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

Bisphosphonates inhibit bone resorption and are therapeutically effective in diseases of increased bone turnover, such as Paget's disease and hypercalcemia of malignancy. The mechanisms by which they act remain unclear. Proposed mechanisms include inhibition of osteoclast formation from precursors and inhibitory or toxic effect on mature osteoclasts. We have developed a new in vitro model to study osteoclast survival and in this paper present in vitro and in vivo evidence that may explain both the observed reduction in osteoclast numbers and in bone resorption by mature osteoclasts, namely that bisphosphonates induce programmed cell death (apoptosis). Three bisphosphonates (risedronate, pamidronate, and clodronate) caused a 4- to 24-fold increase in the proportion of osteoclasts showing the characteristic morphology of apoptosis in vitro. This observation was confirmed in vivo in normal mice, in mice with increased bone resorption, and in nude mice with osteolytic cancer metastases, with similar-fold increases to those observed in vitro. Of the three compounds, risedronate, the most potent inhibitor of bone resorption in vivo, was the strongest inducer of osteoclast apoptosis in vitro. Osteoclast apoptosis may therefore be a major mechanism whereby bisphosphonates reduce osteoclast numbers and activity, and induction of apoptosis could be a therapeutic goal for new antiosteoclast drugs.
 ...
PMID:Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. 868 3

Paget's disease, often an incidental finding, sometimes presents in the form of pain or signs of complications, such as spinal cord compression, malignant transformation or fissures. The diagnosis is established by laboratory tests, but essentially by radiological findings, based on three basic criteria: cortical thickening, loss of cortico-cancellous differentiation and enlargement of the bone, which deformity is a later sign. The diagnosis can usually be made on plain x-rays, but CT is useful in the case of early, difficult or unusual lesions and complications. CT can reveal mouth-eaten, vacuolar, network, clumped or mixed, fibrillary or ivory images. MRI is a last resort examination. Angioma, metastases and ivory vertebrae are the main differential diagnoses.
 ...
PMID:[Vertebral localizations of Paget disease]. 874 98

Epidermotropic metastases from internal malignancies are exceedingly rare. We report two examples of epidermotropic metastatic breast carcinoma with striking intraepidermal involvement. The first case mimicked melanoma because the neoplastic cells contained melanin and were disposed both as single units and as nests at the dermoepidermal junction and throughout the epidermis. In the second case, the neoplastic cells were seen as isolated neoplastic cells with large, pale cytoplasm scattered throughout the epidermis, closely resembling extramammary Paget's disease. Immunohistochemical studies in both cases demonstrated the epithelial nature of intraepidermal neoplastic cells, which showed an immunophenotype identical to the neoplastic cells present in the dermis: positive staining with anti-cytokeratins, CEA, EMA, and GCDFP-15 and negative with anti-S-100 protein and HMB-45. These findings ruled out the possibility of a collision lesion, or simultaneous occurrence of melanoma and metastatic breast carcinoma. Pagetoid intraepidermal spread of metastatic breast carcinoma, as in our two cases, is exceptional. We also discuss the histogenetic similarities between our findings and those of mammary and extramammary Paget's disease, as well as the differential diagnosis of other cutaneous disorders characterized by pagetoid intraepidermal spread of neoplastic cells.
 ...
PMID:Epidermotropically metastatic breast carcinomas. Rare histopathologic variants mimicking melanoma and Paget's disease. 887 3

Adenocarcinoma of the anal glands is a rare slow-growing tumor with a more favorable prognosis compared with colorectal adenocarcinoma, especially if an early diagnosis is established. Clinical symptoms of this disease, often associated with a fistula in ano as in the reported case, include: perianal pain, rectal bleeding and presence of perianal mass. Also perianal Paget's disease may be a not rare association with adenocarcinoma of the anal glands. We believe, therefore, that a histological examination of the resected fistulas in ano should be performed, in searching for the presence of mucinous granules. In addition, it's very important to carry out a careful examination of those patients presenting pruritus ani or eczematous lesions of the anal region. In fact adenocarcinoma of the anal glands may be due to a chronic irritation of the epithelium over a period of years. Radiation therapy and chemotherapy have proved not to provide survival benefit in the treatment of this disease; the same result is obtained with a local excision of the lesion. The only chance for cure, therefore, is early diagnosis followed by radical operation. Miles abdominoperineal resection represents the approach of choice we have adopted for our patient. A radical groin dissection should be carried out only if there are metastases to the inguinal nodes. If necessary, abdomino-perineal resection may be folowed by adjuvant irradiation.
 ...
PMID:[Adenocarcinoma of the anal glands. Description of a clinical case and review of the literature]. 897 62

Glycoproteins of the carcinoembryonic antigen family (CEA) and epithelial membrane antigen (EMA) are established markers for glandular and mucosal tissues. However, their precise ultrastructural distribution in sweat glands has not been determined as yet. Therefore, normal human skin, 19 cases of various sweat gland neoplasms, Paget's disease, and cutaneous metastases of visceral carcinomas were stained with well-defined antibodies using a postembedding immunogold technique. In some cases, a new method of re-embedding paraffin material for immunoelectron microscopy was applied. In normal sweat glands, immunoreactivity of the endoplasmic reticulum and vesicles indicated biosynthesis and processing of CEA and EMA. Along the luminal surfaces both CEA and EMA represented an integral part of microvilli. However, a differential expression of CEA and EMA was demonstrated in apocrine epithelia, mucous cells of eccrine glands, and sweat ducts. In fetal glands, CEA was associated with formation of secretory and ductal lumina. The overall cellular distribution of CEA and EMA was highly preserved in benign sweat gland neoplasms whereas malignant neoplasms were characterized by loss of protein targeting and cellular polarity. In conclusion, these immunoelectron microscopical findings suggest a role of CEA and EMA for cell differentiation and secretory mechanisms of sweat gland epithelia.
 ...
PMID:Ultrastructural localization of carcinoembryonic antigen (CEA) glycoproteins and epithelial membrane antigen (EMA) in normal and neoplastic sweat glands. 900 82

Sweat gland carcinomas are rare malignant tumors of the skin, in addition, the diagnosis of primary sweat gland carcinoma is often difficult. Primary treatment consists of wide surgical excision with regional lymph node dissection, and the tumor is generally not radiosensitive. It has a potential for rapid growth and metastasis. Distant metastasis of sweat gland carcinomas is reputed to have a very poor prognosis because of the chemo-resistance. Most trials of chemotherapy have failed. Numerous single agents have been investigated in this disease, but in only one case did 5-fluorouracil result in complete response. Experience with combination chemotherapy in metastatic disease is limited; only several complete responses and partial responses were reported. In the literature, we found reports on several cases of sweat gland carcinoma with overt disease, which had been treated with different chemotherapeutic agents in various combinations. These studies have suggested the combined use of doxorubicin, cyclophosphamide, mitomycin C, vincristine, cisplatin, 5-fluorouracil, bleomycin and melpharan. Advanced extramammary Paget's disease is also adenocarcinoma of the skin. The recommended treatment for localized extramammary Paget's disease is wide margin resection. The role of therapy in advanced unresectable extramammary Paget's disease is unestablished. A review systemic chemotherapy of extramammary Paget's disease in the literature revealed a few complete responses and partial responses. We tried a new drug combination consisting of epirubicin, mitomycin C. vincristine, carbcplatin and 5-fluorouracil for advanced adenocarcinoma of the skin. Our two patients had excellent responses to this new regimen.
 ...
PMID:[Chemotherapy for advanced adenocarcinoma of the skin: experience with combination chemotherapy and a review of the literature]. 902 Sep 42

Paget's disease is occasionally found as an incidental finding on bone scans performed for the evaluation of metastatic disease, which causes a diagnostic and a subsequent therapeutic dilemma. We have previously described the "Mouse Face" appearance of vertebrae on bone scans (increased uptake in the vertebral body, posterior elements, and the spinous process), which was fairly specific for Paget's disease in a small series. This retrospective study was undertaken to determine if this observation holds true in a larger series. Bone scans performed in 2,881 patients were randomly selected, and were reviewed by 2 physicians. Thirty-nine cases with a "Mouse Face" appearance were identified. Diagnosis was established in 30 of the 39 patients by correlative radiographic studies and/or clinical follow-up. Twenty patients were referred for the evaluation of possible metastases, and 7 were found to have metastases at the sites of "Mouse Face". The other 13 had Paget's disease. However, 6 of the 7 patients with metastases had extravertebral findings compatible with multiple metastases, and the remaining patient had a "Mouse Face" lesion only, with a question of metastases. Ten patients were evaluated for Paget's disease or others, and none of them had metastases at the site of the "Mouse Face". The "Mouse Face" appearance is more suggestive of Paget's disease than metastases even in patients with cancer. These patients should be assumed unlikely to have vertebral metastases, unless proven by another correlative radiologic study.
 ...
PMID:The 'mouse face' appearance of the vertebrae in Paget's disease. 903 68

A case of Paget's disease of the vulva is presented which, over a period of 6 years, was characterized by local recurrences and metastases to the bone marrow. Detailed examination of multiple sections of the primary tumor and of the bone marrow biopsy specimen failed to demonstrate an underlying adenocarcinoma in any of the sites. The routine histologic staining and immunohistochemical staining demonstrated that the metastatic cells strongly correlated with cells from the vulvar lesion. Specifically, immunohistochemical staining of the specimens from the primary and metastatic sites was positive for the gross cystic disease fluid protein-15, which has been associated with extramammary Paget's disease uncomplicated by underlying malignancies. Finally, during several years of close follow-up, no other primary site of Paget's disease declared itself clinically or was found by radiographic studies or analysis of serum tumor markers.
 ...
PMID:Extramammary Paget's disease of the vulva: metastases to the bone marrow in the absence of an underlying adenocarcinoma--case report and literature review. 923 36

Only 27 cases of Paget's disease of the groin have been reported to the present. Our aim was to describe the clinical behavior and treatment of this disease. A retrospective analysis of patients seen at the Mayo Clinic over a period of 25 years (January of 1970 to December of 1995) was undertaken. We included patients with lesions of the groin (isolated or associated with penile/scrotal locations) and with histologic confirmation of the diagnosis. We found seven patients, all male; three patients had isolated lesions. Their mean (SD) age was 73 (8.3) years. Special stains and immunohistochemistry confirmed the diagnosis in all patients. A wide local excision was performed in every patient. Three patients had recurrence; one of them died with multiple pulmonary metastases 4 years later. Two patients presented with history of associated malignancy (prostatic and renal cell carcinoma). Paget's disease of the groin is extremely infrequent. Its origin seems not to be a simple extension from the genital area. Most diagnoses can be made by light microscopy. Wide local excision with free margins is the treatment of choice. Local recurrence occurs in half of patients with tumor-free margins by frozen section; long-term follow-up is warranted. Distant metastases occur rarely, although they can be fatal.
 ...
PMID:Paget's disease of the groin: report of seven cases. 925 99

Cutaneous metastases may be the first clinical manifestation of a visceral carcinoma, its incidence fluctuates between 0.7 and 9% of the carcinomas and normally indicate a dismal prognosis. The most frequent morphologies of cutaneous metastases are metastatic nodules, sclerotic forms that appear as infiltrated and stiff plates, the inflammatory variety that resembles an erysipelatous plate, mammary and extra-mammary Paget's disease that appear as erythematous erosive and crusty plates resembling dermatitis.
 ...
PMID:[Cutaneous metastases. Clinical pathological review]. 933 88


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>