Performance of automatic image segmentation algorithms for calculating total lesion glycolysis for early response monitoring in non-small cell lung cancer patients during concomitant chemoradiotherapy.

Background and purpose This study evaluated the use of total lesion glycolysis (TLG) determined by different automatic segmentation algorithms, for early response monitoring in non-small cell lung cancer (NSCLC) patients during concomitant chemoradiotherapy.Materials and methods Twenty-seven patients with locally advanced NSCLC treated with concomitant chemoradiotherapy underwent (18)F-fluorodeoxyglucose (FDG) PET/CT imaging before and in the second week of treatment. Segmentation of the primary tumours and lymph nodes was performed using fixed threshold segmentation at (i) 40% SUVmax (T40), (ii) 50% SUVmax (T50), (iii) relative-threshold-level (RTL), (iv) signal-to-background ratio (SBR), and (v) fuzzy locally adaptive Bayesian (FLAB) segmentation. Association of primary tumour TLG (TLGT), lymph node TLG (TLGLN), summed TLG (TLGS=TLGT+TLGLN), and relative TLG decrease (ΔTLG) with overall-survival (OS) and progression-free survival (PFS) was determined using univariate Cox regression models.Results Pretreatment TLGT was predictive for PFS and OS, irrespective of the segmentation method used. Inclusion of TLGLN improved disease and early response assessment, with pretreatment TLGS more strongly associated with PFS and OS than TLGT for all segmentation algorithms. This was also the case for ΔTLGS, which was significantly associated with PFS and OS, with the exception of RTL and T40.Conclusions ΔTLGS was significantly associated with PFS and OS, except for RTL and T40. Inclusion of TLGLN improves early treatment response monitoring during concomitant chemoradiotherapy with FDG-PET

Functional microarray analysis suggests repressed cell-cell signaling and cell survival-related modules inhibit progression of head and neck squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Cancer shows a great diversity in its clinical behavior which cannot be easily predicted using the currently available clinical or pathological markers. The identification of pathways associated with lymph node metastasis (N+) and recurrent head and neck squamous cell carcinoma (HNSCC) may increase our understanding of the complex biology of this disease.</p> <p>Methods</p> <p>Tumor samples were obtained from untreated HNSCC patients undergoing surgery. Patients were classified according to pathologic lymph node status (positive or negative) or tumor recurrence (recurrent or non-recurrent tumor) after treatment (surgery with neck dissection followed by radiotherapy). Using microarray gene expression, we screened tumor samples according to modules comprised by genes in the same pathway or functional category.</p> <p>Results</p> <p>The most frequent alterations were the repression of modules in negative lymph node (N0) and in non-recurrent tumors rather than induction of modules in N+ or in recurrent tumors. N0 tumors showed repression of modules that contain cell survival genes and in non-recurrent tumors cell-cell signaling and extracellular region modules were repressed.</p> <p>Conclusions</p> <p>The repression of modules that contain cell survival genes in N0 tumors reinforces the important role that apoptosis plays in the regulation of metastasis. In addition, because tumor samples used here were not microdissected, tumor gene expression data are represented together with the stroma, which may reveal signaling between the microenvironment and tumor cells. For instance, in non-recurrent tumors, extracellular region module was repressed, indicating that the stroma and tumor cells may have fewer interactions, which disable metastasis development. Finally, the genes highlighted in our analysis can be implicated in more than one pathway or characteristic, suggesting that therapeutic approaches to prevent tumor progression should target more than one gene or pathway, specially apoptosis and interactions between tumor cells and the stroma.</p

Раціональність як реляційність: синтетична єдність відмінностей в трансцендентальному просторі границі

У статті висвітлюються проблеми «постсучасної» раціональності, визначальною характеристикою котрої покладається іманентна пограничність. Відношення та Іншість розглядаються як визначальні предикати раціональності, які в класичній парадигмі імплікують принципи рефлексійності, конструктивності, співмірності. Корелятами означених принципів у постструктуралістській раціональності визначаються повторність (ітеративність), фрагментарність, подвоєння, розрізняння. Конгруентність класичної та постсучасної раціональності зумовлена еквівалентністю понять трансцендентальності та пограничності. Синтетична єдність (розбіжність та зв'язок) з її специфікацією принципами пов’язання та розрізняння, визначається через медіативну функцію судження, структура якого фундується параметрами реляційності.В статье освещаются проблемы «постсовременной» рациональности, определяющей характеристикой которой полагается имманентная пограничность. Отношение и Другость рассматриваются как определяющие предикаты рациональности, которые имплицируют принципы рефлексивности, конструктивности, соразмерности в классической парадигме. Коррелятами обозначенных принципов в постструктуралистской рациональности являются повторность (итеративность), фрагментарность, удвоение, различание. Конгруэнтность классической и постсоврменной рациональности обусловлена эквивалентностью понятий трансцендентальности и пограничности. Синтетическое единств (различие и связь) с его спецификацией в позициях увязывания и различания, определяется через медиативную функцию суждения, структура которого фундируется параметрами реляционности.The paper illuminates some problems of the post-contemporary rationality that possesses the immanent borderness as its distinctive feature. The Relationality and the Anotherness are investigaled as the common predicates of rationality that implicate the “classical” principles of reflexity, constructiveness, proportionality. The main principles of the poststructuralistic rationality correlating with the classical ones are recurrence (iterativity), doubleness, fragmentariness, differance. The congruence of the classical rationality and the post-contemporary one is caused by the equivalency of the concepts “transcendentality” and “borderness”. The synthetical unity (relation between deviation and connection) with its specification by the linking and the differance principles is determined by the mediative function of the assertion that is structured by the relationality parameters

Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage

Enzymatically inactive chitinase-like proteins (CLPs) such as BRP-39, Ym1 and Ym2 are established markers of immune activation and pathology, yet their functions are essentially unknown. We found that Ym1 and Ym2 induced the accumulation of neutrophils through the expansion of γδ T cell populations that produced interleukin 17 (IL-17). While BRP-39 did not influence neutrophilia, it was required for IL-17 production in γδ T cells, which suggested that regulation of IL-17 is an inherent feature of mouse CLPs. Analysis of a nematode infection model, in which the parasite migrates through the lungs, revealed that the IL-17 and neutrophilic inflammation induced by Ym1 limited parasite survival but at the cost of enhanced lung injury. Our studies describe effector functions of CLPs consistent with innate host defense traits of the chitinase family

Systematic analysis of 18F-FDG PET and metabolism, proliferation and hypoxia markers for classification of head and neck tumors

Contains fulltext : 136904.pdf (publisher's version ) (Open Access)BACKGROUND: Quantification of molecular cell processes is important for prognostication and treatment individualization of head and neck cancer (HNC). However, individual tumor comparison can show discord in upregulation similarities when analyzing multiple biological mechanisms. Elaborate tumor characterization, integrating multiple pathways reflecting intrinsic and microenvironmental properties, may be beneficial to group most uniform tumors for treatment modification schemes. The goal of this study was to systematically analyze if immunohistochemical (IHC) assessment of molecular markers, involved in treatment resistance, and 18F-FDG PET parameters could accurately distinguish separate HNC tumors. METHODS: Several imaging parameters and texture features for 18F-FDG small-animal PET and immunohistochemical markers related to metabolism, hypoxia, proliferation and tumor blood perfusion were assessed within groups of BALB/c nu/nu mice xenografted with 14 human HNC models. Classification methods were used to predict tumor line based on sets of parameters. RESULTS: We found that 18F-FDG PET could not differentiate between the tumor lines. On the contrary, combined IHC parameters could accurately allocate individual tumors to the correct model. From 9 analyzed IHC parameters, a cluster of 6 random parameters already classified 70.3% correctly. Combining all PET/IHC characteristics resulted in the highest tumor line classification accuracy (81.0%; cross validation 82.0%), which was just 2.2% higher (p = 5.2x10-32) than the performance of the IHC parameter/feature based model. CONCLUSIONS: With a select set of IHC markers representing cellular processes of metabolism, proliferation, hypoxia and perfusion, one can reliably distinguish between HNC tumor lines. Addition of 18F-FDG PET improves classification accuracy of IHC to a significant yet minor degree. These results may form a basis for development of tumor characterization models for treatment allocation purposes

Time and Energy Management During Approach: A Human-in-the-Loop Study

Control & SimulationControl & Operation