Separation of breast cancer and organ microenvironment transcriptomes in metastases

Background: The seed and soil hypothesis was proposed over a century ago to describe why cancer cells (seeds) grow in certain organs (soil). Since then, the genetic properties that define the cancer cells have been heavily investigated; however, genomic mediators within the organ microenvironment that mediate successful metastatic growth are less understood. These studies sought to identify cancer- and organ-specific genomic programs that mediate metastasis. Methods: In these studies, a set of 14 human breast cancer patient-derived xenograft (PDX) metastasis models was developed and then tested for metastatic tropism with two approaches: spontaneous metastases from mammary tumors and intravenous injection of PDX cells. The transcriptomes of the cancer cells when growing as tumors or metastases were separated from the transcriptomes of the microenvironment via species-specific separation of the genomes. Drug treatment of PDX spheroids was performed to determine if genes activated in metastases may identify targetable mediators of viability. Results: The experimental approaches that generated metastases in PDX models were identified. RNA sequencing of 134 tumors, metastases, and normal non-metastatic organs identified cancer- and organ-specific genomic properties that mediated metastasis. A common genomic response of the liver microenvironment was found to occur in reaction to the invading PDX cells. Genes within the cancer cells were found to be either transiently regulated by the microenvironment or permanently altered due to clonal selection of metastatic sublines. Gene Set Enrichment Analyses identified more than 400 gene signatures that were commonly activated in metastases across basal-like PDXs. A Src signaling signature was found to be extensively upregulated in metastases, and Src inhibitors were found to be cytotoxic to PDX spheroids. Conclusions: These studies identified that during the growth of breast cancer metastases, there were genomic changes that occurred within both the cancer cells and the organ microenvironment. We hypothesize that pathways upregulated in metastases are mediators of viability and that simultaneously targeting changes within different cancer cell pathways and/or different tissue compartments may be needed for inhibition of disease progression

Dental Radiographs Ordered by Dental Professionals: an Experience from a Resource Limited Tertiary Public Health Facility Setting at Muhimbili National Hospital in Tanzania

Background: Radiographs remain fundamental tool in diagnosis of dental diseases, their availability and social-economic status of the patient dictates the choice made by professionals. This study was done to determine the indications and types of dental radiographs ordered by dental professionals in a resource limited setting. Methods: This was a cross sectional study involving 520 patients who underwent dental radiographic investigation. Patients were examined and interviewed. Type of radiographs taken and indications were recorded. Results: Out of 520 patients, 189 were male, and the mean age of the participants was 31.7 ± 13.9 years. Most of the patients were aged 20-49 years. The frequent indication was dental caries followed by periapical infection and impacted teeth. Periapical X-rays were taken for 748 teeth of which majority were upper central incisors followed by mandibular molars. Conclusions: Even in resource limited settings dental caries is still the regular indication for taking dental radiographs, and periapical views are the most frequent type of radiograph ordered. Maxillary central incisors and mandibular molars were types of teeth commonly x-rayed mainly due to the aesthetic importance of the former and the preponderance of dental caries in the later group of teeth