Prognosis of colorectal cancer with liver metastasis: value of a prognostic index

The objective of the present study was to explore the factors related to the prognosis of colorectal cancer (CRC) and to establish a prognostic model for the selection of patients who might benefit from hepatic resection for metastatic CRC. A total of 293 patients undergoing liver resection for metastatic CRC (172 males and 80 females ranging in age from 26 to 80 years) were selected and clinical, pathological and outcome data were examined in this retrospective study. The prognostic index (PI) of the patients was calculated on the basis of results of multivariate analysis. Patients were stratified into different groups, with survival curves projected according to PI. The 1-, 3-, and 5-year overall survival rates were 58.3, 26.4, and 11.3%, respectively. Univariate analysis indicated that degree of primary tumor differentiation, resection margin, preoperative carcinoembryonic antigen (CEA) level, number of liver metastases, and resection of liver metastases were associated with prognosis (P < 0.05). In multivariate analysis, the last three factors were found to be independent prognostic factors. The resection of liver metastases was a favorable factor. Patients were classified into three groups according to PI, which differed significantly in survival rate (P < 0.05). The individual survival rate was evaluated based on PI. Resection of hepatic colorectal metastases may produce long-term survival and cure. The proposed PI was easy to use, was highly predictive of patient outcome, and permitted categorization of patients into treatment groups.

Prostate-specific membrane antigen can promote in vivo osseous metastasis of prostate cancer cells in mice

Reports remain insufficient on whether and how prostate-specific membrane antigen (PSMA) can influence in vivo osseous metastasis of prostate cancer (PCa). In the present study, the authors induced stable expression of PSMA in mouse PCa cell line RM-1. In vivo osseous metastasis was induced in 37 6-week-old female C57BL/6 mice weighing 22.45 ± 0.456 g. RM-1 cells were actively injected into the femoral bone cavity, leading to bilateral dissymmetry of bone density in the femoral bone. Tumor cells were also detected in bone tissue by pathological examination. The impact on bone density was demonstrated by the significant difference between animals injected with RM-PSMA cells (0.0738 ± 0.0185 g/cm²) and animals injected with RM-empty plasmid cells (0.0895 ± 0.0241 g/cm²). The lytic bone lesion of the RM-PSMA group (68.4%) was higher than that of the control group (27.8%). Immunohistochemistry showed that the expression of both vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) was distinctly higher in the RM-PSMA group than in the control group, while ELISA and Western blot assay indicated that VEGF and MMP-9 were higher in the RM-PSMA group compared to the control group (in vitro). Thus, the present study proposed and then confirmed for the first time that PSMA can promote in vivo osseous metastasis of PCa by increasing sclerotic destruction of PCa cells. Further analyses also suggested that PSMA functions positively on the invasive ability of RM-1 by increasing the expression of MMP-9 and VEGF by osseous metastases in vivo

Reconstructive dosimetry for cutaneous radiation syndrome

According to the International Atomic Energy Agency (IAEA), a relatively significant number of radiological accidents have occurred in recent years mainly because of the practices referred to as potentially high-risk activities, such as radiotherapy, large irradiators and industrial radiography, especially in gammagraphy assays. In some instances, severe injuries have occurred in exposed persons due to high radiation doses. In industrial radiography, 80 cases involving a total of 120 radiation workers, 110 members of the public including 12 deaths have been recorded up to 2014. Radiological accidents in industrial practices in Brazil have mainly resulted in development of cutaneous radiation syndrome (CRS) in hands and fingers. Brazilian data include 5 serious cases related to industrial gammagraphy, affecting 7 radiation workers and 19 members of the public; however, none of them were fatal. Some methods of reconstructive dosimetry have been used to estimate the radiation dose to assist in prescribing medical treatment. The type and development of cutaneous manifestations in the exposed areas of a person is the first achievable gross dose estimation. This review article presents the state-of-the-art reconstructive dosimetry methods enabling estimation of local radiation doses and provides guidelines for medical handling of the exposed individuals. The review also presents the Chilean and Brazilian radiological accident cases to highlight the importance of reconstructive dosimetry.

Collagen binding integrins and cancer testis antigens in prostate cancer and melanoma

Camilla Pelo Collagen Binding Integrins and Cancer Testis Antigens in Prostate Cancer and Melanoma Department of Biochemistry, MediCity Research Laboratory, University of Turku, Finland Annales Universitatis Turkuensis, Painosalama Oy, Turku, Finland 2016 ABSTRACT Prostate cancer is the second most common cancer in men worldwide. The incidence of melanoma, in turn, is increasing faster than any other cancer incidences. In Finland, more than 5000 prostate cancer and 1200 new melanoma cases are diagnosed each year. One approach to further understand the cellular processes involved in prostate cancer and melanoma is to gain better knowledge about alterations in gene expression and their potential impact on the progression of the diseases. This thesis is focused on expression studies in two gene families; integrins and cancer testis antigens (CT antigens), in human prostate adenocarcinoma and advanced human melanoma. Integrins are heterodimeric transmembrane receptors which regulate many important cellular processes such as cell proliferation, migration and survival. CT antigens are frequently expressed in different types of cancers, but are only expressed in testis in healthy individuals. CT antigens are also highly immunogenic proteins. Due to the properties mentioned above, integrins and CT antigens can function as target molecules for the development of cancer diagnostics and drugs. One of the main purposes of this thesis was to study the expression of the four collagen binding integrins α1β1, α2β1, α10β1, α11β1 and the cancer testis antigen 16 (CT16) in cancer cell lines and human tissues of prostate cancer and metastatic melanoma. Additional aims included studies on the biological role of CT16 and the abundance of CT16 in sera of advanced melanoma patients. The prognostic and diagnostic significance of CT16 and the collagen binding integrins were also evaluated. Expression studies on collagen binding integrins and the CT antigen CT16 in melanoma and prostate cancer were limited and the biological role of CT16 was unknown. In this thesis, the expression levels of α2β1 and α11β1 were found to be significantly altered in prostate cancer tissues. Integrin α2β1 decreased gradually during disease progression while α11 was elevated in prostate carcinoma compared to healthy tissues. In advanced melanoma, enhanced levels of α2 were associated with a significant shorter overall survival in advanced melanoma. In this thesis, CT16 was identified as a frequently expressed melanoma CT antigen with an anti-apoptotic function. To conclude, this thesis presents α2β1 and CT16, as potential and promising biomarkers for advanced melanoma. This thesis reports also the first functional study of CT16. Keywords: Collagen binding integrins, α1β1, α2β1, α10β1, α11β1, Cancer Testis antigens, CT16, melanoma, prostate cancer, expression

Efecto del dicloroacetato de sodio sobre líneas celulares de cáncer in vitro y sobre un modelo de melanoma murino.

Tesis (Maestría en Ciencias con Acentuación en Inmunolobiología) UANL, 2011.

Silenciamiento de Wt1 con RNAi y su combinación con doxorrubicina y cisplatino en un modelo murino de melanoma.

Tesis (Maestría en Ciencias con Acentuación en Inmunolobiología) UANL, 2012.

Efecto de la sobre expresión de WT1 en la expresión de genes angiogénicos en melanoma murino bajo condiciones normales y de hipoxia in vitro.

Tesis (Maestría en Ciencias con Acentuación en Inmunolobiología) UANL, 2013.

Análisis del efecto autofágico de la proteína E2F-1 truncada en células de melanoma humano.

Tesis (Doctor en Ciencias Biológicas con Orientación Terminal en Morfología) UANL, 2010.

Functional organization of cutaneous reflex pathways during locomotion and reorganization following peripheral nerve and/or spinal cord lesions

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Identification of a novel herpesvirus associated with cutaneous ulcers in a fisher (Martes pennanti).

On December 8, 2008, a male fisher (Martes pennanti) housed in a quarantine enclosure at the St-Félicien Zoo was found dead with multiple skin ulcers on the muzzle and plantar pads. At necropsy, no major findings were found, and a specific cause of death was not determined microscopically. However, at the borders of ulcerated sites, there were increased numbers of koilocytes, with perinuclear vacuolation and nuclear enlargement. A pan-herpesvirus nested polymerase chain reaction (PCR) assay was conducted, and an expected PCR product of 230 nucleotides was obtained within tissues collected from around the skin ulcers. Other tissues, including intestines and pool of lung, liver, and kidney, tested negative. The obtained PCR amplicon was sequenced and was highly related to the partial viral DNA polymerase (DPOL) gene of Mustelid herpesvirus 1. Virus isolation was negative, and no virion was detected by electron microscopy. The pathogenic potential of this novel herpesvirus and its role in the death of the fisher are unknown.

Sistema informàtic d’ajut a la detecció i al seguiment del melanoma

Mitjançant les tècniques de visió per computador aquest projecte pretén desenvolupar una aplicació capaç de segmentar la pell, detectar nevus (pigues i altres taques) i poder comparar imatges de pacients amb risc de contreure melanoma preses en moments diferents. Aquest projecte pretén oferir diferents eines informàtiques als dermatòlegs per a propòsits relacionats amb la investigació. L’ objectiu principal d’ aquest projecte és desenvolupar un sistema informàtic que proporcioni als dermatòlegs agilitat a l’hora de gestionar les dades dels pacients amb les sevesimatges corresponents, ajudar-los en la realització de deteccions dels nevus d’aquestes imatges, i ajudar-los en la comparació d’exploracions (amb les deteccions realitzades)de diferents èpoques d’un mateix pacient

Feline cutaneous lymphangioma : case report

This article describes a case report of a feline cutaneous lymphangioma. Lymphangiomas (synonym: lymphangiomatosis) and lymphangiosarcomas are rare tumors, usually associated with skin, some are believed to be congenital in young animals associated with vascular abnormalities. In gross pathology description they are poorly defined, cavernous-spongy, soft and they may be identified along fascial planes, because of this it may be difficult to remove, so tumors tend to recur. In histopathology description we can see interconnecting channels lined by endothelium usually without erythrocytes, but these tumors do not have unique features.

Efeito do tratamento com Tapsigargina nas Isomerases de Dissulfuretos de Melanoma

Os fármacos anticancerígenos indutores de stress de reticulo endoplasmático (RE) podem causar a sobreexpressão e/ ou a translocação das isomerases de dissulfuretos (PDIs), classicamente descritas como proteínas residentes do RE, para a superfície celular, com importantes implicações fisiológicas, como, por exemplo, o aumento da resistência à quimioterapia. O objectivo deste trabalho foi investigar o efeito da tapsigargina (TG) na viabilidade celular e na expressão e localização das PDIs e chaperonas de RE nas linhas celulares de melanoma SK-MEL-30 e MNT-1. Verificou-se que as células MNT-1 têm maior susceptibilidade à TG. Também foi demonstrado que a TG induz uma acentuada sobreexpressão de todas as proteínas em ambas as linhas celulares. Inesperadamente, ao nível da expressão fenotípica, verificou-se uma diminuição da expressão de GRP78, em SKMEL-30 e MNT-1, e de CRT, PDI e TMX4 em SK-MEL-30, sugerindo que estas ou não são traduzidas ou são exportadas. Em MNT-1, a expressão fenotípica da CRT aumentou, não havendo alterações para a PDI. Às diferenças de susceptibilidade à TG observadas nas duas linhas poderão corresponder importantes diferenças ao nível da resposta ao stress de RE, que não se esgotam nas diferenças ao nível transcricional, sendo necessários mais estudos para explicar esses fenómenos.

Tyrosinase activated melanoma prodrugs

Metastatic malignant melanoma remains a highly aggressive form of skin cancer for which no reliable methods for treatment exist. Given the increasing incidence of this cancer, considerable attention has focused on the development of new and improved methods for tackling this disease. Within this article, methods for treating melanoma are reviewed and discussed with particular attention focusing on prodrugs that are activated by the tyrosinase enzyme. This enzyme is up-regulated and is of elevated activity within malignant melanomas compared with healthy melanocytes, providing an ideal in-situ tool for the activation of melanoma prodrugs. By way of background to the prodrug strategies discussed within this review, the causes of melanoma, the enzymology of tyrosinase, and the chemistry of the biosynthetic pathways associated with melanogenesis are presented. Aspects of the design, mode of action, and biological profiles of key prodrugs that are activated by tyrosinase, and that show potential for the treatment of melanoma, are then presented and compared.

Synthesis and evaluation of novel boron-containing complexes of potential use for the selective treatment of malignant melanoma

Boron-containing complexes that have the potential to irreversibly accumulate in melanoma cells have been prepared by reaction of amino acids with 9-methoxy-9-borabicyclo[3.3.1]nonane. The ability of each complex to act as a substrate for tyrosinase has been probed by oximetry. Increased uptake of the lead candidate in a tyrosinase-rich cell line, compared with a tyrosinase-absent cell line, is reported, with results correlating well with that for a drug currently approved for BNCT.