CKD-EPI and Cockcroft-Gault Equations Identify Similar Candidates for Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer

Clinical guidelines suggest neoadjuvant cisplatin-based chemotherapy prior to cystectomy in the setting of muscle-invasive bladder cancer (MIBC). A creatinine clearance (CrCl) >60 mL/min is frequently used to characterize cisplatin-eligible patients, and use of the CKD-EPI equation to estimate CrCl has been advocated. From a prospectively maintained institutional database, patients with MIBC who received cystectomy were identified and clinicopathologic information was ascertained. CrCl prior to surgery was computed using three equations: (1) Cockcroft-Gault (CG), (2) CKD-EPI, and (3) MDRD. The primary objective was to determine if the CG and CKD-EPI equations identified a different proportion of patients who were cisplatin-eligible, based on an estimated CrCl of >60 mL/min. Cisplatin-eligibility was also assessed in subsets based on age, CCI score and race. Actuarial rates of neoadjuvant cisplatin-based chemotherapy use were also reported. Of 126 patients, 70% and 71% of patients were found to be cisplatin-eligible by the CKD-EPI and CG equations, respectively (P = 0.9). The MDRD did not result in significantly different characterization of cisplatin-eligibility as compared to the CKD-EPI and CG equations. In the subset of patients age >80, the CKD-EPI equation identified a much smaller proportion of cisplatin-eligible patients (25%) as compared to the CG equation (50%) or the MDRD equation (63%). Only 34 patients (27%) received neoadjuvant cisplatin-based chemotherapy. Of the 92 patients who did not receive neoadjuvant chemotherapy, 64% had a CrCl >60 mL/min by CG. In contrast to previous reports, the CKD-EPI equation does not appear to characterize a broader span of patients as cisplatin-eligible. Older patients (age >80) may less frequently be characterized as cisplatin-eligible by CKD-EPI. The discordance between actual rates of neoadjuvant chemotherapy use and rates of cisplatin eligibility suggest that other factors (e.g., patient and physician preference) may guide clinical decision-making.     

Adult–Adult Play in Primates: Comparative Analyses of its Origin, Distribution and Evolution

Comparative analyses were conducted on a data set derived from the literature so as to test several hypotheses which were developed to explain the distribution of adult–adult play fighting within the order primates. Ratings for play occurring in sexual and non‐sexual contexts were developed. Three hypotheses were evaluated: (i) that play occurring in non‐sexual social contexts is a byproduct of its use in sex; (ii) that the occurrence of play is related to its use for social assessment and manipulation, and so is more likely to be present in species with reduced familiarity between individuals; and (iii) that phylogenetic affiliation influences the likelihood that species within clades engage in play. We used independent contrasts to test the first two hypotheses, and both were significant, with the presence of play in sexual contexts accounting for 14–16% of the variance of play in non‐sexual contexts, and reduced social familiarity accounting for 30–40% of the variance in the occurrence of play in non‐sexual contexts. To test the third hypothesis, we mapped the occurrence of both types of play onto known phylogenies. The overlap was not congruent, indicating that phylogenetic relationships did not account for the distribution of play. Given that play in both sexual and non‐sexual contexts was more likely to occur in species with a social organization involving reduced frequency of contact between the sexes and other social group members, we suggest that the likely adaptive value of play fighting is as a tool for social assessment and manipulation. The possible factors that mitigate the use of play fighting for these purposes, such as the availability of other forms of communication that could serve similar functions, are discussed.     

On Biological Functions Mapping to the Heterochromatin of DROSOPHILA MELANOGASTER

We examined the behavior of an autosomal recessive maternal-effect mutation, abnormal-oocyte (abo), that is located in the euchromatin of the left arm of chromosome 2. When homozygous in females, abo results in a marked reduction in the probability that an egg produced by a mutant mother will develop into an adult. However, this probability is increased if the fertilizing sperm delivers to the egg either a normal allele of the maternal-effect gene or a specific type of heterochromatin (called ABO) that is located in small regions of the X and Y chromosome constitutive heterochromatin as well as in some autosomal heterochromatin. These regions, moreover, all react to Hoechst 33258 fluorescent dye identically and specifically. The amelioration of the maternal effect produced by this heterochromatin differs temporally from that caused by the normal allele of the euchromatic gene: the heterochromatin reduces only precellular blastoderm mortality, whereas the normal allele of the euchromatic gene reduces only postblastoderm mortality. Thus, although the genome of the preblastoderm Drosophila embryo is apparently mostly silent, the ABO-containing heterochromatin functions at this early time. Finally, preliminary data indicate that abo is but one member of a cluster of linked genes, each of which interacts with its own normal allele and with a different, locus-specific, heterochromatic factor. From these observations, it appears that Drosophila heterochromatin contains developmentally important genetic elements, and that a functional concomitant of heterochromatic location is gene action at a developmental stage during which the activity of the euchromatic genome is as yet undetectable. Some general implications of these inferences are considered.     

In vitro propagation ofMedicago andLotus species by node culture

Summary Nodes ofMedicago sativa, Lotus corniculatus, Lotus tenuis, andLotus pedunculatus were cultured on MS basal media with different growth regulators. InM. sativa each node produced one shoot and the apical dominance was unaffected by high levels of cytokinins, and subsequent cycles of culture. Shoot development was stimulated by the presence ofN ⁶-isopentenyl-adenine in the culture medium and was dependent on the genotype of the explant. Shoot development was not affected by the original position of the node on the plant nor by the plant age. Shoots rooted in MS medium gelled with starch and containing 2 mg·liter⁻¹ indol-3-acetic acid. In the threeLotus species, node culture was a more effective technique than inM. sativa. The number of shoots per node increased with the time of culture and with the presence of 0.05 mg·liter⁻¹ of 6-benzylaminopurine. The highest number of shoots derived from one node was achieved inL. pedunculatus and inL. tenuis by culturing single nodes, whereas inL. corniculatus stem segments had to be totally covered by the medium for success. Rooting was easily achieved in MS medium with or without auxins.     

Effect of ovarian cancer ascites on SKOV-3 cells proteome: new proteins associated with aggressive phenotype in epithelial ovarian cancer

Background

Epithelial ovarian cancer is the second most lethal gynecological cancer worldwide. Ascites can be found in all clinical stages, however in advanced disease stages IIIC and IV it is more frequent and could be massive, associated with worse prognosis. Due to the above, it was our interest to understanding how the ascites of ovarian cancer patients induces the mechanisms by which the cells present in it acquire a more aggressive phenotype and to know new proteins associated to this process.

Methods

A proteomic analysis of SKOV-3 cells treated with five different EOC ascites was performed by two-dimensional electrophoresis coupled to MALDI-TOF. The level of expression of the proteins of interest was validated by RT-PCR because several of these proteins have only been reported at the messenger level.

Results

Among the proteins identified that increased their expression in ascites-treated SKOV-3 cells, were Ran GTPase, ZNF268, and Synaptotagmin like-3. On the other hand, proteins that were negatively regulated by ascites were HLA-I, HSPB1, ARF1, Synaptotagmin 1, and hnRNPH1, among others. Furthermore, an interactome for every one of these proteins was done in order to identify biological processes, molecular actions, and cellular components in which they may participate.

Conclusions

Identified proteins participate in cellular processes highly relevant to the aggressive phenotype such as nuclear transport, regulation of gene expression, vesicular trafficking, evasion of the immune response, invasion, metastasis, and in resistance to chemotherapy. These proteins may represent a source of information which has the potential to be evaluated for the design of therapies directed against these malignant cells that reside on ovarian cancer ascites.

     

Adaptive changes of telocytes in the urinary bladder of patients affected by neurogenic detrusor overactivity

Urinary bladder activity involves central and autonomic nervous systems and bladder wall. Studies on the pathogenesis of voiding disorders such as the neurogenic detrusor overactivity (NDO) due to suprasacral spinal cord lesions have emphasized the importance of an abnormal handling of the afferent signals from urothelium and lamina propria (LP). In the LP (and detrusor), three types of telocytes (TC) are present and form a 3D‐network. TC are stromal cells able to form the scaffold that contains and organizes the connective components, to serve as guide for tissue (re)‐modelling, to produce trophic and/or regulatory molecules, to share privileged contacts with the immune cells. Specimens of full thickness bladder wall from NDO patients were collected with the aim to investigate possible changes of the three TC types using histology, immunohistochemistry and transmission electron microscopy. The results show that NDO causes several morphological TC changes without cell loss or network interruption. With the exception of those underlying the urothelium, all the TC display signs of activation (increase in Caveolin1 and caveolae, αSMA and thin filaments, Calreticulin and amount of cisternae of the rough endoplasmic reticulum, CD34, euchromatic nuclei and large nucleoli). In all the specimens, a cell infiltrate, mainly consisting in plasma cells located in the vicinity or taking contacts with the TC, is present. In conclusion, our findings show that NDO causes significant changes of all the TC. Notably, these changes can be interpreted as TC adaptability to the pathological condition likely preserving each of their peculiar functions.     

Spondias mombin supplementation attenuated cardiac remodelling process induced by tobacco smoke

The objective of this study was to investigate the influence of Spondias mombin (SM) supplementation on the cardiac remodelling process induced by exposure to tobacco smoke (ETS) in rats. Male Wistar rats were divided into 4 groups: group C (control, n = 20) comprised animals not exposed to cigarette smoke and received standard chow; group ETS (n = 20) comprised animals exposed to cigarette smoke and received standard chow; group ETS100 (n = 20) received standard chow supplemented with 100 mg/kg body weight/d of SM; and group ETS250 (n = 20) received standard chow supplemented with 250 mg/kg body weight/d of SM. The observation period was 2 months. The ETS animals had higher values of left cardiac chamber diameters and of left ventricular mass index. SM supplementation attenuated these changes. In addition, the myocyte cross‐sectional area (CSA) was lower in group C compared with the ETS groups; however, the ETS250 group had lower values of CSA compared with the ETS group. The ETS group also showed higher cardiac levels of lipid hydroperoxide (LH) compared with group C; and, groups ETS100 and ETS250 had lower concentrations of LH compared with the ETS group. Regarding energy metabolism, SM supplementation decreased glycolysis and increased the β‐oxidation and the oxidative phosphorylation. There were no differences in the expression of Nrf‐2, SIRT‐1, NF‐κB, interferon‐gamma and interleukin 10. In conclusion, our results suggest that ETS induced the cardiac remodelling process. In addition, SM supplementation attenuated this process, along with oxidative stress reduction and energy metabolism modulation.