Class I HDAC Inhibition Leads to a Downregulation of FANCD2 and RAD51, and the Eradication of Glioblastoma Cells.

HDAC inhibitors (HDACi) hold great potential as anticancer therapies due to their ability to regulate the acetylation of both histone and non-histone proteins, which is frequently disrupted in cancer and contributes to the development and advancement of the disease. Additionally, HDACi have been shown to enhance the cytotoxic effects of DNA-damaging agents such as radiation and cisplatin. In this study, we found that histone deacetylase inhibits valproic acid (VPA), synergized with PARP1 inhibitor (PARPi), talazoparib (BMN-673), and alkylating agent, and temozolomide (TMZ) to induce DNA damage and reduce glioblastoma multiforme. At the molecular level, VPA leads to a downregulation of FANCD2 and RAD51, and the eradication of glioblastoma cells. The results of this study indicate that combining HDACi with PARPi could potentially enhance the treatment of glioblastoma, the most aggressive type of cancer that originates in the brain.

Glomangioma in the hand: diagnosis, treatment, and challenges.

INTRODUCTION: In this paper, we have analysed all hand glomangioma cases referred to our clinic in the context of symptoms, time to diagnosis, and the role of surgical resection of the lesion. MATERIAL AND METHODS: We have collected the following data: the presence of risk factors, manifestation, time to diagnosis, the treatment applied, and follow-up of patients. RESULTS: We have collected medical records from six patients, three males and three females. The median age was 45 (IQR: 29.5-65.75). The main symptom in all patients was severe pain and tenderness. The first-choice physician(s) were: general practitioners, general surgeons, and neurologists. The median time to diagnosis was 7 (IQR: 5-10) years. The main complaint of our patients was severe pain - 9 (IQR: 9-10) on the VAS scale, which was significantly alleviated after surgical treatment - 0 (IQR: 0-0; p = 0.043). CONCLUSIONS: Extremely long times to final diagnosis, and excellent outcomes of surgical treatment, highlight the necessity of raising awareness of glomangiomas among clinicians.

Histone Deacetylases (HDAC) Inhibitor-Valproic Acid Sensitizes Human Melanoma Cells to Dacarbazine and PARP Inhibitor.

The inhibition of histone deacetylases (HDACs) holds promise as a potential anti-cancer therapy as histone and non-histone protein acetylation is frequently disrupted in cancer, leading to cancer initiation and progression. Additionally, the use of a histone deacetylase inhibitor (HDACi) such as the class I HDAC inhibitor-valproic acid (VPA) has been shown to enhance the effectiveness of DNA-damaging factors, such as cisplatin or radiation. In this study, we found that the use of VPA in combination with talazoparib (BMN-673-PARP1 inhibitor-PARPi) and/or Dacarbazine (DTIC-alkylating agent) resulted in an increased rate of DNA double strand breaks (DSBs) and reduced survival (while not affecting primary melanocytes) and the proliferation of melanoma cells. Furthermore, the pharmacological inhibition of class I HDACs sensitizes melanoma cells to apoptosis following exposure to DTIC and BMN-673. In addition, the inhibition of HDACs causes the sensitization of melanoma cells to DTIV and BMN-673 in melanoma xenografts in vivo. At the mRNA and protein level, the histone deacetylase inhibitor downregulated RAD51 and FANCD2. This study aims to demonstrate that combining an HDACi, alkylating agent and PARPi could potentially enhance the treatment of melanoma, which is commonly recognized as being among the most aggressive malignant tumors. The findings presented here point to a scenario in which HDACs, via enhancing the HR-dependent repair of DSBs created during the processing of DNA lesions, are essential nodes in the resistance of malignant melanoma cells to methylating agent-based therapies.

Telovelar versus transvermian approach to tumors of the fourth ventricle and their impact on postoperative neurological complications: A multicenter study.

Background: Tumors of the fourth ventricle are exceedingly rare; however, such lesions are formidable due to the severe postoperative neurological complications (pNCs) which often occur. The adoption of the telovelar approach over the transvermian was created to supposedly mitigate the pNCs; however, there is a lack of sufficient data supporting this theory. Methods: Records from six hospitals were reviewed for patients surgically treated for a single tumor within the 4th ventricle from 2016 to 2022. The pNCs which had 10 or more occurrences among the patients were individually assessed as the dependent variable in a binary logistic regression model against covariates which included the surgical approach. Results: This study of 67 patients confirms no significant differences in risk for pNCs between the transvermian and telovelar approach. Rather, multivariate analysis identified neurophysiological monitoring (IONM) as a protective factor for postoperative speech and swallowing defects (odds ratio [OR]: 0.076, 95% confidence interval [CI] 0.011-0.525). Furthermore, intraoperative external ventricular drainage (EVD) was a protective factor for postoperative gait and focal motor defects (OR: 0.075, 95% CI 0.009-0.648) and for postoperative hydrocephalus (OR: 0.020, 95% CI 0.002-0.233). A univariate meta-analysis pooling the present study's patients and an additional 304 patients from the three additional studies in the literature confirms no significant differences in risk between the transvermian and telovelar approach for pNCs. Conclusion: Intraoperative adjuncts including IONM and EVD may play a significant role in the postoperative outcome. Despite the present study's sample size being a major limitation, the findings may provide great value to neurosurgeons given the scarcity of the current literature.

Intramedullary Spinal Cord Abscess with Concomitant Spinal Degenerative Diseases: A Case Report and Systematic Literature Review.

Intramedullary spinal cord abscess (ISCA) is a rare clinical pathology of the central nervous system that usually accompanies other underlying comorbidities. Traditionally it has been associated with significant mortality and neurological morbidities because it is often difficult to diagnose promptly, owing to its nonspecific clinical and neuroimaging features. The mortality rate and the outcome of these infections have been improved by the introduction into clinical practice of antibiotics, advanced neuroimaging modalities, and immediate surgery. We report the case of a 65-year-old male patient who presented with a progressive spastic gait and lumbar pain, predominantly in the left leg. An MRI image revealed an expansile intramedullary cystic mass in the thoracic spinal cord, which was initially diagnosed as a spinal tumor. He underwent laminectomy and myelotomy, and eventually the pus was drained from the abscess. The follow-up MRI showed improvement, but the patient's paraplegia persisted. In light of his persistent hypoesthesia and paraplegic gait with developing neuropathic pain, he was readmitted, and an MRI of his lumbar spine revealed multilevel degenerative disease and tethered spinal cord syndrome with compression of the medulla at the L2-L3 level. The patient underwent central flavectomy with bilateral foraminotomy at the L2-L3 level, and the medulla was decompressed. Postoperatively, his neurological symptoms were significantly improved, and he was discharged from hospital on the third day after admission. In support of our case, we systematically reviewed the recent literature and analyzed cases published between 1949 and May 2022, including clinical features, mechanisms of infection, predisposing factors, radiological investigations, microbial etiologies, therapies and their duration, follow-ups, and outcomes. Initial clinical presentation can be misleading, and the diagnosis can be challenging, because this condition is rare and coexists with other spinal diseases. Hence, a high index of suspicion for making an accurate diagnosis and timely intervention is required to preclude mortality and unfavorable outcomes. Our case is a clear example thereof. Long-term follow-up is also essential to monitor for abscess recurrences.

What Is Currently Known about Intramedullary Spinal Cord Abscess among Children? A Concise Review.

Intramedullary spinal cord abscesses (ISCA) are rare. Typical symptoms include signs of infection and neurological deficits. Symptoms among (younger) children can be highly uncharacteristic. Therefore, prompt and proper diagnoses may be difficult. Typical therapeutic options include antibiotics and neurosurgical exploration and drainage. In this review, we analyze published cases of ISCA among children. Most pediatric cases were found to be under the age of 6 years. The typical symptoms included motor deficits in 89.06%, infection signs in 85.94%, and sensory deficits in 39.06%. Urinary dysfunction was observed in 43.75%, and bowel dysfunction in 17.19%. The predisposing factors included dermal sinuses, (epi)dermoid cysts, prior infection, iatrogenic disorder, and trauma. The most common pathogens were: Staphylococcus aureus, Mycobacterium tuberculosis, Escherichia coli, and Proteus mirabilis. The pediatric population has good outcomes as 45.93% of patients had complete neurological recovery and only 26.56% had residual neurological deficits. Fifteen (23.44%) had persistent neurological deficits. Only one (1.56%) patient died with an ISCA. In two (3.13%) cases, there were no details about follow-up examinations.

Cervical Paraspinal Chordoma: A Literature Review with a Novel Case Report.

Chordomas are rare malignant neoplasms, accounting for 1-4% of all primary bone tumors. Most spinal chordomas occur in the sacrococcygeal region and the base of the skull; however, 6% of chordomas are observed in the cervical spine. In these cases, the lesion is mainly located in the midline. These tumors slowly grow before becoming symptomatic and encase the surrounding vascular and nerve structures. Patients with advanced chordoma have a poor prognosis due to local recurrence with infiltration and destruction of adjacent bone and tissues. Systemic chemotherapy options have not been fully effective in these tumors, especially for recurrent chordomas. Thus, new combinations of currently available targeted molecular and biological therapies with radiotherapy have been proposed as potential treatment modalities. Here, the present paper describes the case of a 41-year-old male with a C2-C4 chordoma located paravertebrally, who underwent surgical resection with a debulking procedure for a cervical chordoma. Computed tomography angiography revealed a paraspinal mass with bone remodeling and the MRI showed a paravertebral mass penetrating to the spinal canal with a widening of the intervertebral C2-C3 foramen. Initially, the tumor was diagnosed as schwannoma based on its localization and imaging features; however, the histopathology specimen confirmed the diagnosis of chordoma. This case study highlights the effectivity of radical surgical resection as a mainstay treatment for chordomas, discusses neuroimaging, diagnosis, and the use of currently available targeted therapies and forthcoming treatment strategies, as alternative treatment options for chordoma.

Evaluation of changes in cervical sagittal balance and clinical parameters in patients undergoing two-level anterior cervical discectomy and fusion.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) is an effective method in treating cervical sagittal imbalance and spine deformations. OBJECTIVES: The aim of this work was to assess whether changes of the Cobb angle, sagittal vertical axis (SVA) and T1 slope parameters affect the outcomes of surgical treatment. MATERIAL AND METHODS: A prospective study was performed in 30 patients qualified for surgical treatment for cervical degenerative disc disease. The ACDF was performed on 2 levels. Every patient underwent an X-ray examination before surgery and 3 months after the procedure. The following parameters were assessed: the T1 slope, the angle of cervical lordosis, the SVA distance, quality of life assessed using the Neck Disability Index (NDI), and perceived pain measurement assessed using the Visual Analogue Scale (VAS). RESULTS: The cervical lordosis angle significantly changed (p < 0.01) to an average of 11.52°. The SVA C2-C7 distance significantly decreased (p < 0.001) to an average of 21.06 mm. The value of the T1 slope angle did not change significantly before and after surgery (p = 0.706). After surgery, statistically significant improvement was achieved on the NDI scale for neck pain (p < 0.001) to an average of 9. The NDI score significantly decreased over time (p < 0.001), and this change was significantly related to the increased Cobb angle (p = 0.036). CONCLUSIONS: Improvement in cervical lordosis C2-C7 can improve the outcomes of surgical treatment. Preoperative analysis of X-rays and sagittal balance parameters may be beneficial for treatment outcomes.

The Role of ER Stress-Related Phenomena in the Biology of Malignant Peripheral Nerve Sheath Tumors.

Malignant peripheral nerve sheath tumors (MPNST) are rare but one of the most aggressive types of cancer. Currently, there are no effective chemotherapy strategies for these malignancies. The inactivation of the neurofibromatosis type I (NF1) gene, followed by loss of TP53, is an early stage in MPNST carcinogenesis. NF1 is a negative regulator of the Ras proteins family, which are key factors in regulating cell growth, homeostasis and survival. Cell cycle dysregulation induces a stress phenotype, such as proteotoxic stress, metabolic stress, and oxidative stress, which should result in cell death. However, in the case of neoplastic cells, we observe not only the avoidance of apoptosis, but also the impact of stress factors on the treatment effectiveness. This review focuses on the pathomechanisms underlying MPNST cells physiology, and discusses the possible ways to develop a successful treatment based on the molecular background of the disease.

Gross and Micro-Anatomical Study of the Cavernous Segment of the Abducens Nerve and Its Relationships to Internal Carotid Plexus: Application to Skull Base Surgery.

The present study aims to provide detailed observations on the cavernous segment of the abducens nerve (AN), emphasizing anatomical variations and the relationships between the nerve and the internal carotid plexus. A total of 60 sides underwent gross-anatomical study. Five specimens of the AN were stained using Sihler's method. An additional five specimens were subjected to histological examination. Four types of AN course were observed: a single nerve along its entire course, duplication of the nerve, division into separate rootlets at the point of contact with the cavernous part of the internal carotid artery (ICA), and early-branching before entering the orbit. Due to the relationships between the ICA and internal carotid plexus, the cavernous segment of the AN can be subdivided into a carotid portion located at the point of contact with the posterior vertical segment of the cavernous ICA and a prefissural portion. The carotid portion of the cavernous AN segment is a place of angulation, where the nerve always directly adheres to the ICA. The prefissural portion of the AN, in turn, is the primary site of fiber exchange between the internal carotid plexus and either the AN or the lateral wall of the cavernous sinus.

Redox Imbalance and Biochemical Changes in Cancer by Probing Redox-Sensitive Mitochondrial Cytochromes in Label-Free Visible Resonance Raman Imaging.

To monitor redox state changes and biological mechanisms occurring in mitochondrial cytochromes in cancers improving methods are required. We used Raman spectroscopy and Raman imaging to monitor changes in the redox state of the mitochondrial cytochromes in ex vivo human brain and breast tissues at 532 nm, 633 nm, 785 nm. We identified the oncogenic processes that characterize human infiltrating ductal carcinoma (IDC) and human brain tumors: gliomas; astrocytoma and medulloblastoma based on the quantification of cytochrome redox status by exploiting the resonance-enhancement effect of Raman scattering. We visualized localization of cytochromes by Raman imaging in the breast and brain tissues and analyzed cytochrome c vibrations at 750, 1126, 1337 and 1584 cm-1 as a function of malignancy grade. We found that the concentration of reduced cytochrome c becomes abnormally high in human brain tumors and breast cancers and correlates with the grade of cancer. We showed that Raman imaging provides additional insight into the biology of astrocytomas and breast ductal invasive cancer, which can be used for noninvasive grading, differential diagnosis.

Use of O-arm with neuronavigation in percutaneous vertebroplasty reduces the surgeon's exposure to intraoperative radiation.

INTRODUCTION: Percutaneous vertebroplasty is commonly used to treat spinal fractures. The authors compare radiation exposure as potential risk for the surgical team during vertebroplasty guided by O-arm combined with neuronavigation versus vertebroplasty guided by C-arm fluoroscopy. MATERIAL AND METHODS: The clinical material consisted of a group of 29 patients (44 vertebrae) with fractures of the thoracolumbar spine treated with percutaneous vertebroplasty guided by O-arm with neuronavigation. In this new method, the operating room staff leaves the operating room for the duration of the 3D scan of the appropriate spine section using the O-arm. In the next stage, the needle of the vertebroplasty system is introduced using only neuronavigation without the need for a radiological view. Finally, the cement injection was made under O-arm fluoroscopic control. The comparison group consisted of a group of 35 patients (40 vertebrae) treated with the classical method using C-arm fluoroscopy. The two methods were compared in terms of the average dose of emitted ionizing radiation through the device (O-arm vs. C-arm) to which surgeons are exposed during percutaneous vertebroplasty. RESULTS: As a result of vertebroplasty procedures guided by neuronavigation, a statistically significant difference between the values of mean dose of radiation emitted by O-arm and C-arm systems was noted. The O-arm emitted 912 cGy/cm2 vs. 1722 cGy/cm2 emitted by the C-arm during fluoroscopically assisted procedures and 601.28 cGy/cm2 vs. 1506.86 cGy/cm2 per vertebrae. CONCLUSIONS: During vertebroplasty with the O-arm combined with neuronavigation the radiation dose is significantly lower as compared with the C-arm used for fluoroscopic guidance, minimizing the potential risk of radiation exposure to surgeons.

Blood serum concentrations of gonadotropins and α-subunit in patients with gonadotropinomas in relation to the immunoreactivity of pituitary adenoma.

INTRODUCTION: Although active gonadotropin-secreting pituitary adenomas are considered very rare, the vast majority of pituitary tumours diagnosed as "non-functioning" express gonadotropins or their free ß or α subunits. However, systemic investigations comparing the serum concentrations of follitropin (FSH), lutropin (LH), and α-subunit (αSU) before surgery with the immunoreactivity of the respective substances in the excised tumours are still lacking. MATERIAL AND METHODS: Immunostaining of FSH, LH, and αSU was compared in 43 surgically removed gonadotropin - expressing pitu-itary adenomas with serum concentrations of the above-mentioned substances before surgery in the same patients. RESULTS: The serum concentrations of FSH were elevated (> 11.6 mU/mL) in 8/12 (66.7%) cases of FSH-positive adenomas. By contrast, in FSH-negative tumours the elevation of FSH is absent. Moreover, only 1/25 (4%) patients with LH-positive adenoma had the elevated serum concentration of LH (51.5 mU/mL). The overproduction of LH was not observed in adenomas expressing free ß LH or in LH-negative tumours. In patients with αSU-positive adenomas elevated serum levels of αSU were observed in 3/15 (20%) cases. No αSU elevations were observed in patients with αSU-negative adenomas. The mean serum FSH, LH, and αSU concentrations were higher in patients with FSH, LH, and/or αSU immunopositive tumours in comparison with immunonegative. However, the differences are not statistically significant. CONCLUSIONS: Although "silent" gonadotropinomas constitute a frequent subtype of pituitary adenomas, the "active" subtype (i.e. manifesting by gonadotropin excess) are rare (approx. 4% of all pituitary adenomas). Gonadotropinomas are difficult to diagnose before surgery. The measurement of gonadotropins including αSU is needed but often not sufficient for presurgical diagnosis.

The assessment of testosterone and radioisotopic index of bone metabolism and bone mineral density in men with testosterone deficiency after one year of testosterone therapy.

BACKGROUND: Testosterone deficiency in men is characterized by typical symptoms of hypogonadism and negative influence on the preservation of bone mass. In this study, we analysed the relationship between testosterone concentration and bone metabolism. Moreover, we assessed the impact of one-year compensation of testosterone deficiency in elderly men on bone metabolism and bone mineral density. Radioisotopic methods of bone metabolism assessment provide new research opportunities. MATERIALS AND METHODS: Men with total testosterone concentration (TT) ≤ 3 ng/ml were included into this study. Patients with disorders or injuries of bone system, elevated prostate-specific antigen (PSA), enlarged prostate, disorders of thyroid and liver, diabetes mellitus or a history of chemotherapy as well as those treated for a long time with antibiotics were excluded from this study. The results of 50 men aged 57.52 ± 6.71 years obtained before the treatment (I test) and after one year of oral testosterone supplementation (test II) were analysed in this study. The following examinations and analyses were performed: interview and physical examination, orthopaedic, neurological and urological consultations, blood biochemistry, determination of hormones levels, assessment of Testosterone Deficiency Syndrome (TDS), densitometric and radioisotope assessment of bone metabolism. Moreover, radioisotopic index of bone metabolism was calculated. Testosterone therapy with oral preparation Undestor Testo Caps (Organon) containing 40 mg of testosterone lasted for 12 months. Statistical analysis was performed using Statistica 12 and Excel 2010 programs. Correlations between results before and after treatment were analysed. RESULTS: After 12 months of treatment, testosterone concentration increased by mean 78% and the level of luteinizing hormone (LH) decreased by 62%. TDS index increased from 0.53 ± 0.21 (in test I) to 1.91 ± 0.60 (in test II). After the therapy this index was significantly higher in all men (p < 0.0001). Moreover, BMD was also improved following therapy, however, the difference between test I and II was statistically insignificant. The greatest change was found in case of IBM (Index of Bone Metabolism). We observed a positive correlation between IBM and BMD before treatment (r = 0.7991), however, its strength decreased after one-year therapy (r = 0.6757). CONCLUSIONS: In our opinion, IBM is more sensitive than other methods of the assessment of changes occurring in bone system under the influence of testosterone therapy. The observed changes in IBM were proportional to changes in testosterone concentration. Testosterone level, TDS and radioisotopic assessment of bone metabolism may be used as prognostic and therapeutic factors of osteoporosis and bone fractures in elderly men.

Eradication of LIG4-deficient glioblastoma cells by the combination of PARP inhibitor and alkylating agent.

Cancer cells often accumulate spontaneous and treatment-induced DNA damage i.e. potentially lethal DNA double strand breaks (DSBs). Targeting DSB repair mechanisms with specific inhibitors could potentially sensitize cancer cells to the toxic effect of DSBs. Current treatment for glioblastoma includes tumor resection followed by radiotherapy and/or temozolomide (TMZ) - an alkylating agent inducing DNA damage. We hypothesize that combination of PARP inhibitor (PARPi) with TMZ in glioblastoma cells displaying downregulation of DSB repair genes could trigger synthetic lethality. In our study, we observed that PARP inhibitor (BMN673) was able to specifically sensitize DNA ligase 4 (LIG4)-deprived glioblastoma cells to TMZ while normal astrocytes were not affected. LIG4 downregulation resulting in low effectiveness of DNA-PK-mediated non-homologous end-joining (D-NHEJ), which in combination with BMN673 and TMZ resulted in accumulation of lethal DSBs and specific eradication of glioblastoma cells. Restoration of the LIG4 expression caused loss of sensitivity to BMN673+TMZ. In conclusion, PARP inhibitor combined with DNA damage inducing agents can be utilized in patients with glioblastoma displaying defects in D-NHEJ.

Induction of apoptosis in human glioma cell lines of various grades through the ROS-mediated mitochondrial pathway and caspase activation by Rhaponticum carthamoides transformed root extract.

The present study is the first investigation of the inhibitory effect of Rhaponticum carthamoides transformed roots (TR) extract on the proliferation of grade II and III human glioma cells. TR extract showed the cytotoxic effect and inhibited the colony formation of both glioma cell lines in dose-dependent manner. The root extract induced apoptosis by increasing of the reactive oxygen species (about threefold compared to the control cells) leading to a disruption of mitochondrial membrane potential. Additionally, the mRNA levels of the apoptotic factors such as Bax, Tp53, caspase-3, and caspase-9 were observed to increase. These results indicate that the TR extract possesses anticancer activity by inhibiting glioma cell proliferation and inducing apoptotic cell death, and may be used as a promising anticancer agent.

Transformed Root Extract of Leonurus sibiricus Induces Apoptosis through Intrinsic and Extrinsic Pathways in Various Grades of Human Glioma Cells.

This study determines the influence of transformed root (TR) extract of Leonurus sibiricus L. on various grades (I-III) of human glioma cells derived from patients. This plant occurs in southern Asia and Siberia and is widely used as a medicinal plant with various biological activities. Chromatographic profile of TR extract have revealed the presence of various polyphenolic compounds (4-hydroxybenzoic acid, gentisic acid, vanilic acid, 1,3-dicaffeoylquinic acid, α-resorcylic acid). We found TR root extract to have antiproliferative activity on glioma cells after 24 h of treatment. TR root extract induces apoptosis on various grades (I-III) of human glioma cells by the generation of reactive oxygen species (ROS) along with concurrent loss of mitochondrial membrane potential, enhanced S and G2/M phases of the cell cycle, and altered mRNA levels of Bax, Bcl-2, p53, Cas-3, Cas-8 and Cas-9 factors involved in apoptosis. This work for the first time demonstrate that TR extract from L. sibiricus root has the potential to activate apoptosis in grade I-III human glioma cells through the intrinsic and extrinsic pathways.

Inhibition of human glioma cell proliferation by altered Bax/Bcl-2-p53 expression and apoptosis induction by Rhaponticum carthamoides extracts from transformed and normal roots.

OBJECTIVE: The objective of this study was to determine the cytotoxic effect and apoptotic activity of Rhaponticum carthamoides transformed root (TR) and root of soil-grown plant (NR) extracts in a human glioma primary cells. The effect of these root extracts on cell cycle arrest, mitochondrial membrane potential (ΔΨm) and expression levels of apoptosis-related genes (Bcl-2, Bax and p53) were also examined. METHODS: Cytotoxic activity of root extracts was evaluated by MTT assay. Apoptosis and cell cycle were determined by flow cytometry. Expression levels of apoptosis-related gene were analysed by RT-PCR and Western blotting. ΔΨm was examined by the use of JC-1 reagent. KEY FINDINGS: Rhaponticum carthamoides root extracts inhibit cell growth and induce apoptosis in a dose-dependent manner in human glioma cells. The root extracts were found to up-regulate the pro-apoptotic Bax protein and down-regulate the anti-apoptotic Bcl-2 protein, consequently increasing the ratios of Bax/Bcl-2 protein levels. Moreover, an increase of the p53 protein level and reduction of ΔΨm in glioma cells were observed after treatment with NR and TR extracts. CONCLUSION: The results of this study may offer a new insight into the potential anticancer activity of R. carthamoides root extracts.

"Silent" thyrotropin (TSH) expression in acromegaly and clinically non-functioning pituitary adenomas.

INTRODUCTION: The pituitary adenomas secreting thyrotropin (TSH) are considered the rarest type of hormonally active pituitary tumour. In spite of that, many cases are described in the literature. On the other hand, the observations of the co-expression of TSH with other pituitary hormones (mostly with growth hormone [GH]) and "silent" expression of TSH in clinically non-functioning pituitary adenomas (CNFPA) are rather scarce. MATERIAL AND METHODS: Among 93 examined pituitary adenomas, 22 of them were diagnosed as active acromegaly and 71 as clinically non-functioning pituitary adenomas (CNFPA). All of them were immunostained with antibodies against pituitary hormones, including the anti-TSH antibody. TSH-immunopositive adenomas are immunostained also to detect somatostatin receptor subtypes (SSTR 1-5). RESULTS: TSH immunopositivity was found in 4.2% of CNFPA (3/71 tumours) and in 13.6% (3/22) cases of somatotropinomas manifesting as active acromegaly. All of the examined TSH-immunopositive adenomas expressed SSTR subtypes except SSTR4. The symptoms of hyperthyroidism were not observed in any of the acromegalic patients co-expressing TSH with GH. CONCLUSIONS: Our data confirm the relative rarity of TSH expression or co-expression of TSH in pituitary tumours. In most cases TSH is co-expressed with GH in patients with acromegaly and is not accompanied by hyperthyroidism. The "silent" expression of TSH may occur also, although rarely in CNFPA. The strong expression of SSTR in TSH-immunopositive CNFPA ("silent thyrotropinoma") indicates the possibility of the treatment of these tumours with somatostatin analogues. (Endokrynol Pol 2016; 67 (5): 515-518).