Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some of the most dramatic advances in the treatment of cancer have used the immune system in combination with conventional or transplantation chemotherapy. Adoptive immunotherapy has been used for relapses after allogeneic bone marrow transplantation, and it has been particularly effective for chronic myeloid leukemia. Adoptive immunotherapy also has been used for Epstein-Barr virus-related lymphomas developing after allogeneic marrow transplantations. Cellular therapy, including the infusion of tumor-reactive immune cells, has been used to mediate response of established solid tumors. This has been used for therapeutic benefit for renal cell carcinoma, melanoma, lung cancer, and breast cancer. Current research is focusing on reducing the toxicity of these approaches as well as further defining the appropriate target tissue.
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PMID:Adoptive immunotherapy. 937 80

There is an ever growing report of data supporting the evidence that accumulated genetic changes underlie the development of neoplasia. The paradigma of this multistep process is colon cancer were cancer onset is associated, over decades, with at least seven genetic events. The number of genetic alterations increases moving from adenomatous lesions to colon cancer and, although the genetic alterations occur according to a preferred sequence, the total accumulation of changes rather than their sequential order is responsible of tumor biological behavior. It is noteworthy that, at least for this neoplasia, carcinogenesis appears to arise as a result of the mutational activation of oncogenes coupled with the mutational inactivation of tumor suppressor genes. In some cases mutant suppressor genes appear to exert a phenotypic effect even when present in the heterozygous state thus been non "recessive" at the cellular level. The general features of this model may apply also to renal cell cancer (RCC) and prostate cancer (CaP). Extensive literature exists on the cytogenetic and molecular findings in RCC. Only 2% of RCC are familiar, but molecular genetic studies of these cancers have provided important informations on RCC pathogenesis. As with other cancers, familiar RCC is characterized by an early age of onset and frequent multicentricity. A pathological classification useful in studying these patients subdivide renal cancers in papillary (pRCC) and non papillary (RCC) neoplasms. The most common cause of inherited RCC is the Von Hippel Lindau disease (VHL) a dominantly inherited multisystem disorder characterized by retinal and cerebellar hemangioblastomas, pheochromocytomas, pancreatic cysts and RCC. Over 70% of these patients will develop an RCC by their sixth decade. In 1993 the isolation of the tumor suppressor gene in VHL disease at the level of chromosome 3p25-p26 have lead to a better understanding of RCC. Most missense mutations are associated with high risk of RCC, but some are associated with high risk of pheochromocytoma and low risk of RCC. The VHL gene is evolutionary conserved and encodes for a specific protein (pVHL). VHL protein downregulates transcriptional elongation and so suppresses the expression of proto-oncogenes and growth factors. Recently reintroduction of wild-type, non mutant, VHL gene into VHL deficient RCC cell line 786-O had no demonstrable effect on their in vitro growth but inhibited their ability to form tumors in nude mice. So far, VHL mutations or hypermethylations have been found in 76% of sporadic RCC. On the contrary, up to now, no 3p allele loss or VHL mutations have been detected in pRCC. Preliminary studies in familiar pRCC are pointing on genetic changes on chromosomes 1, 7, 16 and 17. As far as prostate cancer is regarded, men with a family history of prostate cancer have an age dependent, significantly increased PCa risk. For familiar clustering, of PCa the two main factors are early age at onset of the disease and the number of multiple affected family members. Hereditary prostate cancer is a subset of familiar prostate cancer with a pattern of distribution consistent with Mendelian inheritance. Hereditary prostate cancer is clinically defined as a clustering of 3 or more relatives within any nuclear family; or the occurrence of prostate cancer in each of 3 generations in either the probands paternal or maternal lineage; or a cluster of 2 relatives affected within 55 years of age or less. Therefore, hereditary prostate cancer may be seen as a multistep carcinogenesis, and clustering may be explained by Mendelian inheritance of a rare (frequency in population 0.36%) dominant, highly penetrant, allele. The estimated cumulative risk of developing PCa, is 88% for carriers as compared with 5% for non carriers. There are conflicting reports of an associated increased incidence of breast cancer in female relatives of men with familiar prostate cancer. In conclusion, there is a clear associatio
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PMID:[Heredity in renal and prostatic neoplasia]. 941 96

Topotecan (Hycamtin; SmithKline Beecham Pharmaceuticals, Philadelphia, PA), a camptothecin analog, is a novel and specific inhibitor of the nuclear enzyme topoisomerase I. In preclinical studies, topotecan demonstrated significant in vitro activity in a variety of solid tumor explants derived from colorectal, breast, ovarian, renal cell, non-small cell lung cancer, and gastrointestinal sources. Notable activity was also demonstrated in vivo in a wide range of animal tumor models. A large number of phase I studies with topotecan have been conducted since 1992 in both adults and children with a broad range of refractory malignancies and as many as 14 different dosing schedules. Complete, partial, or minor responses were demonstrated in patients with recurrent or refractory neuroblastoma, non-small cell lung cancer, small cell lung cancer, ovarian cancer, breast cancer, colon cancer, esophageal cancer, renal cell carcinoma, and squamous cell carcinoma. The antitumor activity of topotecan in these phase I evaluations was associated more often with frequent or continuous dosing schedules compared with less frequent or short exposure schedules. Maximum tolerated doses were predominantly dependent on the dosing schedule used. Myelosuppression was the major dose-limiting toxicity across all schedules, and nonhematologic toxicities were generally mild. Data from phase I studies have provided valuable information about antitumor responses, maximum tolerated doses, and dose-limiting toxicities associated with different dosing schedules. Based on this information, there was substantial enthusiasm for further evaluating topotecan in a wide range of cancer patients in phase II studies.
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PMID:Review of phase I clinical studies with topotecan. 942 56

Immortalization and tumorigenic transformation of many human cell types, including human uroepithelial cells (HUCs), are frequently associated with loss of genetic material from the short arm of chromosome 3 (3p). In addition, losses of 3p have been observed in many human cancers including renal cell carcinoma, lung cancer, breast cancer, and bladder cancer. Genetic studies suggest that there are at least two regions on 3p in which tumor suppressor genes might be located, but the precise location of these genes is not known. We studied chromosome 3 losses that were specifically associated with immortalization of five independent human papilloma virus 16 (HPV16) E6- or E7-transformed HUCs. Cytogenetic analysis showed that the smallest common region of deletion was 3p14.1-->14.2. Fluorescence in situ hybridization using a 3p13-->14-specific yeast artificial chromosome (YAC) contig showed the precise localization of the breakpoints to be in 3p13 and 3p14.2, thus defining the smallest common overlap of 3p deletions in HPV16 E6- or E7-immortalized HUCs. These results suggest the presence in this region of genes involved in the control of senescence in vitro and possibly tumorigenesis in vivo.
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PMID:Minimal deletion of 3p13-->14.2 associated with immortalization of human uroepithelial cells. 944 40

The Her-2/neu oncogene encodes a Mr 185,000 transmembrane protein with homology to the epidermal growth factor receptor. It is overexpressed in 30-40% of breast and ovarian cancers, and this overexpression was shown to correlate with aggressiveness of malignancy and poor prognosis. Using tumor-associated lymphocytes isolated from patients with ovarian or breast cancer, several HLA-A2-restricted, Her-2/neu-derived peptides were identified. Further studies revealed that these tumor-associated CTLs can also lyse other tumors, including non-small cell lung and pancreatic cancer cells, suggesting that Her-2/neu epitopes are shared between several distinct types of epithelial tumors. To analyze whether Her-2/neu epitopes are tumor-associated antigens for renal cell carcinoma (RCC) and colon carcinoma, we induced Her-2/neu peptide-specific CTL responses by primary in vitro immunization and used these CTLs to determine the presentation of Her-2/neu epitopes on human tumor lines. Autologous dendritic cells (DCs) generated from peripheral blood monocytes were pulsed with Her-2/neu-derived peptides E75 and GP2 and used as antigen-presenting cells for CTL priming. High CTL activity toward peptide-pulsed targets was obtained after two weekly restimulations. CTLs induced with DCs generated in the presence of TNF-alpha elicited a higher cytotoxic activity when they were stimulated with the cognate peptide than did CTLs induced with DCs grown in granulocyte macrophage colony-stimulating factor and interleukin 4 alone. The cytotoxicity of induced CTLs was antigen specific and HLA-A2 restricted. Furthermore, these CTLs lysed, in a MHC- and antigen-restricted fashion, not only breast cancer cells but also colon carcinoma and RCC cell lines expressing Her-2/neu. The cytotoxic activity against tumor cells was blocked by cold HLA-A2-positive targets pulsed with the cognate peptide in cold target inhibition assay and by anti-HLA-A2 monoclonal Ab. These results suggest that epitopes derived from Her-2/neu protein might be attractive candidates for broadly applicable vaccines and may prove useful for adoptive immunotherapies designed for colon carcinoma or RCC.
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PMID:Her-2/neu-derived peptides are tumor-associated antigens expressed by human renal cell and colon carcinoma lines and are recognized by in vitro induced specific cytotoxic T lymphocytes. 948 28

We describe two Li-Fraumeni syndrome families. Family A was remarkable for two early childhood cases of adrenocortical tumours, family B for a high incidence of many characteristic cancers, including a childhood case of choroid plexus tumour. Using direct sequencing, we analysed exons 5-9 of the p53 gene in constitutional DNA of individuals from both families and found two novel germline mutations in exon 5. In family A, we detected a point substitution in codon 138 (GCC to CCC), which resulted in the replacement of the alanine by a proline residue. Family B harboured a single-base pair deletion in codon 178 (CAC to -AC), resulting in a frameshift and premature chain termination. Three out of six tumours examined from both families, a renal cell carcinoma, a rhabdomyosarcoma and a breast cancer, showed loss of heterozygosity and contained only the mutant p53 allele. The remaining three neoplasms, both adrenocortical tumours and the choroid plexus tumour retained heterozygosity. Immunohistochemistry with anti-p53 antibody confirmed accumulation of p53 protein in tumours with loss of heterozygosity, while the remaining tumours were p53 negative. These results support the view that complete loss of activity of the wild-type p53 need not be the initial event in the formation of all tumours in Li-Fraumeni individuals.
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PMID:Two Li-Fraumeni syndrome families with novel germline p53 mutations: loss of the wild-type p53 allele in only 50% of tumours. 956 35

Bone is among the most common sites of metastatic disease in cancers of the breast, prostate, and lung. The decision about systemic therapy depends on the histology, presence and extent of extraskeletal disease, and the performance status of the patient. For patients with estrogen-receptor-positive breast cancer or prostate cancer, hormonal treatment represents the treatment of choice. In estrogen-receptor-negative breast cancer, and for patients who have failed hormonal therapy or have liver metastases, chemotherapy should be initiated. All patients with small-cell lung cancer should receive chemotherapy. Bone metastases of differentiated thyroid cancers can be treated with radioisotopes. In non-small-cell lung cancer or renal cell cancer, systemic chemotherapy should be confined to younger patients and patients in good general condition. Radiologic assessment of responses of skeletal metastases to systemic therapy is often difficult. New approaches in measuring bone metabolites in urine might prove helpful.
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PMID:[Systematic hormone- and chemotherapy in the management of skeletal metastases]. 961 83

We describe a patient in whom synchronous breast cancer and small-cell lung cancer, and metachronous renal cell carcinoma were diagnosed within an 11 months period. All three tumors were treated surgically, followed by administration of tamoxifen, adjuvant chemotherapy with etoposide (2.8 g/m2 total) and vindesine, and administration of interferon alpha and flutamide. The patient developed acute myelomonocytic leukemia 26 months after discontinuation of etoposide-containing chemotherapy. This pattern of multiple neoplasms fits the wider disease spectrum associated with germline mutations of the p53 gene; however, analysis of p53 exons 5-8 did not disclose any sequence abnormalities in this patient. In conclusion, clustering of four (synchronous and metachronous) malignancies may on rare occasions occur in an individual patient and in the absence of a family history of cancer; the sequence during which treatment of primary malignancies may result in treatment-related acute myelocytic leukemia is discussed.
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PMID:Acute myelomonocytic leukemia secondary to synchronous carcinomas of the breast and lung, and to metachronous renal cell carcinoma. 962 Feb 29

Bone metastases of the vertebral spine occur frequently after breast cancer, hypernephroma or thyroid carcinoma. Located commonly in the lumbar and thoracic spine, half of the lesions are found in the vertebral body, but in many cases lamina and pedicles are also involved. Pain resistant to conservative treatment, vertebral compression fracture and segmental instability, together with progredient neurologic deficits and para- or tetraplegia, all make operative intervention mandatory. In this article dorsal decompression and stabilization are compared to ventral decompression and compound osteosynthesis. Segmental stability and life-time prognosis of the patient are important factors to decide on the best surgical procedure. Dorsal decompression without stabilization should only be performed as a palliative procedure in patients with an inoperative tumor, poor prognosis, or if the estimated postoperative segmental stability seems to be sufficient. In cases of a solitary metastasis, after radical resection of the primary tumor and when the prognosis is good total vertebrectomy can be performed. In addition to surgical treatment, adjuvant chemotherapy and/or radiation therapy should be performed in a multidisciplinary setting.
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PMID:[Surgical therapy of spinal metastases]. 964 19

A new tumor suppressor gene PTEN/MMAC1 was recently isolated at chromosome 10q23 and found to be inactivated by point mutation or homozygous deletion in glioma, prostate and breast cancer. PTEN/MMAC1 was also identified as the gene predisposing to Cowden disease, an autosomal dominant cancer predisposition syndrome associated with an increased risk of breast, skin and thyroid tumors and occasional cases of other cancers including bladder and renal cell carcinoma. We screened 345 urinary tract cancers by microsatellite analysis and found chromosome 10q to be deleted in 65 of 285 (23%) bladder and 15 of 60 (25%) renal cell cancers. We then screened the entire PTEN/MMAC1 coding region for mutation in 25 bladder and 15 renal cell primary tumors with deletion of chromosome 10q. Two somatic point mutations, a frameshift and a splicing variant, were found in the panel of bladder tumors while no mutation was observed in the renal cell carcinomas. To screen for homozygous deletion, we isolated two polymorphic microsatellite repeats from genomic BAC clones containing the PTEN/MMAC1 gene. Using these new informative markers, we identified apparent retention at the gene locus indicative of homozygous deletion of PTEN/MMAC1 in four of 65 bladder and 0 of 15 renal cell tumors with LOH through chromosome 10q. Identification of the second inactivation event in six bladder tumors with LOH of 10q implies that the PTEN/MMAC1 gene is occasionally involved in bladder tumorigenesis. However, the low frequency of biallelic inactivation suggests that either PTEN/MMAC1 is inactivated by other mechanisms or it is not the only target of chromosome 10q deletion in primary bladder and renal cell cancer.
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PMID:Point mutation and homozygous deletion of PTEN/MMAC1 in primary bladder cancers. 967 2


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