The central nervous system (CNS) represents a complex network of different cells, such as neurons, glial cells, and blood vessels. In tumor pathology, glial cells result in the highest number of ...cancers, and glioblastoma (GB) is considered the most lethal tumor in this region. The development of GB leads to the infiltration of healthy tissue through the interaction between all the elements of the brain network. This results in a GB microenvironment, a complex peritumoral hallo composed of tumor cells and several non-tumor cells (e.g., nervous cells, stem cells, fibroblasts, vascular and immune cells), which might be the principal factor for the ineffective treatment due to the fact that the microenvironment modulates the biologic status of the tumor with the increase in its evasion capacity. Crosstalk between glioma cells and the brain microenvironment finally inhibits the beneficial action of molecular pathways, favoring the development and invasion of the tumor and its increasing resistance to treatment. A deeper understanding of cell-cell interactions in the tumor microenvironment (TME) and with the tumor cells could be the basis for a more efficient therapy.
Multiple Faces of the Glioblastoma Microenvironment Șovrea, Alina Simona; Boșca, Bianca; Melincovici, Carmen Stanca ...
International journal of molecular sciences,
01/2022, Letnik:
23, Številka:
2
Journal Article
Recenzirano
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The tumor microenvironment is a highly dynamic accumulation of resident and infiltrating tumor cells, responsible for growth and invasion. The authors focused on the leading-edge concepts regarding ...the glioblastoma microenvironment. Due to the fact that the modern trend in the research and treatment of glioblastoma is represented by multiple approaches that target not only the primary tumor but also the neighboring tissue, the study of the microenvironment in the peritumoral tissue is an appealing direction for current and future therapies.
Colorectal cancer remains one of the most frequent malignancies (third place at both genders) worldwide in the last decade, owing to significant changes in modern dietary habits. Approximately half ...of the patients develop metastases during the course of their disease. The available therapeutic armamentarium is constantly evolving, raising questions regarding the best approach for improving survival. Bevacizumab remains one of the most widely used therapies for treating metastatic colorectal cancer and can be used after progression. This study aimed to identify the best chemotherapy partner for bevacizumab after progression. We performed a retrospective analysis of patients with metastatic colorectal cancer who were treated with bevacizumab as first- and second-line chemotherapy. Data were collected for 151 patients, 40 of whom were treated with double-dose bevacizumab after the first progression. The two standard chemotherapy regimens combined with bevacizumab were FOLFIRI/CAPIRI and FOLFOX4/CAPEOX. The initiation of first-line treatment with irinotecan-based chemotherapy improved progression-free survival and time to treatment failure but not overall survival. After the first progression, retreatment with the same regimen as that used in the induction phase was the best approach for improving overall survival (median overall survival: 46.5 vs. 27.0 months for the same vs. switched strategy, respectively). No correlations were observed between the dose intensity of irinotecan, oxaliplatin, 5-fluorouracil, or bevacizumab and the overall survival, progression-free survival in the first-/second-line treatment, and time to treatment failure. Interaction between an irinotecan-based regimen as a second-line treatment and double-dose bevacizumab after progression was associated with an improved overall survival (p = 0.06). Initiating systemic treatment with an irinotecan-based regimen in combination with bevacizumab improved the progression-free survival in the first-line treatment and time to treatment failure. In terms of overall survival, bevacizumab treatment after the first progression is better partnered with the same regimen as that used in the induction phase.
Objective: Retinal dehydrogenase 1 (RALDH1) is a cytosolic enzyme which acts both as a source of retinoic acid (RA) and as a detoxification enzyme. RALDH1 has key functions in the midbrain ...dopaminergic system, which influences motivation, cognition, and social behavior. Since dopamine has been increasingly linked to autism spectrum disorders (ASD), we asked whether RALDH1 could contribute to the autistic phenotype. Therefore, we investigated for the first time the levels of RALDH1 in autistic patients. To further assess the detoxification function of RALDH1, we also explored 4-hydroxynonenal protein adducts (4-HNE PAs) and reduced glutathione (GSH) levels. Moreover, considering the effect of testosterone on RALDH1 expression, we measured the second to fourth digit ratio (2D:4D ratio) for both hands, which reflects exposure to prenatal testosterone.
Methods: Male patients with ASD (n=18; age, 62.9±4.3 months) and healthy controls (n=13; age, 78.1±4.9 months) were examined. Erythrocyte RALDH1, serum 4-HNE PAs and erythrocyte GSH levels were measured using colorimetric assays, and digit lengths were measured using digital calipers.
Results: We found significantly lower (−42.9%) RALDH1 levels in autistic patients as compared to controls (p=0.032). However, there was no difference in 4-HNE PAs levels (p=0.368), GSH levels (p=0.586), or 2D:4D ratios (p=0.246 in the left hand, p=0.584 in the right hand) between healthy controls and autistic subjects.
Conclusion: We concluded that a subset of autistic patients had a low RALDH1 level. These results suggest that low RALDH1 levels could contribute to the autistic phenotype by reflecting a dopaminergic dysfunction. KCI Citation Count: 10
The aim of the study was to assess the effects of therapeutic ultrasound (US) on oxidative stress (OS)-induced changes in cultured human chondrocytes (HCH). For this, monolayer HCH were randomized in ...three groups: a control group (CG), a group exposed to OS (OS group), and a group exposed to US and OS (US-OS group). US exposure of the chondrocytes was performed prior to OS induction by hydrogen peroxide. Transmission electron microscopy (TEM) was used to assess the chondrocytes ultrastructure. OS and inflammatory markers were recorded. Malondialdehyde (MDA) and tumor necrosis factor (TNF)-α were significantly higher (p < 0.05) in the OS group than in CG. In the US-OS group MDA and TNF-α were significantly lower (p < 0.05) than in the OS group. Finally, in the US-OS group MDA and TNF-α were lower than in CG, but without statistical significance. TEM showed normal chondrocytes in CG. In the OS group TEM showed necrotic chondrocytes and chondrocytes with a high degree of vacuolation and cell organelles damages. In the US-OS group the chondrocytes ultrastructure was well preserved, and autophagosomes were generated. In conclusion, US could protect chondrocytes from biochemical (lipid peroxidation, inflammatory markers synthesis) and ultrastructural changes induced by OS and could stimulate autophagosomes development.
Recent studies suggest a possible involvement of low paraoxonase 1 (PON1) enzyme activities in the association between schizophrenia, treatment with atypical antipsychotics and increased ...cardiovascular (CVD) risk. In the present study, we aimed at investigating the PON1 status in a group of schizophrenic patients treated with either olanzapine or other antipsychotic, as compared to a group of healthy control participants.
We assessed the arylesterase (AREase) and paraoxonase (POase) activities of PON1, as well as three common polymorphisms of
gene (Q192R, L55M, -108C＞T).
We found significantly lower (-13.3%) AREase activity in schizophrenic patients, along with significantly lower (-18.2%) POase activity in olanzapine-treated patients with QQ genotype. Furthermore, we found a significant difference between groups in L55M polymorphism distribution, whereas Q192R and -108C＞T polymorphisms distributions were similar.
We identified the olanzapine-treated patients with QQ genotype as having the lowest PON1 (POase) activity, providing a possible way of identifying schizophrenic patients exposed to the greatest risk of CVD.
Serum paraoxonase-1 (PON1) binds mainly to high density lipoproteins (HDLs) and protects low density lipoproteins (LDLs) against oxidation. While paraoxonase and arylesterase activities are ...traditionally assayed, lactonase activity, accounting for protection against LDL oxidation, was less investigated in obese children and adolescents. Therefore, we aimed to measure lactonase, paraoxonase and arylesterase activities, oxidized LDL (ox-LDL) and malondialdehyde (MDA) levels in obese children and adolescents.
Study population included 68 children (35 obese and 33 normal-weight). Arylesterase and paraoxonase activities were assayed spectrophotometrically. Lactonase activity, ox-LDL and MDA levels were measured using a pH-sensitive colorimetric assay, an ELISA technique and a fluorimetric method, respectively. The lipid profile was assessed by common methods.
Lactonase and arylesterase activities were decreased in the presence of obesity. MDA, but not ox-LDL levels, showed significant differences between groups. Multiple regression analysis identified a reciprocal relationship and a possible association between lactonase and arylesterase activities and obesity.
Abstract Introduction Hyperhomocysteinemia is considered an independent risk factor for cardiovascular disease. Oxidative stress is one of the major pathogenic mechanisms in non-alcoholic fatty liver ...disease and atherosclerosis. Aim Our study aimed to evaluate serum homocysteine levels and oxidative stress in patients with biopsy-proven non-alcoholic steatohepatitis and possible association with cardiovascular risk measured by carotid artery intima-media thickness (c-IMT). Patients and methods 50 patients with non-alcoholic steatohepatitis and 30 healthy controls, age and gender matched, were recruited. Lipid profile, liver biochemical markers, serum homocysteine, vitamins B6 and B12, folic acid, glutathione (reduced and total), erythrocyte superoxide dismutase, whole blood glutathione peroxidase, malondialdehyde and carotid intima-media thickness were assayed. Results Patients had an altered lipid profile and liver biochemical markers; carotid intima-media thickness and serum homocysteine levels were significantly higher compared to controls, but there were no differences in folate, B12 and B6 vitamins levels. Patients had significantly lower levels of glutathione peroxidase activity, total and reduced glutathione and higher levels of malondialdehyde, but unchanged superoxide dismutase activity compared to control group. Also, serum homocysteine level showed significant positive correlation with waist circumference, body mass index, free cholesterol, triglycerides, LDL-cholesterol, amino transferases and negative correlation with reduced and total glutathione, superoxide dismutase and γ-GT. Conclusion Non-alcoholic steatohepatitis is an independent cardiovascular risk factor, associated with elevated homocysteine levels, oxidative stress and c-IMT. c-IMT could be used as an indicator of early atherosclerotic changes initiated by dyslipidemia and oxidative stress, while higher level of homocysteine might be an effect of liver damage.
Zinc (Zn) and copper (Cu) are important trace elements for cognitive development and normal neurological functioning. Autism spectrum disorder (ASD) is a common neurological disorder, which has ...previously been associated with the levels of some trace elements in the blood. However, clinical data regarding the potential implication of Zn and Cu in patients with ASD are still insufficient. Therefore, the aim of the present study was to investigate the whole blood levels of Zn and Cu in a cohort of 28 children with ASD and 28 age- and gender-matched healthy controls. Whole blood Zn and Cu levels were assessed using inductively-coupled plasma-sector field mass spectrometry. Both in the control and in the ASD group, the values of whole blood Cu and Zn were characterized by a Gaussian distribution. The results indicate that the ASD children were characterized by ~10 % (
p
= 0.005) and ~12 % (
p
= 0.015) lower levels of whole blood Zn and Zn/Cu ratio, respectively, in comparison to controls. No significant difference in whole blood Cu was observed. However, Cu/Zn ratio was ~15 % (
p
= 0.008) higher in ASD children than that in the control ones. The results of the present study may be indicative of Zn deficiency in ASD children. Taking into account Zn-mediated up-regulation of metallothionein (MT) gene expression, these findings suggest a possible alteration in the functioning of the neuroprotective MT system. However, further investigations are required to test this hypothesis.
Autism is a behaviorally defined disorder of unknown etiology that is thought to be influenced by genetic and environmental factors. High levels of homocysteine and oxidative stress are generally ...associated with neuropsychiatric disorders. The purpose of this study was to compare the level of homocysteine and other biomarkers in children with autism to corresponding values in age-matched healthy children. We measured total homocysteine (tHcy), vitamin B
12, paraoxonase and arylesterase activities of human paraoxonase 1 (PON1) in plasma and glutathione peroxidase (GPx) activity in erythrocytes from 21 children: 12 with autism (age: 8.29
±
2.76 years) and 9 controls (age: 8.33
±
1.82 years). We found statistically significant differences in tHcy levels and in arylesterase activity of PON1 in children with autism compared to the control group: 9.83
±
2.75 vs. 7.51
±
0.93 μmol/L (
P
≤
0.01) and 72.57
±
11.73 vs. 81.83
±
7.39 kU/L (
P
≤
0.005). In the autistic group there was a strong negative correlation between tHcy and GPx activity and the vitamin B
12 level was low or suboptimal. In conclusion, our study shows that in children with autism there are higher levels of tHcy, which is negatively correlated with GPx activity, low PON1 arylesterase activity and suboptimal levels of vitamin B
12.
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