Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In aiming to define the characteristics of HIV-infected subjects developing neutropenia and describe the causes, features and effects of neutropenia we undertook a retrospective study in a dedicated HIV unit in London, UK. Two hundred and forty-four patients with documented neutropenia, defined as absolute neutrophil count (ANC) < 1,000/mm3, during a 12-month period were studied. First neutropenia occurred at a median CD4 count of 30 cells/mm3. Low CD4 count was associated with longer episodes of neutropenia with a more profound nadir. Two-thirds of episodes lasted less than 2 weeks. ANC nadir was < 500 cells/mm3 in 45% of episodes. Infections were most frequent in patients with profound but brief neutropenic episodes. Neutropenia was generally mild, short-lived and associated with late-stage disease. However, profound neutropenia did develop suddenly in some patients with no prior history of neutropenia (in 13% first neutropenic ANC recorded was < or =500 cells/mm3), and at CD4 count > 200 cells/mm3. Most patients were receiving multiple myelosuppressive therapies. Infection was associated with brief, profound neutropenia.
Int J STD AIDS 2000 Jan
PMID:A retrospective study of neutropenia in HIV disease. 1066 94

Patients with metastatic breast cancer in complete remission are the ones most likely to have an improved outcome with subsequent high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDC-PBSCT). Peripheral blood stem cells are usually procured following mobilization with single agent chemotherapy and colony-stimulating factor support. We utilized a dose-intense regimen of paclitaxel 200 mg/m2 i.v., etoposide 60 mg/kg i.v., and cyclophosphamide 3 g/m2 i.v. (TEC) followed by daily administration of granulocyte colony-stimulating factor. The aim was not only to mobilize stem cells but also to achieve optimal tumor cytoreduction prior to HDC/PBSCT. One hundred consecutive patients with metastatic breast cancer received 257 cycles of TEC between March 1994 and June 1997, with the aim of collecting 5 x 106 CD34-positive cells/kg usually following the second cycle of chemotherapy. Patient characteristics included a median age of 45 years, a median of two organ systems involved by disease, a median of two prior chemotherapy regimens and eight prior chemotherapy cycles, and a median interval of 8 months from diagnosis of metastases to first cycle of TEC. There were 61 febrile episodes during neutropenia and 13 of these were associated with bacteremia or fungemia. Mortality rate was 1%. An adequate number of stem cells was collected in 90% of patients. The overall response rate of the tumor was 58.8% with 23.7% complete responders among 97 evaluable patients. Multivariate analysis demonstrated chemosensitivity to the most recent standard chemotherapy regimen administered for metastatic disease, an ECOG performance score of 0 as opposed to 1, 2 or 3, and involvement by disease of only one organ system as significant variables for achieving a complete remission with TEC. This novel dose-intense regimen was safe and well tolerated, highly active against metastatic breast cancer, and capable of excellent stem cell mobilization. Bone Marrow Transplantation (2000) 25, 123-130.
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PMID:Dose-intense paclitaxel, etoposide and cyclophosphamide: a safe and active regimen for tumor cytoreduction and stem cell mobilization in metastatic breast cancer. 1067 68

The early diagnostic efficacy of serial Candida antigen detection by the assay kit CAND-TEC (a latex particle agglutination test) was evaluated in 12 episodes in 10 patients with acute leukemia after post-remission chemotherapy. To determine the timing to initiate antifungal chemotherapy, we performed the CAND-TEC assay serially in each patient. When the patients revealed febrile neutropenia after antileukemic chemotherapy and the Candida antigen titer was increased compared to that measured before the antileukemic chemotherapy (even if the increased titer was at a lower level, e.g., from negative to 1:1 positive or from 1:1 to 1:2), azole antifungal agents (fluconazole or miconazole) were administered intravenously. In 9 (81.8%) of the 11 evaluable cases, the antifungal chemotherapy was effective and the titers decreased to less than or equal to the previous titers in all cases. In 2 cases, the antifungal chemotherapy was not effective, and the titers did not decrease. These results suggest that serial Candida antigen detection provides a useful method in the early diagnosis of invasive candidiasis in febrile neutropenia and in determining the timing of the initiation of early antifungal chemotherapy. This method might also be useful in preventing the excess use of antifungal agents; thus preventing the proliferation of azole-resistant Candida infection.
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PMID:Surveillance of the serum Candida antigen titer for initiation of antifungal therapy after post-remission chemotherapy in patients with acute leukemia. 1084 34

We describe the clinical activity of the ABL kinase inhibitor STI571 in a patient with accelerated phase of chronic myeloid leukemia (CML) relapsing after a second allogeneic BMT and with minimal levels of donor chimerism. STI571 resulted in rapid elimination of leukemic cells with ensuing prolonged severe leukopenia and neutropenia complicated by neutropenic fever and colitis. Subsequent hematopoietic recovery was driven by donor derived cells and was associated with grade 3 graft-versus-host disease (GVHD). STI571 induced sustained hematological and cytogenetic remission combined with controllable GvHD, therapeutic goals not achieved by two preceding allogeneic transplants and repeated donor lymphocyte transfusions (DLT).
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PMID:Hematologic and cytogenetic remission by STI571 (Glivec) in a patient relapsing with accelerated phase CML after second allogeneic stem cell transplantation. 1170 99

A 73-year-old woman with chronic myeloid leukemia was treated with interferon-alpha, hydroxyurea, and busulfan before imatinib mesylate treatment. The leukocyte count was 8,400/; hemoglobin concentration, 12.0 g/; and platelet count, 19.7 x 10(4)/. She received 400 mg of imatinib mesylate for 17 days before the agent was discontinued because of pancytopenia. A bone marrow biopsy on the 87th day after the last imatinib mesylate administration demonstrated severe hypocellularity. She needed many RBC and Plt transfusions and filgrastim administration. Grade 4 neutropenia continued for 35 days and Grade 3 thrombocytopenia continued for over 122 days. Imatinib mesylate, an agent targeting BCR-ABL, is expected to be useful as an effective therapeutic agent for chronic myeloid leukemia. However the present case suggests that its appropriate dose is individually variable and we should carefully consider the former treatment, and the clinical stage of the disease before initiating imatinib treatment.
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PMID:[Chronic myeloid leukemia associated with sustained severe pancytopenia after imatinib mesylate therapy]. 1241 95

The safety and efficacy of hydroxyurea with didanosine in combination with stavudine in nucleoside reverse-transcriptase inhibitor (NRTI)-experienced patients was investigated. Entry criteria included HIV-1 infected, NRTI-experienced adults, with CD4(+) counts 50-550 cells/mm(3) and viral loads >or=12,500 copies/mL. Subjects were treated with didanosine 200 mg twice a day (BID), stavudine 40 mg BID, and hydroxyurea 1000 mg daily for 16 weeks. Thirty-one HIV-1 subjects with mean bDNA viral load 1x10(5) log(10) copies/mL and mean CD4(+) T-cell counts of 231 cells/mm(3) were enrolled. A 1.3 log(10) decrease in mean viral load was seen at 12 weeks of therapy. Prior didanosine use resulted in a more rapid response to therapy compared with prior zidovudine use. Side effects consisting of neutropenia, pancreatitis, and peripheral neuropathy occurred in four subjects and resolved upon withdrawal of therapy. This non-randomized study in subjects with a mean CD4(+) T-cell count of 230 cells/mm(3) demonstrates the antiviral activity of hydroxyurea+didanosine and stavudine. Toxicities related to therapy need to be followed closely. The results support the need for a randomized, prospective study to determine the safety and efficacy of hydroxyurea plus didanosine in antiretroviral-experienced patients with CD4(+) cell counts below 300 cells/mm(3).
Int J STD AIDS 2003 May
PMID:Hydroxyurea in combination with didanosine and stavudine in antiretroviral-experienced HIV-infected subjects with a review of the literature. 1280 44

The objective of this study was to compare the safety and efficacy of carboplatin plus epirubicin and paclitaxel (TEC) to carboplatin and paclitaxel (TC), in the treatment of epithelial ovarian, peritoneal, or tubal carcinoma. Between March 1999 and August 2001, 887 patients were randomized to receive six to nine cycles of paclitaxel (175 mg/m2, 3 h intravenously) followed by carboplatin (AUC 5, Calvert formula) with or without epirubicin (75 mg/m2 intravenously prior to paclitaxel), on a 3-weekly schedule. The primary endpoint was progression-free survival. Demographic information: Residual disease <1 cm was reported on 41% of patients. At the end of treatment, 65% in the TEC and 55% in the TC arm had achieved a clinical complete response, and 18 and 25% a clinical partial response resulting in an overall response rate of 83% in the TEC and 80% in the TC arm, whereas 7 and 9% had progressive disease, respectively. The three-drug combination produced a markedly higher myelotoxicity, resulting in a higher frequency of febrile neutropenia (12.5% of the TEC and 1.5% of the TC patients) and a higher number of dose reductions and treatment delays. Cycle prolongation above seven days was seen in 7 and 5% of cycles in the TEC and TC arm, respectively. Stomatitis > or = grade 3 was also higher with TEC (4% TEC and 0.5% TC). Reductions in left ventricular ejection fraction of more than 15% after six courses were slightly more common with the TEC regimen (3% versus 1.5%), but the difference was not statistically significant (P = 0.2). In conclusion, treatment with the TEC combination produced a higher rate of complete responses than treatment with the TC combination. Toxicity was manageable. Long-term survival data are awaited.
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PMID:First-line treatment of ovarian cancer FIGO stages IIb-IV with paclitaxel/epirubicin/carboplatin versus paclitaxel/carboplatin. 1465 76

In this case study authors presented the clinical characteristics of X-linked agammaglobulinemia (XLA) associated with agranulocytosis diagnosed in a 2-year-old boy. Affected child lacked circulating mature B cells, presented low levels of serum immunoglobulins, but did not suffer from recurrent bacterial infections. XLA is a primary immunodeficiency caused by a defective tyrosine kinase (Btk) in B cells. Our patient and his mother have a mutation in the BTK gene, described as W281X. During therapy with intravenous gammaglobulin, the boy has not experienced agranulocytosis. It is important to consider a primary immunodeficiency diagnosis when a child presents agranulocytosis or neutropenia and a recurrent infectious disease.
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PMID:[X-linked agammaglobulinemia (XLA) associated with agranulocytosis--case report]. 1496 69

Imatinib mesylate is a relatively new drug that targets the BCR-ABL chimeric protein, the molecular basis of chronic myeloid leukemia (CML). A phase II clinical trial in 39 Japanese patients in the first chronic phase of CML was conducted with imatinib mesylate at a dose of 400 mg/day. Hematologic complete response was obtained in 92.3% of the patients, complete cytogenetic response (CR) was obtained in 43.6%, and major partial CR was obtained in 20.5% of the patients. Although 29 of 39 patients required an adjustment of dosing because of grade 3 or 4 adverse events, most of the events were reversible, and 25 of the 29 patients were able to resume therapy. Between day 15 and day 35, grade 3 or 4 neutropenia and/or leukocytopenia occurred in 13 patients, and grade 3 thrombocytopenia occurred in 5 patients. Overall, nonhematologic grade 3 adverse events occurred in 28.2% of the patients. These data support the use of imatinib mesylate as the treatment of choice for chronic-phase CML patients.
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PMID:Efficacy and safety of imatinib mesylate for patients in the first chronic phase of chronic myeloid leukemia: results of a Japanese phase II clinical study. 1554 Sep 2

Glycogen storage disease (GSD) 1b is a metabolic disorder characterized by a deficiency of glucose 6-phosphate transporter and neutrophil alterations, which are reduced in number and functionally impaired. The present study aimed at investigating neutrophil dysfunction correlating submembrane and cytoskeletal changes at different ages with or without granulocyte-colony stimulating factor (G-CSF) treatment. GSD1b neutrophils showed reduced expression and diffused localization of focal adhesion kinase (FAK) and actin. No abnormalities were observed in GSD1a patient neutrophils. Gelsolin was also slightly reduced in neutrophils of GSD1b patients. When patients were treated for at least 3 months with G-CSF, the neutrophil number and the expression of FAK and actin were significantly increased. Granulocyte colony-stimulating factor treatment was similarly effective when performed in 1 year old patients. FAK auto- and IL-8-mediated phosphorylations were already affected as early as 1 year of age. G-CSF treatment also improved this alteration. Our data suggest that neutrophil dysfunction in GSD1b patients might be related to functional impairment and disorganization of proteins of the sub-membrane apparatus, and that G-CSF treatment counteracts neutropenia and prevents the progressive alterations of neutrophil sub-membrane proteins.
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PMID:Amelioration of neutrophil membrane function underlies granulocyte-colony stimulating factor action in glycogen storage disease 1b. 1588 52


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