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Abnormal liver blood tests and liver tumor burden are known prognostic factors in neuroendocrine neoplasms (NEN). However, the relationship between biochemical liver parameters and hepatic tumor load is largely unknown in NEN and in high‐grade NEN (G3) specifically. The primary objective of this study was to correlate the biochemical parameters and liver tumor volume of patients with neuroendocrine tumors grade 3 (NET G3) or neuroendocrine carcinomas (NEC). We wanted to investigate whether patients with NET G3 with extensive liver involvement had less severely elevated laboratory liver parameters than NEC patients. In total, 46 patients with NEN were included, 31 had NEC and 15 NET G3. All patients had distant metastatic disease, with liver metastases being the most common (n = 39). Both laboratory results and semiautomatic volumetric measurements of liver tumor burden were obtainable for 34 patients at baseline and 26 patients at follow‐up. Alkaline phosphatase (AP), gamma‐GT (gGT), and lactate dehydrogenase (LDH) increased significantly between the two time periods (p <.01). In a regression model, liver tumor burden significantly affected several blood parameters, for example, increasing AP, gGT, LDH, and aspartate aminotransferase (ASAT) by a factor of 1.02–1.04 per unit increase (1% tumor burden; all p <.001). AP, gGT, and LDH were significantly lower in NET G3 (factor of 0.43–0.68) than in NEC. Here, we found that liver chemistries changed over the NEN disease course, correlated with hepatic tumor burden, and differed by histologic subtype. The current data can potentially guide treatment decisions, for example, with regard to integration of liver‐directed therapies. [ABSTRACT FROM AUTHOR]

Background: Proton therapy is a form of radiotherapy commonly used to treat various cancers. Due to its high conformality, minor variations in patient anatomy can lead to significant alterations in dose distribution, making adaptation crucial. While cone‐beam computed tomography (CBCT) is a well‐established technique for adaptive radiation therapy (ART), it cannot be directly used for adaptive proton therapy (APT) treatments because the stopping power ratio (SPR) cannot be estimated from CBCT images. Purpose: To address this limitation, Deep Learning methods have been suggested for converting pseudo‐CT (pCT) images from CBCT images. In spite of convolutional neural networks (CNNs) have shown consistent improvement in pCT literature, there is still a need for further enhancements to make them suitable for clinical applications. Methods: The authors introduce the 3D vision transformer (ViT) block, studying its performance at various stages of the proposed architectures. Additionally, they conduct a retrospective analysis of a dataset that includes 259 image pairs from 59 patients who underwent treatment for head and neck cancer. The dataset is partitioned into 80% for training, 10% for validation, and 10% for testing purposes. Results: The SPR maps obtained from the pCT using the proposed method present an absolute relative error of less than 5% from those computed from the planning CT, thus improving the results of CBCT. Conclusions: We introduce an enhanced ViT3D architecture for pCT image generation from CBCT images, reducing SPR error within clinical margins for APT workflows. The new method minimizes bias compared to CT‐based SPR estimation and dose calculation, signaling a promising direction for future research in this field. However, further research is needed to assess the robustness and generalizability across different medical imaging applications. [ABSTRACT FROM AUTHOR]

This international study aimed to investigate cross‐modal associations between parosmic sensations and visual information, as well as explore potential cross‐cultural differences; 393 parosmia patients from Argentina, Germany, Japan, and the Philippines participated. The patients were provided with a 63‐color chart encompassing diverse hues and a 20‐shape chart containing polygonal and curved shapes. Their task was to choose one color and one shape that matched their parosmic sensations. Results indicated that patients generally associated their parosmic sensations with brownish or greenish colors, darker colors, and polygonal or cloud‐like shapes. Significant cross‐cultural differences were observed, with Germans tending to select darker colors and edged shapes, while Japanese preferred brighter colors and curved shapes. These differences appeared to be related to the intensity of parosmia, which was higher among Germans. The study suggests a cross‐modal relationship between olfaction and vision, while also highlighting the influence of cultural factors on parosmia perception. Practical Applications: The findings of this study have practical implications for understanding and managing parosmia symptoms, particularly in multicultural settings. Healthcare professionals can use the cross‐modal associations between olfactory sensations and visual information as a tool for assessment and diagnosis of parosmia patients. By considering the cultural background of patients, healthcare providers can better understand the nuances in their descriptions and interpretations of parosmic sensations. Additionally, the observed cross‐cultural differences in color and shape associations can inform the development of standardized assessment tools that are sensitive to cultural variations. This knowledge can enhance communication between patients and healthcare professionals, leading to more accurate diagnosis, personalized treatment approaches, and improved patient outcomes. Furthermore, the study highlights the need for cultural sensitivity in odor‐related research and the development of interventions for parosmia and other olfactory disorders. [ABSTRACT FROM AUTHOR]

The mTOR‐inhibitor everolimus has been approved for the treatment of advanced neuroendocrine tumors (NETs) but is associated with relevant toxicities in clinical practice. Hence, optimal treatment sequencing and the impact of dose reductions have yet to be clarified. This retrospective analysis assessed patients with advanced, well‐differentiated NET treated with everolimus at the Medical University of Vienna. The primary objective was to evaluate the efficacy of everolimus in a real‐world cohort. A total of 52 patients treated with everolimus for advanced NET grade 1 (G1) or G2 (or typical or atypical carcinoid) 2010–2021 were included in this analysis. The most common sites of origin were pancreas (44%) and lung (29%). The initial dose was decided by the treating physician based on clinical assessment and 25 patients (48%) each were started at 10 mg/day and 5 mg/day. Median progression‐free survival (PFS) following everolimus in the overall cohort was 9.8 months (95% CI: 4.3–15.3), with a statistically significant PFS difference (p =.03) between NET G1/typical carcinoids (42.9 months) and NET G2/atypical carcinoids (8.9 months). PFS was numerically but not significantly shorter in patients treated with a reduced dose (7.5 months vs. 12.4 months, p =.359). Even in this mixed full/half dose cohort, 93% developed treatment‐related side effects (mostly grade I, no grade IV), 63% had dose reductions or interruptions, and five stopped due to toxicity. Median survival following treatment was 40.9 months (95% CI: 21.5–60.3) and no difference with regard to dosing was observed (p =.517). These data from an unselected patient cohort show long‐term outcomes similar to those reported in the pivotal studies. Comparing everolimus starting dose, median PFS did not significantly differ for patients treated at a lower dose. While this finding is limited by the sample size and warrants prospective verification, initiating therapy at a reduced dose might be practicable and safe in a distinct subset of patients. [ABSTRACT FROM AUTHOR]

It has been recently shown that in some proteins, tertiary‐structure dynamics occur surprisingly fast, that is on the microsecond or sub‐millisecond time scales. In this State of the Art Review, we discuss how such ultrafast domain motions relate to the function of caseinolytic peptidase B (ClpB), a AAA+ disaggregation machine. ClpB is a large hexameric protein that collaborates with cellular chaperone machinery to rescue protein chains from aggregates. We used single‐molecule FRET spectroscopy to capture the dynamics of essential structural elements within this machine. It was found that the middle domain of ClpB, known to act as its activator, toggles between two states much faster than the overall activity cycle of the protein, suggesting a novel mode of continuous, tunable switching. Motions of the N‐terminal domain were observed to restrict the conformational space of the M domain in the absence of a substrate protein, thereby preventing it from tilting and spuriously activating ClpB. Finally, microsecond dynamics of pore loops responsible for substrate pulling through ClpB's central channel, together with their response to specific perturbations, point to a Brownian‐ratchet mechanism for protein translocation. Based on our findings, we propose a two‐time‐scale model for the activity of ClpB, in which fast conformational dynamics affect slower functional steps, determined by ATP hydrolysis time. Future work on this and other proteins is likely to shed further light on the role of ultrafast dynamics on protein function. [ABSTRACT FROM AUTHOR]

Summary Statement: We propose to add some aspects that are of great complementary importance to broaden the kin recognition, discrimination and selection framework in plants and that need to be considered in future studies. [ABSTRACT FROM AUTHOR]

Long‐distance dispersal is a key factor explaining the success of invasive alien species, particularly across oceanic islands. However, it is often not feasible to reliably measure long‐distance seed dispersal (LDD) over many kilometers in the field. Here, we used a three‐dimensional kinematic trajectory model (Computing Atmospheric Trajectory tool [CAT]) initiated on the basis of regional wind field data to assess the potential for LDD of a wind‐dispersed invasive tree, Spathodea campanulata (African tulip tree), across the Society Islands (French Polynesia, South Pacific Ocean) following its initial planting and spread on the island of Tahiti. The main objective of our study was to determine whether S. campanulata could be expected to spread naturally among islands. Atmospheric dynamics, seed terminal velocity, precipitation, and temperature of air masses were considered to assess the potential for LDD between oceanic islands, with the island of Tahiti serving as the island source for multiple, geographically distant invasions. Aerial trajectories of modeled S. campanulata seeds indicated that wind‐dispersed seeds originating from trees on the island of Tahiti could reach most of the Society Islands and disperse as far as 1364 km. This result suggests that Spathodea can be expected to spread naturally among the Society Islands. When rainfall events were modeled as causal agents of seed settlement, fewer seeds reached distant islands, but more seeds settled on the closest island (20 km away). Including effects of island topography ("barrier effects") also resulted in more seeds settling on the closest island and fewer seeds reaching the most distant islands. Overall, our findings suggest that recent atmospheric models can provide valuable insights into LDD and invasion patterns of wind‐dispersed invasive species. [ABSTRACT FROM AUTHOR]

Background: Recent proposals of high dose rate plans in protontherapy as well as very short proton bunches may pose problems to current beam monitor systems. There is an increasing demand for real‐time proton beam monitoring with high temporal resolution, extended dynamic range and radiation hardness. Plastic scintillators coupled to optical fiber sensors have great potential in this context to become a practical solution towards clinical implementation. Purpose: In this work, we evaluate the capabilities of a very compact fast plastic scintillator with an optical fiber readout by a SiPM and electronics sensor which has been used to provide information on the time structure at the nanosecond level of a clinical proton beam. Materials and methods: A 3 × 3 × 3 mm3 plastic scintillator (EJ‐232Q Eljen Technology) coupled to a 3 × 3 mm2 SiPM (MicroFJ‐SMA‐30035, Onsemi) has been characterized with a 70 MeV clinical proton beam accelerated in a Proteus One synchrocyclotron. The signal was read out by a high sampling rate oscilloscope (5 GS/s). By exposing the sensor directly to the proton beam, the time beam profile of individual spots was recorded. Results: Measurements of detector signal have been obtained with a time sampling period of 0.8 ns. Proton bunch period (16 ns), spot (10 μs) and interspot (1 ms) time structures could be observed in the time profile of the detector signal amplitude. From this, the RF frequency of the accelerator has been extracted, which is found to be 64 MHz. Conclusions: The proposed system was able to measure the fine time structure of a clinical proton accelerator online and with ns time resolution. [ABSTRACT FROM AUTHOR]

Purpose: In ultrahigh dose rate radiotherapy, the FLASH effect can lead to substantially reduced healthy tissue damage without affecting tumor control. Although many studies show promising results, the underlying biological mechanisms and the relevant delivery parameters are still largely unknown. It is unclear, particularly for scanned proton therapy, how treatment plans could be optimized to maximally exploit this protective FLASH effect. Materials and Methods: To investigate the potential of pencil beam scanned proton therapy for FLASH treatments, we present a phenomenological model, which is purely based on experimentally observed phenomena such as potential dose rate and dose thresholds, and which estimates the biologically effective dose during FLASH radiotherapy based on several parameters. We applied this model to a wide variety of patient geometries and proton treatment planning scenarios, including transmission and Bragg peak plans as well as single‐ and multifield plans. Moreover, we performed a sensitivity analysis to estimate the importance of each model parameter. Results: Our results showed an increased plan‐specific FLASH effect for transmission compared with Bragg peak plans (19.7% vs. 4.0%) and for single‐field compared with multifield plans (14.7% vs. 3.7%), typically at the cost of increased integral dose compared to the clinical reference plan. Similar FLASH magnitudes were found across the different treatment sites, whereas the clinical benefits with respect to the clinical reference plan varied strongly. The sensitivity analysis revealed that the threshold dose as well as the dose per fraction strongly impacted the FLASH effect, whereas the persistence time only marginally affected FLASH. An intermediate dependence of the FLASH effect on the dose rate threshold was found. Conclusions: Our model provided a quantitative measure of the FLASH effect for various delivery and patient scenarios, supporting previous assumptions about potentially promising planning approaches for FLASH proton therapy. Positive clinical benefits compared to clinical plans were achieved using hypofractionated, single‐field transmission plans. The dose threshold was found to be an important factor, which may require more investigation. [ABSTRACT FROM AUTHOR]

We review the current status of proton FLASH experimental systems, including preclinical physical and biological results. Technological limitations on preclinical investigation of FLASH biological mechanisms and determination of clinically relevant parameters are discussed. A review of the biological data reveals no reproduced proton FLASH effect in vitro and a significant in vivo FLASH sparing effect of normal tissue toxicity observed with multiple proton FLASH irradiation systems. Importantly, multiple studies suggest little or no difference in tumor growth delay for proton FLASH when compared to conventional dose rate proton radiation. A discussion follows on future areas of development with a focus on the determination of the optimal parameters for maximizing the therapeutic ratio between tumor and normal tissue response and ultimately clinical translation of proton FLASH radiation. [ABSTRACT FROM AUTHOR]

Aquaculture conditions expose fish to internal and environmental stressors that increase their susceptibility to morbidity and mortality. The brain accumulates stress signals and processes them according to the intensity, frequency duration and type of stress, recruiting several brain functions to activate the autonomic or limbic system. Triggering the autonomic system causes the rapid release of catecholamines, such as adrenaline and noradrenaline, into circulation from chromaffin cells in the head kidney. Catecholamines trigger blood cells to release proinflammatory and regulatory cytokines to cope with acute stress. Activation of the limbic axis stimulates the dorsolateral and dorsomedial pallium to process emotions, memory, behaviour and the activation of preoptic nucleus‐pituitary gland‐interrenal cells in the head kidney, releasing glucocorticoids, such as cortisol to the bloodstream. Glucocorticoids cause downregulation of various immune system functions depending on the duration, intensity and type of chronic stress. As stress persists, most immune functions, with the exception of cytotoxic functions, overcome these effects and return to homeostasis. The deterioration of cytotoxic functions during chronic stress appears to be responsible for increased morbidity and mortality. [ABSTRACT FROM AUTHOR]

Abstract: Mutual position of imine and boronic acid moieties in ortho regioisomer of ((ferrocenylimino)methyl)phenylboronic acid (1 a) facilitates and highly favours reversible molecular switching between C=N imine and COR‐NH hemiaminal group. These two states are controllable electrochemically by oxidation/reduction of ferrocenyl moiety and thus a simple dynamic molecular switch for addition/elimination of nucleophile to/from the imine is formed. The exceptional redox behaviour of 1 a in protic primary alcohols is caused by the interaction of both the motif of the boronic acid moiety and imine carbon atom with the alcohol molecule. Thus, the behaviour of acids 1 is influenced by the type of solvent, oxidation state of the ferrocenyl residue and proximity of the boronic acid moiety. Moreover, other multiple equilibria covering majority of possible interactions of imine group and boronic acid moiety with surroundings including influence of various O‐nucleophiles have been addressed and described in detail within the interest in understanding the fundamental factors governing the B–N interaction. [ABSTRACT FROM AUTHOR]

Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, has anticancer effects mediated, at least in part, by parasite-derived products which inhibit growth of tumor cells. We investigated whether immunity to T. cruzi antigens could induce antitumor activity, using two rat models which reproduce human carcinogenesis: colon cancer induced by 1,2-dimethylhydrazine (DMH), and mammary cancer induced by N-nitroso- N-methylurea (NMU). We found that vaccination with T. cruzi epimastigote lysates strongly inhibits tumor development in both animal models. Rats immunized with T. cruzi antigens induce activation of both CD4+ and CD8+ T cells and splenocytes from these animals showed higher cytotoxic responses against tumors as compared to rats receiving adjuvant alone. Tumor-associated immune responses included increasing number of CD11b/c+ His48− MHC II+ cells corresponding to macrophages and/or dendritic cells, which exhibited augmented NADPH-oxidase activity. We also found that T. cruzi lysate vaccination developed antibodies specific for colon and mammary rat cancer cells, which were capable of mediating antibody-dependent cellular cytotoxicity (ADCC) in vitro. Anti- T. cruzi antibodies cross-reacted with human colon and breast cancer cell lines and recognized 41/60 (68%) colon cancer and 38/63 (60%) breast cancer samples in a series of 123 human tumors. Our results suggest that T. cruzi antigens can evoke an integrated antitumor response involving both the cellular and humoral components of the immune response and provide novel insights into the understanding of the intricate relationship between parasite infection and tumor growth. [ABSTRACT FROM AUTHOR]

Normal vision depends on the retinal pigmented epithelium (RPE), a metabolic cell layer that is vital to the development and function of the adjacent retinal photoreceptors. The LIM‐homeodomain transcription factor Lhx2 is important key factor for generation of the progenitors of both RPE and retina during early stages of eye development and is also essential for the generation of different stem cells giving rise to multiple types of organs. The purpose of this project is to understand the gene regulatory network (GRN) and the cis‐regulatory sequences bound by Lhx2/LHX2 in mouse and human in the developing and mature retinal pigment epithelium (RPE) of mammals. The methods include functional studies in vivo using Cre/loxP and knockdown approaches in RPE derived from human embryonic stem cells (hES‐RPE). The functional studies are combined with analyses of the global molecular changes, by identifying and characterizing cis‐regulatory regions bound by the complex and the impact of the mutation on gene expression and tissue differentiation. The results reveal essential role for Lhx2 in maintaining RPE fate in the embryonic optic cup and in differentiated hES‐RPE. Lhx2 seems to function as direct regulator of tissue specific transcription factors as well as cytoskeletal and cell adhesion genes. Conclusions: the GRN and the cis regulatory sequences identified provide novel insight on the activity of an important developmental regulator in controlling RPE differentiation, morphology and function in mice and humans. [ABSTRACT FROM AUTHOR]

Purpose Treatment for adolescents with eating disorders ( ED) is multidimensional and extends after hospitalization. After participating in a four-step reintegration plan, treatment success including post-discharge community and social reintegration were examined from perspectives of patients, family members, and healthcare providers. Design and Methods Six pairs of patients and parents, and seven parents without their children were interviewed 2 to 30 months following discharge. Results All but two adolescents were enrolled in, or had completed school. Five worked in addition to school, and three completed army or national service. Twelve were receiving therapeutic care in the community. Practice Implications Adolescents with ED can benefit from a systematic reintegration program, and nurses should incorporate this into care plans. [ABSTRACT FROM AUTHOR]

Rationale Shape-persistent macrocycles (SPMs) represent innovative molecular building blocks for the development of highly organised supramolecular architectures with application in nanotechnology, chemistry, catalysis and optoelectronics. Systematic mass spectrometric characterisation of SPMs and their collision-activated decay is not available to date. Methods Characterisation of alkoxy-decorated SPMs was performed by matrix-assisted laser desorption/ionisation quadrupole ion trap time-of-flight mass spectrometry (MALDI-QIT-TOFMS) and collision-induced dissociation (CID). Results Laser excitation of SPMs leads to the formation of stable cation radicals which show characteristic fragmentation patterns. All the product ions formed were identified. Photoelectrons generated during the MALDI process and full-ring conjugation were found to be fundamental for the formation of molecular cation radicals and their stabilisation, respectively. Formation of supramolecular aggregates of SPMs by π-π stacking was proven. SPMs are suitable motifs for the preparation of novel fullerene-based donor-acceptor systems. Conclusions Alkoxy-decorated SPMs represent promising electron-donating building blocks that can be exploited in electronics and optoelectronics for the development of robust and highly efficient laser-activated supramolecular switches. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

1,3-Diethynylbicyclo[1.1.1]pentane (DEBCP) has been found to be a valuable molecular building block mostly for the synthesis of extended, rigid, rod-like molecules. With its straightforward linear geometry, DEBCP can be used as a nonconjugated alternative to more frequently used π-conjugated, rod-like building blocks. Examples of reactions that introduce DEBCP into larger structures are (1) the reaction of DEBCP lithium acetylides with electrophiles such as TMSCl, CO2, and Ph2PCl, (2) Sonogashira-Hagihara cross-coupling reactions with aryl or heteroaryl iodides or bromides, and (3) umpolung reactions that afford the corresponding dibromo and diiodo derivatives of DEBCP, which then successfully react with tert- C-cuprates derived from p- and m-dicarbadodecaboranes or bicyclopentanes. These umpolung reactions afforded a new class of molecular rods that combine carborane or bicyclo[1.1.1]pentane cages with ethynylene linkers. Many of the DEBCP derivatives were studied by single-crystal X-ray diffraction. They form well-organized arrays of molecular rotors, the DEBCP units, and so can be considered as examples of artificial molecular-size machines. [ABSTRACT FROM AUTHOR]

Background In a variety of malignant diseases, molecular targeting represents a therapeutic option, whereby, when compared with chemotherapy, fewer side effects are thought to be expected. Especially in renal cell cancer (RCC), tyrosine kinase-inhibitors have been established as useful and highly effective therapy. However, tyrosine kinase-inhibitors currently approved for RCC treatment lack single molecule specificity and bear a variety of side effects of the gastro-intestinal tract, skin, heart and haematopoietic system. Therefore, the identification of novel cell surface markers is sought, which might lead to novel diagnostic and therapeutic strategies in cancer. Material and methods Paraffin-embedded RCCs from a well characterized tissue bank were immunohistochemically quantified for embryonic transmembrane antigen CD98hc (SLC3A2) expression and semi-quantitative analyses were correlated with subtype or grade of differentiation. Results We found increased CD98hc expression in different types of malign RCCs, among them clear cell (cc)RCC, papillary (p)RCC and chromophobe (ch)RCC, but lack of expression in the benign renal oncocytoma. Thereby, the extent of CD98hc expression directly complies with grade of malignancy. Furthermore, the more malignant type II pRCC significantly higher expressed CD98hc than the less malignant and more differentiated type I pRCC (type II 83·34%, type I 4·76% CD98hc positive, P < 0·00001; n = 51). The established marker for type I pRCC, Cytokreatin 7, showed 95·24% expression in type I and 26·67% expression in type II pRCC ( P < 0·00001, n = 51). Conclusions From these data, we conclude that CD98hc is expressed in RCCs, whereby the extent of expression is likely to correlate directly with grade of malignancy. In pRCCs, CD98hc might represent a novel and reliable marker for type II pRCC. [ABSTRACT FROM AUTHOR]

A simple device to check the machine output in rotational mode is described. Integral and instantaneous beam output in absolute dose can be measured and analyzed in a very simple manner. A method to correlate the results with the value obtained during the machine calibration in static beam and the reference value used by the treatment planning system for dose calculation in rotation beam is also described. Using this method and device, the daily output can be performed in rotational conditions which are closer to the treatment conditions. Measurement results using this device show differences in the beam output between static and rotational delivery which have to be considered carefully during the calibration process. [ABSTRACT FROM AUTHOR]

Background: Platelet-derived growth factor (PDGF)-AA isoform and its receptor, PDGF-α receptor (PDGFRA) regulate tooth development and growth. We investigated the expression of both proteins in ameloblastomas, to contribute the understanding of the potential role of the PDGF/PDGFR system in this odontogenic neoplasm. Method: Twenty-nine specimens of ameloblastoma were analyzed for PDGF-AA and PDGFRA expression using immunohistochemistry. The proliferation activity was investigated with the MIB-1 antibody. Additionally, capillary sequencing of genomic DNA was performed to search for mutations in therapeutically relevant exons 12 and 18 of the PDGFRA gene. Results: PDGF-AA and PDGFRA expression were detectable in all cases with the exception of one tumor. However, protein expression levels did neither correlate with each other nor with MIB-1 expression. Unicystic ameloblastomas did not differ from solid tumors with regard to PDGF-AA, PDGFRA, and MIB-1 expression. One tumor revealed a somatic mutation of exon 12 of the PDGFRA gene. Conclusion: PDGF-AA and PDGFRA proteins are regularly expressed in variable levels in ameloblastomas, and somatic mutations of exon 12 and exon 18 of the PDGFRA gene are rare findings. [ABSTRACT FROM AUTHOR]

As often happens, the huge interest in prostate cancer is reflected in the many papers which appear in press, and this is the case in this section, with other papers on renal and testicular cancer. However, the papers come from a wide variety of countries from all over the world: Austria, USA, Japan, UK, Italy, Germany and Canada. It is very pleasing to see the international motif of the Journal being maintained. OBJECTIVE To assess the changing distribution of stage in seminoma and nonseminomatous germ cell tumours (NSGCTs), as recent reports contained no detailed information on pT stage and vascular invasion, important factors in the decision for further treatment. PATIENTS AND METHODS Histopathological reports from 1976 to 2005, from patients who had surgery for testicular tumours at the authors’ institution, were investigated with special focus on pT stage and its distribution. The whole study period was divided into six 5-year periods. The incidence of seminoma was compared with NSGCT, defined according to the Tumour-Nodes-Metastasis (TNM) classification. RESULTS In each 5-year period the median number of tumours treated surgically was 86; the distribution of seminomas and NSGCTs remained stable during the study period ( P = 0.201). pT4 and pT3 tumours declined or disappeared in both histopathological groups, while pT2 and pT1 tumours increased during the study period. Since 1996–2000, pT1 tumours decreased, whereas pT2 tumours increased in seminomas ( P = 0.085) and NSGCTs ( P = 0.003). CONCLUSION The incidence of seminoma and NSGCT has not changed over the last 30 years in Vienna. With the establishment of vascular invasion in the TNM classification in 1997, the incidence of pT1 decreased while that of pT2 increased. Since then, the incidence of pT1 tumours in seminomas was 45.8% and 29.1% in NSGCT. According to generally accepted treatment guidelines, these patients might need no adjuvant treatment after surgery. [ABSTRACT FROM AUTHOR]

Heme oxygenase-1 (HO-1) is the rate limiting enzyme of heme catabolism whereas indoleamine 2,3 dioxygenase (IDO) catabolizes tryptophan through the kynurenine pathway. We analyzed the expression and biological effects of these enzymes in rat and human breast cancer cell lines. We show that rat (NMU and 13762) but not human cells (MCF-7 and T47D) express HO-1. When overexpressed, we found this enzyme to have anti-proliferative and proapoptotic effects by antioxidant mechanisms in these four cell lines. We show that IDO is expressed by rat and human breast cancer cells. IDO inhibition with 1-MT and siRNA leads to diminished proliferation in rat cells. In contrast, HO-1 negative human cell lines increase proliferation upon IDO inhibition. Since we also demonstrate that IDO inhibits the anti-proliferative HO-1, we propose that IDO has opposite effects on proliferation depending on the coexpression or not of HO-1. We also describe that HO-1 inhibits IDO at the posttranslational level through heme starvation. In vivo, we show that rat normal breast expresses HO-1 and IDO. In contrast, N-nitrosomethylurea-induced breast adenocarcinomas only express IDO. In conclusion, we show that HO-1/IDO cross-regulation modulates apoptosis and proliferation in rat and human breast cancer cells. [ABSTRACT FROM AUTHOR]

Abstract Growth rates, photosynthetic responses and the activity, amount and CO2 affinity of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) were determined for common marine macroalgae grown in seawater (containing 14.5 ± 2.1 µM CO2 ) or CO2 -enriched seawater (averaging 52.8 ± 19.2 µM CO2 ). The algae were grown in 40 L fiberglass tanks (outdoor) for 4–15 weeks and in a field experimental setup for 5 days. Growth rates of the species studied (representing the three major divisions, i.e. Chlorophyta, Rhodophyta and Phaeophyta) were generally not significantly affected by the increased CO2 concentrations in the seawater medium. Rubisco characteristics of algae cultivated in CO2 -enriched seawater were similar to those of algae grown in nonenriched seawater. The lack of response of photosynthetic traits in these aquatic plants is likely to be because of the presence of CO2 concentrating mechanisms (CCMs) which rely on HCO3 – utilization, the inorganic carbon (Ci) form that dominates the total Ci pool available in seawater. Significant changes on the productivity of these particular marine algae species would not be anticipated when facing future increasing atmospheric CO2 levels. [ABSTRACT FROM AUTHOR]

Aims: We observed two oncocytomas with prominent intracytoplasmatic vacuoles. To investigate if this previously undescribed finding is a diagnostic feature and compatible with the diagnosis of oncocytoma, we characterized these vacuoles by electron microscopy and immunohistochemistry. Methods and results: The tumours were analysed by transmission electron microscopy. Immunohistochemistry was performed with antimitochondrial antibody, anti-Golgi-zone antibody, anti-lysozyme antibody and anti-human-trans-Golgi-network antibody. By electron microscopy, the vacuoles were found to be double-membrane-bounded, and some contained fragmented christae. Immunohistochemistry showed a positive reaction of the vacuoles with anti‐mitochondrial antibody. Staining with anti-Golgi-zone antibody, anti-lysozyme antibody and anti-human-trans-Golgi-network antibody was negative. Conclusion: Both tumours are benign oncocytomas. The phenomena of cells with prominent intracytoplasmatic vacuoles is not inconsistent with the diagnosis of oncocytoma. The vacuoles are of mitochondrial origin and may develop, by balloon degeneration, as a mechanism of mitochondrial involution and elimination. [ABSTRACT FROM AUTHOR]

Peripheral giant cell granuloma consists of mononuclear cells and osteoclast-like giant cells. The proliferative ability of peripheral giant cell granuloma is restricted to the mononuclear cell compartment, whereas multinucleated giant cells lack mitotic activity. Although the proliferative compartment of peripheral giant cell granuloma has been investigated in detail, the expression and distribution of proteins regulating apoptosis is unknown. The present study demonstrates strong expression of bak and bax in the majority of giant cells. In contrast, giant cells show only weak positivity for bcl-2 and moderate positivity for bcl-x. Mononuclear cells were negative to weakly positive for bcl-x. Only scattered mononuclear cells were positive for bak, bax and bcl-2. The frequency of apoptotic nuclei detected by TUNEL-staining compared to regular nuclei was 18 times higher in giant cells than in mononuclear cells. In summary, our findings support the presumption that giant cells of bone and soft tissue tumors are reactive cell forms and not of neoplastic origin. [ABSTRACT FROM AUTHOR]