No abstract

The evolution of gastric carcinogenesis remains largely unknown. We established two gastric carcinogenesis models in New-World nonhuman primates. In the first model, ACP03 gastric cancer cell line was inoculated in 18 animals. In the second model, we treated 6 animals with N-methyl-nitrosourea (MNU). Animals with gastric cancer were also treated with Canova immunomodulator. Clinical, hematologic, and biochemical, including C-reactive protein, folic acid, and homocysteine, analyses were performed in this study. MYC expression and copy number was also evaluated. We observed that all animals inoculated with ACP03 developed gastric cancer on the 9th day though on the 14th day presented total tumor remission. In the second model, all animals developed pre-neoplastic lesions and five died of drug intoxication before the development of cancer. The last surviving MNU-treated animal developed intestinal-type gastric adenocarcinoma observed by endoscopy on the 940th day. The level of C-reactive protein level and homocysteine concentration increased while the level of folic acid decreased with the presence of tumors in ACP03-inoculated animals and MNU treatment. ACP03 inoculation also led to anemia and leukocytosis. The hematologic and biochemical results corroborate those observed in patients with gastric cancer, supporting that our in vivo models are potentially useful to study this neoplasia. In cell line inoculated animals, we detected MYC immunoreactivity, mRNA overexpression, and amplification, as previously observed in vitro. In MNU-treated animals, mRNA expression and MYC copy number increased during the sequential steps of intestinal-type gastric carcinogenesis and immunoreactivity was only observed in intestinal metaplasia and gastric cancer. Thus, MYC deregulation supports the gastric carcinogenesis process. Canova immunomodulator restored several hematologic measurements and therefore, can be applied during/after chemotherapy to increase the tolerability and duration of anticancer treatments.

Saimiri sciureus is one of the smallest Cebidae native of Amazon region and also found at the biological reserve of northeast Atlantic forest. It is an omnivore animal, with diversified diet that directly influences the lingual mucosa, which includes certain types of papillae with different organization levels. The present study attempted to describe the morphological and ultrastructure aspects of the dorsal surface of the S. sciureus. Five tongues of de S. sciureus were analyzed from three males and two females who died from natural causes and were obtained from breeding colonies of CENP-Ananindeua-PA. Main macroscopic features were a general triangular shape with a craniocaudal elongation pointed apex. Tissue samples--apex, body, and root of tongue--were fixed in modified Karnovsky solution, following standard scanning protocol, mounted in stubs, coated by gold, and analyzed by Scanning Electron Macroscopy (SEM). Four types of papillae were described: filiform (along all tissue extension with 154 μm of diameter), fungiform (along all tissue extension with 272 μm of diameter), vallate [just three units in caudal (dorsal) portion with 830 μm of diameter] and foliate (one pair at caudolateral surface with ∼ 13 projections and 3000 μm in length). Data analysis indicates that the distribution and ultra structural morphology of the S. sciureus lingual papillae are some similar to other primates.

Descrevem-se macroscopicamente o aparelho urogenital em quatro animais da espécie Saimiri sciureus, jovens, nascidos em cativeiro junto ao Centro Nacional de Primatas. A vulva delimitou-se pelos lábios vulvares, apresentando um clitóris bem desenvolvido com aspecto fálico. O vestíbulo vaginal é bastante curto, com espessa parede muscular, estendendo-se da rima da vulva até o óstio da vagina. A vagina vem logo na sequência do vestíbulo, sendo constituída por um tubo muscular com aspecto alongado e achatado dorsoventralmente, com paredes finas, estando disposta entre o vestíbulo vaginal e a cérvix, sendo esta última relativamente curta, porém, com musculatura bem desenvolvida. O útero é simples, com fundo globoso, estando localizado na porção caudal da cavidade abdominal. As tubas uterinas mostraram-se longas e retilíneas, ligando-se aos ovários, que são grandes e elipsóides, com superfície lisa.

Saimiri sciureus is a neotropical primate widely used in research. However, there are still difficulties regarding their reproduction in vivaria due to the high incidence of dystocia. Dystocia in primates can be caused by cephalopelvic disproportion and in Squirrel Monkeys, pregnancy of large fetuses were reported. This paper describes pelvimetry data of adult females and subadults in specimens of Squirrel Monkeys, from a research colony of Para, Brazil. Pelvic radiographs were obtained in ventrodorsal projections and the following measurements were taken: superior bi-iliac diameter (SBID); inferior bi-iliac diameter (IBID); bi-iliac average diameter (BIAD); right diagonal diameter (RDD); left diagonal diameter (LDD); sacro-pubic diameter (SPD); Based on the obtained diameters, the entrance area of the pelvis (EAP) was also calculated. The average values of the pelvic diameters and EAP in adult females were SBID 1.714cm, BIAD 1.957cm, IBID 1.686cm, RDD 2.771cm, LDD 2.764cm, SPD 2.543cm and EAP 3.9056cm2; and subadult females: 1.588cm SBID, 1.850cm BIAD, 1.625cm IBID, 2.50cm RDD, LDD 2.474cm, 1.95cm SPD and 2.8293 cm2 EAP. Saimiri sciureus pelvis is characterized as dolichopelvic. There was statistical significance between the values for adult females and subadults to SBID, BIAD, RDD, LDD, SPD and EAP. The values of SBID and IBID were lower when compared to the published data for the same species. The result found on this paper will serve as a basis for future studies using pelvic measurements and dystocia prediction of neotropical primates and comparison between different vivaria.

O Saimiri sciureus é um primata não humano existente na região amazônica e não consta na lista de animais em perigo de extinção, de acordo com o IBAMA. Neste trabalho, sistematizou-se os ramos colaterais viscerais da aorta abdominal de seis animais sendo três machos e três fêmeas, os quais tiveram o sistema circulatório preenchido com látex Neoprene, adicionado de contraste radiográfico. O resultado observado foi que a aorta abdominal emitiu ventralmente, como ramo colateral visceral, a artéria celíaca, que se trifurcou nas artérias gástrica esquerda, hepática e lienal. Os ramos da artéria celíaca promovem a irrigação do estômago, duodeno, fígado, pâncreas e baço. A seguir, a aorta abdominal emitiu a artéria mesentérica cranial, de calibre maior que a artéria celíaca e justaposta caudalmente. A artéria mesentérica cranial emitiu ramos que vascularizaram a parte final do duodeno, pâncreas, jejuno, íleo, ceco, cólon maior e cólon menor. A aorta abdominal emitiu lateralmente as artérias renais direita e esquerda. A artéria adrenal esquerda surgiu como um ramo colateral direto da artéria celíaca e a artéria adrenal direita surgiu da artéria renal direita. A artéria mesentérica caudal foi emitida da superfície ventral da aorta abdominal, logo abaixo das artérias renais. Em L6, a aorta abdominal se bifurcou, dando origem às artérias ilíacas externas direita e esquerda e estas deram origem à artéria ilíaca interna e femoral direita e esquerda. As artérias testiculares ou ováricas tiveram origem na artéria ilíaca interna. A continuidade da aorta abdominal deu origem à artéria sacral mediana e a continuidade desta é chamada de artéria caudal mediana. O estudo da espécie em questão é de suma importância para gerar conhecimentos a respeito dos primatas não humanos existentes em nosso país. Dessa forma, pode-se dizer que o Saimiri sciureus é um importante modelo biológico para o desenvolvimento de pesquisas biomédicas.

No abstract

Background: Gastric cancer is one of the most incident types of cancer worldwide and presents high mortality rates and poor prognosis. MYC oncogene overexpression is a key event in gastric carcinogenesis and it is known that its protein positively regulates CDC25B expression which, in turn, plays an essential role in the cell division cycle progression. Menadione is a synthetic form of vitamin K that acts as a specific inhibitor of the CDC25 family of phosphatases. Methods: To better understand the menadione mechanism of action in gastric cancer, we evaluated its molecular and cellular effects in cell lines and in Sapajus apella, nonhuman primates from the new world which had gastric carcinogenesis induced by N-Methyl-N-nitrosourea. We tested CDC25B expression by western blot and RT-qPCR. In-vitro assays include proliferation, migration, invasion and flow cytometry to analyze cell cycle arrest. In in-vivo experiments, in addition to the expression analyses, we followed the preneoplastic lesions and the tumor progression by ultrasonography, endoscopy, biopsies, histopathology and immunohistochemistry. Results: Our tests demonstrated menadione reducing CDC25B expression in vivo and in vitro. It was able to reduce migration, invasion and proliferation rates, and induce cell cycle arrest in gastric cancer cell lines. Moreover, our in-vivo experiments demonstrated menadione inhibiting tumor development and progression. Conclusions: We suggest this compound may be an important ally of chemotherapeutics in the treatment of gastric cancer. In addition, CDC25B has proven to be an effective target for investigation and development of new therapeutic strategies for this malignancy.