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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The conventional and accepted treatment for curative resection of colon cancer is laparotomy with hemicolectomy for right or left sided lesions. The technique of colon resection through an open laparotomy incision is well known. Over the past several years, laparoscopically assisted colectomy has been developed and studied, following the explosion of laparoscopic technology from the cholecystectomy experience and with acquisition of advanced general laparoscopic techniques. The right, left or sigmoid colon can be mobilized and regional lymphadenectomy performed using laparoscopic instruments and video-imaging equipment. The advantage of laparoscopic colectomy is the use of small abdominal port site and wound incisions which translate to reduced postoperative pain and analgesic requirement, earlier return of bowel function and normal physical activities, and shorter hospital stay without increasing health care costs. Laparoscopic colectomy compares favorably with open colectomy in terms of surgical morbidity and mortality. The laparoscopic approach has been shown to be technically and oncologically feasible with equivalent lymph node harvest from mesenteric lymphadenectomy and achieves adequate proximal and distal margins of colonic resection. Despite initial early anecdotal reports of port site cancer recurrence in laparoscopically assisted colectomy, port site recurrence is rare and its incidence is similar to incisional recurrences in conventional open colectomy. Recent prospective comparative studies have demonstrated equivalent patient survival and equivalent local or distant colon cancer recurrences for open versus laparoscopic curative resection of colon cancer.
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PMID:Laparoscopic colectomy for cancer: an oncologic feasible option. 1135 41

Colon cancer (CC) is one of the most common malignancies in the Western world. Although surgical resection is the first choice worldwide, at this point an effective approach for the treatment of patients with metastasis and cancer recurrence post-operation has not yet been found. The aim of this study was to investigate the role of the allogeneic dendritomas from fusion of dendritic cells (DC) and metastatic CC cells in the activation of anti-tumour immunity against metastatic CC. Dendritomas were generated by fused allogeneic human peripheral blood DC with metastatic CC cells using 50% polyethylene glycol. The proliferation of the T cells and the toxicity of the cytotoxic T lymphocytes were observed after T cell pulsed with allogeneic dendritomas. The activated ratios of CD4+T helper 1 and CD8+Tc1 cells were about 51.55 and 65.60% after T cells were mixed with fusions for 24 h, which higher than those of controls. The proliferation of T cells were significantly higher than those of control after T cell pulsed with dendritomas (P < 0.01). Significantly, the activated CD8+ T lymphocytes effectively lysed the CC cells. These results demonstrate that allogeneic dendritomas activate T-cell responses against metastatic CC cells.
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PMID:Allogeneic dendritomas induce anti-tumour immunity against metastatic colon cancer. 1585 20

A surrogate endpoint is an endpoint that is observed before a true endpoint and is used to draw conclusions about the effect of intervention on true endpoint. To gauge confidence in the use of a surrogate endpoint, it must be validated. Two simple validation methods using data from multiple trials with surrogate and true endpoints are discussed: an estimation method extending previous work and new method based on hypothesis tests. The validation methods were applied to two data sets, each involving 10 randomized trials: one for patients with early colon cancer where the true endpoint was survival status at eight years and surrogate endpoint was cancer recurrence status at three years, and one for patients with advanced colorectal cancer where the true endpoint was survival status at 12 months and the surrogate endpoint was cancer recurrence status at six months. The estimation method uses the surrogate endpoint in the new trial and a model relating surrogate and true endpoints in previous trials to predict the effect of intervention on true endpoint in the new trial. For validation, each trial was successively treated as the ;new' trial and a comparison was made between predicted and observed effects of intervention on true endpoint. Performance of the surrogate endpoint was good in both data sets. The hypothesis testing method involves the z-statistic for the surrogate endpoint, which is the estimated effect of intervention on surrogate endpoint divided by its standard error. To use this z-statistic to test a null hypothesis of no effect of intervention on true endpoint, the critical value is increased above a standard level of 1.96 to a level determined by the relationships between surrogate and true endpoints in the data sets. This elevated critical value could be used for accelerated approval.
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PMID:Two simple approaches for validating a binary surrogate endpoint using data from multiple trials. 1828 36

The last two decades have seen a lot of development in the area of surrogate marker validation. One of these approaches places the evaluation in a meta-analytic framework, leading to definitions in terms of trial- and individual-level association. A drawback of this methodology is that different settings have led to different measures at the individual level. Using information theory, Alonso et al. proposed a unified framework, leading to a new definition of surrogacy, which offers interpretational advantages and is applicable in a wide range of situations. In this work, we illustrate how this information-theoretic approach can be used to evaluate surrogacy when both endpoints are of a time-to-event type. Two meta-analyses, in early and advanced colon cancer, respectively, are then used to evaluate the performance of time to cancer recurrence as a surrogate for overall survival.
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PMID:Evaluating time to cancer recurrence as a surrogate marker for survival from an information theory perspective. 1828 43

We report two cases of recurrent colorectal cancer in two patients who were treated successfully with a combined oral chemotherapeutic agent folinate/tegafur/uracil (UFT/LV) dosage. The first case was a 74-year-old woman who underwent Hartmann operation for colon cancer perforation. One year and 7 months after surgery, a local recurrence was found on the CT scan and endoscopy. It ended in exploratory laparotomy though we were operated on. Chemotherapy using 5-fluorouracil/Leucovorin (5-FU/LV) was performed six times. Sequentially, UFT/LV internal use was managed at our outpatient clinic. This patient has been living without side effects in the first three postoperative years, and without increase in tumors. The second case was a 65-year-old woman who underwent abdominoperineal resection of the rectum for rectal cancer. The histologic stage of disease aggravation of the patient was stageI. Post operatively, 2 years and 6 months later, we recognized a metastasis node on the lung upper right lobe of the patient and her CA19-9 value climbed dramatically. The patient took UFT/LV during outpatient visits to the hospital, the lung node shadow disappeared two months later, and CA19-9 decreased, too. The patient is living without a cancer recurrence now. UFT/LV treatment is one of the effective modalities against recurrence of colorectal cancer from outpatient treatment while maintaining QOL.
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PMID:[Two cases of recurrent colorectal cancer treated successfully with folinate/tegafur/uracil (UFT/LV) chemotherapy on an outpatient basis]. 1840 40

Survival rates from colorectal cancer (CRC) differ dramatically according to the stage of the tumor at diagnosis, with survival rates of 90% for patients with stage I disease but only 49% for those with stage III cancer. Many serum and tumor markers have been identified but none has provided a significant improvement over tumor stage as a prognostic indicator for cancer recurrence for patients with stage II or III disease. Aberrant activation of the hepatocyte growth factor (HGF)/HGF receptor (MET) signaling pathway is associated with both malignant transformation and metastatic potential of CRC. MACC1 (metastasis-associated in colon cancer-1) is a newly discovered gene that regulates this signaling cascade. The significant correlation between overexpression of MACC1 in CRC and both malignant transformation and subsequent risk for metastases in stage II and III CRC indicates that MACC1 tumor typing may prove valuable for determining risk for CRC recurrence. MACC1 may also be an important therapeutic target for CRC treatment.
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PMID:Overexpression of MACC1 leads to downstream activation of HGF/MET and potentiates metastasis and recurrence of colorectal cancer. 1934 7

It may be important that a sufficient number of lymph nodes are removed and examined at the time of resection for colon and rectal cancers. More extensive nodal resection has been associated with lower rates of cancer recurrence; allows for more accurate cancer staging and thus, more appropriate use of adjuvant chemotherapy for node-positive patients; and has been associated with improved survival following resection for colon and rectal cancers. Many factors affect the number of lymph nodes examined, including extent of surgical resection, patient age, tumor location, and pathology techniques. A 12-node minimum has been endorsed as a consensus standard for hospital-based performance with colectomy for colon cancer. However, using the number of lymph nodes examined on a hospital level may not significantly influence staging, use of adjuvant chemotherapy, or patient survival. For rectal cancer, the increasing emphasis on adequate circumferential radial margins and use of preoperative radiotherapy for intermediateand high-risk tumors may complicate assessment of the relationship between number of lymph nodes examined and patient outcomes; data suggest that the number of lymph nodes (total and number positive) in a rectal specimen is significantly lower following administration of preoperative radiotherapy. While there remains little controversy about the prognostic importance of higher lymph node counts for individual patients, it is not clear that node counts are useful indicators of hospital quality.
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PMID:Lymph node counts and survival rates after resection for colon and rectal cancer. 1946 21

CD133 has been postulated to be a colon cancer stem cell (CSCs) marker. Recent investigations suggest that CSCs might contribute to cancer recurrence and resistance to conventional therapies. This study aimed to evaluate the role of CD133 in residual cancer cells after chemoradiotherapy (CRT) for rectal cancer. Forty patients with rectal cancer underwent CRT followed by surgery. Total RNAs of rectal cancer cells before (n=30) and after (n=40) CRT were isolated. Intratumoral CD133, vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) levels were measured using real-time reverse transcription polymerase chain reaction. Immunohistochemical staining of CD133 after CRT was also investigated. CD133 in residual cancer cells was higher than in stromal cells in post-CRT specimens (p<0.0001). The levels of CD133 were found to have increased in post-CRT specimens (p=0.0184), while VEGF and EGFR levels decreased during CRT (p<0.0001 and p=0.0002, respectively). Patients who developed distant recurrence had a higher post-CRT CD133 compared with those patients without recurrence (p=0.0136). Elevated post-CRT CD133 was associated with poor disease-free survival (p=0.0168). Immunohistochemical staining of the cytoplasmic and apical/endoluminal membranous CD133 was observed in residual cancer cells after CRT. CD133 expression in residual cancer cells after CRT may indicate a treatment resistant phenotype in putative CSCs. Elevated CD133, but not VEGF or EGFR, on FFPE specimens may be a predictive marker of distant recurrence and poor survival after preoperative CRT in rectal cancer.
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PMID:Elevated CD133, but not VEGF or EGFR, as a predictive marker of distant recurrence after preoperative chemoradiotherapy in rectal cancer. 1972 47

Somatic stem cells reside at the base of the crypts throughout the colonic mucosa. These cells are essential for the normal regeneration of the colonic epithelium. The stem cells reside within a special 'niche' comprised of intestinal sub-epithelial myofibroblasts that tightly control their function. It has been postulated that mutations within these adult colonic stem cells may induce neoplastic changes. Such cells can then dissociate from the epithelium and travel into the mesenchyme and thus form invasive cancers. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumour. It is this group of cells that exhibits characteristics of colonic stem cells. Although anti-neoplastic agents can induce remissions by inhibiting cell division, the stem cells appear to be remarkably resistant to both standard chemotherapy and radiotherapy. These stem cells may therefore persist after treatment and form the nucleus for cancer recurrence. Hence, future treatment modalities should focus specifically on controlling the cancer stem cells. In this review, we discuss the biology of normal and malignant colonic stem cells.
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PMID:Colorectal cancer stem cells. 1987 63

Curcumin (diferuloylmethane), which has no discernible toxicity, inhibits initiation, promotion and progression of carcinogenesis. 5-Fluorouracil (5-FU) or 5-FU plus oxaliplatin (FOLFOX) remains the backbone of colorectal cancer chemotherapeutics, but produces an incomplete response resulting in survival of cells (chemo-surviving cells) that may lead to cancer recurrence. The present investigation was, therefore, undertaken to examine whether addition of curcumin to FOLFOX is a superior therapeutic strategy for chemo-surviving cells. Forty-eight-hour treatment of colon cancer HCT-116 and HT-29 cells with FOLFOX resulted in 60-70% survival, accompanied by a marked activation of insulin like growth factor-1 receptor (IGF-1R) and minor to moderate increase in epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (HER-2) as well as v-akt murine thymoma viral oncogene homolog 1 (AKT), cyclooxygenase-2 (COX-2) and cyclin-D1. However, inclusion of curcumin to continued FOLFOX treatment for another 48 h greatly reduced the survival of these cells, accompanied by a concomitant reduction in activation of EGFR, HER-2, IGF-1R and AKT, as well as expression of COX-2 and cyclin-D1. More importantly, EGFR tyrosine kinase inhibitor gefitinib or attenuation of IGF-1R expression by the corresponding si-RNA caused a 30-60% growth inhibition of chemo-surviving HCT-116 cells. However, curcumin alone was found to be more effective than both gefitinib and IGF-1R si-RNA mediated growth inhibition of chemo-surviving HCT-116 cells and addition of FOLFOX to curcumin did not increase the growth inhibitory effect of curcumin. Our data suggest that inclusion of curcumin in conventional chemotherapeutic regimens could be an effective strategy to prevent the emergence of chemoresistant colon cancer cells.
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PMID:Curcumin targets FOLFOX-surviving colon cancer cells via inhibition of EGFRs and IGF-1R. 2033 35


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