Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model

Oral squamous cell carcinoma (OSCC) is a lethal disease whose incidence is increasing. Epidemiologic studies demonstrate an association between periodontitis and oral cancer, and periodontal pathogens are implicated in the pathogenesis of numerous disorders, including rheumatoid arthritis, cardiovascular diseases, diabetes and gastrointestinal malignancies. Nevertheless, a causal role for periodontal pathogens in OSCC has not been shown, partly due to the lack of an appropriate animal model. Here, utilizing a newly-established murine model of periodontitis-associated oral tumorigenesis, we report that chronic bacterial infection promotes OSCC, and that augmented signaling along the IL-6-STAT3 axis underlies this effect. Our results indicate that periodontal pathogens P. gingivalis and F. nucleatum stimulate tumorigenesis via direct interaction with oral epithelial cells through Toll-like receptors. Furthermore, oral pathogens stimulate human OSCC proliferation and induce expression of key molecules implicated in tumorigenesis. To the best of our knowledge, these findings represent the first demonstration of a mechanistic role for oral bacteria in chemically induced OSCC tumorigenesis. These results are highly relevant for the design of effective prevention and treatment strategies for OSCC.     

Micro-Imaging by Interference Microscopy: A Case Study of Orientation-Dependent Guest Diffusion in MFI-Type Zeolite Host Crystals

Because of the small particle size, orientation-dependent diffusion measurements in microporous materials remains a challenging task. We highlight here the potential of micro-imaging by interference microscopy in a case study with MFI-type crystals in which, although with different accuracies, transient concentration profiles in all three directions can be observed. The measurements, which were performed with “rounded-boat” shaped crystals, reproduce the evolution patterns of the guest profiles recorded in previous studies with the more common “coffin-shaped” MFI crystals. The uptake and release patterns through the four principal faces (which in the coffin-shaped crystals extend in the longitudinal direction) are essentially coincident and there is no perceptible mass transfer in the direction of the long axis. The surface resistances of the four crystal faces through which mass transfer occurs are relatively small and have only a minor effect on the mass transfer rate. As a result of the pore structure, diffusion in the crystallographic c direction (which corresponds to the direction of the long axis) is expected to be much slower than in the transverse directions. This could explain the very low rate of mass transfer observed in the direction of the long axis, but it is also possible that the small end faces of the crystal may have high surface resistance. It is not possible to distinguish unequivocally between these two possibilities. All guest molecules studied (methyl-butane, benzene and 4-methyl-2-pentyne) show the same orientation dependence of mass transfer. The long 4-methyl-2-pentyne molecules would be expected to propagate at very different rates through the straight and sinusoidal channels. The coinciding patterns for uptake through the mutually perpendicular crystal faces therefore provide clear evidence that both the coffin shaped crystals and the rounded-boat-shaped crystals considered in this study, must be intergrowths rather than pure single crystals.     

Comprehensive genomic profiling of metastatic collecting duct carcinoma,renal medullary carcinoma,and clear cell renal cell carcinoma

Introduction and ObjectiveUnlike clear cell renal cell carcinoma (CCRCC), collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) are rare tumors that progress rapidly and appear resistant to current systemic therapies. We queried comprehensive genomic profiling to uncover opportunities for targeted therapy and immunotherapy.Material and MethodsDNA was extracted from 40 microns of formalin-fixed, paraffin-embedded specimen from relapsed, mCDC (n = 46), mRMC (n = 24), and refractory and metastatic (m) mCCRCC (n = 626). Comprehensive genomic profiling was performed, and Tumor mutational burden (TMB) and microsatellite instability (MSI) were calculated. We analyzed all classes of genomic alterations.ResultsmCDC had 1.7 versus 2.7 genomic alterations/tumor in mCCRCC ( = 0.04). Mutations in VHL (P < 0.0001) and TSC1 (P = 0.04) were more frequent in mCCRCC. SMARCB1 (P < 0.0001), NF2 (P = 0.0007), RB1 (P = 0.02) and RET (P = 0.0003) alterations were more frequent in mCDC versus mCCRCC. No VHL alterations in mRMC and mCDC were identified. SMARCB1 genomic alterations were significantly more frequent in mRMC than mCDC (P = 0.0002), but were the most common alterations in both subtypes. Mutations to EGFR, RET, NF2, and TSC2 were more frequently identified in mCDC versus mRMC. The median TMB and MSI-High status was low with <1% of mCCRC, mCDC, and mRMC having ≥ 20 mut/Mb.ConclusionGenomic alteration patterns in mCDC and mRMC differ significantly from mCCRCC. Targeted therapies for mCDC and mRMC appear limited with rare opportunities to target alterations in receptor tyrosine kinase and MTOR pathways. Similarly, TMB and absence of MSI-High status in mCDC and mRMC suggest resistance to immunotherapies.     

Acne Knowledge of Hispanic Parents of Teenagers with Mild to Moderate Acne

We performed a cross‐sectional study of Hispanic and non‐Hispanic parents of children with acne using a survey designed to determine their level of awareness of acne and its treatment; 82% of Hispanic parents and 40% of non‐Hispanic parents agreed that a health care provider should treat mild acne (p < 0.001). Hispanic parents of adolescents with acne agreed more frequently than non‐Hispanic parents that children with mild and moderate acne should be taken to a health care provider for treatment, but they tended not to visit health care providers. Future studies should aim to determine the reasons for this discrepancy, after which culturally sensitive educational programs can be developed to address this disparity.