Language and medicine in the Zamenhof family.

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.

Relationships between hypoxia markers and the leptin system, estrogen receptors in human primary and metastatic breast cancer: effects of preoperative chemotherapy.

BACKGROUND: Tumor hypoxia is marked by enhanced expression of hypoxia-inducible factor-alpha (HIF-1alpha) and glucose transporter-1 (Glut-1). Hypoxic conditions have also been associated with overexpression of angiogenic factors, such as leptin. The aim of our study was to analyze the relationships between hypoxia markers HIF-1alpha, Glut-1, leptin, leptin receptor (ObR) and other breast cancer biomarkers in primary and metastatic breast cancer in patients treated or untreated with preoperative chemotherapy. METHODS: The expression of different biomarkers was examined by immunohistochemistry in 116 primary breast cancers and 65 lymph node metastases. Forty five of these samples were obtained form patients who received preoperative chemotherapy and 71 from untreated patients. RESULTS: In primary tumors without preoperative chemotherapy, HIF-1alpha and Glut-1 were positively correlated (p = 0.02, r = 0.437). HIF-1alpha in primary and metastatic tumors without preoperative therapy positively correlated with leptin (p < 0.0001, r = 0.532; p = 0.013, r = 0.533, respectively) and ObR (p = 0.002, r = 0.319; p = 0.083, r = 0.387, respectively). Hypoxia markers HIF-1alpha and Glut-1 were negatively associated with estrogen receptor alpha (ERalpha) and positively correlated with estrogen receptor beta (ERbeta). In this group of tumors, a positive correlation between Glut-1 and proliferation marker Ki-67 (p = 0.017, r = 0.433) was noted. The associations between HIF-1alpha and Glut-1, HIF-1alpha and leptin, HIF-1alpha and ERalpha as well as Glut-1 and ERbeta were lost following preoperative chemotherapy. CONCLUSIONS: Intratumoral hypoxia in breast cancer is marked by coordinated expression of such markers as HIF-1alpha, Glut-1, leptin and ObR. The relationships among these proteins can be altered by preoperative chemotherapy.

Aberrant distributions and relationships among E-cadherin, beta-catenin, and connexin 26 and 43 in endometrioid adenocarcinomas.

During carcinogenesis, loss of intracellular cohesion is observed among cancer cells with altered expression of such adhesion molecules as E-cadherin and beta-catenin, and aberrant expression and cellular location of intercellular gap junction proteins-connexins. The aim of this study was to evaluate immunohistochemically the expression and relationship between E-cadherin and beta-catenin, and the connexins Cx26 and Cx43 in 86 endometrioid adenocarcinomas. The aberrant cytoplasmic translocation of the studied proteins was a predominant finding, whereas only a minority of cases showed normal, nuclear beta-catenin labeling or membranous distribution of the remaining molecules. E-cadherin was positively and significantly associated with beta-catenin (P=0.001, r=0.366), as was Cx26 with Cx43 (P<0.001, r=0.719), E-cadherin with Cx26 (P<0.001, r=0.413), and E-cadherin and Cx43 (P<0.001, r=0.434) in all cancers. A subgroup of endometrioid adenocarcinomas (FIGO IB+II) exclusively showed a positive significant association between the expression of beta-catenin and Cx26 (P=0.038, r=0.339). In addition, there were significantly more beta-catenin-positive carcinomas among superficially spreading cancers (FIGO IA) than among deeper invading neoplasms (FIGO IB+II) (P=0.056). The altered location of the studied proteins indicates impairment of their physiological functions. In particular, normal membranous distribution of E-cadherin and connexins is lost and replaced by abnormal cytoplasmic accumulation in most cancers, and thus intercellular ties are expected to be weakened and loosened as a consequence. In contrast, the lack of relationship between beta-catenin and connexins, E-cadherin seems to be closely associated with the expression of Cx26 and Cx43 in endometrioid adenocarcinomas.

Gradual loss of functional gap junction within progression of colorectal cancer -- a shift from membranous CX32 and CX43 expression to cytoplasmic pattern during colorectal carcinogenesis.

UNLABELLED: The aim of this study was the assessment of expression and location of CX32 and CX43 in colorectal adenomas and carcinomas as well as analysis of expression of these proteins in association with clinical and pathological features of tumors and evaluation of mutual relationships between CX32 and CX43. PATIENTS AND METHODS: The study included 151 primary colorectal carcinoma and 71 colorectal adenomas. The control group comprised 30 colon samples. Connexins were detected with immunohistochemistry. RESULTS: There was a lack of membranous distribution of connexins or a shift from moderately membranous immunoreactivity to predominantly cytoplasmic accumulation of CX32 and CX43 in studied colon tumors. Mentioned alterations were found in adenomas and augmented in cancer. Expression of Cx32 was significantly associated with grading of colorectal cancer, implicating a role of intracellular CX32 in regulation of tumor growth and differentiation. A strong correlation was present between CX32 and CX43 in node-positive cases and absent from node-negative ones. CONCLUSION: To our knowledge, our study is the first illustration for a gradual loss of functional gap junctions within progression of colorectal neoplasia. An intracellular location of connexins, the site of their common and the most frequent detection within cancer cells in our study may be of significance. Independently of its role in functional gap-junctions, cytoplasmic CX32 could be involved in cancer differentiation, resulting in a higher rate of CX32 positive moderately differentiated tumors (G3) than poorly differentiated CX32-positive ones (G3).

Comparison of beta-catenin with TGF-beta1, HIF-1alpha and patients' disease-free survival in human colorectal cancer.

Beta-catenin accumulation is suppressed by TGF-beta1 (transforming growth factor beta1) in intestinal epithelium suggesting negative feedback between these two factors. Besides that, beta-catenin interacts with HIF-1alpha (hypoxia-inducible factor-1alpha) at the promoter region of HIF-1 target genes. Our study was aimed at comparison of beta-catenin with HIF-1alpha, TGF-beta1, Ki67 and survival of sporadic colorectal cancer patients. Expressions of beta-catenin, TGF-beta1, HIF-1alpha, Ki67 were evaluated in triads of specimens of each primary tumor of 72 sporadic colorectal cancers with immunohistochemistry due to limited availability of tissue material. Disease-free survival was analyzed in case of all 100 beta-catenin stained tumors, in 85 cancers stained for HIF-1 and in 72 neoplasms with TGFbeta1 staining. Beta-catenin, TGF-beta1 and HIF-1alpha accumulated in 72 colorectal cancer cells. Beta-catenin correlated both with HIF-1alpha and TGF-beta1 in all colorectal cancers (p < 0.009, r = 0.307 and p = 0.003, r = 0.342, respectively) and in subgroups of different clinico-pathological profile. Beta-catenin failed to correlate with Ki67. In case of beta-catenin, TGF-beta1 and HIF-1alpha, disease-free survival curves failed to show any statistically significant differences between groups of marker negative tumors, cancers with low expression and neoplasms with higher protein expression. Positive correlations between beta-catenin and TGF-beta1 may indicate ineffective attempts of TGF-beta1 to reduce intracellular level of beta-catenin in colorectal cancer. Associations between beta-catenin and HIF-1alpha reflect previously detected interactions between HIF-1alpha with beta-catenin and are confirmative for presence of such reactions in human colorectal cancer.

Comparative evaluation of estrogen and progesterone receptor expression with connexins 26 and 43 in endometrial cancer.

Progression of numerous neoplasms could involve alterations of gap junction channels composed of connexins (Cxs). Disorders of expression and cellular displacement of Cxs were also found in endometrial cancer. Gap junctional intercellular communication can be regulated by wide array of agents, for instance, growth factors, oncogenes, and steroid hormones. Nevertheless, expressions of Cxs and progesterone receptor (PR) were not compared in human tissues. This study focused on assessment of expression of estrogen receptor alpha (ERalpha) and PRs in relation to the expression of Cx26 and Cx43 in 88 cases of endometrial cancer and analysis of these proteins' expression in comparison with anatomoclinical features. Positive ERalpha and PR nuclear staining was present in 66 (75%) and 60 (68.2%) of all studied tumors, respectively. Positive correlation was found between expression of PR and histopathologic type of tumor (P = 0.026), and negative correlation was drawn with grading (G) (P = 0.002). There were positive reactions to Cx26 and Cx43 of mainly cytoplasmic location in 60 (68.2%) and 66 (75%) of studied cancers, respectively. Progesterone receptor expression correlated negatively with Cx26 in endometrial cancers (P = 0.016, r = -0.256). Moreover, ERalpha expression positively correlated with PR expression (P < 0.001, r = 0.678). On the ground of our findings, disorders of Cx expression and altered distribution pattern occur during endometrial carcinogenesis, and it seems that PR could participate in this fact. Loss of functional gap junctions may occur because of the aberrant expression and localization of Cx26 and Cx43 in endometrial cancer.

Relationships of P53 and Bak with EPO and EPOR in human colorectal cancer.

BACKGROUND: EPO (erythropoietin) counteracts p53-dependent apoptosis. EPO, which acts via its receptor EPOR, protects cells and inhibits apoptosis in normal cells and some cancer tissues by severe down-regulation of Bak. We aimed to investigate the relationship between p53 and Bak expression and EPO and EPOR in human colorectal carcinomas. MATERIALS AND METHODS: The expression of p53 was compared with Bak, EPO and EPOR in 96 colorectal carcinomas by means of immunohistochemistry. RESULTS: Purely nuclear p53 was significantly higher expressed in the moderately differentiated cancers in comparison with the poorly differentiated ones (p=0.007). P53 expression did not correlate with cytoplasmic markers: Bak, EPO and EPOR, but EPO and EPOR were significantly associated with Bak expression (p<0.001, r=0.524 and p<0.001, r=0.455, respectively). p53 expression was not associated with disease-free survival during the 3 years and 9 months long follow-up. CONCLUSION: A complete disruption of association between p53 and Bak could impair of p53-dependent apoptotic pathway that involves Bak. The relationship of Bak with EPO and EPOR is evidence of their co-expression suggesting competition between EPO mediated cell survival and Bak associated apoptosis in colorectal carcinomas.

Hypoxia related growth factors and p53 in preoperative sera from patients with colorectal cancer--evaluation of the prognostic significance of these agents.

BACKGROUND: Insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) belong to a group of hypoxia related proteins. IGF-I induces expression of VEGF and decomposes wild type p53 in cancer cell lines. The goal of our study was to evaluate serum IGF-I, VEGF and p53 with respect to overall and disease free survival of patients with colorectal cancer (CRC) patients compared with healthy volunteers. METHODS: Preoperative blood samples from 125 patients with CRC and 16 healthy volunteers were examined using ELISA for serum IGF-I, p53 and VEGF concentrations. RESULTS: Concentrations of p53 and VEGF were significantly higher in CRC patients than in controls (p<0.0006 and p<0.0001, respectively). IGF-I was not statistically different between both groups. Serum IGF-I showed negative correlation with p53 in CRC patients (p<0.04, r=-0.193). IGF-I and VEGF showed negative correlation in poorly differentiated cancers (G3) (p<0.03, r=-0.339). Patients with VEGF concentrations that were above average for the cancer population survived for a shorter period of time (p=0.065 in evaluation of overall survival and 0.071 in estimation of disease-free survival during a 3-year follow-up) compared with patients with serum VEGF lower than the highest values seen in controls. CONCLUSIONS: Comparisons between serum IGF-I and p53 appear to confirm the metabolism of p53 by IGF-I. Serum VEGF showed prognostic significance in our study. Serum concentrations of IGF-I and VEGF did not show positive correlation, as expected due to IGF-I induction of VEGF in malignant colon cell lines.

Transforming growth factor-beta1 and regulators of apoptosis.

Growth inhibitory function of transforming growth factor-beta1 (TGF-beta1) is abolished in colorectal cancer cells as a consequence of mutations of various downstream signaling agents, such as p53, which fail to respond to TGF-beta1 stimulation. TGF-beta1 could also suppress T-cell-mediated anticancer immunity. We aimed at a comparison between cancer expressions of apoptosis regulators, such as p53, BCL-2-associated X protein (Bax), and B-cell leukemia/lymphoma extra-long protein (Bcl-xL), with TGF-beta1 in malignant and adjacent inflammatory cells in immunohistochemical evaluations of 108 colorectal cancers. Cytoplasm compartment of cancer cells was overloaded with TGF-beta1, and 87% of all cancers were TGF-beta1 positive (94/108). A very strong pattern of staining was detected for TGF-beta1 in cytoplasm of inflammatory cells at tumor margins. TGF-beta1 correlated with Bcl-xL and Bax in all colorectal cancers (P < 0.001, r= 0.473 and P < 0.001, r= 0.435, respectively) and subgroups of different clinicopathological features, especially in deeply invading cancers (pT3+pT4) instead of superficially growing tumors (pT1+pT2). Expression of TGF-beta1 in inflammatory infiltrates correlated with immunoreactivities to Bcl-xL of cancer cells (P= 0.024, r= 0.217). TGF-beta1 did not associate with p53, nor did TGF-beta1 of inflammatory cells correlate with Bax expression in cancer cells. Lack of correlations between TGF-beta1 and p53 proteins could indicate mutations at the TGF-beta1-dependent apoptotic pathway. Dominant positive linkage between TGF-beta1 and Bcl-xL and selective lack of association with Bax suggest TGF-beta1 could support colorectal cancer cell survival. The pattern of correlations seems to confirm a remarkable shift from TGF-beta1-dependent suppression of cancer growth by apoptosis to inhibition of anticancer immunity by TGF-beta1.

Dr Adam Zamenhof (1888-1940) and his insight into ophthalmology.

Adam Zamenhof was greatly influenced by his father, Ludwik Zamenhof, who designed the international language Esperanto. Like his father, he became an ophthalmologist and joined the Esperanto movement. He published in the field of ophthalmology and was soon chosen as head of an ophthalmology department. He subsequently became Chief of the Orthodox Jewish Hospital at Czystem in Warsaw. He was active in the leadership of the Bialystok-Warsaw Chamber of Medical Doctors. He perished in the Nazi Holocaust (Shoah) but all Zamenhof's ideals that Adam served as a doctor and social activist remain still alive.

Relations of TGF-beta1 with HIF-1 alpha, GLUT-1 and longer survival of colorectal cancer patients.

AIMS AND METHODS: During colorectal carcinogenesis, transforming growth factor beta 1 (TGF-beta1) undergoes a functional change from suppression of cancer cell proliferation to inhibition of T cell mediated anti-cancer immunity. We aimed to evaluate relations among TGF-beta1 and cancer cell survival factors hypoxia inducible factor-1 alpha (HIF-1 alpha) and glucose transporter 1 (GLUT-1) by immunohistochemistry in 108 colorectal cancers. RESULTS: TGF-beta1 was detected in 87% (94/108), HIF-1 alpha in 85% (92/108), and GLUT-1 in 65% (70/108) of colorectal cancers. Not only did TGF-beta1 accumulate in cytoplasm of cancer cells but also there was strong immunoreactivity to TGF-beta1 in adjacent inflammatory cells. GLUT-1 was visualised in a membranous fashion while HIF-1 was expressed in a paranuclear pattern and occasionally in nuclei of malignant cells. Cancer immunoreactivities to TGF-beta1 correlated with HIF-1 alpha (p < 0.001, r = 0.516) and GLUT-1 (p < [corrected] 0.001, r = 0.355) in general and subgroups of different clinicopathological traits. TGF-beta1 expressions of inflammatory infiltrates correlated with longer patient survival (p = 0.05, r = 0.449) and immunoreactivities to HIF-1 alpha of cancer cells (p = 0.008, r = 0.254) particularly in node positive and deeply invading cancers but failed to associate significantly with GLUT-1. CONCLUSIONS: HIF-1 alpha and GLUT-1 could cooperate with TGF-beta1, and TGF-beta1 might mediate cross-talk between the inflammatory environment and tumour with a favourable impact on patient survival.

Laryngologist Leon Zamenhof--brother of Dr. Esperanto.

PURPOSE: To reconstruct the biography of the Polish otorhinolaryngologist Leon Zamenhof (1875-1934), a brother of Ludwik Zamenhof, who is famous for invention of the international language Esperanto. METHOD: Biographical information was collected from pre-World War II resources. RESULTS: Zamenhof developed several important new forms of treatment to help the hearing impaired. Zamenhof was especially interested in the education of deaf children and the therapy necessary to facilitate their integration into society. His significant achievements were a phonetic method of therapy for the hearing impaired and an automatic device for ear insufflation that was considered indispensable in the management of pyorrhea. In addition, Zamenhof initiated various forms of social support among physicians within the medical community of Warsaw, Poland; made health care available to children with hearing impairments; and organized a Jewish school for deaf children. Zamenhof tried to change public attitudes toward deafness, working to promote the integration of the deaf into wider society. He also translated Polish literature into Esperanto. CONCLUSIONS: With similar aims to his brother Ludwik, Leon Zamenhof strived to enhance and broaden communication among people who could not hear and to persuade people to change their attitudes about deafness.

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.

[Structure and physiological function of connexin proteins]. / Struktura i fizjologiczna funkcja bialek koneksynowych.

Connexins are integral transmembrane proteins which form specialized hemichannels (connexons) in the plasma membrane. These structures make up gap junctions in adjacent cells which allow for rapid propagation of action potential and slow diffusion of nonorganic ions, secondary messengers, and other small water-soluble molecules (<1.0-2.0 kDa). Connexin proteins are crucial for the formation of gap junctions. Twenty human and 21 murine connexin isoforms (23-64 kDa) have been described so far. Traditional nomenclature in the CxMW format takes into account only the molecular weight of a given connexin. A more recent classification is based on structural gene similarities, their homology and sequence, as well as the length of connexins' cytoplasmic domains. Connexins, as all proteins, have a unique amino-acid sequences and molecular weights and exhibit specific biochemical properties. However, all of them have a common 3-D structure with four hydrophobic transmembrane domains (TM1-TM4), one cytoplasmic (CL) and two extracellular (E1-2) loops, and C- and N-terminal cytoplasmic regions. The cytoplasmic loop and C-terminal regions bind other structural proteins, creating a protein complex crucial for synchronized intercellular communication.

Comparison of STAT3 with HIF-1alpha, Ob and ObR expressions in human endometrioid adenocarcinomas.

Signal transducer and activator of transcription (STAT3) maintained invasiveness of endometrial cancer cell line. STAT3 mediated signaling for oncogenic growth stimulated by leptin (Ob) and hypoxia-inducible factor 1 (HIF-1). Therefore, we studied STAT3 in relation with HIF-1alpha, Ob, leptin receptor (ObR) and clinical and pathological variables with immunohistochemistry in 48 human endometrioid adenocarcinomas. Nuclear location was a proof of activity of STAT3 and HIF-1 and it was mainly characteristic for granular anti-STAT3 staining and rarely for diffuse HIF-1alpha expression. HIF-1alpha, Ob and ObR presented cytoplasmic granular immunoreactivities. Positive staining for STAT3, HIF-1, Ob and ObR occurred in 75%, 79%, 60% and 31% of cancers, respectively. Anti-STAT3 staining did not significantly vary with grading, staging and patients' age. STAT3 correlated with Ob (p=0.048, r=0.290) and with HIF-1alpha (p=0.004, r=0.407) in all cancers but it failed to associate with ObR at all. In opposition to the absence of significant relationship between STAT3 and Ob, STAT3 correlated with HIF-1alpha in well differentiated cancers (G1), poorly differentiated tumors (G3), pT1b neoplasms, compound group of pT1c, pT2a, pT2b tumors, and older patients over their sixties. STAT3 mediated signaling pathways that engage leptin and HIF-1alpha could only be partially reflected in correlations between STAT3 and Ob or STAT3 and HIF-1alpha in the examined neoplasms. Nevertheless, STAT3 failed to mark cancer advancement, so progressive significance of STAT3 is questionable in endometrioid adenocarcinomas.

Expression of connexin 26 in endometrial adenocarcinoma--analysis of correlations with some anatomoclinical features.

Alterations of gap junctional intercellular communication appear to play a role in the development and progression of cancer. Gap junction channel is composed of two connexons - hexameric units formed of transmembrane proteins called connexins (Cxs). The aim of the study was to evaluate the expression and localization of Cx26 in 73 cases of endometrial cancers and to estimate the relationships between expression of this protein and selected anatomoclinical features. The control group consisted of 20 sections of normal endometrium in various menstrual cycle phases, obtained from premenopausal women. In the normal endometrium punctate, membrane-associated immunoreactivity for Cx26 was observed. 54 of 73 endometrial cancers showed Cx26 expression, but 46/54 (85%) immunopositive sections revealed cytoplasmic localization for Cx26 with granular or occasionally diffuse immunostaining pattern. In addition, part of Cx26-positive tumours showed mixed: cytoplasmic and membranous staining pattern and focally also nuclear or perinuclear immunostaining was present. In 21/54 (39%) of Cx26-positive cases weak staining pattern was seen, however in 33/54 (61%) cancers strong reaction was noted. We did not find relationship between Cx26 expression and patients' age, histological type of cancer and histological grade, nevertheless we observed positive association between Cx26 expression and tumour size (p=0.037). In conclusion, our results suggest that transformed malignant cells continue to produce Cx26, which are probably not assembled into functional gap junction channels, but could still play other roles in endometrial cancer cells.

Erythropoietin and erythropoietin receptor in colorectal cancer.

Erythropoietin via erythropoietin receptor effectively prevents anemia, giving reasons for a clinical use of erythropoietin in patients with colorectal cancers. However, erythropoietin seems to promote survival of the neoplastic cells in hypoxic environment. The aim of this study was to evaluate immunohistochemically the expression of erythropoietin and erythropoietin receptor in 136 primary colorectal cancers with a correlation to different anatomo-clinical features. Erythropoietin correlated with erythropoietin receptor in colorectal cancers (r = 0.547, P < .00001). Erythropoietin and erythropoietin receptor expressions were statistically higher in adenocarcinomas versus mucinous carcinomas (P = .05 and P = .03, respectively) and in moderately (G2) versus poorly differentiated (G3) tumors (P = .001 and P = .02, respectively). This in vivo study is the first study that provides evidences for the presence of erythropoietin and erythropoietin receptor in human colorectal cancer. The expressions of these proteins strictly depended on grading because the better histological differentiation probably comes from trophic influence of erythropoietin and erythropoietin receptor.

Tadeus Reichstein, co-winner of the Nobel Prize for Physiology or Medicine: on the occasion of the 110th anniversary of his birth in Poland.

Tadeus Reichstein (1897-1996) was the first scientist born in Poland to receive the Nobel Prize in Medicine or Physiology (1950) for the "discovery of hormones of the adrenal cortex, their structure and biological effects", as stated by the Nobel Prize Committee. His family being deeply devoted to Polish cultural and historical heritage, his first name was given to him after Tadeus Kosciuszko, a chief commander of the 18th century Polish uprising named the Kosciuszko Insurrection. As a child, he emigrated with his family to Switzerland, where he was much later to become involved in numerous research studies on steroids on an international scale. It was Tadeus Reichstein who isolated and synthesized desoxycorticosterone, which still remains the drug of first choice in the treatment of Addison's disease. Additionally, thanks to his strategy for the mass production of Vitamin C, the cost of this agent was drastically reduced thus enabling its widespread therapeutic use. In our divided world so often torn by tremendous conflicts, there is a great need to both remember and commemorate such distinguished people as Tadeus Reichstein who, despite the apparent "borders" between different nationalities and cultures, have demonstrated through their work the huge need for harmonious collaboration in the development of science.

Overexpression of the obesity hormone leptin in human colorectal cancer.

BACKGROUND: Leptin is an adipocyte-derived neurohormone, high levels of which are found in obese individuals. Leptin controls energy expenditure, acting in the brain, and regulates different processes in peripheral organs. Recent studies have suggested that leptin may be involved in cancer development and progression. AIMS: To analyse leptin expression in human colorectal cancer as well as in colorectal mucosa and colorectal adenomas. METHODS: Leptin expression was assessed by immunohistochemistry in 166 colorectal cancers, 101 samples of colorectal mucosa and 41 adenomas. Leptin concentration in colorectal cancer was correlated with selected clinicopathological features. RESULTS: Immunoreactivity for leptin was observed in 51.2% (85/166) of primary colorectal cancers. In adenomas leptin expression was observed in 14.6% (6/41) of studied cases. In normal mucosa, leptin was present at low levels, except in tumour bordering areas where its concentration appeared to reflect levels in the adjacent cancer tissue. Leptin expression in colorectal cancer significantly correlated with tumour G2 grade (p = 0.002) as well as with histological type (adenocarcinoma) of tumours (p = 0.044). CONCLUSIONS: Results indicate that leptin is overexpressed in human colorectal cancer, which suggests that the hormone might contribute to colorectal cancer development and progression.

To heal the mind's eye of hate--Dr. Ludwik Zamenhof.

Ludwik Zamenhof (1859-1917), born in Poland, invented and propagated Esperanto - an artificial, easy-to-learn language. Literally meaning "language of hope," Esperanto was constructed to avoid misunderstandings, establish communication and facilitate harmony among different nationalities. Simply, he wanted people to accept one another despite observed differences. He was a skilled ophthalmologist, but figuratively, he wished to heal the eyes of humankind to look without hate, just as the biblical Tobias removed the cataract from the corners of his father's eyes to restore his sight.