Δευτέρα 18 Ιουλίου 2016

Biochemical composition of malignant ascites determines high aggressiveness of undifferentiated ovarian tumors

Abstract

Although undifferentiated tumors are the most lethal among all ovarian cancer histotypes, the exact reasons for this situation are unclear. This report was aimed at investigating whether the high aggressiveness of undifferentiated ovarian cancer may be associated with a biochemical composition of malignant ascites accumulating in the peritoneal cavity. We analyzed ascites from patients with undifferentiated, high-grade serous, endometrioid and clear-cell ovarian cancers, and from non-cancerous patients with respect to a group of soluble agents involved in cancer cell progression. Moreover, the effect of these fluids on proliferation and migration of ovarian cancer cells (A2780, OVCAR-3 and SKOV-3) was evaluated. The study showed that the level of all tested proteins in malignant ascites was higher than in the benign fluids. Concentration of 9/11 agents (CCL2, CXCL1, CXCL5, CXCL8, CXCL12, HGF, PAI-1, TGF-β1 and VEGF) was the greatest in the fluids from undifferentiated cancer, while the level of remaining 2 (IL-6 and uPA) was the highest in ascites from serous carcinoma. Proliferation of cancer cells was the most effective when they were subjected to ascites from patients with undifferentiated and serous cancer, whereas the migration was the highest in the case of undifferentiated tumors. Our findings indicate that the aggressiveness of undifferentiated ovarian tumors may be associated with the composition of malignant ascites, in particular the concentration of specific proinflammatory, cancer-promoting agents.



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Randomized, Double-Blind, Placebo Controlled Study of Methylphenidate for the Treatment of Depression in SSRI-Treated Cancer Patients Receiving Palliative Care

Abstract

Objective

To determine the effectiveness of methylphenidate for depression treatment in advanced cancer patients.

Methods

An 18-day randomized, double-blind, placebo-controlled clinical trial of methylphenidate for treatment of depression in selective serotonin reuptake inhibitor (SSRI)-treated patients with advanced cancer in hospice or receiving palliative care. The primary outcome was depression remission, defined as a ≥50% reduction in score on the Montgomery-Asberg Depression Rating Scale.

Results

Among 47 enrolled participants, 35 were randomized. At study day 18, 85% of the methylphenidate and 60% of the placebo group were in depression remission (p = 0.22). Mean time to depression remission was 10.3 days [standard error (SE) 1.8] in the methylphenidate and 8.1 (SE 1.3) in the placebo group (p = 0.48). The mean baseline score for the Hospital Anxiety and Depression Scale (HADS) was 10.4 in each group and decreased by 3.6 (SE 1.1) in the methylphenidate and 2.3 (SE 1.2) in the placebo group (p = 0.51) by day 18. Once in remission, 1 methylphenidate and 5 placebo participants relapsed to depression (p = 0.18). There was no difference in mortality between the groups during the trial. Trial results were limited by small sample size attributed to difficulties in recruiting terminally ill patients.

Conclusions

This trial failed to demonstrate that methylphenidate treatment in SSRI-treated patients had a significant effect on depression remission in advanced cancer patients. This study underscores the difficulties in conducting trials for symptom management in patients with shortened life expectancy.



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Prostate-specific antigen testing for prostate cancer: Depleting a limited pool of susceptible individuals?

Abstract

After the introduction of the prostate specific antigen (PSA) test in the 1980s, a sharp increase in the incidence rate of prostate cancer was seen in the United States. The age-specific incidence patterns exhibited remarkable shifts to younger ages, and declining rates were observed at old ages. Similar trends were seen in Norway. We investigate whether these features could, in combination with PSA testing, be explained by a varying degree of susceptibility to prostate cancer in the populations. We analyzed incidence data from the United States' Surveillance, Epidemiology, and End Results program for 1973–2010, comprising 511,027 prostate cancers in men ≥40 years old, and Norwegian national incidence data for 1953–2011, comprising 113,837 prostate cancers in men ≥50 years old. We developed a frailty model where only a proportion of the population could develop prostate cancer, and where the increased risk of diagnosis due to the massive use of PSA testing was modelled by encompassing this heterogeneity in risk. The frailty model fits the observed data well, and captures the changing age-specific incidence patterns across birth cohorts. The susceptible proportion of men is \(39.9\,\%\,\left( {95\,\%\,{\text{CI}}\, 38.2, 41.6\,\% } \right)\) in the United States and \(30.4\,\%\, \left( {95\,\%\, {\text{CI}} \,28.9, 32.0\,\% } \right)\) in Norway. Cumulative incidence rates at old age are unchanged across birth cohort exposed to PSA testing at younger and younger ages. The peaking cohort-specific age-incidence curves of prostate cancer may be explained by the underlying heterogeneity in prostate cancer risk. The introduction of the PSA test has led to a larger number of diagnosed men. However, no more cases are being diagnosed in total in birth cohorts exposed to the PSA era at younger and younger ages, even though they are diagnosed at younger ages. Together with the earlier peak in the age-incidence curves for younger cohorts, and the strong familial association of the cancer, this constitutes convincing evidence that the PSA test has led to a higher proportion, and an earlier timing, of diagnoses in a limited pool of susceptible individuals.



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Cerebral malperfusion in acute aortic dissection

Abstract

Cerebral malperfusion in association with acute type A aortic dissection is uncommon but can have a considerable effect on the outcome of treatment. Successful treatment requires the individual and effective removal of each of the factors associated with malperfusion. In addition to the conventional surgical procedures, endovascular treatment has become an option for restoring perfusion. However, artificial perfusion and/or surgical procedures can lead to new malperfusion, which is not necessarily apparent to surgeons and which is difficult to predict. Thus, a number of modalities need to be applied to monitoring the current status of perfusion to enable timely treatment. Since each of the diagnostic modalities has its merits and demerits, one should use them effectively while being mindful of the pitfalls. In addition, a delay in the diagnosis in the pre-hospital stage is an important determinant of the surgical outcomes of aortic dissection. Portable echocardiography, which has been recently developed, may be useful for improving this situation. However, an early diagnosis largely depends on the physician's awareness and basic echocardiography skills. Surgeons should make general physicians aware of this message.



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Role of fibronectin in the process of human intestinal cell disruption during E. histolytica infection

Abstract

Entamoeba histolytica is a protozoan that causes amoebiasis in humans which in extreme cases can result in death. One of the virulence factors of E. histolytica is cysteine proteinase which is involved with disruption, inflammation, and apoptosis of the intestinal cell layers. This disruption facilitates the amoeba's penetration into the vascular system and hence to metastasize into other organs. Cysteine proteinase blocks activity of several human proteins in the extracellular matrix, such as mucin-2, collagen, fibronectin, and laminin. Inhibition of several protein activities are predicted to lead the disruption of intestinal mucus, but the detailed mechanism is still unclear. We examined the mechanism using topology networks and functional analysis and the result showed links to 765 proteins, of which fibronectin was predominant in the network. Fibronectin interacts with ubiquitin conjugate, insulin-like factor binding protein-3, and integrin alpha chain-2 which play pivotal roles in maintaining cell cycle, survival, and apoptosis. Therefore, inhibition of the protein results in intestinal cells losing the ability to maintain homeostasis mechanism by which the disruption of intestinal cell occurs.



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Acute renal failure by use of dipyrone in Cavia porcellus

Abstract

Renal failure is a condition that occurs when one or more functions of the kidneys are changed and in guinea pig (Cavia porcellus) its occurrence is uncommon but always lethal. This paper reports the occurrence of acute renal failure in a patient mistakenly treated with dipyrone for 5 days in a veterinary hospital of UNOESC/Xanxerê-SC, presenting apathy, anorexia and hematuria diagnosed through laboratory tests. The use of dipyrone generated an eminent intoxication condition and the specific knowledge of therapy and familiarity with exotic animal species is extremely important to avoid cases of iatrogenic intoxication.



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Developing Sustainable Cancer Education Programs: Training Public Health Students to Deliver Cancer 101 in Puerto Rico

Abstract

The use of promotores to educate Hispanic communities about different health topics has been proven successful, albeit with limitations in program sustainability. The goal of this study was to develop a sustainable train-the-trainer model to train graduate public health (PH) students to disseminate cancer education among communities in Puerto Rico (PR). Graduate students (n = 32) from Ponce Health Sciences University's (PHSU) PH program participated in a 2-day Cáncer 101 training, where they learned how to deliver nine cancer modules to the community. Cancer knowledge was assessed before and after the training via 54 items measuring discussed concepts. Participants also assessed the training's effectiveness by completing a training evaluation informed by social cognitive theory (SCT) constructs of self-efficacy, outcome expectations, facilitation, and observational learning. Participants were mainly female (78.1 %), 26.7 ± 3.9 years old, and enrolled in a Masters-level program (81.3 %). Participants reported an average 11.38-point increase in cancer knowledge after attending the training [t(31) = 14.88, p < .001]. Participants also evaluated the training favorably upon completion, reporting satisfactory comments in the open-ended responses and high scores on measured SCT constructs. The Cáncer 101 training program effectively prepared students to deliver cancer education to local communities. Training graduate PH students to educate communities about health issues is an innovative, and potentially sustainable, way to reach underserved populations.



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