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

Dinitrotoluenes (DNTs) are byproducts of the explosive trinitrotoluene (TNT), and exist as a mixture of 2 to 6 isomers, with 2,4-DNT and 2,6-DNT being the most significant. The main route of human exposure at ammunition facilities is inhalation. The primary targets of DNTs toxicity are the hematopoietic system, cardiovascular system, nervous system and reproductive system. In factory workers, exposure to DNTs has been linked to many adverse health effects, including: cyanosis, vertigo, headache, metallic taste, dyspnea, weakness and lassitude, loss of appetite, nausea, and vomiting. Other symptoms including pain or parasthesia in extremities, abdominal discomfort, tremors, paralysis, chest pain, and unconsciousness have been documented. An association between DNTs exposure and increased risk of hepatocellular carcinomas and subcutaneous tumors in rats, as well as renal tumors in mice, has been established. This research was therefore designed targeting the liver to assess the cellular and molecular responses of human liver carcinoma cells following exposure to 2,4-DNT and 2,6-DNT. Cytotoxicity was evaluated using the MTT assay. Upon 48 hrs of exposure, LC50 values of 245 +/- 14.724 microg/mL, and 300 +/- 5.92 microg/mL were recorded for 2,6-DNT and 2,4-DNT respectively, indicating that both DNTs are moderately toxic, and 2,6-DNT is slightly more toxic to HepG2 cells than 2,4-DNT. A dose response relationship was recorded with respect to the cytotoxicity of both DNTs. Western blot analysis resulted in a significant expression (p<0.05) of the 70-kDa heat shock protein in 2,6-DNT-treated cells compared to the control cells and at the 200 microg/mL dose for 2,4-DNT. A statistically significant expression in c-fos was also observed at the 200 and 250 microg/mL treatment level for 2,4- and 2,6-DNT, respectively. However, no statistically significant expression of this protooncogene-related protein was observed at the doses of 0, 100, or 300 microg/mL or within the dose range of 0-200 microg/mL for 2,6-DNT. The 45-kDa growth arrest and damage protein was significantly expressed at the dose range of 200 - 250 microg/mL for 2,6-DNT and at the dose range of 200 - 400 microg/mL for 2,4-DNT. Expression of 153-kDa growth arrest and DNA damage protein was significant at the 100, 200, and 250 microg/mL doses for 2,6-DNT and at the 200 microg/mL dose for 2,4-DNT. Overall, these results indicate the potential of DNTs to induce cytotoxic, proteotoxic (HSP70), and genotoxic (GADD45/153) effects, as well as oxidative stress and pro-inflammatory reactions (c-fos).
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PMID:Cytotoxicity and expression of c-fos, HSP70, and GADD45/153 proteins in human liver carcinoma (HepG2) cells exposed to dinitrotoluenes. 1670 39

Tanespimycin, a heat shock protein 90 (HSP90) inhibitor, induces apoptosis in drug-sensitive and -resistant MM cell lines and in tumour cells from patients with relapsed MM. In this phase 1 dose-escalation study, the safety, plasma pharmacokinetics, and biological/antitumour activity of tanespimycin were evaluated in heavily pretreated patients with relapsed/refractory MM. Tanespimycin (150-525 mg/m(2)) was given on days 1, 4, 8, and 11 of each 3-week cycle for up to 8 cycles. Non-haematological AEs included diarrhoea (59%), back pain (35%), fatigue (38%), and nausea (35%); haematological AEs included anaemia (24%) and thrombocytopenia (21%). One patient (3%) achieved minimal response (MR), with a progression-free survival (PFS) of 3 months, a 41% decrease from baseline in urine M protein, and a 33% decrease from baseline in serum M protein. Fifteen patients (52%) achieved SD with a median PFS of 2.1 months; 5/15 had reductions in serum M protein ranging from 7% to 38% and in urine M protein ranging from 6% to 91%. Mean HSP70 levels increased from day 1 h 0 to day 1 h 4 with further increases on day 11 h 0 and day 11 h 4, consistent with a therapeutic treatment effect. Tanespimycin monotherapy was well tolerated and demonstrated activity across all doses tested.
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PMID:Tanespimycin monotherapy in relapsed multiple myeloma: results of a phase 1 dose-escalation study. 2061 37

A novel Cryptosporidium genotype was identified, among travellers with gastro-intestinal symptoms returning to Great Britain from the Indian subcontinent, for which we propose the name Cryptosporidium viatorum n. sp. The epidemiology of these cases was distinctly different from those with Cryptosporidium parvum and Cryptosporidium hominis. Of the 10 cases identified involving C. viatorum, most were in the first quarter of the year. One occurred in 2007, one in 2008, three in 2010 and five to end March 2011. The median age was 19 years but most were in the 20-29 years age group and seven were male. The symptoms included diarrhoea, abdominal pain, nausea, vomiting and fever. Compared with cases due to C. hominis and C. parvum, vomiting was reported less often, although the duration of gastro-intestinal symptoms was longer. The cases of C. viatorum were all travellers to the Indian subcontinent, whereas cases of C. hominis and C. parvum were more likely to have travelled elsewhere. Cryptosporidium viatorum isolates had indistinguishable sequences at each of the 70 kDa heat shock protein (HSP70), actin and ssrRNA loci which did not match any published previously and, although phylogenetically most similar to Cryptosporidium fayeri, they were distinct (<98% similarity) at the ssrRNA, HSP70 and actin genes. Morphologically, oocysts were typical of predominantly human-infecting species. Cryptosporidium viatorum n. sp. is proposed and work is warranted to investigate further the public health significance and occurrence elsewhere of this emerging parasite.
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PMID:Cryptosporidium viatorum n. sp. (Apicomplexa: Cryptosporidiidae) among travellers returning to Great Britain from the Indian subcontinent, 2007-2011. 2263 52