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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

All known tumor types have been reported in the neonate. A numerical listing and discussion are beyond the scope of this review. Wells and Fraumeni give some insight into common congenital malignant neoplasms. Table 2 lists the percentage of neonatal deaths caused by type-specific cancers. Retinoblastoma is probably the most common malignant tumor in the neonate. About seven per cent of these tumors have been apparent at birth. This tumor is not discussed in either article because it is not lethal until muypes in neonatal and pediatric patients. Some congenital malformations in the in the neonate are recognized as being frankly benign (cysts), potentially malignant (teratomas), and frankly malignant (neuroblastoma). A high percentage of teratomas are benign in the newborn period. Leukemia in the newborn appears to be more aggressive yet neuroblastoma has a better prognosis. More studies are needed to help us define why the neonate does better with some tumors and worse with others. Surface cell markers on neonatal leukemia, B and T cell function studies, and other immunologic surveillance studies are needed. Study of neonatal oncology may add to our knowledge of carcinogenesis and oncogenesis in the future.
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PMID:Neonatal oncology. 19 75

Somatic mutations are a common event in multicellular organisms and, therefore, have a significant impact on health. They can lead to either heterozygosity or homozygosity. Since the multistep concept of carcinogenesis presupposes that mutations/deletions of several genes are acquired, the identification and location of the critical genes involved in this sequence is attempted either by the observation of cytogenetic or molecular abnormalities in tumorous tissue or by linkage analysis, or both. The retinoblastoma paradigm of loss of heterozygosity with respect to the loss of the only wild-type allele can be applied to familial neoplasias occurring in all organs as they are summarized in this review. The development of homozygosity in non-malignant tissue has not been extensively investigated. However, its study has contributed to the identification of new genetic phenomena such as parental unidisomy and genomic imprinting.
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PMID:Hereditary conditions in which the loss of heterozygosity may be important. 127 87

Multiple genome alterations can be seen within a tumor and continue to accumulate throughout development of the growth. Chromosome deletions occurring in tumors are generating much interest. To date, the best known model is retinoblastoma whose study gave rise to the concepts of anti-oncogene or tumor suppressor gene. Studies of genetic anomalies in colorectal tumors have led to an elegant model of colonic carcinogenesis in which multiple steps, each with its corresponding genetic anomaly, successively accumulate, with deletion of the p53 gene occurring as a late event. Successive anomalies of the p53 gene (mutations, deletions) occur during passage from a low-grade astrocytoma to a higher-grade astrocytoma. Studies of familial forms of breast cancer and of breast and ovarian cancer have also provided insight into the biology of these tumors, with the identification of a predisposing chromosomal area whose location is 17 q-12-21. These approaches open up possibilities for screening techniques and use of preventive treatments in highly selected patients. However they raise many ethical problems. There is a need for developing a charter for these family studies in the near future.
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PMID:[Genetics and cancers]. 130 91

The dose response of the enhanced reactivation (ER) of herpes simplex virus type 1 has been studied in UV-irradiated normal human skin fibroblasts and fibroblasts from the following hereditary cancer-prone syndromes: retinoblastoma, aniridia, polyposis coli, neurofibromatosis type 1 and 2, dysplastic nevus syndrome, Von Hippel-Lindau syndrome, multiple endocrine neoplasia type 2, and Bloom's syndrome. Surprisingly, much higher levels of ER were observed in all these genetically heterogeneous hereditary disorders than in normal human skin fibroblasts. These results suggest that loss of one allele of putative tumor suppressor genes may activate cellular processes that result in the induction of the ER response, and they support our previous observation suggesting that ER may somehow be related to the process of carcinogenesis (P. J. Abrahams et al., Cancer Res., 48: 6054-6057, 1988).
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PMID:High levels of enhanced reactivation of herpes simplex virus in skin fibroblasts from various hereditary cancer-prone syndromes. 130 28

Retinoblastoma (RB) and the familial adenomatous polyposis/colorectal cancer (FAP/CRC) complex provide well-characterised examples of multistage carcinogenesis and inheritance of a predisposition to cancer. Retinoblastoma appears to conform to the simple two-step model first proposed by Knudson. The gene responsible for RB, now called Rb1, has been located in chromosome region 13q14. The Rb1 gene has been cloned and subjected to extensive analysis. It is probable that the Rb1 gene product has a role in the regulation of transcription. The familial form of RB occurs as the result of a germline mutation of one of the copies of the Rb1 gene. Colorectal cancer, in contrast, appears to be the result of four or five steps involving both activation of oncogenes and inactivation of antioncogenes. The FAP gene has been located in chromosome region 5q21 by genetic linkage, and a candidate gene, MCC (mutated in colon cancer), has been cloned. Other mutations in previously-identified genes that have been identified as important in the genesis of CRC include the activation of p53 and of Ki-ras. A gene lying in chromosome region 18q which is deleted in colorectal cancer, and hence named DCC has been cloned. Its protein product has sequence homology to neural cell adhesion molecules and other related cell-surface glycoproteins. Delineation of the genes involved in the development of tumours such as RB and CRC provides insight into the mechanisms by which sequential mutations result in carcinogenesis.
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PMID:Multistage carcinogenesis in paediatric and adult cancers. 131 30

The adenovirus E1A gene product, the simian virus 40 large tumor antigen, and the human papillomavirus E7 protein share a short amino acid sequence that constitutes a domain required for the transforming activity of these proteins. These sequences are also required for these proteins to bind to the retinoblastoma gene product (pRb). Recent experiments have shown that E1A can dissociate complexes containing the transcription factor E2F bound to pRb, dependent on this conserved sequence element. We now show that the E7 protein and the simian virus 40 large tumor antigen can dissociate the E2F-pRb complex, dependent on this conserved sequence element. We also find that the E2F-pRb complex is absent in various human cervical carcinoma cell lines that either express the E7 protein or harbor an RB1 mutation, suggesting that the loss of the E2F-pRb interaction may be an important aspect in human cervical carcinogenesis. We suggest that the ability of E1A, the simian virus 40 large tumor antigen, and E7 to dissociate the E2F-pRb complex may be a common activity of these viral proteins that has evolved to stimulate quiescent cells into a proliferating state so that viral replication can proceed efficiently. In circumstances in which a lytic infection does not proceed, the consequence of this action may be to initiate the oncogenic process in a manner analogous to the mutation of the RB1 gene.
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PMID:Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7 protein share the capacity to disrupt the interaction between transcription factor E2F and the retinoblastoma gene product. 131 11

The HPVs associated with anogenital cancers encode two oncoproteins, E6 and E7. Both E6 and E7 can form specific complexes with tumour suppressor gene products. The E7 protein binds to the retinoblastoma tumour suppressor gene product pRB, with a preference for the underphosphorylated, "active" form of pRB. The E7 proteins derived from the "high risk" HPVs bind to pRB with a higher affinity than the E7 proteins from the "low risk" HPVs. The "high risk" HPV E6 proteins can associate with the p53 tumour suppressor protein. This interaction promotes the degradation of p53 in vitro, which presumably accounts for the very low levels of p53 in cervical carcinoma cell lines. The functional inactivation of pRB and p53 by the HPV oncoproteins E7 and E6, respectively, are likely to be important steps in cervical carcinogenesis, since mutations in the RB and p53 genes were detected in HPV negative but not HPV positive cervical carcinoma cell lines. Cytogenetic studies strongly suggest, however, that additional chromosomal changes may be necessary for carcinogenic progression of HPV induced anogenital lesions.
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PMID:Interactions of HPV E6 and E7 oncoproteins with tumour suppressor gene products. 132 42

Two aspects can be distinguished in multistage carcinogenesis: etiological one (every stage is induced by a specific for this stage agent) and morphobiological aspect (every stage is characterized by specific morphological, genetic and other properties). The schema of the multistage carcinogenesis is presented in which morphological stages (diffuse and focal hyperplasia, benign tumours, dysplasia, carcinoma in situ, various phases of malignant tumour progression) are placed against genetic alterations. L. Foulds concept of tumour progression is discussed with special emphasis on precancerous stages, possibilities of cancer development de novo, and independent progression of different tumour characters. The following types of carcinogenesis are listed on the basis of interrelationship between etiological and genetic factors: 1) carcinogenesis induced by genotoxic agents; a) one agent is acting at high dose and for a long time thus ensuring the activation of protooncogenes and all stages of tumour progression (initiation, promotion, various phases of malignant tumour); b) those acting during a very short time, however sufficient for developing the genetic program working automatically without further exposure to known carcinogens (irradiation in case of the atomic bomb explosion or effect of short-living alkylating agents): in this case there is no stage of promotion; 2) carcinogenesis by non-genotoxic carcinogens (their mode of action is still unclear, the only human example is carcinogenesis by hormones); 3) development of tumours in frane of the two (or three) stage carcinogenesis when every stage is provoked by its own etiological factor, no human examples are known as yet; 4) development of tumours due to the genetic mechanism making the organism highly susceptible to the minimal doses of carcinogens as is the case with skin cancer by ultraviolet light in patients with xeroderma pigmentosum, the genetic damage in itself has nothing to do with tumour formation; 5) genetic damage leading to the development of tumour without visible participation of any known carcinogens or promoters (gene Rb in retinoblastoma, gene Wt in Wilms tumour, etc.).
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PMID:[Progression of tumors: etiologic, morphologic and molecular-biological aspects]. 147 43

Twenty-five mouse lung tumors induced by a single urethan treatment in female A/J, BALB/c, and (A/J x C3H/He)F1 (AC3) mice were analyzed for the presence of mutations at codon 61 of the Ki-ras gene and for the expression of the surfactant protein A (SP-A), retinoblastoma (Rb), growth arrest-specific-3 (gas-3), p53, c-myc, and thymidylate synthase (TS) genes. Ki-ras codon 61 mutations were detected in 22 of 25 tumor samples without differences among strains. In comparison with normal lungs, all the tumors showed increased SP-A mRNA levels, indicating their derivation from alveolar type II pneumocytes or Clara cells. Rb and gas-3 transcripts were instead found in all tumors at about tenfold and about 20-fold reduced levels, respectively. No apparent structural alterations or loss of heterozygosity at the Rb locus was detected in any tumors. The p53 mRNA was observed without variation in quantity or size in lung tumors and normal tissue. A threefold to fivefold c-myc overexpression was observed, without amplification of the gene. TS expression was only slightly increased, indicating no great differences in cell proliferation between lung tumors and normal tissue. Our data suggest that the pathogenesis of urethan-induced lung tumors in mice involves specific and recurrent molecular alterations (Ki-ras mutations, decrease of Rb and gas-3 expression, and increase of c-myc expression) that could represent different steps in lung carcinogenesis.
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PMID:Multiple molecular alterations in mouse lung tumors. 155 14

Some of the cellular changes underlying the presentation of cancer in a patient can already be understood in terms of mutations affecting specific gene functions. So far, only a few of the mutated genes responsible for carcinogenesis have been identified and these are chiefly involved in deregulation of cell growth rather than with the processes of invasion and metastasis. Proto-oncogenes are important cellular genes which can acquire gain in function mutations as random events in somatic cells. In their mutated, activated forms they are called cellular oncogenes or c-oncs. This distinguishes them from homologous DNA sequences captured by viruses from host cells in the course of retroviral evolution that cause cancers in animal hosts (viral oncogenes or v-oncs). In recent years, loss of function mutations have been identified in regulatory genes that normally serve to constrain cell growth. These are called tumour suppressor genes. Loss of function mutations may be transmitted in the germline, as in hereditary retinoblastoma, or arise de novo in somatic cells. The normal molecular mechanisms disrupted by mutations in tumour suppressor genes include processes regulating progression through the cell cycle.
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PMID:What are cancer genes, and how do they upset cell behaviour? 156 75


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