STAT3 and hypoxia induced proteins--HIF-1alpha, EPO and EPOR in relation with Bax and Bcl-xL in nodal metastases of ductal breast cancers.

STAT3 contributes to increase of EPO expression which is also HIF-1 dependent. EPO receptor activates STAT3. Expressions of STAT3 and hypoxia induced proteins: HIF-1, EPO and EPOR show mutual correlations in primary ductal breast cancers, which suggest co-operation among these proteins. Moreover, EPO-EPOR signaling was reported to mediate cell survival by targeting Bcl-xL in competition with Bax-dependent apoptosis. Our present study was focused on immunohistochemical evaluation of STAT3, HIF-1alpha, EPO and EPOR in relation to apoptosis regulators, Bax and Bcl-xL in 39 metastases of ductal breast cancers to lymph nodes. The proteins were abundantly expressed by cancer cells. HIF-1alpha correlated with EPOR in all and in chemotherapy treated metastases (r=0.428, p=0.007 and r=0.462, p=0.040, respectively). HIF-1 associated significantly with EPO in chemotherapy spared metastases (r=0.549, p=0.015) and comparison between those proteins almost reached statistical significance in entire number of metastatic breast cancers (r=0.309, p=0.056). Metastases from T2 primary tumors had significantly higher expressions of HIF-1alpha, EPO and EPOR compared to T1 originating metastases (p=0.020, p=0.028, p=0.021, respectively). Bax correlated with EPO and EPOR in all studied nodal metastases (r=0.449, p=0.006 and r=0.421, p=0.011, respectively) and so did Bcl-xL with HIF-1alpha (r=0.440, p=0.007), EPO and EPOR (r=0.383, p=0.021, r=0.495, p=0.002, respectively). Metastatic breast cancers seem to be areas of intensive signaling by STAT3, HIF-1, EPO and EPOR. Strong Bax and Bcl-xL labeling reflects accelerated cell turnover in nodal metastases. By means of association with Bcl-xL, HIF-1alpha, EPO and EPOR could favor growth of nodal metastases and survival of breast cancers cells

Detaljna analiza istraživanja i prakse pedijatrijske kirurginje u istočnom dijelu Srednje Europe u XX. stoljeću – primjer profesorice Zofije Umiastowske-Sawicke

Professor Zofia Umiastowska Sawicka laid the foundations for modern pediatric surgery in Poland, first in Bialystok, and subsequently in Kielce. She was a student of Prof. Jan Kossakowski from Warsaw Medical University to be counted among his most talented and skilled disciples. Professor Umiastowska became the head of the first Department of Pediatric Surgery in Bialystok, which was later incorporated into the Medical Academy of Bialystok. In 1977 she moved to Kielce to run the Department of Pediatric Surgery until her retirement in 1991. In these locations she was the one who trained generations of pediatric surgeons with special emphasis on surgical management of exstrophy of the bladder, vaginal labial adhesion (synechia), injuries of the male urethra, liver and hepatic ligament. During her professional lifetime she focused on congenital diaphragmatic hernia, Meckel’s diverticulum, and some aspects of pediatric oncology as well. Every school she attended enriched her with the best of knowledge and skills that made her a perfect teacher for others. However, the Warsaw Medical University essentially played the main role at the core of her surgical training: here she was taught and she learnt how to be pediatric surgeon for good of public health of the society in concord with the motto of the Warsaw Medical University: Saluti publicae.Profesorica Zofia Umiastowska Sawicka postavila je temelje moderne pedijatrijske kirurgije u Poljskoj, najprije u Bialystoku, potom u Kielceu. Bila je jedna od najsposobnijih i najiskusnijih studentica profesora Jana Kossakowskog s Varšavskoga medicinskog sveučilišta. Profesorica Umiastowska postala je pročelnica prvog Odjela za pedijatrijsku kirurgiju u Bialystoku, koji je poslije pridružen Medicinskoj akademiji Bialystok. Godine 1977. preselila se u Kielce kako bi vodila Odjel pedijatrijske kirurgije sve do svoga umirovljenja 1991. godine. Obučavala je generacije pedijatrijskih kirurga, s posebnim naglaskom na kirurško liječenje ekstrofije mokraćnog mjehura, vaginalne labijalne adhezije (synechia), ozljede uretre u pacijenata muškog spola te jetre i jetrenih ligamenata. U svom se profesionalnom životu usredotočila na kongenitalnu dijafragmatsku herniju, Meckelov divertikul te na neka područja pedijatrijske onkologije. Svaka škola koju je pohađala obogatila ju je najboljim znanjem i vještinama koji su ju učinili savršenim učiteljem. Međutim, Varšavsko medicinsko sveučilište imalo je glavnu ulogu u njezinoj kirurškoj izobrazbi: ovdje je učila i naučila kako biti pedijatrijski kirurg za dobrobit javnog zdravlja društva u skladu s motom Varšavskoga medicinskog sveučilišta: Saluti publicae

The relationships between hypoxia-dependent markers: HIF-1alpha, EPO and EPOR in colorectal cancer

Abstract: Hypoxia triggers production of several cytoprotective proteins. Hypoxia-inducible factor 1alpha (HIF-1α) is a powerful stimulator of transcription of many genes, including erythropoietin (EPO) in hypoxia-affected cells. Recent data have also implicated signaling by EPO receptor (EPOR) as a new factor influencing tumor progression. The aim of the study was to detect by immunohistochemistry the presence of HIF-1α, EPO and EPOR in colorectal cancer (CRC) in reference to clinicopathological variables. We found the presence of the studied proteins in specimens of all 125 CRC patients which is suggestive of the occurrence of hypoxia in colorectal cancer tissues. The expression of HIF-1α correlated significantly with the presence of EPO and EPOR in all samples (P < 0.001, r = 0.549 and P < 0.001, r = 0.536, respectively). Significant correlations (from P < 0.024 to P < 0.001) were found in the analyses of CRC subgroups such as histopathological type tumor, tumor grade, tumor stage and patients with lymph nodes metastases. The same high significant correlations (P < 0.001) were observed in group of sex, age and tumor location. However, the values of the correlation coefficients (r) which usually ranged from 0.5 to 0.6 suggest the existence of independent or concurrent mechanism stimulating generation of these proteins in colorectal cancer

Jezik i medicina u obitelji Zamenhof

The Zamenhof family is famous for Dr Ludwik Lejzer Zamenhof (1859-1917), who created the artificial language Esperanto and who initiated a social movement for peace and against any sort of discrimination. Ludwik was an ophthalmologist. Adam, Leon, Alexander, and Julian Zamenhof were medical doctors and noted surgeons, while Sophia Zamenhof was a paediatrician. Ludwik Zamenhof often referred to the biblical story of the Tower of Babel, in which diversity of languages was the punishment for builders who were arrogant and uncaring. With the help of Esperanto, the Zamenhofs metaphorically wanted to overcome the curse of Babel and restore the sense of human unity.Obitelj Zamenhof znana je po dr. Ludwiku Zamenhof Lejzeru (1859.–1917), tvorcu umjetnog jezika esperanta i pokretaču socijalnog pokreta za mir i protiv svih oblika diskriminacije. Uz Ludwika koji je bio oftalmolog, od Zamanhofovih doktori medicine i poznati kuruzi bili su Adam, Leon, Aleksandar i Julian, dok je Sofija bila pedijatarica. Ideju o novom zajedničkom jeziku Ludwik Zamenhof pronašao je u legendi iz Biblije o graditeljima babilonske kule koji su zbog oholosti i objesti bili kažnjeni tako da su im promijenjeni i pomiješani jezici te se više nisu moglu sporazumijevati. Uz pomoć esperanta, Zamenhof je, dakle, metaforički želio prevladati babilonsko prokletstvo i vratiti osjećaj ljudskog zajedništva

STAT3, HIF-1alpha, EPO and EPOR - signaling proteins in human primary ductal breast cancers.

STAT3 upregulates expression of HIF-1 induced EPO. Receptor EPOR was reported to activate STAT3. Our study was aimed at demonstration of tissue immunoreactivities of those proteins and determination of their relationships in reference to clinicopathological variables of breast cancers. We detected STAT3, HIF-1alpha, EPO and EPOR in specimens of 76 human, female, ductal breast cancers by immunohistochemistry. STAT3 was detected in 38 of 76 cancers (50%). HIF-1alpha was found in 55 cases (72%). EPO positive tumors comprised 89% of all the cancers (68 cases). EPOR was also visualized in 55 cases (72%). Anti-HIF-1alpha and anti-STAT3 stained nuclei and cytoplasm of breast cancer cells in diffuse and finely granular fashion. Strong membranous expressions of EPO and EPOR were distributed in cytoplasmic and membranous granularity or diffuse staining. STAT3 correlated with HIF-1 in general (r=0.4012,

Review of prognostic and predictive aspects of mutated TP53 in Wilms’ tumor biology with morphological report and molecular analysis of 37-year-old man’s nephroblastoma

Here we review prognostic and predictive aspects of mutated TP53 in Wilms’ tumor biology on the basis of the morphological report and molecular analysis of adult nephroblastoma (diffuse blastemal pattern) of a 37-year-old man. Among quite different proteins, TP53 affects expression of several genes such as hypoxia inducible proteins GLUT1 and EPO as well as multidrug resistance (MDR) mediated by P-glycoprotein (Pgp/MDR1) and multidrug-resistant related protein (MRP1), with certain clinical implications. TP53 mutation was found both in our primary tumor (c.746G>T p.R249M frequency 92%) and in nodal metastasis (c.746G>T p.R249M frequency 90%), and the common polymorphism p.P72R in the same gene was revealed with frequency of about 97% in both primary tumor and metastatic disease with appliance of NGS technology (IonTorrent – LifeTechnology) using Ion AmpliSeq Cancer Hotspot Panel v2

STAT3, HIF-1alpha, EPO and EPOR - signaling proteins in human primary ductal breast cancers.

STAT3 upregulates expression of HIF-1 induced EPO. Receptor EPOR was reported to activate STAT3. Our study was aimed at demonstration of tissue immunoreactivities of those proteins and determination of their relationships in reference to clinicopathological variables of breast cancers. We detected STAT3, HIF-1alpha, EPO and EPOR in specimens of 76 human, female, ductal breast cancers by immunohistochemistry. STAT3 was detected in 38 of 76 cancers (50%). HIF-1alpha was found in 55 cases (72%). EPO positive tumors comprised 89% of all the cancers (68 cases). EPOR was also visualized in 55 cases (72%). Anti-HIF-1alpha and anti-STAT3 stained nuclei and cytoplasm of breast cancer cells in diffuse and finely granular fashion. Strong membranous expressions of EPO and EPOR were distributed in cytoplasmic and membranous granularity or diffuse staining. STAT3 correlated with HIF-1 in general (r=0.4012, p<0.0001) and in different patients' subgroups. STAT3 was significantly associated with EPO and EPOR in all the cancers (r=0.2370, p=0.039 and r=0.3336, p=0.003, respectively). Besides a correlation between STAT3 and EPOR in node negative ones, STAT3 wasn't related to EPO and EPOR in remaining subgroups. HIF-1alpha correlated with EPO and EPOR in most of analyzed groups. Immunoreactivity to EPO generally was associated with EPOR (r=0.3520, p=0.002). Statistically analyzed distributions of the proteins reflected functional dependences among STAT3, HIF-1alpha, EPO and EPOR in cellular signal conduction