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)

Since 1982, high-grade B-cell non-Hodgkin's lymphomas (NHLs) have been reported among persons with human immunodeficiency virus (HIV) infection (1); in 1985, CDC revised the surveillance case definition for acquired immunodeficiency syndrome (AIDS) to include certain high-grade NHLs. Recent surveillance findings indicate that NHLs occur among approximately 3% of all adults with AIDS reported to CDC. This report characterizes the occurrence of NHLs in a cohort of persons with AIDS or severe HIV infection who have received long-term zidovudine (AZT)-based therapy.
 ...
PMID:Opportunistic non-Hodgkin's lymphomas among severely immunocompromised HIV-infected patients surviving for prolonged periods on antiretroviral therapy--United States. 187 May 60

The Inter-Company Collaboration for AIDS Drug Development (ICC) represents a collaborative effort among member companies to facilitate the conduct of clinical trials on AIDS drugs. One of the goals of the ICC is to expedite the development of combination antiretroviral therapy through data and compound sharing. Recently, the ICC formed a consensus master protocol to evaluate rapidly the safety and efficacy of triple-drug combinations of antiretroviral therapy for treatment of HIV-infected patients. This concept builds upon historical work with combination chemotherapy that resulted in treatments to successfully control chronic immunosuppressive, infectious or malignant diseases, such as tuberculosis, leprosy, childhood acute lymphoblastic leukemia, and Hodgkin's lymphoma. Because of limitations on potency and the continuing emergence of drug resistance seen with use of currently available antiretroviral agents in monotherapy and two-drug combination regimens, triple-combination regimens should represent a more promising approach to maximize antiviral activity, maintain long-term efficacy, and reduce the incidence of drug resistance. The ICC master protocol is a randomized, controlled, double-blind study with a treatment duration of 52 weeks. Patients eligible to enroll in this study must have documented HIV infection, with CD4 counts between 200 and 500 cells/mm3, and no history of antiretroviral therapy. The first four triple-drug combinations will be evaluated in two trials. These regimens have been selected based on encouraging data from laboratory and clinical studies. Each ICC trial will consist of three arms, with 75 patients per arm. Protocol ICC 001 will include AZT + zalcitabine (ddC) + saquinavir, AZT + ddC + nevirapine, and AZT + ddC as the control arm.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Inter-Company Collaboration Combination Trials. Clinical Trial Subcommittee of the Inter-Company Collaboration for AIDS Drug Development. 755 20

Infection with human immunodeficiency virus type 1 (HIV-1) primarily involves a subgroup of T-lymphocytic cells, but other cell types are also invaded by the virus, including cell lines within the haematopoietic system. Together with infectious, inflammatory and neoplasic processes, invasion of haematopoietic tissue explains the haematological alterations which are seen during the course of infection with HIV-1. Anaemia develops in the large proportion of patients. Thrombocytopenia frequently occurs during the course of the disease, but may be seen in some patients already at the time of diagnosis, where the condition may be misdiagnosed as "idiopathic" thrombocytopenic purpura. Neutropenia is seen in all disease stages, but is most severe in patients with advanced disease. Bone marrow changes include varying degrees of dysplasia in one or more cell lines, which in some patients may mimic a myelodysplastic syndrome. The number of plasma cells is always increased. In many patients the bone marrow stroma exhibits an increased amount of reticular fibres. HIV-1 infection is associated with an increased risk of non-Hodgkin malignant lymphoma. Acute myelogenous leukaemia and myelomatosis have been described in patients with advanced disease. Treatment of the above mentioned haematological abnormalities aims primarily at reducing replication of HIV-1, thereby diminishing suppression of haematopoiesis by the virus infection, and at controlling the opportunistic infections during the course of the disease. Specific antiviral therapy (AZT) is most successful in correcting thrombocytopenia. The possibility of bone marrow suppression mediated by a toxic drug effect should always be considered in this patient group.
 ...
PMID:[Hematological changes associated with human immunodeficiency virus (HIV-1) infection]. 831 70

AZT is a thymidine analogue useful in the treatment of AIDS. It has been demonstrated that this compound can possess a significant antineoplastic activity when combined with de novo thymidylate synthesis inhibitors, such as 5-fluorouracil (5FU) and methotrexate (MTX). Here we report a review of our data concerning the efficacy and tolerance of the combination AZT + MTX in HIV-related non Hodgkin's lymphomas (NHL). Twenty-nine patients were treated, at weekly intervals, with three (patient 1 to 10) or six (patient 11 to 29) consecutive courses of MTX 1g/m2 and increasing doses of oral AZT (2, 4 and 6g/m2) with leucovorin rescue. Of 26 evaluable patients, a total (complete + partial) response rate of 77% was obtained. The median complete response duration was 16.8 months. There was one therapy-related death due to septic shock. Grade III-IV neutropenia was observed after 19% of the courses, but was prevented by G-CSF administration in 82/119 courses. Grade III-IV anemia was observed after 9% of the courses. In conclusion, the combination AZT + MTX was effective and well tolerated in our series of HIV-related NHL patients.
 ...
PMID:AZT plus methotrexate in HIV-related non-Hodgkin's lymphomas. 966 87

About twenty years ago, the leaders of the National Cancer Institute (NCI) decided to start a new branch in the Clinical Oncology Program of the Division of Cancer Treatment. That new entity was named the Clinical Pharmacology Branch (CPB), and its first leader was a brilliant, young, promising investigator named Bruce A. Chabner. Chabner was educated at Yale and Harvard, and appeared to have an extraordinary grasp of novel concepts that were being developed in the emerging area of cancer chemotherapy. What the NCI leaders did not fully appreciate at the time was that they had just given birth to one of the most extraordinary careers in academic medicine. From the early seventies through the early eighties, Bruce Chabner developed a strong laboratory program that was based on scientific discovery and on the development of new talent. The CPB focused on new drug development, elucidation of drug mechanism(s) of action, and the development of new ways to use drugs that were already available. Concurrent with this laboratory effort was active participation in the development of clinical treatment regimens for Hodgkin's disease, non-Hodgkin's lymphoma, and other malignancies. Individuals who trained under Chabner are now cancer center directors, department heads, laboratory chiefs, and hold many other high-profile positions. From 1981 to 1995 Bruce Chabner was Director of the Division of Cancer Treatment (DCT) of the NCI. In that capacity he was Scientific Director of the Intramural Program within DCT, and he had oversight responsibility for the direction of extramural studies that were funded through the NCI, which were focused on the development of new treatments for human malignant disease. The NCI has five divisions for which the NCI Director has ultimate responsibility. While working with one NCI Director from 1981 to 1988, and with another from 1988 to 1995, and during the transition year of 1988, Bruce Chabner provided stability for the DCT while many changes were occurring throughout the five divisions of the NCI. How does one assess the impact of a career on a discipline such as cancer treatment? It's not easy! Each of the articles contributed to this tribute were written by a person who trained directly with Bruce Chabner, or was otherwise directly impacted by Bruce's guidance. As can be seen from the list of contributors to these Proceedings, each individual has made major contributions to the area of cancer treatment in his or her own right. However, Bruce's contribution to cancer treatment goes far beyond the individuals he trained. The many thousands of human lives who have benefited from his efforts cannot be accurately estimated, because his contributions have been so wide-ranging, as indicated below. Being "Scientific Director" is similar in a number of ways to being a football quarterback. One of those ways is that when things go well the quarterback may get a little too much credit, and when things go not-so-well the quarterback may get too much blame. However, it is the quarterback who "calls the plays." With that in mind, a partial list of the accomplishments of the Intramural Program of the DCT while Bruce Chabner was "quarterback" includes the following: * The first human retroviruses, HTLV-1 and HTLV-2, were discovered and shown to be directly linked to the development of specific human malignancies. * Adoptive immunotherapy for human cancer was developed, offering exciting new additions to the anticancer armamentarium. * Paclitaxel (Taxol®) was developed, and shown to be the most important new anticancer agent in the past two decades. * The human genes responsible for the development of several specific malignancies were discovered, such as those for kidney cancer. * Development of blood tests to detect HIV-tainted blood. * Treatment strategies for pediatric AIDS were developed. * The AIDS Drug Development Program within the NIH was established. * New drugs for the treatment of AIDS and AIDS-related conditions were developed. * The only three drugs to date that have been specifically approved for the treatment of AIDS-AZT, DDI, and DDC-were developed under the guidance of the DCT, with Bruce Chabner as Scientific Director. * The first clinical trials conducted with each of these agents-AZT, DDI, and DDC-were performed in the Intramural Program of the DCT. * Concurrently, many of the exciting findings reported by the National Surgical Adjuvant Breast and Bowel Project over the past 10 years (as well as other cooperative groups) were a direct result of the strong support shown by Bruce Chabner during his tenure as Director of the Division of Cancer Treatment. Further, the list above does not include his personal labortory and clinical accomplishments, some of which are: * Development of the principles of use of important antimetabolites, such as methotrexate. * Elucidation of biochemical pathways affected, and the mechanisms of action, of antifols and other antimetabolites. * The conduct of seminal studies in the clinical staging of non-Hodgkin's lymphomas, using laparoscopy as a primary tool. * Important contributions to the development of multiagent regimens in the clinical treatment of lymphomas, and of Hodgkin's disease. * Developed and is editor of the textbook which is considered to be the primary reference source for anticancer chemotherapeutic agents [1]. With all of these accomplishments, his career is long from over. Having just become the Medical Director of the Cancer Center at the Massachusetts General Hospital, Bruce Chabner is uniquely poised to have an even more far-reaching impact on a discipline in which he has played such a strong seminal role. This author was never a postdoctoral fellow in Bruce Chabner's laboratory. However, more than any other single person, he has played a central role in my professional development. I know of many others for whom the same statement would be true. It is a pleasure for me to witness the launching of the second phase of an already tremendous career. From Advances in Cancer Treatment: The Chabner Symposium. Stem Cells 1996;14:64-65.
 ...
PMID:Closing Remarks. 1038 2

Treatment of Epstein-Barr virus (EBV)-related lymphomas with lytic-inducing agents is an attractive targeted approach for eliminating virus-infected tumor cells. Zidovudine (AZT) is an excellent substrate for EBV-thymidine kinase: it can induce EBV lytic gene expression and apoptosis in primary EBV+ lymphoma cell lines. We hypothesized that the combination of AZT with lytic-inducing chemotherapy agents would be effective in treating EBV+ lymphomas. We report a retrospective analysis of 19 patients with aggressive EBV+ non-Hodgkin lymphoma, including nine cases of acquired immune deficiency syndrome-associated primary central nervous system lymphoma (AIDS-PCNSL) treated with AZT-based chemotherapy. Our results demonstrate that high-dose AZT-methotrexate is efficacious in treating highly aggressive systemic EBV+ lymphomas in the upfront setting. In primary EBV+ lymphoma cell lines, the combination of AZT with hydroxyurea resulted in synergistic EBV lytic induction and cell death. Further, AZT-hydroxyurea treatment resulted in dramatic responses in patients with AIDS-PCNSL. The combination of AZT with chemotherapy, especially lytic-inducing agents, should be explored further in clinical trials for the treatment of EBV-related lymphomas.
 ...
PMID:Zidovudine-based lytic-inducing chemotherapy for Epstein-Barr virus-related lymphomas. 2383 93