Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic alterations of various cancers have been clarified by recent development of molecular biology. Multiple genetic alterations occur through the development of cancer. Both activation of proto-oncogenes and inactivation of tumor suppressor genes are important for the development of cancer. Alterations of oncogenes such as K-ras, c-erbB-2/HER-2/neu and c-myc, and those of tumor suppressor genes such as p53, RB and DCC have been reported in ovarian cancer. Allelic losses of the specific chromosomes, which suggest the existence of tumor suppressor genes on those chromosomes, also have been reported in ovarian cancer. Further studies on genetic alterations of ovarian cancer will clarify the mechanisms for the development of ovarian cancer and also will develop new methods for prevention, diagnosis and treatment in clinical.
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PMID:[Genetic alterations in the genesis and development of ovarian cancer]. 135 31

It is apparent that multiple genetic events occur in the development and progression of breast cancer. From the limited data available, no consistent temporal pattern of mutational events is required. This conclusion is consistent with data in colorectal carcinoma, where the number of mutational events, and not the order, appears to be relevant. Several authors have questioned whether the multiple mutational events occur independently or whether significant associations were evident. Cropp et al. postulated that two sets of mutational events occurred simultaneously in a higher degree of breast tumors than expected based on chance: Set 1 consisted of deletions on 11p, 17p, 18q, and int-2 and myc amplifications; set 2 consisted of 17q, 1p, and 3p deletions. Sato et al., analyzing another tumor cohort for simultaneous mutations, noted a correlation of 17p and 16q deletions, 13q and 17p deletions, and 17p deletion with erbB-2 amplification. Clearly, concordant data on this issue will require the use of large breast tumor cohorts for a comprehensive set of probes. The reasons why mutations to specific genes on different chromosomes tend to occur coordinately is unknown, but may involve common flanking and/or intron sequences at high risk for certain types of mutational events. Another interesting question is the degree to which alterations, but not homozygous inactivation, of suppressor genes occur and its phenotypic consequences. In this chapter, evidence was presented for the amplification of a DCC allele in breast cancer and for variable RB protein expression in breast tumors as a consequence of allelic deletion. For many of the metastasis suppressor genes, a simple reduction in their expression, or an alteration in their expression over the normal cellular regulatory controls, may be sufficient to fuel the metastatic process. The data suggest a more complex regulation of the cancer phenotype by suppressor genes than by recessive inactivation alone. Why do many sporadic cancers, including breast cancer, appear to require alterations to multiple suppressor genes, as compared to diseases such as retinoblastoma, where a single suppressor gene appears to control the cancer phenotype? The answer to this question is unknown, but most theories are based on the hypothesis that suppressor genes act to control cellular responses to either other cells or signals in the microenvironment. In retinoblastoma all cells can carry a germ-line mutation. Cells carrying the RB mutation can interact with both the embryonic and differentiated microenvironments; the specific interaction of mutated cells with the embryonic retinal microenvironment may trigger the onset of retinoblastoma.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Suppressor genes in breast cancer: an overview. 136 Feb 44

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

Gastric cancer involves changes in multiple oncogenes and multiple suppressor genes, and it causes genetic instability. Aberrant expression and amplification of the c-met gene, inactivation of the p53 gene, and CD44 abnormal transcripts are common events of both well differentiated and poorly differentiated gastric cancers. Amplification of the cyclin E gene is also observed in gastric cancer regardless of histologic type. Decreased expression of the pic1 (p21) gene occurs independent of the p53 mutations. In addition, K-ras mutations, c-erbB-2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC gene, LOH of the bcl-2 gene, and LOH at the DCC locus are preferentially associated with well differentiated gastric cancer. Moreover, LOH on chromosome 1q is involved in the progression of well differentiated cancer. Precancerous lesions, including hyperplastic polyp, intestinal metaplasia, and adenoma, share genetic changes found in well differentiated cancers. Conversely, genetic instability may be involved in the first step of stomach carcinogenesis of the poorly differentiated type. Reduction or loss of cadherin and catenins, K-sam gene amplification, and c-met gene amplification are necessary for the development and progression of poorly differentiated or scirrhous carcinoma. Interaction between cell-adhesion molecules in the c-met expressed tumor cells and hepatocyte growth factor from stromal cells is implicated in the morphogenesis of two types of gastric cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular biology of gastric cancer. 767 88

The following developments have considerably influenced the pathological management of breast materials: The wide use of aspiration cytology, increase of specimens from small non palpable lesions detected by mammography, an increase of cases difficult to diagnose histologically, increase in the number of conservative surgery cases which require examination of semi-serial sections, and the development of immunohistochemical procedures using breast cancer tissues. Under these changing circumstances in the department of pathology, we report our current practices and some of the results; About 75% of breast cancer cases initially treated in our hospital were diagnosed by aspiration cytology only. A retrospective, simulation study on quadrantectomy of breast cancers for selected T1N0N1a examined by semi-serial sections in non-conservative mastectomy cases revealed residual carcinoma foci located in a region outside the primary quadrant in about 25% cases. GCDFP-15 (Gross cystic disease fluid protein-15) is a fairly specific marker for breast cancer. Good correlation was obtained using estrogen and progesterone receptors routinely measured by ICA (Immunocytochemical assay), instead of the biochemical method using DCC (Dextran-coated charcoal). c-erbB-2 and p53 which were positive in 45.8%, and 28.6%, respectively, in our breast cancer cases, seemed to be good markers of biological malignancy in the breast cancer.
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PMID:[The current state of surgical pathology of the breast--the practice in our department]. 825 55

Pancreatic cancer is the fifth leading cause of cancer death in the United States, and despite improvements in the results of surgical treatment for this disease, little impact has been made upon overall mortality. New advances in treatment will depend upon improved adjuvant therapy, early diagnosis, and a better understanding of tumor biology. This article summarizes the results of molecular genetic studies in pancreatic cancer and their potential clinical significance. Familial predisposition to pancreatic cancer, cytogenic studies, DNA ploidy analysis, and examination of specific oncogenes and tumor suppressor genes are reviewed. The most frequent mutations detected have been in the K-ras oncogene, which occur in 80% of pancreatic cancers. These mutations do not correlate with tumor stage or survival, but can be useful in differentiating pancreatic exocrine from endocrine tumors and chronic pancreatitis. Mutations in the p53 gene occur in approximately 50% of tumors, and appear to be an independent prognostic factor for patient survival. Mutations in the CDKN2 gene are frequently seen in sporadic pancreatic cancers, and have been implicated in cases of familial pancreatic cancer. The significance of mutations in APC, MCC, DCC, c-erbB-2, RB-1, and mismatch repair genes in the genesis of pancreatic cancer is less clear.
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PMID:The molecular genetics of pancreatic cancer. 936 57

We investigated the clinicopathological and genetic characteristics including patients' gender, age, tumour location, growth pattern, Dukes' stage, DNA ploidy, S-phase fraction, PCNA, apoptosis, c-erbB-2, bcl-2, K-ras, p53, DCC and heat shock protein in 32 mucinous carcinomas versus 261 non-mucinous carcinomas in the colorectum. Sixty percent of mucinous carcinomas were located in the right colon, 13% in the left colon and 27% in the rectum (p=0.01). More mucinous carcinomas grew in expanding pattern than non-mucinous carcinomas (66% vs 39%, p=0.005). Compared with non-mucinous carcinoma, mucinous carcinoma had more K-ras mutations (50% vs 25%, p=0.02), but less p53 expression (72% vs 49%, p=0.02) and less apoptotic activity (19% vs 51%, p=0.01). We further confirm that the mucinous carcinoma in the colorectum represents a distinct clinicopathologic and genetic features as compared to non-mucinous tumour, and may have a different biological behaviour.
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PMID:Clinicopathological and genetic characteristics of mucinous carcinomas in the colorectum. 1033 57

Alterations in the cellular genome affecting the expression or function of genes controlling cell growth and differentiation are considered to be the main cause of cancer. Genes that cause cancer are of two distinct types: oncogenes and onco-suppressor genes. The normal proto-oncogene can be converted into an active oncogene by deletion or point mutation in its coding sequence, gene amplification, and by specific chromosome rearrangements. Mutations and abnormal expression in ras, myc, c-erbB-2, and other oncogenes have been reported in several types of gynecological cancer. Onco-suppressor genes are involved in gynecological cancer, their functions are localized in different phases of the cell cycle. Structural changes and deletions of these genes can cause cancer. Mutations in the p53, BRCA1, DCC, and PTEN genes have been reported in gynecological cancers such as ovarian, cervical, and endometrial cancer. Human papillomaviruses are of major interest because specific types (HPV-16, -18, and several others) have been identified as causative agents in at least 90% of cancers of the cervix. In this study we summarize the available information regarding the implication of specific oncogenes, onco-suppressor genes, and HPV in the development of female genital malignancies.
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PMID:Molecular basis of gynecological cancer. 1081 92

The prognostic value of disseminated tumour cells derived from 353 breast cancer patients was evaluated. Disseminated tumour cells were purified from blood using a newly established method and nucleic acids were subsequently isolated. We investigated genomic imbalances (GI) such as mutation, amplification and loss of heterozygosity of 13 tumour suppressor genes and 2 proto-oncogenes using DNA from isolated minimal residual cancer cells. Significant correlations were found between genomic alterations of the DCC - and c-erbB-2 genes in disseminated breast cancer cells and actuarial relapse-free survival. Furthermore, increasing numbers of genomic imbalances measured in disseminated tumour cells were significantly associated with worse prognosis of recurrent disease. Logistic regression and Cox multivariate analysis led to the identification of genomic imbalances as an independent prognostic factor. Determination of disseminated tumour cells by genotyping of oncogenes and tumour suppressor genes seems not only to be a useful adjunct in follow up of carcinoma patients but provides also valuable additional individualized prognostic and predictive information in breast cancer patients beyond the TNM system.
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PMID:Prognostic value of genomic alterations in minimal residual cancer cells purified from the blood of breast cancer patients. 1110 64

In order to determine the molecular genetic alterations associated with tumor invasion, Barrett's adenocarcinoma and its non-invasive precursor lesions were investigated by comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), and loss of heterozygosity (LOH). Along the metaplasia-dysplasia-carcinoma sequence in Barrett's adenocarcinoma gains on 7q, 8q, 20q, 2p, 10q and 17q, and losses on Y, 4q, 5q, 9p 18q and 14q became steadily more frequent. FISH demonstrated increasing DNA copy of numbers of c-erbB-2, 20q13.2 (AIB), c-myc and cyclin D1 during the development of Barrett's adenocarcinoma, and LOH confirmed DNA losses on 5q21 (APC) and 18q (DCC). Some of the chromosomal changes of the non-invasive precursor lesions were significantly different from the alterations detected in invasive carcinoma. Although molecular pathology may be used as diagnostic adjunct in future, the histopathological determination of invasion remains the most important diagnostic criterion of malignancy in Barrett's adenocarcinoma.
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PMID:[Morphology and biology of invasion with Barret's carcinoma as an example]. 1121 50


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