Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

People with deficient cell-mediated immunity have an increased susceptibility to viral infections and certain cancers, particularly non-Hodgkin's lymphomas and cancers of the skin and anogenital region. These are linked to viral origins. Anogenital neoplasms in immunodeficient patients show a strong association with HPV infection; often occur at relatively young ages; involve multifocal locations; and tend to persist, recur, and progress rapidly, despite standard therapy. Because standard therapy of anogenital HPV lesions and neoplasia is often not effective in immunodeficient patients (and others with an anogenital neoplastic syndrome), special treatment is required. 5-Fluorouracil chemosurgery, followed by maintenance 5-fluorouracil therapy, is often effective and provides field suppression against recurrent HPV infection and neoplasia, with minimal damage to affected organs. After removal of all detectable HPV and neoplastic lesions, immunodeficient patients require close surveillance of the entire anogenital tract. Immunodeficient patients are an in vivo human laboratory in which to study the natural history of HPV and its oncogenic effects on the anogenital tract. The theory of HPV oncogenesis is supported by the evidence gathered from these patients.
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PMID:Anogenital papillomavirus infection and neoplasia in immunodeficient women: an update. 164 9

Mitoxantrone is similar to Adriblastin in its mechanism of action and antitumor activity. Objective remissions were obtained in 20-30% pretreated patients and in 23-44% of untreated patients by single-drug treatment of patients suffering from metastatic breast cancer. The objective response rates to Mitoxantrone in combination with CTX, 5-FU, MTX, VCR, MMC. Prednimustine or Vindesine were 16-46% in treatment and 38-89% in primary treatment. Randomized studies comparing Mitoxantrone with Adriblastin in single-drug and combination treatment did not show any significant differences in efficacy. However, Mitoxantrone was significantly less toxic. Remission rates of between 24 and 54% were achieved by single-drug treatment in pretreated patients suffering from non-Hodgkin lymphoma. Mitoxantrone appears to be active in ovarian cancer, lung cancer and hepatocellular carcinoma.
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PMID:Mitoxantrone: mechanism of action, antitumor activity, pharmacokinetics, efficacy in the treatment of solid tumors and lymphomas, and toxicity. 332 53

Concurrent administration of allopurinol allows escalation of 5-FU doses in man when 5-FU is given by continuous infusion for 5 days. Forty-nine patients received 81 courses of treatment with 5-FU and allopurinol in phase I and II trials. The dose-limiting toxicity was mucositis; marrow toxicity was mild. Neurotoxicity, possibly related to 5-FU, occurred in eight patients. No responses were seen in 14 evaluable patients with colon cancer, 11 of whom had had prior 5-FU. One patient with Hodgkin's disease had a partial response; one patient with diffuse histiocytic lymphoma had transient disease regression. Although allopurinol does modify the toxicity of 5-FU, permitting dose escalation, it does not increase the therapeutic index in colon cancer. Infusional 5-FU deserves further study in lymphoma.
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PMID:5-FU and allopurinol: toxicity modulation and phase II results in colon cancer. 708 15

Secondary acute myeloid leukemia (s-AML) and secondary myelodysplastic syndrome (s-MDS) probably represent the worst possible long-term complications of cancer therapy in patients originally cured of their primary malignancy. The frequency and type of s-AML and s-MDS are reviewed for patients treated with standard and/or high-dose chemotherapy for Hodgkin's disease, non-Hodgkin's lymphoma (NHL), and breast or testicular cancer. Patients treated for Hodgkin's disease, have a 20- to 40-fold increased risk of developing s-AML, this risk increasing with the number of mechlorethamine-containing cycles given as well as following splenectomy and in patients more than 40-50 years of age. Generally, patients with NHL, breast or testicular cancer experience a lower, 2- to 15-fold, risk of developing s-AML. Epipodophyllotoxins appear to be the most important factor for s-AML in patients treated for testicular cancer. Doses of 2g/m2 or more are associated with an increased risk of s-AML and, with these high doses, a cumulative incidence of 2% 3% at 5 years is observed. Adjuvant cyclophosphomide, methobrexate, 5-Fu therapy in breast cancer patients does not appear to increase risk significantly as compared to the general population. The extent of the leukemogenic potential of anthracyclines remains to be defined. NHL patients receiving mechlorethamine, prednimustine or long-term maintenance therapy are also at an increased risk of s-AML. A considerably increased risk of developing AML, with a cumulative incidence of approximately 9% at 5 years, has been observed following allogenic bone marrow transplantation (ABMT) or peripheral stem cell transplantation (PBSCT) in patients with NHL. It is likely that the increased risk of s-AML/s-MDS following high-dose chemotherapy with ABMT or PBSCT is related to prior treatment rather than to high-dose chemotherapy itself. However, this issue remains to be conclusively addressed. s-AML or s-MDS rarely develops after allogenic bone marrow transplantation. s-AML and s-MDS increasingly represent a problem in modern cancer therapy because of better treatment strategies, which result in improved cure rates. Patients who receive chemotherapy must be informed about the potential risk of developing s-AML or s-MDS. Future studies should include a follow-up long enough to record the occurrence of all s-AML/s-MDS and all potential influencing factors reliably. These data would enable risk factors to be defined and risk/benefit analyses to be carried out, allowing the correct assessment of current and future therapy strategies.
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PMID:Risk of secondary myeloid leukemia and myelodysplastic syndrome following standard-dose chemotherapy or high-dose chemotherapy with stem cell support in patients with potentially curable malignancies. 961 48

In a prospective multi-centre collaborative study, 516 patients with advanced cancer were treated by epirubicin (pararubicin, EPI) containing regimens. After CEOP (cyclophosphamide CTX, EPI, vincristine VCR and prednisone PDN) was used in the treatment of 213 patients with non-Hodgkin's lymphomas, 87 patients had complete remission (CR) and 99 partial remission (PR). Their response rate was 87.3%. However, there were 2 CR and 71 PR in 161 patients with non-small cell lung cancer treated by CEP regimen (CTX, EPI and cisplatin PDD), with a response rate of 45.3%. In 70 breast cancer patients treated by EMF regimen (EPI, Methotrexate MTX and 5-fluorouracil 5-FU), 8 had CR and 28 PR, with a response rate of 51.4%. The EPI containing regimens were also effective in dealing with gastro-intestinal tract and nasopharyngeal cancers. Adverse effects of epirubicin containing regimens were mainly nausea and vommiting, and the dose-qlimit toxicity was leucopenia. Hepatic, cardiac and renal toxicities were rather mild. The current phase III study revealed that the effect of epirubicin is similar to that of adriamycin, but the cardiac toxicity is relatively mild. So the effects can be improved by increasing the dose-intensity.
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PMID:[Epirubicin containing regimens in advanced malignant tumors report of 516 cases. Epirubicin Collaborative Study Group]. 1037 13

Even though a malignant tumor during pregnancy is very rare it occurs in 0.02-0.1%. With the tendency in society to postpone childbirth to an older age, there will be more cancers diagnosed during pregnancy. The coincidence of malignant disease with pregnancy leads to an enormous emotional burden to the patient, the couple and the medical staff. Surgery for malignant tumors during pregnancy seems to be save. Radiotherapy on the other hand should be avoided. Chemotherapy is regarded to be save during the second and third trimester but it should not be applied during the first trimester because of its teratogenic effects. The most frequent malignant disorders during pregnancy are cervical cancer, breast cancer, melanoma and Hodgkin lymphoma. We discuss possible treatment options for breast cancer and gynecological tumors during pregnancy. Ovarian Cancer is a rare event during pregnancy. Because of frequent prenatal visits most of them are diagnosed at an early stage, with good prognosis. In case of advanced stage of ovarian cancer chemotherapy besides surgery is necessary. The former usually is preferred as monotherapy during pregnancy. To treat breast cancer during pregnancy a mastectomy with axillary lymphonodectomy is necessary to avoid radiotherapy. Indications for chemotherapy are the same as for not pregnant patients. Usually AC with and without 5-FU is used. For invasive cervical cancer surgery or radiotherapy +/- chemotherapy is indicated after induced abortion or cesarean section. Early termination of pregnancy is of no survival benefit to the mother in case of breast cancer and ovarian cancer. In these cases systemic therapy during pregnancy and delivery at 34 weeks is recommended.
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PMID:[Chemotherapy for gynecological malignancies--a contraindication during pregnancy?]. 1570 7

Hodgkin/Reed-Sternberg lymphoma (HL) is a clonal B-cell-related malignancy. Although many patients with HL can be cured by the current regimen of high-dose multi-agent chemotherapy, the treatment causes high risks of later pathologies including secondary malignancies. This fact highlights the demand to develop rational treatment for HL. Survival and growth of HL cells are largely dependent on their microenvironment. In this study, using the HL cell lines L1236 and KM-H2 as model systems, we investigated the role of IL-4/IL-13 signaling in regulation of drug sensitivity and resistance in HL. We show that specific blocking of IL-4 and IL-13-mediated STAT6 activation by either an IL-4-binding fusion protein APG598 or an IL-4R antagonist APG201 (R121D/Y124D) renders HL cells more prone to apoptotic killing by chemotherapeutic drugs such as Mitomycin C, 5-Fluorouracil, Etopside, Doxorubicin and Paclitaxel. This effect is due to inhibition of STAT6-mediated elevation of expression of the anti-apoptotic Bcl-2 family protein Bcl-xL. Employing ChIP analysis in combination with APG201 or STAT6-specific siRNA we identified a defined STAT6-binding site in the Bcl-xL promoter region from -1967 to -1957 of the transcription start site. Our data demonstrate that the IL-4/IL-13-STAT6-Bcl-xL axis may be an important target for HL treatment. This study also suggests that combination of classical chemotherapeutic drugs with the IL-4/IL-13 antagonists may enhance efficacy and reduce risks of toxicity from high dose of drugs in HL treatment.
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PMID:Targeting the IL-4/IL-13 signaling pathway sensitizes Hodgkin lymphoma cells to chemotherapeutic drugs. 2355 37