Heparin-binding protein 17 (HBp17), first purified in 1991 from the conditioned medium of the human A431 squamous cell carcinoma (SCC) cell line, was later renamed fibroblast growth factor-binding ...protein 1 (FGFBP-1). HBp17/FGFBP-1 is specifically expressed and secreted by epithelial cells, and it reversibly binds to fibroblast growth factor (FGF)-1 and FGF-2, as well as FGFs-7, -10, and -22, indicating a crucial involvement in the transportation and function of these FGFs. Our laboratory has investigated and reported several studies to elucidate the function of HBp17/FGFBP-1 in SCC cells and its potential as a molecular therapeutic target. HBp17/FGFBP-1 transgene exoression in A431-4 cells, a clonal subline of A431 that lacks tumorigenicity and does not express HBp17/FGFBP-1, demonstrated a significantly enhanced proliferation in vitro compared with A431-4 cells, and it acquired tumorigenicity in the subcutis of nude mice. Knockout (KO) of the HBp17/FGFBP-1 by genome editing significantly suppressed tumor growth, cell motility, and tumorigenicity compared with control cells. A comprehensive analysis of expressed molecules in both cell types revealed that molecules that promote epithelial cell differentiation were highly expressed in HBp17/FGFBP-1 KO cells. Additionally, we reported that 1α,25(OH)
2
D
3
or eldecalcitol (ED-71), which is an analog of 1α,25(OH)
2
D
3
, suppresses HBp17/FGFBP-1 expression and tumor growth in vitro and in vivo by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway. Here, we discuss the prospects of molecular targeted therapy targeting HBp17/FGFBP-1 with 1α,25(OH)
2
D
3
or ED71 in SCC and oral SCC.
Vascular endothelial growth factor A (VEGF-A) and its receptors (VEGFR1 and R2) play important roles in the progression of malignant melanoma through tumor angiogenesis. However, it is not clear ...whether the VEGF-A/VEGFR1 signaling pathway is involved in the proliferation and migration of melanoma cells. Thus, the effect of VEGF-A on cell migration was investigated in human melanoma cell lines. Of several splicing variants of VEGF-A, VEGF
165
is the most abundant and responsible for VEGF-A biological potency. VEGF
165
facilitated the migration of melanoma cells in both a chemotactic and chemokinetic manner, but cell proliferation was not affected by VEGF
165
. VEGF
165
also induced the phosphorylation of Akt. In addition, VEGF
165
-induced cell migration was inhibited significantly by VEGFR1/2 or a VEGFR1-neutralizing antibody. Furthermore, the downregulation of VEGFR1 via the transfection of VEGFR1-targeting antisense oligonucleotides suppressed VEGF
165
-induced cell migration. Moreover, wortmannin, an inhibitor of phosphatidylinositol-3 kinase (PI3K) in the PI3K/Akt pathway, suppressed VEGF
165
-induced Akt phosphorylation and VEGF
165
-induced cell migration. These findings suggest that the motility of melanoma cells is regulated by signals mediated through the PI3K/Akt kinase pathway with the activation of VEGFR1 tyrosine kinase by VEGF
165
. Thus, the downregulation of signaling via VEGF-A/VEGFR1 might be an effective therapeutic approach that could prevent the progression of malignant melanoma.
Resin components, such as methyl methacrylate (MMA) can cause allergic contact dermatitis (ACD). Allergic reactions to resin are usually delayed. Only a few studies have reported dental resin allergy ...with acute symptoms. Here, a case of ACD with acute facial swelling after dental treatment using resin material is reported. A 55-year-old woman with a history of periungual inflammation when using gel nail polish had repeated episodes of facial swelling after dental treatment with resin material. The resin temporary crown was removed, and symptoms were alleviated with antihistamines and corticosteroids. With the suspicion of resin allergy, skin tests were performed. Patch testing revealed positive reactions to self-adhesive resin cement (primer and polymerized), self-curing acrylic resin (liquid and polymerized), 2-hydroxyethyl methacrylate (2-HEMA), and ethylene glycol dimethacrylate (EGDMA), whereas the prick test was negative for all allergens. Complement C4 and C1 inhibitor activity were reference values in the tests for hereditary angioedema. Based on these findings, the patient was diagnosed with ACD to 2-HEMA and EGDMA. Since diagnosis, no similar symptoms have been observed in subsequent dental treatment with non-resin materials. The use of dental resin materials may cause ACD with an acute reaction. This report alerts dentists who routinely use resin materials.
Atrial fibrillation (AF) is associated with a fivefold risk of stroke and thrombotic embolism, which are usually derived from the left atrial appendage (LAA). Spontaneous echo contrast (SEC) is known ...as a risk factor for thrombosis.
Porphyromonas gingivalis
(
P.
gingivalis
) has some prothrombotic effects and plays a key role in periodontitis and oral-systemic disease connection. We aimed to clarify the relationship between
P. gingivalis
and LAA SEC among AF patients. A total of 569 AF ablation candidates were enrolled in the present study. LAA SEC was categorized into nondense SEC and dense SEC based on transesophageal echocardiography. Serum immunoglobulin G antibody titers of
P. gingivalis
fimA subtypes (types I–IV) were measured with an enzyme-linked immunosorbent assay. The levels of antibody titers were categorized into high (> mean + 3 standard deviation) and low values. A total of 513 (90%) patients were included in the nondense SEC group, and 56 (10%) were included in the dense SEC group. Multivariate regression analysis revealed that the high-value serum antibody titers of
P. gingivalis
types II and IV were independently associated with dense SEC type II: adjusted odds ratio (OR) 2.220; 95% confidence interval (CI) 1.062–4.643;
P
= 0.02; and type IV: adjusted OR 3.169; 95% CI 1.058–6.657;
P
= 0.002. The results revealed that
P. gingivalis
types II and IV are related to LAA SEC severity among AF patients who receive appropriate anticoagulation therapy.
Heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1) has been observed to induce the tumorigenic potential of epithelial cells and is highly expressed in oral cancer ...cell lines and tissues. It is also recognized as a pro-angiogenic molecule because of its interaction with fibroblast growth factor (FGF)-2. In this study, we examined the functional role of HBp17/FGFBP-1 in A431 and HO-1-N-1 cells. Originally, HBp17/FGFBP-1 was purified from A431 cell-conditioned media based on its capacity to bind to FGF-1 and FGF-2. We isolated and established HBp17/FGFBP-1-knockout (KO)-A431 and KO-HO-1-N-1 cell lines using the clusters of regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) gene editing technology. The amount of FGF-2 secreted into conditioned medium decreased for A431-HBp17-KO and HO-1-N-1-HBp17-KO cells compared to their WT counterparts. Functional assessment showed that HBp17/FGFBP-1 KO inhibited cell proliferation, colony formation, and cell motility in vitro. It also inhibited tumor growth in vivo compared to controls, which confirmed the significant difference in growth in vitro between HBp17-KO cells and wild-type (WT) cells, indicating that HBp17/FGFBP-1 is a potent therapeutic target in squamous cell carcinomas (SCC) and oral squamous cell carcinomas (OSCC). In addition, complementary DNA/protein expression analysis followed by Gene Ontology and protein–protein interaction (PPI) analysis using the Database for Visualization and Integrated Discovery and Search Tool for the Retrieval of Interacting Genes/Proteins showed that both gene and protein expression related to epidermal development, cornification, and keratinization were upregulated in A431-HBp17-KO and HO-1-N-1-KO cells. This is the first discovery of a novel role of HBp17/FGFBP-1 that regulates SCC and OSCC cell differentiation.
The impact of gut and oral microbiota on the clinical outcomes of patients with oral squamous cell carcinoma (OSCC) is unknown. We compared the bacterial composition of dental plaque and feces ...between patients with OSCC and healthy controls (HCs). Fecal and dental plaque samples were collected from 7 HCs and 18 patients with OSCC before treatment initiation. Terminal restriction fragment-length polymorphism analysis of 16S rRNA genes was performed. Differences in bacterial diversity between the HC and OSCC groups were examined. We compared the occupancy of each bacterial species in samples taken from patients with OSCC and HCs and analyzed the correlation between PD-L1 expression in the tumor specimens and the occupancy of each bacterial species. The gut and oral microbiota of patients with OSCC were more varied than those of HCs. Porphyromonas and Prevotella were significantly more abundant in patients with OSCC than in HCs. The abundance of Clostridium subcluster XIVa in the gut microbiota of the PD-L1-positive group was significantly greater than that in the PD-L1-negative group. The oral and gut microbiomes of patients with OSCC were in a state of dysbiosis. Our results suggest the possibility of new cancer therapies targeting these disease-specific microbiomes using probiotics and synbiotics.
Current status of dental metal allergy in Japan Kitagawa, Masae; Murakami, Satoshi; Akashi, Yoshihiko ...
Journal of prosthodontic research,
07/2019, Letnik:
63, Številka:
3
Journal Article
Recenzirano
To assess the current status of patients with dental metal allergies in Japan.
This study analyzed dental metal allergy in 1225 patients (1:3 male to female ratio; average age 53.0 ±16.5 years), ...including 300 who were scheduled to undergo dental implant surgery, between 2006 and 2016. For diagnosis of metal allergy, patch tests using metal allergens were performed. Additionally, when necessary, metal element analysis of dental alloys was performed in the mouths of some patients using an X-ray fluorescence analyzer for those who exhibited positive reactions.
Among 925 patients (i.e., excluding those scheduled to undergo dental implant surgery n=300), nearly one-half (44.0%) exhibited a positive response to any metal element in the patch test. The positivity rates were as follows: nickel (22.5%); palladium (14.8%); and zinc (11.5%). Almost one-half (42.3%) of the patients had diseases associated with metal allergy. Among patients who exhibited a positive reaction to any metal element in the patch test, more than two-thirds (67.9%) had dental alloys containing the positive metal element(s). One-half (55.6%) of the patients who underwent treatment to remove the metal experienced improvement in symptoms. In patients who underwent patch testing as an implant preoperative examination, several (2.7%) exhibited a positive reaction to titanium.
Dental metals, including nickel, palladium and zinc, which are indispensable to dental treatment in Japan, had high positivity rates in patch testing, and one-half of the patients improved following removal of the metal. Additionally, there were several patients with allergy to titanium.
Porphyromonas gingivalis (P.g.), a major periodontal pathogen is a known risk factor for various systemic diseases. However, the relationship between P.g. and nonalcoholic steatohepatitis ...(NASH)-related hepatocellular carcinoma (HCC) is unclear. Thus, we aimed to elucidate whether P.g.-odontogenic infection promotes NASH-related HCC development/progression and to clarify its mechanism. Using high-fat diet (HFD)-induced NASH mouse model, P.g. was infected odontogenically. After 60 weeks of infection, tumor profiles were examined. Chow diet (CD) groups were also prepared at 60 weeks. Nodule formation was only seen in HFD-mice. P.g.-odontogenic infection significantly increased the mean nodule area (P = 0.0188) and tended to promote histological progression score after 60 weeks (P = 0.0956). Interestingly, P.g. was detected in the liver. HFD-P.g. (+) showed numerous TNF-α positive hepatic crown-like structures and 8-OHdG expression in the non-neoplastic liver. In P.g.-infected hepatocytes, phosphorylation of integrin β1 signaling molecules (FAK/ERK/AKT) was upregulated in vitro. In fact, total AKT in the liver of HFD-P.g. (+) was higher than that of HFD-P.g. (-). P.g.-infected hepatocytes showed increased cell proliferation and migration, and decreased doxorubicin-mediated apoptosis. Integrin β1 knockdown inhibited these phenotypic changes. P.g.-odontogenic infection may promote the progression of neoplastic nodule formation in an HFD-induced NASH mouse model via integrin signaling and TNF-α induced oxidative DNA damage.
Purpose
Chemotherapy-induced taste alteration is a side effect that can result in malnutrition and reduced quality of life in cancer patients. However, the underlying causes of this phenomenon remain ...unclear, and evidence-based treatments have not been established. This study focused on patients’ subjective symptoms of taste alterations aimed to explore how the sensitivity to basic tastes changes due to anticancer agents and how alterations in one taste perception are associated with changes in other tastes during chemotherapy.
Methods
A cross-sectional questionnaire-based interview survey was conducted on 215 patients undergoing chemotherapy. The subjective sensitivity to each basic taste was assessed using a visual analog scale, and the incidence of taste alterations due to different chemotherapy regimens was calculated. Multivariate logistic regression analysis was performed to determine whether there were associations between changes in one taste sensitivity and changes in other taste sensitivities.
Results
Approximately half (49.5%) of the patients experienced chemotherapy-induced taste alterations. An analysis of subjective changes in basic tastes revealed that the salt and umami taste systems were more sensitive to chemotherapy than other taste systems. Patients with altered sensitivity to sweet taste were significantly more likely to report altered sensitivity to salt, bitter, and sour tastes. Moreover, umami–salt and bitter–sour taste sensitivities were significantly related to each other.
Conclusion
This study suggests that changes in subjective sensitivities to one basic taste during chemotherapy may be accompanied by changes in other tastes in specific combinations. Considering taste associations in dietary guidance may help improve the nutritional status of cancer patients experiencing taste alterations due to chemotherapy.
Purpose
Oral hygiene is crucial in the management of oral and febrile complications during chemotherapy for cancer. This study aimed to investigate the impact of oral hygiene on the incidence of ...febrile neutropenia (FN) throughout the course of chemotherapy for breast cancer.
Methods
A total of 137 patients with breast cancer who underwent four cycles of adjuvant chemotherapy with docetaxel and cyclophosphamide (TC) combination therapy or docetaxel alone were assessed for oral hygiene by quantifying the number of oral bacteria they harbored. These patients received professional oral health care (POHC). Eighteen patients underwent primary prophylaxis with granulocyte colony-stimulating factors. The relationship between oral bacteria count and FN incidence was retrospectively assessed.
Results
The FN incidence rate was 47.4% throughout all treatment cycles (32.8%, 13.5%, 14.3%, and 14.4% in cycles 1, 2, 3, and 4, respectively). The oral bacteria count decreased with each treatment cycle (cycle 1: 9.10 × 10
6
colony-forming units (CFU)/mL, cycle 2: 5.89 × 10
6
CFU/mL, cycle 3: 4.61 × 10
6
CFU/mL, cycle 4: 5.85 × 10
6
CFU/mL,
P
= 0.004). Among 281 treatment cycles, FN occurred in 63 (22.4%). In the treatment cycle-based analysis, high oral bacteria count was an independent risk factor for FN.
Conclusion
FN incidence decreased with each treatment cycle and was associated with changes in oral bacteria counts. The oral bacterial count was one of risk factors for FN development in breast cancer.
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