Search

The expression and function of podoplanin (PDPN) in the normal human placenta has been debated in placental evaluation. This study emphasizes the importance of a multimodal approach of PDPN expression in normal human placentas. A complete examination is performed using immunohistochemistry, RNAscope and automated Digital Image examination (DIA) interpretation. QuPath DIA-based analysis automatically generated the stromal and histological scores of PDPN expression for immunohistochemistry and RNAscope stains. The umbilical cord’s isolated fibroblasts and luminal structures expressed PDPN protein and PDPN_mRNA. RNAscope detected PDPN_mRNA upregulation in syncytial placental knots trophoblastic cells, but immunohistochemistry did not certify this at the protein level. The study found a significant correlation between the IHC and RNAscope H-Score (p = 0.033) and Allred Score (p = 0.05). A successful multimodal strategy for PDPN assessment in human placentas confirmed PDPN expression heterogeneity in the full-term human normal placenta and umbilical cord at the protein and mRNA level. In placental syncytial knots trophoblastic cells, PDPN showed mRNA overexpression, suggesting a potential role in placenta maturation.

Backround: Depression is a significant concern in clinical and preclinical psychoneurobiological sciences due to its high prevalence and its individual and collective consequences. Identifying efficient biomarkers for accurate diagnosis is crucial, with ideal biomarkers having detectable serum levels and conformational and thermal stability. This study aims to identify stable plasma biomarkers for the diagnosis and prognosis of major depressive disorder, as the pathogenesis of the disorder remains incompletely understood, affecting diagnosis accuracy. Methods: Thus, this study included ten MDD patients and eight healthy controls. The present work analyzed miRNAs in patients with major depressive disorder compared to healthy controls. Results: Eleven specific miRNAs, particularly hsa-miR-874-3p; hsa-let-7d-5p; and hsa-miR-93-3p showed upregulation-type plasma variations in the group of patients with major depressive disorder. miRNA functionality is linked to depressive pathophysiology. Conclusions: This study identifies a “bouquet” of miRNAs with significant upregulation variations in patients with major depressive disorder, suggesting further research to determine their suitability for personalization and evaluation, ultimately becoming integral components of major depression serological evaluations.

Vasculogenesis, which refers to the development of blood vessels from precursor cells, is a process that occurs predominantly during early embryonic life. It plays a crucial role in the establishment of the primitive vascular network. Vasculogenesis diminishes throughout the fetal vascular remodeling process, giving way to angiogenesis, which becomes the predominant mechanism after birth. At first, the development of the kidney’s blood vessels depends on vasculogenesis, and then both vasculogenesis and angiogenesis happen simultaneously. Both processes are necessary for the normal development of the renal vasculature. Although the kidneys are highly vascularized, our understanding of normal kidney vasculogenesis is still incomplete. This lack of knowledge may explain the limited data available on the role of vasculogenesis in the progression and spread of renal cancers. In other types of cancer, researchers have well documented the phenomenon of tumor vasculogenesis. However, there is currently limited and fragmented information about the occurrence of clear-cell renal cell carcinomas (cc-RCC). In this article, we provide a comprehensive review of the current understanding of normal kidney vasculogenesis and vasculogenic pathways in clear cell renal cell carcinoma (cc-RCC). We specifically focus on cellular precursors, growth factors, and the influence of the normal and tumor environments on these processes. It will carefully look at how tumor vasculogenesis might affect the growth and metastasis of clear cell renal cell carcinoma (cc-RCC), as well as how it might affect the effectiveness of drugs and the development of therapy resistance.

Background and Objectives: Our aim was to perform a retrospective analysis of the volume of cervical screening tests, the number of patients treated with an excision method, and the incidence of invasive and non-invasive cervical during a pandemic and pre-pandemic period of 24 months. Materials and Methods: The study compared 404 patients who underwent cervical cone biopsy for cervical cancer. The study examined patients’ specimens based on histopathological characteristics and categorized cervical lesions based on pap smear. Results: There was a statistically significant age difference between the two study periods. The mean difference was 32 years before the pandemic and 35 years during the pandemic (p-value > 0.05). The biggest patient loss ratio identified by age group was in the 50–59-year group, with a 14.53% loss in the pre-pandemic period and a 9.1% loss in the pandemic period. In the pandemic period, patients from rural areas presented in the clinical trial with a lower rate of 39.52% (83 patients) vs. 60.47% (127 patients) in urban areas. A higher percentage of patients experiencing cervicorrhagia as a clinical manifestation in the pandemic period vs. the pre-pandemic period, with an increase in more severe lesions in the pandemic period, had a statistical significance of 8% more newly diagnosed compared to the pre-pandemic period. Conclusions: The addressability of the patients during the COVID period was not affected in a drastic way in our study. We encountered a decrease in appointments in the age group of 50–59 years and a decrease in patients with rural residence. In our study, we found an increase in cervical bleeding as a reason for consultation in the pandemic period with a higher lesion degree, both on a pap smear and on a cervical biopsy.

This systematic review evaluates the clinical outcomes and molecular predictors of response to pembrolizumab in patients with advanced and metastatic cervical cancer. We adhered to the PRISMA guidelines for systematic reviews, conducting a database search in PubMed, Scopus, and Embase. The eligibility criteria centered on clinical outcomes, including the overall survival (OS), progression-free survival (PFS), and immune-related biomarkers post-pembrolizumab therapy. We included both prospective and retrospective studies that detailed clinical outcomes and molecular characteristics predictive of therapeutic response. Our search yielded six studies involving 846 patients treated with pembrolizumab from 2017 to 2022. The meta-analysis of these studies showed that pembrolizumab, used as monotherapy or in combination with chemotherapy, extended the OS by a weighted median of 10.35 months and the PFS by 8.50 months. The treatment demonstrated a pooled objective response rate (ORR) of 22.39%, although the I2 test result of 67.49% showed a high heterogeneity among the studies. Notably, patients with high PD-L1 expression (CPS ≥ 10) experienced improved outcomes in terms of the PFS and OS. The most common complications were fatigue, diarrhea, and immune-related adverse events. Pembrolizumab significantly enhances clinical outcomes in metastatic cervical cancer, particularly among patients with high PD-L1 expression. The drug maintains a good safety profile, reinforcing its treatment potential for patients with advanced and metastatic cervical cancer. Future studies should explore long-term effects and strategies to integrate pembrolizumab optimally into current treatment regimens, aiming to maximize patient benefits and effectively manage side effects.

Type I collagen, prevalent in the extracellular matrix, is biocompatible and crucial for tissue engineering and wound healing, including angiogenesis and vascular maturation/stabilization as required processes of newly formed tissue constructs or regeneration. Sometimes, improper vascularization causes unexpected outcomes. Vascularization failure may be caused by extracellular matrix collagen and non-collagen components heterogeneously. This study compares the angiogenic potential of collagen type I-based scaffolds and collagen type I/glycosaminoglycans scaffolds by using the chick embryo chorioallantoic membrane (CAM) model and IKOSA digital image analysis. Two clinically used biomaterials, Xenoderm (containing type I collagen derived from decellularized porcine extracellular matrix) and a dual-layer collagen sponge (DLC, with a biphasic composition of type I collagen combined with glycosaminoglycans) were tested for their ability to induce new vascular network formation. The AI-based IKOSA app enhanced the research by calculating from stereomicroscopic images angiogenic parameters such as total vascular area, branching sites, vessel length, and vascular thickness. The study confirmed that Xenoderm caused a fast angiogenic response and substantial vascular growth, but was unable to mature the vascular network. DLC scaffold, in turn, produced a slower angiogenic response, but a more steady and organic vascular maturation and stabilization. This research can improve collagen-based knowledge by better assessing angiogenesis processes. DLC may be preferable to Xenoderm or other materials for functional neovascularization, according to the findings.

Background–digitalization in eastern European medical education is a stringent need of teaching and assessment processes, which must be updated to challenges continuously launched by medical students. In this context, our university implemented an e-learning and e-assessment system in histology, a preclinical education subject. Aim–to evaluate the impact of replacing a classic learning and assessment methods with a completely digitized one. Methodology–the new system impact on students’ skills and teacher’s performance, was evaluated by using an opinion pool questionnaire including as assessment criteria system compliance, student-teacher interaction, online access improvement and new facilities regarding e-assessment and time management was performed. Results–“computer gaming” was delightful for students. Management of information’s given to students was improved by a higher standardization and this, helped them to pass evaluations easier.

Background: Tertiary lymphoid structures (TLSs) mediate local antitumor immunity, and interest in them significantly increased since cancer immunotherapy was implemented. We examined TLS− tumor stromal blood vessel interplay for each breast cancer (BC) molecular subtype related to recurrence, lymphovascular invasion (LVI), and perineural invasion (PnI). Methods: TLSs were quantified on hematoxylin and eosin stain specimens followed by CD34/smooth muscle actin (SMA) double immunostaining for stromal blood vessel maturation assessment. Statistical analysis linked microscopy to recurrence, LVI, and PnI. Results: TLS negative (TLS−) subgroups in each BC molecular subtype (except to Luminal A) have higher LVI, PnI, and recurrence. A significant rise in LVI and PnI were observed for the HER2+/TLS− subgroup (p < 0.001). The triple negative breast cancer (TNBC)/TLS− subgroup had the highest recurrence and invasion risk which was also significantly related to tumor grade. PnI but not LVI significantly influenced recurrence in the TNBC/TLS+ subgroup (p < 0.001). TLS−stromal blood vessel interrelation was different amongst BC molecular subtypes. Conclusion: BC invasion and recurrence are strongly influenced by TLS presence and stromal blood vessels, especially for HER2 and TNBC BC molecular subtypes.

A rare, uncommon disorder called PHACE(S) (P-posterior fossa anomalies, H-hemangioma, A-arterial anomalies, C-cardiac anomalies, E-eye anomalies, and S-sternal cleft) of unknown etiology was rarely reported. Children are susceptible to developing PHACE(S) syndrome from the moment they are born. It may be challenging for a physician to appropriately diagnose and treat children with PHACE due to the multifaceted nature of the disease and the extensive range of consequences that may be associated with it. A one-month-old newborn girl was admitted to hospital with extensive, multiple facial infantile hemangiomas, ulceration of the lower lip hemangioma-like lesion, cardiovascular, sternal, and neurological concomitant malformations. Five days following the initial application of the medication, systemic treatment with propranolol and topical treatment with silver sulfadiazine produced their first noticeable benefits. The lip ulceration was mostly healed and facial hemangioma started to regress. The regression continued under therapy and this effect persists for 6 months since Propranolol therapy ended. No cardiovascular or neurological clinical events have been registered during follow-up. The present case has three peculiarities: (1) high number of facial hemangiomas; (2) presence of subependymal cyst not yet reported in the literature associated with PHACE syndrome; and (3) lack of cardiovascular events during therapy knowing that these events frequently appear in PHACE syndrome patients.

Background. Infantile hemangiomas may have unexpected behavior. Initial regression (spontaneously or drug-induced) may be followed by unexplained recurrences. At this moment, there are no well-established criteria to predict infantile hemangioma reccurrences. Methods. We compared the VEGF pathway gene expression profile for one case of involuting infantile hemangioma versus one case of recurrent proliferative infantile hemangioma using TaqMan Array. Results. We found ten genes upregulated for both involuting and recurrent proliferative hemangiomas: ACTB, KRAS, MAP2K1, HRAS, NOS3, BAD, HSPB1, HPRT1, GUSB, and CASP9. Thirteen genes were downregulated for both involuting and proliferative hemangiomas: FIGF, ACTG1, GRB2, MAPKAPK2, ACTG2, MAP2K2, MAPK3, HSP90AA1, MAP2K6, NRAS, ACTA1, KDR, and MAPK1. Three genes showed divergent expression between proliferating and involuting hemangiomas. Proliferating hemangioma had MAPK14 and AKT1 gene upregulation and ACTA2 downregulation. Involuting infantile hemangioma was characterized by ACTA2 upregulation and AKT1 and MAPK14 downregulation. Conclusions. Three genes, AKT1, p38/MAPK14, and ACTA2, were found to have divergent expression in proliferating and involuting infantile hemangiomas. Excepting AKT1, which was mentioned in the last ISSVA classification (strictly related to Proteus Syndrome), none of the other genes were reported. An accurate gene expression profile mapping of infantile hemangiomas together with a gene expression-based hemangioma classification is stringently needed.

Background: Due to its anti-apoptotic and anti-proliferative contradictory functions, BCL2 role in breast carcinoma progression is not clearly understood. The purpose of this study was to highlight BCL2 expression during metastatic progression of invasive breast carcinoma of no special type (NST). Materials and methods: The specimens, primary tumors and corresponding lymph node metastases (LNM) from 84 patients were immunostained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER)-2, basal cytokeratin CK5, nuclear protein Ki67 and B-cell lymphoma (Bcl)-2 receptor. Results: BCL2 expression was higher at primary site than in axillary metastases. Its score correlates positively with hormone receptors’ level and negatively with HER2, CK5 and Ki67 at both sites. Switch of molecular profile was determined in 22.62% of cases. BCL2 expression was not influenced by subtypes switch. Changes of BCL2 expression were found in 25% of cases with stable molecular subtype. The Luminal A and Luminal B/Ki67 were encountered in the majority of BCL2 transitions, mainly from positive to negative state. Conclusions: Molecular subtypes and BCL2 expression are not stable during tumor progression and metastatic development. In the present study we established immunohistochemically that BCL2 is not influenced by subtypes’ transitions. BCL2 switches were encountered only in cases with a stable HER2, Luminal A or B phenotypes. We expect a further confirmation of our results by other research groups.

Otolaryngology is mainly associated with clinical practice. Despite of this actual evidence, otolaryngology can be considered, from historical point of view as a complex speciality made up of a mixture of several preclinical specialities as anatomy, histology, pathology and physiology. Several scientists who studied these specialities first, became then otolaryngologists and others were known in the medical literature because of their studies in other specialities than otolaryngology. Most of the historical papers were focused on the ear, other regions being neglected. This review presents the forgotten part of otolaryngology, especially its preclinical facts with importance in etiology and pathogenesis of various disease of the ear, nose and throat structures and thus, present work can be considered as a particular overview of „forgotten” otolaryngology

VEGF (vascular endothelial growth factor) and the receptor for VEGF- Flk-1 (fetal liver kinase 1) are important players of normal and pathologic angiogenesis. Also, it was proved that they are involved in tumor progression and metastasis in many tumors types by overexpression in cancer cells. Liver malignances and premalignant lesions represent controversial issues concerning VEGF and VEGFR2 (vascular endothelial growth factor receptor 2) expression and their potential involvement in the progression of inflammatory and cirrhotic lesions and also in malignant transformation is virtually unknown. The aim of this work was to describe the differentiate expression and distribution of VEGF and VEGFR2 in chronic hepatitis and liver cirrhosis, and according to these findings to better characterize the molecular profiling of liver disease with malignant transformation potential. We investigated 20 cases with chronic hepatitis and cirrhosis on specimens taken during surgery. Immunohistochemistry was performed in all cases for VEGF, VEGFR2, and FVIII related antigen (Von Willebrand factor). We found significant correlation between HAI (histological activity index) value, VEGF and VEGFR2 expression and factor FVIII related antigen in central part of specimens with chronic hepatitis. Liver cirrhosis lacks this correlation. Our findings suggested that VEGF dependent angiogenesis is more active in chronic hepatitis in the center of the lesion compared with cirrhosis where MVD (microvessel density) is higher at the periphery of the nodules. We hypothesize that the involvement of VEGF and VEGFR2 complex in development of chronic hepatitis and liver cirrhosis could be considered for the use of anti VEGF antibodies as adjuvant therapy in early stages of these diseases

The present study proposes a classification of renal cancer tumor blood vessels according to their morphology and maturation grade. We identified four vascular patterns: reticular, diffuse, fasciculated and trabecular. The reticular pattern was present in 63% of cases, being characterized by the predominance of mature CD34+/SMAct+ tumor vessels, highly interconnected. For this pattern, 74% of cases had vascular invasion, and a significant correlation was observed between tumor grade and immature state of tumor vessels (p = 0.022). The diffuse pattern was observed in 23% of cases and was characterized by non-interconnected vessels predominantly of mature CD34+/SMAct+ type and vascular invasion in 64% of cases. Only 8% of cases, had a fasciculate model of vessels distribution, all of them being of mature type, located in the connective axis of papillary renal tumors. For this pattern vascular invasion was found in 50% of cases. In 6% of cases a trabecular pattern was observed and the lowest rate of vascular invasion was registered. We defined here four distinct vascular patterns in renal cell carcinomas showing a strong impact on vascular invasion. A complete morphological and molecular characterization of tumor vessels would be beneficial in elucidating the mechanisms that underlie the ineffectiveness of antiangiogenic/antitumor therapies.

Angiogenesis in normal and pathological conditions is a multi-step process governed by positive and negative endogenous regulators. Many growth factors are involved in different steps of angiogenesis, like vascular endothelial growth factors (VEGF), fibroblast growth factor (FGF)-2 or platelet-derived growth factors (PDGF). From these, VEGF and FGF-2 were extensively investigated and it was shown that they significantly contribute to the induction and progression of angiogenesis. A lot of evidence has been accumulated in last 10 years that supports the contribution of PDGF/PDGFR axis in developing angiogenesis in both normal and tumoral conditions. The crucial role of PDGF-B and PDGFR-β in angiogenesis has been demonstrated by gene targeting experiments, and their expression correlates with increased vascularity and maturation of the vascular wall. PDGF and their receptors were identified in a large variety of human tumor cells. In experimental models it was shown that inhibition of PDGF reduces interstitial fluid pressure in tumors and enhances the effect of chemotherapy. PDGFR have been involved in the cardiovascular development and their loss leads to a disruption in yolk sac blood vessels development. PDGFRβ expression by pericytes is necessary for their recruitment and integration in the wall of tumor vessels. Endothelial cells of tumor-associated blood vessels can express PDGFR. Based on these data, it was suggested the potential benefit of targeting PDGFR in the treatment of solid tumors. The molecular mechanisms of PDGF/PDGFR-mediated angiogenesis are not fully understood, but it was shown that tyrosine kinase inhibitors reduce tumor growth and angiogenesis in experimental xenograft models, and recent data demonstrated their efficacy in chemoresistant tumors. The in vivo effects of PDGFR inhibitors are more complex, based on the cross-talk with other angiogenic factors. In this review, we summarize data regarding the mechanisms and significance of PDGF/PDGFR expression in normal conditions and tumors, focusing on this axis as a potential target for antitumor and antiangiogenic therapy.

We compared the immunoprofile of pituitary adenomas from Romania and Moldova. One hundred and eighty cases coming from Romania (94 cases, group 1) and Moldova (86 cases, group 2) were assessed by immunohistochemistry regarding all six basic hormones expressed in pituitary adenomas. Specific differences and similarities were found and stated for both groups. In group 1, 70% of cases were pituitary adenomas positive for one hormone, 13% were plurihormonal, while 17% were negative. In group 2, 50,3% of the cases expressed only one hormone and 12,5% were negative for all hormones. The highest difference was observed for plurihormonal adenomas, found in about 37,2% of cases for group 2 (2.86 times higher for group 2 compared with group 1). A higher incidence of GH-secreting adenomas characterized group “1,” while group “2” had the highest percent of LH-secreting adenomas, 55% of cases being positive. Triple association was noticed in 4.25% of cases of group 1 and in 8,13% out of total cases, from group 2. Four-hormone association was found only in group 2, noticed in 15,56% of the cases. The present paper highlights strong evidences of a particular and different immunoprofile of pituitary adenomas coming from Romania and Moldova.

Objective Controversial, heterogeneous, and inconsistent responses to beta-blockers have been reported in some cases of infantile proliferative hemangiomas. On the basis of these clinical observations, we aimed to examine the β1 adrenergic receptor (β1-AR) protein expression distribution among different types of pediatric vascular anomalies. Methods Immunohistochemistry (IHC) was performed for β1-AR on 43 surgical specimens. Results We found positive β1-AR IHC staining in all intramuscular hemangiomas, capillary–lymphatic, lymphatic, venous, and combined malformations, and Masson’s tumor cases, as well as in 7 of 10 cases of proliferative infantile hemangiomas. Conclusions Our research demonstrates, for the first time, the degree of heterogeneous expression of β1-AR among pediatric vascular malformations. Our results support the need for β1-AR assessment in pediatric vascular anomalies to select cases with a robust response to β1-selective blockers. β1-AR assessment may have a strong impact on therapeutic refinement for pediatric vascular anomalies by selecting cases with a stronger response to beta-blockers.

Vascular endothelial growth factor (VEGF), its inhibitory splice variant, VEGF165b and Endocrine Gland derived VEGF (EG-VEGF) have a controversial role in pituitary gland. We aim to study VEGF, VEGF165b and EG-VEGF expression in pituitary adenomas. A significant correlation was found between growth hormone (GH) and VEGF secretion (P=0.024). For prolactinomas, VEGF and prolactin expression, had a P-value of 0.02 for Kendall coefficient and a P-value of 0.043 for the Spearman coefficient. VEGF-mRNA amplification was detected in both tumor cells and folliculostellate cells. VEGF165b was positive in 16.66% of pituitary adenomas. EG-VEGF was significantly correlated with prolactin (P=0.025) and luteinizing hormone (P=0.028). Our data strongly support VEGF, VEGF165b and EG-VEGF as important players of pituitary adenomas tumorigenesis. Particular hormonal milieu heterogeneity, special vascular network with an unusual reactivity to tumor growth correlated with variability of VEGF, VEGF165b and EG-VEGF secretion may stratify pituitary adenomas in several molecular groups with a direct impact on therapy and prognosis.

Objective. Breast cancer is a one of the most common cancers in females worldwide. Basal cytokeratin CK5 represent the marker of progenitors for glandular and myoepithelial lineages of mammary epithelium. During epithelial differentiation there is a gradual decrease of CK5 expression. The purpose of this study was to compare the expression of basal cytokeratin CK5 vs hormone receptors, HER2, Ki67 and molecular subtypes immunohistochemically defined in the primary breast carcinoma of NST type and axillar lymph node metastasis. Material and Methods. We processed immunohistochemically 91 invasive breast carcinomas of NST type and their ipsilateral axillar lymph node metastasis (LNM). Results. The majority of primary tumors were evaluated as CK5 negative (78 cases/85.7%). The majority of cases were evaluated as Luminal B (50 cases/54.9%) and Luminal A (28 cases/30.8%) tumors. The HER2 subtype was confirmed in 8 cases/8.8%, 5NP in 3 cases/3.3% and Basal-like in 2 cases/2.2%. The parallel comparison of CK5 expression at both sites, primary and metastatic, revealed that this marker is not stable during metastatic progression. The molecular subtypes were not stable during metastatic process in 21 cases/23.1%. Conclusions. The majority of NST invasive ductal breast carcinomas are CK5 negative. The molecular subtypes and CK5 are not stable during metastatic process. Cancerous cells prefer to lose this marker in the lymph node environment. The presence of cases with simultaneous expression of CK5 and hormone receptors is an open field to debate the existence of other, transient molecular subtypes. We expect a further confirmation in larger study groups.

Purpose. Epidermal growth factor receptor (EGFR, HER1) and human epidermal receptor 2 (HER2) assessement in pituitary adenomas related to hormone profile. Design and methods. For 60 retrospective cases of pituitary adenomas, we established the histopathologic diagnosis by using morphological stains, followed by case selection for immunoprofile and EGFR and HER 2 assessement. Results. More than one third of the studied pituitary adenomas (33,33%) were positive for HER2, with membranar pattern in basophilic cells and with predominantly cytoplasmic, granular pattern for acidophils cells. HER2 immuno-expression characterized PRL secreting adenomas (p=0.005) and associations between FSH-LH (p< 0.001) TSH-FSH (p=0,024) and TSH-LH (p=0.028). In situ hybridization confirmed HER2 gene amplification in 33,34% out of all positive cases for HER2 by immunohistochemistry. EGFR positivity was found significantly for GH-prolactin (p=0.000) and prolactin-ACTH (p=0.045) co-expressing pituitary adenomas, peritumoral macrophages and folliculostellate cells. Conclusions. Differential HER2 and EGFR expression related to hormone profile heterogeneity can define different subclasses of pituitary adenomas and could explain clinical, prognostic and therapeutic heterogeneity which are observed in clinical practice. Our results support re-classification of pituitary adenomas based on molecular approach which should include markers with well certified prognostic and therapeutic impact.

Pituitary adenomas represent the third most common primary intracranial tumor in neurosurgical practice. To understand the biological behaviour of the pituitary adenomas previous studies have determined the tumor proliferation rate using monoclonal antibodies targeted against the Ki-67 antigen. The aim of this study was to correlate the Ki-67 index with hormonal profiles of pituitary adenomas. The study included 50 pituitary adenomas. For histopathologic evaluation, the sections were stained with routine hematoxylin and eosin method. Additional paraffin sections from each tumor were immunostained using primary antibodies against the following pituitary hormones: somatotropin (STH), prolactin (PRL), adrenocorticotrophic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). To detect the expression of Ki-67 we used a mouse anti-human monoclonal antibody (clone K2). The percentage of Ki-67 positive nuclei (Ki-67 labeling index) was assessed by counting approximately 1000 nuclei of the tumor cells at ×400 magnification. Out of the 50 tumor samples, 31 (62%) pituitary adenomas showed proliferative activity, and the proliferation rate was variable in this group. The overall mean Ki-67 labeling index was 1.59 ± 1.47, ranging from 0.3% to 6.6%. In 5 cases, the Ki-67 index was >3%, all of them being prolactinomas. The Ki-67 index was higher in PRL-secreting adenomas (mean ± SD was 3.37 ± 1.80, range 0.9 - 6.6%). Our study provides the evidence that a higher Ki-67 value is associated with pituitary adenomas that secrete PRL (prolactinomas and mixed STH/PRL-secreting adenomas).

A lot of data suggests endocrine gland-derived vascular endothelial growth factor (EG-VEGF) to be restricted to endocrine glands and to some endocrine-dependent organs. Many evidences show that EG-VEGF stimulates angiogenesis and cell proliferation, although it is not a member of the VEGF family. At the time, a lot of data regarding the role of this growth factor in normal development are available. However, controversial results have been published in the case of pathological conditions and particularly in malignant tumors. Thus, our present paper has been focused on the role of EG-VEGF in normal tissues and various malignant tumors and their angiogenic processes.

OBJECTIVES The aim of our study was to assess the effect of autologous fat graft on nerve regeneration by creating a suitable experimental model. MATERIALS AND METHODS The rat sciatic nerve was used, followed by transaction. Primary neurorrhaphy was made on both hind legs, but a processed fat graft was applied on one side, surrounding the nerve. RESULTS We used histological examination for the followup, at 4 and 10 weeks. The results showed an increased and a more organised neural regeneration on the side where the fat graft was used. CONCLUSIONS The adipose-derived stem cell has clearly demonstrated its capacity to transdifferentiate. However, its specific role in this process is not yet clearly understood. We attempted to explore the blunt effect of this cell on direct neurrorhaphy. We did not observe a categorical differentiation towards Schwann like cell, but mostly an antifibrotic and antiinflammatory effect. Graphical abstract: Technical aspects of fat grafting on neurorrhaphy. REFERENCES 1. Raposio E, Caruana G, Bonomini S, Libondi G. A novel and effective strategy for the isolation of adipose-derived stem cells: minimally manipulated adipose-derived stem cells for more rapid and safe stem cell therapy. Plast Reconstr Surg. 2014;133:1406-9. 2. Zack-Williams SDL, Butler PE, Kalaskar DM. Current progress in use of adipose derived stem cells in peripheral nerve regeneration. World J Stem Cells. 2015; 7: 51–64. 3. Zuk PA. The Adipose-derived Stem Cell: Looking Back and Looking Ahead. Mol Biol Cell. 2010;21:1783–1787.