Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
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Query: UMLS:C0027627 (
metastases
)
103,950
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The authors assessed the diagnostic accuracy of the static telepathology (sTP) for practical consultations in the controversial pulmonary oncology cases. The short characteristics of the diagnostic cases is included. We reported the results of 6 difficult clinico-pathological cases submitted to Dept Quantitative Pathology [DQP] for consultations (5F and 1M, age: 26-68 yrs). Digital images of histological or cytological samples were captured at DQP and transmitted to telepathologist (TPat) in Thoraxklinik, Heidelberg or AFIP, Washington DC. Simultaneously, the same slides (or with a paraffin block) were mailed to TPats for re-evaluation with the conventional microscope (dgn-zwPat). The controversial cases presented 2 types of diagnostic problems: 1/rare entities, 2/common difficulties in the routine work of pathologist, but with indefinitely proved diagnosis. The first group encounters TPat diagnoses as follows: * case A: pulmonary plasma cell granuloma with lymphoidal interstitial infiltrates [LIP]--
preleukemia
; * case B: microfoci of early
metastases
of benign uterine leiomyoma; * case D: small cell carcinoma spreading along pleura. The second group included: * case C: invasive epidermoidal carcinoma in bronchus; *case E: probably metastatic adenocarcinoma of colon; *case F: synchronous or metastasising 2 lung tumours sharing NE morphology or NE immunohistochemical features. There was very high concordance between referring pathologist (ref-Pat) diagnoses and TPat diagnoses as well as a consensus in zw-TPat diagnoses. In 2 cases the conceptual problem was solved by TPat. Telepathology offered a support or improved the quality of the final diagnosis. The implementation of sTP remarkably reduced the time of consultations and allowed to present the diagnostic problems to the international group of experts.
...
PMID:[Telepathology in diagnostic consultations for controversial neoplastic growths in the lung--personal experience]. 1173 86
The case of a primary cardiac epithelioid hemangioendothelioma (EHE) arising multifocally in the papillary muscle of the tricuspid valve and the deeper trabecular muscle in a 68-year-old male with
myelodysplastic syndrome
is presented. The tumor was an incidental autopsy finding. Histologically the tumor is characterized by proliferation of plump epithelial-like endothelial cells with the vascular differentiation being mostly expressed at a cellular level in the form of cytoplasmic vacuoles. In the differential diagnosis, metastatic carcinoma, cardiac myxoma as well as other epithelioid vascular neoplasms should be considered. EHEs are indolent tumors of intermediate malignancy with the potential to
metastasize
, even after a long time. Primary cardiac EHE is extremely rare. To our knowledge, only four EHEs of the heart have been reported in the literature. We believe, this is the first report of a cardiac EHE in this localization and the first one in association with
myelodysplastic syndrome
.
...
PMID:[Epithelioid hemangioendothelioma of the heart in association with myelodysplastic syndrome]. 1206 9
A nondifferentiating mouse myeloid leukemia cell line produces differentiation-inhibiting factors. One of these factors was purified as a homologue of nm23. The nm23 gene was isolated as a metastasis-suppressor gene that exhibits low expression in high-level
metastatic cancer
cells. The nm23 gene was overexpressed in acute myelogenous leukemia (AML) cells and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML. Multivariate analysis of putative prognostic factors revealed that elevated nm23-H1 mRNA levels significantly contributed to the prognosis of patients with AML. The overexpression of nm23-H1 was also observed in various hematological neoplasms. To use nm23 overexpression to determine the prognosis for lymphoma, we established an enzyme-linked immunosorbent assay (ELISA) technique to determine the serum level of nm23-H1 protein. This assay is far simpler than that used to determine nm23 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). Using this system, we measured nm23-H1 protein levels in many hematological malignancies. Serum nm23-HI levels were significantly higher in patients with all of the hematological neoplasms tested (AML, chronic myelogenous leukemia, acute lymphoblastic leukemia, (ALL)
myelodysplastic syndrome
(
MDS
) and malignant lymphomas) than in normal controls. An elevated serum nm23-H1 protein concentration predicted a poor outcome for AML and non-Hodgkin's lymphoma. Especially in diffuse large B-cell lymphoma (DLBCL), seram nm23-H1 protein levels were an important prognostic factor in planning an appropriate treatment strategy for DLBCL. The serum nm23-H I protein levels probably depend on the total mass of malignant cells overexpressing nm23-H1.
...
PMID:Serum nm23-H1 protein as a prognostic factor in hematological malignancies. 1215 76
Rubitecan [Orathecin, 9-nitrocamptothecin, 9NC, RFS 2000] is a topoisomerase I inhibitor extracted from the bark and leaves of the Camptotheca acuminata tree, which is native to China. Rubitecan is an oral compound being developed for the treatment of pancreatic cancer and other solid tumours by SuperGen. One of the major benefits of rubitecan is that it can be administered in an outpatient setting, so patients can be treated in their homes. Rubitecan was isolated by the Stehlin Foundation in the US. SuperGen is currently awaiting regulatory approval in the US and the EU for rubitecan in the treatment of pancreatic cancer. At the BIO-2004 conference, SuperGen announced it is seeking a partner for rubitecan for territories outside the US. SuperGen acquired exclusive worldwide rights to rubitecan from the Stehlin Foundation in 1997 except in Mexico, Canada, Spain, Japan, the UK, France, Italy and Germany. SuperGen has also received approval from the US FDA to use its own manufactured rubitecan in clinical trials. SuperGen and the Stehlin Foundation have an 8-year research agreement that secures global rights to other camptothecins and additional anticancer compounds for the former. In December 1999, SuperGen and Abbott signed a worldwide sales and marketing agreement for rubitecan. Under the terms of the agreement, Abbott had exclusive distribution and promotion rights for rubitecan outside the US, and co-promotion rights with SuperGen within the US. In return, Abbott made an initial equity investment in SuperGen. SuperGen and Abbott Laboratories ended their collaboration agreement in February 2002 by mutual consent with SuperGen stating that the dissolution of the agreement was based on commercial motivation rather than anything to do with rubitecan's safety or efficacy. Abbott no longer has rights or obligations to purchase shares of SuperGen stock or an option to purchase up to 49% of the company. For its part, SuperGen will no longer receive milestone payments worth up to $US57 million. SuperGen has formed a clinical and business alliance with US Oncology (created by the merger between American Oncology Resources and Physician Reliance Network in the US), and will collaborate on clinical trials of rubitecan. SuperGen believes that this relationship will increase the patient population available for trials and enable it to market the drug directly to Oncologists. SuperGen and Capital Research and Management Company have completed a $US16.6 million private placement transaction that will enable future funding for the rubitecan programme as well as other oncology programmes. In July 2004, SuperGen's European subsidiary, EuroGen Pharmaceuticals, submitted a Marketing Authorisation Application for rubitecan in the treatment of pancreatic cancer. The application will be reviewed under the EMEA Centralised Procedure. In June 2003, the EMEA granted SuperGen orphan drug status for rubitecan for the treatment of pancreatic cancer. The US FDA has also granted orphan drug status for rubitecan in the treatment of pancreatic cancer and fast-track status for rubitecan for the treatment of locally advanced or metastatic pancreatic cancer that is resistant or refractory to chemotherapy. SuperGen has conducted three phase III pivotal trials in patients with pancreatic cancer. A phase III randomised trial in chemotherapy-naive patients was conducted at 132 centres throughout the US. The trial enrolled approximately 994 patients who were randomised to receive rubitecan or gemcitabine. Enrollment was completed in October 2001. Another phase III trial has compared rubitecan with the most appropriate chemotherapy in chemotherapy-resistant patients. Enrollment of over 400 patients at 200 medical centres across the US was completed in June 2001. Results from the trial were presented at the 39th Annual Meeting of the American Society of Clinical Oncology (ASCO-2003) [Chicago, US; 31 May - 3 June 2003], after they had been compiled, analysed and submitted to the FDA. The results of the study showed that rubitecan could not help all chemotherapy-resistant patients, but could increase survival in those that do respond. The other phase III pivotal trial was conducted in patients with pancreatic cancer who had failed treatment with gemcitabine. This trial completed enrollment in October 2001, and had enrolled approximately 448 patients. SuperGen is conducting phase II trials of rubitecan in patients with solid tumours in the UK, Italy, France, Germany, the Netherlands and Denmark. Each trial will enroll 100-150 patients with various tumour types, including colorectal, lung, breast, gastric, prostate, cervical and head and neck cancers. Phase I/II trials are underway to investigate rubitecan as a radiosensitiser in patients with lung cancer, and phase II trials in patients with breast cancer are also being conducted. A phase II study in ovarian cancer patients is also being conducted. Results from an ongoing phase II study in cancer patients have shown that rubitecan was effective against chordomas, a rare type of bone cancer. Phase II studies are also underway in haematological malignancies including
myelodysplastic syndrome
(preleukaemia) and chronic myelomonocytic leukaemia. In February 2000, SuperGen announced that its IND submission for rubitecan had been approved by the Therapeutics Products Programme of Canada. The company stated that it intended to begin clinical trials in Canada in the near future. In February 2004, SuperGen announced an offering of shares of its common stock to finance the commercialisation of rubitecan capsules. In July 2003, SuperGen was granted a US patent covering combination therapies with chemotherapeutic anthracycline agents and structural modifications that may one day lead to next-generation rubitecan compounds. In December 2002, SuperGen was granted US patent No. 6,482,830, covering its polymorphic formulations of rubitecan. The patent also covers a class of polymorphs that are similar to the one at the centre of rubitecan. In addition, SuperGen was also issued US patent No. 6,485,514 in December 2002, covering the local delivery of rubitecan via stents and/or catheters to sites of proliferating cells. Stent- or catheter-delivered rubitecan may be beneficial in certain types of cardiac procedures, such as ablation or angioplasty, as well as for direct injection into a certain number of solid tumours. SuperGen is also developing an inhaled, liposomal formulation of rubitecan. It acquired the worldwide rights to this formulation from the Clayton Foundation in December 1999. Inhaled rubitecan is in clinical trials in the US for the treatment of lung cancer and pulmonary
metastatic cancer
.
...
PMID:Rubitecan: 9-NC, 9-Nitro-20(S)-camptothecin, 9-nitro-camptothecin, 9-nitrocamptothecin, RFS 2000, RFS2000. 1535 30
Basal cell carcinoma (BCC) is usually a benign and indolent cancer cured in greater than 95 percent of cases. Nevertheless, it can be locally destructive or occasionally
metastasize
to distant organs. We report a case of BCC metastatic to the lungs, occurring 17 years after the primary BCC was noticed, that responded to carboplatin and paclitaxel on 3 occasions. The patient also developed pure red cell aplasia (PRCA). Work-up did not reveal underlying thymoma or infectious, rheumatologic, or lymphoproliferative disorders. Parvovirus serologies were negative, and antibodies against erythropoetin were not detected. There was no history of exposure to drugs associated with PRCA. Bone marrow biopsy on 2 different occasions did not show evidence of
myelodysplasia
. PRCA may represent an unusual paraneoplastic syndrome associated with BCC as reported with other carcinomas. This is the first report of PRCA associated with metastatic BCC or the drugs carboplatin and paclitaxel, which were used to treat it. The literature on chemotherapy for metastatic BCC is reviewed.
...
PMID:Metastatic basal cell carcinoma: complete response to chemotherapy and associated pure red cell aplasia. 1677 92
Fever of unknown origin (FUO) is a common clinical diagnostic dilemma. In the elderly, causes of FUO most commonly include malignancy or infection, and less commonly include collagen vascular diseases. Among the collagen vascular diseases causing FUO in the elderly, polymyalgia rheumatica/temporal arteritis, and adult Still's disease (adult juvenile rheumatoid arthritis) are difficult diagnoses to prove. Among the infectious causes of FUO in the elderly are subacute bacterial endocarditis, intra-abdominal abscesses, and extrapulmonary tuberculosis. In the elderly, neoplastic causes of FUO include lymphomas, hepatomas, renal cell carcinomas, and hepatic or central nervous system
metastases
. Acute leukemias, particularly during "blast" transformation, may present as acute fevers in the absence of infection, but are rare causes of FUO.
Preleukemia
/
myelodysplastic syndromes
are exceedingly rare causes of FUO. We present a case of an elderly man who presented with findings that initially suggested adult Still's disease. Prolonged and profound monocytosis provided the key clue to his subsequent diagnosis of
preleukemia
/
myelodysplastic syndrome
. In this patient, a positive Naprosyn test result also suggested a neoplastic cause for his FUO. After months of prolonged fevers, myelocytes/metamyelocytes were eventually demonstrated in his peripheral smear during hospital evaluation. These findings, in concert with the persistent monocytosis, highly elevated ferritin levels, polyclonal gammopathy on serum protein electrophoresis, and eventual presence of myelocytes/metamyelocytes on peripheral smear, prompted a bone marrow test that demonstrated blast cells confirming the diagnosis of
preleukemia
myelodysplastic syndrome
as the cause of this patient's FUO.
...
PMID:Fever of unknown origin due to preleukemia/myelodysplastic syndrome: the diagnostic importance of monocytosis with elevated serum ferritin levels. 1686
This study describes the magnitude of risk of therapy-related
myelodysplasia
and acute myeloid leukemia (t-
MDS
/AML) in 578 individuals diagnosed with Ewing sarcoma and enrolled on Children's Oncology Group therapeutic protocol, INT-0091. Between 1988 and 1992, patients with or without
metastatic disease
were randomized to receive doxorubicin, vincristine, cyclophosphamide, and dactinomycin (regimen A) or these 4 drugs alternating with etoposide and ifosfamide (regimen B). Between 1992 and 1994, patients with
metastatic disease
were nonrandomly assigned to receive high-intensity therapy (regimen C: regimen B therapy with higher doses of doxorubicin, cyclophosphamide, and ifosfamide). Median age at diagnosis of Ewing sarcoma was 12 years, and median length of follow-up, 8 years. Eleven patients developed t-
MDS
/AML, resulting in a cumulative incidence of 2% at 5 years. While patients treated on regimens A and B were at a low risk for development of t-
MDS
/AML (cumulative incidence: 0.4% and 0.9% at 5 years, respectively), patients treated on regimen C were at a 16-fold increased risk of developing t-
MDS
/AML (cumulative incidence: 11% at 5 years), when compared with those treated on regimen A. Increasing exposure to ifosfamide from 90 to 140 g/m2, cyclophosphamide from 9.6 to 17.6 g/m2, and doxorubicin from 375 to 450 mg/m2 increased the risk of t-
MDS
/AML significantly.
...
PMID:Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: A report from the Children's Oncology Group. 1698 82
There is lack of information about the relative prevalence of haematological disorders in Yemen and other Middle East countries. The aim of this study was to evaluate the pattern of haematological diseases diagnosed by bone marrow examination in Yemen considering the limited diagnostic facilities. At the referral haematology centre in Yemen, between November 1999 and November 2005, 785 patients >14 years old were evaluated by bone marrow examination. Relevant investigations were performed when needed. A total of 627 patients had haematological disorders other than lymphoma, and their data were analysed. There were 273 females and 354 males. A total of 159 patients had Acute myeloid leukaemia, 75 had acute lymphocytic leukaemia, 87 had chronic myeloid leukaemia, 36 chronic lymphocytic leukaemia, eight had multiple myeloma, 13
myelodysplastic syndromes
, seven myelofibrosis, seven polycythaemia vera, three primary thrombocythaemia, two hairy cell leukaemia, two
metastases
, 36 aplastic anaemia, 29 immune thrombocytopenic purpura (ITP), nine autoimmune haemolytic anaemia, three pernicious anaemia, 65 iron deficiency anaemia, 57 megaloblastic anaemia and malaria, 18 mixed deficiencies, and 11 patients had visceral leishmaniasis. Sex- and age-related distribution of the various disorders was also presented. In conclusion, the leukaemias were the most frequently encountered diagnosis followed by iron deficiency anaemia, megaloblastic anaemia and malaria, aplastic anaemia and ITP respectively. The other haematological disorders were less common. These findings are comparable with that seen in other developing and developed countries.
...
PMID:Pattern of haematological diseases diagnosed by bone marrow examination in Yemen: a developing country experience. 1710 90
Tumor-specific immunotherapy with a Wilms' tumor 1 (WT1) peptide has been on clinical trial for leukemia,
myelodysplastic syndrome
, breast and lung cancers and is producing promising results. In this study, we treated three patients with renal cell carcinoma with an anchor modified, HLA-A*2402 binding WT1 peptide which was emulsified in Freund's incomplete adjuvant. In two patients tumor growth was suppressed and clinical response was evaluated as stable disease by the RECIST criteria after 3 months of weekly immunizations. Notably, development of new
metastases
has stopped in these patients for a prolonged period. No deleterious side effects were observed. Peptide-specific T cells were expanded in PBMCs of the patients and a substantial fraction of them bore the surface phenotype consistent with a CD8+ cytotoxic effector population. Although established tumors did not regress further, considering the component of the vaccine, i.e. peptide alone, the stabilization effect suggested the potential of WT1 peptide to develop into a more effective vaccine. To our knowledge, this is the first report of WT1 immunotherapy for renal cell carcinoma. Hopefully, the results will stimulate more extensive clinical studies.
...
PMID:WT1 (Wilms' tumor 1) peptide immunotherapy for renal cell carcinoma. 1757 61
Alveolar rhabdomyosarcoma (RMS) accounts for 20% to 30% of childhood RMS and is associated with a prognosis worse than embryonal RMS. Disseminated RMS can present with extensive bone marrow involvement. Assessing the extent of the tumor is critical, because therapy and prognosis depend on the degree to which the mass has spread beyond the primary site. The value of F-18 FDG PET in patients with RMS has been reported in some series but none specifically involving bone marrow. Children have a highly cellular hematopoietic bone marrow and differentiation of a highly cellular marrow from neoplastic infiltration may be difficult. Various other conditions associated with diffuse FDG uptake in the bone marrow include marrow hyperplasia resulting from hemolytic/iron-deficiency/blood-loss anemia, after chemotherapy with granulocyte/macrophage colony-stimulating factor and recombinant erythropoietin treatment, leukemia, non-Hodgkin lymphoma, and
myelodysplasia
. It is therefore important to consider the above differential diagnoses in mind when evaluating cases of unexpected marrow uptake in F-18 FDG PET studies. We report here a case of RMS with diffuse bone marrow involvement detected on F-18 FDG PET wherein FDG PET was useful in determining the true extent (primary and
metastases
) of RMS before definitive therapy and the valuable adjunct role it has with structural imaging in management.
...
PMID:Rhabdomyosarcoma with widespread bone marrow infiltration: beneficial management role of F-18 FDG PET. 1788 59
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