Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixty-six patients with ovarian cancer were treated with low-dose consecutive CP (LDC-CP) consisting of cyclophosphamide (CPM: 500 mg/m2, day 1) and CDDP (10 mg/m2, days 1-7). Two-9 (median: 4) courses of LDC-CP were given following reduction surgery (42 cases) or preceding primary debulking (24 cases). Among 66 cases, 12 with stage Ic were not evaluable (NE). The response rate (CR + PR/evaluable) for stages II-IV was 57.4% (12 + 19/54). Histologically, serous and endometrioid type showed a significantly (p < 0.001) higher response rate (77.5% among 40 evaluable) compared to the other histologic type (0% among 14). Toxicities including nausea/vomiting and renal impairment were markedly mild or almost absent despite the lack of any particular care. Grade 3 leucopenia and thrombocytopenia were observed only in 4.2%, and 2.5% of total 284 courses, respectively. Mean survival time by stage was 1,309 days for stage I, 809 days for stage II, 1,180 days for stage III, and 691 days for stage IV, with a significant difference among stages (p = 0.0452). In stages III and IV disease, significant prognostic factors included 1) response to chemotherapy, 2) no. of LDC-CP courses, 3) histologic subtype, 4) performance status, and 5) tumor size. Thus, LDC-CP is considered to be a useful chemotherapeutic regimen for serous and endometrioid type ovarian cancer.
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PMID:[Chemotherapy of ovarian cancer with a combination of low-dose consecutive CDDP and cyclophosphamide]. 849 34

Acetyl Cholinesterase (AChE) inhibitors such as Donepezil, Rivastigmine and Galantamine are approved by US-FDA as first line drugs to treat the cognitive symptoms of Alzheimer's disease (AD). Their beneficial effects are attributed to their ability to elevate endogenous acetylcholine (ACh) at the M1 muscarinic receptor in the brain. However, their side effects such as nausea, vomiting, dizziness, insomnia, loss of appetite and altered heart rate are related to non-specific activation of M2-M5 muscarinic subtypes in various tissues. It is logical, therefore, to develop agonists with M1 receptor selectivity. Unfortunately, this is limited due to a high degree of orthosteric site homology among the receptor subtypes. In contrast, their allosteric sites are unique and, therefore, allow selective targeting using positive allosteric modulators (PAMs). PAMs of M1 receptors are devoid of agonist activity, however, when bound they enhance the binding affinity of orthosteric ligand, ACh. The major limitation of these PAMs is their bioavailability in the brain. In the current hypothesis, we propose surface modified nano-lipid drug conjugates (LDC-NPs) of PAMs of M1 receptors to improve their bioavailability in brain. When co-administered with AChE inhibitors they are expected to increase their efficacy and reduce their therapeutic dose and side effects.
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PMID:Surface modified nano-lipid drug conjugates of positive allosteric modulators of M1 muscarinic acetylcholine receptor for the treatment of Alzheimer's disease. 2835 83