Optical manipulation of Saccharomyces cerevisiae cells reveals that green light protection against UV irradiation is favored by low Ca2+ and requires intact UPR pathway

AbstractOptical manipulation of Saccharomyces cerevisiae cells with high density green photons conferred protection against the deleterious effects of UV radiation. Combining chemical screening with UV irradiation of yeast cells, it was noted that the high density green photons relied on the presence of intact unfolded protein response (UPR) pathway to exert their protective effect and that the low Ca2+ conditions boosted the effect. UPR chemical inducers tunicamycin, dithiotreitol and calcium chelators augmented the green light effect in a synergic action against UV-induced damage. Photo-manipulation of cells was a critical factor since the maximum protection was achieved only when cells were pre-exposed to green light

Validation of a New Prognostic Score in Patients with Ovarian Adenocarcinoma

Background and Objectives: This study aimed to assess the impact of clinical prognostic factors and propose a prognostic score that aids the clinician’s decision in estimating the risk for patients in clinical practice. Materials and Methods: The study included 195 patients diagnosed with ovarian adenocarcinoma. The therapeutic strategy involved multidisciplinary decisions: surgery followed by adjuvant chemotherapy (80%), neoadjuvant chemotherapy followed by surgery (16.4%), and only chemotherapy in selected cases (3.6%). Results: After a median follow-up of 68 months, in terms of progression-free survival (PFS) and overall survival (OS), Eastern Cooperative Oncology Group (ECOG) performance status of 1 and 2 vs. 0 (hazard ratio—HR = 2.71, 95% confidence interval—CI, 1.96–3.73, p < 0.001 for PFS and HR = 3.19, 95%CI, 2.20–4.64, p < 0.001 for OS), menopausal vs. premenopausal status (HR = 2.02, 95%CI, 1.35–3,0 p < 0.001 and HR = 2.25, 95%CI = 1.41–3.59, p < 0.001), ascites (HR = 1.95, 95%CI 1.35–2.80, p = 0.03, HR = 2.31, 95%CI = 1.52–3.5, p < 0.007), residual disease (HR = 5.12, 95%CI 3.43–7.65, p < 0.0001 and HR = 4.07, 95%CI = 2.59–6.39, p < 0.0001), and thrombocytosis (HR = 2.48 95%CI = 1.72–3.58, p < 0.0001, HR = 3.33, 95%CI = 2.16–5.13, p < 0.0001) were associated with a poor prognosis. An original prognostic score including these characteristics was validated using receiver operating characteristic (ROC) curves (area under the curve—AUC = 0.799 for PFS and AUC = 0.726 for OS, p < 0.001). The median PFS for patients with none, one, two, three, or four (or more) prognostic factors was not reached, 70, 36, 20, and 12 months, respectively. The corresponding median overall survival (OS) was not reached, 108, 77, 60, and 34 months, respectively. Conclusions: Several negative prognostic factors were identified: ECOG performance status ≥ 1, the presence of ascites and residual disease after surgery, thrombocytosis, and menopausal status. These led to the development of an original prognostic score that can be helpful in clinical practice

The Dual Action of Epigallocatechin Gallate (EGCG), the Main Constituent of Green Tea, against the Deleterious Effects of Visible Light and Singlet Oxygen-Generating Conditions as Seen in Yeast Cells

Green tea extracts (GTEs) as well as their main component, the polyphenol epigallocatechin gallate (EGCG), are known for their versatile antioxidant, antimicrobial, antitumoral or anti-inflammatory effects. In spite of the huge beneficial action, there is increasing evidence that under certain conditions green tea and its components can be detrimental to living organisms. Using &lt;em&gt;Saccharomyces cerevisiae &lt;/em&gt;strains&lt;em&gt; &lt;/em&gt;with various defects in the response to oxidative stress, we found that GTEs or EGCG act in synergy with visible light, exhibiting either deleterious or protective effects depending on the solvent employed. Similar synergistic effects could be observed under singlet oxygen-generating conditions, such as light exposure in the presence of photosensitizers or UV-A irradiation, therefore solvent variance may represent a powerful tool to modulate the preparation of green tea extracts, depending on the intended target

Impact Behavior of the Ballistic Targets Package Composed of Dyneema Polymer and High Entropy Alloy Structures

Ballistic targets are multi-material assemblies that can be made of various materials, such as metal alloys, ceramics, and polymers. Their role is to provide collective or individual ballistic protection against high-speed dynamic penetrators or kinetic fragments. The paper presents the impact behavior with incendiary perforating bullets having 7.62 mm of ballistic packages made of combinations between Dyneema ultra-high-molecular-weight polyethylene and high entropy alloy from alloying system AlCoCrFeNi, by analyzing the dynamic phenomena (deformation, perforation) that take place at high speeds. The geometry evolution of the physical model subjected to numerical simulation allows a very good control over the discretization network and also allows the export for modeling to nonlinear transient phenomena. The results obtained by numerical simulation showed that the analyzed ballistic package does not allow sufficient protection for values of impact velocities over 500 m/sec

Risk of Myelopathy Following Second Local Treatment after Initial Irradiation of Spine Metastasis

Metastatic lesions of the spine occur in up to 40% of cancer patients and are a frequent source of pain and neurologic deficit due to cord compression. Palliative radiotherapy is the main first-intent local treatment in the form of single-fraction radiotherapy or fractionated courses. Reirradiation is a viable option for inoperable patients where spinal decompression is needed but with an increased risk of radiation-induced myelopathy (RM) and subsequent neurologic damage. This review summarizes reported data on local treatment options after initial irradiation in patients with relapsed spine metastasis and key dosimetric correlations between the risk of spinal cord injury and reirradiation technique, total dose, and time between treatments. The Linear Quadratic (LQ) model was used to convert all the published doses into biologically effective doses and normalize them to EQD2. For 3D radiotherapy, authors used cumulative doses from 55.2 Gy2/2 to 65.5 Gy2/2 EQD2 with no cases of RM mentioned. We found little evidence of RM after SBRT in the papers that met our criteria of inclusion, usually at the median reported dose to critical neural tissue around 93.5 Gy2/2. There is a lack of consistency in reporting the spinal cord dose, which leads to difficulty in pooling data

Antidiabetics, Anthelmintics, Statins, and Beta-Blockers as Co-Adjuvant Drugs in Cancer Therapy

Over the last years, repurposed agents have provided growing evidence of fast implementation in oncology treatment such as certain antimalarial, anthelmintic, antibiotics, anti-inflammatory, antihypertensive, antihyperlipidemic, antidiabetic agents. In this study, the four agents of choice were present in our patients&rsquo; daily treatment for nonmalignant-associated pathology and have known, light toxicity profiles. It is quite common for a given patient&rsquo;s daily administration schedule to include two or three of these drugs for the duration of their treatment. We chose to review the latest literature concerning metformin, employed as a first-line treatment for type 2 diabetes; mebendazole, as an anthelmintic; atorvastatin, as a cholesterol-lowering drug; propranolol, used in cardiovascular diseases as a nonspecific inhibitor of beta-1 and beta-2 adrenergic receptors. At the same time, certain key action mechanisms make them feasible antitumor agents such as for mitochondrial ETC inhibition, activation of the enzyme adenosine monophosphate-activated protein kinase, amelioration of endogenous hyperinsulinemia, inhibition of selective tyrosine kinases (i.e., VEGFR2, TNIK, and BRAF), and mevalonate pathway inhibition. Despite the abundance of results from in vitro and in vivo studies, the only solid data from randomized clinical trials confirm metformin-related oncological benefits for only a small subset of nondiabetic patients with HER2-positive breast cancer and early-stage colorectal cancer. At the same time, clinical studies confirm metformin-related detrimental/lack of an effect for lung, breast, prostate cancer, and glioblastoma. For atorvastatin we see a clinical oncological benefit in patients and head and neck cancer, with a trend towards radioprotection of critical structures, thus supporting the role of atorvastatin as a promising agent for concomitant association with radiotherapy. Propranolol-related increased outcomes were seen in clinical studies in patients with melanoma, breast cancer, and sarcoma

Prognostic Role of Vascular Endothelial Growth Factor and Correlation with Oxidative Stress Markers in Locally Advanced and Metastatic Ovarian Cancer Patients

Background: Vascular endothelial growth factor (VEGF) plays an important role in tumor progression in ovarian cancer, but the complex mechanism and interaction with oxidative stress are not fully understood. Methods: A prospective study included 52 patients with ovarian adenocarcinoma stage IIIA-IV. Serum VEGF and reactive oxygen species (ROS) such as malondialdehyde and ceruloplasmin were measured. Results: VEGF levels were elevated (mean 1014.7 ± 165 pg/mL), especially in patients with macroscopic residual disease (1058 vs. 810 pg/mL, p = 0.0001). Median progression-free survival (PFS) and overall survival (OS) were 6 and 40 months in patients with a very high VEGF (over 1200 pg/mL), 11 and 48 months in patients with VEGF between 1000–1200 pg/mL, 18 and 84 months in patients with VEGF between 800–1000 pg/mL, and not reached in patients with normal VEGF. Increased VEGF values were associated with a 2.6-fold increased risk of disease progression (HR = 2.60, 95% CI 1.69–3.99), and a 1.4-fold increased risk of death (HR = 1.4, 95% CI 1.15–1.91, p = 0.002). Receiver operator characteristic (ROC) curves were used to validate VEGF as a prognostic factor and the area under the curve (AUC) was 0.814, p = 0.036 for PFS and 0.729, p = 0.043, for OS. There was a positive correlation between VEGF and malondialdehyde, Pearson coefficient of 0.35, p = 0.0001. Conclusions: VEGF and malondialdehyde are important prognostic markers in ovarian cancer, especially in macroscopic residual disease, and there is a positive correlation between angiogenesis and oxidative stress

Prognostic Role of Vascular Endothelial Growth Factor and Correlation with Oxidative Stress Markers in Locally Advanced and Metastatic Ovarian Cancer Patients

Background: Vascular endothelial growth factor (VEGF) plays an important role in tumor progression in ovarian cancer, but the complex mechanism and interaction with oxidative stress are not fully understood. Methods: A prospective study included 52 patients with ovarian adenocarcinoma stage IIIA-IV. Serum VEGF and reactive oxygen species (ROS) such as malondialdehyde and ceruloplasmin were measured. Results: VEGF levels were elevated (mean 1014.7 &plusmn; 165 pg/mL), especially in patients with macroscopic residual disease (1058 vs. 810 pg/mL, p = 0.0001). Median progression-free survival (PFS) and overall survival (OS) were 6 and 40 months in patients with a very high VEGF (over 1200 pg/mL), 11 and 48 months in patients with VEGF between 1000&ndash;1200 pg/mL, 18 and 84 months in patients with VEGF between 800&ndash;1000 pg/mL, and not reached in patients with normal VEGF. Increased VEGF values were associated with a 2.6-fold increased risk of disease progression (HR = 2.60, 95% CI 1.69&ndash;3.99), and a 1.4-fold increased risk of death (HR = 1.4, 95% CI 1.15&ndash;1.91, p = 0.002). Receiver operator characteristic (ROC) curves were used to validate VEGF as a prognostic factor and the area under the curve (AUC) was 0.814, p = 0.036 for PFS and 0.729, p = 0.043, for OS. There was a positive correlation between VEGF and malondialdehyde, Pearson coefficient of 0.35, p = 0.0001. Conclusions: VEGF and malondialdehyde are important prognostic markers in ovarian cancer, especially in macroscopic residual disease, and there is a positive correlation between angiogenesis and oxidative stress