Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two main distinct subtypes of epithelial skin cancers can be distinguished, both arising from keratinocytes, most frequently at sun-exposed body sites. Basal cell carcinomas (BCC) grow slowly, nearly never metastases, whereas squamous carcinomas (SCC) are locally more invasive tumors, which have a greater metastatic potential. Skin carcinogenesis is a multiple step process, in which UV light play a major role. Numerous genetic lesions occur, either inactivating tumor suppressor genes (which normally repress cell growth), or activating oncogenes (which promote cellular multiplication). The most important tumor suppressor gene involved in both skin neoplasms is p53, which is inactivated in 40-50% of cases, by specific UV induced mutations. Yet, some differences exist between these two subtypes, which could explain their difference in invasiveness.
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PMID:[Skin carcinogenesis]. 1033 91

We have studied 25 cases of squamous cell carcinoma in chronic venous leg ulcers. Twenty-three of the patients were dead and two were alive. The mean age at cancer diagnosis was 78.5 years. The median survival was 1 year. Eleven tumours were well-differentiated, 10 moderately and four poorly. All patients with a poorly differentiated tumour died within a year. Metastases were certain in eight cases. The disease was lethal in 10 cases which included all poorly differentiated tumours. The survival of the study group was significantly shortened compared with a control group of patients with lower limb non-melanoma skin cancer (n = 433) from the Swedish Cancer Registry (P = 0.0084). When diagnosed, squamous cell carcinoma in chronic leg ulcers merits a thorough investigation of the degree of differentiation and spread. Assertive treatment is indicated as poorly differentiated tumours and some moderately differentiated tumours may be fatal.
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PMID:Squamous cell carcinoma complicating chronic venous leg ulceration: a study of the histopathology, course and survival in 25 patients. 1035 87

Merkel cell carcinoma of the lower lip is a rare clinical entity. It is generally thought to be more aggressive than the more common skin cancers of the lips and oral cavity. The literature reveals that delayed diagnoses and poor survival are common among patients with these malignancies. Recommended treatment is surgical excision with wide margins and treatment of cervical metastases with either surgery or radiotherapy or both. Unlike other malignant neoplasms, the occurrence of Merkel cell carcinoma in a relatively older population makes comorbid conditions a key factor in treatment planning.
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PMID:Merkel cell carcinoma of the lower lip: a case report and histopathologic study. 1044 39

Our previous study in extramammary Paget's disease showed neither p53 mutations nor allelic loss at selected loci implicated in other cancers, suggesting a pathogenesis of this skin cancer different from other common epithelial malignancies. To examine further the genetic defects in extramammary Paget's disease, we carried out molecular genetic analyses in 31 tumor samples obtained from 27 cases of extramammary Paget's disease without underlying malignancies. Immunohistochemistry using CB-11 monoclonal antibody revealed either membrane or cytoplasmic erbB-2 oncoprotein overexpression in none of the 13 primary in situ tumors, but in one recurrent in situ tumor, 10 of 13 invasive primary tumors and two of four lymph node metastases. Sensitive dual color fluorescence in situ hybridization analysis using probes for erbB-2 gene locus and chromosome 17 pericentromere, however, revealed different erbB-2 gene status in the erbB-2 overexpressing tumors. One recurrent in situ tumor and one lymph node metastasis showed definite gene amplification characterized by multiple scattered signals or a few large clustered erbB-2 signals, whereas four tumors with predominantly cytoplasmic erbB-2 overexpression were thought to have low-grade gene amplification. The remaining six tumors overexpressing erbB-2 showed no increase of erbB-2 copy numbers. No evidence of abnormal activation of the beta-catenin gene, a critical mediator of Wnt signaling pathway, in any tumor by immunohistochemical staining and by direct sequencing and reverse transcription-polymerase chain reaction analysis was found. Frequent overexpression of erbB-2 by either gene amplification or possible transcriptional activation in invasive primary tumors and metastases suggests an important part for this oncogene in the progression of extramammary Paget's disease.
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PMID:erbB-2 overexpression but no activation of beta-Catenin gene in extramammary Paget's disease. 1046 13

We describe herein a brother and sister diagnosed with xeroderma pigmentosum variant (XP-V) in early adult life, who presented with increased sensitivity to sunlight and with cutaneous carcinomas on sun-damaged skin. The 27-year-old male farmer (Case 1.) was diagnosed with advanced squamous cell carcinoma (SCC) and multiple actinic lesions. Surgical removal of these lesions was performed. Three months later he died of multiple pelvic metastases of SCC. His 29-year-old sister (Case 2.) was operated on for different tumors, histologically SCC-s or basal cell carcinomas (BCC), or praecancerous conditions many times. After a two year interval she was treated with low dose isotretinoin (2 mg/body weight). Diagnosis of XP-V was based on unscheduled DNA analysis (USD) and on clinical symptoms. We observed that during the long lasting isotretinoin treatment the tumor frequency dropped to a quarter. Therefore, the isotretinoin treatment seems to be a good approach for cancer prevention in conditions with high predisposition to skin cancer, such as in XP-V.
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PMID:Cancer protection in xeroderma pigmentosum variant (XP-V). 1047 30

In the general population Merkel's cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. More than 600 cases have been reported. MCC seems to be common in transplant recipients, with 41 cases being reported to the Cincinnati Transplant Tumor Registry, and another 11 in the transplant literature. In the general population, it is a disease of older adults, with only 51% of cases occurring below the age of 50 years. In transplant patients, the mean age at diagnosis was 53 (range 33-78) years, and 29% of recipients were <50 years old. The tumor appeared from 5 to 286 (mean 91.5) months after the transplant. Of 44 lesions that occurred in 41 patients, the distribution was similar to that seen in the general population, with 36% occurring on the head and neck, 32% on the upper extremities, 16% on the trunk, 9% at unknown sites, and 7% on the lower extremities. Twenty of the patients (49%) had 22 other malignancies, the great majority of which (91%) were other skin cancers. Treatment depended on the stage of the disease and included wide surgical excision, radical lymph node dissection, radiation therapy, and chemotherapy. In transplant patients, MCC probably proved to be more aggressive than in the general population in that 68% of patients developed lymph node metastases and 56% died of their malignancies. Furthermore, one third of surviving patients still have active cancers from which they may die. Also, follow-up of survivors has been relatively short, with a mean of only 18 (range 0-135) months.
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PMID:Merkel's cell carcinoma in organ recipients: report of 41 cases. 1060 48

Cyclooxygenase (COX)-2 levels are elevated in several types of human cancer tissues. Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both the COX-1 and COX-2 protein, the two enzymes that convert arachidonic acids to prostaglandins. Regular use of such NSAIDs significantly reduces the risk and spread of some cancers. The objective of this study was to elucidate the molecular pathology of neoplasms that overexpress COX-2. Epidemiological data and clinical studies were analyzed and compared with results of studies of human tumor tissues, animal models, and cultured tumor cells. COX-2, but not COX-1, is highly expressed in human colon carcinoma, squamous cell carcinoma of the esophagus, and skin cancer. COX-2 is inducible by oncogenes ras and scr, interleukin-1, hypoxia, benzo[a]pyrene, ultraviolet light, epidermal growth factor, transforming growth factor beta, and tumor necrosis factor alpha. Dexamethasone, antioxidants, and tumor-suppressor protein p53 suppress COX-2 expression. COX-2 synthesizes prostaglandin E2 (PGE2) which stimulates bcl-2 and inhibits apoptosis, and induces interleukin-6 (IL-6) which enhances haptoglobin synthesis. PGE2 is associated with tumor metastases, IL-6 with cancer cell invasion, and haptoglobin with implantation and angiogenesis. Drastic reduction in polyp number results from COX-2 gene knockout as well as from selective COX-2 inhibition in a mouse model of human familial adenomatous polyposis. Nonselective NSAIDs, for instance aspirin, and selective COX-2 inhibitors such as celecoxib (SC-58635) and NS-398 suppress azoxymethane-induced colon carcinogenesis in rats. Aspirin, indomethacin, and ibuprofen decrease cultured lung cancer cell proliferation. Selective inhibition of COX-2 is preferable to nonselective inhibition. It reduces cancer cell proliferation, induces cancer cell apoptosis, and spares COX-1-induced cytoprotection of the gastrointestinal tract.
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PMID:Molecular pathology of cyclooxygenase-2 in neoplasia. 1067 79

Photodynamic therapy (PDT) uses exogenously administered photosensitizers activated by light to induce cell death or modulation of immunological cascades, presumably via formation of reactive oxygen species (ROS). 5-Aminolevulinic acid (ALA) mediated photosensitization is increasingly used for the treatment of nonmelanoma skin cancer and other indications including benign skin disorders. Long-term side effects of this investigational modality are presently unknown. Just as tumor treatments such as ionizing radiation and chemotherapy can cause secondary tumor induction, PDT may potentially have a carcinogenic risk. Evaluation of the biological effects of ALA in absence of activating light and analysis of the mechanism of ALA-PDT and porphyrin-type photosensitizers mediated photosensitization indicate that this therapy has a pro-oxidant and genotoxic potential. However, porphyrin type molecules also possess antioxidant and antimutagenic properties. ALA-PDT delays photocarcinogenesis in mice, and topical ALA alone does not increase skin cancer incidence in these animals. Patients with increased tissue levels of ALA have an increased incidence of internal carcinoma, however, it is not clear whether this relationship is casual or causal. There is no evidence indicating higher rates of skin cancer in patients with photosensitivity diseases due to presence of high protoporphyrin IX (PP) levels in skin. Overall, the presently available data indicate that the risk for secondary skin carcinoma after topical ALA-PDT seems to be low, but further studies must be carried out to evaluate the carcinogenic risk of ALA-PDT in conditions predisposed to skin cancer.
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PMID:Genotoxic potential of porphyrin type photosensitizers with particular emphasis on 5-aminolevulinic acid: implications for clinical photodynamic therapy. 1071 35

The incidence of both melanoma and nonmelanoma skin cancer is increasing, and an accurate and timely diagnosis is important to reduce the morbidity and mortality associated with these malignancies. Clinical features and examination techniques are discussed, and the need to recognize important secondary tumor characteristics, which supplement the primary diagnosis, is reviewed. Recent evidence on etiologic factors and their importance are addressed to highlight the role of primary prevention. Pediatricians, family physicians, and all primary care physicians are encouraged to promote skin cancer awareness among children and their parents.
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PMID:Overview of skin cancer detection and prevention for the primary care physician. 1080 78

The incidence of skin cancer is increasing by epidemic proportions. Basal cell cancer remains the most common skin neoplasm, and simple excision is generally curative. Squamous cell cancers may be preceded by actinic keratoses-premalignant lesions that are treated with cryotherapy, excision, curettage or topical 5-fluorouracil. While squamous cell carcinoma is usually easily cured with local excision, it may invade deeper structures and metastasize. Aggressive local growth and metastasis are common features of malignant melanoma, which accounts for 75 percent of all deaths associated with skin cancer. Early detection greatly improves the prognosis of patients with malignant melanoma. The differential diagnosis of pigmented lesions is challenging, although the ABCD and seven-point checklists are helpful in determining which pigmented lesions require excision. Sun exposure remains the most important risk factor for all skin neoplasms. Thus, patients should be taught basic "safe sun" measures: sun avoidance during peak ultraviolet-B hours; proper use of sunscreen and protective clothing; and avoidance of suntanning.
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PMID:Early detection and treatment of skin cancer. 1092


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