Frequent expression of PD‐L1 on circulating breast cancer cells

Immune checkpoint regulators such as PD‐L1 have become exciting new therapeutic targets leading to long lasting remissions in patients with advanced malignancies. However, in view of the remarkable costs and the toxicity profiles of these therapies, predictive biomarkers able to discriminate responders from non‐responders are urgently needed. In the present paper, we provide evidence that PD‐L1 is frequently expressed on metastatic cells circulating in the blood of hormone receptor‐positive, HER2‐negative breast cancer patients. We performed western blot, flow cytometry and immunocytochemical analyses to demonstrate the specificity of the PDL1 antibody used in our study and established immunoscores for PDL1 expression on single tumor cells. We then selected sixteen patients with circulating tumor cells (CTCs) using the CellSearch® system and found PD‐L1(+) CTCs in 11 patients (68.8%). The fraction of PD‐L1(+) CTCs varied from 0.2 to 100% in individual patients. This is the first report demonstrating the expression of PD‐L1 on CTCs. The established CTC/PD‐L1 assay can be used for liquid biopsy in future clinical trials for stratification and monitoring of cancer patients undergoing immune checkpoint blockade.     

Interobserver variability,detection rate,and lesion patterns of 68Ga-PSMA-11-PET/CT in early-stage biochemical recurrence of prostate cancer after radical prostatectomy

European Journal of Nuclear Medicine and Molecular Imaging - 68Ga-PSMA-11-PET/CT is increasingly used in early-stage biochemical recurrence of prostate cancer to detect potential lesions for an...     

Mechanical Properties of Different Nanopatterned TiO2 Substrates and Their Effect on Hydrothermally Synthesized Bioactive Hydroxyapatite Coatings

Nanotechnology is a very attractive tool for tailoring the surface of an orthopedic implant to optimize its interaction with the biological environment. Nanostructured interfaces are promising, especially for orthopedic applications. They can not only improve osseointegration between the implant and the living bone but also may be used as drug delivery platforms. The nanoporous structure can be used as a drug carrier to the surrounding tissue, with the intention to accelerate tissue–implant integration as well as to reduce and treat bacterial infections occurring after implantation. Titanium oxide nanotubes are promising for such applications; however, their brittle nature could be a significantly limiting factor. In this work, we modified the topography of commercially used titanium foil by the anodization process and hydrothermal treatment. As a result, we obtained a crystalline nanoporous u-shaped structure (US) of anodized titanium oxide with improved resistance to scratch compared to TiO₂ nanotubes. The US titanium substrate was successfully modified with hydroxyapatite coating and investigated for bioactivity. Results showed high bioactivity in simulated body fluid (SBF) after two weeks of incubation.     

Nanocellulose Production Using Ionic Liquids with Enzymatic Pretreatment

Nanocellulose has gained increasing attention during the past decade, which is related to its unique properties and wide application. In this paper, nanocellulose samples were produced via hydrolysis with ionic liquids (1-ethyl-3-methylimidazole acetate (EmimOAc) and 1-allyl-3-methylimidazolium chloride (AmimCl)) from microcrystalline celluloses (Avicel and Whatman) subjected to enzymatic pretreatment. The obtained material was characterized using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), scanning electron microscopy (SEM), and thermogravimetric analysis (TG). The results showed that the nanocellulose had a regular and spherical structure with diameters of 30–40 nm and exhibited lower crystallinity and thermal stability than the material obtained after hydrolysis with Trichoderma reesei enzymes. However, the enzyme-pretreated Avicel had a particle size of about 200 nm and a cellulose II structure. A two-step process involving enzyme pretreatment and hydrolysis with ionic liquids resulted in the production of nanocellulose. Moreover, the particle size of nanocellulose and its structure depend on the ionic liquid used.     

Five‐grass pollen 300IR SLIT tablets: efficacy and safety in children and adolescents

Halken S, Agertoft L, Seidenberg J, Bauer C‐P, Payot F, Martin‐Muñoz MF, Bartkowiak‐Emeryk M, Vereda A, Jean‐Alphonse S, Melac M, Le Gall M, Wahn U. Five‐grass pollen 300IR SLIT tablets: efficacy and safety in children and adolescents.
Pediatr Allergy Immunol 2010: 21: 970–976.
© 2010 John Wiley & Sons A/S The efficacy and safety of five‐grass pollen 300IR sublingual immunotherapy (SLIT) tablets (Stallergènes SA, France) have previously been demonstrated in paediatric patients. This report presents additional data concerning efficacy at pollen peak, efficacy and safety according to age, nasal and ocular symptoms, use of rescue medication, satisfaction with treatment and compliance. Children (5–11 yr) and adolescents (12–17 yr) with grass pollen–allergic rhinoconjunctivitis were included in a multinational, randomized, double‐blind, placebo‐controlled study and received either a 300IR five‐grass pollen tablet or placebo daily in a pre‐ (4 months) and co‐seasonal protocol. The severity of six symptoms (sneezing, rhinorrhoea, nasal congestion, nasal and ocular pruritis, and tearing) was scored, and rescue medication use was recorded daily during the pollen season. Patient satisfaction was recorded at the season end. A total of 161 children and 117 adolescents were evaluated (n = 267). 300IR SLIT was effective over the whole season (p = 0.0010) and at the pollen peak (p = 0.0009). The adjusted mean difference between 300IR and placebo groups was significant for both nasal (p = 0.0183) and ocular (p < 0.0001) symptoms. Rescue medication use was statistically lower in the SLIT group during the pollen season and at the pollen peak (both p < 0.05). More patients in the SLIT group were satisfied with their treatment compared to placebo (83.2% vs. 68.1%, p = 0.0030), and compliance was high (SLIT 93.9% of patients were compliant, placebo 94.8% of patients were compliant). SLIT was well tolerated by children and adolescents. 300IR five‐grass pollen tablets are effective and safe during the pollen season and at the pollen peak in children and adolescents with grass pollen rhinoconjunctivitis.     

Salvage radiotherapy in patients with persistently detectable PSA or PSA rising from an undetectable range after radical prostatectomy gives comparable results

Purpose

Salvage radiotherapy (SRT) is applied routinely in patients with a biochemical relapse after radical prostatectomy (RP). Although the detection threshold for relapse after RP has steadily been lowered, only about 30 % of the SRT patients achieve a durable response. We have previously shown the association between a PSA decrease below detectable levels after SRT and biochemical progression-free survival (BPFS). After recalculating our data according to a more recent definition of biochemical failure after SRT, we now show the significance of the post-RP PSA nadir.

Materials and methods

Among 159 prostate cancer patients without hormonal treatment after RP, SRT was given to 72 patients with persistently detectable PSA after RP and to 87 whose PSA increased out of an undetectable range. The median pre-SRT PSA was 0.29 ng/ml for the former group and 0.34 ng/ml for the latter group. A radiation dose of 66.6 Gy was applied to the prostate bed.

Results

The overall median follow-up time was 41.7 months. The probability for BPFS after this period was 52.8 % in 72 patients with persistently detectable PSA after RP and 65.4 % in 87 patients who had a post-RP PSA nadir below detection limit. Univariate and multivariate analyses showed no significant difference in BPFS of both patient groups (p > 0.05).

Conclusion

Our findings suggest that SRT is a viable treatment option for patients with persistently detectable PSA, giving similar results as in patients whose PSA increases out of an undetectable range after RP.     

Radiotherapy after radical prostatectomy: immediate or early delayed?

Background

Biochemical recurrence after radical prostatectomy (RP) is associated with risk indicators, including Gleason score, preoperative PSA level, tumor stage, seminal vesicle invasion, and positive surgical margins. The 5-year biochemical progression rate among predisposed patients is as high as 50?C70%. Post-RP treatment options include adjuvant radiotherapy (ART, for men with undetectable PSA) or salvage radiotherapy (SRT, for PSA persisting or re-rising above detection threshold). Presently, there are no published randomized trials evaluating ART vs. SRT directly.

Methods

Published data on ART and SRT were reviewed to allow a comparison of the two treatment approaches.

Results

Three randomized phase III trials demonstrated an almost 20% absolute benefit for biochemical progression-free survival after ART (60?C64?Gy) compared to a ??wait and see?? policy. The greatest benefit was achieved in patients with positive margins and pT3 tumors. SRT can be offered to patients with elevated PSA after RP. In 30?C70% of SRT patients, PSA will decrease to an undetectable level, thus giving a second curative chance. The rate of side effects for both treatments is comparably low. The role of irradiation of pelvic lymph nodes and the additional use of hormone therapy and radiation dose are discussed.

Conclusion

It remains unclear whether early SRT initiated after PSA failure is equivalent to ART. Where SRT is indicated, it should be started as early as possible.