Perioperative Evaluation of the Physical Quality of Life of Patients with Non-Small Cell Lung Cancer: A Prospective Study.

Surgery is the most effective treatment for early-stage lung cancer; however, it poses a higher physical burden than other treatment options. Therefore, understanding the perioperative course of patients is important. Using the Short Form Health Survey 36, we prospectively measured the physical quality of life of patients who underwent anatomical pulmonary resection for non-small cell lung cancer at Shonan Kamakura General Hospital, Kanagawa, Japan (n = 87). In the preoperative setting, patients who had lower performance status and lived alone had significantly worse physical quality of life scores on multivariate analysis (regression coefficient (95% confidence interval), -9.37 (-13.43--5.32) and -10.22 (-13.74--7.40), respectively, p < 0.0001 for both). At 6 months postoperatively, patients who stopped smoking within 1 year preoperatively (stopped smoking within 1 year vs. remote or never smokers, 41.0 ± 10.5 vs. 48.6 ± 7.2, p = 0.002), had lower performance status (0 vs. 1-2, 49.3 ± 6.6 vs. 38.6 ± 9.6, p < 0.0001), lived alone (living alone vs. living with somebody, 41.6 ± 9.7 vs. 48.1 ± 7.9, p = 0.021), and had higher comorbid burden (Charlson comorbidity index <3 vs. ≥3, 48.2 ± 6.9 vs. 39.1 ± 14.7, p = 0.003) had significantly worse physical quality of life scores on univariate analysis. More recent smoking (regression coefficient (95% confidence interval), -4.90 (-8.78-1.0), p = 0.014), lower performance status (8.90 (5.10-12.70), p < 0.0001), living alone (5.76 (1.39-10.13), p = 0.01), and higher comorbid burden (-6.94 (-11.78--2.10), p = 0.006) were significant independent predictors of worse postoperative physical quality of life on multivariate analysis. Therefore, patients with these conditions might need additional support to maintain their physical condition after anatomical lung cancer surgery.

Susceptibility to cytosine arabinoside (Ara-C)-induced cytotoxicity in human leukemia cell lines.

Cytosine arabinoside (1-beta-d-arabinofuranosylcytosine; Ara-C) is the most important antimetabolite chemotherapeutic drug used for acute leukemia. We examined the difference in susceptibility to Ara-C-induced cell death among a number of typical human leukemia cell lines, NALM-6, MOLT-4, Jurkat, U937 and HL-60. NALM-6, which had a high expression level of p53, a tumor suppressor gene, was most susceptible to Ara-C. U937 and HL-60, with p53-null human leukemia cell lines were little affected by Ara-C. There was not always a correlation between susceptibility and the uptake of Ara-C. The production of reactive oxygen species (ROS) was increased in all leukemia cells. Pifithrin-alpha, a chemical inhibitor of wild-type p53, ameliorated the cytotoxicity of Ara-C in NALM-6 and MOLT-4, but not Jurkat, U937 or HL-60. Our data suggest that the mechanism of Ara-C-induced cell death is a common one, involving an increase in the production of ROS and p53-dependent cell death.

Effects of naringin on cytosine arabinoside (Ara-C)-induced cytotoxicity and apoptosis in P388 cells.

Naringin (NG), a flavonoid in grapefruit and citrus, has been reported to exhibit antioxidant effects and pharmacological actions. Recently, we have reported that NG suppressed the cytotoxicity and apoptosis induced by H(2)O(2), a typical pro-oxidant, in mouse leukemia P388 cells. Cytosine arabinoside (1-beta-d-arabinofuranosylcytosine; Ara-C) is the most important antimetabolite chemotherapeutic drug used for acute leukemia. It has been suggested that Ara-C-induced cytotoxicity is caused by apoptosis, which is mediated by reactive oxygen species (ROS). In this study, we examined the effect of NG on the cytotoxicity and apoptosis in mouse leukemia P388 cells treated with Ara-C. Ara-C caused cytotoxicity in a concentration and time-dependent manner in the cells. N-Acetyl-L-cysteine (NAC), cystamine (CysA) or a reduced form of glutathione (GSH), typical antioxidants significantly blocked Ara-C-induced cytotoxicity. Similarly, Ara-C-induced cell death was completely prevented by NG. NG strongly reduced ROS production caused by Ara-C in the cells. NG slightly increased the activities of antioxidant enzymes, catalase and glutathione peroxidase. Ara-C caused apoptosis with nuclear morphological change and DNA fragmentation. NG remarkably attenuated the Ara-C-induced apoptosis. NG completely blocked the DNA damage caused by Ara-C treatment at 6 h using the Comet assay. Our data suggest that NG reduces Ara-C-induced oxidative stress through both an inhibition of the generation of ROS production and an increase in antioxidant enzyme activities. Consequently, NG blocked apoptosis caused by Ara-C-induced oxidative stress, resulting in the inhibition of the cytotoxicity of Ara-C.

Effects of naringin on hydrogen peroxide-induced cytotoxicity and apoptosis in P388 cells.

Flavonoids are widely recognized as naturally occurring antioxidants. Naringin (NG) is one of the flavonoid components in citrus fruits such as grapefruit. Hydrogen peroxide (H2O2) causes cytotoxicity through oxidative stress and apoptosis. In this paper, we examined the effects of NG on H2O2-induced cytotoxicity and apoptosis in mouse leukemia P388 cells. Cytotoxicity was determined by mitochondrial activity (MTT assay). Apoptosis and DNA damage were analyzed by measuring chromatin condensation and Comet assay (alkaline single cell gel electrophoresis), respectively. H2O2-induced cytotoxicity was significantly attenuated by NG or the reduced form of glutathione (GSH), a typical intracellular antioxidant. NG suppressed chromatin condensation and DNA damage induced by H2O2. These results indicate that NG from natural products is a useful drug having antioxidant and anti-apoptopic properties.

Diethyldithiocarbamate-induced cytotoxicity and apoptosis in leukemia cell lines.

Diethyldithiocarbamate (DDTC) has been shown to induce cytotoxicity in several different systems. We examined whether the DDTC-induced cytotoxicity was via apoptosis, or in relation to intracellular glutathione (GSH) in various murine and human leukemia cell lines. The cells most sensitive to DDTC-induced cytotoxicity were P388 lymphoid neoplasma cells and NALM-6, a B cell line of acute lymphocytic leukemia (ALL). The next level of susceptible cells included J774.1, having a macrophage function, HL-60 premyelocytic leukemia cells, MOLT-4, an acute lymphoblastic leukemia cell, and Jurkat, a T-cell leukemia. U937 (expressing many monocyte-like characteristics), K562 erythroleukemia and K562/DXR (a multidrug-resistant clone derived from K562) were almost unaffected by DDTC. P388 was also highly susceptible to H(2)O(2), a most useful exogenous reactive oxygen species generator, and was lower in intracellular total GSH content than other leukemia cells. DDTC-induced cytotoxicity was closely related to intracellular GSH, but the level of cellular GSH did not always correlate with H(2)O(2)-induced cytotoxicity in this experiment. K562 had a higher intracellular total GSH content and showed lower susceptibility to DDTC and H(2)O(2), but with the combination of DDTC and DL-buthionine-(S,R)-sulfoximine (BSO), cytotoxicity increased significantly. The ratio of GSH/GSSG in P388 was reduced by DDTC or H(2)O(2). H(2)O(2)-induced cytotoxicity was completely blocked by catalase (CAT), while it was enhanced by superoxide dismutase (SOD). CAT or SOD did not affect DDTC-induced cytotoxicity. N-Acetylcysteine (NAC: 1 mM), a vanguard substance of GSH, and aurintricarboxylic acid (ATA: 100 microM), an endonuclease inhibitor, ameliorated DDTC-induced cytotoxicity and apoptosis. In conclusion, we suggest that DDTC-induced cytotoxicity was via an oxidative shift in the intracellular redox state, and accompanied the activation of endonuclease through apoptosis in leukemia cell lines.