Human Papillomavirus Modulates Matrix Metalloproteinases During Carcinogenesis: Clinical Significance and Role of Viral Oncoproteins.

Human papillomavirus (HPV) infections are associated with cervical cancer and other anogenital cancers. Despite progresses in HPV vaccination and screening, these cancers still show high incidence and mortality, requiring improved prognostic markers and tailored therapies. This review addresses the role of Matrix metalloproteinases (MMPs) in HPV-induced cancers and the modulation of MMP expression by HPV oncoproteins. Scientific literature indexed in PubMed and ScienceDirect about Human papillomavirus modulates matrix metalloproteinases was retrieved and critically analyzed, to obtain an overview of expression patterns and their implications for carcinogenesis and patient prognosis. Matrix metalloproteinases such as MMP1, MMP9 and MMP13 have been associated with patient prognosis in HPV-induced cancers and play a major role in the degradation of the extracellular matrix, tumor invasion and metastasis. The HPV E2 and E7 oncoproteins regulate MMP expression via AKT, MEK/ERK and AP-1 signaling among other mechanisms. Increased expression of MMPs is associated with cancer progression and poor prognosis in multiple HPV-induced cancers, suggesting their potential use as prognostic markers. The identification of specific signaling pathways that mediate MMP regulation by HPV is essential for developing efficient new cancer therapies.

CRISPR-Cas9 therapies in experimental mouse models of cancer.

The CRISPR-Cas9, a part of the defence mechanism from bacteria, has rapidly become the simplest, fastest and the most precise genome-editing tool available. The therapeutic applications of CRISPR are boundless: correction of mutations in several disorders, inactivation of oncogenes and viral oncoproteins, and activation of tumor suppressor genes. In this review, we expose recent advances concerning animal models of cancer that use CRISPR-Cas9, addressing also the current efforts to develop CRISPR-Cas9-based therapies, focusing on proof-of-concept studies. Finally, the review exposes some of the main challenges that this genome-editing tool faces. The key issue remains: does CRISPR-Cas9 have real potential for therapeutic application or will it just remain a wonderful research tool?

Cytogenetic characterization of an N-butyl-N-(4-hydroxybutyl) nitrosamine-induced mouse papillary urothelial carcinoma.

Chemically-induced urinary bladder cancer in rodents has long been used as a reliable model to study the biopathology of urinary bladder neoplasia and to develop therapeutic strategies against human tumors. Knowledge of the genetic basis underlying carcinogenesis would greatly enhance usability and usefulness of this model for the purposes of comparative pathology. However, little is known about the cytogenetic characteristics of rodent urinary bladder tumors. Accordingly, pathological and negative control specimens were collected for cytogenetic evaluation, from an ongoing mouse urinary bladder N-butyl-N-(4-hydroxybutyl) nitrosamine-induced carcinogenesis study. Histopathological analysis characterized the pathological sample as a papillary urothelial carcinoma. Conventional cytogenetic analysis revealed the presence of 66.3 % tetraploid cells. Fluorescent in situ hybridization using chromosome paint probes allowed the detection of a reciprocal translocation involving chromosomes 4 and 14 (containing the murine homologues to human p16 and retinoblastoma tumor-suppressor genes) in 42 % of tetraploid cells. The control sample showed no histological or cytogenetic changes. CDKN2A and RB1 loss of heterozygosity is associated with human early and advanced urinary bladder cancer, respectively. Thus, the present data paves the way for further studies concerning the molecular mechanisms of urinary bladder carcinogenesis.

Estimation of rat mammary tumor volume using caliper and ultrasonography measurements.

Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. Determining tumor volume is a useful and quantitative way to monitor tumor progression. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. They then used different formulas to calculate tumor volume from these tumor measurements and compared the calculated tumor volumes with the real tumor volume to identify the formulas that gave the most accurate volume calculations. They found that caliper and ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas varied substantially. Mammary tumors seemed to take on an oblate spheroid geometry. The most accurate volume calculations were obtained using the formula V = (W(2) × L)/2 for caliper measurements and the formula V = (4/3) × π × (L/2) × (L/2) × (D/2) for ultrasonography measurements, where V is tumor volume, W is tumor width, L is tumor length and D is tumor depth.