Circulating tumor cells in patients with breast cancer dormancy.

PURPOSE: The purpose of this study was to test the hypothesis that circulating tumor cells (CTCs) are present in patients many years after mastectomy without evidence of disease and that these CTCs are shed from persisting tumor in patients with breast cancer dormancy. EXPERIMENTAL DESIGN: We searched for CTCs in 36 dormancy candidate patients and 26 age-matched controls using stringent criteria for cytomorphology, immunophenotype, and aneusomy. RESULTS: Thirteen of 36 dormancy candidates, 7 to 22 years after mastectomy and without evidence of clinical disease, had CTCs, usually on more than one occasion. Only 1 of 26 controls had a possible CTC (no aneusomy). The statistical difference of these two distributions was significant (exact P = 0.0043). The CTCs in patients whose primary breast cancer was just removed had a half-life measured in 1 to 2.4 hours. CONCLUSIONS: The CTCs that are dying must be replenished every few hours by replicating tumor cells somewhere in the tissues. Hence, there appears to be a balance between tumor replication and cell death for as long as 22 years in dormancy candidates. We conclude that this is one mechanism underlying tumor dormancy.     

Chemotherapie des Endometriumkarzinoms

Zusammenfassung Das Endometriumkarzinom wird in 75% der Fälle im Stadium I diagnostiziert und hat damit eine günstige Prognose. Die Standardtherapie besteht in einer radikalen Operation, welche in Abhängigkeit der histologischen Ergebnisse mit einer Strahlentherapie kombiniert wird. Dieser Beitrag beschreibt die Hauptindikationsgebiete für eine Chemotherapie beim Endometriumkarzinom stellen die rezidivierende bzw. primär metastasierte Erkrankung dar. Die Wertigkeit einer adjuvanten Chemotherapie für Patientinnen mit primär fortgeschrittenen Stadien oder bei serös-papillären Tumoren ist bisher nicht eindeutig definiert.     

精胺对精子获能和受精的影响

精胺广泛存在于动物组织和体液中,它在生殖过程中的作用还存在着很大的争议,作者综述了这些研究成果,并对其今后的发展动态作了展望．     

Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant.

PURPOSE: Numerous studies of circulating epithelial cells (CECs)have been described in cancer patients, and genetic abnormalities have been well documented. However, with one exception in colorectal cancer, there has been no report of matching the genetic abnormalities in the CECs with the primary tumor. The purpose of this investigation was to determine (a) whether CECs in patients including those with early tumors are aneusomic and (b) whether their aneusomic patterns match those from the primary tumor, indicating common clonality. EXPERIMENTAL DESIGN: Thirty-one cancer patients had CECs identified by immunofluorescence staining using a monoclonal anti-cytokeratin antibody. Their CECs were analyzed by enumerator DNA probes for chromosomes 1, 3, 4, 7, 8, 11, or 17 by dual or tricolor fluorescence in situ hybridization. Touch preparations of the primary tumor tissue were available from 17 of 31 patients and hybridized with the same set of probes used to genotype the CECs. RESULTS: The number of CECs from each patient ranged from 1-92 cells/cytospin. CECs showed abnormal copy numbers for at least one of the probes in 25 of 31 patients. Touch preparations from the primary tumors of 13 patients with aneusomic CECs were available. The pattern of aneusomy matched a clone in the primary tumor in 10 patients. CONCLUSIONS: We conclude that the vast majority of CECs in breast, kidney, prostate, and colon cancer patients are aneusomic and derived from the primary tumor.     

Aktuelles Management beim Ovarialkarzinomrezidiv

best practice onkologie -     

含L-4-氧代赖氨酸寡肽的合成及其抗白念珠菌活性

本文运用“违法传送”概念,根据白念珠菌对寡肽的传送特点,设计并合成了十个含L-4-氧代赖氨酸(以下称I-677)的寡肽,以提高I-677的抗白念珠菌活性。体外抗白念珠菌试验表明:I-677-肽(I-677-X₁,I-677-X₁-X₂和I-677-X₁-X₂-Gly,其中X₁,X₂=Met,Leu,Ile,Ala,β-Ala,Gly)较I-677单体摩尔活性提高了2.1～28倍,其摩尔最低抑菌浓度为8.7×10^-8～9.3×10^-9mol/ml,传送肽和赖氨酸分别逆转I-677-肽抗菌活性的实验结果证实了I-677的“违法传送”途径。     

Melatonin acutely improves the neuroendocrine architecture of sleep in blind individuals

In blind individuals, the absence of light cues results in disturbances of sleep and sleep-related neuroendocrine patterns. The Zeitgeber influence of light on the timing of sleep is assumed to be mediated by melatonin, a hormone of the pineal gland, whose secretion is inhibited by light and enhanced during darkness. Here, we investigated whether a single administration of melatonin improves sleep and associated neuroendocrine patterns in blind individuals. In a double-blind crossover study, 12 totally blind subjects received 5 mg melatonin and placebo orally 1 h before bedtime starting at 2300 h. The dose used enhanced blood melatonin concentrations to clearly supraphysiological levels. Melatonin increased total sleep time and sleep efficiency (P < 0.05, respectively) and reduced time awake (P < 0.05). The increment in total sleep time was primarily due to an increase in stage 2 sleep (P < 0.01) and a slight increase in rapid eye movement sleep (P < 0.06). Most important, melatonin normalized in parallel the temporal pattern of ACTH and cortisol plasma concentration. While after placebo, ACTH and cortisol levels did not differ between early and late sleep, melatonin induced the typical suppression of pituitary-adrenal activity during early sleep and a distinct rise during late sleep (P < 0.01, respectively). Cortisol nadir values were also decreased after melatonin (P < 0.05). We conclude from these data that in totally blind individuals the single administration of a clearly pharmacological dose of melatonin can improve sleep function by synchronizing in time the inhibition of pituitary-adrenal activity with central nervous sleep processes.     

肠道通透性试验及其临床意义

肠道对大分子物质的通透性试验是评估肠道粘膜屏障功能的方法之一.肠粘膜通透性是指某一特定物质在肠粘膜表面通过非易化扩散方式渗透的能力.肠道对大分子物质的通透性增加,意味着肠道结构有变化,肠道内的细菌或毒素有可能通过肠道屏障进入血循环,引起败血症或毒血症.自从20世纪70年代引入非代谢性寡糖类物质作为肠道通透性试验的示踪物以来,检测肠道粘膜屏障功能的肠道通透性试验已广泛应用于临床[1].     

Glucose metabolism rather than insulin is a main determinant of leptin secretion in humans

Circulating plasma insulin and glucose levels are thought to be major regulators of leptin secretion. There is evidence from in vitro and animal experiments that glucose metabolism rather than insulin alone is a main determinant of leptin expression. Here, we tested the hypothesis that in humans also leptin secretion is primarily regulated by glucose uptake and only secondarily by plasma insulin and glucose. In 30 lean and healthy men we induced 4 experimental conditions by using the blood glucose clamp technique. A total of 60 hypoglycemic and euglycemic clamps, lasting 6 h each, were performed. During these clamps insulin was infused at either high (15.0 mU/min x kg) or low (1.5 mU/min x kg) rates, resulting in low-insulin-hypo, high-insulin-hypo, low-insulin-eu, and high-insulin-eu conditions. Serum leptin increased from 0-360 min by 20.5 +/- 4.1% in the low-insulin-hypo, 33.6 +/- 7.6% in the high-insulin-hypo, 39.6 +/- 6.0% in the low-insulin-eu, and 60.4 +/- 7.6% in the high-insulin-eu condition. Multiple regression analysis revealed a significant effect of circulating insulin (low vs. high insulin; P = 0.001) and blood glucose (hypoglycemia vs. euglycemia; P = 0.001) on the rise of serum leptin. However, when the total amount of dextrose infused during the clamp (grams of dextrose per kg BW) was included into the regression model, this variable was significantly related to the changes in serum leptin (P = 0.001), whereas circulating insulin and glucose had no additional effect. These findings in humans support previous in vitro data that leptin secretion is mainly related to glucose metabolism.