Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CD34 antigen is expressed by 1% to 4% of human and baboon marrow cells, including virtually all hematopoietic progenitors detectable by in vitro assays. Previous work from our laboratory has shown that CD34+ marrow cells can engraft lethally irradiated baboons. Because the CD34 antigen has not been detected on most solid tumors, positive selection of CD34+ cells may be used to provide marrow cells capable of engraftment, but depleted of tumor cells. In seven patients with stage IV breast cancer and two patients with stage IV neuroblastoma, 2.5 to 17.5 x 10(9) marrow cells were separated by immunoadsorption with the anti-CD34 antibody 12-8 and 50 to 260 x 10(6) positively selected cells were recovered that were 64 +/- 16% (range 35% to 92%) CD34+. The patients received 1.0 to 5.2 x 10(6) CD34-enriched cells/kg after marrow ablative therapy. Six patients engrafted, achieving granulocyte counts of greater than 500/mm3 at 34 +/- 10 (range 21 to 47) days and platelets counts of greater than 20,000/mm3 at 46 +/- 14 (range 28 to 66) days posttransplant. Five of these patients showed durable engraftment until the time of death 82 to 386 days posttransplant. One patient failed to sustain engraftment associated with metastatic marrow disease. Three patients died at days 14, 14, and 17 posttransplant, two of whom had evidence of early engraftment. These studies suggest that CD34+ marrow cells are capable of reconstituting hematopoiesis in humans.
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PMID:Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma. 170 96

Tropomyosin receptor kinases receptor C is expressed at high levels on the surface of tumors from metastatic breast cancer, metastatic melanoma, glioblastoma, and neuroblastoma. Previous studies have shown synthetic TrkC ligands bearing agents for photodynamic therapy could be used to completely ablate 4T1 metastatic breast tumors and suppress metastatic spread in vivo. Modification of these probes (A in the text) to make them suitable for near infrared optical imaging in vivo would require a substantial increase in molecular mass (and hence increased vulnerability to undesirable absorption, metabolism and immunogenicity effects), or significant changes to the probe design which might compromise binding to TrkC in histochemical studies and on live cells. The research featured here was undertaken to investigate if the second strategy could be achieved without compromising binding to TrkC-expressing tissues. Specifically, an "aza-BODIPY" probe was synthesized to replace a spacer fragment in the original probe A. In the event, this new probe design (1a in the text) binds TrkC+ breast cancer in live cell cultures, in histochemical studies and in an in vivo murine model. Probe 1a binds TrkC+ tissues with good contrast with respect to healthy tissues, and much more strongly than an isomeric, non-TrkC binding, probe (1b) prepared as a negative control.
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PMID:An agent for optical imaging of TrkC-expressing, breast cancer. 3010 15

Drug repositioning offers two main advantages in drug discovery - the process is less tedious and less costly. In the past, many drugs like thalidomide and sildenafil were successfully repositioned but the process was entirely serendipitous. These days drug repositioning is widely accepted as an alternate method of drug discovery and the process is based on building a strong hypothesis guided by systematic computational and experimental methods. One of the methods used in drug repositioning is based on shared side effects by drugs of different pharmacological categories. This method rests on the principle that drugs that share side effects might also share common biological targets and therefore same pharmacological indications. Old drugs can be repositioned for new uses by identifying the shared side effects of existing drugs and by modulating their chemical structure if required. Breast cancer is the most common type of cancer in women and the second leading cause of death worldwide after lung cancer in both men and women. Letrozole, an aromatase inhibitor, is used in the treatment of advanced, recurrent and metastatic breast cancer in post-menopausal women. Identification of drugs that share side effects with letrozole might help us to identify a potential drug for repositioning in the treatment of breast cancer. Ropinirole, a dopaminergic agonist was found to share the maximum number of side effects with letrozole. Studies have proposed that dopaminergic agonists induce apoptosis in breast, colon, ovarian cancer cells and leukemia neuroblastoma. This is consistent with our hypothesis that ropinirole that shares the maximum number of side effects with letrozole might be effective in the management of breast cancer. This hypothesis was further validated by preliminary molecular docking and in-vitro cell-line studies.
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PMID:Ropinirole, a potential drug for systematic repositioning based on side effect profile for management and treatment of breast cancer. 3276 25