Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered. 相似文献
Introduction: The treatment of classical Hodgkin lymphoma (cHL) in children is a story of success. Nowadays, more than 90% of patients are cured and overall survival is nearly 100% at 5 years. Efforts have been made to avoid related effects of therapies; therefore, children are treated using different chemotherapy schemes in comparison with adults.
Areas covered: This review includes a view of the clinical classification and risk assessment in children suffering from HL. The chemotherapy more commonly employed is revisited. The use of PET/CT to evaluate the disease in order to guide therapy is analyzed. New options of chemotherapy and emerging immunotherapy are also included.
Expert opinion: In order to make the right treatment choice, a proper initial assessment of risk is mandatory. The choice of therapy in these kinds of patients must be done according to the experience of the team, and also, the cost and logistics related to the eligible scheme are very important. If possible, efforts must be made to include PET/CT in guiding therapy and avoiding overtreatment and long-term adverse effects in children. New options in immunotherapy are emerging and must be considered with caution in selected patients. 相似文献
The present study aimed at measuring seropositivities for infection by
Ascaris suum and Toxocara canis using the
excretory/secretory (E/S) antigens from Ascaris suum (AES) and
Toxocara canis (TES) within an indigenous population. In
addition, quantification of cytokine expressions in peripheral blood cells was
determined. A total of 50 Warao indigenous were included; of which 43 were adults and
seven children. In adults, 44.1% were seropositive for both parasites; whereas
children had only seropositivity to one or the other helminth. For ascariosis, the
percentage of AES seropositivity in adults and children was high; 23.3% and 57.1%,
respectively. While that for toxocariosis, the percentage of TES seropositivity in
adults and children was low; 9.3% and 14.3%, respectively. The percentage of
seronegativity was comparable for AES and TES antigens in adults (27.9%) and children
(28.6%). When positive sera were analyzed by Western blotting technique using AES
antigens; three bands of 97.2, 193.6 and 200.2 kDas were mostly recognized. When the
TES antigens were used, nine major bands were mostly identified; 47.4, 52.2, 84.9,
98.2, 119.1, 131.3, 175.6, 184.4 and 193.6 kDas. Stool examinations showed that
Blastocystis hominis, Hymenolepis nana and
Entamoeba coli were the most commonly observed intestinal
parasites. Quantification of cytokines IFN-γ, IL-2, IL-6, TGF-β, TNF-α, IL-10 and
IL-4 expressions showed that there was only a significant increased expression of
IL-4 in indigenous with TES seropositivity (p < 0.002).
Ascaris and Toxocara seropositivity was
prevalent among Warao indigenous. 相似文献
To determine the incidence of incisional hernia (IH) in the extraction incision (EI) in colorectal resection for cancer. To analyze whether the location of the incision has any relationship with the incidence of hernias and whether mesh could be useful for prevention in high-risk patients.
Methods
Retrospective review of the colon and rectal surgery database from January 2015 to December 2016. Data were classified into 2 groups, transverse (TI) and midline incision (MI), and the latter was divided into 2 subgroups (mesh [MIM] and suture [MIS]). Patients were classified using the HERNIAscore. Hernias were diagnosed by clinical and/or CT examination.
Results
A total of 182 out of 210 surgical patients were included. After a median follow-up of 13.0 months, 39 IH (21.9%) were detected, 23 of which (13.4%) were in the EI; their frequency was lower in the TI group (3.4%) and in the MIM group (5.9%) than in the MIS group (29.5%; p = 0.007). The probability of developing IH in the MIS group showed an OR = 11.7 (95%CI: 3.3-42.0) compared to the TI group and 4.3 (IC 95%: 1.1-16.3) versus the MIM group.
Conclusions
The location of the incision is relevant to avoid incisional hernias. Transverse incisions should be used as the first option. When a midline incision is needed, a prophylactic mesh could be considered in high risk patients because it is safe and associated with low morbidity. 相似文献