Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular radiosensitivity, assessed by loss of clonogenicity, has been shown to correlate with the number of radiation-induced chromosomal aberrations. Also an increased radiosensitivity by hyperthermia has been shown to correlate with an increase in chromosomal aberrations. Therefore, determination of the number of chromosomal aberrations might be used as an assay to predict the radiosensitivity of tumors pre-treated with hyperthermia at clinically relevant temperatures. The use of premature chromosome condensation combined with fluorescent in situ hybridisation (PCC-FISH) has been shown to be clinically applicable. Therefore, the use of chromosomal aberrations as determined with PCC-FISH for the prediction of hyperthermia-induced radio-sensitization in human tumor cells was investigated. Confluent cultures of SW-1573 (human lung carcinoma) and RKO (human colorectal carcinoma) cells were treated with 1 h 41 degrees C or 43 degrees C hyperthermia prior to gamma-irradiation. Clonogenic cell survival and induction of chromosomal aberrations (unrejoined chromosomal fragments and translocations), by PCC-FISH, were studied at 24 h after treatment. Pre-treatment with hyperthermia at 41 degrees C for 1 h enhanced the radiosensitivity of RKO cells but not of SW-1573 cells. Increasing the temperature to 43 degrees C for 1 h enhanced the radiosensitivity of SW-1573 cells. When radio-sensitization was observed, a significant increase in the number of unrejoined chromosomal fragments was found but the frequency of translocations was not increased. Hyperthermia-induced radio-sensitization is correlated with an increase in unrejoined chromosomal fragments. This suggests that determination of the number of chromosomal fragments after hyperthermia and radiation treatment might be used for the prediction of combined treatment response in cancer patients.
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PMID:Chromosome fragments have the potential to predict hyperthermia-induced radio-sensitization in two different human tumor cell lines. 1841 79

The thioredoxin (Trx) system, comprising Trx, the selenoprotein thioredoxin reductase (TrxR), and NADPH, functions as an antioxidant system. Trx has various biological activities including growth control and anti-apoptotic properties, and the Trx system offers a target for the development of drugs to treat and/or prevent cancer. We evaluated the role of TrxR inhibition in the release of arachidonic acid (AA), cell toxicity, and intracellular signaling pathways in L929 mouse fibrosarcoma cells. Treatment with 1-chloro-2,4-dinitrobenzene (DNCB, an inhibitor of TrxR) under conditions involving limited inhibition of TrxR activity in cells, released AA before causing cytotoxicity. Treatment with an inhibitor of p38 kinase, a downstream enzyme of the apoptosis signal-regulating kinase 1 pathway, and pyrrophenone (an inhibitor of alpha-type cytosolic phospholipase A(2), cPLA(2)alpha) partially but significantly decreased the DNCB-induced release of AA and cell death. The responses were much weaker in cPLA(2)alpha knockdown L929 cells. Exogenously added AA showed cytotoxicity. DNCB increased intracellular reactive oxygen species (ROS) levels, and butylated hydroxyanisole (an antioxidant) reduced DNCB-induced ROS formation and cell toxicity but not the phosphorylation of p38 kinase and release of AA. Auranofin, another inhibitor of TrxR having a different formula, released AA resulting in toxicity in L929 cells. DNCB caused the release of AA and cytotoxicity in A549 human lung carcinoma cells, and caused p38 kinase-dependent toxicity in PC12 rat pheochromocytoma cells. Our data suggest that a dysfunctional Trx system triggers multiple signaling pathways, and that the AA released by cPLA(2)alpha-dependent and -independent pathways is important to cytotoxicity. J. Cell. Physiol. 219: 606-616, 2009. (c) 2009 Wiley-Liss, Inc.
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PMID:Cytotoxicity induced by inhibition of thioredoxin reductases via multiple signaling pathways: role of cytosolic phospholipase A(2)alpha-dependent and -independent release of arachidonic acid. 1917 71

We report a rare synchronous presentation of primary lung cancer and adrenal pheochromocytoma. A 59-year-old woman was diagnosed with right upper lobe non-small cell lung carcinoma measuring 2.8 cm and a right adrenal gland mass measuring 3.5 cm, which displayed increased metabolic activity on (18)F-fluorodeoxyglucose positron emission tomography-computed tomography. The adrenal lesion was revealed to be asymptomatic. The patient underwent right adrenalectomy and histological examination revealed a pheochromocytoma. Ten days later, right upper lobectomy was performed for lung cancer. This case indicates that incidental adrenal lesions found in cases of resectable primary lung cancer should be investigated.
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PMID:A case of synchronous presentation of primary non-small cell lung carcinoma and pheochromocytoma. 2367 60

Background and Importance. Treatment of spinal column metastatic tumors is challenging, especially in the setting of progressive disease despite previous radiation and chemotherapy. Intra-arterial chemotherapy is an uncommonly used but established treatment for head and neck cancers, retinoblastoma, and glioblastoma. The author reports extension of the IAC concept to vertebral metastatic tumors. Clinical Presentation. Two patients with intractable spinal pain secondary to spinal metastatic involvement at T11-L1 segments were treated with intra-arterial injections of cisplatin, with simultaneous sodium thiosulfate chelation. The first patient, a 60-year old female with metastatic lung carcinoma underwent, three cycles of therapy over a 9-week period; the treated regions demonstrated bone remodeling and sclerosis. The second case was a 40-year old male with malignant pheochromocytoma, who underwent a single treatment and succumbed 5 weeks later from progressive widespread disease. Both patients reported significant pain relief and neither of them exhibited a decline in neurologic function. Conclusion. The intra-arterial delivery of cisplatin appeared to be well tolerated in the two cases. In the case with the longest survival, the treated vertebral segments became more sclerotic, consistent with biomechanical stabilization. Endovascular treatment of spinal metastases may hold promise, especially as newer categories of biologic agents become more widely available.
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PMID:Endovascular treatment of vertebral column metastases using intra-arterial Cisplatin: pilot experience. 2496 3


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