Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Henle, Gertrude (Children's Hospital of Philadelphia, Philadelphia, Pa.), and Werner Henle. Evidence for a persistent viral infection in a cell line derived from Burkitt's lymphoma. J. Bacteriol. 89:252-258. 1965.-Exposure of a cell line (EB2) derived from Burkitt's lymphoma to vesicular stomatitis (VSV) and certain other viruses revealed a marked resistance of the cultures to infection. Intact, but not disintegrated lymphoma cells induced resistance to VSV in human embryonic kidney, amnion and diploid, as well as in green monkey kidney cells employed as feeder layers. A line of rabbit kidney or Earle's strain L cells was not protected under similar conditions. Depending upon the number of EB2 cells initially transferred, resistance developed within 1 day or in more than 2 weeks. Cell-free media collected from cultures of EB2 cells in the presence or absence of feeder layers of human cells were capable of conferring rapid protection against VSV to human-cell cultures but not to L cells. The protective principle complies with present criteria for an interferon. The results are compatible with the suggestion that EB2 cultures are latently infected with an as yet unidentified virus.
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PMID:EVIDENCE FOR A PERSISTENT VIRAL INFECTION IN A CELL LINE DERIVED FROM BURKITT'S LYMPHOMA. 1425 73

A retrospective review was performed on the toxicity and response to one cycle of dose-intense cyclophosphamide/etoposide, followed by consolidation in patients with refractory or previously untreated, high-risk non-Hodgkin's lymphoma (NHL). Fifty-five patients with refractory NHL and 13 with untreated, high-risk NHL were administered one cycle of daily cyclophosphamide 1.5 g/m2 intravenously on days 1-4 and etoposide 300 mg/m2 intravenously every 12 hours on days 1-3. Responders then received other consolidated regimens. Twenty-seven percent of patients with refractory disease had moderate or severe stomatitis, and 44% had moderate or severe infections with 6 (11%) dying of this complication. Similar complication rates were noted in the previously untreated, high-risk group, but there was no treatment-related mortality. The overall response rate to this one cycle of therapy was 31% in the refractory group, with 18% complete response and 13% partial response. The overall response rate in the previously untreated, high-risk group was 69%, with 54% complete and 15% partial responses. In responders, the 2-year event-free survival was 27% in the refractory group and 56% in high-risk group. Dose-intense cyclophosphamide/etoposide has promising efficacy; however, nonhematologic toxicity can be considerable. The better tolerance, high response rate, and encouraging 2-year survival of this regimen in combination with further dose-dense consolidation in patients with high-risk NHL are encouraging.
Clin Lymphoma 2004 Sep
PMID:Dose-intense cyclophosphamide and etoposide for patients with refractory or high-risk non-Hodgkin's lymphoma. 1545 27

Nasal NK/T-cell lymphoma is EB virus-associated aggressive lymphoma, which is more prevalent in Asia. Previously, this lymphoma which was recognized as lethal midline granuloma, commonly presents with midline facial destructive lesions. In early stage I/II disease, radiation therapy exerts a powerful treatment outcome, however, toxic adverse events are indispensable and the tolerability of radiation therapy with chemotherapy has not been fully studied. It is imperative to offer an appropriate treatment for cure of this disease. We report consecutive 4 cases of nasal NK/T-cell lymphoma, which was treated with 56 Gy intensified local radiation therapy followed by systemic chemotherapy. Two cases complicated with grade 3 stomatitis during the treatment course and 3 cases were hospitalized due to the decrease of oral intake. The scheduled radiation chemotherapy was completed and resulted in complete response of disease in all cases. High intensified radiation therapy followed by chemotherapy may be effective for localized nasal NK/T-cell lymphoma.
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PMID:[Case series of localized nasal NK/T-cell lymphoma treated with preceding intensified local radiation therapy before systemic chemotherapy]. 1668 74

A German Hodgkin's lymphoma (HL) study group designed the BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone) regimen. In the BEACOPP regimen, treatment intervals were shortened and the dose-intensity was increased compared with those in the ABVD regimen (doxorubicin, bleomycin, vinblastine and darcarbacine), resulting in a long-term disease-free survival rate of approximately 75-80%. In the present study, we evaluated the safety and efficacy of the BEACOPP regimen. Between April 2001 and February 2004, 20 patients with HL of stage IIB or higher who had received no previous treatment were enrolled. The patients were aged 17-69 years (median 22 years). The histologic types were mixed cellularity in four cases and nodular sclerosis in 16 cases. The stages were stage IIB in four cases, stage III in 12 cases, and stage IV in four cases. Nineteen (95%) of the 20 patients achieved complete remission. The 3-year survival rate was 100% and the 3-year progression-free survival rate was 89.7%. Adverse drug reactions were grade 4 neutropenia in 12 patients, grade 3-4 thrombocytopenia in seven patients, and grade 3 or higher non-hematologic toxicities in two patients (stomatitis in one patient and ALT/AST elevation in one patient). The BEACOPP regimen for advanced-stage HL showed an excellent complete remission rate and high efficacy even in stage III/IV patients. However, a long-term risk of the BEACOPP regimen is the development of secondary leukemia or myelodysplastic syndrome. Therefore, long-term follow-up of these patients, including monitoring for toxicities, is necessary.
Leuk Lymphoma 2006 Sep
PMID:Multicentre phase II study of the baseline BEACOPP regimen for patients with advanced-stage Hodgkin's lymphoma. 1706 5

Paraneoplastic pemphigus (PNP) is a rare autoimmune bullous disease associated with neoplasm, which is clinically characterized by mucocutaneous lesions resembling pemphigus vulgaris or erythema multiforme. A case presented with PNP refractory to chemotherapy including rituximab, predonisolone and cyclophosphamide (RCHOP regimen). A 36-year-old man, who had been diagnosed as extended follicular lymphoma, presented with a polymorphous skin eruption of the trunk, sclera conjunctivitis, and severe mucosal erosions of the lips and oral cavity. He was diagnosed as pemphigus pathologically by a biopsy of the oral mucosa. However, 3 courses of rituximab and CHOP therapy, which exert a partial response with lymphoma lesions, did not prove effective for oral stomatitis due to pemphigus. He received corticosteroid therapy (prednisolone 40 mg/day) and went into a state of temporally remission regarding pemphigus. However, the mucosal lesions were again exacerbated despite control of the lymphoma status after chemotherapy. Oral stomatitis extended to the upper respiratory system through the larynx and resulted in bronchiolitis obliterance clinically presented likely as severe chronic obstructive pulmonary disease (COPD). Because it is known that PNP refractory to long-term steroid and cytoreductive therapy has a progressive character and poor prognosis, supportive care would be warranted for these patients.
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PMID:[A case of follicular lymphoma complicated with lethal pemphigus]. 1710 41

Chronic lymphocytic leukemia (CLL) is characterized by clonal accumulation of CD5(+) CD19(+) B lymphocytes that are arrested in the G(0)/G(1) phase of the cell cycle and fail to undergo apoptosis because of overexpression of the antiapoptotic B-cell CLL/lymphoma 2 (BCL-2) protein. Oncolytic viruses, such as vesicular stomatitis virus (VSV), have emerged as potential anticancer agents that selectively target and kill malignant cells via the intrinsic mitochondrial pathway. Although primary CLL cells are largely resistant to VSV oncolysis, we postulated that targeting the apoptotic pathway via inhibition of BCL-2 may sensitize CLL cells to VSV oncolysis. In the present study, we examined the capacity of EM20-25--a small-molecule antagonist of the BCL-2 protein--to overcome CLL resistance to VSV oncolysis. We demonstrate a synergistic effect of the two agents in primary ex vivo CLL cells (combination index of 0.5; P < 0.0001). In a direct comparison of peripheral blood mononuclear cells from healthy volunteers with primary CLL, the two agents combined showed a therapeutic index of 19-fold; furthermore, the combination of VSV and EM20-25 increased apoptotic cell death in Karpas-422 and Granta-519 B-lymphoma cell lines (P < 0.005) via the intrinsic mitochondrial pathway. Mechanistically, EM20-25 blocked the ability of the BCL-2 protein to dimerize with proapoptotic BAX protein, thus sensitizing CLL to VSV oncolytic stress. Together, these data indicate that the use of BCL-2 inhibitors may improve VSV oncolysis in treatment-resistant hematological malignancies, such as CLL, with characterized defects in the apoptotic response.
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PMID:Targeting the apoptotic pathway with BCL-2 inhibitors sensitizes primary chronic lymphocytic leukemia cells to vesicular stomatitis virus-induced oncolysis. 1857 92

Pediatric lymphoblastic lymphoma (LL) has utilized treatment strategies similar to childhood acute lymphoblastic leukaemia (ALL) with prolonged maintenance chemotherapy. We report the results of a pilot study to estimate the feasibility, toxicity and efficacy of a 12-month aggressive multi-agent chemotherapy regimen in children and adolescents with advanced LL. Between July 1994 and June 1997, 85 eligible children and adolescents with advanced LL (Stage III/IV) were enrolled on this pilot study. Patients achieving a complete response following induction and consolidation received six cycles of maintenance chemotherapy for a total duration of 12 months. Grade III/IV toxicities included: hematological (80%), infections (20%), stomatitis and elevated transaminases, (29%). There were a total of 19 events, 13 relapses, two secondary acute myeloid leukaemia and four toxic deaths (5%). The 5-year event-free survival (EFS) and overall survival (OS) was 78 +/- 4.5% and 85 +/- 3.9%, respectively. Relapsed patients had a 5-year OS of only 33 +/- 14%. Multivariate analysis failed to demonstrate age, gender, lactate dehydrogenase level, presence of marrow and/or central nervous system disease to have independent prognostic value. These results suggest that this experimental approach is safe and results in similar outcomes as more prolonged childhood ALL regimens.
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PMID:Shortened intensified multi-agent chemotherapy and non-cross resistant maintenance therapy for advanced lymphoblastic lymphoma in children and adolescents: report from the Children's Oncology Group. 1875 68

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease. Like other herpesviruses, KSHV establishes life-long latency in the human host with intermittent periods of reactivation. Physiological triggers of herpesviral reactivation are poorly defined. Toll-like receptors (TLRs) recognize pathogens and are vital for the host innate immune response. We screened multiple TLR agonists for their ability to initiate KSHV replication in latently infected PEL. Agonists specific for TLR7/8 reactivated latent KSHV and induced viral lytic gene transcription and replication. Furthermore, vesicular stomatitis virus (VSV), a bonafide physiological activator of TLR7/8, also reactivated KSHV from latency. This demonstrates that secondary pathogen infection of latently infected cells can reactivate KSHV. Human herpesviruses establish life-long latency in the host, and it is plausible that a latently infected cell will encounter multiple pathogens during its lifetime and that these encounters lead to episodic reactivation. Our findings have broad implications for physiological triggers of latent viral infections, such as herpesviral reactivation and persistence in the host.
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PMID:Toll-like receptor signaling controls reactivation of KSHV from latency. 1956 11

Elderly individuals are susceptible to autoimmune bullous dermatoses (ABDs), which may be associated with high morbidity and mortality. ABDs result from an autoimmune response to components of the basement membrane zone at the dermal-epidermal junction or desmosomes. Bullous pemphigoid results from autoimmunity to hemidesmosomal proteins present in the basement membrane of stratified squamous epithelia. Patients present with tense blisters in flexural areas of the skin. Mild disease may be treated with potent topical corticosteroids, while extensive disease usually requires systemic corticosteroids or systemic immunosuppressive agents such as azathioprine. Mucosal pemphigoid affects one or more mucous membranes that are lined by stratified squamous epithelia. The two most commonly involved sites are the eye and the oral cavity. Lesions frequently result in scar formation that may cause blindness. Patients with severe disease or ocular involvement require aggressive therapy with corticosteroids and cyclophosphamide. Epidermolysis bullosa acquisita results from autoimmunity to type VII collagen in the anchoring fibrils of the basement membrane. Lesions may either arise on an inflammatory base or be non-inflammatory and result primarily from trauma. Treatment options include corticosteroids, dapsone, ciclosporin, methotrexate and plasmapheresis/immunoapheresis. Paraneoplastic pemphigus results from autoimmunity to multiple desmosomal antigens. The disorder is associated with neoplasms, especially leukaemia, lymphoma and thymoma. Patients present with stomatitis and polymorphous skin eruption. The disease may respond to successful treatment of the underlying neoplasm or may require immunosuppressive therapy.
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PMID:Autoimmune bullous dermatoses in the elderly: an update on pathophysiology, diagnosis and management. 2003 Apr 29

In chronic lymphocytic leukemia (CLL), overexpression of antiapoptotic B-cell leukemia/lymphoma 2 (BCL-2) family members contributes to leukemogenesis by interfering with apoptosis; BCL-2 expression also impairs vesicular stomatitis virus (VSV)-mediated oncolysis of primary CLL cells. In the effort to reverse resistance to VSV-mediated oncolysis, we combined VSV with obatoclax (GX15-070)-a small-molecule BCL-2 inhibitor currently in phase 2 clinical trials-and examined the molecular mechanisms governing the in vitro and in vivo antitumor efficiency of combining the two agents. In combination with VSV, obatoclax synergistically induced cell death in primary CLL samples and reduced tumor growth in severe combined immunodeficient (SCID) mice-bearing A20 lymphoma tumors. Mechanistically, the combination stimulated the mitochondrial apoptotic pathway, as reflected by caspase-3 and -9 cleavage, cytochrome c release and BAX translocation. Combination treatment triggered the release of BAX from BCL-2 and myeloid cell leukemia-1 (MCL-1) from BAK, whereas VSV infection induced NOXA expression and increased the formation of a novel BAX-NOXA heterodimer. Finally, NOXA was identified as an important inducer of VSV-obatoclax driven apoptosis via knockdown and overexpression of NOXA. These studies offer insight into the synergy between small-molecule BCL-2 inhibitors such as obatoclax and VSV as a combination strategy to overcome apoptosis resistance in CLL.
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PMID:VSV oncolysis in combination with the BCL-2 inhibitor obatoclax overcomes apoptosis resistance in chronic lymphocytic leukemia. 2084 5


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