Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is generally accepted that cancer is caused by environmental and inherited factors but these are only partially identified. Family studies can be informative but they do not separate shared lifestyles and genes. We estimate familial risks for concordant cancers between spouses in common cancers of both sexes in order to quantify cancer risks from the shared environment. The risks are compared to those seen between parents and offspring in order to estimate the inherited component. The nation-wide Family-Cancer Database was used as the source of family and cancer data. Standardized incidence ratios (SIRs) were calculated for concordant cancer in offspring by parental cancer and in spouses. Among the 23 cancer sites considered, all but two showed an increased SIR for offspring by father or mother. Only two sites, stomach and lung, showed an increase in SIR of concordant cancer among spouses. Additionally, pancreatic cancer and melanoma were increased in couples where at least one spouse was diagnosed before age 50. If both spouses presented melanoma before age 40, SIR was 3.82 for husbands. SIRs of colon, renal, and skin (squamous cell) cancers were unchanged by spouses' concordant cancer. Shared lifestyle among spouses seems to explain only a small proportion of cancer susceptibility. Because lifestyles are likely to differ more between parents and offspring than between spouses, familial cancer risks between parents and offspring are likely to be more due to heritable rather than environmental effects.
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PMID:Cancer risks to spouses and offspring in the Family-Cancer Database. 1118 Apr 50

Approximately 5% to 10% of patients with pancreatic cancer have one or more first-degree relatives with this disease. A subset of these individuals have a hereditary form of pancreatic cancer designated by association with such hereditary disorders as familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, hereditary pancreatitis, or familial atypical multiple mole melanoma (FAMMM) syndrome. A subset of those FAMMM kindred with the CDKN2A (p16) germline mutation that expresses both pancreatic cancer and malignant melanoma may constitute a new hereditary pancreatic cancer-prone syndrome.
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PMID:Update on familial pancreatic cancer. 1127 79

Co-administration of synthetic chemically modified oligonucleotides with irinotecan, a selective topoisomerase I inhibitor, provided a significant enhancement in the antitumor activity of irinotecan. The enhancement of antitumor activity of irinotecan with co-administration of chemically modified oligonucleotides was observed in several tumor models--pancreatic cancer (Panc-1), colon cancer (HCT-116) and melanoma (A375). Inhibition of tumor growth in all three models required the co-administration of irinotecan and chemically modified oligonucleotides, but was independent of the nucleotide sequence of the oligonucleotides. The potentiation of antitumor activity was dependent on the dose of irinotecan and chemically modified oligonucleotides administered. The enhancement of antitumor activity of irinotecan was also observed by co-administration of a phosphorothioate oligonucleotide, however, to a lesser extent than did chemically modified oligonucleotides, suggesting that metabolic stability of the oligonucleotide contributes to the enhancement of antitumor activity seen with irinotecan. The co-administration of dextran sulfate sodium with irinotecan showed insignificant potentiation of antitumor activity of irinotecan, suggesting that the enhancement of antitumor activity of irinotecan observed was not a result of polyanionic characteristic of oligonucleotides. Co-administration of irinotecan and chemically modified oligonucleotides did not result in increased toxicity in the tumor models studied. Potentiation of antitumor activity of irinotecan observed with co-administration of oligonucleotides suggests that the oligonucleotides affect the pharmacokinetics and/or metabolism of irinotecan. The use of chemically modified oligonucleotides together with irinotecan may increase the therapeutic index of irinotecan in cancer patients and continued development of such agents should be considered.
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PMID:Potentiation of antitumor activity of irinotecan by chemically modified oligonucleotides. 1129 57

Pancreatic cancer is an extremely aggressive neoplasm whose incidence equals its death rate. Despite intensive analysis, the genetic changes that mediate pancreatic cancer development and effective therapies for diminishing the morbidity associated with this disease remain unresolved. Through subtraction hybridization, we have identified a gene associated with induction of irreversible growth arrest, cancer reversion, and terminal differentiation in human melanoma cells, melanoma differentiation associated gene-7 (mda-7). Ectopic expression of mda-7 when using a recombinant adenovirus, Ad.mda-7, results in growth suppression and apoptosis in a broad spectrum of human cancers with diverse genetic defects, without exerting deleterious effects in normal human epithelial or fibroblast cells. Despite the apparently ubiquitous antitumor effects of mda-7, pancreatic carcinoma cells are remarkably refractory to Ad.mda-7 induced growth suppression and apoptosis. In contrast, the combination of Ad.mda-7 with antisense phosphorothioate oligonucleotides, which target the K-ras oncogene (a gene that is mutated in 85 to 95% of pancreatic carcinomas), induces a dramatic suppression in growth and a decrease in cell viability by induction of apoptosis. In mutant K-ras pancreatic carcinoma cells, programmed cell death correlates with expression and an increase, respectively, in MDA-7 and BAX proteins and increases in the ratio of BAX to BCL-2 proteins. Moreover, transfection of mutant K-ras pancreatic carcinoma cells with an antisense K-ras expression vector and infection with Ad.mda-7 inhibits colony formation in vitro and tumorigenesis in vivo in nude mice. These intriguing observations demonstrate that a combinatorial approach, consisting of a cancer-specific apoptosis-inducing gene and an oncogene inactivation strategy, may provide the foundation for developing an effective therapy for pancreatic cancer.
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PMID:A combinatorial approach for selectively inducing programmed cell death in human pancreatic cancer cells. 1152 25

Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States and will be responsible for an estimated 28,900 deaths in 2001. Relatively little is known of its etiology, and the only well-established risk factor is cigarette smoking. Studies over the past 3 decades have shown that 4%-16% of patients with pancreatic cancer have a family history of the disease. A small fraction of this aggregation can be accounted for in inherited cancer syndromes, including familial atypical multiple-mole melanoma, Peutz-Jeghers syndrome, hereditary breast-ovarian cancer, hereditary pancreatitis, and hereditary nonpolyposis colorectal cancer. These syndromes arise as a result of germline mutations in the BRCA2, pl6 (familial atypical multiple-mole melanoma), mismatch repair (hereditary nonpolyposis colorectal cancer), and STK11 (Peutz-Jeghers syndrome) genes. In addition, hereditary plays a role in predisposing certain patients with apparently sporadic pancreatic cancer. Many patients with pancreatic cancers caused by a germline mutation in a cancer-causing gene do not have a pedigree that is suggestive of a familial cancer syndrome. A recent prospective analysis of the pedigrees in the National Familial Pancreatic Tumor Registry found that individuals with a family history of pancreatic cancer in multiple first-degree relatives have a high risk of pancreatic cancer themselves. The identification of such high-risk individuals will help clinicians target screening programs and develop preventive interventions with the hope of reducing the mortality of pancreatic cancer in these families.
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PMID:Familial pancreatic cancer. 1156 3

Cell Genesys (formerly Somatix Therapy Corp) is developing GVAX as a potential cancer vaccine for various tumor types. Clinical trials have commenced for melanoma, renal tumor, lung tumor, pancreatic tumor, prostate tumor and multiple myeloma [191143], [287470], [298308], [367408], [401114]; trials are planned for 2001 in leukemia (phase I) and pancreatic cancer (phase II) [366918], [388814]. A worldwide collaboration was signed with Japan Tobacco in December 1998, covering the application of GVAX in prostate cancer trials [312213]. This collaboration may be extended to lung cancer and melanoma, depending on the clinical trial results for prostate cancer [309873], [311835]. The Japanese clinical trials were put on hold on 21 September 2000 due to problems with the mass production of cells by Cell Genesys [384885]. Somatix was developing GVAX until its merger with Cell Genesys in June 1997 [248422]. In April 2001, Cell Genesys initiated the first in a series of trials of a high-potency version of GVAX prostate cancer vaccine following encouraging phase II data reported for its first-generation product. The high-potency form of GVAX is similar to the first-generation product except that it releases an increased quantity of immune system stimulant [405932].
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PMID:GVAX (Cell Genesys). 1157 68

Induction chemotherapy can be effective in reducing locally advanced or aggressive cancers to improve their prospects of cure by planned follow-up surgery and/or radiotherapy. Systemic (intravenous) delivery is the simplest and most readily available method of administering induction chemotherapy. In some situations, a greater chemotherapy impact can be achieved by delivering a more concentrated dose of effective anti-cancer agents into the arterial blood supply of the cancer. Intra-arterial (i.a.) chemotherapy may or may not be advantageous. To achieve an advantage, the tumour must be fully contained in tissue supplied by one or more arteries that can be effectively cannulated and infused. The cancer must also be one known to respond better to concentrated chemotherapy and the agents used must be effective in the state in which they are delivered. The advantages must outweigh the likely increased risks of regional toxicity and experienced personnel and appropriate specialized equipment must be available to reduce any risk of mistakes made by the more exacting techniques of delivery. In general, systemic chemotherapy is most appropriate in treating tumours without a single artery of supply; when certain agents that are inactive until modified in body tissues (such as cyclophosphamide or DTIC) are to be used; when satisfactory responses can be achieved safely and more easily by systemic delivery; when technical skills and facilities for regional delivery are not available; or when the patient's general health, poor co-operation or long-term prognosis precludes the additional complexity of regional delivery. Intra-arterial infusion may have advantages in treating some locally advanced malignancies in the head and neck, a limb, some invasive stomach cancers and some breast cancers. Primary and some metastatic liver cancers, some pelvic cancers and possibly pancreatic malignancies may also respond well to initial direct chemotherapy infusion and are the subject of several studies. Closed circuit perfusion (Creech-Krementz), chemofiltration infusion and "stop-flow" perfusion (Aigner) and regional limb infusion (Thompson) are more complex techniques aimed at even greater localized initial tissue chemotherapy concentrations over a short time span. These are the subject of ongoing studies in highly specialized units. Their use is designed to achieve tumour responses in treating such malignancies as melanoma, some sarcomas or pancreatic cancer that usually show a poor response to standard systemic chemotherapy.
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PMID:Induction chemotherapy: to downgrade aggressive cancers to improve curability by surgery and/or radiotherapy. 1166 97

The paper presents the findings of the first Russian study of possible cancer risks in printing workers. For the first time, the historical cohort study included women. The cohort comprised 1,553 males and 3,473 females who were followed up for 15 years (01/01/79-12/31/93). A significant increase in the rates of death from pancreatic cancer was registered among males employed as compositors exposed to inorganic lead dust and vapors. Raised mortality from malignancies of the stomach urinary bladder, skin melanoma and mesothelioma was identified in females exposed to a PAU-containing oil paint aerosol and paper dust. Significant death risks from esophageal and ovarian malignancies due to exposure to glue vapors and paper dust were observed in bookbinders.
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PMID:[Epidemiology of occupational neoplasms in the printing industry]. 1171 Feb 82

The INK4a-ARF locus, localized on 9p21, encodes two tumor suppressor proteins, p16INK4a and p14ARF, acting respectively through the CDK4-pRb and the p53 pathways. Familial melanoma (comprising between 8 and 12% of all melanoma cases) is a genodermatosis transmitted as an autosomal dominant trait, often associated with clinically atypical moles (AN). Germline mutations of p16INK4a are found in up to 20-30% of melanoma prone families. Mutated families often contain more than three family members affected and/or comprise at least one relative with multiple melanomas. Most of these mutations have been shown to affect p16INK4a protein function (i.e. CDK4 binding or pRB phosphorylation). Germline mutations of p16INK4a are also found in a lesser extend in sporadic multiple melanoma and in familial pancreatic cancer. The INK4a-ARF locus plays also an important role in skin carcinogenesis. P16INK4a UV induced mutations (CC:GG > TT:AA tandem transition or C:G > T:A transition at dipyrimidic site) are found in 12% of sporadic skin carcinomas, mainly in epidermoid tumors, and seem to occur independently of p53 mutations. Xeroderma pigmentosum (XP) is characterized by an inheritable DNA repair defect (involving the nucleotid excision repair (NER) system) predisposing to skin carcinomas. In skin tumors from (XP) patients, p16INK4a UV induced mutations occur more frequently, are often multiple, and significantly associated with the presence of p53 mutations. Such data, which could be related to the XP genetic instability and indicates a possible cooperative effect of inactivation of these pathways in the tumoral process of XP skin tumors.
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PMID:[The INK4a-ARF locus: role in the genetic predisposition to familial melanoma and in skin carcinogenesis]. 1174 99

CDKN2A germline mutation frequency estimates are commonly based on families with several melanoma cases. When we started counseling in a research setting on gene susceptibility analysis in northern and central Italy, however, we mostly found small families with few cases. Here we briefly characterize those kindred, estimate CDKN2A/CDK4 mutation test yields, and provide indications on the possibility of implementing formal DNA testing for melanoma-prone families in Italy. In September 1995 we started genetic counseling in a research setting at our Medical Genetics Center. Screening for CDKN2A/CDK4 mutations was performed on families with two melanoma patients, one of whom was younger than 50 years at onset, the other complying with one of the following: 1) being a first-degree relative, 2) having an additional relative with pancreatic cancer, or 3) having multiple primary melanomas. Sixty-two of 67 (80%) melanoma cases met our criteria. Four previously described CDKN2A mutations (G101W, R24P, V126D, and N71S) were found in 21 of the 62 families (34%) with a high prevalence of G101W (18/21). The percentage of families with two melanoma cases/family harboring a mutation was low (7%, 2/27), but rose to 45% (9/20) if one of the melanoma patients carried multiple melanomas or if pancreatic cancer was present in that family. In the 15 families with three melanoma cases the presence of a mutation was higher (67%, 10/15) and reached 100% in the 4 families with four or more melanoma cases. Our results suggest that CDKN2A/CDK4 counseling-based mutational analysis may be reasonably efficient also for families with two melanoma cases, if one patient carries multiple melanomas or if pancreatic cancer is present in the family.
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PMID:High prevalence of the G101W germline mutation in the CDKN2A (P16(ink4a)) gene in 62 Italian malignant melanoma families. 1180 2


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