scholarly journals Structural and functional state of Heren carcinoma after local fractional X-irradiation and irradiation combined with meloxicam

Author(s):  
O.P. Lukashova

Background. One of the most important problems of oncology is the overcoming of therapeutic resistance of tumors, which occurs in particular due to increased levels of the enzyme cyclooxygenase 2 (COX-2). It is known that the growth of COX-2 and the product of its activity, prostaglandin-E2 in cancer, promotes such processes in the body as tumor growth, stimulation of proliferation, induction of cancer stem cells, inhibition of apoptosis, activation of angiogenesis, invasion, metastasis and development of chemoresistance. The use of COX-2 inhibitors, which are nonsteroidal anti-inflammatory drugs (NSAIDs), significantly limits these processes and improves survival and mortality in cancer patients, and in combination with chemotherapeutics eliminates the resistance they cause. Purpose – study of the structural and functional state of Guerin’s carcinoma cells after the combined use of nonsteroidal anti-inflammatory drug meloxicam and local X-irradiation in total doses of 1.0 and 10 Gy. Materials and methods. On 33 rats with inoculated Guerin’s carcinoma, the ultrastructure of tumor cells (TC) was studied using standard methods of electron microscopy 24 hours after the combined use of the meloxicam drug at a dose of 0.2 mg per 1 kg of body weight one day before the first and 2 hours before the second session fractional local X-irradiation in total doses of 1 and 10 Gy (twice daily at 0.5 and 5.0 Gy, respectively. The mitotic index (the number of cells in the state of mitosis per 100 TC,%), the apoptosis index (the number of cells in the state of apoptotic death per 100 TC,%) and the frequency of TC with small nuclei (%). Results. It was found that irradiation of Guerin’s tumor in a total dose of 10 Gy causes disturbances in the ultrastructure associated with damage to the nuclear apparatus of the TC. Pleiomorphism of the nuclei, the appearance of binucleated cells and micronuclei, a significant decrease in mitotic activity and a slight increase in the apoptosis index are observed. Stimulation of the functional activity of macrophages is also noted. Under irradiation in a total dose of 1 Gy, such effects are less pronounced or completely absent, such as, for example, the processes of phagocytosis. The frequency index of TC with small nuclei is equally reliably increased at both radiation doses. The administration of the drug meloxicam leads to a significant decrease in mitotic activity and an increase in the frequency of small cells, while the ultrastructural picture of the tumor remains almost unchanged. With the combined action of the drug and radiation in both doses, violations of the fine structure of the OC are identical to those found during irradiation. At the same time, the mitotic index in the group with the combined effect of the drug and radiation at a dose of 10 Gy is significantly lower than with only irradiation.In addition, at both doses, the frequency of small forms of PC significantly increases in comparison with the indicators of both the intact control group and the corresponding irradiation groups. Only in combination with radiation does meloxicam reliably stimulate apoptosis, while in other groups its index remains at the level of control values. The relationship was confirmed, which was constantly revealed in all experimental groups, between a decrease in the level of the mitotic index and an increase in the frequency of TC with small nuclei in Guerin’s carcinoma. An inverse correlation was found between these indicators (r = 0.80, P = 0.05). Conclusions. The combined action of the drug and irradiation significantly increases the effectiveness of both therapeutic factors due to the property of meloxicam to reliably inhibit proliferative activity and promote post-radiation development of apoptosis in tumor tissue. The presence of a correlation between the mitotic index and the frequency of cells with small nuclei in Guerin’s tumor may indicate the relationship between cell growth and division. Under the combined action of both investigated factors, changes in the tumor ultrastructure are mainly caused by irradiation. The administration of meloxicam increases the efficiency of the combined use of both therapeutic agents due to its ability to reliably inhibit proliferative activity and promote post-radiation development of apoptosis in tumor tissue. The presence of a correlation dependence between the mitotic index and the frequency of cells with small nuclei in Guerin’s tumor may indicate the relationship between the processes of cell growth and division.

Author(s):  
Lovel Kukuljan ◽  
Franci Gabrovšek ◽  
Matthew D. Covington ◽  
Vanessa E. Johnston

AbstractUnderstanding the dynamics and distribution of CO2 in the subsurface atmosphere of carbonate karst massifs provides important insights into dissolution and precipitation processes, the role of karst systems in the global carbon cycle, and the use of speleothems for paleoclimate reconstructions. We discuss long-term microclimatic observations in a passage of Postojna Cave, Slovenia, focusing on high spatial and temporal variations of pCO2. We show (1) that the airflow through the massif is determined by the combined action of the chimney effect and external winds and (2) that the relationship between the direction of the airflow, the geometry of the airflow pathways, and the position of the observation point explains the observed variations of pCO2. Namely, in the terminal chamber of the passage, the pCO2 is low and uniform during updraft, when outside air flows to the site through a system of large open galleries. When the airflow reverses direction to downdraft, the chamber is fed by inlets with diverse flow rates and pCO2, which enter via small conduits and fractures embedded in a CO2-rich vadose zone. If the spatial distribution of inlets and outlets produces minimal mixing between low and high pCO2 inflows, high and persistent gradients in pCO2 are formed. Such is the case in the chamber, where vertical gradients of up to 1000 ppm/m are observed during downdraft. The results presented in this work provide new insights into the dynamics and composition of the subsurface atmosphere and demonstrate the importance of long-term and spatially distributed observations.


Author(s):  
Kevin A. Rider ◽  
Bernard J. Martin

Terrain-induced vibration of a moving vehicle adversely affects the ability to quickly and accurately perform in-vehicle pointing tasks by altering the planned fingertip trajectory. The relationship between movement speed and accuracy is a result of the combined use of visual and somatosensory feedbacks which are used to discern movement deviations and make necessary compensatory movements. Participants (N=20) performed three-dimensional rapid pointing tasks under stationary and ride motion conditions to three touchpanel displays. Ride motion contributed to increased reaction and movement times and increased endpoint variability. Trajectory deviations were correlated to the principal direction of vehicle acceleration. Reaches orthogonal to the dominant vehicle acceleration exhibited larger endpoint variability, and reaches to the elevated touchpanel resulted in the largest variability across all motion conditions. Principal axes of endpoint ellipses were along the on-axis and off-axis directions of fingertip movement.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Milan Jovanovic ◽  
Nevena Gajovic ◽  
Natasa Zdravkovic ◽  
Marina Jovanovic ◽  
Milena Jurisevic ◽  
...  

Background and Objectives. The aim of the study was to determine systemic and fecal values of galectin-3 and pro- and anti-inflammatory cytokines in patients with CRC and the relationship with clinicopathological aspects. Methods. Concentrations of galectin-3, TNF-α, TGF-β, IL-10, and IL-1β were analyzed in samples of blood and stool of 60 patients with CRC. Results. Systemic concentration of TNF-α was significantly lower in patients with severe diseases (advanced TNM stage, nuclear grade, and poor histological differentiation) as in patients with more progressive CRC (lymph and blood vessel invasion, presence of metastasis). Fecal values of anti-inflammatory cytokines TGF-β and IL-10 were increased in patients with severe stadium of CRC. Fecal concentration of Gal-3 was enhanced in CRC patients with higher nuclear grade, poor tumor tissue differentiation, advanced TNM stage, and metastatic disease. Gal-3/TNF-α ratio in sera and feces had a higher trend in patients with severe and advanced diseases. Positive correlation between fecal Gal-3 and disease severity, tumor progression, and biomarkers AFP and CEA, respectively, was also observed. Conclusions. Predomination of Gal-3 in patients with advanced diseases may implicate on its role in limiting ongoing proinflammatory processes. The fecal values of Gal-3 can be used as a valuable marker for CRC severity and progression.


2017 ◽  
Vol 48 (3) ◽  
pp. 616-633 ◽  
Author(s):  
G. Farina ◽  
S. Alvisi ◽  
M. Franchini

This paper presents a procedure for estimating discharge in a river cross-section based on the combined use of dimensionless isovels and point velocity measurements. Specifically, taking the Biot–Savart law on the magnetic field induced by an electric current in a wire as their basis as already done by other researchers, the authors propose a new formulation of the relationship characterizing the effect of the wetted perimeter on the range of velocities in a cross-section in order to take explicit account of roughness, expressed by means of Manning's coefficient. Once appropriately nondimensionalized, the isoeffect contours can be read as dimensionless isovels. Assuming in situ velocity measurements are available, discharge at a cross-section can be computed using two different methods. The proposed procedure was applied to six case studies characterized by river cross-sections which differed greatly from one another. The results show that the two methods proposed for estimating discharge lead to equivalent outcomes, and in all the cases the procedure as a whole enables a sufficiently accurate estimation of discharge, even when it is based on a limited number of velocity measurements or on the measurement of maximum surface-water velocity alone.


2021 ◽  
Author(s):  
Gelena Kakurina ◽  
Olga V Cheremisina ◽  
Elena E Sereda ◽  
Elena S Kolegova ◽  
Irina V Kondakova ◽  
...  

Abstract Purpose: Actin-binding proteins (ABPs) and various signaling systems are involved in the metastasis of squamous cell carcinoma of the larynx and hypopharynx (SCCLH). The clinical significance of these proteins has not yet been determined. We analyzed the relationship between the mRNA level of cofilin 1 (CFL1), profilin 1 (PFN1), adenylyl cyclase-associated protein 1 (CAP1), SNAIL and RND3 with metastasis in the SCCLH tissue. The serum level of the listed ABPs was estimated and the relationship of them with the expression of the corresponding mRNA was carried out. Materials and methods: The expression level of ABPs mRNA was measured by real-time RT-PCR in paired tissue samples taken from 54 patients with SCCLH (T 1-4 N 0-1 M 0 ). Expression analysis was performed using the 2 - ΔΔ CT method. The level of ABPs in the blood serum was measured by ELISA. Statistical analysis was carried out using the SPSS Statistica 20.0 software package. Results: The mRNA expression of the studied genes in tumor tissue of patients with SCCLH T 1-3 N 0 M 0 and T 2-4 N 1-2 M 0 did not differ significantly. High expression of RND3 mRNA was accompanied by an increase in mRNA expression of all studied ABPs. In the blood serum of T 2-4 N 1-2 M 0 patients the level of PFN1 was significantly lower by 21% and the level of CAP1 was higher by 75% compared with the group of patients with T 1-4 N 0 M 0 stage. Conclusion: According to our data RND3 is involved in the regulation of molecular cascades SCCLH metastasis. PFN1 and CAP1 serum level can be a good classifier of metastases in patients with SCCLH.


1960 ◽  
Vol 198 (4) ◽  
pp. 762-764 ◽  
Author(s):  
Bernard D. Newsom ◽  
Donald J. Kimeldorf

The relationship between altitude tolerance and food consumption was investigated in irradiated and nonirradiated animals of several species. Food consumption was measured for 3 days following a mid-lethal dose of x-irradiation to assess the degree of postirradiation anorexia. Seventy-two hours after irradiation those animals, as well as ad libitum-fed and food-deprived nonirradiated animals were exposed to a simulated altitude tolerance test. The mortality produced in 4 hours was used as the criterion of hypoxic tolerance for each species. Irradiated rabbits and rats exhibited a severe decrease in food consumption and an increased hypoxic tolerance. Food consumption of mice was depressed during the 3 days following irradiation although the effect was much less than that observed for rats and rabbits. Guinea pigs and hamsters exhibited only a slight decrease in food consumption with recovery occurring after 24 hours. Mice, guinea pigs and hamsters did not exhibit a significant increase in hypoxic tolerance 3 days after radiation exposure. When nonirradiated rabbits, rats, mice and guinea pigs were food deprived, the hypoxic tolerance was significantly increased in all species.


1984 ◽  
Vol 11 (6) ◽  
pp. 764-766 ◽  
Author(s):  
K. E. Ekstrand ◽  
R. L. Dixon ◽  
C. W. Scarantino ◽  
C. J. Kovacs

2011 ◽  
Vol 48 (6) ◽  
pp. 1204-1211 ◽  
Author(s):  
C. M. Martínez ◽  
C. Peñafiel-Verdú ◽  
M. Vilafranca ◽  
G. Ramírez ◽  
M. Méndez-Gallego ◽  
...  

A direct relationship has been firmly established between cyclooxygenase-2 (COX-2) expression and malignant behavior in human melanoma. This report examines the relationship between COX-2 expression and tumor location, mitotic and proliferative indices, degree of T CD3+ lymphocyte infiltration, overall survival, and frequency of recurrence and metastasis of 57 melanocytic tumors (25 oral and 32 cutaneous). COX-2 was highly or moderately expressed in 88% of oral neoplasms (22 of 25), whereas for their cutaneous counterparts, COX-2 expression was low or insignificant in 75% of cases (24 of 32). High and moderate COX-2 expression levels were observed in 73% of melanocytic tumors with a mitotic index ≥ 3 per 10 high-power fields (26 of 36), whereas in 81% of tumors with a mitotic index < 3 (17 of 21), expression was mild or absent. There were 41 cases with known clinical outcomes; of those showing high, moderate, and mild COX-2 expression, 83.3% (10 of 12), 37.5% (3 of 8), and 25% (2 of 8) died, respectively, whereas 100% of animals showing no COX-2 expression (13 of 13) were still alive at the last follow-up. COX-2 expression was statistically correlated with tumor location, mitotic and percentage Ki-67 proliferative indices, and overall survival, frequency of neoplastic recurrence and metastasis. Regression analysis also showed disease-specific predictive value for COX-2 expression for subjects with melanocytic neoplasms. Additionally, only high COX-2 expression showed significant differences in overall survival, in comparison with moderate, mild, or absent expression. These results suggest that high COX-2 expression may be considered a prognostic biomarker and potentially as a target for therapeutic and preventive strategies in canine melanocytic neoplasms.


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