Evaluation of metastatic and angiogenic potentials of human colon carcinoma cells in chick embryo model systems

Increased metastatic and angiogenic potentials of aggressive human colon carcinoma cells were verified in independent chick embryo models by comparing in vivo highly metastatic SW620 colon carcinoma cell line with its isogenic, non-metastatic SW480 cell variant. In the experimental metastasis model, both cell types rapidly arrested in the chorioallantoic membrane (CAM) vasculature as demonstrated by quantitative PCR and immunohistochemistry. Live cell imaging also indicated that both SW620 and SW480 cells efficiently extravasated from the CAM capillary system. However, only few SW480 cells were present in the CAM tissue after 24–48 h. In contrast, the numbers of SW620 cells increased exponentially, indicating proliferative and survival advantages of metastatic colon carcinoma cells in vivo. Multicellular SW620 foci were identified in close proximity to CAM blood vessels. A positive correlation between increased metastatic ability and VEGF-expression of colon carcinoma SW620 cells was demonstrated by the substantial inhibitory effects of anti-VEGF treatment on the levels of metastatic colonization and density of blood vessels adjacent to tumor cell foci. Furthermore, the chick embryo angiogenesis model confirmed high levels of VEGF-dependent angiogenesis induced by SW620 cells, but not SW480 cells. Thus, chick embryo experimental metastasis and CAM angiogenesis models appear to coordinately reflect critical features of advanced colon carcinomas, i.e., the acquisition of enhanced survival and increased angiogenic potentials, both constituting critical determinants of colon cancer progression. The use of rapid and quantitative chick embryo models might provide alternative approaches to conventional mammalian model systems for screening anti-cancer agents.     

Subjective visual vertical and subjective visual horizontal measures in patients with chronic dizziness

OBJECTIVES: We aimed to find the frequency of otolith organ pathologies in the clinical picture of common dizziness etiologies in the chronic stage. METHOD: Subjective visual vertical and subjective visual horizontal measures were assessed in patients who had persistent or recurrent dizziness at least 2 months after the acute period. Every patient was tested in three head positions: neutral, right, or left deviation in the roll plane. Test results were compared with those of the control group. RESULTS: Seventy-three patients and 18 controls were examined. Fifty-eight of the patients had peripheral vestibular disease; 15 of them had central vestibular disease. Left subjective visual horizontal (SVH) and right SVH measures of the peripheral group were significantly different from those of the control group (p < .01). There was no difference in any test between the peripheral and central groups. When we put a cut off point for abnormality (0, 1) according to mean +/- 2 SD of the control group, the peripheral and central groups had very high significant differences from the control group. Approximately 25 to 50% of our patients had pathologic subjective visual vertical or SVH measures according to test type. CONCLUSION: These results showed that the otolith system must be evaluated in the chronic period of dizziness, especially in patients who frequently visit their physician, and modifications in treatment programs must be conducted.     

A questionnaire survey among Turkish physicians about sleep disorders

We aimed to assess the knowledge of Turkish physicians about sleep disorders and the attitude of the physicians towards sleep medicine. We prepared a 24-item-questionnaire, 7 of the questions were about the attitudes of the physicians and 17 of them were about the knowledge of the physicians. We applied the questionnaire in all university and educational hospitals in Ankara, which is the capital city and the second largest city of Turkey. Two-hundred-fifteen medical doctors from 5 different specialties accepted to answer the questionnaire, and 168 (78%) of them completed the questionnaire. 47% of the physicians rated themselves as they had little knowledge about sleep disorders, and 45% as they had enough knowledge about sleep disorders, however, the overall score was not high. They answered only 45.3% of the questions correctly. In the light of this survey, we concluded that medical education on sleep disorders should be extended both in length and in content to improve the quality of sleep disorders medicine in Turkey.     

Reversal of cytosine arabinoside (ara-C) resistance by the synergistic combination of 6-thioguanine plus ara-C plus PEG-asparaginase (TGAP) in human leukemia lines lacking or expressing p53 protein

BACKGROUND: Sequence-specific combinations of purine analogs, such as fludarabine or 6-mercaptopurine (6-MP), administered prior to cytosine arabinoside (ara-C) have been shown to abrogate ara-C resistance in human leukemia cells in vitro and in patients with relapsed acute myeloid or lymphoblastic leukemias. The two-drug combination of 6-MP plus ara-C results in greater cytotoxicity than that achieved with either ara-C or 6-MP alone. Further preclinical investigations have shown that the addition of PEG-asparaginase (PEG-ASNase) to the combination of 6-MP plus ara-C (6-MP + ara-C + PEG-ASNase) results in 15.6-fold synergism over that achieved with the two-drug regimen. This is due to increased DNA damage leading to apoptotic cell death. PURPOSE: Since the intravenous preparation of 6-MP is no longer available and since oral 6-thioguanine (6-TG) provides higher levels of intracellular thioguanine nucleotides than an isotoxic dose of oral 6-MP, we investigated the potential drug synergism of 6-TG plus ara-C plus PEG-ASNase (TGAP) in myeloid (HL60/S, HL60/SN3, U937) and lymphoblastic (CEM/0, CEM/ ara-C/B, CEM/ara-C/I, MOLT-4) leukemia cell lines. The CEM clones, MOLT-4 and HL60/SN3 cell lines expressed functional or measurable p53 protein, while the other cell lines did not. METHODS: The MTT and trypan blue dye exclusion assays were used to determine drug cytotoxicity. In addition, cellular apoptosis and cellular p53, p21/waf-1 and bcl-2 protein concentrations were determined by FACS analysis and ELISA assays. RESULTS: Sequential exposure to 6-TG (24 h) plus ara-C (24 h) plus PEG-ASNase (24 h) produced 1.3- to 18.3-fold drug synergism over the two-drug combination of 6-TG plus ara-C. The molecular mechanism of synergism was due to the fact that the three-drug combination was capable of downregulating bcl-2 oncoprotein levels in these cell lines even when p53 was absent. CONCLUSION: These studies strongly demonstrate that the TGAP regimen is highly synergistic in p53-null and p53-expressing leukemia cell lines. We conclude that this combination regimen is collaterally sensitive with ara-C and further evaluation in an investigational phase I trial in relapsed leukemia patients is warranted.     

Effects of valproate on vestibular symptoms and electronystagmographic findings in migraine patients

OBJECTIVES: To investigate the effects of valproic acid on vestibular symptoms and electronystagmography (ENG) findings in patients with migraine-related vestibulopathy. METHODS: Thirty-seven patients with migraine (13 with vertigo, 13 with dizziness, and 11 without vestibular symptoms) were included in the study. Slow-released valproic acid (500 mg/d) was given for 3 months. Frequency of headache and vestibular symptoms in the first, second, and third months of the therapy were recorded and compared with the pretreatment values. The ENG findings were also evaluated before and 2 months after the therapy. RESULTS: We determined that prophylactic low-dose valproic acid decreased the frequency of headache and vestibular symptoms, although it does not cause any statistically meaningful change in ENG findings. CONCLUSIONS: Valproate can be used satisfactorily for patients with migraine who have vestibular complaints. Ineffectiveness of valproic acid on ENG findings can be clarified by the permanent effect of migraine on the vestibular system.     

Adaptation of functional outcomes of sleep questionnaire (FOSQ) to Turkish population

Turkish version of functional outcomes of sleep questionnaire (FOSQ.tr) was examined for its psychometric properties in patients with obstructive sleep apnoea hypopnoea syndrome (OSAHS). The FOSQ was translated into Turkish using a forward-backward translation. For the psychometric evaluation, 73 consecutive patients were selected along with 73 control subjects. Internal consistency, test-retest reliability, concurrent and discriminant validity were investigated. Values of Cronbach's alpha for the total FOSQ.tr (alpha= 0.92) and its sub-scales (alpha= 0.76-0.80) suggest that the questionnaire was consistent internally. Test-retest reliability of the FOSQ.tr was significant for the total score (r= 0.7) and the sub-scales apart from social outcome (r= 0.5 to 0.8, all p< 0.01). FOSQ.tr correlated moderately with Epworth sleepiness scale (ESS), with coefficients ranging from r= -0.5 to -0.62, (all p< 0.05) for the sub-scales, and r= -0.64 (p< 0.01) for total score. Discriminant analysis showed that FOSQ.tr could significantly distinguish the patients from normal subjects (p< 0.03). The psychometric properties of the FOSQ.tr suggest that it is a valid and reliable instrument for the assessment of the impact of disorders of excessive sleepiness on daily behaviour.     

Striatal Dopamine Mediates the Interface between Motivational and Cognitive Control in Humans: Evidence from Genetic Imaging

Dopamine has been hypothesized to provide the basis for the interaction between motivational and cognitive control. However, there is no evidence for this hypothesis in humans. We fill this gap by using fMRI, a novel behavioral paradigm and a common polymorphism in the DAT1 gene (SLC6A3). Carriers of the 9-repeat (9R) allele of a 40 base pair repeat polymorphism in the 3′ untranslated region of DAT1, associated with high striatal dopamine, showed greater activity in the ventromedial striatum during reward anticipation than homozygotes for the 10-repeat allele, replicating previous genetic imaging studies. The crucial novel finding is that 9R carriers also exhibited a greater influence of anticipated reward on switch costs, as well as greater activity in the dorsomedial striatum during task switching in anticipation of high reward relative to low reward. These data establish a crucial role for human striatal dopamine in the modulation of cognitive flexibility by reward anticipation, thus, elucidating the neurochemical mechanism of the interaction between motivation and cognitive control.     

Serum S100B protein: a useful marker in obstructive sleep apnea syndrome

Background and purposeWe aimed to underline the importance of serum S100B protein as a useful biochemical marker in patients with obstructive sleep apnea syndrome (OSAS).Material and methodsForty-three newly diagnosed patients with OSAS (median apnea-hypopnea index [AHI, events/hour]: 37.5 [range 11.3–137]) and 25 subjects with AHI < 5 (median AHI: 4.4 [range 0.7–4.8]) were included in the study. Serum S100B protein level was tested in serum samples taken after polysomnography in both groups and the difference between OSAS patients and the control group regarding that level was assessed. In addition, the association of S100B protein serum level with age, body mass index, AHI, mean O₂ saturation percentage during sleep, minimum O₂ saturation value (%) at the end of the apneas, and the time spent at an O₂ saturation less than 90% were analyzed in the OSAS patient group.ResultsMedian serum S100B protein level was 133.7 pg/mL (range 20.97–230.70 pg/mL) in patients with OSAS and 16.1 pg/mL (range 10.1–22.9 pg/mL) in the control group (p < 0.005). Serum S100B protein level did not correlate with any studied variable (p > 0.05 for each correlation coefficient).ConclusionsSerum S100B protein level is increased in patients with OSAS and may be a useful biochemical marker in those patients.