Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009. / Härtill 6 uppsatser.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2007. / Title from PDF title page (viewed on Feb. 4, 2010). Includes bibliographical references.

Pedicle screw-rod instrumentation is considered a standard treatment for spinal instability, and titanium is the most common material for this application. Cobalt-chromium has several advantages over titanium and is generating interest in orthopedic practice. The aim of this study was to compare titanium versus cobalt-chromium rods in posterior fusion, with and without transverse connectors, through in vitro biomechanical testing and determine the optimal configuration. Six cadaveric lumbar spines (L1-S1) were used. Posterior and middle column injuries were simulated at L3-L5 and different pedicle screw constructs were implanted. Specimens were subjected to flexibility tests and range of motion, intradiscal pressure and axial rotation energy loss were statistically compared among the following conditions: intact, titanium rods (without transverse connectors), titanium rods with transverse connectors, cobalt-chromium rods (without transverse connectors) and cobalt-chromium rods with transverse connectors. The novel measurement of energy loss was examined to determine its viability in fusion investigations. All fusion constructs significantly (p0.05) were observed in axial rotation among all conditions. Intradiscal pressure significantly increased (p≤0.01) after fusion, except for the cobalt-chrome conditions in extension (p≥0.06), and no significant differences (p>0.99) were found among fixation constructs. Energy loss, differences became significant between the cobalt-chrome with transverse connector condition with respect to the cobalt-chrome (p=0.05) and titanium (p There is not enough evidence to support that the cobalt-chrome rods performed biomechanically different than the titanium rods. The use of titanium rods may be more beneficial because there is a lower probability of corrosion. The inclusion of the transverse connector only increased stability for the cobalt-chromium construct in axial rotation, which suggests that it is beneficial in complete facetectomy procedures.

Οι ανθρώπινοι όγκοι συνοδεύονται από κάποιου βαθμού φλεγμονή. Οι παράγοντες του καρκινικού κυττάρου που προκαλούν και ρυθμίζουν τη φλεγμονή, καθώς και οι επιδράσεις της φλεγμονής αυτής πάνω στον ίδιο τον όγκο αποτελούν σημαντικά ερευνητικά ζητούμενα. Τρέχοντα δεδομένα υποστηρίζουν ότι συγκεκριμένες γενετικές βλάβες του καρκινικού κυττάρου αποτελούν σημαντικούς τελεστές της παρανεοπλασματικής φλεγμονής. Συγκεκριμένα, μεταλλάξεις του ογκογονιδίου Kras, συχνές σε καρκίνους των πνευμόνων, του παγκρέατος και του εντέρου πιθανά συντελούν στη δημιουργία ενός φλεγμονώδους-ογκοπροαγωγού μικροπεριβάλλοντος. Στόχος της παρούσας εργασίας ήταν η μελέτη του ρόλου των μεταλλάξεων Kras στη νεοπλασματική πρόοδο και την παρανεοπλασματική φλεγμονή. Για το σκοπό αυτό, πραγματοποιήθηκε γονοτύπηση καρκινικών σειρών ποντικού για μεταλλάξεις Kras. Σε κυτταρική σειρά που φέρει ενεργοποιητική μετάλλαξη Kras αποσιωπήθηκε σταθερά η έκφραση του με shRNA. Η μητρική και η θυγατρική σειρές εμφυτεύθηκαν στο υποδόριο και τον υπεζωκότα ανοσοεπαρκών ποντικών. Η αποσιώπηση του Kras οδήγησε σε μικρότερου βαθμού φλεγμονή και νεοπλασματική αύξηση, σε σύγκριση με τους μητρικούς όγκους. Ο κύριος πληθυσμός ανοσολογικών κυττάρων στους όγκους ήταν CD45+CD11b+ μυελοκύτταρα, τα οποία πρόσφατα βρέθηκε πως ρυθμίζονται φαινοτυπικά στο σπλήνα. Η σπληνεκτομή δεν επηρέασε την ανάπτυξη υποδόριων όγκων και νεοπλασματικής φλεγμονής από μητρικά και shKras κύτταρα. Αντίθετα, η σπληνεκτομή είχε ευεργετικά αποτελέσματα σε ζωϊκό πρότυπο κακοήθους υπεζωκοτικής συλλογής οδηγώντας σε ελάττωση συσσώρευσης υγρού και φλεγμονωδών κυττάρων. Συμπερασματικά, οι μεταλλάξεις Kras φαίνεται να παίζουν ρόλο στη νεοπλασματική πρόοδο και τη σχετιζόμενη φλεγμονή, αλληλεπιδρώντας με κάποιο σπληνοεξαρτώμενο πληθυσμό μυελοκυττάρων. Οι δράσεις αυτού του κυτταρικού πληθυσμού εξαρτώνται από το νεοπλασματικό μικροπεριβάλλον. / The human tumors are accompanied with some kind of inflammation. The factors of the cancer cell that cause and regulate this inflammation, as well as the influence of this inflammation on the tumor itself constitute an important research aim. Current data argue that specific genetic damage of the cancer cell constitute important operands of the paraneoplastic inflammation. In particular, mutations of the oncogene Kras, common in cancers of the lungs, the pancreas and the colon, possibly contribute to the initiation of a an inflammatory-tumorpromoting microenvironment. The aim of the current thesis was the study of the role of the Kras mutations in the neoplastic progression and the paraneoplastic inflammation. For this purpose, genotyping of murine cancer cell lines for Kras mutations was performed. In cancer cell line with activating Kras mutation, the expression of the Kras was silenced through shRNA. Both the parental and the daughter cell lines were implanted both subcutaneously and in the pleural cavity of immunocompetent mice. The silencing of the Kras led to a lower rate of inflammation and neoplastic growth, in comparison with the parental tumors. The main immunological population in the tumors was CD45+CD11b+ myeloid derived cells which were recently found to be phenotypically regulated in the spleen. The splenectomy did not influence the growth of subcutaneous tumors or neoplastic inflammation from parental and shKras cells. In contrast, the splenectomy had positive results on animal model of malignant pleural effusion, leading to lower collection of liquid and inflammatory cells. In conclusion, the mutations of Kras are shown to play a role in the neoplastic progression and the associated inflammation, interacting with a spleen- dependent population of myeloid derived cells. The actions of this cell population depend on the neoplastic microenvironment.

Uveal Melanoma (UM) is the most common malignant intra-ocular tumor in adults. Forty-five percent of UM patients develop metastasis within fifteen years of the initial diagnosis. Cutaneous Melanoma (CM) is a highly metastatic cancer that accounts for the majority of skin cancer deaths. Current treatments are not especially effective for the metastatic phase of the disease. Therefore, the identification of new molecular targets that can be exploited in the clinic are needed. / KISS1 is a putative human metastasis suppressor gene. The purpose of this study was to investigate the expression of KISS1 in melanoma and its potential value as a prognostic marker. / From results in vitro and in vivo we were able to characterize KISS1 in UM for the first time as well as its expression at the protein level, in CM. The correlation between KISS1 expression and UM survival rate suggests an important role for KISS1 as a prognostic marker in this tumor.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Alabama at Birmingham, 2006. / Title from first page of PDF file (viewed Oct. 31, 2007). Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 4 uppsatser.