Our results strongly suggest that in early breast cancer patients with SN micrometastasis, selective SN lymphadenectomy suffices to control locoregional and distant disease, with no significant effects on survival.
Cholesterol mediates its proliferative and metastatic effects via the metabolite 27-hydroxycholesterol (27-HC), at least in breast and endometrial cancer. We determined the serum lipoprotein profile, intratumoral cholesterol and 27-HC levels in a cohort of patients with well-differentiated papillary thyroid carcinoma (PTC; low/intermediate and high risk), advanced thyroid cancers (poorly differentiated, PDTC and anaplastic thyroid carcinoma, ATC) and benign thyroid tumors, as well as the expression of genes involved in cholesterol metabolism. We investigated the gene expression profile, cellular proliferation, and migration in Nthy-ori 3.1 and CAL-62 cell lines loaded with human low-density lipoprotein (LDL). Patients with more aggressive tumors (high-risk PTC and PDTC/ATC) showed a decrease in blood LDL cholesterol and apolipoprotein B. These changes were associated with an increase in the expression of the thyroid’s LDL receptor, whereas 3-hydroxy-3-methylglutaryl-CoA reductase and 25-hydroxycholesterol 7-alpha-hydroxylase were downregulated, with an intratumoral increase of the 27-HC metabolite. Furthermore, LDL promoted proliferation in both the Nthy-ori 3.1 and CAL-62 thyroid cellular models, but only in ATC cells was its cellular migration increased significantly. We conclude that cholesterol and intratumoral accumulation of 27-HC promote the aggressive behavior process of PTC. Targeting cholesterol metabolism could be a new therapeutic strategy in thyroid tumors with poor prognosis.
The objective demonstration of improved postoperative recovery suggests that the surgical injury response induced by the laparoscopic approach is less intensive than that after open surgery. Twenty-five patients diagnosed as having noncomplicated gallstones were studied prospectively. They were operated by laparoscopy (group I, n = 12) or open surgery (group II, n = 13). Analgesia requirements (p < 0.026) and postoperative stay (p < 0.001) were significantly less in group 1. Cholecystectomy performed by either technical options induced a significant increase over basal values of glucose, lactate, white blood cell count, prolactin, ACTH, cortisol, interleukin 6, C-reactive protein, and PCO2. Both surgical procedures induced a significant reduction of total proteins, albumin, prealbumin, free fatty acids hemoglobin, hematocrit, and pH. There were no differences between the levels of growth hormone, insulin, glucagon, or PO2 during any of the periods studied. Comparison of the results of the two cholecystectomy techniques showed that laparoscopic cholecystectomy induced a significantly less intensive acute-phase response (area under the curve) of interleukin 6 (17 +/- 17 versus 47 +/- 26 pg/ml x hr x 10(2); p < 0.003), C-reactive protein (16 +/- 12 versus 35 +/-16 mg/dl x hr x 10; p < 0.004), and prealbumin (16 +/- 2.7 versus 13.8 +/- 2.3 mg/dl x hr x 10(2); p < 0.05). The surgical injury response after laparoscopic cholecystectomy is similar to that after open cholecystectomy, but the aeute-phase response component is less intense. This finding may be a consequence of the reduced size of the operative wound with laparoscopic cholecystectomy.
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