ABSTRACT
Bacterial infection is a common finding in patients, who develop medication-related osteonecrosis of the jaw (MRONJ) by the long-term and/or high-dose use of anti-resorptive agents such as bisphosphonate (BPs). However, pathological role of bacteria in MRONJ development at the early stage remains controversial. Here, we demonstrated that commensal microbiota protects against MRONJ development in the pulp-exposed periapical periodontitis mouse model. C57/BL6 female mice were treated with intragastric broad-spectrum antibiotics for 1 week. Zoledronic acid (ZOL) through intravenous injection and antibiotics in drinking water were administered for throughout the experiment. Pulp was exposed on the left maxillary first molar, then the mice were left for 5 weeks after which bilateral maxillary first molar was extracted and mice were left for additional 3 weeks to heal. All mice were harvested, and cecum, maxilla, and femurs were collected. ONJ development was assessed using μCT and histologic analyses. When antibiotic was treated in mice, these mice had no weight changes, but developed significantly enlarged ceca compared to the control group (CTL mice). Periapical bone resorption prior to the tooth extraction was similarly prevented when treated with antibiotics, which was confirmed by decreased osteoclasts and inflammation. ZOL treatment with pulp exposure significantly increased bone necrosis as determined by empty lacunae and necrotic bone amount. Furthermore, antibiotics treatment could further exacerbate bone necrosis, with increased osteoclast number. Our findings suggest that the commensal microbiome may play protective role, rather than pathological role, in the early stages of MRONJ development.
Subject(s)
Animals , Female , Humans , Mice , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Bone Density Conservation Agents , Diphosphonates , Microbiota , Periapical Diseases , Zoledronic AcidABSTRACT
High-risk human papillomaviruses (HPVs) are involved in the development of several human cancers, including oropharyngeal squamous cell carcinomas. However, many studies have demonstrated that HPV alone is not sufficient for the oncogenic transformation of normal human epithelial cells, indicating that additional cofactors are required for the oncogenic conversion of HPV-infected cells. Inasmuch as chronic inflammation is also closely associated with carcinogenesis, we investigated the effect of chronic exposure to tumor necrosis factor α (TNFα), the major proinflammatory cytokine, on oncogenesis in two immortalized oral keratinocyte cell lines, namely, HPV16-immortalized and human telomerase reverse transcriptase (hTERT)-immortalized cells. TNFα treatment led to the acquisition of malignant growth properties in HPV16-immortalized cells, such as (1) calcium resistance, (2) anchorage independence, and (3) increased cell proliferation in vivo. Moreover, TNFα increased the cancer stem cell-like population and stemness phenotype in HPV16-immortalized cells. However, such transforming effects were not observed in hTERT-immortalized cells, suggesting an HPV-specific role in TNFα-promoted oncogenesis. We also generated hTERT-immortalized cells that express HPV16 E6 and E7. Chronic TNFα exposure successfully induced the malignant growth and stemness phenotype in the E6-expressing cells but not in the control and E7-expressing cells. We further demonstrated that HPV16 E6 played a key role in TNFα-induced cancer stemness via suppression of the stemness-inhibiting microRNAs miR-203 and miR-200c. Overexpression of miR-203 and miR-200c suppressed cancer stemness in TNFα-treated HPV16-immortalized cells. Overall, our study suggests that chronic inflammation promotes cancer stemness in HPV-infected cells, thereby promoting HPV-associated oral carcinogenesis.
ABSTRACT
A poroma is a benign adnexal neoplasm originating from the sweat gland duct. It usually presents clinically as a soft erythematous or flesh-colored papule, plaque, or nodule on the palms and soles. In most cases, poromas manifest as a solitary lesion, but rarely, multiple lesions have been reported and are defined as poromatosis.Although the pathogenesis is unclear, poromatosis is known to be associated with actinic damage, human papillomavirus infection, radiation therapy, or polychemotherapy. Herein, we describe a 53-year-old woman who had multiple erythematous papules on her feet for a year. She had a medical history of acute lymphoblastic leukemia and had undergone polychemotherapy with stem cell transplantation. To our knowledge, poromatosis related to chemotherapy is a rare entity, and our case could be attributed to the theory that using polychemotherapy can induce poromatosis.
ABSTRACT
Background@#Tumoral calcinosis is characterized by the deposition of calcific masses around major joints, and it often causes significant impairment of joint function. Dermatologists sometimes encounter patients with a subcutaneous hard mass around the joint. However, there are few studies about tumoral calcinosis in the dermatologic literature, especially in Korea. @*Objective@#The aim of this study was to determine the clinical characteristics of tumoral calcinosis. @*Methods@#We reviewed the clinical photographs, medical records, and biopsy specimens of 11 cases of tumoral calcinosis seen at our clinic in 10 years. @*Results@#All 11 patients were female, and the mean age at onset was 58.5 years. The mean duration of the disease was 7.1 years. Most patients (9, 81.8%) presented with an asymptomatic subcutaneous hard mass around the iliac crest. None of the patients had a family history, or abnormal serum calcium, phosphorus, and parathyroid hormone levels. All patients underwent surgery for treatment. @*Conclusion@#Tumoral calcinosis can occur sporadically without metabolic disease. Therefore, careful history taking and biochemical work-up involving the metabolism of calcium and phosphorus should be performed. If there is no peculiarityon examination, the lesion is cured by resection. Although the sample size of this study is small, it can be inferred that the characteristics of tumoral calcinosis in Korea can be described by its predominant sex preponderance and location, that is, the female sex and the iliac crest, respectively.