Twenty years of anti-HER2 therapy-associated cardiotoxicity

Over the past 20...years, the prognosis of HER2-positive breast cancer has been transformed by the development of anti-HER2 targeted therapies. In early clinical trials of trastuzumab (ie, the first anti-HER2 agent to be developed) cardiotoxicity became a major concern. In the first published phase 3 trial of trastuzumab, 27% of patients receiving anthracyclines and trastuzumab experienced cardiac events and 16% suffered from severe congestive heart failure. In subsequent trials conducted in advanced and early settings, the incidence of cardiac events was reduced through changes in chemotherapy regimens, more strict patient selection and close cardiac assessment. However, cardiotoxicity remains a significant problem in clinical practice that is likely to increase as new agents are approved and exposure times increase through improved patients' survival. Though numerous trials have led to improved understanding of many aspects of anti-HER2 therapy-related cardiotoxicity, its underlying physiopathology mechanisms are not well understood. The purpose of this article is to provide an in-depth review on anti-HER2 therapy-related cardiotoxicity, including data on both trastuzumab and the recently developed anti-HER2 targeted agents

Interactive effects of elevated temperature and CO2 on two phylogeographically distinct clones of common reed (Phragmites australis)

The aboveground growth, physiological and biochemical parameters of two clones of the cosmopolitan wetland grass Phragmites australis, grown at four treatment combinations of temperature and O2, were investigated to elucidate whether their climate response differed due to inherent differences in their ecological adaptation. The two phylogeographically distinct P. australis clones (DK clone, European genetic background; ALG clone, Mediterranean genetic background) were grown for 151 days in phytotrons at 19/12 8C (day/night temperature) and 390 ppm CO2, and at elevated temperature (+5 8C) and CO2 (700 ppm) with treatment factors alone or in combination. The ALG clone had 2–4 times higher aboveground biomass, higher light-saturated rates of photosynthesis (Pmax), maximum electron transport rates (ETRmax) and Rubisco activity, and higher photosynthetic nitrogen-use efficiency than the DK clone. The DK clone, however, produced more shoots, leaves and sideshoots, and had 9–51 % higher specific leaf area and 15–39 % higher leaf nitrogen concentration than the ALG clone. Although elevated atmospheric CO2 alone barely affected the aboveground growth of the two P. australis clones, simultaneously elevated temperature and CO2 stimulated growth and aboveground biomass. Overall, elevated CO2 stimulated photosynthesis, but the clones responded differently to a concomitant increase in CO2 and temperature, depending on the phylogeographic background of the plant. The DK clone showed overall stronger responses, and can be considered the more plastic of the two clones with respect to CO2 and temperature. Thus, the DK clone may be better adapted to climate change than the ALG clone, at least in the short term

Hybridization of Common Reed in North America? The Answer is Blowing in the Wind

Background and aims: We review evidence for hybridization of Phragmites australis in North America and the implications for the persistence of native P. australis ssp. americanus populations in North America. We also highlight the need for an updated classification system, which takes P. australis intraspecific variation and hybridization into account. Methodology: We reviewed available published, in press, and in preparation literature to assess the likelihood of hybridization and interbreeding in genotypes of Phragmites australis present in North America. Principal results: Experimental results demonstrate that hybridization among introduced and native haplotypes is possible within the genus Phragmites, yet evidence that hybridization has naturally occurred is only starting to emerge. The lag in identifying hybridization in Phragmites in North America may be related to undersampling in some parts of North America and to a lack of molecular tools that provide the capability to recognize hybrids. Conclusions: Our understanding of the gene flow within and between species in the genus Phragmites is moving at a fast pace, especially on the east and Gulf coasts of North America. More attention should also be focused on the Great Lakes region, the southwestern and the west coast of the U.S. where sympatry has created opportunities for hybridization. Where hybridizations have been detected, there is currently no published data on how hybridization affects plant vigor, morphology, invasiveness, or conservation of the genetic integrity of the North American native subspecies. We conclude that detection of more hybridization is highly likely and that there is a need to develop new markers for the different Phragmites species and lineages to fill current knowledge gaps. Finally, we suggest that the classification system for P. australis should be updated and published to help clarify the nomenclature

Selective Laser Sintering versus Multi Jet Fusion: A Comprehensive Comparison Study Based on the Properties of Glass Beads-Reinforced Polyamide 12

Selective laser sintering (SLS) and multi jet fusion (MJF) are the most widespreadpowder bed fusion additive manufacturing techniques for fabricating polymericparts since they offer great designflexibility, productivity, and geometricalaccuracy. However, these technologies differ in the thermal energy source usedto melt the powders as well as the innovative use of printing agents featured inthe latter one to promote material consolidation and to avoid thermal bleeding atthe part contours. The use of a single powder made of glass beads-reinforcedpolyamide 12 (PA12/GB) for the fabrication of MJF and SLS samples makespossible a systematic comparison of the printed parts properties. A thoughtfulanalysis of the microstructure and mechanical properties of the samples revealsdifferences and peculiarities between the two technologies. SLS exhibits lowerporosity and higher mechanical performances when the parts are printed alongthe build plane thanks to the powerful heating ensured by the laser. In contrast,MJF samples show higher mechanical isotropy with greatflexural and tensilebehavior for vertically oriented parts. The role of glass beads in the materialbehavior is defined by their mechanical properties, meaning higher rigidity andlower strength compared to neat PA12, and fracture mechanism

Triple-negative breast cancer: Current perspective on the evolving therapeutic landscape

Triple-negative breast cancer (TNBC) is known to have a poor prognosis and limited treatment options, namely chemotherapy. Different molecular studies have recently classified TNBC into different subtypes opening the door to potential new-targeted treatment options. In this review, we discuss the current standard of care in the treatment of TNBC in the neoadjuvant, adjuvant and metastatic settings. In addition, we summarize the ongoing phase III clinical trials evaluating different associations between the 3 pillars of anticancer treatment: chemotherapy, targeted therapy and immunotherapy

Historical dynamics of Batrachochytrium dendrobatidis in Amazonia

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The Amazon forest is known for its astonishing amphibian diversity, yet the potential distribution and underlying impacts of the most important amphibian pathogen is unknown for most of Amazonia. In this retrospective survey of preserved Leptodactylus frogs, collected over a 119 yr period, we used quantitative PCR to detect the fungal pathogen Batrachochytrium dendrobatidis (Bd) and performed spatial scan analyses to identify spatiotemporal clusters of Bd. We also quantified the potential effect of environmental factors on the likelihood of Bd occurrence and generated an updated suitability map for Bd in the Amazon that included our retrospective sampling. We detected Bd in lowland Amazon as early as 1935, in the state of Para, Brazil, and we found low prevalence (approximate to 3.8%) over time. We identified two statistically significant spatiotemporal clusters of Bd: a recent and narrow cluster in the Amazon River delta and a spatiotemporally broad cluster in the southern edge of Amazon and Brazilian savanna. Furthermore, we found an increase in Bd-positive samples in the southwestern Amazon after the 1990s, coinciding with reported amphibian declines in neighboring high elevation sites on Andean slopes of Peru. Spatial regressions indicated that higher human interference, higher precipitation, and lower temperatures were significant predictors of Bd occurrence. Environmental niche modeling predicted some narrow areas of suitable climates along the Amazon's periphery and generally low climatic suitability for Bd in the central Amazon; although, we found clusters of Bd-positive samples with unexpectedly high infection loads in areas of predicted low suitability. Our study indicates that accelerated human development may put Amazonian amphibians at risk from Bd introductions, and it highlights the potential need to monitor Bd dynamics near Amazonian port cities.The Amazon forest is known for its astonishing amphibian diversity, yet the potential distribution and underlying impacts of the most important amphibian pathogen is unknown for most of Amazonia. In this retrospective survey of preserved Leptodactylus fro3910954960CNQP - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)312895/2014-3405285/2013-2302589/2013-92013/50741-7302518/2013-4We thank T. S. Jenkinson, and M. F. K. Becker for feedback on the manuscriptN. Pupin, A. Mesquita, E. Garcia, D. B. Delgado T. Carvalho, P. Mourao, A. F. R. Missassi, and L. F. Moreno for help with swabbing the specimens. Christopher J. Raxworthy, Da

Pro‑differentiating compounds for human intervertebral disc cells are present in Violina pumpkin leaf extracts

The intervertebral disc degeneration (IDD) is closely associated with inflammation, oxidative stress and loss of the discogenic phenotype which current therapies are unable to reverse. Here, the effects of acetone extract from Violina pumpkin (Cucurbita moschata) leaves on degenerated intervertebral disc (IVD) cells was investigated. IVD cells were isolated from degenerated disc tissue of patients undergoing spinal surgery, and exposed to acetone extract and three major thin layer chromatography subfractions. We found that the cells benefit from exposure in particular to subfraction 7 consisting almost entirely of p-Coumaric acid. Subfraction 7-treated cells showed a significant increase of discogenic transcription factors (SOX9, TRPS1), extracellular matrix components (aggrecan, collagen type II), cellular homeostasis and stress response regulators (FOXO3a, Nrf2, SOD2, SIRT1). Migratory ability and the expression of OCT4, two important markers related to the presence and activity of stem cells also increased. Moreover, subfraction 7 counteractes H2O2-triggered cell damage preventing in particular the increase of the pro-inflammatory and antichondrogenic microRNA, miR-221. This strengthens the hypothesis that adequate stimuli can support resident cells to repopulate the degenerate IVD and restart the anabolic machinery. Taken together, the data we obtained contribute to the discovery of molecules potentially effective in slowing the progression of IDD, a disease for which there is currently no effective treatment. Moreover, the enhancement of a part of plant, the pumpkin leaves, considered a waste product in the Western world, demonstrating that it contains substances with potential beneficial effects on human health

Cutaneous sarcoid-like reaction in a patient treated with target therapy for metastatic melanoma: the hue is the clue

Cutaneous sarcoid-like reaction in a patient treated with target therapy for metastatic melanoma: the hue is the clu

Emetogenicity of Antibody-Drug Conjugates (ADCs) in Solid Tumors with a Focus on Trastuzumab Deruxtecan: Insights from an Italian Expert Panel

In the past decade, nine antibody-drug conjugates (ADCs) have been approved for the treatment of various tumors, four of which specifically for solid malignancies. ADCs deliver the cytotoxic payload to the cancer site, thereby improving chemotherapy efficacy while reducing systemic drug exposure and toxicity. With their high selectivity, ADCs are associated with a manageable side-effect profile, with nausea and vomiting being among the most frequent toxicities, although this may vary according to the respective ADC and the associated payload. Information about the emetic risk of the new ADC compounds is limited. Three virtual focus groups of Italian oncologists were held to raise awareness on the importance of an antiemetic prophylaxis regimen to prevent and mitigate ADC-associated emesis and its sequelae. After reviewing published evidence and guidelines, the three expert panels shared their experience on the early use of ADCs gained through the participation in specific clinical trials and their clinical practice. The following issues were discussed: antiemetic therapy during trastuzumab deruxtecan treatment, with a protocol adopted at the San Raffaele Hospital (Milan, Italy); the use of steroids; the management of anticipatory nausea during trastuzumab deruxtecan therapy; nutritional counselling; and effective doctor\u2013patient communication. The experts acknowledged that recommendations should be drug-specific, and formulated opinion-based advice intended to guide physicians in their daily practice until further evidence emerges