate the patient's adaptive immune system, targeting it towards the patient's own tumour cells to eradicate residual disease following local treatment. In one approach, this is done by autologous tumour cell vaccinations as adjuvant treatment for colon cancer patients and, in a second approach, by giving chemo-imunotherapy before local treatment to women with locally advanced breast cancer. BioEssays 25:79,86, 2003. 2002 Wiley Periodicals, Inc. [source]

Model-based prediction of defective DNA mismatch repair using clinicopathological variables in sporadic colon cancer patients

CANCER, Issue 7 2010
Frank Sinicrope MD
Abstract BACKGROUND: Colon cancers with defective DNA mismatch repair (MMR) have a favorable prognosis and may lack benefit from 5-fluorouracil,based adjuvant chemotherapy. The authors developed models to predict MMR deficiency in sporadic colon cancer patients using routine clinical and pathological data. METHODS: TNM stage II and III colon carcinomas (n = 982) from 6 5-fluorouracil,based adjuvant therapy trials were analyzed for microsatellite instability and/or MMR protein expression. Tumor-infiltrating lymphocytes (TILs) were quantified (n = 326). Logistic regression and a recursive partitioning and amalgamation analysis were used to identify predictive factors for MMR status. RESULTS: Defective MMR was detected in 147 (15%) cancers. Tumor site and histologic grade were the most important predictors of MMR status. Distal tumors had a low likelihood of defective MMR (3%; 13 of 468); proximal tumors had a greater likelihood (26%; 130 of 506). By using tumor site, grade, and sex, the logistic regression model showed excellent discrimination (c statistic = 0.81). Proximal site, female sex, and poor differentiation showed a positive predictive value (PPV) of 51% for defective MMR. In a patient subset (n = 326), a model including proximal site, TILs (>2/high-power field), and female sex showed even better discrimination (c statistic = 0.86), with a PPV of 81%. CONCLUSIONS: Defective MMR is rare in distal, sporadic colon cancers, which should generally not undergo MMR testing. Proximal site, poor differentiation, and female sex detect 51% of tumors with defective MMR; substituting TILs for grade increases the PPV to 81%. These data can increase the efficiency of MMR testing to assist in clinical decisions. Cancer 2010. 2010 American Cancer Society. [source]

The intratumoral distribution of nuclear ,-catenin is a prognostic marker in colon cancer

CANCER, Issue 10 2009
David Horst MD
Abstract BACKGROUND: Most colon cancers harbor mutations of APC or ,-catenin, both of which may lead to nuclear ,-catenin accumulation in the tumor cells and constitutively activated expression of its target genes. In many colon cancers, however, nuclear ,-catenin accumulation is heterogeneous throughout the tumor and often confined to the tumor margin. Herein, the authors investigated whether the intratumoral distribution of nuclear ,-catenin can serve as a prognostic marker for survival and tumor progression of stage IIA colon cancer patients. METHODS: In total, 142 patients with primarily resected, moderately differentiated stage IIA colon cancer were included in this study. The patterning of nuclear ,-catenin expression was evaluated on immunohistochemically stained whole tissue sections of the tumors and was correlated with cancer-specific survival and disease-free survival using univariate and multivariate statistical analyses. RESULTS: Four distinct patterns of nuclear ,-catenin expression were identified, and 2 main categories comprising tumors with or without intratumoral regulation of nuclear ,-catenin were distinguished. Moreover, the results demonstrated that the patterning, and especially the regulation or absence of regulation of nuclear ,-catenin expression, was a strong predictive marker of patient survival and tumor progression. CONCLUSIONS: The current results indicated that the distribution of nuclear ,-catenin expression can be used as a good prognostic marker in patients with stage IIA colon cancer. Thus, the evaluation of nuclear ,-catenin may help to identify patients who will have a shorter than average survival and patients with a greater risk of disease progression who may be considered for adjuvant therapeutic modalities and intensified clinical aftercare in the future. Cancer 2009. 2009 American Cancer Society. [source]

Adiponectin, ghrelin, and leptin in cancer cachexia in breast and colon cancer patients

CANCER, Issue 4 2006
Ido Wolf M.D.
Abstract BACKGROUND The hormone ghrelin and the adipocytokines leptin and adiponectin participate in body weight regulation. In response to weight loss, ghrelin and adiponectin levels increase and leptin decreases. Cancer cachexia is a complex metabolic state, characterized by loss of muscle mass and adipose tissue together with anorexia. The authors hypothesized that responses of these hormones may be attenuated in cancer cachexia. METHODS Fasting plasma ghrelin, adiponectin, and leptin levels, as well as weight loss, were determined in 40 cancer patients: 18 of them suffered from cancer-induced cachexia, and 22 served as a comparison group. Hormone levels were measured before administration of cancer therapy. RESULTS A similar distribution of age, gender, and diagnosis was observed in both study groups, but the cachectic patients had higher rates of metastatic disease and lower albumin levels. No significant correlation was observed between plasma adiponectin levels and weight loss. Mean plasma ghrelin levels were higher among cachectic compared with noncachectic patients. Notably, the association between ghrelin levels and weight loss was only modest, and in a third of the cachectic patients, ghrelin levels were equal to or lower than those in the noncachectic group. Plasma leptin levels showed gender-dependent associations, and significantly lower levels were found among cachectic women but not among cachectic men. CONCLUSIONS Results suggested a gender-dependent attenuation of expected physiologic responses to weight loss among cancer cachexia patients. Thus, impaired response of adiponectin, ghrelin, and leptin may play a role in the pathogenesis of cancer cachexia syndrome. Cancer 2006. 2006 American Cancer Society. [source]

Tumour location is a prognostic factor for survival in colonic cancer patients

O. H. Sjo
Abstract Objective, To evaluate survival and prognostic factors in a consecutive series of colon cancer patients from a defined city population in Norway. Method, All patients with adenocarcinoma of the colon diagnosed between 1993 and 2000 were registered prospectively. Five-year actuarial survival and 5-year relative survival rates were calculated. Cox regression analyses were used to study the effect of prognostic factors on survival. Results, In the study period 627 patients were admitted. Overall 5-year relative survival was 50% in females and 52% in males. Five-year relative survival in 410 (65%) patients operated with curative intent, was 74% for females and 79% for males. Tumour location in the transverse colon, splenic flexure and descending colon (OR = 1.8), emergency operation (OR = 1.7), TNM stage (OR = 1.8,2.9), blood transfusion of more than two units (OR = 1.8) and age (OR = 4.0,7.1) were independent negative prognostic factors. Conclusion, Colon cancer located in the transverse and descending colon is associated with poor prognosis. Comparison of results from different centres is difficult due to selection and classification differences, and different methods used for calculation of survival. [source]