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)

HIV-associated immunosuppression has been linked to an increased risk of a number of cancers, including Kaposi sarcoma (KS), non-Hodgkin's lymphoma (NHL), and invasive cervical cancer. Because prison inmates constitute one of the highest HIV/AIDS prevalent populations in the US, understanding the link between HIV infection and cancer in the correctional setting holds particular public health relevance. The study population consisted of 336,668 Texas Department of Criminal Justice inmates who were incarcerated, for any duration, between 1 January 1999 and 31 December 2001. Inmates diagnosed with HIV infection exhibited elevated rates of KS, NHL, anal cancer, and Hodgkin's disease, after adjusting for age and race. The elevated rates of cancer among HIV-infected individuals, particularly prison inmates, may be mediated, in part, by high-risk behaviours. HIV-associated risk behaviours, including unsafe sexual practices, injection drug use, and prostitution may be associated with cancer-related risk behaviours, such as smoking, excessive alcohol consumption, and poor diet. It will be important for future investigators to examine the association between HIV infection and cancer risk with sufficiently large study cohorts and appropriate longitudinal designs.
Int J STD AIDS 2004 May
PMID:The association of neoplasms and HIV infection in the correctional setting. 1511 7

Recent improved treatments for lymphoid malignancies produce more long-term survivors, yet increase the risk for secondary malignancies. Therapy-related myelodysplasia and acute myeloid leukemia are well described, but secondary chronic myeloid leukemia (CML) has only rarely been reported. We report three patients with CML diagnosed 8, 10 and 2.5 years following Hodgkin's disease, non-Hodgkin's lymphoma and chronic lymphocytic leukemia therapy, respectively. BCR-ABL transcripts were not detected after completion of primary therapy in two cases. All three patients received imatinib therapy, with one patient subsequently undergoing allogeneic hematopoietic stem cell transplantation. All three patients have ongoing favorable responses to CML therapy.
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PMID:Chronic myeloid leukemia after treatment of lymphoid malignancies: response to imatinib mesylate and favorable outcomes in three patients. 1633 96

Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder. The precise incidence is unknown, although it is more common in HIV-positive than HIV-negative individuals. The pathological features of MCD strongly suggest a chronic antigen stimulation response, and human herpes virus 8 (HHV8) has been found to be universal in cases of HIV-related MCD. The presentation is non-specific with a wide differential diagnosis, which often results in a significant delay in its diagnosis. Diagnosis is made on the clinical presentation of a lymphoproliferative disorder, with evidence of multisystem involvement with classical histopathology on lymph node biopsy. Although no standard of care has been established for its treatment, symptomatic recurrences are often treated with corticosteroids and chemotherapy. The contribution of highly active antiretroviral treatment to the treatment of MCD remains debated. Novel treatments targeted at HHV8 show promising results, although evidence is currently limited to case reports. Randomized control trials assessing whether 'prophylactic' treatment with ganciclovir may prevent flares as currently used against cytomegalovirus disease in transplant patients are proposed. The prognosis of MCD in HIV-positive patients remains generally poor with a median survival of 48 months from diagnosis, and a 15-fold increased risk of non-Hodgkin's lymphoma.
Int J STD AIDS 2006 Jan
PMID:Multicentric Castleman's disease in HIV infection. 1651 1

Src kinases are involved in multiple cellular contexts such as proliferation, adhesion, tumor invasiveness, angiogenesis, cell cycle control and apoptosis. We here demonstrate that three newly developed dual selective Src/Abl kinase inhibitors (SrcK-I) (AZM559756, AZD0530 and AZD0424) are able to induce apoptosis and cell cycle arrest in BCR-ABL, c-KIT and platelet-derived growth factor-negative lymphoma cell lines. Treatment of DOHH-2, WSU-NHL, Raji, Karpas-299, HUT78 and Jurkat cells with SrcK-I revealed that the tested substances were effective on these parameters in the cell lines DOHH-2 and WSU-NHL, whereas the other tested cell lines remained unaffected. Phosphorylation of Lyn and in particular Lck were affected most heavily by treatment with the SrcK-I. Extrinsic as well as intrinsic apoptosis pathways were activated and elicited unique expressional patterns of apoptosis-relevant proteins such as downregulation of survivin, Bcl-XL and c-FLIP. Protein levels of c-abl were downregulated and Akt phosphorylation was decreased by treatment with SrcK-I. Basal expression levels of c-Myc were notably lower in sensitive cell lines as compared with nonsensitive cell lines, possibly providing an explanation for sensitivity versus resistance against these novel substances. This study provides the first basis for establishing novel SrcK-I as weapons in the arsenal against lymphoma cells.
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PMID:Src kinase inhibitors induce apoptosis and mediate cell cycle arrest in lymphoma cells. 1770 48

Plasmablastic lymphoma (PBL) is an HIV-associated non-Hodgkin's lymphoma that primarily affects the oral cavity. We describe the case of an HIV patient with a lesion in the maxilla that lasted four months. He was diagnosed with PBL and received highly active antiretroviral therapy as well as chemotherapy and local radiotherapy. The lesion regressed after the third cycle of chemotherapy. The patient interrupted antiretroviral treatment and the lesion recurred. The immune reconstitution secondary to the use of antiretroviral therapy seems to participate in the regression of PBL and maintains the remission of the tumour, but it might not be enough to prevent the development of PBL.
Int J STD AIDS 2010 Jan
PMID:HIV-associated oral plasmablastic lymphoma and role of adherence to highly active antiretroviral therapy. 1988 61

With highly active antiretroviral therapy (HAART), AIDS-defining malignancies are becoming less common. The outcomes with standard chemotherapy are improving. In the last 10 years there have been significant changes in our patient demographics due to immigration. The aim of this study was to review the demographics and outcomes of patients with cancer in the post-HAART era and to assess the impact of changing demographics and HAART through comparing them with previously published pre-HAART data from the same centre. A retrospective chart review of 42 patients diagnosed with malignancy from 2000 to 2007 was performed and compared with pre-HAART (1987-1994) data. The incidence of malignancies has decreased from 5.2% to 2.4%. The incidence of Kaposi's sarcoma and primary cerebral lymphoma has decreased. Non-Hodgkin's lymphoma incidence has remained stable, but survival has improved with 44% of patients achieving remission. Non-AIDS-defining malignancies have increased and were associated with longer duration of HIV infection. The change in patient demographics did not have an impact on the type of malignancies diagnosed. Overall the incidence of malignancy has decreased; however, the increase in non-AIDS-defining malignancies highlights the importance of early diagnosis, use of HAART and prospective surveillance.
Int J STD AIDS 2010 May
PMID:HIV-related malignancies pre- and post-highly active antiretroviral therapy: experiences in an inner city tertiary referral centre. 2049 2

Aberrant signal transducer and activator of transcription (STAT)3 signaling participates in the development and progress of human cancers. We previously generated a highly cytotoxic fusion toxin designated rGel/BLyS for receptor-mediated delivery of the rGel toxin to malignant B-cells. In this study, we examined this fusion toxin for its ability to impact STAT3 signaling in diffuse large B-cell lymphoma (DLBCL). The activated B cell-like DLBCL lines were found to express higher levels of interleukin-6 receptor (IL-6R) and STAT3 than did the germinal center B cell-like DLBCL lines. Treatment of DLBCL cells with rGel/BLyS resulted in down-regulation of IL-6R and inhibited STAT3 phosphorylation, STAT3-DNA binding activity, and IL-6-inducible STAT3 reporter gene activity. In agreement with these results, we additionally found that rGel/BLyS down-regulated levels of several STAT3 targets (c-Myc, p21, Mcl-1, and Bcl-x(L)) and p-SYK, a positive regulator of STAT3. Inhibition of IL-6R-mediated STAT3 signaling by rGel/BLyS led to growth inhibition, triggered accumulation of cells in the sub-G(1) phase of the cell cycle, and induced apoptosis. Our results indicate that rGel/BLyS is an excellent candidate for the treatment of aggressive DLBCL which is resistant to conventional chemotherapeutic regimens and STAT3 signaling pathway may be an attractive therapeutic target for non-Hodgkin's lymphoma.
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PMID:The rGel/BLyS fusion toxin inhibits STAT3 signaling via down-regulation of interleukin-6 receptor in diffuse large B-cell lymphoma. 2065 81

We describe here the rare coexistence, at the time of diagnosis, of a myeloproliferative neoplasm (MPN) and non-Hodgkin's lymphoma (NHL) in a 74-year-old patient who presented with thrombocytosis and signs of portal hypertension on physical examination. Abdominal computed tomography scan demonstrated extensive portal vein system thrombosis. Secondary causes of thrombocytosis were excluded. JAK2 V617F mutation was present in the peripheral blood, while bone marrow biopsy revealed marginal zone B-cell lymphoma. Molecular analysis failed to detect BCR-ABL rearrangement in peripheral blood cells. Simultaneous occurrence of MPN and NHL was diagnosed. This case may be of interest not only due to the rare coexistence of PMN and NHL, but also because of the undetermined clinical significance of JAK2 mutation in this subset of patients.
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PMID:Concomitant diagnosis of myeloproliferative neoplasm and non-Hodgkin's lymphoma in a patient with portal vein thrombosis. 2150 4

Natural killer (NK)/T-cell lymphoma is a rare form of non-Hodgkin's lymphoma that is seen with increased frequency in HIV infection and in transplant recipients. This case report describes an unusual case of extranodal NK/T-cell lymphoma in a patient with advanced HIV disease in which gastric involvement was a significant feature.
Int J STD AIDS 2012 Jan
PMID:HIV-associated gastric natural killer/T-cell lymphoma. 2236 96

B-cell receptor signaling plays varied and critical roles in B-cell development, homeostasis and disease. The key players of the pathway and its many signaling modulators have been identified as well as some of the mechanisms by which the pathway is regulated. With the increased incidence of non-Hodgkin's lymphoma in recent years, there is a clear clinical need for novel agents to offer new options in resistant disease to potentially improve outcomes in curative settings. With the tremendous insight gained in the last 2 decades from basic science research, our understanding of the pathobiology of the B-cell receptor is leading to the discovery and clinical development of many new therapeutic targets such as Syk, Bruton's tyrosine kinase, and phosphatidylinositol 3-kinase. This review will emphasize contemporary and salient findings on novel agents targeting the B-cell receptor signaling pathway for the treatment of non-Hodgkin's lymphoma.
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PMID:B-cell receptor pathobiology and targeting in NHL. 2286 93


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