4 months. Further therapies are needed to improve survival in men with hormone-resistant prostate cancer (HRPC), and a variety of potential avenues are under exploration to fill this void. Immunotherapy has become standard treatment in a wide variety of tumors. Such therapy includes www.selleckchem.com/B-Raf.html cytokine administration (eg, interleukin [IL] 2 in metastatic renal cell carcinoma), monoclonal antibody therapy (eg, trastuzumab in breast cancer), and local immune stimulation (eg, Bacillus Calmette-Guéerin [BCG] for carcinoma in situ of the bladder). In prostate cancer, effective

immune strategies have been investigated for 25 years. Recent progress Inhibitors,research,lifescience,medical has been made in a variety of agents. This review outlines some of the recent advances in immunotherapy strategies for prostate malignancy. Tumor Immunology The immune system is divided into 2 components, innate and adaptive. The innate immune system includes neutrophils, macrophages/monocytes, mast cells, and natural killer cells. These cells are not specific to the invader and function by secreting cytokines, presenting antigens, Inhibitors,research,lifescience,medical and mediating cell lysis. Adaptive immunity includes lymphocytes, namely B cells and T cells, each of which responds to a specific antigen. Their

activity is modulated by exposure to that specific antigen. This portion of the immune system can be amplified and develops memory. Activated B cells mature into Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical plasma cells, which are responsible for antibody production. T cells exist in subsets based on cell-surface marker expression. CD8 cells are referred to as cytotoxic T cells, whereas CD4 cells are termed helper T cells. CD4 cells direct the immune response through the secretion of cytokines, the maturation of B-cell/antibody responses, the

stimulation of CD8 T-cell cytotoxic responses, and antigen-presenting cell (APC) activity. In general, antitumor response is controlled by T cells, Inhibitors,research,lifescience,medical an overview of which is provided in Figure 1. Activation of T cells requires 2 signals, 1 signal through the T-cell receptor (TCR) and a second signal. The TCR interacts with major histocompatibility complex (MHC) class 1 and class 2 molecules (also termed human leukocyte antigen [HLA] 1 and 2) expressed on the cell surface. MHC 1 is expressed on all nucleated cells, presents peptide antigens from the cell itself, and interacts with the TCR of CD8 T cells. MHC 2 is expressed exclusively on APCs, before presents peptide antigens taken up from the cellular environment, and interacts with the TCR on CD4 T cells. APCs include monocytes, macrophages, B cells, and dendritic cells. The second signal for T-cell activation often occurs through interaction of coreceptors between the two cells, the major one for the purposes of this review being an interaction between B7-1 on the APC and CD28 on the T cell. Figure 1 Schematic representation of the antitumor response and its modification by immunotherapy.

These separable features are detected in parallel and can often be identified without actually being located (Treisman and Gelade 1980). Neural processing of the feature search task begins with basic visual processing in the occipital lobe and then transfers to a frontoparietal attentional network

(Corbetta and Shulman 2002). Recent research into feature search using sophisticated model-based analysis Inhibitors,research,lifescience,medical has further identified contributions from specific neural regions in parietal and occipital cortical structures, as well as the temporoparietal junction (TPJ) in the response to the relevant saliency of targets (Mavritsaki et al. 2010). Conjunctive visual search (CVS) is a low-capacity serial search process in which the search target is defined by two or more unique features. CVS Inhibitors,research,lifescience,medical requires conscious processing and engagement

of additional higher level neural resources (Kristjansson et al. 2002). The anatomical locations of these additional resources vary to some extent in the literature, with increased activation being found in the superior parietal cortex (Corbetta et al. 1995), a superior region of the frontal cortex associated Inhibitors,research,lifescience,medical with working memory (Leonards et al. 2000), and frontoparietal regions that include the frontal eye fields (O’Shea et al. 2006). More generally, conjunction is associated with a significantly higher slope of the search time versus number of distractors Inhibitors,research,lifescience,medical curve (Wolfe 1998) compared with feature search, and thus may generate greater activation in basic visual processing regions (Nobre et al. 2003). Furthermore, Kahneman and Henik (1981) have shown that selective attention is impacted by the spatial distribution of objects during VS, and that it is not possible to distribute selective attention over a subset of items which have a random spatial distribution. This work was further confirmed by Treisman (1982), and find more indicates that the size and shape of the visual attention “spotlight” are constrained (Eriksen and Hoffman 1972). The enhanced activation properties of

the CVS are also useful in clinical fMRI for presurgical Inhibitors,research,lifescience,medical planning in which already decreased activation and neural function may be present due to necrosis, secondly edema, or tumor mass effect. Although a number of studies have developed and evaluated CVS tasks for fMRI, the majority have used low numbers of distractors (typically less than 10, maximum of 24). The number of distractors is directly related to task difficulty, and it is of interest to evaluate higher numbers of distractors for mimicking complex and challenging work environments. Furthermore, the majority of previous methods have used contrast conditions that represent different implementations of VS tasks or simply lack visual stimuli. An optimal CVS task for human performance evaluation and clinical fMRI involves a contrast condition which mimics the visual stimuli of the CVS, but does not allow searching.

The number of viable and dead cells was counted by trypan blue staining and hemocytometer slides. The treated cells were cultured for 24 h and then stained with neutral red. The cells were fixed with calcium formol for one min and washed with PBS. One

milliliter of 0.05% neutral red (wt/vol) in PBS was added to each well and left at 37°C for 2 h. The viable cells were red after staining. Permeabiliztion of the Cells The harvested fibroblasts were washed three times with cold PBS-. The cells were resuspended Inhibitors,research,lifescience,medical in cold HBSS and aliquoted in 20000 cells per 16.4 µL. The cells were incubated at 37°C for 2 min and subsequently, 4.6µL of streptolysin O (Sigma) at a final concentration of 230 ng/mL was added and incubated at 37°C for 50 min. Twenty µL of the extract containing ATP-regenerating system [ATP, GTP, creatine phosphate, and creatine kinase (Sigma)] and 25 mM of dNTP (Sigma) were added to the cells and they were incubated at 37°C for one h. Warmed culture media (37°C) containing Inhibitors,research,lifescience,medical 2 mM CaCl2 was added to the cells and then transferred to 24-well tissue culture plates until they attached within 2-4 h. Inhibitors,research,lifescience,medical The culture medium was replaced by DMEM containing 15% FCS, 1% Penicillin/Streptomycin, and 1% L glutamine and left in the incubator for 1, 10, and 21 days.27 To assay the effects of TSA and 5-aza-dC

on the expression of the cardiomyocyte markers, some untreated cells were exposed to the cardiomyocyte extract as well. For control, the TSA and 5-aza-dC-treated cells and also the untreated Inhibitors,research,lifescience,medical cells were exposed to the same volume of HBSS instead of the extract. Permeabilization Assay To ensure that the cells were permeabilized effectively, the permeabilization assay was done. The assay was based on the uptake of the FITC-conjugated 70000 Mr Dextran (Sigma) by permeabilized cells. The uptake was detected with florescent microscopy.28 Immunofluorescence Cardiomyocyte markers were detected by anti-α actinin (15 µg/mL), anti-cardiac troponin

Inhibitors,research,lifescience,medical T (2 µg/mL), anti-atrial natriuretic peptide (1:100 dilution), and anti-myosin-heavy-chain (1:100 dilution) antibodies (all from R&D). The secondary FITC-conjugated anti-mouse antibody (Sigma) at 1:100 dilution for anti α actinin, myosin heavy chain, and cardiac troponin T and Ketanserin FITC-conjugated donkey anti-rabbit antibody (Santa Cruz) for atrial natriuretic peptide with the same dilution were used. The samples were washed with PBS and fixed in 4% paraformaldehyde for 20 min. The cells were washed and incubated in PBS- containing 10% goat serum, 1% BSA, and 1% triton X100 for 45 min. The primary and secondary FITC-conjugated antibodies were used for one h (each). The cells were counterstained with DAPI, mounted, and observed by fluorescence microscopy (Zeiss E600). Pluripotency Markers VX-770 mw Detection The 5-aza-dC and TSA-treated cells were cultured in the embryonic stem cell culture medium in the presence or absence of LIF for 3 and 10 days.

42, 43 Between 1985–1999 and 2000–2007, Plasmodium falciparum prevalence rates among children aged 2 to 10 years

in sub-Saharan Africa declined from 37% in 1985–1999 to 17% in 2000–2007.14, HA-1077 manufacturer 33 In Zanzibar, data from routine health services and clinico-parasitological surveys have been used to demonstrate that between 2002 and 2006, malaria-related admissions, blood transfusions, and malaria-attributed mortality declined by 77%, 67% and 75% respectively. A further 10-fold reduction in malaria parasite prevalence was achieved in that country in 2006 after the introduction of long-lasting insecticidal nets. 44 In The Gambia, findings from a retrospective analysis of records on numbers and proportions of malaria in-patients, deaths, blood-slide examinations at five health facilities over periods ranging from 7 years to 9 years has suggested that a “large proportion of the burden of malaria in that country has been alleviated.”45 In Uganda, a study in four districts in 2007 found dramatically lower-than-expected levels of parasitaemia among children with fever presenting to health facilities. Parasitaemia

ranged from 13.9% in patients ≥5 years in medium-to-high transmission areas to 50.5% for children <5 years in very high transmission areas. These districts www.selleckchem.com/btk.html had historically been known to record some of the highest entomological inoculation rates (between 564 and 1,564 infective bytes per person per year) in the world. 46 Table 1 provides examples Endonuclease of recent reports of reduction in the burden of malaria in sub-Saharan Africa and the factors

reported to be underlying the reductions. Table 1 Examples of studies that report reduction in the burden of malaria in sub-Saharan Africa. Ghana is classified as being high malaria-transmission. Evidence is however emerging about substantial reduction in malaria transmission in the country. The findings of the recent Multiple Indicator Cluster Survey (MICS) confirm dramatically low levels of malaria parasitaemia among under-five children across the country. The proportions of under-five children found to have parasitaemia ranged from as low as 4% in Accra to 51% in the Upper-West region (Figure 1).47 These findings contrast with much higher prevalence recorded in similar surveys in the past. 12, 48 Figure 1 Prevalence of malaria parasitaemia among under-five children in the ten regions of Ghana (Source: MICS 201147) The National Malaria Programme (NMCP) is in the process of establishing sentinel sites across the country where all febrile cases presenting to sentinel facilities will be tested and malaria parasitaemia recorded will be used as a proxy indicator of levels of malaria transmission. Research into the development of alternative simple tools for monitoring the burden of malaria in Ghana is also underway.

We created a dichotomous variable in which visits categorized as mental health-related by this algorithm were coded affirmatively. For the second dependent variable, we measured whether a visit had a primary diagnosis of a substance use disorder. Two of the NYU ED algorithm categories were used to create this variable: alcohol and other substance use-related visits. We coded visits affirmatively

Inhibitors,research,lifescience,medical if the algorithm indicated that a visit was related to alcohol or other substance use. For the third dependent variable, we measured whether a visit had a primary diagnosis of an ambulatory care sensitive condition [30]. These conditions include several common physical health-related conditions such as asthma, hypertension, and diabetes. We coded visits with an ICD-9-CM code indicating a primary diagnosis of an ambulatory care sensitive condition affirmatively. The study’s independent variable was click here ex-prisoner status, defined as an index release from the state’s correctional facility within the year prior to the ED visit. In these analyses, we do not differentiate between those visits Inhibitors,research,lifescience,medical occurring while an individual was living in the community and visits occurring

while re-incarcerated during the year following Inhibitors,research,lifescience,medical the index release. Study covariates At the individual-level, we included variables for age (measured as a continuous variable), gender, race/ethnicity (black, Hispanic, white, other race), and the hospital facility in which the visit occurred. We excluded visits by individuals under 18 and over 70 years of age from the general population

sample to ensure appropriate Inhibitors,research,lifescience,medical comparison with the ex-prisoner sample, which did not include children and included few older adults. Indicator variables for year controlled for changes in ED visitation patterns over time. At the ZIP code-level, we measured unemployment rate (measured as tenths of a percentage point) Inhibitors,research,lifescience,medical as a surrogate measure of both economic disadvantage and rate of uninsurance. Finally, we measured community population at the ZIP code-level. As these population data were highly positively skewed, a natural logarithmic transformation was performed to decrease the influence of extreme values. Data analysis We first performed descriptive statistics within the ex-prisoner cohort (N=1434). We determined the timing of first of ED visit after release, both overall and for the three diagnosis types of interest. We examined the relationship between first release from prison and first ED visit and used the chi-square test to assess associations between the timing of first ED visits and several relevant individual-level characteristics. We next compared visits by the ex-prisoner and general populations across several patient- and community-level characteristics. We used the chi-square test for differences in categorical variables and analysis of variance (ANOVA) for differences in continuous variables.

Breakfast is the first meal of the day and is typically taken no later than mid-morning. It is frequently branded as the most important meal of the day, owing to a number of benefits including prevention of overweight, obesity and reduction in risk of cardiovascular diseases.1 Skipping breakfast is a common practice Epacadostat ic50 by people around the world. The 1999–2006 National Health and Nutrition Survey of the United States reported that between 20% and 30% of children and adolescents skipped breakfast frequently.2 In India, the proportion of children skipping breakfast regularly was even higher (over 50%).3 Breakfast is important in meeting the day’s nutritional needs. Children who consume breakfast are

likely to meet their energy and overall nutrient requirement compared to those who do not have breakfast.4, 5,6,7,8 In India, children between 10 and 15 years who consumed breakfast met about one quarter to one third of their daily energy and protein intakes from the breakfast meal.3 Breakfast consumption also contributes to increase intakes of other nutrients. In a longitudinal study among girls 9–19 years, in which energy intake was adjusted

for, breakfast cereal consumption was related to increased consumption of fibre, calcium, iron, folic acid, vitamin C, and zinc, and a decrease Buparlisib nmr in fat and cholesterol intake.9 Breakfast skippers in most cases are unable to compensate for the nutrients lost during the rest of the day.4 Breakfast meals contribute to improving cognition among school age children.10,11 The amount of time between the consumption of the last meal of the day and breakfast the next morning is generally longer compared to the time interval between other Dichloromethane dehalogenase meals such as breakfast and lunch or lunch and dinner.11 The long-time interval results in metabolic changes that interfere with cognitive function and school performance.10 Among American children, 9–11 years old, those who took breakfast had higher

mental arithmetic task performance, showed better creative thinking and improvement on performance of tasks involving processing of complex visual display.11,12,13 Other studies report improvements in tasks regarding memory function with the intake of breakfast.10,13,14 Studies on breakfast habits among Ghanaian children are lacking. The objective of this study was to determine the breakfast habits of Ghanaian school children and to determine the contribution of the breakfast meal to the total energy and nutrient intake for the day. Methods Subjects and study area A cross-sectional design was used for this study. Primary school children (n=359) were selected from 10 public schools in the Upper and Lower Manya-Krobo Districts of the Eastern Region of Ghana. The schools were selected based on ease of access to the communities in which they are located. The main economic activities in the district are farming, fishing and trading.

Born as Manuel Diaz

Soeiro in Portugal, he was brought to Amsterdam as a young child. He became a brilliant Jewish theologian, wrote religious texts in five languages, and in 1626 founded the first Hebrew printing press in the Netherlands. His image is known to us from the portraits by Rembrandt and others.6 Ben Israel published Inhibitors,research,lifescience,medical on religious topics and engaged in diplomatic and scholarly exchanges with leading Puritan theologians and government officials in England. He was tireless in seeking to obtain permission for Jews to be readmitted in England, from which country they had been banished since 1290. He obtained an unofficial permit from Oliver Cromwell in 1656, and after his death a charter was granted Inhibitors,research,lifescience,medical by Charles II in 1664. His most famous book, El

Conciliador (1632–1651), was intended to make the Old Testament more accessible to simple people and Judaism more understandable to the Gentiles. This work made him known to both Jewish and Christian scholars throughout Western Europe. The third participant in the intellectual center of Amsterdam’s Jewish quarter was Dr Ephraim Bueno, alias Martin Alvarez. Who was this physician? The Bueno medical dynasty flourished in the GSK2118436 in vivo Netherlands after having been thrice exiled from other Inhibitors,research,lifescience,medical countries. At first, being exiled from their birthplace in Spain, the Buenos settled in Portugal. The Jews remained in their new country until 1498. After their fortunes had been exhausted, the king expelled them unless they converted, which instantly exposed them to the Inquisition. Once they Inhibitors,research,lifescience,medical left, they needed an alias name. In order to protect the Bueno family members left behind, Ephraim became Martin Alvarez. The Buenos then settled in southern France where, unlike in Spain, they were accepted after conversion and were not persecuted for clandestinely practicing their old religion. Inhibitors,research,lifescience,medical At that time Jews were permitted to study medicine in France, but not to practice the profession. This situation continued until 1615, when once again they were exiled. Their next

refuge was in the semi-tolerant Dutch lands. The Bueno family members listed in the biographical dictionary of Dutch physicians are: Abraham, practiced medicine until 1633; Benjamin, eventually PD184352 (CI-1040) emigrated to New York and died in 1683; Jacob, a graduate of Salamanca Medical School, practiced in Amsterdam until 1661; Joseph Morenu, practiced in Amsterdam until 1669; Solomon, practiced in Amsterdam until 1681; Joseph, a graduate of Bordeaux, served as a private physician to the Regent of the Netherlands until 1631; and his son Ephraim, born in 1599 in the village Castello Rodrigo in Portugal, graduate of Bordeaux in 1641, practiced medicine in Amsterdam until 1665.7,8 The tolerance of the Dutch was well known, but it was incomplete.

22 This specific finding deserves careful consideration, once again emphasizing the need for ongoing longitudinal studies in populations of children and adolescents at risk for severe mood dysregulation. Moreover, in contrast to mania in adult patients with BD, productivity in patients with ADHD may not be improved, as indexed by problems in daily working life. Sleep disturbances would also be more likely to be observed in bipolar patients.22 Here again, in similarity to children Inhibitors,research,lifescience,medical and juveniles,

it has been argued that treatment of ADHD with comorbid BD is challenging, in that treatment-emergent mania and the exacerbation of bipolar symptoms can occur while receiving treatment with stimulants.22 A recent review article22 comprising four studies examining LY2157299 nmr phenomenological aspects of ADHD and BD in adults detected two significant levels of overlap between Inhibitors,research,lifescience,medical these two disorders.22,26 One level was based on the overlap in DSM-IV symptoms for ADHD (ic, excessive talking, difficulties in sustaining attention or remaining seated, blurting out answers before questions have been completed, etc).22 A second level identified an overlap between ADHD symptoms and bipolar mania, indexed by excessive talking in bipolar mania and to a lesser extent in ADHD,distractibility in BD as

opposed to difficulties in sustaining attention in ADHD, and Inhibitors,research,lifescience,medical increased activity and physical restlessness in BD as opposed to hypcrmotoric behavior in ADHD (for a summary see Wingo and Ghaemi22 ). Two studies examining the course of illness found an earlier age of onset in adults with ADHD Inhibitors,research,lifescience,medical and comorbid BD compared with subjects with a single diagnosis of adult BD.24,25 In consequence, studies investigating the overlap in clinical symptom Inhibitors,research,lifescience,medical patterns of PBD and ADHD should focus on potential developmental changes demanding large longitudinal investigations

from childhood through adolescence to later adulthood. Neuroimaging For an investigation of the underlying neural components and processes of affective regulation, the prefrontal cortex (PFC) and the amygdala are of particular interest and relevance for PBD.27 With the neurotransmitter serotonin (5-HT) in frontal brain areas being involved in the inhibition of amygdala activation, the serotonergic system holds a significant position in the regulation of mood and behavior. However, as cognitive disturbances in PBD have been shown almost to arise regardless of illness stage or medication status, the differentiation between affective and cognitive circuitries in PBD is a matter of considerable scientific relevance in which the reciprocal connections of the PFC and the amygdala are of particular interest.27-29 A recent review analysis has supported this view, indicating that PBD could be associated with abnormalities in a circuit comprising the ventral PFC, the striatum, and the amygdala.

Adequate

inhibitory control can thus be viewed as action error-monitoring of responses, and motor inhibition is necessary to ensure adaptive behavior with positive long-term outcomes. Stimulant dependence has been repeatedly associated with high motor impulsivity or a lack of inhibition (Evenden 1999; Fillmore and Rush 2002; Fillmore et al. 2002, 2003; Morgan et al. 2006; Inhibitors,research,lifescience,medical Quednow et al. 2007; Verdejo-Garcia et al. 2008) contributing to loss of control over drug use and excessive drug-taking behavior (Lyvers 1998). The most common objective measures for motor inhibition are the Stop-Signal task (Logan et al. 1984), the Circle Tracing task (Bachorowski and Newman 1990), and the Go/No-go task. Whereas the difficulty of the Stop-Signal task involves stopping an already initiated

response several milliseconds following a go-stimulus, the Go/No-go task measures impulse Inhibitors,research,lifescience,medical inhibition without a directly initiated response. These tasks require rapid, repeated target responses, Inhibitors,research,lifescience,medical while also demanding suppression of pre-potent or automated responses when faced with a stop or no-go stimulus. Performance can be characterized in terms of stop-signal reaction time (Stop Signal Task) and commission or omission errors (Go/No-go task). Commission errors are responses while a no-go target was CHIR-99021 mw presented and omission errors are nonresponses while a go target was presented. The Stroop task (see Section 2) can similarly be used to measure inhibition of an automated response, as this task requires suppression of an overlearned response (word reading) in favor of an atypical and Inhibitors,research,lifescience,medical hence effortful response

(color naming). However, as discussed previously, this task additionally includes selective attention as cognitive process, making it more difficult to assess motor inhibition unrelated to cognitive Inhibitors,research,lifescience,medical interference components. In a study using a Stop-Signal task, cocaine abusers showed reduced motor inhibition compared with HCs, and acute cocaine administration in Mephenoxalone cocaine abusers resulted in decreased inhibition compared with saline administration (Fillmore and Rush 2002; Fillmore et al. 2002). Using the Stroop task as a measure of motor impulsivity, no performance differences were found in male cocaine abusers compared to male HCs (Selby and Azrin 1998). Another study found a small (nonsignificant) decrement in performance during the Stroop task in abstinent cocaine abusers (Bolla et al. 1999). In adolescent smokers, performance on a Stroop task improved following smoking, whereas abstinence from smoking resulted in impaired inhibition (Zack et al. 2001). Cognitive impulsivity Cognitive impulsivity, or impaired delay discounting, constitutes an important aspect of decision making (Monterosso and Ainslie 1999; Cardinal et al. 2004; Deakin et al.

3% versus 22.6%, P = 0.0042; median PFS 9.2 months versus 7.5 months; HR = 0.73, P = 0.017) and partially sensitive disease with median

PFS of 7.4 months versus 5.5 months in PLD/TRAB versus PLD arm (HR = 0.65, P = 0.0152). An unplanned hypothesis-generating analysis adjusting for the PFI imbalance and other prognostic factors suggested an improvement in OS associated with the trabectedin/PLD arm (HR = 0.82; 95% CI: 0.69–0.98; P = 0.0285). In another unplanned exploratory analysis, the subset of click here patients with a PFI of 6–12 months Inhibitors,research,lifescience,medical had the largest difference in OS (HR = 0.64; 95% CI: 0.47–0.86; P = 0.0027). Data showed a longer time to the following platinum therapy, and Inhibitors,research,lifescience,medical this imbalance in platinum-free interval was suggested as a possible cause of the increased OS [78]. Thus, these data suggest that the treatment with an effective nonplatinum combination may artificially prolong the platinum-free interval giving more chance of activity to further platinum therapy. This hypothesis will be investigated in a phase III trial, called INNOVATYION. As expected the combination Inhibitors,research,lifescience,medical regimen of TRAB/PLD has been associated to a

greater haematological toxicity (grade 3/4 anaemia 14%, neutropenia and thrombocytopenia 63%). Among other toxicities, short-lived grade 3/4 hypertransaminasemia (38%) and HFS were documented in 4% of the PLD/TRAB arm compared to 20% in the PLD alone arm [79]. In September 2009, based on these results, which support the PLD/TRAB combination as the most effective nonplatinum-based combination in platinum-sensitive disease, the PLD (30mg/m2) and TRAB (1.1mg/m2) association every 3 weeks has Inhibitors,research,lifescience,medical been approved by the EMA for treatment of patients with relapsed platinum-sensitive OvCa [80]. Based on the phase-II trials in platinum-sensitive OvCa the combination of PLD/carboplatin has Inhibitors,research,lifescience,medical been explored in phase-III trials [53]. Markman et al. compared single-agent carboplatin to

its combination with PLD in recurrent ovarian cancer, showing a statistically significant improvement of PFS with carboplatin/PLD, without an overall survival benefit. Interestingly, for unknown reasons, the association drastically reduced the rate of hypersensitivity reactions compared to carboplatin alone (9% versus 0%, P = 0.0008) [53]. Later on the results of the CALYPSO trial have been reported [81, 82]. This international open-label phase-III trial compared carboplatin Thalidomide PLD (CD) with carboplatin-paclitaxel (CP) in patients with platinum-sensitive recurrent ovarian cancer (ROC). A total of 976 recurrent patients relapsing >6 months after first- or second-line therapy were randomized to receive CD or CP for six cycles. Designed as a noninferiority trial, CALYPSO demonstrated that the combination of CD was not only noninferior to CP in terms of PFS, but indeed it was more effective (HR = 0.82, P = 0.005) in patients with platinum-sensitive recurrent ovarian cancer.