Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Esophageal cancer is an important problem in the United States. It results in more deaths (over 10,000 annually) than rectal cancer. Furthermore, the incidence of esophageal adenocarcinoma is increasing at a rate faster than that of nearly any other cancer and the reasons for the increase are not well understood. A variety of tumor-suppressor genes (including p53, APC, DCC and Rb) and proto-oncogenes (including prad1, EGFR, c-erb-2 and TGF alpha) may be involved in the development and progression of esophageal cancer. Clinical prognostic factors include stage, Karnofsky performance status, sex, age, anatomic location of the tumor, and degree of weight loss. A new staging system based on depth of wall penetration and lymph node involvement correlates well with prognosis for patients undergoing esophagectomy. Newer staging procedures including endoscopic ultrasound as well as the use of minimally invasive surgery, such as thoracoscopy and laparoscopy, may allow accurate staging without esophagectomy. Surgical resection provides excellent palliation; however, the chance for cure with esophagectomy alone is only 10% to 20%. Adjuvant treatment with pre- or postesophagectomy radiation may improve local-regional control but does not improve survival. Nor has preoperative chemotherapy been shown to improve survival; however, it remains an active area of investigation. Multimodality therapy, namely, chemotherapy and radiation (chemoradiation), given concurrently prior to surgical resection shows promise, with one study indicating a 5-year survival of 34%. A complete pathologic response to chemoradiation correlates with improved survival. Chemoradiation has been shown to be superior to radiation as primary management of esophageal cancer. There has been no successfully completed randomized trial of surgery versus definitive radiation or chemoradiation. However, chemoradiation represents a reasonable alternative to esophagectomy in the primary management of squamous cell carcinoma of the esophagus and chemoradiation also appears to be effective in the treatment of patients with adenocarcinoma of the esophagus, offering significant palliation and a chance for long-term survival as well. Randomized studies of preoperative chemoradiation versus surgery or versus chemoradiation alone are needed. The treatment of advanced esophageal cancer must be directed toward palliation of symptoms. Newer endoscopic techniques, including the use of expansile metal stents, laser ablation, intraluminal high-dose rate brachytherapy, BICAP tumor probe, or photodynamic therapy, offer selected patients short-term palliation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Esophageal cancer. 753 69

We present the clinical and laboratory findings in an institutionalised adult patient originally referred for autism. A high risk of colorectal cancer was predicted when an interstitial deletion of the long arm of chromosome 5, del(5)(q15q22.3), was detected in her lymphocytes and deletion of the MCC and APC genes confirmed by molecular analysis. Adenomatous polyposis coli and carcinoma of the rectum were subsequently diagnosed in the patient. She was profoundly mentally retarded, autistic, and had minor dysmorphic features consistent with those of previous patients with similar deletions. The deletion arose as a result of recombination within the small insertion loop formed at meiosis by the direct insertion (dir ins(5)(q22.3q14.2q15)) found in the patient's mother. This family further confirms the cytogenetic mapping of both MCC and APC genes to 5q22 and comparison with other recent cases suggests that both genes and their closely linked markers lie within the 5q22.1 subband.
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PMID:Adenomatous polyposis coli and a cytogenetic deletion of chromosome 5 resulting from a maternal intrachromosomal insertion. 807 57

Familial juvenile polyposis has been known to have malignant potential, but their genetic relation to familial adenomatous polyposis has not been proven yet. Two young brothers with intermittent rectal bleeding revealed multiple juvenile polyposis. Their father had a history of rectal cancer with multiple colonic polyps. Four frequent exons of APC gene mutation were tested from these patients' white blood cells by polyacrylamide gel electrophoresis and sequencing. The 21-yr-old brother had a missense mutation (GAA-->GGA) at codon 1309, whereas the 18-yr-old brother showed a missense mutation (ATA-->GTA) at codon 1304 in exon 15 of APC gene. Three of four first-degree relatives were affected with familial juvenile polyposis, familial juvenile polyposis with adenomatous change, and rectal cancer with multiple polyps. The APC gene mutation of familial juvenile polyposis in this case suggests a genetic relationship with familial adenomatous polyposis.
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PMID:Familial juvenile polyposis coli with APC gene mutation. 938 65

Evolving trends in the management of rectal cancer have focused on organ preservation, improved quality of life, and survival of patients. A significant shift is underway in our thinking about what constitutes the true rectum and defining the "proximal" and "distal" segments of the rectum. Tumor mobility remains a dominant prognostic factor in patient selection and choice of surgery. A clinical staging with tumor location in the rectum provides a logical algorithm for treatment decision making with either chemoradiation therapy or surgery as initial treatment of choice. Current rectal cancer management has largely focused on postoperative adjuvant radiation strategies with improvement reported for T3 and N+ cases. Recent data from Europe suggests that preoperative radiation has a significant advantage over surgery alone or postoperative treatment. This appears to be borne out by institutional studies of high-dose preoperative radiation (>45 Gy) in the United States. Aggressive preoperative combined chemoradiation has also led to significant downstaging of cancer with pathological complete response rates of 20% to 30%. This offers new options for surgical management of residual disease with endocavitary radiation or local excision. The development of new agents Gemcitabine, paclitaxel, and CPT-11 may also prove beneficial. New treatment strategies need to be coordinated with evolving knowledge of the biological behavior of the tumor based on its genetic fingerprints. c-Ki-ras and C-myc mutations have been implicated in tumor initiation and progression. A number of other tumor suppressor genes, APC gene, p53, and DCC have also been implicated in colorectal tumor carcigenesis. The modification of biological behavior by mutations in these genes is currently under study. This may guide new treatment strategies significantly reducing the death rates from rectal cancer and improving functional results of treatment.
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PMID:Critical issues in the evolving management of rectal cancer. 942 68

A 37-year-old man was diagnosed as having a rectal cancer with familial adenomatous polyposis, with the mutation of APC gene, and gastric polyposis, hypertrophy of the retinal pigment epithelium and a lipoma of the left arm. The patient underwent a total colectomy for the rectal cancer and a partial resection of the liver for metastasis (S3) which was detected on laparotomy, followed by cannulation in the hepatic artery. After the operation, 5-FU alone and low doses of CDDP and 5-FU were administered, but the level of serum CEA elevated and CT scanning showed multiple liver metastases. Then, low doses of leucovorin (30 mg/body bolus) and 5-FU (500 mg/body/h) were injected through an injection port every week. After 6 months, the level of serum CEA reduced and CT scanning showed minor response (about 30% on the decrease rate), without side effects, including diarrhea, stomatitis and bone marrow suppression.
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PMID:[A case of hepatic metastasis of rectal cancer with familial adenomatous polyposis treated by transarterial administration of low-dose leucovorin and 5-FU]. 949 38

Restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) is considered the operative therapy of choice for the prophylactic treatment of FAP. Recently, Vasen and coworkers [5] after correlating the incidence of metachronous rectal cancer with the site of the causative APC mutation suggested subtotal colectomy and IRA to be the primary treatment in patients with mutations proximal to codon 1250, whereas IPAA should be performed in those with mutations beyond this codon. Mutation analysis in our patients after IRA, however, shows the majority of APC mutations to be located proximal to codon 1250 even in those patients with severe rectal polyposis and metachronous rectal cancer, thus not supporting the therapeutic recommendations of Vasen and coworkers.
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PMID:[Mutation localization as a guide for surgical approach in familial adenomatous polyposis?]. 993 13

Hereditary non-polyposis colorectal cancer (HNPCC) is characterized by familial clustering and early onset. It is unclear, however, whether the early onset of colorectal cancer necessarily represents HNPCC. A 13-year-old patient had rectal cancer and underwent curative surgery. DNA from this patient was examined for replication errors (RER) and genes related to familial colorectal cancer (APC, hMSH2, and hMLH1). The patient had a negative family history of colorectal cancer, did not show the RER phenotype, and had no germline mutation of the APC, hMSH2, and hMLH1 genes. The present case suggests that an unusually young patient with colorectal cancer is not always an HNPCC proband. Observation over time, however, will be needed, as a first mutator of familial colorectal cancer could be missed.
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PMID:Rectal cancer in a 13-year-old boy without a detectable germline mutation in FAP and HNPCC genes. 1043 9

Increased transcriptional activation through beta-catenin stabilization plays a central role in colorectal tumorigenesis. Alterations of phosphorylation sites within the CTNNB1 gene, which codes for beta-catenin has been reported to occur in about one-half of colorectal tumors without APC-gene mutations. We assessed the importance of mutations in the regulatory domain, located within exon 3 of CTNNB1, in 103 rectal carcinomas and correlated these data with presence of microsatellite instability, somatic frame-shift alterations of the TCF-4 gene, and APC-gene mutations in the tumors. No mutation was detected in exon 3 of the CTNNB1 gene and our results thus demonstrate that beta-catenin activation through mutation rarely contributes to the development of sporadic and microsatellite instability stable rectal cancer.
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PMID:Beta-catenin activation through mutation is rare in rectal cancer. 1145 29

Observations support the theory that development of left- and right-sided colorectal cancers may involve different mechanisms. This study investigated different genes involved in oncogenesis of colon and rectal cancers and analysed their prognostic value. The study group comprised 35 colon and 42 rectal cancers. Rectal cancer patients had been treated with standardized surgery performed by an experienced rectal cancer surgeon. Mutation analysis was performed for p53 in eight colon cancers and for APC and p53 in 22 rectal cancers. MLH1, MSH2, Bcl-2, p53, E-cadherin and beta-catenin were investigated by immunohistochemistry in all colorectal tumours. APC mutation analysis of the MCR showed truncating mutations in 18 of 22 rectal tumours (82%), but the presence of an APC mutation was not related to nuclear beta-catenin expression (p=0.75). Rectal cancers showed significantly more nuclear beta-catenin than colon cancers (65% versus 40%, p=0.04). p53 mutation analysis corresponded well with p53 immunohistochemistry (p<0.001). Rectal cancers showed significantly more immunohistochemical expression of p53 than colon cancers (64% versus 29%, p=0.003). In rectal cancers, a significant correlation was found between positive p53 expression and worse disease-free survival (p=0.008), but not in colon cancers. Cox regression showed that p53-expression (p=0.03) was an independent predictor for disease-free survival in rectal cancers. This study concluded that rectal cancer may involve more nuclear beta-catenin in the APC/beta-catenin pathway than colon cancer and/or nuclear beta-catenin may have another role in rectal cancer independently of APC. The p53-pathway seems to be more important in rectal cancer, in which it also has independent prognostic value. When prognostic markers are investigated in larger series, differences in biological behaviour between colon and rectal cancer should be considered.
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PMID:Mechanisms of oncogenesis in colon versus rectal cancer. 1159 95

The I1307K APC germline mutation is associated with an increased risk to colo-rectal cancer (CRC). Whether and to what extent the phenotype of CRC in mutation carriers differs from sporadic cases, remains unknown. To gain insight into this issue, we analysed 307 unselected Israeli patients with CRC, who were treated in a single medical centre, for harbouring the I1307K mutation. Twenty-eight mutation carriers (9.1%) were detected. Two of 28 mutation carriers (7.1%) and 93/277 (33.6%) of non-carriers, were of non-Ashkenazi origin (P < 0.01). In 74/278 (26.6%) of the sporadic cases, and only 1/28 (3.6%) of mutation carriers (3.6%) the tumour was located in the right colon (P < 0.01). Mutation carriers had a more advanced disease stage (14/28 - 50% Dukes C), as compared with 60 (19.5%) of non-carriers (P = 0.02). The mean age at diagnosis was similar: 65 (+/- 9.7) years and 66.3 (+/- 11.6) years, for mutation carriers and non-carriers, respectively. No statistical differences were noted between the two groups in sex distribution, tumour grade, and family history of cancer. We conclude that early age at diagnosis and family history of cancer cannot be used to predict who is likely to harbour the I1307K APC germline mutation carriers. However, the tumours in patients with this mutation appear different than those without, are less likely to be proximal and more likely to be advanced than tumours in non-carriers.
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PMID:Phenotypic characteristics of colo-rectal cancer in I1307K APC germline mutation carriers compared with sporadic cases. 1172 Apr 76


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