Pre-Exposure Prophylaxis and Treatment with Tixagevimab/Cilgavimab for COVID-19 among Immunocompromised Pediatric Patients.

Background: Patients treated with hemato-oncological malignancies (HO) or undergoing cellular therapies such as hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cells (CAR-T) were significantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the success of SARS-CoV-2 vaccination, immunocompromised patients remain at increased risk for severe coronavirus disease (COVID-19), rendering this group of population a high priority for additional prevention and treatment options. Tixagevimab and Cilgavimab (TIXA/CILGA, AZD7442, Evusheld®) is a combination of two fully human, long-acting monoclonal antibodies. TIXA/CILGA have been approved as pre-exposure prophylaxis and treatment in patients at risk of severe disease with impaired vaccine response. Our objective was to describe the efficacy and safety among immunocompromised pediatric patients. Methods: This was an observational multicenter cohort study of immunocompromised pediatric patients receiving TIXA/CILGA conducted at nine Polish centers of Pediatric Oncology, Hematology and Bone Marrow Transplantation. We analyzed patients in two groups; those treated with HO and those undergoing cellular therapies: HSCT or CAR-T cells. In addition, two other cohorts were identified: patients given TIXA/CILGA as pre-exposure prophylactic and therapeutic intervention. Results: A total of 78 patients were evaluated during the study period: 69 (88.5%) received TIXA/CILGA as pre-exposure prophylaxis and 9 (11.5%) as a treatment strategy. A total of 52 (66.6%) patients were treated with standard chemotherapy at HO departments; 21 (27%) underwent HSCT, and 5 (6.4%) received CAR-T cell therapy. All children with COVID-19 receiving TIXA/CILGA presented a mild degree of severity. The most common clinical manifestations were fever, cough and coryza. At least one adverse event (AE) was reported in two (3.8%) patients excluding standard injection site reactions. Reported AEs were mild or moderate in intensity. One child reported mild myalgia and one reported moderate bone pain and weakness. Conclusions: In our observational multicenter cohort study, we explored the use of TIXA/CILGA as pre-exposure prophylaxis and treatment for COVID-19 among immunocompromised pediatric patients. While our findings suggest a potential benefit in preventing and managing COVID-19 in this vulnerable population, it is important to note the study's non-comparative design. Our results highlight the need for well-designed clinical trials to confirm these observations and further assess the efficacy and safety of TIXA/CILGA in immunocompromised children.

The Immunohistochemical Expression of Epithelial-Mesenchymal Transition Markers in Precancerous Lesions and Cervical Cancer.

In the epithelial-mesenchymal transition (EMT) process, cells lose their epithelial phenotype and gain mesenchymal features. This phenomenon was observed in the metastatic phase of neoplastic diseases, e.g., cervical cancer. There are specific markers that are expressed in the EMT. The aim of this study was to determine the localization of and associations between the immunohistochemical (IHC) expression of TWIST, SNAIL, and SLUG proteins in precancerous lesions and cervical cancer. The IHC analysis disclosed higher expressions of EMT markers in precancerous lesions and cervical cancer than in the control group. Moreover, stronger expression of TWIST, SNAIL, and SLUG was observed in cervical intraepithelial neoplasia grade 3 (CIN3) vs. CIN1, CIN3 vs. CIN2, and CIN2 vs. CIN1 cases (p < 0.05). In cervical cancer, IHC reactions demonstrated differences in TWIST, SNAIL, and SLUG expression in grade 1 (G1) vs. grade 2 (G2) (p < 0.0011; p < 0.0017; p < 0.0001, respectively) and in G1 vs. grade 3 (G3) (p < 0.0029; p < 0.0005; p < 0.0001, respectively). The results of our study clearly showed that existing differences in the expression of the tested markers in precancerous vs. cancerous lesions may be utilized in the diagnosis of cervical cancer. Further studies on bigger populations, as well as in comparison with well-known markers, may improve our outcomes.

The Expression of Testin, Ki-67 and p16 in Cervical Cancer Diagnostics.

Testin is a protein expressed in normal human tissues, being responsible, with other cytoskeleton proteins, for the proper functioning of cell−cell junction areas and focal adhesion plaques. It takes part in the regulation of actin filament changes during cell spreading and motility. Loss of heterozygosity in the testin-encoding gene results in altered protein expression in many malignancies, as partly described for cervical cancer. The aim of our study was the assessment of the immunohistochemical (IHC) expression of testin in cervical cancer and its analysis in regard to clinical data as well the expression of the Ki-67 antigen and p16 protein. Moreover, testin expression was assessed by Western blot (WB) in commercially available cell lines. The IHC analysis disclosed that the expression of testin inversely correlated with p16 (r = −0.2104, p < 0.0465) and Ki-67 expression (r = −0.2359, p < 0.0278). Moreover, weaker testin expression was observed in cancer cases vs. control ones (p < 0.0113). The WB analysis of testin expression in the cervical cancer cell lines corresponded to the IHC results and showed a weaker expression compared to that in the control cell line. When we compared the expression of testin in cervical cancer cell lines, we found a weaker expression in HPV-negative cell lines. In summary, we found that the intensity of testin expression and the number of positive cells inversely correlated with the expression of Ki-67 (a marker of proliferation) and p16 (a marker of cell cycle dysregulation). This study shows that the combined assessment of testin, Ki-67 and p16 expression may improve cervical cancer diagnostics.

The Immunohistochemical Expression of MCM-3, -5, and -7 Proteins in the Uterine Fibroids.

Uterine fibroids are the most common mesenchymal uterine neoplasms; their prevalence is estimated in 40%-60% of women under 35 and in 70%-80% of women over 50 years of age. The current research aims to focus on the etiopathogenesis of uterine fibroids, the factors that affect their growth, and markers with diagnostic and prognostic properties. The MCM (minichromosome maintenance) protein family consists of peptides whose primary function is participation in the molecular mechanism of creating replication forks while regulating DNA synthesis. The aim of this work was to determine the proliferative potential of uterine fibroid cells based on the expression of the Ki-67 antigen and the MCMs-i.e., MCM-3, MCM-5, and MCM-7. In addition, the expression of estrogen (ER) and progesterone (PgR) receptors was evaluated and correlated with the expression of the abovementioned observations. Ultimately, received results were analyzed in terms of clinical and pathological data. MATERIALS AND METHODS: In forty-four cases of uterine fibroids, immunohistochemical reactions were performed. A tissue microarray (TMA) technique was utilized and analyzed cases were assessed in triplicate. Immunohistochemistry was performed using antibodies against Ki-67 antigen, ER, PgR, MCM-3, MCM-5, and MCM-8 on an automated staining platform. Reactions were digitalized by a histologic scanner and quantified utilizing dedicated software for nuclear analysis. Assessment was based on quantification expression of the three histiospots, each representing one case in TMA. RESULTS: In the study group (uterine fibroids), statistically significant stronger expression of all the investigated MCMs was observed, as compared to the control group. In addition, moderate and strong positive correlations were found between all tested proliferative markers. The expression of the MCM-7 protein also correlated positively with ER and PgR. With regard to clinical and pathological data, there was a negative correlation between the expression of MCMs and the number of both pregnancies and births. Significant reductions in MCM-5 and MCM-7 expression were observed in the group of women receiving oral hormonal contraceptives, while smoking women showed an increase in MCM-7, ER, and PgR. CONCLUSIONS: Uterine fibroid cells have greater proliferative potential, as evaluated by expression of the Ki-67 antigen and MCMs, than unaltered myometrial cells of the uterine corpus. The expression of MCM-7 was found to have strong or moderate correlations in all assessed relations. In the context of the clinical data, as well evident proliferative potential of MCMs, further studies are strongly recommended.

Preliminary Study on the Expression of Testin, p16 and Ki-67 in the Cervical Intraepithelial Neoplasia.

Cervical cancer is one of the most common malignant cancers in women worldwide. The 5-year survival rate is 65%; nevertheless, it depends on race, age, and clinical stage. In the oncogenesis of cervical cancer, persistent HPV infection plays a pivotal role. It disrupts the expression of key proteins as Ki-67, p16, involved in regulating the cell cycle. This study aimed to identify the potential role of testin in the diagnosis of cervical precancerous lesions (CIN). The study was performed on selected archival paraffin-embedded specimens of CIN1 (31), CIN2 (75), and CIN3 (123). Moderate positive correlation was observed between testin and Ki-67 as well as testin and p16 expression in all dysplastic lesions (r = 0.4209, r = 0.5681; p < 0.0001 for both). Statistical analysis showed stronger expression of the testin in dysplastic lesions vs. control group (p < 0.0001); moreover, expression was significantly higher in HSIL than LSIL group (p < 0.0024). In addition, a significantly stronger expression of testin was observed in CIN3 vs. CIN1 and CIN3 vs. CIN2. In our study, expression of Ki-67, p16, and testin increased gradually as the lesion progressed from LSIL to HSIL. The three markers complemented each other effectively, which may improve test sensitivity and specificity when used jointly.

Comparison of TMA Technique and Routine Whole Slide Analysis in Evaluation of Proliferative Markers Expression in Laryngeal Squamous Cell Cancer.

BACKGROUND/AIM: Comparison of the expression of Ki-67, MCM3, 5, 7 and MTI/II proteins using immunohistochemistry (IHC) on whole section (WS) and tissue microarray (TMA) of laryngeal squamous cell carcinoma (LSCC) samples. MATERIALS AND METHODS: A total of 51 archival paraffin blocks of LSCC were used. TMAs were prepared from 1.5 mm core punches. IHC reactions were performed using antibodies against Ki-67, minichromosome maintenance proteins (MCM3, 5, 7) and metallothionein (MTI/II). RESULTS: Spearman rank correlation test revealed moderate positive correlation in the case of Ki-67: WS vs. TMA (r=0.38, p=0.07) and strong positive correlation in regard to the rest of tested markers: MCM3, WS vs. TMA (r=0.49, p=0.0004); MCM5, WS vs. TMA (r=0.61, p<0.0001); MCM7, WS vs. TMA (r=0.59, p<0.0001); MTI/II, WS vs. TMA (r=0.66, p<0.0001). Mann Whitney U-test showed no significant differences in the case of Ki-67 and MCM5. Moreover, Bland-Altman test showed a low level of bias in regard to Ki-67, WS vs. TMA and MCM5, WS vs. TMA. CONCLUSION: TMA may be an effective and reliable method of assessment of Ki-67 and MCM5 expression in LSCC.

The usefulness of periostin determination in gynecology and obstetrics.

Periostin (POSTN) is a multifunctional glycoprotein that belongs to the group of extracellular matrix (ECM) proteins. Due to the molecular structure, cellular interactions, tissue locations as well functions of POSTN, we realize that its pivotal role is organization and regulation of ECM microenvironment. In available databases there is a lack of data summarizing current knowledge about POSTN expression in the field of gynecology and obstetrics. We conducted a search in PubMed of the National Library of Medicine and Google Scholar. Databases were extensively searched for all original and review articles/book chapters published in English until December 2019 and related to periostin expression. All relevant articles were reviewed and presented as appropriate. In the field of POSTN expression there is only one paper evaluating its involvement in cervical cancer cell metabolism and only two studies analyzing its myometrial commitment: maintenance during pregnancy and induction of parturition in physiology as well control of fibroids biology in pathology. Much more attention has been devoted to the expression of described protein in the endometriosis, and above all in ovarian cancer. Finally, a few studies carried out among pregnant women were presented. In this review study we presented current knowledge about periostin expression in the field of gynecology and obstetrics. Many achieved results are interesting and further studies are needed to verify some hypotheses. Structure, signaling pathways as well many functions of periostin are well-described. However, as it was clearly shown there is a lot of unknown issues which are waiting to be explored.

Effect of Physical Training on the Levels of Sex Hormones and the Expression of Their Receptors in Rats With Induced Mammary Cancer in Secondary Prevention Model - Preliminary Study.

BACKGROUND/AIM: Breast cancer is the most common malignant tumor among women worldwide. In previous work, we presented results of physical activity in primary prevention in a model of induced mammary gland cancer. In the present study, we assessed the influence of physical activity on sex hormone levels (estradiol and progesterone) and the expression of their receptors (ER, PR), as well as the level of apoptosis of tumor cells in secondary prevention. MATERIALS AND METHODS: Fifty 1-month-old female Sprague-Dawley rats received intraperitoneal injection of 180 mg/kg body weight of N-methyl-N-nitrosourea (MNU) for tumor induction. Three months after the administration of MNU, rats were divided into four groups: low-intensity, moderate-intensity, and high-intensity physical training groups (combined as PT) and a sedentary control (SC) group. Physical training was conducted 5 days per week with a three-position treadmill according to a precisely described protocol. The entire training was completed by 32 rats from which tissue and blood were collected for further analysis. Immunohistochemistry for ER and PR expression, terminal deoxynucleotidyl transferase dUTP nick-end labeling method for detection of apoptosis, and enzyme-linked fluorescent assay for detection of plasma hormone levels (estradiol and progesterone) were performed. Statistical analysis used p<0.05 as the significance level. RESULTS: Significantly stronger expression of ER and PR was found in the SC in comparison to the PT group (p=0.035 and p=0.036, respectively). No statistically significant differences were found in estradiol or progesterone concentrations between SC and PT groups. Apoptosis was non-significantly increased in the PT group in comparison with the SC group. Stronger apoptosis in the PT group correlated positively with the level of training intensity (r=0.35, p=0.05). CONCLUSION: Physical training may reduce ER and PR expression in breast cancer cells, and reduce cell sensitivity to pro-proliferative and anti-apoptotic effects of estrogens, ultimately leading to apoptosis.

The Usefulness of Immunohistochemistry in the Differential Diagnosis of Lesions Originating from the Myometrium.

Uterine leiomyomas (LMs), currently the most common gynecological complaint around the world, are a serious medical, social and economic problem. Accurate diagnosis is the necessary prerequisite of the diagnostic-therapeutic process. Statistically, mistakes may occur more often in case of disease entities with high prevalence rates. Histopathology, based on increasingly advanced immunohistochemistry methods, is routinely used in the diagnosis of neoplastic diseases. Markers of the highest sensitivity and specificity profiles are used in the process. As far as LMs are concerned, the crux of the matter is to identify patients with seemingly benign lesions which turn out to be suspicious (e.g., atypical LM) or malignant (e.g., leiomyosarcoma (LMS)), which is not uncommon. In this study, we present the current state of knowledge about the use of immunohistochemical markers in the differential diagnosis of LM, atypical LM, smooth muscle tumors of uncertain malignant potential (STUMP), and LMS, as well as their clinical predictive value.

The large intestine from fetal period to adulthood and its impact on the course of colonoscopy.

The human large intestine in the living adult has a total length of about 1300 mm, ranging from 1100 to 2108 mm. The development of the gut continues after birth, up to the age 4-5. The large intestine ascends at the beginning in the right abdominal quadrant, then it traverses the abdominal cavity, and finally it descends to the anus. The left and right colic flexures are the basic flexions between the transverse, ascending and descending colon, respectively. Additionally, there are secondary bendings between intestinal segments. The angles between the neighbouring parts can vary between examined subjects. Most of the angulations can be found in the transverse (range 2-9) and sigmoid colon (range 1-9), making them the most troublesome parts to pass with a colonoscope. Colonoscopy (usually performed in the left lateral or supine position) is one of the most important examination of the large intestine mucus membrane. During this procedure the endoscope is passed through the colon into the cecum or terminal ilium. The individual anatomical features (tortuosity, supernumerary loops and elongation) may slow down or interfere with the progress of the scope. We summarize current knowledge on the human large intestine from the fetal period to adulthood and carve out some aspects that are currently less known to colonoscopists.

The Role of Testin in Human Cancers.

Testin is a protein expressed in almost all normal human tissues. It locates in the cytoplasm along stress fibers being recruited to focal adhesions. Together with zyxin and vasodilator stimulated protein it forms complexes with various cytoskeleton proteins such as actin, talin and paxilin. They jointly play significant role in cell motility and adhesion. In addition, their involvement in the cell cycle has been demonstrated. Expression of testin protein level correlates positively with percentage of cells in G1 phase, while overexpression can induce apoptosis and decreased colony forming ability. Decreased testin expression associate with loss by cells epithelial morphology and gain migratory and invasive properties of mesenchymal cells. Latest reports indicate that TES is a tumor suppressor gene which can contribute to cancerogenesis but the mechanism of loss TES gene expression is still unknown. Some authors point out hypermethylation of the CpG island as a main factor, however loss of heterozygosity may also play an important role [4, 5]. The altered expression of testin was found in malignant neoplasm, i.a. ovarian, lung, head and neck squamous cell cancer, breast, endometrial, colorectal, prostate and gastric cancers [1-9]. Testin participate in the processes of tumor growth, angiogenesis, and metastasis [10]. Many researchers stated involvement of testin in tumor progression, what suggest its potential usage in immunotherapy [7, 11]. Understanding the molecular functions of testin may be crucial in development personalized treatment. In the present manuscript up-to-date review of literature can be found.

The Role of Tumor Necrosis Factor α in the Biology of Uterine Fibroids and the Related Symptoms.

Uterine fibroids (UFs) are the most common benign tumors of the female genital tract. The incidence of UFs has been estimated at 25⁻80% depending on selected population. The pathophysiology of UFs remains poorly understood. The transformation of smooth muscle cells of the uterus into abnormal, immortal cells, capable of clonal division, is the main component of all pathways leading to UF tumor formation and tumor necrosis factor α (TNF-α) is believed to be one of the key factors in this field. TNF-α is a cell signaling protein involved in systemic inflammation and is one of the cytokines responsible for the acute phase reaction. This publication presents current data about the role of tumor necrosis factor α in the biology of UFs and the related symptoms. TNF-α is an extremely important cytokine associated with the biology of UFs, UF-related symptoms and complaints. Its concentration has been proven to be elevated in women with clinically symptomatic UFs. The presented data suggest the presence of an "inflammation-like" state in women with UFs where TNF-α is a potent inflammation inducer. The origin of numerous symptoms reported by women with UFs can be traced back to the TNF-α influence. Nevertheless, our knowledge on this subject remains limited and TNF-α dependent pathways in UF pathophysiology should be investigated further.

Matrix metalloproteinases-2, -7 and tissue metalloproteinase inhibitor-1 expression in human endometrium.

INTRODUCTION: Endometrium undergoes regular, cyclic tissue remodeling mostly associated to the endocrine system status. It is well-known fact that steroid hormones are strongly responsible for changes in endometrium. The precise mechanism of their action is still under investigation. The aim of the study was to evaluate the expression of metalloproteinases 2 and 7 (MMP-2, -7) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in human endometrium in relation to serum concentrations of estradiol and progesterone during different phases of menstrual cycle. MATERIAL AND METHODS: The study material consisted of 52 biopsy samples; 12 obtained in the proliferative phase, 11 in the secretory phase and 29 during menstruation. Expression of MMP-2, MMP-7 and TIMP-1 was assessed by immunohistochemistry. Serum concentrations of estradiol and progesterone at time of biopsy were evaluated by immunochemistry assay. Results of the study were statistically assessed by linear regression model. RESULTS: Increased serum concentration of estradiol was associated with increased MMP-2 expression in proliferative phase but decreased in secretory phase and during menstruation. No significant relationship was found between progesterone concentration and MMP-2 expression. Moreover, no difference in the expression of MMP-7 and TIMP-1 in the endometrium in relation to hormone levels and menstrual cycle phases were observed. CONCLUSIONS: The results of the study indicate that estradiol influence MMP-2 expression in the endometrium depends on the phase of menstrual cycle. Such relationships were not found for MMP-7 and TIMP-1 and further tests clarifying association between estradiol and MMPs are needed.

Expression of p16 and SATB1 in Invasive Ductal Breast Cancer - A Preliminary Study.

BACKGROUND/AIM: An impaired cell-cycle control and genetic material organization are crucial elements of carcinogenesis. p16 is a tumor suppressor protein which decelerates promotion of the cells from G1 to S phase, whereas special AT-rich sequence-binding protein 1 (SATB1) is a nuclear matrix protein that binds to specific regions of the DNA and ensures its proper organization and function. Increased levels of both markers are observed in various types of cancers. The aim of this study was to investigate the expression of p16 and SATB1 proteins in regard to expression of the Ki-67 antigen and available clinicopathological data (i.a. receptor status, staging and grading). MATERIALS AND METHODS: The study was performed on 130 samples of archived invasive ductal breast cancers. Immunohistochemical reactions were performed on freshly prepared tissue microarrays and subsequently scanned by a histologic scanner. Reactions were evaluated separately in the cytoplasm (p16c, SATB1c) and nucleus (p16n, SATB1n, Ki-67) with use of a quantification software under researcher supervision. RESULTS: Expression was observed for Ki-67 in 100%, p16c in 90%, p16n in 89.2%, SATB1c in 98.5% and SATB1n in 87.7% of cancer cases. Statistical analysis showed strong positive correlations: p16c vs. p16n and SATB1c vs. SATB1n (p<0.001 for both) and weak positive correlations: p16c vs. SATB1c and p16c vs. SATB1n (p=0.008, p=0.027; respectively). Expression of p16n was stronger in G1 vs. G2 (p=0.034) while Ki-67 expression was stronger in cases with negative progesterone receptor status (p=0.011). All other analyzed associations were statistically insignificant. CONCLUSION: A weak association between immunohistochemical expression of p16 and SATB1 indicated limited possibility of their independent usage. Further studies concerning determination of a wider panel of proteins controlling cell cycle should be considered.

The Impact of Exercise Training on Breast Cancer.

BACKGROUND/AIM: Physical exercise is increasingly considered by many authors to be a factor reducing the risk of cancer development and premature cancer-related death. Data indicate higher cure rates and longer times of survival in cancer patients who regularly exercise. MATERIALS AND METHODS: A total of 50 female Sprague-Dawley rats were used in the experiment. Animals at 1 month of age were intraperitoneally injected with N-methyl-N-nitrosourea. Three months following drug administration, rats underwent supervised physical training. The animals were divided into four groups: control untrained group and 3 groups trained with different intensities - i.e. low, moderate and high. Routine histopathological examination of tumors was performed and mitotic activity was assessed by immunohistochemical expression of the Ki-67 antigen. RESULTS: Ki-67 antigen expression was observed in all analyzed tumors. The increase in Ki-67 antigen expression correlated positively with the increase in training intensity. CONCLUSION: It can be assumed that low-intensity physical training is safe for patients with breast cancer. However, moderate- and high-intensity training may induce tumor cell proliferation worsening patients' prognosis.

Carvedilol Inhibits Matrix Metalloproteinase-2 Activation in Experimental Autoimmune Myocarditis: Possibilities of Cardioprotective Application.

AIMS: Acute myocarditis is a potentially lethal inflammatory heart disease that frequently precedes the development of dilated cardiomyopathy and subsequent heart failure. At present, there is no effective standardized therapy for acute myocarditis, besides the optimal care of heart failure and arrhythmias in accordance with evidence-based guidelines and specific etiology-driven therapy for infectious myocarditis. Carvedilol has been shown to be cardioprotective by reducing cardiac pro-inflammatory cytokines present in oxidative stress in certain heart diseases. However, effects of carvedilol administration in acute myocarditis with its impact on matrix metalloproteinases' (MMPs) activation have not been elucidated. METHODS AND RESULTS: Carvedilol in 3 doses (2, 10, and 30 mg/kg) was given daily to 3 study groups of rats (n = 8) with experimental autoimmune myocarditis by gastric gavage for 3 weeks. In comparison to untreated rats (n = 8) with induced myocarditis, carvedilol significantly prevented the left ventricle enlargement and/or systolic dysfunction depending on the dose in study groups. Performed zymography showed enhanced MMP-2 activity in untreated rats, while carvedilol administration reduced alterations. This was accompanied by prevention of troponin I release and myofilaments degradation in cardiac muscle tissue. Additionally, severe inflammatory cell infiltration was detected in the nontreated group. Carvedilol in all doses tested, had no impact on severity of inflammation. The severity of inflammation did not differ between study groups and in relation to the untreated group. CONCLUSIONS: The protective effects of carvedilol on heart function observed in the acute phase of experimental autoimmune myocarditis seem to be associated with its ability to decrease MMP-2 activity and subsequently prevent degradation of myofilaments and release of troponin I while not related to suppression of inflammation.

Correlation of Pyruvate Kinase M2 Expression with Clinicopathological Data in Ovarian Cancer.

BACKGROUND/AIM: It has been shown in many studies that expression of pyruvate kinase (PK) enzyme plays a key role during cellular metabolism. There is evidence that cancer cells manifesting very dynamic proliferation may control their division in various mechanisms, i.a. by expression of PKM2 isoform. The exact role of PKM2 in ovarian cancer (OC) cells and cancer associated fibroblasts (CAFs) have not been elucidated. MATERIALS AND METHODS: The present study was focused on analysis of PKM2 expression in cancer cells and CAFs in 97 OC cases, mostly of serous histological type. Moreover, relationships between expression of PKM2 and proliferation (Ki-67; MCM-2, -3, -7; cyclin D1), vascular (CD31, D2-40) and mesenchymal (Vim and αSMA) markers as well as receptors (ER, PR, HER2, EGFR) were examined. All observations were evaluated in regard to available clinicopathological data. RESULTS: The expression of PKM2 was disclosed only in cytoplasm of OC cells. No statistically significant correlation between PKM2 and tested markers was found. In regard to available clinicopathological data only an increasing trend of PKM2 expression with increasing grade of histological malignancy G was found (p=0.07). CONCLUSION: Due to achieved results concerning expression of PKM2 there is a lack of evidence for its diagnostic and prognostic usage in OC.

Circulating tumor cells in urological cancers.

Circulating tumor cells (CTC) represent a very small subpopulation of the cancer cells found in the bloodstream of patients in the metastatic phase of neoplastic disease. Due to the timeline of the disease, they are regarded as a negative prognostic marker. This study focused on determining CTC percentages; these values vary be-tween different types of cancer. In addition to their diagnostic use, CTCs may also be used to treat the disease. Calculating CTC population size and analyzing their biology in patients in advanced stages of cancer may prove valuable in creating a molecular profile for the disease. This would strongly encourage diagnostics and enable personalized treatment. We here present an analysis of recent data on CTCs in urological cancers and their potential uses.

Impact of Physical Training on Sex Hormones and Their Receptors During N-Methyl-N-nitrosourea-induced Carcinogenesis in Rats.

BACKGROUND/AIM: The risk of breast cancer is related to duration of exposure to sex hormones, especially estrogen. The aim of this study was to assess the impact of physical training (PT) on estrogen and progesterone levels and expression of their receptors during carcinogenesis induced by N-methyl-N-nitrosourea (MNU) in rats. MATERIALS AND METHODS: Fifty female Sprague-Dawley rats were intraperitoneally administered MNU and divided into four groups: low-, moderate-, and high-intensity PT, and no PT (control). Plasma levels of sex hormones and tissue expression of their receptors were quantified and statistically analyzed. RESULTS: In the group of rats subjected to PT, a significantly higher progesterone level was observed. The highest progesterone level was noted in the low-intensity PT group. An increase in apoptosis of MNU-induced tumor cells was also demonstrated in the PT groups. CONCLUSION: PT stimulates apoptosis of tumor cells without an increase in their proliferative activity. The increase in apoptosis of tumor cells correlates positively with the progesterone level.

Podoplanin Expression Correlates with Disease Progression in Mycosis Fungoides.

The aim of this study was to investigate the role of lymphangiogenesis in the clinical progression and outcome of mycosis fungoides. Immunohistochemistry and Western blot techniques were used to assess the expression of podoplanin and vascular endothelial growth factor C in mycosis fungoides. Expression of vascular endothelial growth factor C measured by immunohistochemistry was significantly higher in mycosis fungoides samples in comparison with control cases (chronic benign dermatoses) (p = 0.0012). Increased expression of podoplanin was found in advanced vs. early mycosis fungoides (p < 0.0001), and was positively correlated with cutaneous and nodal involvement (p < 0.001, p < 0.0001; respectively). Higher podoplanin expression was also significantly associated with shorter survival (p < 0.001). Strong positive correlation was observed between expression of podoplanin analysed by immunohistochemistry and Western blot (r = 0.75, p < 0.0001). A similar association was shown regarding expression of vascular endothelial growth factor C (r = 0.68, p = 0.0007). In conclusion, these results suggest that increased expression of podoplanin is associated with poor clinical course, as well as shorter survival, of patients with mycosis fungoides.