Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MDM2 oncogene is overexpressed in many human cancers including breast, colon, and prostate cancer, and MDM2 levels are associated with poor prognosis in patients with cancer. Here, we summarize the investigation of the functions of MDM2 oncogene in human cancer growth and the value of MDM2 as a drug target for prostate cancer therapy by using antisense to inhibit MDM2 expression. Antisense anti-human-MDM2 oligonucleotides and mismatch controls were tested in in vitro and in vivo human cancer models for antitumor activity. Targeted gene products and related proteins were analyzed and the antitumor activity was determined when the oligonucleotides were used alone or in combination with cancer chemotherapeutics and radiation therapy. The antisense oligonucleotide specifically inhibited MDM2 expression in a dose- and time-dependent manner, resulting in significant antitumor activity in vitro and in vivo. The antisense oligonucleotides also potentiated the effects of p53 activation and p21 induction by chemotherapeutic agents 10-hydroxycamptothecin, adriamycin, 5-fluorouracil, and paclitaxel. In a dose-dependent manner, the antisense oligonucleotide showed antitumor activity in nude mice bearing human cancer xenografts and increased therapeutic effectiveness of the chemotherapeutic agents irinotecan, paclitaxel, and Rituxan and radiation therapy. These results indicate that MDM2 has a role in various tumor growth through both p53-dependent and p53-independent mechanisms, indicating that MDM2 inhibitors have a broad spectrum of antitumor activities in human cancers regardless of p53 status. These results provide a basis for clinical evaluation of antisense anti-MDM2 oligonucleotides as chemosensitizer and radiosensitizer.
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PMID:Chemosensitization and radiosensitization of human cancer by antisense anti-MDM2 oligonucleotides: in vitro and in vivo activities and mechanisms. 1475 37

Several monoclonal antibodies that target cell surface receptors have gained approval by the U.S. Food and Drug Administration and are widely used in the treatment of some cancers. These include but are not limited to the anti-CD20 antibody Rituximab, used in lymphoma treatment, as well as anti-HER-2 antibody for breast cancer therapy. The efficacy of this cancer immunotherapy modality is, however, limited by the large size of the antibody (160 kd) and its relatively nonspecific binding to the reticuloendothelial system. This latter property is particularly problematic if the antibody is used as a vehicle to deliver radionuclides, cytotoxic drugs, or toxins to the tumor site. Peptides, peptidomimetic, or small molecules are thus attractive as alternative cell surface targeting agents for cancer imaging and therapy. Cancer cell surface targeting peptides can be derived from known native peptide hormones such as somatostatin and bombesin, or they can be identified through screening combinatorial peptide libraries against unknown cell surface receptor targets. Phage-display peptide library and one-bead one-compound (OBOC) combinatorial library methods have been successfully used to discover peptides that target cancer cells or tumor blood vessel endothelial cells. The phage-display peptide library method, because of its biological nature, can only display l-amino acid peptides. In contrast, the OBOC combinatorial library method allows for bead-surface display of peptides that contain l-amino acids, d-amino acids, unnatural amino acids, or other organic moieties. We have successfully used the OBOC method to discover and optimize ligands against unique cell surface receptors of prostate cancer, T- and B-cell lymphoma, as well as ovarian and lung cancers, and we have used some of these peptides to image xenografts in nude mice with high specificity. Here, we (i) review the literature on the use of phage-display and OBOC combinatorial library methods to discover cancer and tumor blood vessel targeting ligands, and (ii) report on the use of an ovarian cancer targeting ligand, OA02, as an in vivo PET imaging probe in a xenograft model in nude mice.
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PMID:From combinatorial chemistry to cancer-targeting peptides. 1788 Jan 66

Revlimid (Lenalidomide, CC-5013) and CC-4047 are IMiDs immunomodulatory drugs that have been described as having immunomodulatory properties and anti-tumor activity. Here we report proapoptotic effects of CC-5013 and CC-4047 on tumor cells in a co-culture model of PBMC and tumor cells. CC-5013 and CC-4047 enhanced PBMC activity leading to tumor cell apoptosis in K562/PBMC co-culture model. We also demonstrate that the natural killer (NK) cell population of PBMC was essential in inducing K562 apoptosis. Increases of NK and natural killer T (NKT) cell populations by CC-5013 and CC-4047 was observed along with modulation of NK cell CD56 adhesion marker. In addition, our data indicate that NK activation by CC-4047 was dependent on other cell types of PBMC. We expanded the application of K562/PBMC co-culture model to other hematological and solid tumors. In Raji/PBMC co-culture model, CC-5013 and CC-4047 dose-dependently augmented tumor cell apoptosis. Pre-treatment of Raji cells with Rituximab further enhanced apoptosis induced by CC-5013 or CC-4047-treated PBMC. Moreover, CC-5013 and CC-4047 significantly increased PC-3 prostate cancer cell apoptosis in PC-3/PBMC co-culture, either as single agent or in combination with Docetaxel. Together, the results reveal that co-culture models are suitable cellular systems to assess anti-tumor activities of these compounds. Our findings support clinical evaluation of CC-5013 and CC-4047 in relapsed NHL with Rituximab and in prostate cancer with Docetaxel.
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PMID:Immunomodulatory drugs Revlimid (lenalidomide) and CC-4047 induce apoptosis of both hematological and solid tumor cells through NK cell activation. 1839 23

The clinical management of cancer in senior adult patients is based on the results of clinical trials which were performed in adults, generally younger adult patients. It is therefore difficult to assess the feasibility of such treatments, mainly chemotherapy, in older patients. The evaluation of health status is an important step in the decision making of cancer treatment in senior adults. In non Hodgkin lymphomas, the standard treatment remains chemotherapy with Rituximab. Specific protocols and treatment adaptation have been proposed in very old seniors. Surgery is a very efficient treatment in breast cancer, colorectal cancer and sometimes in non small cell lung cancer. Radiotherapy is important in the curative management of prostate cancer and in the multidisciplinary treatment of breast, colorectal and lung cancers. Chemotherapy is generally feasible in senior adults. However, Cisplatin is often too much toxic. Chemotherapy has a palliative impact in the treatment of metastatic prostate and breast cancers. It would be discussed in some high-risk groups of patients with breast and colorectal cancers. New targeted drugs are active in breast, colorectal cancers and in non Hodgkin lymphomas. Indications of treatment tailored on health status evaluation are discussed in the manuscript.
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PMID:[Clinical management of the most important cancers in older patients]. 1940 78

A role for CD20 antibodies in treating prostate cancer has not yet been established. We report a case of advanced prostate cancer presenting with generalized lymphadenopathy that expressed CCR7 and CD20. CCR7 expression in prostate cancer has been previously reported only once; the expression of CD20 has not been reported before. Rituximab therapy was initiated in this case and resulted in a significant biochemical response. This unique metastatic and biochemical pattern may signify a distinct subtype of prostate cancer that may be amenable to treatment with anti-CD20 antibodies.
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PMID:Rituximab for treating CD20+ prostate cancer with generalized lymphadenopathy: a case report and review of the literature. 2444 68