Cathepsins H and L in colorectal cancer

Cysteine cathepsins are important regulators and signaling molecules of an unimaginable number of biologi­cal processes while they also play an essential role in cancer progression, invasion and metastasis. The purpose of our study was: first to compare the expression levels of cathepsins H and L in the supernatants of colon cancer tissues from 74 patients versus the same enzymic expressions of the supernatants of the adjacent normal colorectal tissues and second to correlate our findings to the grade of the malignancy by using an enzyme-linked immunosorbent assay (ELISA). The results indicated that the cathepsins H and L of all malignant tissues presented significant higher expression’s values than the corresponding control. Specifically the concentration of cathepsin H that has been found increased significantly as malignancy proceeded, was higher than the corresponding control as following: 155% in B1 stage and 204,44% in D stage. Between the two inves­tigated proteases cathepsin L has showed the greatest increase, which in D stage was 261,03% higher than the corresponding control. According to these results, the expression of cysteine proteases H and L could be of critical value in the diagnosis and progression of colon cance

Radiation-induced intracranial vasculopathy after radiotherapy (laser surgery) for craniopharyngioma: a study case report

Brain irradiation is commonly used for many primary brain malignancies. After radiotherapy, the potential for the development of radiation-induced vasculopathy exists and should be kept in mind. Craniopharyngioma is one rare slowly developing, usually benign tumor. In the majority of cases, such tumors grow above the anterior upper lip of pituitary gland and are located mainly on Sella Turcica or on side sella areas. Macroscopically, they seem like big globe tumors with the white or red-blooded surface. Histologically, have ascertained two types, adamantinomatous and papillary type (though they have ascertained and mixed types). However, independently of their main type, they usually have cystic form. The size of craniopharyngioma is between 2 to 4 cm. Strike 0,12-2/100.000 people a year, 30 to 50% of all cases presenting during childhood and adolescence and they constitute the 2-5% of all brain tumors. The peak incidence rates have been shown in children of ages 5 to 14 years and adults of ages 50 to 74 years.  The study below presents one case of post-radiation vasculopathy of the brain arteries of the patient who received radiation therapy to the brain as part of his craniopharingioma management. It will be underscored the significance of this patient condition and also will be described possible routes to prevent the occurrence of vasculopathy.

Cytogenetic behaviour of crocin on cultured lymphocytes from leukemic patients

Crocin is isolated from saffron, an important spice rich in carotenoids obtained from the stigmas of Crocus sativus L, commonly consumed all around the world and used as a medical drug to treat numerous diseases. In the present work a comparative study of the cytogenetic behaviour of crocin between cultured lymphocytes from chronic lymphocytic leukemic patients as well as from healthy individuals was undertaken in order to test the hypothesis that the sister chromatid exchange assay in vitro can be used for the prediction of the in vivo tumor response to the potential chemotherapeutic action of crocin. Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in cultured lymphocytes from peripheral blood of all donors. Results showed that all tested crocin solutions didn’t cause remarkable changes to the PRI values of lymphocytes neither of the leukemic patients, nor of healthy individual. Contrariwise, after crocin affection a statistically significant decrease of the SCEs frequency of lymphocytes of leukemic patients had been observed (p<0,001, t-test) whereas the SCEs of the healthy donor’s cells presented slight, but not statistically significant increase. Our results indicate that crocin did not prove to be cytostatic in the tested concentrations, but it mainly reduced significantly the DNA damages along with being demonstrated as cytoprotectiv

Colon cancer: An epidemiological study in Northern Greece

Colorectal or colon cancer is the third most common form of cancer with 655,000 deaths worldwide per year and the second leading cause of cancer-related death in the Western world.  variety of risk factors have been linked to colon cancer including genetic factors (age, sex and hereditary mutations of repair enzymes genes), environmental exposures, daily life habits (diet, smoking, obesity and sedentary habits) and inflam­matory conditions of the digestive tract. The present research is a retrospective epidemiological study concerning 280 patients with colon cancer who were hospitalized at Theagenion Cancer Hospital of Thessaloniki during 2006, 2007 and 2008. They were classified according to their age, sex, place of residence, occupation and tobacco consumption. The results revealed that 58.57% were males and 41,43% females, 82,49% of the patients were older than 60 years of age, 38,93% were urban and 60% rural district inhabitants. Pensioners represented 47,50%, farmers 18,93%, housekeepers 13,57%, employers or free lancers 10,71%. For the rest 9,29% no in­formation has been recorded. Regarding the consumption of tobacco, 16,79% of them were smokers, 34,64% non smokers, whereas there was no information about the smoking habits of the remaining (48,57%). The results of this research with respect to age and sex of the patients are in agreement with bibliographical data, but conclu­sions can not be drawn about the connection between occupation and colon cancer onset. The fact that among the patients the non smokers were more than smokers, which is in contrast with the international data, could be attributed to the insufficiency of respective information for 48,57% of the patients. The unexpectedly higher frequency of colorectal cancer appearance among rural district inhabitants rather than among urban district inhabitants should be researched as soon as possible. The deficiency of information about fundamental risk factors of colon cancer, as genetic and environmental factors and life­style among Greek population requires the continuation and the extension of this epidemiological study, because prevention is the best cure and epidemiological studies have offered substantial contribution to prevention

A rare case of Eosinophilic Pneumonia in an infant patient and review of the current English literature regarding this disease

We report a case of eosinophilic pneumonia (EP) in an infant patient. Such cases are rare and the purpose of this study is to combine this case and the english literature available in order to expand our knowledge regarding the therapeutic strategies for this disease.Currently we can define a specific therapeutic guideline for patients with EP.It is important to expand our knowledge and experience regarding this ailment.More studies are needed to better understand this rare disease, to more precisely define diagnostic and therapeutic strategies and to find out and asses new treatment methods

Role of Vanadium in Cellular and Molecular Immunology: Association with Immune-Related Inflammation and Pharmacotoxicology Mechanisms

Over the last decade, a diverse spectrum of vanadium compounds has arisen as anti-inflammatory therapeutic metallodrugs targeting various diseases. Recent studies have demonstrated that select well-defined vanadium species are involved in many immune-driven molecular mechanisms that regulate and influence immune responses. In addition, advances in cell immunotherapy have relied on the use of metallodrugs to create a “safe,” highly regulated, environment for optimal control of immune response. Emerging findings include optimal regulation of B/T cell signaling and expression of immune suppressive or anti-inflammatory cytokines, critical for immune cell effector functions. Furthermore, in-depth perusals have explored NF-κB and Toll-like receptor signaling mechanisms in order to enhance adaptive immune responses and promote recruitment or conversion of inflammatory cells to immunodeficient tissues. Consequently, well-defined vanadium metallodrugs, poised to access and resensitize the immune microenvironment, interact with various biomolecular targets, such as B cells, T cells, interleukin markers, and transcription factors, thereby influencing and affecting immune signaling. A synthetically formulated and structure-based (bio)chemical reactivity account of vanadoforms emerges as a plausible strategy for designing drugs characterized by selectivity and specificity, with respect to the cellular molecular targets intimately linked to immune responses, thereby giving rise to a challenging field linked to the development of immune system vanadodrugs

Cutaneous skull metastasis from uterine leiomyosarcoma: a case report

<p>Abstract</p> <p>Background</p> <p>Cutaneous metastases in the facial region occur in less than 0.5% of patients with metastatic cancer.</p> <p>Case presentation</p> <p>A 52-year-old woman who admitted with a lung and a skull skin nodule is presented. She had a known diagnosis of uterine leiomyosarcoma following an extended total hysterectomy two years ago. Excision biopsy of both nodules revealed metastatic disease.</p> <p>Conclusion</p> <p>The appearance of a cutaneous nodule in a patient with a history of uterine leiomyosarcoma might indicate a metastatic tumor lesion. Biopsy and immunohistochemistry are essential for correct diagnosis.</p

Assessment of the roles of cathepsins in the pregression of colorectal cancer

For a long time it was thought that cathepsins are a group of intracellular hydrolases involved in the lysosomal degradation of proteins. Recently the development of new technology and the impressive closer look at the research of cellular molecular mechanisms, revealed specialized, vital functions for various members of the family of cathepsins. In addition to their involvement in various physiological processes, cathepsins were implicated in the mechanisms of carcinogenesis, in the development and metastasis of a variety of tumors , including colon cancer (CRC), the second leading cause of death worldwide and the third most common cancer in both men and women in Europe . The discovery of prognostic markers for CRC, like any other form of cancer, is a very important quest for methods of therapeutic intervention. Apart from the established molecular markers like EGFR, KRAS, several researchers have proposed cathepsin B as a tumor marker of CRC. In the present study, we investigated the expression of five cathepsins: the aspartyl-cathepsin D, the serine-protease G and the cysteine-cathepsins B, H and L in human CRC tissues of various stages, and in corresponding normal tissues, in order to contribute to clarify the role of these cathepsins in the development of CRC. The study involved 74 patients, 35 men and 39 women with colorectal adenocarcinoma (CRC), which underwent surgical resection at Theagenio Cancer Hospital. The tumours were removed and divided according to their histology into groups in accordance with the Astler-Coller staging. A biochemical assay for determining the level of expression of each cathepsin was applied to the supernatant of the homogenate specimens from all malignant tissue with the method of ELIZA. In parallel the histological sections of 40 surgical specimens were studied. The expression levels of all five cathepsins in all stages of malignancy were more than doubled of the adjacent normal tissues. The expression of cathepsin H showed a statistically significant increase in all malignant stages which increased progressively with increasing malignancy. The immunohistochemical detection of expression of cathepsin B showed that 80% of the surgical specimens, the extent of staining in tumors related percentage of cells>50%. The intensity of staining was characterized moderate in 12 tumours and strong in 20. The immunohistochemical detection of expression of cathepsin D showed that 75% of the surgical specimens, the extent of staining cells concerned rate>50%. The intensity of staining was characterized moderate in 10 tumours and strong in 20. The conclusions drawn from the results of this study are: a) determining the expression of cathepsins H and L could help in the diagnosis and staging of colon cancer, b) cathepsins B, D and G could play an important role in the prognosis of the disease and perhaps in response to specific therapy. Already proteases are an attraction in research to find substances with therapeutic applications. Therefore, the clarification of the role of proteases, especially cathepsins in the course of colon cancer is important, both within the study and understanding of the biology of the disease and the other in an effort to find specific and sensitive prognostic markers.Παλαιότερα επικρατούσε η άποψη ότι οι καθεψίνες είναι μία ομάδα ενδοκυττάριων υδρολασών που συμμετέχουν στην ανακύκλωση των πρωτεϊνών μέσα στο λυσόσωμα. Η ανάπτυξη της τεχνολογίας και η εντυπωσιακή εμβάθυνση στους μοριακούς μηχανισμούς του κυττάρου, τα τελευταία χρόνια, αποκάλυψε εξειδικευμένες, ζωτικής σημασίας λειτουργίες για διάφορα μέλη της οικογένειας των καθεψινών. Εκτός από τη συμμετοχή τους σε διάφορες φυσιολογικές διεργασίες, οι καθεψίνες ενοχοποιούνται για ουσιαστική συμμετοχή στην καρκινογένεση, στην εξέλιξη και στη μετάσταση μιας ποικιλίας όγκων, μεταξύ των οποίων και ο καρκίνος του παχέος εντέρου (ΚΠΕ-CRC ), η δεύτερη κύρια αιτία θανάτου παγκοσμίως και η τρίτη πιο κοινή μορφή καρκίνου τόσο στους άνδρες, όσο και στις γυναίκες στην Ευρώπη. Η εξεύρεση προγνωστικών/προβλεπτικών δεικτών για τον ΚΠΕ, όπως και για κάθε άλλη μορφή καρκίνου, αποτελεί μια πολύ σημαντική προσπάθεια αναζήτησης μεθόδων θεραπευτικής παρέμβασης. Εκτός από τους καθιερωμένους μοριακούς δείκτες EGFR, KRAS, από αρκετούς ερευνητές έχει προταθεί ως καρκινικός δείκτης του ΚΠΕ και η καθεψίνη Β. Στην παρούσα διατριβή μελετήθηκε η έκφραση πέντε καθεψινών: της ασπαρτυλο-καθεψίνης D, της σέρινο-πρωτεάσης G και των κυστεϊνο-καθεψινών B, H και L σε καρκινικούς ιστούς εντέρου ανθρώπου διαφόρων σταδίων, καθώς και σε αντίστοιχους φυσιολογικούς ιστούς, με στόχο τη συμβολή στην αποσαφήνιση του ρόλου των καθεψινών αυτών στην εξέλιξη του ΚΠΕ. Στη μελέτη συμμετείχαν 74 ασθενείς, 35 άνδρες και 39 γυναίκες, με CRC, οι οποίοι υποβλήθηκε σε εντερεκτομή στο Θεαγένειο Α.Ν.Θ.. Οι όγκοι που αφαιρέθηκαν υποδιαιρέθηκαν με βάση την ιστολογική τους εικόνα σε ομάδες σύμφωνα με τη σταδιοποίηση κατά Astler-Coller. Στο υπερκείμενο του ομογενοποιήματος ιστοτεμαχίων από όλους τους κακοήθεις ιστούς πραγματοποιήθηκε βιοχημικός ποσοτικός προσδιορισμός της έκφρασης των καθεψινών με την μέθοδο ELIZA. Παράλληλα στα χειρουργικά παρασκευάσματα 40 από τους 74 ασθενείς πραγματοποιήθηκε ανοσοϊστοχημικός έλεγχος για την έκφραση των καθεψινών B και D. Η έκφραση και των πέντε καθεψινών σε όλα τα στάδια εξέλιξης βρέθηκε υπερδιπλάσια από την αντίστοιχη των παρακείμενων φυσιολογικών ιστών. Το υψηλό επίπεδο έκφρασης των καθεψίνης Β, G, L, D παρέμεινε ουσιαστικά αμετάβλητο σε όλα τα στάδια, ενώ η έκφραση της καθεψίνης Η εμφάνισε μια στατιστικά σημαντική άνοδο σε όλα τα στάδια, η οποία αύξανε προϊούσας της νόσου. Η ανοσοϊστοχημική ανίχνευση της καθεψίνης Β έδειξε θετική έκφραση αυτής στο 80% των περιστατικών και για την καθεψίνη D το αντίστοιχο ποσοστό ήταν 75%. Τα συμπεράσματα που προκύπτουν είναι τα εξής: α) ο προσδιορισμός της έκφρασης των καθεψινών Η και L θα μπορούσε να συμβάλλει στη διάγνωση και στη σταδιοποίηση του καρκίνου του παχέος εντέρου, β) οι καθεψίνες Β, D και G θα μπορούσαν να παίξουν σημαντικό ρόλο στην πρόγνωση της ασθένειας και ίσως και στην απόκριση σε συγκεκριμένη θεραπεία. Ήδη οι πρωτεάσες αποτελούν πόλο έλξης στην έρευνα για την εύρεση ουσιών με θεραπευτικές εφαρμογές. Επομένως η αποσαφήνιση του ρόλου των πρωτεασών και ιδιαίτερα των καθεψινών στην πορεία του καρκίνου του εντέρου είναι σημαντική, αφενός στα πλαίσια της μελέτης και κατανόησης της βιολογίας της νόσου και αφετέρου στη προσπάθεια ανεύρεσης εξειδικευμένων και ευαίσθητων προγνωστικών / προβλεπτικών δεικτών

Differential expression of IL-17, 22 and 23 in the progression of colorectal cancer in patients with K-ras mutation: Ras signal inhibition and crosstalk with GM-CSF and IFN-γ.

Recent studies have suggested that aberrant K-ras signaling is responsible for triggering immunological responses and inflammation-driven tumorigenesis. Interleukins IL-17, IL-22, and IL-23 have been reported in various types of malignancies, but the exact mechanistic role of these molecules remains to be elucidated. Given the role of K-ras and the involvement of interleukins in colorectal tumorigenesis, research efforts are reported for the first time, showing that differentially expressed interleukin IL-17, IL-22, and IL-23 levels are associated with K-ras in a stage-specific fashion along colorectal cancer progression. Specifically, a) the effect of K-ras signaling was investigated in the overall expression of interleukins in patients with colorectal cancer and healthy controls, and b) an association was established between mutant K-ras and cytokines GM-CSF and IFN-γ. The results indicate that specific interleukins are differentially expressed in K-ras positive patients and the use of K-ras inhibitor Manumycin A decreases both interleukin levels and apoptosis in Caco-2 cells by inhibiting cell viability. Finally, inflammation-driven GM-CSF and IFN-γ levels are modulated through interleukin expression in tumor patients, with interleukin expression in the intestinal lumen and cancerous tissue mediated by aberrant K-ras signaling. Collectively, the findings a) indicate that interleukin expression is influenced by ras signaling and specific interleukins play an oncogenic promoter role in colorectal cancer, highlighting the molecular link between inflammation and tumorigenesis, and b) accentuate the interwoven molecular correlations as leads to new therapeutic approaches in the future