The effects of the combination of temozolomide and Eribulin on T98G human glioblastoma cell line: an ultrastructural study.

Glioblastoma tumors are the most aggressive primary brain tumors that develop resistance to temozolomide (TMZ). Eribulin (ERB) exhibits a unique mechanism of action by inhibiting microtubule dynamics during the G2/M cell cycle phase. We utilized the T98G human glioma cell line to investigate the effects of ERB and TMZ, both individually and in combination. The experimental groups were established as follows: control, E5 (5 nM ERB), T0.75 (0.75 mM TMZ), T1 (1.0 mM TMZ), and combination groups (E5+T0.75 and E5+T1). All groups showed a significant decrease in cell proliferation. Apoptotic markers revealed a time-dependent increase in annexin-V expression, across all treatment groups at the 48-hour time point. Caspase-3, exhibited an increase in the combination treatment groups at the 48-hour mark. Transmission electron microscopy (TEM) revealed normal ultrastructural features in the glioma cells of the control group. However, treatments induced ultrastructural changes within the spheroid glioblastoma model, particularly in the combination groups. These changes included a dose-dependent increase in autophagic vacuoles and apoptotic morphology of the cells. In conclusion, the similarity in the mechanism of action between ERB and TMZ suggests the potential for synergistic effects when combined. Our results highlight that this combination induced severe damage and autophagy in glioma spheroids after 48 hours.

Modified and alternative bone cements can improve the induced membrane: Critical size bone defect model in rat femur.

BACKGROUND: As a two-stage surgical procedure, Masquelet's technique has been used to care for critical-size bone defects (CSD). We aimed to determine the effects of modified and altered bone cement with biological or chemical enriching agents on the progression of Masquelet's induced membrane (IM) applied to a rat femur CSD model, and to compare the histopathological, biochemical, and immunohistochemical findings of these cements to enhance IM capacity. METHODS: Thirty-five male rats were included in five groups: plain polymethyl methacrylate (PMMA), estrogen-impregnated PMMA (E+PMMA), bone chip added PMMA (BC+PMMA), hydroxyapatite-coated PMMA (HA) and calcium phosphate cement (CPC). The levels of bone alkaline phosphatase (BALP), osteocalcin (OC), and tumor necrosis factor-alpha (TNF-α) were analyzed in intracardiac blood samples collected at the end of 4 weeks of the right femur CSD intervention. All IMs collected were fixed and prepared for histopathological scoring. The tissue levels of rat-specific Transforming Growth Factor-Beta (TGF-ß), Runt-related Transcription Factor 2 (Runx2), and Vascular Endothelial Growth Factor (VEGF) were analyzed immunohistochemically. RESULTS: Serum levels of BALP and OC were significantly higher in E+PMMA and BC+PMMA groups than those of other groups (P = 0.0061 and 0.0019, respectively). In contrast, TNF-α levels of all groups with alternative bone cement significantly decreased compared to bare PMMA (P = 0.0116). Histopathological scores of E+PMMA, BC+PMMA, and CPC groups were 6.86 ± 1.57, 4.71 ± 0.76, and 6.57 ± 1.51, respectively, which were considerably higher than those of PMMA and HA groups (3.14 ± 0.70 and 1.86 ± 0.69, respectively) (P < 0.0001). Significant increases in TGF-ß and VEGF expressions were observed in E+PMMA and CPC groups (P = 0.0001 and <0.0001, respectively) whereas Runx2 expression significantly increased only in the HA group compared to other groups (P < 0.0001). CONCLUSIONS: The modified PMMA with E and BC, and CPC as an alternative spacer resulted in a well-differentiated IM and increased IM progression by elevating BALP and OC levels in serum and by mediating expressions of TGF-ß and VEGF at the tissue level. Estrogen-supplemented cement spacer has yielded promising findings between modified and alternative bone cement.

Investigation of apoptotic and antiproliferative effects of Turkish natural tetraploids Trifolium pratense L. extract on C6 glioblastoma cells via light and electron microscopy.

Glioblastoma (GBM) is the most common type of primary brain tumors in adults, characterized by its ability to proliferate rapidly and its tendency to aggressively and strongly invaded the surrounding brain tissue. The standard treatment approach of GBM is surgical resection followed by simultaneous chemotherapy and radiation. However, a significant number of GBM cases develop resistance to currently used chemotherapeutic drugs. Therefore, there is a need for the development of new chemotherapeutic agents. Trifoliumpratense L. is an endemic plant containing various isoflavones such as biochanin A, genistein, daidzein, and formononetin in high concentrations, and it has been shown in various studies that these molecules can function as anticancer agents. The present study was designed to determine the effect of the possible anticarcinogenic effects of the Trifolium pratense L. which grown in our country and to obtain new treatment approaches alternative to the classical treatment protocols applied in the treatment of GBM. C6 glioblastoma cells were cultured with Trifolium pratense L. Cell proliferation, apoptotic cell morphology, and cell structure were evaluated with CCK8, Annexin V, cytochrome c, CD117, and Betatubulin labeling, respectively. And also, investigated effects of this Turkish tetraploid on GBM by TEM. Decreased cell proliferation and increased number of apoptotic cells were observed depending on the increasing doses of Trifolium pratense L. In addition, intense morphological changes were detected depending on increasing doses. In this context, we believe that the plant Trifolium pratense L., may be a new alternative and adjuvant agent for the treatment of GBM.

The antibiotics supplemented bone cement improved the masquelet's induced membrane in a rat femur critical size defect model.

BACKGROUND: Masquelet technique is a two-stage surgical procedure used in the treatment of critical-size bone defects (CSD). Adding antibiotics to polymethylmethacrylate (PMMA) is still questionable to create higher quality induced membrane (IM). The aim of the study was to evaluate the effects of three antibiotic-supplemented cement, fusidic acid, teicoplanin, and gentamicin, on osteogenesis and IM progression applied to rat femur CSD model by comparing histopathological, biochemical, and immunohistochemical findings. METHODS: Twenty-eight male rats were divided into four groups control, gentamicin (G), teicoplanin (T), and fusidic acid (FA). A 10 mm CSD was created in rat femurs. In the postoperative 4th week, intracardiac blood samples were collected for biochemical analysis of bone alkaline phosphatase (BALP), osteocalcin (OC), and tumor necrosis factor-alpha (TNF-α) levels. IMs obtained in secondary operation were fixed and prepared for histopathological scoring of membrane progression and immunohistochemical evaluation of rat-specific Transforming Growth Factor-Beta (TGF-ß), Runt-related Transcription Factor 2 (Runx2), and Vascular Endothelial Growth Factor (VEGF) expressions. RESULTS: Levels of BALP and OC in serum didn't change among groups significantly while serum TNF-α levels significantly decreased in all antibiotic groups compared to the control group (P = 0.017). Histological scores of groups FA and T were significantly higher than those of groups Control and G (P = 0.0007). IMs of groups T and FA showed good progression while those of groups Control and G were also moderately progressed. A significant increase in TGF-ß expression was observed in group G and FA (P = 0.001) while a significant increase in the expression of VEGF was observed in groups G and T compared to the control group (P = 0.036). CONCLUSIONS: The bone cement impregnated with thermostable and safe antibiotics, gentamicin, fusidic acid, and teicoplanin can increase osteogenesis and support IM progression by increasing the expressions of TGF-ß and VEGF. Anabolic effects of induced membranes used in the treatment of critical-size bone defects can be enhanced by antibiotic-supplemented PMMAs applied by altering the original technique.

The Keystone, Scroll Complex, and Interdomal Area of the Nose: Histologic and Anatomical Observations.

Comprehensive knowledge of nasal anatomy is essential for obtaining aesthetically and functionally pleasing results in rhinoplasty. In this study, the authors described the anatomy, histology, and clinical relevance of the interdomal region, keystone, and scroll complex. The current study examined these areas in 26 fresh cadaver heads. All cadavers were fresh, and no conservation or freezing processes were applied. All dissections were performed by the first author. It was determined that the structure that connected the middle crura in the interdomal region actually came together in the transverse plane and contained abundant capillaries within. It was observed that chondroblasts with high regenerative potential were present in the keystone area, and there was very tight attachment between periosteum and perichondrium. The scroll complex was found to be more flexible and thin and had fewer regenerative cells compared to the keystone region. With its unique anatomy and histology, the keystone acts as a transition area between the flexible and fixed units of the nose. The scroll complex should be taken into consideration during rhinoplasty because of its effects on fixation of the skin in the lateral supratip area and functional effects on internal and external nasal valves. The interdomal ligament, in contrast, acts as a transition between both middle crura rather than a real ligament.