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4T1 metastatic breast cancer model have been widely used to study stage IV human breast cancer. However, the frequent inoculation of a large number of cells, gives rise to fast growing tumors, as well as to a surprisingly low metastatic take rate. The present work aimed at establishing the conditions enabling high metastatic take rate of the triple-negative murine 4T1 syngeneic breast cancer model. An 87% 4T1 tumor incidence was observed when as few as 500 cancer cells were implanted. 4T1 cancer cells colonized primarily the lungs with 100% efficiency, and distant lesions were also commonly identified in the mesentery and pancreas. The drastic reduction of the number of inoculated cells resulted in increased tumor doubling times and decreased specific growth rates, following a Gompertzian tumor expansion. The established conditions for the 4T1 mouse model were further validated in a therapeutic study with peguilated liposomal doxorubicin, in clinical used in the setting of metastatic breast cancer. Inoculated cell density was proven to be a key methodological aspect towards the reproducible development of macrometastases in the 4T1 mouse model and a more reliable pre-clinical assessment of antimetastatic therapies. [ABSTRACT FROM AUTHOR]

Introduction: American tegumentary leishmaniasis (ATL) can affect the skin or mucosa (mucocutaneous leishmaniasis – MCL) including the oral cavity. MCL oral lesions are often confused with other oral diseases, delaying diagnosis and specific treatment, and increasing the likelihood of sequelae. Thus, increasing the knowledge of the evolution of ATL oral lesions can facilitate its early diagnosis improving the prognosis of healing. Objectives: Evaluate the frequency of ATL oral lesion and describe its clinical, laboratory and therapeutic peculiarities. Methods: A descriptive transversal study was carried out, using data from medical records of 206 patients with MCL examined at the outpatient clinics-IPEC-Fiocruz between 1989 and 2013. Proportions were calculated for the categorical variables and the association among them was assessed by the Pearson's chi-square test. Measures of central tendency and dispersion were used for the continuous variables and their differences were assessed by both parametric (t test) and non parametric (Mann-Whitney) tests. P-values <0.05 were considered as significant. Results: The most affected site was the nose, followed by the mouth, pharynx and larynx. Seventy eight (37.9%) have oral lesions and the disease presented a lower median of the evolution time than in other mucous sites as well as an increased time to heal. The presence of oral lesion was associated with: the presence of lesions in the other three mucosal sites; a smaller median of the leishmanin skin test values; a longer healing time of the mucosal lesions; a higher recurrence frequency; and a smaller frequency of treatment finishing and healing. When the oral lesion was isolated, it was associated with an age 20 years lower than when the oral lesion was associated with other mucosal sites. Conclusion: Considering the worst therapy results associated with the presence of oral lesions, we suggest that lesions in this location represent a factor of worse prognosis for MCL. [ABSTRACT FROM AUTHOR]