Group Of Colon Cancer Patients Research Articles

Comparison of NOD-like and Toll-like receptors gene expression levels in blood monocytes of colon cancer patients.

Colon cancer is one of the most common cancers affecting many people worldwide. This disease can be treated if diagnosed in the early stages. Therefore, with the hypothesis that the level of expression of inflammatory genes in peripheral blood monocytes of patients with colon cancer is different from that of healthy people, this research was done to find out the role of inflammation in the development of colon cancer by relying on its immunopathological profile to help diagnose it in the early stages. In this case-control study, the expression levels of TLR4, TLR2, NLRP3, and NOS2 genes in 15 patients with confirmed stage II colon cancer were determined by the TNM method. Also, 15 healthy people referred for this cancer screening were selected as the control group. First, RNA was extracted from the blood monocytes of two groups, and after making cDNA, the comparison was created using the qPCR method. In this study, the β-actin gene was used as a reference gene. The expression levels of TLR2 and TLR4 at the mRNA level were significantly lower in colon cancer patients compared to the healthy control group (P<0.05). The expression level of NLRP3 in the group of colon cancer patients showed a relative increase. Still, it was not significant, while the expression level of the NOS2 gene in the group of colon cancer patients increased significantly compared to the healthy control group (P<0.05). Considering the significant changes in TLR4, TLR2, and NOS2 gene expression in monocytes of patients with grade II colon cancer and the role of inflammatory reactions in the development of this cancer, these findings can be used to diagnose and determine the prognosis. However, this requires further studies.

Safety and Feasibility of ≤24-h Short-Stay Right Colectomies for Primary Colon Cancer.

Hospital length of stay (LOS) has been used as a surgical quality metric. This study seeks to determine the safety and feasibility of right colectomy as a ≤24-h short-stay procedure for colon cancer patients. This was a retrospective cohort study using the ACS-NSQIP database and its Procedure Targeted Colectomy database (2012-2020). Adult patients with colon cancer who underwent right colectomies were identified. Patients were categorized into LOS ≤1day (≤24-h short-stay), LOS 2-4days, LOS 5-6days, and LOS ≥7days groups. Primary outcomes were 30-day overall and serious morbidity. Secondary outcomes were 30-day mortality, readmission, and anastomotic leak. The association between LOS and overall and serious morbidity was assessed using multivariable logistic regression. 19,401 adult patients were identified, with 371 patients (1.9%) undergoing short-stay right colectomies. Patients undergoing short-stay surgery were generally younger with fewer comorbidities. Overall morbidity for the short-stay group was 6.5%, compared to 11.3%, 23.4%, and 42.0% for LOS 2-4days, LOS 5-6days, and LOS ≥7days groups, respectively (p < 0.001). There were no differences in anastomotic leak, mortality, and readmission rates in the short-stay group compared to patients with LOS 2-4days. Patients with LOS 2-4days had increased odds of overall morbidity (OR 1.71, 95% CI 1.10-2.65, p = 0.016) compared to patients with short-stay but no differences in odds of serious morbidity (OR 1.20, 95% CI 0.61-2.36, p = 0.590). ≤24-h short-stay right colectomy is safe and feasible for a highly-select group of colon cancer patients. Optimizing patients preoperatively and implementing targeted readmission prevention strategies may aid patient selection.

Constructing a prognostic immune-related lncRNA model for colon cancer.

Colon cancer is a common digestive tract tumor. Although many gene prognostic indicators have been used to predict the prognosis of colon cancer patients, the accuracy of these prognostic indicators is still uncertain. Thus, it is necessary to construct a model for the prognostic analysis of colon cancer. We downloaded the original transcriptome data of colon cancer and performed a differential coexpression analysis of immune-related genes to obtain different immune-related long noncoding RNAs, which were paired as differentially expressed immune-related lncRNA pairs (DEirlncRNAPs). Then, the 1-year overall survival rate receiver operating characteristic curve was calculated, and the Akaike information criterion value was evaluated to determine the maximum inflection point, which was used as the cutoff point to identify groups of colon cancer patients at high and low risk for death. Subsequently, the optimal prediction model was established. Finally, we used the patients’ survival times, clinicopathological features, tumor infiltrating immune cells, chemotherapy responses, and immunosuppressive biomarkers to verify the DEirlncRNAP model. Seventy-one DEirlncRNAPs were obtained to build the risk assessment model. The patients were divided into a high-risk group and a low-risk group according to the cutoff point. Then, the DEirlncRNAP model was verified using patient survival times, clinicopathological features, tumor-infiltrating immune cells, chemotherapy responses, and immunosuppressive biomarkers. A new DEirlncRNAP model for predicting the prognosis of colon cancer patients was established, which could reveal new insights into the relationships of colon cancer with tumor-infiltrating immune cells and antitumor immunotherapy.

Study of Correlation between Intestinal Microbiota and Traditional Chinese Medicine Syndrome of Patients with Colon Cancer.

Objective This research aims to study the material basis of the formation and specific bacteria of traditional Chinese medicine (TCM) syndrome from the characteristics of the intestinal microbiota of patients with colon cancer (CC) before and after the operation. Methods A cross-sectional study was conducted on 84 patients with CC and 24 healthy controls. A total of 168 and 24 stool samples were collected from CC patients before and after the operation and healthy controls. DNA was extracted from 192 stool samples and then amplified using PCR. The V3-V4 high variable areas were analyzed by 16s rDNA sequencing. Results The community diversity, in descending order, was the healthy control group and postoperative and preoperative groups of CC patients. The abundance of beneficial bacteria was postoperative group of CC patients > healthy control group > preoperative group of CC patients. Among the comparisons of the intestinal microbiota of preoperative groups of CC patients with different TCM syndromes, the community diversity in descending order was damp heat accumulation (DHA), spleen deficiency and dampness (SDD), spleen and kidney yang deficiency (SKYD), liver and kidney yin deficiency (LKYD), and deficiency of qi and blood (QBD), respectively. Specific microbiome analysis showed that the differences in the abundance of 42 taxons were statistically significant among the preoperative groups of CC patients with the five TCM syndromes and the healthy control group. While comparing the intestinal microbiota of postoperative groups with the five TCM syndromes, the community diversity in descending order is DHA, SDD, LKYD, SKYD, and QBD. Specific microbiome analysis showed that the differences in the abundance of 46 taxons were statistically significant among the postoperative groups of CC patients with the five TCM syndromes and the healthy control group. Streptococcus and Streptococcus mutans showed no statistical significance between the preoperative group and postoperative groups of CC with DHA syndrome (P > 0.05). Bacteroides at phylum and genus levels showed that there was no statistical significance between the preoperative group and the postoperative group of CC with SKYD syndrome (P > 0.05). Conclusions Before and after surgery, with the deterioration of TCM syndrome: DHA ⟶ SDD ⟶ SKYD ⟶ LKYD ⟶ QBD, the number of beneficial bacteria in CC patients' intestines decreased while the number of pathogenic bacteria increased, and the community structure of intestinal microbiota tends to be unitized, indicating a serious intestinal microbiological disorder. After radical surgery and perioperative intervention, the intestinal microbiota diversity and community structure of postoperative CC patients were closer to those of healthy people than preoperative. However, they were still imbalanced. The intestinal microbiota of CC patients with different TCM syndromes differs significantly, which is important for understanding the pathogenesis of CC in TCM. The DHA and SKYD syndromes in CC patients before and after surgery showed significant differences in the microbial structure. Streptococcus and Streptococcus mutans were the specific species with a significant difference in CC patients with DHA syndrome, while bacteroides were the specific species in CC patients with SKYD syndrome.

Abstract 5266: Prognostic role of molecular subclassification based on mutational profiling and tumor-associated neutrophil status in stage III colon cancer

Abstract The traditional prognostic prediction of colon cancer (CC) is based on the tumor-node-metastasis (TNM) system. This, however, is not adequate for clinical decision making due to the existence of inter-patient variations and heterogeneity of underlying molecular pathways. We aim to investigate the prognostic value of molecular subclassification utilizing i) tumor-associated neutrophil (TAN) status by immunohistochemical (IHC) staining; ii) microsatellite instability (MSI) and elevated microsatellite alteration at selected tetranucleotide repeats (EMAST) status by PCR-based microsatellite typing; and iii) next-generation sequencing (NGS) mutational profiling by deep sequencing of a 77-gene oncology panel. In the discovery phase, 130 pairs of archived normal and tumor formalin-fixed paraffin-embedded (FFPE) specimens of stage III CC patients were retrospectively recruited from Queen Mary Hospital. CC patients will be categorized into different molecular subclasses (MSCs) based on the status of TAN/MSI/EMAST/NGS mutational profiling molecular biomarkers. Kaplan-Meier analysis, log rank test, univariate and multivariate Cox proportional hazards regression analysis will be used for estimation of progression-free survival (PFS) and overall survival (OS) between the two groups of CC patients. We expect our data to provide useful information for improved stratification of stage III CC patients into high or low risk of recurrence and survival. Acknowledgement: The Health and Medical Research Fund (07181536) to JMYK. Citation Format: CY Chan, AWI Lo, KO Lam, HY Ng, CC Chen, ML Lung, JMY Ko. Prognostic role of molecular subclassification based on mutational profiling and tumor-associated neutrophil status in stage III colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5266.

Incidence of colon cancer in younger population and lower incidence in Asians and females in central balley of California: Health disparity and epigenetic study model.

e19028 Background: California acts as a boiling pot for immigration and the perfect ecosystem to study epigenetic changes from dietary and environmental factors in various ethnicities. It has a significant immigrant population, with approximately a quarter of the 40 million residents being foreign-born. The impact of migration on colon cancer incidences over time has not yet been characterized on a broad-scale level in the Northern Central Valley. This provides a unique opportunity to study the influence of migration, socio-economic gradient, environmental, and racial identity on the incidence of cancer in a subset of California’s San Joaquin County Population. Colon cancer affects around 100,000 annually, with white and African Americans being more often affected than Asians or Hispanics. Methods: This study is a retrospective, single-institution study that compared the socio-demographic variables and clinical characteristics of the patients who had a history of colon cancer in an academic central valley institution. We reviewed all the patient charts with a diagnosis of colon cancer from 2014-2019 and compared the age, demographics, socioeconomic status, comorbidities, pathology, treatment, and outcomes in the population. Appropriate statistics have been used for analyzing the data. Results: A retrospective chart review of all patients diagnosed with colon cancer from our Hospital from 2014-2019 which revealed that 23.9% of patients were younger than 50 years at diagnosis, and mean age of diagnosis is 56.6 years, compared to the national average where younger population constituted at 11% and mean age for men and women are 68 years and 72 years respectively. 36.5% were 50-60 years old, and 39.2% were &gt; 60 years old. Women constituted 31% in our group compared to compared to 35.6% nationally. Asians are 23% of the central California population, but only 11.4% of patients in our group of colon cancer patients were Asian/pacific islanders, with 6.4% being average weight. 36.7% of patients have obesity. 67.4% were &gt; 25 BMI, of which 12.8% were younger Hispanics with BMI 25-30. Adenocarcinoma is seen in 91.4% of patients. Conclusions: The younger population with male predominance is seen. Asians see a surge in colon cancer incidence, but the incidence rate is still lower. Epigenetic, western lifestyle, and environmental are responsible factors. Younger overweight Hispanics are increasing in number as well. We will present further subgroup analysis at presentation.

Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers.

PD-1 plus CTLA-4 blockade is highly effective in advanced-stage, mismatch repair (MMR)-deficient (dMMR) colorectal cancers, yet not in MMR-proficient (pMMR) tumors. We postulated a higher efficacy of neoadjuvant immunotherapy in early-stage colon cancers. In the exploratory NICHE study (ClinicalTrials.gov: NCT03026140), patients with dMMR or pMMR tumors received a single dose of ipilimumab and two doses of nivolumab before surgery, the pMMR group with or without celecoxib. The primary objective was safety and feasibility; 40 patients with 21 dMMR and 20 pMMR tumors were treated, and 3 patients received nivolumab monotherapy in the safety run-in. Treatment was well tolerated and all patients underwent radical resections without delays, meeting the primary endpoint. Of the patients who received ipilimumab + nivolumab (20 dMMR and 15 pMMR tumors), 35 were evaluable for efficacy and translational endpoints. Pathological response was observed in 20/20 (100%; 95% exact confidence interval (CI): 86-100%) dMMR tumors, with 19 major pathological responses (MPRs, ≤10% residual viable tumor) and 12 pathological complete responses. In pMMR tumors, 4/15 (27%; 95% exact CI: 8-55%) showed pathological responses, with 3 MPRs and 1 partial response. CD8+PD-1+ T cell infiltration was predictive of response in pMMR tumors. These data indicate that neoadjuvant immunotherapy may have the potential to become the standard of care for a defined group of colon cancer patients when validated in larger studies with at least 3 years of disease-free survival data.

Serum protein profiling using an aptamer array predicts clinical outcomes of stage IIA colon cancer: A leave-one-out crossvalidation.

BackgroundIn this study, we established and validated a model for predicting prognosis of stage IIA colon cancer patients based on expression profiles of aptamers in serum.MethodsBloods samples were collected from 227 consecutive patients with pathologic T3N0M0 (stage IIA) colon cancer. We incubated 1,149 serum molecule-binding aptamer pools of clinical significance with serum from patients to obtain aptamers bound to serum molecules, which were then amplified and marked. Oligonucleotide arrays were constructed with the base sequences of the 1,149 aptamers, and the marked products identified above were reacted with one another to produce profiles of the aptamers bound to serum molecules. These profiles were organized into low- and high-risk groups of colon cancer patients based on clinical information for the serum samples. Cox proportional hazards model and leave-one-out cross-validation (LOOCV) were used to evaluate predictive performance.ResultsDuring a median follow-up period of 5 years, 29 of the 227 patients (11.9%) experienced recurrence. There were 212 patients (93.4%) in the low-risk group and 15 patients (6.6%) in the high-risk group in our aptamer prognosis model. Postoperative recurrence significantly correlated with age and aptamer risk stratification (p = 0.046 and p = 0.001, respectively). In multivariate analysis, aptamer risk stratification (p < 0.001) was an independent predictor of recurrence. Disease-free survival curves calculated according to aptamer risk level predicted through a LOOCV procedure and age showed significant differences (p < 0.001 from permutations).ConclusionAptamer risk stratification can be a valuable prognostic factor in stage II colon cancer patients.

Co‐expression of CD133+/CD44+ in human colon cancer and liver metastasis

Although relatively good therapeutic results are achieved in non-advanced cancer, the prognosis of the advanced colon cancer still remains poor, dependent on local or distant recurrence of the disease. One of the factors responsible for recurrence is supposed to be cancer stem cells (CSCs) or tumor-initiating cells, which are a population of cancer cells with ability to perpetuate themselves through self-renewal and to generate differentiated cells, thought to be responsible for tumor recurrence. This study globally approach the possible role of tissue-derived stem cells in the initiation of colon cancer and its metastatic process in the liver. Fresh surgical specimens from colon cancer, non-tumor tissue and liver metastasis were obtained directly from the operating room, examined, and immediately processed. CSCs were selected under serum-free conditions and characterized by CD44 and CD133 expression levels. CD133(+)/CD44(+) cell populations were then investigated in paraffin-embedded tissues and circulating tumor cells isolated from peripheral blood of the same group of colon cancer patients. Our data demonstrate that metastatic properties of cell populations from blood and liver metastasis, differently from primitive tumors, seem to be strictly related to the phenotype CD133 positive and CD44 positive.

Golgi protein 73 (gp73) is a useful tumor marker in patients with colon cancer.

e14089 Background: Golgi protein 73 (gp73) is a 400 kD trans-membrane protein expressed in hepatocytes when induced by cytokines or exposed to viruses. Gp73 is also expressed in various tumor cells including colon cancer. In this study, we aimed to evaluate the value of the serum gp73 as a tumor marker in patients with colon cancer. Methods: A total of 126 patients with liver only metastases, with non-liver metastases, without distant metastasis (both preoperative and postoperative period), and a group of colon cancer patients in remission at least 3 years and not relapsed within at least 6 months after obtaining blood samples and a healthy group with similar age and gender were included in the study. The serum gp73 levels were measured by ELISA and compared with serum CEA and CA 19.9 levels. Results: Serum gp73 was higher than the lower detection limit of the test in the majority of the test subjects. The diagnostic performance of gp73 was better than both CEA and CA19.9 for colon cancer metastases (AUC= 0.974±0.003 [95%CI: 0.912-1.037] for gp73; AUC=0.859±0.089 [95%CI: 0.684-1.034] for CEA; and AUC=0.782±0.106 [95%CI: 0.574-0.990] for CA19.9) (p<0.05). The diagnostic performance of gp73 as a tumor marker was especially more prominent in the subgroup of liver only metastases. For the non-liver metastases, the performance of CEA was similar to gp73. At the cut-off level of 15 ng/mL, the sensitivity of gp73 was 80% and specificity 100%. The sensitivity and specificity of CEA were 72% and 100% at the level of 5 ng/mL and of CA 19.9 69% and 100% at the level of 45 U/mL. Conclusions: The serum gp73 seems to be a useful tumor marker in patients with colon cancer.

Sa1593 Long-Term Oncologic Outcomes in Colon Cancer Patients With “Bridge to Surgery” Stenting. Comparative Study With TNM Matched Controls

Long-Term Oncologic Outcomes in Colon Cancer Patients With “Bridge to Surgery” Stenting. Comparative Study With TNM Matched Controls Francisco Igea, Sergio Maestro, Rocio Silvana Castillo, Antonio Perez Millan, Henar Nunez, Rosa Eva Madrigal, Esther Saracibar, Javier Barcenilla Complejo Hospitalario de Palencia, Palencia, Spain Background: Expandable metal stents are frecquently used as a bridge to surgery in colon cancer occlusions. Recently worse oncologic outcomes have been described comparing stented patients with control group matched by TNM staging (1). This could be a serious limitation for continuing stenting occluded colon cancers. At present moment,there are no randomized, prospective data. Aims: Compare oncologic outcomes of patients stented vs controls matched by age,sex,TNM stage and year of diagnosis. Methods: We reviewed all our colon cancer patients stented as bridge to surgery during the period nov 1999 nov 2007. A control group of colon cancer patients matched by sex , age, TNM staging and year of diagnosis was extracted from our database. All the patients were treated in our institution by the same surgeons and oncologysts. Global survival and presence of disease at 3 and five years were compared. Results: Population and TNM stagin carachteristics are reflected in Table 1. We found 41 stent patients and 73 non-stented matched controls. Stage IV was finally excluded in this study because serious difference in treatment approach between both groups. Three year survival in groups II & III was 65,7 % in stented group vs 75% in control group (ns.). Presence of disease was 13 % vs 7,8% in control group. Results at five years follow up in stage II & III are summarized in table 2 No significant difference was observed between both groups. Conclusions: 1) There are no significant diference in survival and disease free survival at 3 and five years in our experience 2)Prospective randomized studies are needed to elucidate this point(1)World J Surg. 2009 Jun;33(6)1281-6. Oncologic outcomes of selfexpanding metallic stent insertion as a bridge to surgery in the management of left-sided colon cancer obstruction: comparison with nonobstructing elective surgery. Kim JS,et al.

Role of Insulin-Like Growth Factor-1 in Colon Cancerogenesis: A Case-Control Study

Our aim was to establish whether individuals who developed colon cancer have elevated blood levels of insulin-like growth factor-1 (IGF-1). This was a case/control study in which 52 patients with colon cancer and a corresponding control group were investigated. Data on age, weight, height, and sex of subjects were recorded and levels of IGF-1 and growth hormone, as well as insulin and C-peptide levels, were measured in the morning before eating, 90 min after breakfast and again 90 min after lunch. We found significantly higher levels of IGF-1 in blood of colon cancer patients compared to the control group. No differences in the levels of growth hormone, insulin and C-peptide in blood were found between colon cancer patients and the control group. It was found that the increase of IGF-1 level was followed by a 3.15-fold increased risk for developing colon cancer. There were no differences in the levels of IGF-1 in blood in all three measurements in the group of colon cancer patients, whereas differences were found in the control group. We found differences in the levels of insulin and C-peptide in blood in all three measurements in both groups of patients. No differences were found in the levels of growth hormone in blood in all three measurements in both groups of patients. The results of this study suggest a positive correlation between the increased levels of IGF-1 and colon cancer and are thus consistent with the hypothesis that the level of IGF-1 plays an important role in the development of colon cancer.

Detection in Fecal DNA of Colon Cancer–Specific Methylation of the Nonexpressed Vimentin Gene

Increased DNA methylation is an epigenetic alteration that is common in human cancers and is often associated with transcriptional silencing. Aberrantly methylated DNA has also been proposed as a potential tumor marker. However, genes such as vimentin, which are transcriptionally silent in normal epithelium, have not until now been considered as targets for cancer-associated aberrant methylation and for use as cancer markers. We applied methylation-specific polymerase chain reaction to the vimentin gene, which is transcriptionally silent in normal colonocytes, and compared methylation of vimentin exon 1 in cancer tissues and in fecal DNA from colon cancer patients versus control samples from healthy subjects. Vimentin exon-1 sequences were unmethylated in 45 of 46 normal colon tissues. In contrast, vimentin exon-1 sequences were methylated in 83% (38 of 46) and 53% (57 of 107) of tumors from two independently collected groups of colon cancer patients. When evaluated as a marker for colon cancer detection in fecal DNA from another set of colon cancer patients, aberrant vimentin methylation was detected in fecal DNA from 43 of 94 patients, for a sensitivity of 46% (95% confidence interval [CI] = 35% to 56%). The sensitivity for detecting stage I and II cancers was 43% (26 of 60 case patients) (95% CI = 31% to 57%). Only 10% (20 of 198 case patients) of control fecal DNA samples from cancer-free individuals tested positive for vimentin methylation, for a specificity of 90% (95% CI = 85% to 94%). Aberrant methylation of exon-1 sequences within the nontranscribed vimentin gene is a novel molecular biomarker of colon cancer and can be successfully detected in fecal DNA to identify nearly half of individuals with colon cancer.

Insulin increase in colon cancerogenesis: a case-control study

Our aim was to establish whether individuals who develop colon cancer have elevated blood insulin concentrations. This was a case-control study in which 56 normoglycemic patients with colon cancer and a corresponding control group were investigated at the Clinical Hospital Split from April 1998 to April 1999. Data on age, weight, height, and sex of examinees were recorded and concentrations of glucose, insulin, and C-peptide were measured first in the morning before breakfast and again 90 min after breakfast. In the male group of colon cancer patients, we found statistically significant higher blood insulin concentrations 90 min after breakfast (median 34.7 mIU/L, range 3.3–162.6 mIU/L) in comparison to male control group (median 20.7 mIU/L, range 3.1–122.1 mIU/L) (p = 0.044). Concentration of C-peptide in blood 90 min after breakfast (median 3.28 nmol/L, range 0.38–6.1 nmol/L) was higher in the male group of colon cancer patients than in male control group (median 1.68 nmol/L, range 0.26–4.26 nmol/L) (p = 0.001). No difference was found in concentrations of insulin, C-peptide, and glucose in blood measured in the morning before breakfast between the male group of colon cancer patients and male control group. Ratio of insulin 90 min after breakfast with respect to insulin in the morning before breakfast was higher in the male group of colon cancer patients (median 4.65, range 0.83–22.1) than in male control group (median 1.78, range 0.38–8.75) (p = 0.005). Ratio of C-peptide 90 min after breakfast with respect to fasting C-peptide was higher in the male group of colon cancer patients (median 3.22, range 0.74–11.9) than in male control group (median 1.42, range 0.54–6.0) (p = 0.001). Women with colon cancer also had statistically significant higher ratio of insulin and C-peptide with respect to female control group. In the female group of colon cancer patients, median for ratio of C-peptide was 2.42 (range 0.43–8.87), while in female control group it was 1.19 (range 0.62–15.4) (p = 0.025). Median for ratio of insulin in the female group of colon cancer patients was 4.23 (range 0.25–8.54), while in female control group it was 1.17 (range 0.29–26.89) (p = 0.007). There was a higher increase of insulin 90 min after breakfast in the group of patients with colon cancer than in control group.

Insulin increase in colon cancerogenesis: a case-control study

Background Our aim was to establish whether individuals who develop colon cancer have elevated blood insulin concentrations. Methods This was a case-control study in which 56 normoglycemic patients with colon cancer and a corresponding control group were investigated at the Clinical Hospital Split from April 1998 to April 1999. Data on age, weight, height, and sex of examinees were recorded and concentrations of glucose, insulin, and C-peptide were measured first in the morning before breakfast and again 90 min after breakfast. Results In the male group of colon cancer patients, we found statistically significant higher blood insulin concentrations 90 min after breakfast (median 34.7 mIU/L, range 3.3–162.6 mIU/L) in comparison to male control group (median 20.7 mIU/L, range 3.1–122.1 mIU/L) ( p = 0.044). Concentration of C-peptide in blood 90 min after breakfast (median 3.28 nmol/L, range 0.38–6.1 nmol/L) was higher in the male group of colon cancer patients than in male control group (median 1.68 nmol/L, range 0.26–4.26 nmol/L) ( p = 0.001). No difference was found in concentrations of insulin, C-peptide, and glucose in blood measured in the morning before breakfast between the male group of colon cancer patients and male control group. Ratio of insulin 90 min after breakfast with respect to insulin in the morning before breakfast was higher in the male group of colon cancer patients (median 4.65, range 0.83–22.1) than in male control group (median 1.78, range 0.38–8.75) ( p = 0.005). Ratio of C-peptide 90 min after breakfast with respect to fasting C-peptide was higher in the male group of colon cancer patients (median 3.22, range 0.74–11.9) than in male control group (median 1.42, range 0.54–6.0) ( p = 0.001). Women with colon cancer also had statistically significant higher ratio of insulin and C-peptide with respect to female control group. In the female group of colon cancer patients, median for ratio of C-peptide was 2.42 (range 0.43–8.87), while in female control group it was 1.19 (range 0.62–15.4) ( p = 0.025). Median for ratio of insulin in the female group of colon cancer patients was 4.23 (range 0.25–8.54), while in female control group it was 1.17 (range 0.29–26.89) ( p = 0.007). Conclusions There was a higher increase of insulin 90 min after breakfast in the group of patients with colon cancer than in control group.

Mutation Detection in KRAS Exon 1 by Constant Denaturant Capillary Electrophoresis in 96 Parallel Capillaries

Mutations in KRAS exon 1 oncogene are frequently found in colon carcinomas. A correlation between the mutated KRAS and the prognosis and outcome of treatment of colon cancer patients was reported in the literature. The object of our work was to establish a high-throughput method with high sensitivity to enable screening of tumor mutation status of KRAS exon 1 in large groups of colon cancer patients. KRAS exon 1 sequences from DNA isolated from 191 sporadic colon cancers were PCR amplified using one primer labeled with fluorescein and a second primer extended by a GC-clamp. After PCR amplification samples were subjected to automated 96-array constant denaturant capillary electrophoresis using a modified MegaBACE 1000 sequencing instrument. Mutant samples were identified by characteristic peak patterns. The sensitivity of detection of a mutant allele in a background of the wild-type alleles was 0.3%. Using the 96-array instrument a typical screening of 191 samples for KRAS mutation status could be performed within 2 h. A KRAS exon 1 mutation was found in 66 of 191 (34.6%) of the samples. The 96-array constant denaturant capillary electrophoresis provides an opportunity for the high-sensitivity screening of large cancer populations for KRAS exon 1 mutations.

Metabolic response to chemotherapy in colon cancer patients.

The goal of this investigation was to identify the metabolic abnormalities in a group of colon cancer patients before and during 5-fluorouracil chemotherapy. Twenty-two colon cancer patients were prospectively enrolled into a Clinical Research Center for measurement of counter regulatory hormones, fasting hepatic glucose production (HGP), intravenous glucose tolerance test, plasma leucine appearance (LA), and leucine oxidation (LO). Both the cancer group and the normal volunteers were matched for nutrition status (109 +/- 5% of ideal body weight vs 104 +/- 4%, mean +/- SEM, respectively) and history of weight loss (6.3 +/- 2.6 kg vs 4.4 +/- 4.8). Plasma growth hormone was significantly elevated in the colon cancer patients (3.22 +/- 0.62 ng/mL vs 0.73 +/- 0.18, p < .05) despite the fact that insulin-like growth factor-1 levels were not different. Plasma glucose, insulin, cortisol, glucagon, epinephrine, and norepinephrine levels were not significantly different than those of the normal volunteers. Fasting HGP rates were slightly but not significantly elevated in the group of colon cancer patients compared with the normal volunteers (2.09 +/- 0.11 mg/kg per minute vs 1.79 +/- 0.10, p = .10). Plasma LA was not significantly elevated in the colon cancer group (63.3 +/- 3.0 mumol/kg per hour vs 57.7 +/- 4.2; p = .25). Five days of continuous 5-fluorouracil chemotherapy was associated with a significant elevation in both the fasting glucose level (97 +/- 3 mg/dL vs 106 +/- 5, p < .05), and HGP (2.09 +/- 0.11 mg/kg per minute vs 2.27 +/- 0.10; p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Soluble Fecal Acidic Lipids and Colorectal Epithelial Cell Proliferation in Normal Subjects and in Patients with Colon Cancer

Soluble fecal acidic lipid concentrations and colonic epithelial cell proliferation rates, two biologic markers for colon cancer, were compared in a group of colon cancer patients and a group of healthy controls. No significant difference was found in the concentration of bile acids (155 (136) microM, n = 33, versus 103 (89) microM, n = 19) in the aqueous phase of feces from patients and controls or in proliferation rates between the two groups, the volume density of tritiated thymidine-labeled epithelial cells being 0.153 (0.050), n = 8, for the patients and 0.164 (0.072), n = 11, for the controls. When the dietary intake of three food components known to influence both of the above factors (that is, fat, fiber, and calcium) was ascertained for the year preceding the study, the only significant difference observed was the higher calcium intake in the female patients than in the controls. The authors conclude that it may be premature to rely too heavily on either of the above markers to predict risk for developing this disease.

Significance of the labeling index and labeling distribution as kinetic parameters in colorectal mucosa of cancer patients and DMH treated animals.

To shed light on the more elevated labeling index (LI) found in the normal appearing mucosa of a group of colon cancer patients previously reported by Maskens and Deschner, the same data together with that from patients with an isolated adenoma, DMH treated CF1 mice and BD IX rats were analyzed on the basis of individual crypt values. One of 13 control patients had crypt values over 15% in contrast to 17 of the 26 cancer and polyp patients (P 15% revealed the Stage I defect in addition to an upward shift in the major zone of DNA synthesis from the lower to the middle and upper thirds of glands (Stage II abnormality), although both abnormalities were more emphatically expressed in glands with a high LI. Individual crypts in DMH treated mice had LI far higher than controls whereas no real differences in crypt LI were found between DMH treated rats and controls. Similar to colon cancer patients, both categories of crypts in DMH treated mice had the Stage I and II proliferative defects. Crypts in DMH treated rats, however, showed a downward shift of the major zone of DNA synthesis from the middle and upper third of glands. That DMH induces primarily microinvasive carcinomas in rats while in mice predominantly adenomas form, a proportion of which becomes malignant, would suggest a relationship between the direction of the shift of the major zone of proliferation and the type lesion induced. In man and mouse, hyperactive crypts would have a selective advantage over other glands allowing earlier expression of neoplastic transformation within them. Furthermore, their recognition as a marker along with the Stage II defect may be useful in tissues at high risk for colorectal tumorigenesis.

Serial CEA levels in colorectal carcinoma on adjuvant immuno (chemo) therapy.

Serial CEA levels have been studied preoperatively, and one day, 10--15 days, four months, and eight months after surgery in a group of colon cancer patients who started soon after surgery a protocol of adjuvant immuno(chemo)therapy with Levamisole R and BCG R. Results showed a decrease of mean values of plasma CEA levels from preoperatively to four months after surgery, while eight months after surgery a slight increase was noted. Some of the patients in whom disease recurred showed persistent high levels of CEA, while one patient was consistently a false-negative notwithstanding a bone recurrence. While the prognostic value of serial CEA determinations is confirmed, the possibility of restarting (or intensifying) a protocol of adjuvant immunochemotherapy given high CEA levels and a negative clinical picture is discussed.