Association or Causation? Exploring the Oral Microbiome and Cancer Links.

Several epidemiological investigations have found associations between poor oral health and different types of cancer, including colorectal, lung, pancreatic, and oral malignancies. The oral health parameters underlying these relationships include deficient oral hygiene, gingival bleeding, and bone and tooth loss. These parameters are related to periodontal diseases, which are directly and indirectly mediated by oral bacteria. Given the increased accessibility of microbial sequencing platforms, many recent studies have investigated the link between the oral microbiome and these cancers. Overall, it seems that oral dysbiotic states can contribute to tumorigenesis in the oral cavity as well as in distant body sites. Further, it appears that certain oral bacterial species can contribute to carcinogenesis, in particular, Fusobacterium nucleatum and Porphyromonas gingivalis, based on results from epidemiological as well as mechanistic studies. Yet, the strength of the findings from these investigations is hampered by the heterogeneity of the methods used to measure oral diseases, the treatment of confounding factors, the study design, the platforms employed for microbial analysis, and types of samples analyzed. Despite these limitations, there is an overall indication that the presence of oral dysbiosis that leads to oral diseases may directly and/or indirectly contribute to carcinogenesis. Proper methodological standardized approaches should be implemented in future epidemiological studies as well as in the mechanistic investigations carried out to explore these results.

Relapse of herpes simplex encephalitis in a patient with metastatic small cell lung cancer following scalp sparing whole brain radiotherapy.

Herpes simplex virus is the most common cause of severe and potentially fatal sporadic encephalitis worldwide. Recurrence of neurologic symptoms after resolution of the initial episode of HSV encephalitis and despite adequate treatment with intravenous acyclovir is well recognized albeit rare. Most of these recurrences had no evidence of replicating virus and are immune in nature with only a minority of these recurrences representing true virologic relapses. Immunocompromised patients are predominantly at greater risk for virologic relapse of HSV encephalitis with potentially severe and at times fatal consequences. We describe a patient with small cell lung cancer and brain metastasis who underwent chemotherapy, treatment with dexamethasone and whole brain radiotherapy who subsequently suffered two episodes of HSV encephalitis three months and seven months after completion of radiotherapy and while on dexamethasone treatment.

Cellular Plasticity-Targeted Therapy in Head and Neck Cancers.

Head and neck cancer is one of the most frequent human malignancies worldwide, with a high rate of recurrence and metastasis. Head and neck squamous cell carcinoma (HNSCC) is cellularly and molecularly heterogeneous, with subsets of undifferentiated cancer cells exhibiting stem cell-like properties, called cancer stem cells (CSCs). Epithelial-mesenchymal transition, gene mutation, and epigenetic modification are associated with the formation of cellular plasticity of tumor cells in HNSCC, contributing to the acquisition of invasive, recurrent, and metastatic properties and therapeutic resistance. Tumor microenvironment (TME) plays a supportive role in the initiation, progression, and metastasis of head and neck cancer. Stromal fibroblasts, vasculature, immune cells, cytokines, and hypoxia constitute the main components of TME in HNSCC, which contributes not only to the acquisition of CSC properties but also to the recurrence and therapeutic resistance of the malignancies. In this review, we discuss the potential mechanisms underlying the development of cellular plasticity, especially the emergence of CSCs, in HNSCC. We also highlight recent studies implicating the complex interplays among TME components, plastic CSCs, tumorigenesis, recurrence, and therapeutic resistance of HNSCC. Finally, we summarize the treatment modalities of HNSCC and reinforce the novel concept of therapeutic targeting CSCs in HNSCC.

Translational studies on a ready-to-use intramuscular injection of penethamate for bovine mastitis.

Bovine mastitis caused by bacterial infections of the mammary gland (udder) of dairy cows is a costly pathology for the dairy industry due to direct and indirect losses in production. Penethamate, a pro-drug of benzylpenicillin, is used by intramuscular injection (IM). The existing products are powders which must be reconstituted in water-for-injection and this presents difficulties in the field. Penethamate is too unstable to be formulated as an aqueous formulation but a chemically stable suspension formulation was possible in certain oils; however, some literature suggests that such formulations would have unacceptable prolonged release. The translational research proceeded iteratively from lab to the target species, rather than via laboratory animal trials. Pilot studies in cows suggested that some oily suspensions would give concentrations of benzylpenicillin, (in both blood and milk) comparable with those of the reconstituted product. A physicochemical screen and a low level in vitro-in vivo correlation (IVIVC) was cautiously used to guide selection of formulations for subsequent animal trials which have resulted in a lead formulation for good laboratory practices (GLP), good clinical practices (GCP) studies.

Gene expression dynamics during diabetic periodontitis.

Diabetes impairs the resolution of periodontal inflammation. We explored pathways altered by inflammation in the diabetic periodontium by using ligatures to induce periodontitis in type-2 diabetic Goto-Kakizaki rats. Ligatures were removed after 7 days, and rats were then treated with TNF inhibitor (pegsunercept) or vehicle alone and euthanized 4 days later. RNA was extracted from periodontal tissue, examined by mRNA profiling, and further analyzed by functional criteria. We found that 1,754 genes were significantly up-regulated and 1,243 were down-regulated by pegsunercept (p < 0.05). Functional analysis revealed up-regulation of neuron-associated and retina-associated gene clusters as well as those related to cell activity and signaling. Others were down-regulated by TNF inhibition and included genes associated with host defense, apoptosis, cell signaling and activity, and coagulation/hemostasis/complement. For selected genes, findings with microarray and rt-PCR agreed. PPAR-α was investigated further by immunohistochemistry due to its anti-inflammatory function and was found to be up-regulated in the gingiva during the resolution of periodontal inflammation and suppressed by diabetes. The results indicate that diabetes-enhanced inflammation both up- and down-regulates genes involved in cellular activity and cell signaling, while it predominantly up-regulates genes involved in the host response, apoptosis, and coagulation/homeostasis/complement and down-regulates mRNA levels of neuron, retina, and energy/metabolism-associated genes.

Laboratory test performance in young adults during influenza outbreaks at World Youth Day 2008.

BACKGROUND: The performance of influenza laboratory diagnostics in young adults and in the setting of outbreaks during mass gatherings has not been well studied. OBJECTIVES: We compare the performance of point-of-care tests (POCTs) and immunofluorescence assays (IFAs) with nucleic acid tests (NATs) and viral culture in pilgrims attending influenza clinics established during a large influenza outbreak (World Youth Day, Sydney, Australia, 2008) to assess their performance under the real-life pressures of a mass influenza outbreak. STUDY DESIGN: Patients with an influenza-like illness (ILI) underwent respiratory specimen sampling. Combined deep nares and throat swabs were collected for POCT by trained or untrained clinic staff; type-specific IFA; NAT and viral culture. Laboratory-confirmed influenza occurred if viral culture and/or NAT were positive; the performance of laboratory tests was calculated against this 'gold standard'. RESULTS: A total of 230 samples were collected from 227 patients (median age, 20 years; interquartile range, 18-28 years), with 95 samples (41.3%) having laboratory-confirmed influenza infection (influenza A, 57; influenza B, 38). IFA and POCT sensitivities were 74.5% and 55%, respectively. Four of 51 (8%) culture-positive specimens were negative by NAT, and several errors in influenza virus typing occurred with IFA, POCT and NAT. A non-significant trend towards better POCT performance with increased operator training was demonstrated. CONCLUSION: Different environments, patient populations, operator experience, laboratory access and practicalities associated with performing tests during mass influenza outbreaks may affect performance of influenza-specific laboratory tests.

Transgenic mice that express normal and mutated amelogenins.

Amelogenin proteins are secreted by ameloblasts within the enamel organ during tooth development. To better understand the function of the 180-amino-acid amelogenin (M180), and to test the hypothesis that a single proline-to-threonine (P70T) change would lead to an enamel defect similar to amelogenesis imperfecta (AI) in humans, we generated transgenic mice with expression of M180, or M180 with the proline-to-threonine (P70T) mutation, under control of the Amelx gene regulatory regions. M180 teeth had a relatively normal phenotype; however, P70T mineral was abnormally porous, with aprismatic regions similar to those in enamel of male amelogenesis imperfecta patients with an identical mutation. When Amelx null females were mated with P70T transgenic males, offspring developed structures similar to calcifying epithelial odontogenic tumors in humans. The phenotype argues for dominant-negative activity for the P70T amelogenin, and for the robust nature of the process of amelogenesis.

Metastatic calcification of the nasal septum presenting as an intraoral mass: a case report with a review of the literature.

Metastatic calcification is a pathologic condition characterized by deposition of calcified product in otherwise normal tissues as a result of hyperphosphatemia with or without concurrent hypercalcemia. Metastatic calcification presenting clinically as an oral lesion is extremely rare. To date, only 7 cases of metastatic calcification involving the oral soft tissues have been described. This report describes a case of metastatic calcification of the nasal septum presenting as a mass of the anterior maxillary vestibule in a patient with end-stage renal disease. The case reported is only the second example with nasal septum involvement. A brief review of the clinical and histopathologic features of previously reported intraoral cases is also presented.

Solitary fibrous tumor of the oral soft tissues: a clinicopathologic and immunohistochemical study of 16 cases.

We describe the clinicopathologic and immunohistochemical features of 16 solitary fibrous tumors (SFTs) originating within the oral soft tissues. There were 10 women and six men with a mean age at diagnosis of 56 years. In all cases the tumors were slow-growing, asymptomatic, submucosal growths of variable size and duration. The buccal mucosa was involved in 12 cases, and the tongue and lower lip were affected in two cases, respectively. Thirteen tumors developed on the left side of the mouth. Follow-up information was available in 10 cases and averaged 44.7 months, with no evidence of recurrence or metastasis. All 16 tumors were well circumscribed and demonstrated histologic features that were invariably benign. In all cases they were composed of an admixture of alternating hypercellular and hypocellular, collagenous zones; haphazardly arranged, cytologically bland spindle and ovoid cells that in areas were intimately intermixed with collagen; a prominent vasculature; and perivascular hyalinization. Immunohistochemically, the tumors were consistently positive for CD34, bcl-2, factor XIIIa, and vimentin, whereas 75% of the tumors were reactive for CD99. To further define the clinicopathologic profile of intraoral SFT, we include a review of the previously reported cases. We also include a comparison and brief review of the clinicopathologic and immunohistochemical features of other spindle cell tumors of the oral cavity, from which SFTs must be differentiated.