Perspectivas de novos tratamentos para o carcinoma tireoidiano avançado

In the treatment of thyroid cancer, the greatest problem existis in tumors that continue to grow or express recurrences, despite surgical, radioidine or t4 supressive therapies. Improved knowledge of the molecular biology of tumors showed that elevated expression of oncogeneses, uncontrolled ativation of tyrosine cinase receptors and their signaling pathways, and inibition of programmed apoptosis are all important factors in the origin and evolution of tumors and their metastasis. The development of therapies targeted against especific molecular deregulation envolved in tumor progression is now been evaluated, with sucess, in various types of cancer. In thyroid cancer, target therapies using drugs, antibodies, genes, and small molecules are in development in preclinical studies and show a potential role in the managment of thyroid cancer, in the future. In this review, some of these studies are discussed.

Tratamento cirúrgico na recidiva retroperitoneal tardia por carcinoma renal de células claras após nefrectomia radical

Late renal cell carcinoma recurrence in the renal fossa is a rare event. This condition occurs in 1 to 2% of radical nephrectomies. We reported a late recurrence at the renal fossa about four and half years after radical nephrectomy due to a renal cell carcinoma (RCC) without metastasis elsewhere. Diagnosis in an outpatient follow-up was made during an abdominal computed tomography and we observed a retroperitoneal mass in the renal fossa. The excision at the recurrence area was made through a subcostal transversal incision without any difficulty. After 6 months from this second procedure, there was no evidence of recurrence. The surgical aggressive treatment for late retroperitoneal RCC recurrence is a good method in this rare situation. Abdominal computed tomography must be done during long periods of follow-up for patients with radical nephrectomy for RCC to search for late retroperitoneal recurrences.

Tumores testiculares na infância

Testicular and paratesticular prepuberal tumors are rare. They represent around 1% of the total of tumors of infancy. They subdivide in 2 groups: germ cells tumors and non germ cells tumors, being able to occur in all the ages, and about 75% are malignant, and about 19% of these they present metastasis. The tumors of germ cells tumors represent 60 75% of the tumors testiculars in infancy, having as main example the yolk sac tumor (65% of the neoplasms), followed for teratomas (14%); although some works to exist where teratoma, if presents as most common .The non germ cells tumors include the Leydig cell tumor and Sertoli cell tumor. The Leydig cell tumor, are most frequent between the non germ cells tumors testicular. This review article on epidemiology, diagnosis and treatment of to testicular and to paratesticular tumors in child.

Abdome agudo como manifestação inicial de melanoma metastático: relato de caso

The malignant melanoma is a relatively common neoplasia, with origin generally in the melanocytics cells in the skin, but with presentation of other possible primary lesions, being presented in this, a case witnessed of liver and mesentery metastases with unknown primary sites.

Linfadenectomia Axilar Conservadora no Câncer de Mama Estádio Clínico I

Objetivo: determinar a eficácia da linfadenectomia axilar conservadora (esvaziamento dos níveis I e II) no tratamento cirúrgico do câncer da mama estádio I. Métodos: foram avaliados os resultados de 142 cirurgias realizadas em pacientes portadoras de câncer mamário estádio I (T1NO) entre janeiro/93 e dezembro/98. Removidos os linfonodos axilares presentes nos níveis I e II com preservação dos músculos peitorais, os mesmos foram dissecados pelo próprio autor (LAGB), sendo posteriormente examinados histopatologicamente com a realização de apenas 1 corte por linfonodo. A quadrantectomia foi realizada em 138 casos e a mastectomia modificada segundo Patey em 4 casos. Houve predomínio dos casos T1c (130 casos). Resultados: foram removidos 3.282 linfonodos (2.456 presentes no nível I e 826 no nível II) com um número médio de 23,1 linfonodos por axila. Desse total, apenas 68 estavam comprometidos (2,1%). Skip metastasis estava presente em apenas um caso (0,7%). Foram observados 35 casos de falso-negativos clínicos (24,6%), estando o nível I comprometido em 34 casos (97,1%) e o nível II em apenas 2 casos (5,7%). A axila estava negativa nos 107 casos restantes (75,4%). Conclusão: a dissecção axilar dos níveis I e II é suficiente para tratar a axila no estádio I do câncer de mama. Se linfonodos suspeitos são identificados durante a cirurgia, os gânglios do nível III e o grupo interpeitoral de Rotter deverão ser retirados.

Criteria for prediction of metastatic axillary lymph nodes in early-stage breast cancer

PURPOSE: To estimate the likelihood of axillary lymph node involvement for patients with early-stage breast cancer, based on a variety of clinical and pathological factors. METHODS: A retrospective analysis was done in hospital databases from 1999 to 2007. Two hundred thirty-nine patients were diagnosed with early-stage breast cancer. Predictive factors, such as patient age, tumor size, lymphovascular invasion, histological grade and immunohistochemical subtype were analyzed to identify variables that may be associated with axillary lymph node metastasis. RESULTS: Patients with tumors that are negative for estrogen receptor, progesterone receptor, and HER2 had approximately a 90% lower chance of developing lymph node metastasis than those with luminal A tumors (e.g., ER+ and/or PR+ and HER2-) - Odds Ratio: 0.11; 95% confidence interval: 0.01-0.88; p=0.01. Furthermore, the risk for lymph node metastasis of luminal A tumors seemed to decrease as patient age increased, and it was directly correlated with tumor size. CONCLUSION: The molecular classification of early-stage breast cancer using immunohistochemistry may help predicting the probability of developing axillary lymph node metastasis. Further studies are needed to optimize predictions for nodal involvement, with the aim of aiding the decision-making process for breast cancer treatment.

The maspin expression in canine mammary tumors: an immunohistochemical and molecular study

The serpin maspin, a tumor suppressor in breast cancer was described as an inhibitor of cell migration and inducer of cell adhesion between the basement membrane and extracellular matrix resulting in inhibition of tumor metastasis. In contrast, overexpression of maspin is correlated with poor prognosis in other types of cancer. Little is known about expression, regulation and function of maspin in canine mammary tumors. It was demonstrated in this study, a loss of maspin expression in malignant canine mammary cells compared with a pool of normal canine mammary tissue, analyzed by quantitative real-time PCR; weak maspin expression in malignant canine mammary tumors were observed by immunohistochemistry. It was also demonstrated that a correlation with nuclear maspin expression and a good prognosis. It is suggested that maspin could be used as a prognostic marker in canine mammary neoplasia.

Uterine lymphangiography: comparison of two methods for locating the medial iliac lymph node

Different methods for lymphatic mapping in dogs, such as infusing tissues with vital dyes or radioactive substances, have been studied, aiming at the early detection of lymph node metastasis. Thus, one could anticipate therapeutic measures and, consequently, prolong the survival and improve the quality of life of the patients. The objectives of this experiment were to locate the nodes responsible for draining the uterine body and horns and to try to establish the relationship between the uterus and the medial iliac lymph nodes to contribute to the early diagnosis and prognosis of uterine disorders. We studied 15 female dogs divided into two groups (5 dead and 10 intraoperative ovariohysterectomy bitches). The dye used was patent blue V (Patent Bleu V®). It was observed that the iliac lymph node chain receives much of the uterine (horns) drainage. This method should be considered for safer studies of uterine sanity. This information suggests that evaluating these lymph nodes will allow correlating changes in their physiological status with uterine pathologies.

Retrospective canine skin peripheral nerve sheath tumors data with emphasis on histologic, immunohistochemical and prognostic factors

Abstract: In this retrospective study was determined the frequency of canine skin peripheral nerve sheath tumors (PNST) in cases diagnosed by the Setor de Patologia Veterinária of the Universidade Federal do Rio Grande do Sul (SPV-UFRGS), Brazil, between the years 2000 and 2012. The canine profiles, as well as histological, immunohistochemical and prognostic aspects of the tumors were based on 70 samples, comprising 40 females, 29 males and one unspecified sample. Between 2000 and 2012, 2,984 skin tumors of dogs were diagnosed in the SPV-UFRGS, totaling 2.34% of skin neoplasms in dogs. Animals that comprised the largest amount of samples (43%) were those with no breed (SRD), followed by German Shepherds (10%). Females were more affected than males (40/70 - 57% and 29/70 - 41% respectively). Skin PNST of this research showed predominant localization on the limbs (40% in the forelimbs and 29% in the hindlimbs); affecting adult dogs, mostly aged between 8 and 11 years (54%). The samples were routinely processed for hematoxylin and eosin, and were also evaluated by toluidine blue and Masson's trichrome staining, and immunohistochemistry (IHC) anti-vimentin, -S-100, -GFAP, -actin, von Willebrand factor and neurofilament. Anisocytosis and anisokaryosis, mitotic index, intratumoral necrosis, invasion of adjacent tissues, tumor location, local recurrence and metastasis were related to the diagnosis of benign (49/70) or malignant tumor (21/70). The Antoni A histological pattern was observed more frequently in benign tumors. The immunohistochemistry helped to diagnose PNST, and anti-vimentin and anti-protein S-100 showed the highest rates of immunostaining. Throughout statistical analysis of animals with tumor recurrence, it was found that the chance of an animal with a malignant peripheral nerve sheath tumor to develop recurrence is 4.61 times higher than in an animal that had a benign tumor.

Hyperthermia increases the metastatic potential of murine melanoma

Hyperthermia, either alone or combined with radio-, immuno- or chemotherapy, can control tumor growth, but its effect on metastasis is still controversial. In the present study, we investigated the influence of hyperthermia on the metastatic potential of B16-F10 murine melanoma cells. Incubation of melanoma cells at 43ºC for 30 min led to a significant decrease in cell viability. About half of the cells survived the acute exposure to heat. These thermoresistant cells displayed a longer lag phase as compared to control unheated B16-F10 melanoma cells. Other parameters of cell growth such as doubling time and saturation density were equivalent in both control and thermoresistant cells. Both control and treated cells were adherent, but thermoresistant cells failed to spread during the first 48 h after heat exposure. B16-F10 cells colonize the lungs of C57BL/6J mice when injected intravenously; the number of lung colonies is a measure of the metastatic potential of injected cells. Median values of 22, 10.5 and 31 colonies per injected mouse were observed for control cells, cells heated to 43ºC for 30 min and thermoresistant cells, respectively, with statistically significant differences between groups (Mann-Whitney test, P<0.02). Thus, despite its cytotoxic action, heat exposure induced the acquisition of a more metastatic phenotype in a subpopulation of B16-F10 cells

Analysis of p53 expression and proliferative assessment using PCNA in localized prostate carcinoma

The surgical specimens from 51 men submitted to radical prostatectomy for localized prostate cancer were examined by immunohistochemistry using proliferation cell nuclear antigen (PCNA) monoclonal antibody to evaluate the proliferative index (PI). The relationship between PI, biological variables and p53 protein expression was evaluated by immunohistochemistry. PI was low in invasive localized prostate carcinoma (mean, 12.4%) and the incidence of PCNA-positive cells was significantly higher in tumors with p53 expression (P = 0.0226). There was no statistical difference in PCNA values when biological parameters such as Gleason score, tumor volume, extraprostatic involvement, seminal vesicle infiltration or lymph node metastasis were considered. We conclude that proliferative activity is usually low in prostate carcinoma but is correlated with p53 immune staining, indicating that p53 is important in cell cycle control in this neoplasm.

Galectins: a key intersection between glycobiology and immunology

Galectins are a family of evolutionarily conserved animal lectins, widely distributed from lower invertebrates to mammals. They share sequence and structure similarities in the carbohydrate recognition domain and specificity for polylactosamine-enriched glycoconjugates. In the last few years significant experimental data have been accumulated concerning their participation in different biological processes requiring carbohydrate recognition such as cell adhesion, cell growth regulation, inflammation, immunomodulation, apoptosis and metastasis. In the present review we will discuss some exciting questions and advances in galectin research, highlighting the significance of these proteins in immunological processes and their implications in biomedical research, disease diagnosis and clinical intervention. Designing novel therapeutic strategies based on carbohydrate recognition will provide answers for the treatment of autoimmune disorders, inflammatory processes, allergic reactions and tumor spreading.

Oncogene-mediated downregulation of RECK, a novel transformation suppressor gene

The RECK gene was initially isolated as a transformation suppressor gene encoding a novel membrane-anchored glycoprotein and later found to suppress tumor invasion and metastasis by regulating matrix metalloproteinase-9. Its expression is ubiquitous in normal tissues, but undetectable in many tumor cell lines and in fibroblastic lines transformed by various oncogenes. The RECK gene promoter has been cloned and characterized. One of the elements responsible for the oncogene-mediated downregulation of mouse RECK gene is the Sp1 site, where the Sp1 and Sp3 factors bind. Sp1 transcription factor family is involved in the basal level of promoter activity of many genes, as well as in dynamic regulation of gene expression; in a majority of cases as a positive regulator, or, as exemplified by the oncogene-mediated suppression of RECK gene expression, as a negative transcription regulator. The molecular mechanisms of the downregulation of mouse RECK gene and other tumor suppressor genes are just beginning to be uncovered. Understanding the regulation of these genes may help to develop strategies to restore their expression in tumor cells and, hence, suppress the cells' malignant behavior.

RNA and DNA aptamers as potential tools to prevent cell adhesion in disease

Recent research has shown that receptor-ligand interactions between surfaces of communicating cells are necessary prerequisites for cell proliferation, cell differentiation and immune defense. Cell-adhesion events have also been proposed for pathological conditions such as cancer growth, metastasis, and host-cell invasion by parasites such as Trypanosoma cruzi. RNA and DNA aptamers (aptus = Latin, fit) that have been selected from combinatorial nucleic acid libraries are capable of binding to cell-adhesion receptors leading to a halt in cellular processes induced by outside signals as a consequence of blockage of receptor-ligand interactions. We outline here a novel approach using RNA aptamers that bind to T. cruzi receptors and interrupt host-cell invasion in analogy to existing procedures of blocking selectin adhesion and function in vitro and in vivo.

Functional differences between two morphologically distinct cell subpopulations within a human colorectal carcinoma cell line

The LISP-I human colorectal adenocarcinoma cell line was isolated from a hepatic metastasis at the Ludwig Institute, São Paulo, SP, Brazil. The objective of the present study was to isolate morphologically different subpopulations within the LISP-I cell line, and characterize some of their behavioral aspects such as adhesion to and migration towards extracellular matrix components, expression of intercellular adhesion molecules and tumorigenicity in vitro. Once isolated, the subpopulations were submitted to adhesion and migration assays on laminin and fibronectin (crucial proteins to invasion and metastasis), as well as to anchorage-independent growth. Two morphologically different subpopulations were isolated: LISP-A10 and LISP-E11. LISP-A10 presents a differentiated epithelial pattern, and LISP-E11 is fibroblastoid, suggesting a poorly differentiated pattern. LISP-A10 expressed the two intercellular adhesion molecules tested, carcinoembryonic antigen (CEA) and desmoglein, while LISP-E11 expressed only low amounts of CEA. On the other hand, adhesion to laminin and fibronectin as well as migration towards these extracellular matrix proteins were higher in LISP-E11, as expected from its poorly differentiated phenotype. Both subpopulations showed anchorage-independent growth on a semi-solid substrate. These results raise the possibility that the heterogeneity found in the LISP-I cell line, which might have contributed to its ability to metastasize, was due to at least two different subpopulations herein identified.