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)

Phyllodes tumor is an uncommon biphasic breast tumor, with the ability to recur and metastasize, and it behaves biologically like a stromal neoplasm. Traditionally, phyllodes tumors are graded by the use of a set of histologic data into benign, borderline, and malignant. In most series, all phyllodes tumors may recur, but only the borderline and malignant phyllodes tumors metastasize. On the basis of histologic features, prediction of behavior is difficult. The expression of many biological markers, including p53, hormone receptors, proliferation markers, angiogenesis group of markers, c-kit, CD10 and epidermal growth factor receptor have been explored, and many have been shown to be variably expressed, depending on the grade of the tumor. These markers are, however, of limited value in predicting the behavior of the tumor. Recently investigators have reported a plethora of genetic changes in phyllodes tumors, the most consistent of which seems to be 1q gain by comparative genomic hybridization. Some candidate genes have been mapped to various sites, and preliminary data suggest that some of these changes may be related to recurrence. It is foreseeable that more exciting data will be generated to help us to understand the etiology and pathogenesis of phyllodes tumor.
 ...
PMID:Phyllodes tumor of the breast: an update. 1943 72

A 61-year-old woman with no significant past history underwent gastric biopsies demonstrating a strongly c-kit-positive epithelioid malignancy, initially thought to represent gastrointestinal stromal tumor (GIST). Subsequent clinical and immunohistochemical evaluation proved the neoplasm to represent metastatic lobular carcinoma. This case illustrates that although c-kit is highly specific and sensitive for GIST, its expression may occur in a variety of other neoplasms, some of which morphologically resemble GIST and may present in the gastrointestinal tract as metastases. Therefore, a review of other c-kit-positive lesions is also highlighted.
 ...
PMID:C-kit-positive gastric metastasis of lobular carcinoma of the breast masquerading as gastrointestinal stromal tumor. 1946 11

A 67-year-old woman underwent resection of a gastric tumor and a synchronous metastatic lesion of the liver in 1991. Histopathologically, both the primary and metastatic tumors were diagnosed as leiomyosarcoma. Four years after the initial resection, another liver metastasis was detected in the caudate lobe, and a partial hepatectomy was performed. Multiple bilateral lung metastases were identified 7 years later and one was resected. Immunohistochemically, tissues from both the primary and metastatic sites were positive for KIT and CD34, and a c-kit gene mutation was found in the resected lung lesion. The remaining lung metastases responded to treatment with imatinib mesylate, but the treatment was discontinued because of toxicity. The patient remains under observation and the lung lesions have not progressed. At present she has no symptoms, and she has had no further recurrences in the past 3 years. This case is extremely unusual; a slowly progressing gastrointestinal stromal tumor over the course of 17 years from the initial diagnosis, with hematogenous metastases at multiple sites.
 ...
PMID:Gastrointestinal stromal tumor of the stomach with extremely slow-growing hematogenous metastasis. 1959 21

Breast phyllodes tumors are rare fibroepithelial neoplasms that need to be distinguished from the common morphologically similar fibroadenomas, because phyllodes tumors can recur and progress to malignancy. Their potentially recurring and metastasizing behavior is attributed to their stromal characteristics, for which categorization between benign, borderline and malignant tumors have not been universally established. Previous clonality studies revealing monoclonal stromal cells versus a polyclonal epithelial component theorized that phyllodes tumors are mainly stromal neoplasms, possibly arising from fibroadenomas. More recent chromosomal imbalances in both epithelium and stroma have challenged this theory to favor neoplasia of both epithelium and stroma, with initial interdependence between the two components. Inverse correlations between epithelial and stromal overexpression for various biological markers like estrogen receptor, p53, c-kit, Ki-67, endothelin-1, epidermal growth factor receptor, heparan sulfate, in addition to findings of epithelial Wnt signalling with stromal insulin growth factors and beta-catenin expression, suggest an initial epithelial-stromal interdependence at the benign phase. Upon progression to malignancy, the stroma is hypothesized to assume an autonomous growth overriding any epithelial influence. Frequent genetic alterations are chromosomal gains of 1q and losses at chromosome 13. Acquisition of new genetic imbalances within the tumor consistent with intratumoral heterogeneity, and subclones within histologically benign phyllodes tumors that recur or metastasize are the current theories explaining these tumors' unpredictable clinical behavior.
 ...
PMID:Molecular pathogenesis of progression and recurrence in breast phyllodes tumors. 1996 35

This case series presents a unique and unreported variant of feline intestinal mast cell tumour recognized at the CSU Veterinary Diagnostic Laboratory. Fifty cases of feline intestinal mast cell tumours described as having a significant stromal component were reviewed. Neoplastic cells formed a trabecular pattern admixed with moderate to abundant dense stromal collagen (sclerosis). Neoplastic cells had poorly discernible intracytoplasmic granules which demonstrated metachromasia with special histochemical stains consistent with mast cell granules. Additionally, a subset of cases stained for mast cell-specific tryptase and c-kit demonstrated positive immunoreactivity. Eosinophilic infiltrates were moderate to marked in almost all cases. Lymph node and hepatic metastases were present in 66% of the cases. Treatment and clinical outcome was available in 25/50 cases. Twenty-three of these patients died or were euthanized within 2 months of initial diagnosis. This is the first case series to characterize a sclerosing variant of intestinal mast cell tumour in the cat which appears to have a high propensity for metastasis and a guarded prognosis.
 ...
PMID:Feline intestinal sclerosing mast cell tumour: 50 cases (1997-2008). 2069 Oct 31

Emerging data suggests that host immune cells with a suppressive phenotype represent a significant hurdle to successful therapy for metastatic cancer. Among the suppressor cells, T regulatory cells (Treg) and myeloid-derived suppressor cells (MDSC) are significantly increased in hosts with advanced malignancies. MDSC mediate the suppression of the tumor antigen-specific T cell response through the induction of T cell anergy and the development of Treg in tumor-bearing mice. These results provide robust evidence of an in vivo immunoregulatory function of MDSC in the establishment of tumor antigen-specific tolerance and the development of Treg in tumor-bearing hosts. To achieve effective anti-tumor immunity, tumor-induced immunosuppression must be reversed. Our preliminary results indicate that c-kit ligand (stem cell factor) expressed by tumor cells may be required for MDSC accumulation in tumor-bearing mice, and that blocking the c-kit ligand/c-kit receptor interaction can prevent the development of Treg and reverse immune tolerance induced by MDSC. Since c-kit can be readily inhibited by several small molecule inhibitors including imatinib, sunitinib and dasatinib, targeting immune suppressing cells can be readily accomplished in the clinic.
 ...
PMID:Targeting immune suppressing myeloid-derived suppressor cells in oncology. 2030 69

Nasopharyngeal carcinoma (NPC) represents one of the most frequent epithelial tumours of the child in intermediate risk regions. In the Maghreb, it represents the first cancer of teenagers of 15-20 years old. The Epstein Barr virus (EBV) is the most important etiologic factor. Its role in the pathogeneses of NPC has been confirmed by several studies. Young NPCs are characterized by a low rate of EBV antibodies and a high level of LMP1 cell expression than in adult's NPC. The undifferentiated carcinoma nasopharyngeal type (UCNT) represents the most frequent histological type. Immunohistochemical analyses of North Africa early onset NPC is characterized by a weak expression of bcl-2 and p53 and a strong expression of LMP1 and c-kit what makes them different from the adult's NPC. Clinically, cervical node involvement is constantly present. Juvenile NPC is characterized by a very important locoregional extension as well as a high rate of distant metastases. More than 15% of patients had metastases at diagnosis. Radiotherapy is still the standard therapy of NPC. Only some retrospectives studies have been published to determine the benefit, the type and the timing of the chemotherapy in the treatment of juvenile NPC. Metastatic relapses constitute the main cause of death at these young patients. An improvement of the prognosis can be waited with concomitant chemotherapy and intensity modulated radiotherapy. However, randomized multi institutional studies are necessary to standardize the treatment of the NPC in childhood.
 ...
PMID:[Juvenile nasopharyngeal carcinoma: anatomoclinic, biologic, therapeutic and evolutive aspects]. 2038 20

Soft tissue leiomyosarcoma is a relatively rare malignant tumor. It may be difficult to be distinguished from gastrointestinal stromal tumors and Schwann cell neoplasms. To make a correct identification of soft tissue leiomyosarcoma, immunostaining with several smooth muscle differentiation markers (actin, calponin and desmin), and negative staining results with S100 (to rule out Schwann cell neoplasm), c-kit and CD34 (to rule out gastrointestinal stromal tumors) is needed. Prompt diagnosis and referral are desirable, since the size of the tumor at presentation is a continuous variable for the risk of local recurrence and metastatic disease. Chemosensitivity varies according to the tumor subtype, and the tumor grade, the patient's age, performance status, and the timing of metastatic disease further influence the likelihood of a response and survival. Chemotherapy is palliative for most patients with unresectable or metastatic disease. Ifosfamide and doxorubicin are routinely used in this setting; doxorubicin as a single agent is considered the drug of choice.
 ...
PMID:Axillary and perianal leiomyosarcoma: report of two cases. 2049 60

Sorafenib, a molecular-targeted agent that inhibits tumor cell proliferation and angiogenesis by inhibiting RAF serine-threonine kinase and VEGF, PDGF, Flt-3, c-Kit receptor tyrosine kinase, was approved in Europe and North America in 2007 and in Japan on May 20, 2009. In the 10 months since its approval, sorafenib has been prescribed for more than 3,700 patients with advanced hepatocellular carcinoma (HCC), and its efficacy has been confirmed in many cases. According to the consensus statements of the Japan Society of Hepatology in 2010, sorafenib is recommended for advanced HCC with extrahepatic spread or major vascular invasion such as invasion of the 1st branch of the portal vein or the main portal branch of the portal vein in patients with Child-Pugh A liver function. In addition to that, transcatheter arterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) refractory HCC patients with Child-Pugh A liver function are also candidates of sorafenib monotherapy as a second-line treatment option. To date, 15 cases with complete remission (CR) to sorafenib in metastatic advanced HCC patients have been reported in Japan, an event that is rarely reported in other countries. Of the 90 cases treated by ourselves, 2 achieved CR. Factors indicating systemic cancer spread, including multiple liver lesions, lymph node metastases, adrenal metastases, lung metastases and vascular invasion, were completely absent in both cases of CR by 2 and 1 year, respectively. Similarly, three tumor markers (AFP, PIVKA-II, and AFP-L3) completely returned to normal values. Although cases of CR are rare, it seems that there might be racial differences in terms of gene mutations. Clinical trials for other molecular-targeted agents, including sunitinib, brivanib, or linifanib, are ongoing and their outcomes are eagerly awaited. According to a subanalysis of the SHARP study, it is expected that sorafenib in combination with resection, ablation, TACE or HAIC will markedly prolong the overall survival in early-, intermediate- and advanced- stage HCCs.
 ...
PMID:Positioning of a molecular-targeted agent, sorafenib, in the treatment algorithm for hepatocellular carcinoma and implication of many complete remission cases in Japan. 2061 99

We examined a series of 667 patients with node-negative breast carcinomas in order to identify prognostic immunohistochemical molecular signatures for the prediction of early metastasis, and potential new therapeutic targets. We used a standardized quantitative immunocytochemical approach with 37 antibodies, based on high-throughput tissue microarrays and image analysis, and analyzed the results with respect to metastatic status after a mean follow-up of 86 months. Complete data were obtained for 586 patients. The predictive value of the markers was first analyzed individually by univariate analysis (log rank test) in 586 node-negative tumors, according to metastatic status during follow-up. Twenty-seven markers had significant prognostic value. ROC curve analysis (logistic regression) was then used to determine the marker combination that best classified the patients with and without metastases. A 15-marker signature (Bcl2, P16, P21, P27, P53, CD34, CA IX, c-kit, FGF-R1, P38, JAK, pSTAT3, CK9, STAT1 and ER) correctly classified 84.8% of the patients (sensitivity 85.5%, specificity 84.6%). When ER, PR and c-erb B2 were excluded from the analysis, a very similar signature, in which CK8-18 replaced ER, correctly classified 83.6% of the patients (sensitivity 84.5%, specificity 83.4%). These results show that quantitative immunoprofiling, independently of ER, PR and c-erb B2 status, can provide a basal-like signature, can properly predict the metastatic risk of node-negative breast carcinomas at diagnostic time. This may be helpful for selecting patients who do not need aggressive adjuvant chemotherapy, and for developing tailored therapies.
 ...
PMID:[Early breast carcinoma profiling based on quantitative immunocytochemistry can help predict the risk of early distant metastasis]. 2066 17


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