The addition of pembrolizumab to chemotherapy for metastatic lung cancer without
EGFR
or
ALK
mutations resulted in better progression-free and overall survival than chemotherapy alone. Immune-related ...adverse effects were more common with the combination.
CEA, CYFRA21-1 and NSE are tumor markers used for monitoring the response to chemotherapy in advanced adenocarcinoma, squamous cell carcinoma and small-cell lung cancer, respectively. Their role in ...cancer immunotherapy needs to be elucidated.
Patients with advanced non-small cell lung cancer (NSCLC) were treated with nivolumab 3 mg/kg every 2 weeks within the Italian Nivolumab Expanded Access Program. Blood samples were collected at baseline, at each cycle up to cycle 5 and then every two cycles until patient's withdrawn from the study. All patients underwent a CT-scan after every 4 cycles of treatment and responses were classified according to RECIST 1.1. The biomarkers serum levels were measured with a chemiluminescent microparticle immunoassay for CEA and with an immuno radiometric assay for CYFRA21-1 and NSE. The markers values at baseline and after 4 cycles were used to analyze the relationship between their variation over baseline and the tumor response, evaluated as disease control rate (DCR: CR + PR + SD), and survival (PFS and OS).
A total of 70 patients were evaluable for the analysis. Overall, a disease control was obtained in 24 patients (35.8%, 4 PR + 20 SD). After 4 cycles of nivolumab a CEA or CYFRA21-1 reduction ≥ 20% over the baseline was significantly associated with DCR (CEA, p = 0.021; CYFRA21-1, p < 0.001), PFS (CEA, p = 0.028; CYFRA21-1, p < 0.001) and OS (CEA, p = 0.026; CYFRA21-1, p = 0.019). Multivariate analysis confirmed the ability of CYFRA21-1 reduction ≥ 20% to predict DCR (p = 0.002) and PFS (p < 0.001).
The reduction in serum level of CYFRA21-1 or CEA might be a reliable biomarker to predict immunotherapy efficacy in NSCLC patients. NSE was not significant for monitoring the efficacy of nivolumab.
The spring phytoplankton bloom is the main event influencing ecosystem richness in the pelagic realm of the Northwestern Mediterranean Sea (NW Med Sea). The Marine Strategy Framework Directive ...requires the achievement of a good ecological status for the pelagic habitat, and phytoplankton bloom phenology has been used as an indicator of the status of offshore waters. In this work we investigate interannual changes in the timing and magnitude of the phytoplankton bloom in the NW Med Sea, using phenological metrics. Daily maps of Chl-a concentration from 1998 to 2022 obtained by CMEMS were used to analyse bloom phenological metrics in 5 representative sites in the area. Chlorophyll-a data from 1998 to 2007 were used for determining the climatological behaviour, while 2008–2022 was identified as the study period. For this latter period, yearly spring bloom were identified and interannual variability and overall trends were analysed for each of the phenological metrics considered. Winter oceanographic and meteorological data were analysed to investigate possible correlations with the subsequent spring bloom. The frequency of anomalous years is increasing, both for bloom intensity and sea temperature. Bloom analysis revealed a negative trend only in some areas, but a steep decrease in the last 7 years was noticeable for all sites considered. Correlations of the Chl-a concentration during bloom with oceanographic variables revealed the importance of temperature, both marine and atmospheric, while Mixed Layer Depth played a lesser role. This work contributes to a better understanding of the dynamics of an area already under severe threat from human activities.
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•Bloom phenology is a good indicator of the ecological status of pelagic habitat.•Phenological indices are obtained for spring bloom in NW Med from 2008 to 2022.•Anomalies and trends of blooms are identified for different years and areas.•Correlation with environmental parameters suggests links to climate change.•Need to monitor climate change impact on the pelagic habitat.
Purpose To present outcomes in a series of patients with Ehlers-Danlos syndrome (EDS)–hypermobility type who underwent hip arthroscopy for associated hip pain and extreme capsular laxity. Methods A ...retrospective chart review identified 16 hips with confirmed EDS–hypermobility type that underwent hip arthroscopy for continued pain and capsular laxity. All patients had complaints of “giving way” and pain, an easily distractible hip with manual traction under fluoroscopy, and a patulous capsule at the time of surgery. No patient had osseous evidence of acetabular hip dysplasia or prior confirmed hip dislocation. Outcomes were evaluated preoperatively and postoperatively with the modified Harris Hip Score (mHHS), the 12-Item Short Form Health Survey (SF-12), and a visual analog scale (VAS) for pain. Results Evidence of symptomatic femoroacetabular impingement (FAI) was found in 15 hips (93.8%). The 16th hip had subjective giving way with a positive anterior impingement test and was easily distractible, had a labral tear, and had a patulous capsule at the time of surgery. The mean follow-up period was 44.61 months (range, 12 to 99 months). The mean preoperative lateral center-edge angle was 31.8° (range, 25° to 44°), and the mean Tönnis angle was 3.6° (range, −2° to 8°). Mean femoral version measured on computed tomography (CT) scans was 19.2° (range, −4.0° to 31.0°). Of the hips, 13 underwent primary arthroscopy and 3 underwent revision. All hips underwent hip arthroscopy with an interportal capsular cut only and arthroscopic capsular plication. There were 13 labral repairs, 2 labral debridements, 8 rim resections, 15 femoral resections, 2 psoas tenotomies, and 1 microfracture. Improved stability with an inability to distract the hip with manual traction under fluoroscopy was noted in all hips after plication. The mean alpha angle preoperatively was 58.7° on anteroposterior radiographs and 63.6° on lateral radiographs compared with 47.4° and 46.1°, respectively, postoperatively. There were significant improvements for all outcomes (mHHS, P = .002; SF-12 score, P = .027; and VAS score, P = .0004). The mean mHHS, SF-12 score, and VAS score were 45.6 points, 62.4 points, and 6.5 points, respectively, preoperatively compared with 88.5 points, 79.3 points, and 1.6 points, respectively, at a mean follow-up of 45 months. No EDS patients were lost to follow-up or excluded from analysis. The mean improvement in mHHS from preoperatively to postoperatively was 42.9 points, and there were no iatrogenic dislocations. One patient underwent further revision arthroscopy for recurrent pain, subjective giving way, and capsular laxity. Conclusions FAI and extreme capsular laxity can be seen in the setting of EDS. Although increased femoral version was common, acetabular dysplasia was not common in our study. Meticulous capsular plication, arthroscopic correction of FAI when present, and labral preservation led to dramatic improvements in outcomes and subjective stability without any iatrogenic dislocations in this potentially challenging patient population. Level of Evidence Level IV, therapeutic case series.
The aim of this open label phase II study (NCT00407459) was to assess the activity of the vascular endothelial growth factor (VEGF) inhibitor bevacizumab combined with pemetrexed and carboplatin in ...patients with previously untreated, unresectable malignant pleural mesothelioma (MPM).
Eligible patients received pemetrexed 500 mg m(-2), carboplatin area under the plasma concentration-time curve (AUC) 5 mg ml(-1) per minute and bevacizumab 15 mg kg(-1), administered intravenously every 21 days for six cycles, followed by maintenance bevacizumab. The primary end point of the study was progression-free survival (PFS). A 50% improvement in median PFS in comparison with standard pemetrexed/platinum combinations (from 6 to 9 months) was postulated.
Seventy-six patients were evaluable for analysis. A partial response was achieved in 26 cases (34.2%, 95% CI 23.7-46.0%). Forty-four (57.9%, 95% CI 46.0-69.1%) had stable disease. Median PFS and overall survival were 6.9 and 15.3 months, respectively. Haematological and non-haematological toxicities were generally mild; however, some severe adverse events were reported, including grade 3-4 fatigue in 8% and bowel perforation in 4% of patients. Three toxic deaths occurred.
The primary end point of the trial was not reached. However, due to the limitation of a non-randomised phase II design, further data are needed before drawing any definite conclusion on the role of bevacizumab in MPM.
Several studies have described the effects of seed exudates against microorganisms, but only few of them have investigated the proteins that have defensive activity particularly against nematode ...parasites. This study focused on the proteins released in the exudates of soybean seeds and evaluated their nematicidal properties against Meloidogyne incognita. A proteomic approach indicated the existence of 63 exuded proteins, including β-1,3-glucanase, chitinase, lectin, trypsin inhibitor, and lipoxygenase, all of which are related to plant defense. The presence of some of these proteins was confirmed by their in vitro activity. The soybean exudates were able to reduce the hatching of nematode eggs and to cause 100% mortality of second-stage juveniles (J2). The pretreatment of J2 with these exudates resulted in a 90% reduction of the gall number in tobacco plants. These findings suggest that the exuded proteins are directly involved in plant defense against soil pathogens, including nematodes, during seed germination.
The living euryhaline species Cyprideis torosa (Jones) undergoes morphometric variations in size, noding and sieve-pore shape linked to the environmental salinity. In particular it is known that ...salinity values around 8–9psu represent the osmoregulation threshold and also the turning point between smaller and greater valve dimensions and prevailingly noded against un-noded valves. The variation of the percentage of round-, elongate- and irregular-shaped sieve-pores on the valves has shown an empiric logarithmic correlation with the water salinity from 0 to 100psu. Due to this ecologically cued polymorphism, C. torosa represents an invaluable paleosalinometer for the Quaternary brackish basins.
In this paper we attempt to verify whether the ecophenotypical behavior of the post-evaporitic Messinian species Cyprideis agrigentina Decima was comparable with that of Cyprideis torosa. To reach this goal, three morphometric characters have been analyzed: 1) size variability; 2) noding and ornamentation; and 3) variability of the percentage of the sieve-pore shapes. The paleoenvironmental interpretation was made using synecological and geochemical approaches stable isotopes, trace elements, Sr-isotopes and natural radioactivity (NRD). For this study, the 250m-thick Messinian Lago-Mare succession of Eraclea Minoa (Agrigento, Sicily) was chosen for the presence of monotypic assemblages made only by C. agrigentina for around 70m of thickness.
The results of the morphometric analyses showed that: 1) size variations are not related to the salinity changes recognized both from synecological and geochemical analyses; 2) no noded specimens have been recovered along the Section; 3) the salinities calculated on the basis of the percentage of the sieve-pore shape are not correlated with the salinities inferred from the synecological and geochemical analyses. Thus, in this paper we conclude that Cyprideis agrigentina cannot be considered a paleosalinometer for the Messinian Salinity Crisis.
There is a correlation of the δ13C with the percentages of sieve-pore shapes, linking them to the behavior of the dissolved inorganic carbon (DIC) and to the oxygen availability at the bottom of the basin.
•We study in a paleoenvironmental perspective a post-evaporitic ostracod assemblage.•We perform morphometric and geochemical analyses on Cyprideis agrigentina valves.•C. agrigentina sizes and ornamentation are not affected by salinity variations.•Sieve-pore shapes in C. agrigentina seem linked to the bottom oxygen availability.•C. agrigentina is not a paleosalinometer for the Messinian Salinity Crisis.
Cowpea (Vigna unguiculata L. Walp) is an important legume species well adapted to low fertility soils and prolonged drought periods. One of the main problems that cause severe yield losses in cowpea ...is the root‐knot nematode Meloidogyne incognita. The aim of this work was to analyze the differential expression of proteins in the contrasting cultivars of cowpea CE 31 (highly resistant) and CE 109 (slightly resistant) during early stages of M. incognita infection. Cowpea roots were collected at 3, 6, and 9 days after inoculation and used for protein extraction and 2‐DE analysis. From a total of 59 differential spots, 37 proteins were identified, mostly involved in plant defense, such as spermidine synthase, patatin, proteasome component, and nitrile‐specifier protein. A follow‐up study was performed by quantitative RT‐PCR analysis of nine selected proteins and the results revealed a very similar upregulation trend between the protein expression profiles and the corresponding transcripts. This study also identified ACT and GAPDH as a good combination of reference genes for quantitative RT‐PCR analysis of the pathosystem cowpea/nematode. Additionally, an interactome analysis showed three major pathways affected by nematode infection: proteasome endopeptidase complex, oxidative phosphorylation, and flavonoid biosynthesis. Taken together, the results obtained by proteome, transcriptome, and interactome approaches suggest that oxidative stress, ubiquitination, and glucosinolate degradation may be part of cowpea CE 31 resistance mechanisms in response to nematode infection.
Over the years, several studies have been performed to analyse plant-pathogen interactions. Recently, functional genomic strategies, including proteomics and transcriptomics, have contributed to the ...effort of defining gene and protein function and expression profiles. Using these 'omic' approaches, pathogenicity- and defence-related genes and proteins expressed during phytopathogen infections have been identified and enormous datasets have been accumulated. However, the understanding of molecular plant-pathogen interactions is still an intriguing area of investigation. Proteomics has dramatically evolved in the pursuit of large-scale functional assignment of candidate proteins and, by using this approach, several proteins expressed during phytopathogenic interactions have been identified. In this review, we highlight the proteins expressed during plant-virus, plant-bacterium, plant-fungus and plant-nematode interactions reported in proteomic studies, and discuss these findings considering the advantages and limitations of current proteomic tools.
Malignant mesothelioma (MM) is an aggressive tumor, mainly derived from the pleura, which is predominantly associated with exposure to asbestos fibers. The prognosis of MM patients is particularly ...severe, with a median survival of approximately 9–12 months and latency between exposure and diagnosis ranging from 20–50 years (median 30 years). Emerging evidence has demonstrated that tumor aggressiveness is associated with genome and gene expression abnormalities; therefore, several studies have recently focused on the role of microRNAs (miRNAs) in MM tumorigenesis. miRNAs are small non-protein coding single-stranded RNAs (17–22 nucleotides) involved in numerous cellular processes that negatively regulate gene expression by modulating the expression of downstream target genes. miRNAs are often deregulated in cancer; in particular, the differential miRNA expression profiles of MM cells compared to unaffected mesothelial cells have suggested potential roles of miRNAs as either oncogenes or tumor suppressor genes in MM oncogenesis. In this review, the mechanism of MM carcinogenesis was evaluated through the analysis of the published miRNA expression data. The roles of miRNAs as diagnostic biomarkers and prognostic factors for potential therapeutic strategies will be presented and discussed.
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