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)

Most adenocarcinomas of the colorectum arise in a visible benign precursor lesion, the adenoma, which is a monoclonal proliferation of dysplastic nonmalignant epithelial cells. The resultant adenoma-adenocarcinoma sequence represents the predominant pathogenetic pathway, in contrast to de novo carcinoma. Therefore, the adenoma is a tempting endpoint for chemoprevention trials. The adenoma-adenocarcinoma sequence occurs in diverse clinical settings. In familial adenomatous polyposis (FAP) syndrome, autosomal dominant inheritance of the mutated APC (adenomatous polyposis coli) gene on chromosome 5q21 typically results in thousands of adenomas in the colorectum and in lesser numbers in the proximal small bowel. Adenocarcinoma usually develops in only a few of these adenomas, typically in the left colon and duodenum. In hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, autosomal dominant inheritance of an unidentified gene appears to result in small numbers of adenomas which progress frequently to adenocarcinoma, predominantly in the right or transverse colon. In familial aggregation of colorectal cancer without a recognizable syndrome, cancer and/or adenomas occur in pedigree members. In "sporadic" cancers and adenomas, family history is absent and the tumors are mainly in the left colon. Colorectal adenomas have variable characteristics including size, shape (polypoid vs. flat), villous architecture, and dysplasia. A variety of oncogenes and tumor suppressor genes are altered during progression. Epigenetic factors are important as evidenced by the disappearance of adenomas in FAP patients after ileorectal anastomosis or treatment with the nonsteroidal antiinflammatory drug sulindac. Several variations on the theme of the adenoma-carcinoma sequence are evident. Identification of the inherited and acquired genetic alterations as well as the interacting environmental factors will provide a rational basis for chemoprevention.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The adenoma-adenocarcinoma sequence in the large bowel: variations on a theme. 133 99

Uterine papillary serous carcinoma (UPSC) is an aggressive malignancy that accounts for a disproportionate number of intraabdominal failures among endometrial carcinoma patients. The histologic appearance and tendency toward intraabdominal spread resemble those of papillary serous adenocarcinoma of the ovary. Because approximately 70% of untreated ovarian carcinoma patients respond to platinum-based chemotherapy, it has been suggested that UPSC patients might respond to similar treatment regimens. Twenty patients with UPSC were treated with cisplatin, doxorubicin (Adriamycin), cyclophosphamide (PAC) chemotherapy between January 1982 and December 1989. They included 9 patients with advanced primary disease, 5 with recurrence, and 6 who received PAC as adjuvant therapy. Patients received a mean of five cycles of PAC. Only 2 of 11 patients with measurable disease greater than 2 cm achieved complete clinical responses of 12 and 31 months duration; there were no partial responses. Actuarial 5-year survival for all patients was 23%. The mean progression-free interval was 9 months. Patients with clinical stages I or II disease had a higher survival rate than those with stage III or IV disease (P = 0.003). Survival did not correlate with depth of myometrial invasion (P = 0.81) or size of residual tumor following initial surgery (P = 0.16). Estrogen or progesterone receptors were detected in 10 of 11 tumors tested. Seven of 9 patients tested had elevated serum levels of CA-125 (greater than 35 U/ml). Correlation between CA-125 value and clinical course was demonstrated in 3 of 5 patients who had serial measurements. Of all patients, 3 are currently alive; 1 has documented disease. Moderate to severe toxicity was seen in 14 patients (70%). There was one possible treatment-related death from cardiomyopathy. UPSC, despite its histologic and clinical similarities to ovarian carcinoma, was relatively resistant to PAC chemotherapy in this mixed group of patients.
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PMID:Uterine papillary serous carcinoma (UPSC) treated with cisplatin, doxorubicin, and cyclophosphamide (PAC). 152 8

Thirty patients with adenocarcinoma of the fallopian tube, treated between 1950 and 1981, were studied. Median age was 55 years, and mean parity was 1.3. Bleeding or discharge occurred as a presenting complaint in 47% of patients, abdominal distention or mass in 50%, and pain in 30%. Lesions were staged using a system analogous to the International Federation of Gynecology and Obstetrics (FIGO) classification for ovarian carcinoma. Nine patients had Stage I disease; 11, Stage II; 7, Stage III; and 3, Stage IV. Histologic differentiation was Grade 1 in 39% of the patients, Grade 2 in 18%, and Grade 3 in 43%. Primary surgical treatment consisted of total abdominal hysterectomy and bilateral salpingectomy in 70% of the patients; 23% had more extensive surgery, whereas 13% had less extensive surgery. Three patients with Stage I tumors were treated with surgery alone, and the remainder received postoperative radiation, chemotherapy, or both. Survival was unrelated to grade, but highly dependent upon stage. Survival at 5 years was 56% for Stage I, 27% for Stage II, 14% for Stage III, and 0% for Stage IV. Four of five patients treated after surgery with a combination of cisplatin, doxorubicin, and cyclophosphamide (PAC) survived at least 3 years. Patterns of initial treatment failure showed 56% with a component of pelvic failure, 50% with a component of upper abdominal failure, and 44% with extraperitoneal metastases as a component of failure. These results suggest the need for aggressive postoperative adjuvant therapy targeted at upper abdominal and distant sites for metastasis in all lesions beyond Stage I.
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PMID:Carcinoma of the fallopian tube. Management and sites of failure. 375 22

A patient with stage I fallopian tube adenocarcinoma had disease recurrence in both lungs shortly after completing adjuvant therapy with intraperitoneal 32P and parenteral cyclophosphamide. She achieved a complete clinical response to cisplatin, Adriamycin, and cyclophosphamide (PAC) chemotherapy, but was subsequently found to have brain metastasis. The implications of these observations for understanding the natural history and optimal therapy of this disease are discussed.
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PMID:Adenocarcinoma of the fallopian tube: report of a case with an unusual pattern of metastasis and response to combination chemotherapy. 654 33

Murine strains which bear constitutive inactivating mutations of either the APC or the p53 tumor suppressor genes are characterised by spontaneous tumors. APC mutated (Min) mice develop large and small bowel adenomas, a small proportion of which, in time, become malignant. p53 deficient mice develop predominantly lymphoma and sarcoma. By interbreeding these strains we have shown that there is co-operativity between these mutations, leading to a shift in phenotype. Most notably, this was characterised by a range of abnormalities of the exocrine pancreas in 83% of animals heterozygous for the APC mutation and constitutively null for functional p53. Dysplasia and preneoplastic foci were seen in 61% of these animals and pancreatic acinar cell adenocarcinoma in 22%. Analysis of these tumors showed them to have lost the remaining wild-type copy of APC. Similar loss of APC was not associated with the development of other extra-intestinal tumors. Surprisingly, given the proposed role for loss of function mutations of the p53 gene in the development of human colorectal cancer, we have found no evidence for either an increase in the rate of adenoma formation in APC +/-, p53 -/- animals, or an increased rate of progression to malignancy compared with APC +/- p53 +/+ mice. These findings highlight striking tissue-specific differences in the tumor suppressor effects of p53.
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PMID:Interaction between murine germline mutations in p53 and APC predisposes to pancreatic neoplasia but not to increased intestinal malignancy. 747 22

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

Frequent loss of heterozygosity in ovarian carcinoma (OC) has been reported on several different chromosomes. We have studied 27 OCs and corresponding normal tissue for loss of heterozygosity (LOH) using 10 markers detecting polymorphisms on chromosome 5 (two on 5p and eight on 5q). Three tumours showed extra copies, rather than loss, of one homologue. Twelve of 24 remaining tumours showed LOH on 5q (50%), and 8 of 21 on 5p (38%). Of the 12 showing LOH on 5q, 7 showed reduction to homozygosity at all informative markers over the chromosome. The remaining 5 showed LOH over all of 5q. These data are consistent with the localisation of a tumour suppressor gene on 5q involved in OC. A good candidate is the APC gene, which is mutated in a number of adenocarcinoma derived from several tissues and is located at 5q21-22. The APC gene was studied in 40 ovarian tumours, including all the OCs showing LOH, by single-strand conformation polymorphism (SSCP). Analysis of all the exons containing published mutations (approximately 4.7 kb of the cDNA) did not reveal any band shifts that could be attributed to mutations. However, a new polymorphism was detected, as well as 7 known polymorphisms. Together, these data indicate that (1) LOH is common on chromosome 5 in OC, (2) APC is not mutated in OC, and (3) another gene (or genes) on chromosome 5q is responsible for the LOH seen.
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PMID:Loss of heterozygosity on chromosome 5 in sporadic ovarian carcinoma is a late event and is not associated with mutations in APC at 5q21-22. 801 64

Genetic and environmental aspects play an important role in the development of colorectal cancer. However, the common molecular alteration in both hereditary and sporadic colon cancer is localized in the APC gene. the APC gene maps in the long arm of chromosome 5 and was discovered in patients with familial adenomatous polyposis (FAP). The search for the APC gene led to the identification of restriction fragment length polymorphisms (RFLPs) in FAP patients. Using these RFLPs in relatives of FAP patients it is possible to make the presymptomatic and prenatal diagnosis. The FAP syndrome is an interesting model of carcinogenesis in vivo. Thus the different stages involved in the FAP syndrome which include hyperproliferative epithelium, adenoma, adenocarcinoma and metastases, have allowed the analysis of molecular alterations in oncogenes and tumor suppressor genes. The APC gene alteration if not inherited, occurs as the earliest molecular alteration in the development of colorectal cancer whereas structural alterations of the genes myc, ras, p53, MCC and DCC are considered to be late events. All these investigations have lead to 1) a better understanding of the ethiology of cancer and 2) early diagnosis of colorectal cancer in both the hereditary and sporadic forms of the disease.
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PMID:[Molecular genetics of colorectal cancer and carcinogenesis]. 813 31

Knowledge of the patterns of allelic loss has been useful in identifying the spectrum of the tumor suppressor genes involved in various tumor types. Such analyses in pancreatic carcinoma have been difficult due to the characteristic host desmoplastic reaction to the neoplasm. We have assembled the first allelotype of pancreatic adenocarcinoma, a survey for allelic loss among each chromosomal arm, using seven cryostat-dissected neoplasms. The fractional allelic loss in these seven neoplasms was 0.18, a value similar to that seen previously in colorectal carcinoma. Alleles of chromosome 18q (lost in five of six informative tumors) and of chromosome 17p (lost in four of five informative tumors) were commonly affected. Neither APC mutations (33 neoplasms), allelic shifts of dinucleotide repeats (26 neoplasms), nor immunohistochemical evidence of retinoblastoma protein underexpression (7 neoplasms) were found. Further evaluation of allelic loss in pancreatic cancer would benefit from improved methods for the analysis of lost genetic material which overcome the problems posed by the high admixture of nonneoplastic stromal and inflammatory cells in these tumors.
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PMID:Allelotype of pancreatic adenocarcinoma. 816 8

We have examined whether alterations of simple (CA)n DNA repeats, as observed in human colon cancers, occur during human gastric carcinogenesis and whether such alterations reflect genomic instability that could lead to other genetic changes. A total of 22 gastric cancer samples were analyzed: 15 well or moderately differentiated adenocarcinomas, 6 signet-ring cell carcinomas, and 1 poorly differentiated adenocarcinoma. When (CA)n repeat sequences were examined at 10 loci, one adenocarcinoma showed a loss of repeat sequences at five loci, three adenocarcinomas gained a repeat at one locus, and one adenocarcinoma had new, repeated sequences at five loci. Three samples showed mutations in the p53 gene, two in exon 5 (both GC to AT transition at a CpG dinucleotide) and one in exon 7 (AT to GC transition). Only one sample with a p53 mutation also showed altered (CA)n repeats. A putative tumor suppressor gene, connexin 32, was not altered as assessed by single-strand conformation polymorphism analysis. These results suggest that genomic instability revealed by (CA)n repeat changes does not seem to contribute to induction of point mutations in p53 or connexin 32 genes but may participate in loss of heterozygosity at APC/MCC loci. The results are consistent with the hypothesis that different mechanisms are involved in the gain and loss of (CA)n repeats.
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PMID:Alterations of (CA)n DNA repeats and tumor suppressor genes in human gastric cancer. 826 59


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