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)

Melanoma often develops from clinically and histologically well-defined precursor lesions. During progression of normal melanocytes to benign nevi, dramatic changes in the expression of adhesion receptors are observed, most notably loss of E-cadherin which mediates adhesion of melanocytes to keratinocytes, and gain of Mel-CAM which predominantly mediates heterotypic adhesion between cells. Major changes in adhesion receptors also occur when cells progress from dysplastic nevi or biologically early radial-growth-phase primary melanomas to biologically late (tumorigenic) vertical-growth-phase primary melanomas. The integrin subunit beta 3 is up-regulated, whereas other integrins such as alpha 6 beta 1 and alpha V beta 1 are down-regulated. This review highlights the major changes in adhesion receptor expression on melanocytes at various stages of tumor progression.
Invasion Metastasis
PMID:Adhesion receptors in human melanoma progression. 765 8

We report 25 cases of a peculiar sclerosing epithelioid variant of fibrosarcoma (SEF) simulating an infiltrating carcinoma. The tumors occurred primarily in the deep musculature and were frequently associated with the adjacent fascia or periosteum. The patients' ages were 14 to 87 years (median, 45). Fourteen were male and 11 female. The tumors were located in the lower extremities and limb girdles (12 cases), trunk (9), upper limb girdles (2), and neck (2). They measured 2 to 14.5 cm in greatest dimension (median size, 7 cm) and were gray to white and firm. Histologically, the lesions were characterized by a proliferation of rather uniform, small, slightly angulated, round to ovoid epithelioid cells with sparse, often clear cytoplasm arranged in distinct nests and cords. In all cases there was prominent hyaline sclerosis, sometimes reminiscent of osteoid or cartilage and foci of conventional fibrosarcoma. Occasional myxoid zones with cyst formation and foci of hyaline cartilage, calcification, and metaplastic bone were also seen. Mitotic figures were generally scarce. Vimentin was detected in 13 of 14 cases, epithelial membrane antigen in seven, S100 protein in four, and neuron-specific enolase in two. Cytokeratins were detected with AE1/AE3 and CAM 5.2 in two cases. Leukocyte common antigen, CD68 antigen, HMB45, desmin, and alpha-smooth muscle actin were negative in all cases. In 13 of 14 cases, 75% or more of the cells stained for proliferating cell nuclear antigen (PCNA). Ki67 immunostaining with MIB 1 showed low proliferative activity in all cases, averaging 5% of tumor cells or less. In all cases, p53 was detected by immunohistochemical methods; bcl-2, an antiapoptosis marker, was detected in more than 90% of the cells in 11 of 12 cases. Ultrastructurally, both the epithelioid and spindled tumor cells had features of fibroblasts. Follow-up in 16 cases ranging from 13 months to 17 years 3 months (median, 11 years 4 months) revealed persistent disease or local recurrences in 53% of patients and metastases in 43%. The metastases were to the lungs (4 cases), skeleton (3), chest wall/pleura (3), pericardium (1), and brain (1). Four patients died of disease, four were alive with disease, two were known to be alive but disease status unknown, and six had no evidence of further disease at last follow-up. The data suggest that SEF is a relatively low-grade fibrosarcoma; yet it is fully malignant despite the presence of histologically benign-appearing foci. The proliferation markers PCNA and Ki67 did not correlate with prognosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sclerosing epithelioid fibrosarcoma. A variant of fibrosarcoma simulating carcinoma. 766 Dec 86

In recent years, the incidence of endometrial cancer has tended to increase gradually in Japan. Most cases (early cancer of stage I and II) are treated by hysterectomy alone, and the prognosis has been relatively good. From analysis of the poor prognostic factors in endometrial cancer, we understood that additional therapy is necessary for patients who have the following factors: degree of differentiation: G3; invasion to > 1/2 myometrium; metastases to pelvic or para-aortic lymph node, isthumus-cervix extension; surgical stage III and more. However, for patients with advanced inoperable and recurrent cancer, a radiotherapy, is not so sensitive to endometrial cancer has been used. A first line establish a chemotherapy has not been established either. Various attempts have been made to establish a chemotherapy for endometrial cancer. As a result, adriamycin (ADR) and cisplatin (CDDP) have proved effective as single agents. For patients with early cancer who have the poor prognostic factors mentional above, irradiation and polychemotherapy regimens (CAP and AP) are effective. Since the progression of endometrial cancer is dependent on sex steroid hormones, antitumor effects of Medroxyprogesterone acetate (MPA) are expected to be effective for patients with estrogen receptor (ER) positive and progesterone receptor (PR) positive cancer, or with well-differentiated adenocarcinoma (G1 type) histologically. Although several forms of therapy are capable of inducing objective remission as adjuvant treatment, all treatment for advanced and recurrent disease remains palliative, and responses and survival for patients treated with irradiation and chemotherapy remain short. Furthermore, we should examine new methods such as new drug application of key drugs like ADR and Pt pharmaceutical preparation, improvement of Dose intensity of the key drugs and Biochemical modulation, CPT-11, Taxol and assembly of key drugs, along with the Circadian approach in the light of Biochronology.
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PMID:[Chemotherapy of uterine endometrial cancer]. 766 68

We evaluated three cases of pigmented pulmonary carcinoid tumors that were retrieved from the files of the Armed Forces Institute of Pathology, Washington, DC. Clinical follow-up showed no indication of tumor recurrence or metastases, nor was there evidence of malignant melanoma. All three cases exhibited histologic features of typical carcinoid tumor; there were focal oncocytic changes in two cases. Finely dispersed, brown pigment, believed to be melanin, was distributed in two different patterns: in sustentacular cells (case 1) or within the tumor cells (cases 2 and 3). Fontana-Masson stain was positive in areas of this pigment in all cases. The tumor cells showed immunoreactivity for chromogranin, synaptophysin, keratin (AE1/AE3 and CAM-5.2), and S100 protein in all cases. Focal staining for vimentin and corticotropin was seen within neoplastic cells in two cases. The pigmented sustentacular cells in case 1 showed focal immunoreactivity for S100 protein and HMB-45. Ultrastructural studies of paraffin-embedded tissues were performed in two cases. They showed well-developed melanosomes in the pigmented sustentacular cells in case 1. In both cases, cytoplasmic neurosecretory-type granules were identified in neoplastic cells. These findings demonstrate that pigmented pulmonary carcinoid tumor has an immunohistochemical profile similar to that of typical pulmonary carcinoid tumor. In some instances, pigmented pulmonary carcinoid tumors may show ultrastructural evidence of melanocytic and neuroendocrine differentiation. These immunohistologic and ultrastructural findings distinguish pigmented pulmonary carcinoid tumor from malignant melanoma and support the concept of "multidirectional cellular differentiation."
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PMID:Pigmented pulmonary carcinoid tumor. An immunohistochemical and ultrastructural study. 768 14

One hundred patients with metastatic breast cancer were randomly selected to receive combined chemotherapy treatment with adriamycin (50 mg/m2) or mitoxantrone (12 mg/m2) associated with 5-fluorouracil (600 mg/m2) and cyclophosphamide (600 mg/m2) administered intravenously every 21 days with a maximum of ten cycles. All patients included in this study were under 75 years of age and had ECOG performance status of less than 4. They had not been treated previously with chemotherapy for metastatic disease. Patients treated with adjuvant chemotherapy, which could not have included anthracyclines, had to have relapsed at least 12 months after the completion of therapy. There were no statistically significant differences in pretreatment characteristics or metastatic disease location between the two groups. Ninety-four patients were assessable for response. No differences were observed in response rate or in survival between the groups. The response rate (complete response (CR) and partial response (PR)) was 68% (13% CR and 55% PR for CAF; 0% CR and 68% PR for CNF). Median survival for all patients was 19 months (18 months with CAF and 19 months with CNF). All patients were assessable for toxicity. There were no differences in gastrointestinal and cardiac toxicity. More grade I-II hematologic toxicity episodes (p < 0.001) and treatment delays (p = 0.05) due to leucopenia were observed with the CNF group, and more grade III alopecia (p < 0.001) was observed with the CAF group. Patients received further therapeutic manoeuvres after finishing the study with a sequential treatment consisting of hormonal therapy and chemotherapy with mitomycin (M) -vinblastine (Vbl) (M 10 mg/m2 day 1, Vbl 5 mg/m2 days 1, 15 and 29; maximum 5 cycles). This chemotherapy treatment was received by 32 patients, with a response rate of 34% and grade III-IV hematologic toxicity of 37%. Treatment with CNF can be considered a good alternative to CAF for first-line treatment of metastatic breast cancer. M-Vbl treatment is useful as second-line treatment in patients with prior adriamycin exposure.
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PMID:A phase III randomized trial of cyclophosphamide, mitoxantrone, and 5-fluorouracil (CNF) versus cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) in patients with metastatic breast cancer. 774 56

We document a case of a patient who had been treated for a medullary cell carcinoma of the thyroid three years previously and who presented with a three month history of ataxia, weakness and headache. A CT scan showed contrast enhancing lesions in the posterior fossa. An MIBG uptake scan showed that there was some uptake in the cerebellar lesions; however, it was not sufficient to rely on this alone for treatment. The larger of these lesions was therefore surgically resected. Immunocytochemistry, using CAM 5.2, CEA and chromogranin, demonstrated a positive reaction which strongly favoured a diagnosis of metastases from a medullary cell carcinoma of the thyroid. However, absolute confirmation of the diagnosis was obtained using immunocytochemistry with calcitonin. Medullary cell carcinomas of the thyroid usually spread locally and metastasis to the brain has never before been reported.
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PMID:Medullary cell carcinoma of the thyroid: metastases to the central nervous system. 778 10

The purpose of this study was to determine whether methotrexate, vinblastine, doxorubicin, and cisplatin, each individually active in metastatic breast cancer (MBC), could, in combination, produce an overall response rate, median survival, and long-term survival sufficiently promising to merit its consideration for phase III trials in MBC and as induction therapy prior to autologous bone marrow transplant. From July 1986 through February 1990, 30 patients with stage IV, measurable breast carcinoma received M-VAC: methotrexate--30 mg/m2 days 1, 15, 22; vinblastine--3 mg/m2 days 2, 15, 22; doxorubicin--30 mg/m2 day 2; cisplatin--70 mg/m2 day 2. Cycles were repeated at 4-week intervals for up to six courses. Median age was 53 years (range 34-64 years). Prior treatment included adjuvant cyclophosphamide, methotrexate, and 5-Fluorouracil in 12 patients, radiotherapy in 13 patients, and hormonal therapy in 14 patients. Eleven patients were ER (+) at the time of initial diagnosis. Five patients had disease restricted to bone and/or nodes; the other 25 had visceral-dominant sites of metastases, with or without bone involvement, or evidence of rapid, inflammatory chest wall relapse. Twenty-nine of 30 patients were evaluable for toxicity and response; all were evaluable for survival. The major overall response rate was 83%, with a 21% complete remission rate. The chief toxicity was bone marrow suppression, with grade 4 granulocytopenia in 20 patients, grade 3 in 7 patients, and grade 3 and 4 thrombocytopenia in 5 patients. Grade 3 stomatitis occurred in 9 patients. Renal insufficiency was clinically insignificant, and neurotoxicity mild, with 7 patients sustaining grade 1 or 2 paresthesias. Median time to progression was 9 months and median survival 19 months (range, 5-84+ months) with 4 patients still alive at least 45+ months or more from the start of treatment and 2 presently free of progressive disease. Although highly toxic, M-VAC produces a response rate and survival duration in visceral-dominant MBC competitive with, if not superior to, conventional regimens such as CAF (Cytoxan, doxorubicin, 5-fluorouracil); it therefore merits further investigation in conjunction with hematopoietic growth factors and as cytoreductive therapy prior to autologous bone marrow transplantation.
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PMID:Phase II evaluation of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) in advanced, measurable breast carcinoma. 787 68

Loss of cell adhesion is a critical event in the development of tumour invasiveness and metastases. Although loss of cadherin expression has been demonstrated to be associated with increased invasiveness and metastatic potential in some tumours, others, including renal carcinoma, show no such correlation. The aim of this study was to demonstrate that cell adhesion could be lost in phorbol ester-treated renal epithelial cells and renal tumour cells without loss of A-CAM expression. The model used has been shown previously to mimic changes that occur in the progression of renal carcinoma. We found that A-CAM expression persists on the lateral surfaces of phorbol ester-treated cells even though these cells lose cell-cell adhesion. Similar findings were seen in renal carcinoma cells in culture. We conclude that loss of cell adhesion between tumour cells may other either by loss of cadherins or as a result of loss cadherin function occurring as a consequence of cell transformation.
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PMID:Disruption of cell adhesion in renal epithelium without cadherin loss. 789 Dec 26

Surgical resection is the treatment of choice for patients with localized non-small cell lung cancer. However, the long-term survival rate of patients after such surgery is disappointing. Even in stage I patients who have undergone potentially curative operation, over 30% of them recur within five years. Most of the recurrences are caused by hematogenous metastases to the distant organs. However, all of the comparative study to evaluate postoperative adjuvant therapy, ie, chemotherapy, immunotherapy, radiotherapy, or their combination, showed negative results, except for a few positive outcomes. To date, there is no evidence that pre- and postoperative adjuvant therapy have shown a favorable impact on survival of postoperative patients with stage I disease. LCSG has had reportedly favorable results on survival of stage II and III adenocarcinoma and large cell carcinoma by postoperative CAP-chemotherapy. Postoperative chemotherapy and/or radiotherapy showed no impact on survival of stage III patients who underwent surgical intervention. However, preoperative induction therapy (IT) using combination chemotherapy (with or without radiotherapy) has improved the survival of patients with resected stage III disease, although most reports are of phase II trial or interim results. It seems to be true that the IT can render an advanced lung cancer resectable and also can control pre-existing micro-metastases in the distant organs. However, randomized prospective trials are required for evaluating an impact on the survival rate of the advanced non-small cell lung cancer.
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PMID:[Combined multimodality treatment for non-small cell lung cancer--with special reference to pre- and post-operative adjuvant therapy]. 797 13

This paper presents a case with lung metastases from breast cancer. Complete response was obtained by combined chemoendocrine therapy with 5'-DFUR and MPA. The patient was a 62-year-old female. She underwent a standard radical mastectomy in April, 1988. The primary legion was ER (-) and PgR (-). Postoperative treatments using CMF and CAF were eventually discontinued owing to profound damage to the bone marrow. An adjuvant chemotherapy with UFT has been employed since. Two years and 7 months later, hemosputum and coughing appeared, and metastases to the lung were revealed. Combined chemoendocrine therapy with 5'-DFUR and MPA was undertaken. A significant decrease in tumor size was observed 3 months after the chemoendocrine therapy was begun, and complete response was obtained at the 8th month. The state has been maintained for one year and 9 months. The use of combined chemoendocrine therapy with 5'-DFUR and MPA in patients for whom intensive chemotherapy is not possible due to damage to bone marrow function is considered effective for its antitumor effects or maintaining patients' quality of life.
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PMID:[A case of complete response of breast cancer with pulmonary metastases to combination therapy of 5'-DFUR and MPA]. 797 28


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