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Conventional therapeutic approaches like chemotherapy, surgery and radiation for cancer and other malignancies have limited success rate. Several factors such as drug resistance, non-penetrability into solid tumors and unwanted toxicity due to non-specific action contribute to treatment failure. To overcome these issues, immunotoxins were developed having a target specific action. Immunotoxins are chimeric cytotoxic proteins which are formed by linking a toxin moiety to intact antibody or its fragment. Bacterial and plant based toxins are used in immunotoxins construction but they have many drawbacks in terms of immunogenicity and non-specific toxicity. Recently, a novel class of immunotoxins of human origin has been introduced. Immunotoxins fight back cancers by targeting the neoplastic cells and cause cells death by inhibiting protein synthesis. They have been categorized into two main classes, chemically conjugated immunotoxins and recombinant immunotoxins. This review summarizes recent advances in immunotoxins development and present a comprehensive illustration of sources and generations of immunotoxins. Moreover, it also highlights future directions to be explored. This review also focuses the limitations in immunotoxins development and its use.
Pheochromocytomas are rare tumors arising from the adrenal medulla. The diagnosis of malignancy remains a dogma between surgeon, pathologist and oncologist. We present a case of voluminous pheochromocytoma in a 53-year-old female patient, suspect of malignancy in the pathologic examination, while emphasizing the importance of the clinical and radiological long-term monitoring.
Content available Malignancy-associated kidney disease
Malignancy or its treatment affect kidney in several ways. The most common are acute kidney injury and chronic kidney disease. Other form of kidney diseases can also be present such as nephrotic syndrome, tubulointerstitial nephritis, thrombotic microangipathy etc. In addition, electrolyte abnormalities such as hypercalcemia, hyponatremia and hypernatremia, hypokalemia and hyperkalemia, and hypomagnesemia. are observed. Treatment of malignancy associated kidney disease is usually symptomatic. Cessation of the offending agent or other supportive measures if needed i.e. renal replacement therapy are also implemented.
Large intestine malignancy is the second most common malignancy and second leading cause of cancer mortality in Poland. This is related to late detection of these lesions, e.g. due to lack of effective screening tests. Lesions found by a surgeon are clinically advanced, making the treatment often ineffective and sometimes even completely impossible. Discovery of a substance that would be able to stop key processes for the development of malignancy could change such situation. Activity of certain enzymes was found to increase in malignant cells and invasion of malignancy could be triggered by inadequate amount of endogenous inhibitors of these enzymes in the surrounding healthy tissues. Inhibitors identical with that produced in human cells were found in egg whites.The aim of the study was to determine ability of cystatin isolated from egg whites to inhibit activity of cathepsin B and L.Material and methods. Immunohistochemistry and histology of tissue specimen collected from malignant lesions resected from 60 patients diagnosed with large intestine adenocarcinoma, who underwent surgical treatment in 2nd Department of General and Oncological Surgery, Medical University of Wrocław between 2007 and 2009.Results. Differences were fund between health tissues, margins and center of the malignant lesions with regard to amount and distribution of stained cathepsin B - cystatin complexes. The above mentioned inhibitors were able to inhibit 90% of primary activity of cathepsin B and L in malignant tissues.Conclusions. Cystatins obtained from egg whites could be used as substances supporting anti-cancer therapy in the future.
Content available remote Regulation of gastrointestinal mucosal growth during aging
The increase in the aging population has led to a growing interest in achieving a better understanding of the aging process and of diseases that are predominantly expressed during advancing age. Since the structural and, in turn, the functional integrity of the mucosa of the gastrointestinal tract (GI) are maintained by constant renewal of cells, a detailed knowledge of the events that initiate and regulate mucosal proliferative processes is essential for a better understanding of the normal aging process as well as age-associated dysfunctions, including malignancy that represent disorders of tissue growth. In Fischer-344 rats, aging is associated with increased mucosal proliferative activity in much of the GI tract. On the other hand, the functional properties are either decreased or remain unchanged during advancing age. Basal gastric acid and pepsin output decline during aging, as is gastrin secretion. In contrast, antral gastrin levels increase during this period, as is mucosal histidine decarboxylase activity. The age-related decline in gastrin secretion could partly be attributed to a higher ratio of somatostatin (D) to gastrin (G) cells in the antral mucosa. The age-related rise in GI mucosal proliferative activity could not be attributed to the trophic action of either gastrin or bombesin, since they caused no significant change in mucosal proliferation in aged rats. On the other hand, EGF and TGF-alphalpha appear to be involved in regulating mucosal proliferation during aging. Aging is associated with increased activation of EGF-receptor (EGFR), the common receptor for EGF and TGF-alpha. This could be due to (a) increased levels of membrane-bound precursor form(s) of TGF-alpha resulting in increased activation EGFR signaling processes through an autocrine/paracrine mechanism, (b) heightened sensitivity of mucosal EGFR to EGF and TGF-alpha such that comparatively lower levels of these peptides are required to activate EGFR in aged than in young animals and/or (c) loss of EGFR regulatory factor(s) such as ERRP (EGFR Related Protein), a "negative regulator" of EGFR.
Choroba nowotworowa niezmiennie kojarzy się z zaburzeniami układu hemostazy. Wpływ rozwijającego się nowotworu na układ hemostazy powoduje najczęściej indukcję stanu nadkrzepliwości.
Cancer invariably associated with disorders of hemostasis. Effect of tumor growing hemostatic system is in most cases the induction of a hypercoagulable state.
Epstein-Barr virus (EBV) is a ubiquitous virus with infections commonly resulting in a latency carrier state. Although the exact role of EBV in cancer pathogenesis remains not entirely clear, it is highly probable that it causes several lymphoid and epithelial malignancies, such as Hodgkin’s lymphoma, NK-T cell lymphoma, Burkitt’s lymphoma, and nasopharyngeal carcinoma. EBV-associated malignancies are associated with a latent form of infection, and several of these EBV-encoded latent proteins are known to mediate cellular transformation. These include six nuclear antigens and three latent membrane proteins. Studies have shown that EBV displays distinct patterns of viral latent gene expression in these lymphoid and epithelial tumors. The constant expression of latent membrane protein 2A (LMP2A) at the RNA level in both primary and metastatic tumors suggests that this protein might be a driving factor in the tumorigenesis of EBV-associated malignancies. LMP2A may cooperate with the aberrant host genome, and thereby contribute to malignant transformation by intervening in signaling pathways at multiple points, especially in the cell cycle and apoptotic pathway. This review summarizes the role of EBV-encoded LMP2A in EBV-associated viral latency and cancers. We will focus our discussions on the molecular interactions of each of the conserved motifs in LMP2A, and their involvement in various signaling pathways, namely the B-cell receptor blockade mechanism, the ubiquitin-mediated (Notch and Wnt) pathways, and the MAPK, PI3-K/Akt, NK-κB and STAT pathways, which can provide us with important insights into the roles of LMP2A in the EBV-associated latency state and various malignancies.
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