Addressing radiotherapy-induced fibrosis: the potential of platelet-rich plasma and infliximab for improved breast cancer management.

Breast cancer treatment encompasses various therapeutic modalities, including surgery, radiotherapy, and chemotherapy. Breast-conserving surgery has been an integral part of breast cancer management. However, radiotherapy, an important component of breast cancer management, can lead to complications, particularly fibrosis, affecting reconstructive surgery outcomes. We conducted an in vivo study using 48 female Wistar Albino rats, employing segmental mastectomy and radiotherapy to simulate post-mastectomy conditions. The rats were divided into six groups: control, mastectomy, mastectomy + radiotherapy, mastectomy + platelet-rich plasma (PRP) + radiotherapy, mastectomy + infliximab + radiotherapy, and mastectomy + infliximab + PRP + radiotherapy. Edema, hyperemia, inflammation, and fibrosis were assessed as indicators of tissue response. Histopathological analysis revealed that mastectomy + infliximab and mastectomy + infliximab + PRP groups showed significant reductions in fibrosis compared to other groups. Edema, hyperemia, and inflammation were also less severe in these groups compared to the control group. Radiotherapy-induced fibrosis is a major concern in breast reconstruction. Our study suggests that local PRP application and systemic infliximab administration, either alone or in combination, could mitigate the adverse effects of radiotherapy. This approach has the potential to improve reconstructive outcomes in patients undergoing or having the possibility to undergo radiotherapy. This is the first study showing the effectiveness of infliximab and PRP combination on wound healing. The provided experimental rat model might offer guidance for further research. This study provides insights into optimizing outcomes in reconstructive breast surgery, paving the way for further research and clinical studies.

Ultrastructural effects of nerve growth factor and betamethasone on nerve regeneration after experimental nerve injury.

Peripheral nerve injuries (PNI) are an important health problem in the world. In this study, the effects of nerve growth factor (NGF) and betamethasone on nerve regeneration after sciatic nerve crush injury were examined by footprint analysis, electron microscopic, histomorphometric, and biochemical methods. Fifty Wistar rats were divided into five groups as intact control, experimental control, NGF, betamethasone, and NGF+betamethasone combined treatment groups. After the injury, betamethasone was subcutaneously injected into the lesion area of the treatment groups three times during the first day. NGF was subcutaneously injected into the lesion area of treatment groups for 14 days. Footprint analysis was made on 7, 14, 21, 28, and 35 days and after 6 weeks, tissue samples were obtained from all groups. In the experimental control group, there were severe degenerative changes in most of the axons and myelin sheaths of the nerve fibers. Moreover, an increase of MDA levels and a decrease in SOD activities were found in this group. On the other hand, malondialdehyde (MDA) levels decreased, superoxide dismutase (SOD) activities increased and significant motor functional recovery were found in the combined treatment group. The number of axons, axon diameters, and myelin thickness were significantly greater in the combined treatment group when compared with experimental control and other treatment groups. It was thought that nerve regenerative effects of NGF and anti-inflammatory and/or anti-edematous effects of betamethasone could induce functional recovery in the combined treatment group. In conclusion, combined therapy of NGF and betamethasone may be an effective approach for the treatment of PNI.

Neutrophil-Lymphocyte Ratio Connected to Treatment Options and Inflammation Markers of Ankylosing Spondylitis.

BACKGROUND: In recent years, white blood cells (WBCs) and their subtypes have been studied in relation to inflammation. The aim of our study was to assess the relationship between neutrophil-lymphocyte ratio (NLR) and ankylosing spondylitis (AS). MATERIALS AND METHODS: We enrolled a total of 177 patients, 96 AS and 81 healthy controls. Complete blood count, WBC, neutrophil and lymphocyte levels were measured, and the NLR was calculated. In the assessment of AS, we used the erythrocyte sedimentation rate, C-reactive protein (CRP), the Bath Ankylosing Spondylitis Disease Activity Index, and the Bath Ankylosing Spondylitis Functional Index. RESULTS: In the present study, 96 AS and 81 healthy individuals were enrolled. The mean age was 43.8 ± 12.9 and 46.5 ± 11.2 years, respectively. Mean disease duration of AS patients was 6.9 ± 5.6 years (median = 5, min-max = 1-25). The patients with AS had a higher NLR than the control individuals (mean NLR, 2.24 ± 1.23 and 1.73 ± 0.70, respectively, P < 0.001). A statistically significant positive correlation was observed between NLR and CRP (r = 0.322, P = 0.01). The patients receiving antitumor necrosis factor α therapy had a lower NLR than the patients receiving nonsteroidal anti-inflammatory drug therapy (mean NLR, 1.71 ± 0.62 and 2.41 ± 1.33, respectively, P = 0.02). CONCLUSION: NLR may be seen as a useful marker for demonstrating inflammation together with acute phase reactants such as CRP and in evaluating the effectiveness of anti-TNF-α therapy.

Association between mean platelet volume and bone mineral density in patients with ankylosing spondylitis and diagnostic value of diffusion-weighted magnetic resonance imaging.

[Purpose] The aim this study was to assess the relation between bone mineral density (BMD) and mean platelet volume (MPV) in ankylosing spondylitis (AS) patients, and evaluate the diagnostic role of the diffusion-weighted magnetic resonance imaging (MRI). [Subjects and Methods] Fifty patients diagnosed with AS were divided into two groups on the basis of BMD, a normal group (n=30) and an osteopenic (n=20) group. [Results] Duration of disease in the group with a normal BMD was 10.3±7.0 years, while it was 16.7±12.2 years in the osteopenia group. MPV was high in the osteopenia group, while no significant differences were observed between the groups in terms of apparent diffusion coefficient (ADC) and platelet distribution width (PDW). There was a positive correlation between MPV and duration of disease. Correlations between ADC value and the lumbar T score, femoral neck T score, and duration of disease were insignificant. A negative correlation was observed between BMD and disease duration. [Conclusion] Diffusion-weighted imaging provides valuable results in osteoporosis but is not a suitable technique for evaluating BMD in patients with AS because of the local and systemic inflammatory effects in the musculoskeletal system. The common pathophysiology of atherosclerosis and osteoporosis plays an important role in the negative correlation observed between MPV and BMD in patients with AS.

Data cluster analysis-based classification of overlapping nuclei in Pap smear samples.

BACKGROUND: The extraction of overlapping cell nuclei is a critical issue in automated diagnosis systems. Due to the similarities between overlapping and malignant nuclei, misclassification of the overlapped regions can affect the automated systems' final decision. In this paper, we present a method for detecting overlapping cell nuclei in Pap smear samples. METHOD: Judgement about the presence of overlapping nuclei is performed in three steps using an unsupervised clustering approach: candidate nuclei regions are located and refined with morphological operations; key features are extracted; and candidate nuclei regions are clustered into two groups, overlapping or non-overlapping, A new combination of features containing two local minima-based and three shape-dependent features are extracted for determination of the presence or absence of overlapping. F1 score, precision, and recall values are used to evaluate the method's classification performance. RESULTS: In order to make evaluation, we compared the segmentation results of the proposed system with empirical contours. Experimental results indicate that applied morphological operations can locate most of the nuclei and produces accurate boundaries. Independent features significance test indicates that our feature combination is significant for overlapping nuclei. Comparisons of the classification results of a fuzzy clustering algorithm and a non-fuzzy clustering algorithm show that the fuzzy approach would be a more convenient mechanism for classification of overlapping. CONCLUSION: The main contribution of this study is the development of a decision mechanism for identifying overlapping nuclei to further improve the extraction process with respect to the segmentation of interregional borders, nuclei area, and radius. Experimental results showed that our unsupervised approach with proposed feature combination yields acceptable performance for detection of overlapping nuclei.

Impact of 18F-FDG PET/CT in the management decisions of breast cancer board on early-stage breast cancer.

PURPOSE: Breast cancer is the most common malignancy accounting for 11.7% of all cancer cases, with a rising incidence rate. Various diagnostic methods, including 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT), play a crucial role in breast cancer diagnosis and staging. However, the unnecessary use of advanced imaging techniques such as PET/CT in early-stage breast cancer can have negative effects on both economics and patients. We aimed to investigate the impact of PET/CT on the management decisions of early-stage breast cancer patients by the breast cancer tumor board. METHODS: A retrospective analysis was performed on a cohort of 81 patients with early-stage breast cancer who were evaluated by breast cancer tumor board from January 2015 to December 2020. Demographic, clinical, and radiographic data, along with surgical procedures and treatment options, were documented and analyzed. RESULTS: The results showed that 18F-FDG PET/CT had a moderate impact on treatment decisions of breast cancer tumor board, as only treatment decisions were changed in 14,86% of the patients. The surgical procedure decision of breast cancer tumor board changed in 12.35% of patients, while 87.65% of patients had consistent decisions before and after PET/CT. Pathological assessments revealed invasive ductal carcinoma as the most prevalent tumor type, and molecular subtypes were predominantly luminal B. PET/CT use had limited impact on surgical procedures and did not significantly alter treatment decisions of breast cancer tumor board in this early-stage breast cancer cohort. CONCLUSIONS: In conclusion, this study highlights the importance of adherence to the guidelines and appropriate use of PET/CT in early-stage breast cancer management. PET/CT should be reserved for cases where it is clinically warranted, considering the potential economic burden and minimal impact on treatment decisions of breast cancer tumor board in this patient population.

Exploring the combined anti-cancer effects of sodium butyrate and celastrol in glioblastoma cell lines: a novel therapeutic approach.

Glioblastoma, a highly aggressive and lethal brain cancer, lacks effective treatment options and has a poor prognosis. In our study, we explored the potential anti-cancer effects of sodium butyrate (SB) and celastrol (CEL) in two glioblastoma cell lines. SB, a histone deacetylase inhibitor, and CEL, derived from the tripterygium wilfordii plant, act as mTOR and proteasome inhibitors. Both can cross the blood-brain barrier, and they exhibit chemo- and radiosensitive properties in various cancer models. GB cell lines LN-405 and T98G were treated with SB and CEL. Cell viability was assessed by MTT assay and IC50 values were obtained. Gene expression of DNA repair, apoptosis, and autophagy-related genes was analyzed by RT-PCR. Cell cycle distribution was determined using flow cytometry. Viability assays using MTT assay revealed IC50 values of 26 mM and 22.7 mM for SB and 6.77 µM, and 9.11 µM for CEL in LN-405 and T98G cells, respectively. Furthermore, we examined the expression levels of DNA repair genes (MGMT, MLH-1, MSH-2, MSH-6), apoptosis genes (caspase-3, caspase-8, caspase-9), and an autophagy gene (ATG-6) using real-time polymerase chain reaction. Additionally, flow cytometry analysis revealed alterations in cell cycle distribution following treatment with SB, CEL and their combination. These findings indicate that SB and CEL may act through multiple mechanisms, including DNA repair inhibition, apoptosis induction, and autophagy modulation, to exert their anti-cancer effects in glioblastoma cells. This is the first study providing novel insights into the potential therapeutic effects of SB and CEL in glioblastoma.

The antagonistic effects of temozolomide and trichostatin a combination on MGMT and DNA mismatch repair pathways in Glioblastoma.

Glioblastoma is the most aggressive and fatal form of brain cancer. Despite new advancements in treatment, the desired outcomes have not been achieved. Temozolomide (TMZ) is the first-choice treatment for the last two decades and has improved survival rates. Emerging studies have shown that targeting epigenetics in glioblastoma can be beneficial when combined with clinically used treatments. Trichostatin A (TSA), a histone deacetylase inhibitor, has anti-cancer properties in various cancers. No data concerning the TMZ and TSA relationship was shown previously in glioblastoma therefore, we aimed to determine the likely therapeutic effect of the TMZ and TSA combination in glioblastoma. The T98G and U-373 MG, glioblastoma cell lines, were used in this study. TMZ and TSA cytotoxicity and combination index were performed by MTT assay. The expression of DNA repair genes (MGMT, MLH-1, PMS2, MSH2 and MSH6) was detected using RT-PCR. One-way analysis of variance (ANOVA) was used for statistical analysis. Combination index calculations revealed antagonistic effects of TMZ and TSA in terms of cytotoxicity. Antagonistic effects were more apparent in the T98G cell line, which is expressing MGMT relatively higher. MGMT and DNA Mismatch Repair (MMR) genes were upregulated in the T98G cell line, whereas downregulated in the U373-MG cell lines under TMZ and TSA combination treatment. It is concluded that MGMT might be playing a more active part than MMR genes in TMZ resistance to TMZ and TSA antagonism. This is the first study elucidating the TMZ and TSA relationship in cancer cell lines.

CD133+/CD44+ prostate cancer stem cells exhibit embryo-like behavior patterns.

Cancer stem cells (CSCs), which act as an important bridge between cancer formation and embryonic development, represent a small population associated with tumor initiation, drug resistance, metastasis and recurrence. CSCs have the ability to form spheroids in three-dimensional culture systems. Tumor spheroids derived from CSCs with symmetric and asymmetric division patterns were found to contain highly heterogeneous cell groups. The biological behavior patterns which some CSCs display serve as an important bridge between cancer formation and embryonic development. The cell population in the DU-145 prostate cancer cell line with surface markers CD133+/CD44+ was isolated by FACS. Prostate spheroids were formed by using agarose-coated plates. The morphological characteristics of the cell population within spheroid structure and the expression of Ki-67 and Caspase-3 were investigated by histochemical methods. In this study, we observed that CD133+/CD44+ prostate CSCs form different spheroid structures as well as normal spheroid structures: i) some spheroid structures formed with a highly transparent zone on the outer part of the spheroid, in addition to the normal spheroidal zones and ii) spheroidal structures obtained from prostate CD1334+/CD44+ CSCs that share the same microenvironment are hollow spheres similar to the blastula-like structure in the embryo. These spheroidal structures exhibiting embryo-like properties indicate that the expression of embryonic factors might be reiterated in CSCs. Further investigation of the formation mechanism of the transparent zone and the hollow sphere will shed light on the embryonic origin of prostate cancer and the design of new therapeutic strategies.

Remote Cerebellar Hemorrhage Presenting with Cerebellar Mutism after Spinal Surgery: An Unusual Case Report.

Dural injury during spinal surgery can subsequently give rise to a remote cerebellar hemorrhage (RCH). Although the incidence of such injury is low, the resulting hemorrhage can be life threatening. The mechanism underlying the formation of the hemorrhage is not known, but it is mostly thought to develop after venous infarction. Cerebellar mutism (CM) is a frequent complication of posterior fossa operations in children, but it is rarely seen in adults. The development of CM after an RCH has not been described. We describe the case of a 65-year old female who lost cerebrospinal fluid after inadvertent opening of the dura during surgery. Computerized tomography performed when the patient became unable to speak revealed a bilateral cerebellar hemorrhage.

The Axon Protective Effects of Syringic Acid on Ischemia/Reperfusion Injury in a Rat Sciatic Nerve Model.

AIM: In the relevant literature, there is no experimental study that investigated the axon protective effects of syringic acid- a polyphenol compound- with an anti-oxidant capacity on ischemia/reperfusion injury. MATERIAL AND METHODS: The rats were randomly divided into four groups: Control group (no medication or surgical procedure), Sham group, Syringic acid group, and Methyprednisolone (MP) Group. Ischemia was achieved by abdominal aorta clamping and all animals were sacrificed 24 hours after ischemia. Harvested sciatic nerve segments were investigated histopathologically and for tissue biochemistry. RESULTS: Ischemic fiber degeneration scores were found significantly lower in syringic acid and MP groups than sham group. Additionally, apoptosis-related cysteine peptidase caspase-3 immunostaining scores were lower in syringic acid and MP groups. Biochemically, superoxide dismutase and nuclear respiratory factor 1 values were significantly higher in syringic acid group compared to those of control and sham groups while malondialdehyde levels were significantly lower in the syringic acid group. CONCLUSION: Syringic acid reduces oxidative stress and axonal degeneration in rat sciatic nerve after ischemia/reperfusion injury. Therefore, syringic acid may play a role in the treatment of peripheral nerve injuries due to ischemia/reperfusion.

The actions of lamotrigine and levetiracetam on the conduction properties of isolated rat sciatic nerve.

The purpose of this study was to investigate the actions of lamotrigine and levetiracetam on the conduction properties of isolated rat sciatic nerves in-vitro. Compound action potentials from rat sciatic nerves were recorded using a sucrose-gap technique with single and repetitive stimulation. Lamotrigine, at 0.01 to 1 mM, reduced the amplitude of compound action potentials (3.9+/-0.6% to 47.9+/-2.4%) and produced at high frequency dependent (phasic) and independent (tonic) conduction block. Lamotrigine extended the peak time of the compound action potentials significantly without changing the half falling-time (P<0.05). Lamotrigine reduced the amplitude of the delayed depolarization, which was more pronounced than that of the amplitude of the compound action potentials in the presence of 4-aminopyridine. With tonic and phasic stimulation, 0.1 to 10 mM of levetiracetam did not alter the amplitude, peak time and half falling time of the compound action potentials. In addition, levetiracetam did not change the amplitude of the delayed depolarization and the area of the compound action potentials following application of 4-aminopyridine. These results indicate that lamotrigine produces a powerful tonic block with delayed depolarization, whereas it produces a weaker phasic block in rat sciatic nerve. Levetiracetam has no effect on peripheral nerve conduction even at high concentrations. These results may have the relevance to our understanding of the peripheral effects of lamotrigine and levetiracetam.

Effects of AP5 infusion into the lateral ventricle on the activities and hippocampal electrical patterns of sleep episodes in rats.

Although N-methyl-D-aspartate (NMDA) receptors of the hippocampus are mainly associated with learning and memory that might occur "on-line" during sharp waves (SPWs) and theta-rhythm, the participation of hippocampal NMDA receptors in sleep-related processes has not been well studied. In this study, the activity of sleep episodes, hippocampal SPWs and theta-rhythm were recorded in rats received a repeated infusion of NMDA receptor antagonist, D,L-2-amino-5-phosphonopentanoic acid (AP5), into the lateral ventricle in a 5-h daytime sleep. The first trial AP5 infusion (30 mM/2 microl) did not change measures of the activity of slow wave sleep (SWS), paradoxical sleep (PS) and awake episodes, but induced a delay in the latency of the first onset of PS; in the hippocampal EEG, it increased the amplitude of SPWs within SWS and shifted the amplitude/spectral power of theta-rhythm from high to low frequency within PS. The repeated AP5 infusion augmented the activity of SWS, and impaired PS and awake episodes; in the EEG-sleep picture, it maintained high scores of SPWs with the complete blockade of theta-rhythm generation. When AP5 rat was woken, the theta-rhythm was seen during exploratory behavior. These findings provide evidence that hippocampal NMDA receptors via SPWs or directly associated with the synaptic events of theta-rhythm generation are critical for the PS activities.

The effect of aloe vera on ischemia--Reperfusion injury of sciatic nerve in rats.

PURPOSE: Aloe vera is compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of aloe vera treatment in rats with experimental sciatic nerve ischemia/reperfusion injury. METHODS: Twenty-eight male Wistar Albino rats were divided equally into 4 groups. Groups; Control group (no surgical procedure or medication), sciatic nerve ischemia/reperfusion group, sciatic nerve ischemia/reperfusion+aloe vera group and sciatic nerve ischemia/reperfusion+methylprednisolone group. Ischemia was performed by clamping the infrarenal abdominal aorta. 24 hours after ischemia, all animals were sacrificed. Sciatic nerve tissues were also examined histopathologically and biochemically. RESULTS: Ischemic fiber degeneration significantly decreased in the pre-treated with aloe vera and treated with methylprednisolone groups, especially in the pre-treated with aloe vera group, compared to the sciatic nerve ischemia/reperfusion group (p<0.05). A significant decrease in MDA, an increase in NRF1 level and SOD activity were observed in the groups which obtained from the AV and MP groups when compared to the sciatic nerve ischemia/reperfusion group. When all results were analysed it was seen that the aloe vera group was not statistically different compared to the MP group (p>0.05). CONCLUSIONS: Aloe vera is effective neuroprotective against sciatic nerve ischemia/reperfusion injury via antioxidant and anti-inflammatory properties. Also aloe vera was found to be as effective as MP.

Evaluation of the Association Between Matrix Metalloproteinase 11 and Intervertebral Disc Disease.

AIM: The intervertebral disc starts to degenerate when a human being begins to stand and learn to walk. It is known that many extrinsic, intrinsic and genetic factors play a role in disc degeneration. In this study, we examined whether the matrix metalloproteinase 11 might be associated with intervertebral disc degeneration. MATERIAL AND METHODS: Fifty-six patients with lumbar disc herniations who were operated at Göztepe Education and Research Hospital, Neurosurgery Clinic between September 2008 and December 2009 were prospectively reviewed. History and complaints were obtained from the case reports. Neuroradiological evaluation was performed with magnetic resonance imaging. Surgical findings of cases were reported in the operation notes. Microscopic posterior hemipartial laminectomy and discectomy were performed in all cases. Degenerated herniated disc material of all cases extracted during surgery was evaluated with immunohistochemical staining in Marmara University, Institute of Neurological Sciences, Pathology Laboratory. RESULTS: Comparing the immunohistochemical staining of cases who were 50 years or younger and cases who were over 50 years old, statistical significance was determined. CONCLUSION: Matrix metalloproteinase 11 has a role in degenerating intervertebral disc disease, but it is not the only factor. Matrix metalloproteinase 11 might be a genetic factor in young-middle aged patients.

Effect of Using High-Speed Drill in Anterior Cervical Discectomy and Fusion.

AIM: The objective of this study was to investigate the effect of using 2 different surgical techniques (curette or high-speed drill) in anterior cervical discectomy surgery on the healing of cases. MATERIAL AND METHODS: Fifty-four operated cervical disc hernia cases were retrospectively examined in 2 groups. Discectomy and osteophytectomy were carried out in Group A by using a high-speed drill, while a curette was used for group B. Preoperative and postoperative computerized tomography and direct radiography were performed. Cervical disc height, cervical and segmental lordotic angles were calculated. The visual analogue scale and Odom's criteria were used in the assessment of pain and clinical healing. The fusion ratio of both groups was compared. The Mann-Whitney U test was used to compare data from the groups. RESULTS: Satisfactory results were obtained in the groups where high-speed drill and curette were used. Independently from the surgical technique, pain scores were significantly reduced in both groups after surgery. No radiologically significant differences were identified between the two groups within the postoperative period. CONCLUSION: Either high-speed drill or curette can be chosen for the osteophytectomy and discectomy stages of anterior cervical discectomy operations.

Cabazitaxel causes a dose-dependent central nervous system toxicity in rats.

BACKGROUND: Chemotherapeutic agents may lead to serious neurological side effects, which in turn can deteriorate the quality of life and cause dose limiting. Direct toxic effect or metabolic derangement of chemotherapeutic agents may cause these complications. Cabazitaxel is a next generation semi-synthetic taxane derivative, which is effective in both preclinical models of human tumors sensitive or resistant to chemotherapy and in patients with progressive prostate cancer despite docetaxel treatment. AIM: The primary aim of this study was to investigate the central nervous system toxicity of Cabazitaxel. Secondary aim was to investigate the safety dose of Cabazitaxel for the central nervous system. METHODS: A total of 24 adult male Wistar-Albino rats were equally and randomly divided into four groups as follows: group 1 (Controls), group 2 (Cabazitaxel 0.5mg/kg), group 3 (Cabazitaxel 1.0mg/kg) and group 4 (Cabazitaxel 1.5mg/kg). Cabazitaxel (Jevtana, Sanofi-Aventis USA) was intraperitoneally administered to groups 2, 3 and 4 at 0.5, 1.0 and 1.5mg/kg (body-weight/week) doses, respectively for four consecutive weeks. Beside this, group 1 received only i.p. saline at the same volume and time. At the end of the study, animals were sacrificed and bilateral brain hemispheres were removed for biochemical, histopathological and immunohistochemical examinations. RESULTS: Intraperitoneal administration of Cabazitaxel has exerted neurotoxic effect on rat brain. We have observed that biochemical and immunohistochemical results became worse in a dose dependent manner. CONCLUSION: Our findings have suggested that Cabazitaxel may be a neurotoxic agent and can trigger apoptosis in neuron cells especially at high doses.