Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because Cisplatin potentiates the effect of radiotherapy in animal tumor systems and because Cisplatin is capable of causing regressions of human malignant melanomas, a study was initiated in patients with malignant melanoma metastatic to brain to investigate the feasibility of administering Cisplatin once a week during cranial irradiation. Cisplatin 40 mg/m2/week (three doses) was given I.V. to 18 patients during whole brain irradiation, 3 000 rads in 12 fractions over 21/2 weeks. Eleven patients also received Cisplatin 120 mg/m2 every three weeks, starting three weeks after cranial irradiation. Median survival was ten weeks, and only one of 13 patients whose brain metastases had not been resected experienced neurological and CT scan improvement. Thirteen patients have died, and brain metastases were a major cause. No regression of extracerebral tumor was seen in 15 patients with evaluable extracerebral lesions. During weekly low-dose Cisplatin administration, nausea and vomiting were moderate to severe. No granulocytopenia was noted, although three courses were associated with mild thrombocytopenia. Mucositis, peri orbital swelling, vertigo, and headache were each noted in two of 51 courses of treatment and seizures, ototoxicity, pancreatitis, and hiccups were each noted in one course. Renal toxicity and ototoxicity each developed in three of the 11 patients receiving Cisplatin 120 mg/m2, and nausea and vomiting were severe.
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PMID:Weekly Cisplatin during cranial irradiation for malignant melanoma metastatic to brain. 668 94

There are three types of interferons (IFN), alpha, beta and gamma. IFN-alpha is produced in the leukocytes infected with virus, while IFN-beta is from fibroblasts infected with virus. IFN-gamma is induced by the stimulation of sensitized lymphocytes with antigen or non-sensitized lymphocytes with mitogens. It is believed that IFN-alpha and beta originated from the same ancestral gene, whereas IFN-gamma did not. IFN has not only an antiviral activity, but also various kinds of biological activities including cell growth inhibition, immunosuppressive effects, enhancement of macrophage, natural killer (NK) cell, killer (K) cell and neutrophil functions, and cell differentiation-inducing activity. IFN also shows the antitumor activity resulting from the integration of the above-mentioned biological activities. IFN is also deeply involved in the pathogenesis of various diseases, e.g., collagen diseases such as SLE and rheumatoid arthritis, insulin-dependent diabetes mellitus, fulminant hepatitis, severe pancreatitis, nephritis, multiple sclerosis, allergic diseases, and atherosclerosis. At present, IFN is clinically used in therapy against virus infections such as hepatitis B and C, and for malignancies such as renal cell carcinoma, multiple myeloma, malignant melanoma, glioblastoma, skin cancers, malignant lymphoma and chronic myelogenous leukemia.
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PMID:[Interferon-alpha, beta, gamma]. 799 28

The diagnosis of pancreatic cancer usually depends upon symptoms; consequently it is late when there is no chance for cure. At this point, pain, anorexia, early satiety, sleep problems and weight loss are present. Back pain also may be prominent, which predicts unresectability and shortened survival after resection. However, earlier recognition of symptoms of pancreatic cancer might improve early detection of the cancer. For example, 25% of patients have symptoms compatible with upper abdominal disease up to 6 months prior to diagnosis and 15% of patients may seek medical attention more than 6 months prior to diagnosis. These symptoms erroneously may be attributed to problems such as irritable syndrome. Symptoms, however, may be less common. For example a quarter of patients with pancreatic cancer may have no pain at diagnosis, and half, particularly those with pancreatic head tumors, may have little pain compared with patients with body-tail tumors. However, if the tumor is suspected because of predisposing conditions, earlier diagnosis may be possible. These conditions include diseases such as chronic pancreatitis, intraductal papillary mucinous tumor (IPMT), and recent onset of diabetes mellitus, particularly if the diabetes occurs during or beyond the sixth decade. In addition inherited syndromes also are associated with an increased risk of pancreatic cancer including familial pancreatic cancer, hereditary pancreatitis, familial adenomatous polyposis syndrome (FAP) and familial atypical multiple mole melanoma (FAMMM) syndrome (hereditary dysplastic nevus syndrome). Of these conditions, recent onset of diabetes may be the best clue and should be included in a clinical profile of patients prior to the onset of symptoms to identify a high-risk group to apply screening strategies for detection of early disease. Contrary to a clinical aphorism that pancreatic cancer patients are elderly, lean and recently may have developed diabetes, we found that patients who develop pancreatic cancer are overweight prior to onset of symptoms compared to controls (body mass index, 28 vs 25). Forty percent had the diagnosis of diabetes made at the time of diagnosis of pancreatic cancer and more patients with a resectable tumor had diabetes (58%) compared to patients with locally unresectable or metastatic disease (37%). Perhaps, screening overweight persons who have new-onset diabetes may lead to a diagnosis of asymptomatic, early, resectable pancreatic cancer.
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PMID:Pancreatic cancer: clinical presentation, pitfalls and early clues. 1043 7

Pancreatitis associated protein I is a secretory stress protein first characterized in pancreas during pancreatitis but also expressed in several tissues including hepatic, gastric, and colon cancer. Its concentration in serum can be significant. The relationship of pancreatitis associated protein I to skin cancers was investigated in normal melanocytes, melanoma tumors, and melanoma cell lines. None of them expressed pancreatitis associated protein I, even after stress induction. Adenovirus-mediated pancreatitis associated protein I expression, however, reduced cell adhesion to laminin-1 and fibronectin with a loss of integrin participation. Pancreatitis associated protein I expression stimulated haptotactic and directed migrations of some melanoma cells, but only directed migration was activated in normal melanocytes. Importantly, directed migration and spreading on fibronectin of the responsive melanoma cells were also enhanced when purified rat pancreatitis associated protein I was added to the culture medium of noninfected cells. This indicates that effects in infected cells were elicited by pancreatitis associated protein I after its secretion. Exogenous pancreatitis associated protein I can therefore modify the adhesion and motility of normal and transformed melanocytes, suggesting a potential interaction with melanoma invasivity.
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PMID:Pancreatitis associated protein I (PAP-I) alters adhesion and motility of human melanocytes and melanoma cells. 1123 17

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

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

Hereditary pancreatic cancer (PC) appears to be exceedingly heterogeneous, as evidenced by its association with a variety of integrally associated diverse cancers and/or differing mendelian inherited cancer syndromes, which include the Lynch syndrome II variant of hereditary nonpolyposis colorectal cancer, hereditary breast-ovarian cancer syndrome in families with the BRCA2 mutation, hereditary pancreatitis, Peutz-Jeghers polyposis and the familial atypical multiple-mole melanoma syndrome in families with the CDKN2A (p16) germline mutation. Because of this heterogeneity, we provide a conservative estimate that about 5% (1,460) of PC cases in the US annually are hereditary. Although this number is relatively small, members of hereditary PC families serve as excellent models for studying the etiology, natural history, biomarkers, pathogenesis, potential carcinogenic exposures and their perturbation of underlying genetic events, and treatment of PC. These individuals would benefit greatly from method(s) capable of detecting cancer at an early stage, and such knowledge would also be useful for improving the diagnosis of the much more common 'sporadic' form of PC.
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PMID:Hereditary pancreatic cancer. 1212 Feb 26

Family history of pancreatic cancer, the fifth leading cause of cancer death in the United States, confers a 1.5-13-fold higher risk of developing pancreatic cancer. Pancreatic cancer is associated with several genetic syndromes, including hereditary breast cancer (BRCA2), familial atypical multiple mole melanoma (FAMMM) syndrome, Peutz-Jeghers syndrome, hereditary pancreatitis, and hereditary nonpolyposis colorectal cancer (HNPCC). However, these syndromes explain little of the observed familial aggregation of pancreatic cancer. We performed complex segregation analysis on 287 families ascertained through an index case diagnosed with pancreatic cancer at the Johns Hopkins Medical Institutions between January 1, 1994 and December 31, 1999. We tested for the presence of a major gene controlling either the "age-at-onset of pancreatic cancer" of "susceptibility to pancreatic cancer," and incorporated smoking data on kindred members as a covariate. We found evidence for involvement of a major gene in the etiology of pancreatic cancer. Whether inheritance was modeled as "age-at-onset" or "susceptibility," nongenetic transmission models were strongly rejected. However, modeling "age-at-onset" provided a better fit to the observed data than did modeling "susceptibility." The most parsimonious models included autosomal-dominant inheritance of a rare allele. Under the age-at-onset model, approximately 0.7% of the population appears to be at high risk of developing pancreatic cancer due to this putative gene, whereas 0.4% of the population is at high risk under the susceptibility model. Inclusion of smoking as a covariate did not significantly improve the fit of these models. This hospital-based segregation analysis of pancreatic cancer found evidence supporting the role of a rare major gene influencing risk of pancreatic cancer.
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PMID:Evidence for a major gene influencing risk of pancreatic cancer. 1221 7

The genetic basis for invasive and preoneoplastic neoplasms of the exocrine and endocrine pancreas has been the subject of a number of investigations in recent years. The purpose of this paper was to briefly review and summarize the pertinent findings. High frequency changes associated with pancreatic adenocarcinomas include mutations of the k-ras oncogene, and inactivating alterations of the p53, p16, and DPC4 tumor suppressor genes. Hereditary syndromes that have a known predisposition for pancreatic adenocarcinoma development include hereditary pancreatitis, familial atypical multiple mole melanoma (FAMM) syndrome, Peutz-Jeghers syndrome, familial breast cancer (BRCA-2), hereditary nonpolyposis colorectal cancer syndrome (HNPCC), and Li-Fraumeni syndrome. The underlying genetic defects have been identified and are currently being studied. Germline mutations of the men-1 gene are responsible for the MEN-1 syndrome, known to be associated with pancreatic endocrine tumors. It appears that somatic mutations of the gene are present in at least a subset of sporadic tumors. In addition, alterations in the Rb/p16 pathway appear to be commonly associated with pancreatic endocrine tumors. Further characterization of pancreatic tumors will result in a better understanding of the cellular pathways involved in pancreatic tumorigenesis and holds promise to identify targets for novel diagnostic and therapeutic strategies.
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PMID:The genetics of pancreatic cancer. 1294 33

The dismal prognosis of ductal pancreatic adenocarcinoma is mainly attributable to advanced tumor stages at the time of diagnosis. Meanwhile, familial pancreatic cancer is an established hereditary tumor entity that is responsible for approximately 3% of pancreatic cancer (PC) cases. Therefore, analysis of the family history may help to identify individuals at increased risk of developing PC. These include members of families with a history of PC as well as those of families with distinct hereditary cancer syndromes such as Peutz-Jeghers syndrome, hereditary pancreatitis, familial atypical multiple mole melanoma syndrome, hereditary breast and ovarian cancer syndrome and hereditary non-polyposis colorectal cancer. In future, the identification of germline mutations in genes predisposing to PC, together with the analysis of exogenous risk factors, could be used for a more precise risk assessment for the development of PC. This may allow the application of invasive screening methods for the identification of early PC or, even better, its precursor lesions in high-risk individuals, providing the option of timely curative pancreatectomy.
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PMID:Familial pancreatic cancer. 1513 9


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