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Background: Embryonal rhabdomyosarcoma (ERMS) is a highly aggressive form of soft-tissue sarcoma that predominantly affects children. Due to limited benefits and resistance to therapy, there is an unmet need to explore alternative therapeutic strategies., Case Presentation: In this report, we present a rare case of pediatric ERMS located on the right side of the maxillary gingiva. A composite reference guide integrating clinical, radiographic, and histopathologic findings was used for a definitive diagnosis. Targeted next-generation sequencing of tumor biopsy was performed to identify genetic alterations. A 12-year-old female was admitted to the Pediatric Intensive Care Unit (PICU) and underwent a tracheotomy to relieve asphyxiation caused by a 5.5 cm diameter mass compressing the tongue root and pharyngeal cavity. Hematoxylin and eosin staining revealed a hybrid morphology characterized by clusters of round and spindle cells. Further immunohistochemistry assays indicated positive immunoreactivity for desmin, myogenin, and MyoD1. Various genetic alterations were identified, including mutations in GNAS, HRAS, LRP1B, amplification of MDM2 and IGF1R, and two novel IGF1R fusions. Negative PAX-FOXO1 fusion status supported the clinical diagnosis of ERMS. Initial treatment involved standard chemotherapy; however, the tumor persisted in its growth, reaching a maximum volume of 12 cm × 6 cm × 4 cm by the completion of treatment. Subsequent oral administration of anlotinib yielded a significant antitumor response, characterized by substantial tumor necrosis and size reduction. Following the ligation of the tumor pedicle and its removal, the patient developed a stabilized condition and was successfully discharged from PICU., Conclusions: Our study highlights the importance of accurate diagnosis established on multifaceted assessment for the effective treatment of ERMS. We present compelling evidence supporting the clinical use of anlotinib as a promising treatment strategy for pediatric ERMS patients, especially for those resistant to conventional chemotherapy., (© 2024. The Author(s).)

Carnosol, a rosemary polyphenol, displays anticancer properties and is suggested as a safer alternative to conventional surgery, radiotherapy, and chemotherapy. Given that its effects on gingiva carcinoma have not yet been investigated, the aim of this study was to explore its anti-tumor selectivity and to unravel its underlying mechanisms of action. Hence, oral tongue and gingiva carcinoma cell lines exposed to carnosol were analyzed to estimate cytotoxicity, cell viability, cell proliferation, and colony formation potential as compared with those of normal cells. Key cell cycle and apoptotic markers were also measured. Finally, cell migration, oxidative stress, and crucial cell signaling pathways were assessed. Selective anti-gingiva carcinoma activity was disclosed. Overall, carnosol mediated colony formation and proliferation suppression in addition to cytotoxicity induction. Cell cycle arrest was highlighted by the disruption of the c-myc oncogene/p53 tumor suppressor balance. Carnosol also increased apoptosis, oxidative stress, and antioxidant activity. On a larger scale, the alteration of cell cycle and apoptotic profiles was also demonstrated by QPCR array. This was most likely achieved by controlling the STAT5, ERK1/2, p38, and NF-ĸB signaling pathways. Lastly, carnosol reduced inflammation and invasion ability by modulating IL-6 and MMP9/TIMP-1 axes. This study establishes a robust foundation, urging extensive inquiry both in vivo and in clinical settings, to substantiate the efficacy of carnosol in managing gingiva carcinoma., (© 2024. Crown.)

Adoption of plant-derived compounds for the management of oral cancer is encouraged by the scientific community due to emerging chemoresistance and conventional treatments adverse effects. Considering that very few studies investigated eugenol clinical relevance for gingival carcinoma, we ought to explore its selectivity and performance according to aggressiveness level. For this purpose, non-oncogenic human oral epithelial cells (GMSM-K) were used together with the Tongue (SCC-9) and Gingival (Ca9-22) squamous cell carcinoma lines to assess key tumorigenesis processes. Overall, eugenol inhibited cell proliferation and colony formation while inducing cytotoxicity in cancer cells as compared to normal counterparts. The recorded effect was greater in gingival carcinoma and appears to be mediated through apoptosis induction and promotion of p21/p27/cyclin D1 modulation and subsequent Ca9-22 cell cycle arrest at the G0/G1 phase, in a p53-independent manner. At these levels, distinct genetic profiles were uncovered for both cell lines by QPCR array. Moreover, it seems that our active component limited Ca9-22 and SCC-9 cell migration respectively through MMP1/3 downregulation and stimulation of inactive MMPs complex formation. Finally, Ca9-22 behaviour appears to be mainly modulated by the P38/STAT5/NFkB pathways. In summary, we can disclose that eugenol is cancer selective and that its mediated anti-cancer mechanisms vary according to the cell line with gingival squamous cell carcinoma being more sensitive to this phytotherapy agent., (© 2024. The Author(s).)

Oral squamous cell carcinoma (OSCC) is the most common epithelial tumor of the oral cavity. Gingival tumors, a unique type of OSCC, account for 10% of these malignant tumors. The antineoplastic properties of statins, including pitavastatin (PV), and the essential oil of the Pinus densiflora leaf (Pd oil) have been adequately reported. The goal of this investigation was to develop nanostructured lipid carriers (NLCs) containing PV combined with Pd oil and to determine their cytotoxicity against the cell line of human gingival fibroblasts (HGF-1). A central composite quadratic design was adopted to optimize the nanocarriers. The particle size and stability index of the nano-formulations were measured to evaluate various characteristics. TEM analysis, the entrapment efficiency, dissolution efficiency, and the cytotoxic efficiency of the optimized PV-loaded nanostructured lipid carrier drug delivery system (PV-Pd-NLCs) were evaluated. Then, the optimal PV-Pd-NLCs was incorporated into a Carbopol 940® gel base and tested for its rheological features and its properties of release and cell viability. The optimized NLCs had a particle size of 98 nm and a stability index of 89%. The gel containing optimum PV-Pd-NLCs had reasonable dissolution efficiency and acceptable rheological behavior and acquired the best cytotoxic activity against HGF-1 cell line among all the formulations developed for the study. The in vitro cell viability studies revealed a synergistic effect between PV and Pd oil in the treatment of gingival cancer. These findings illustrated that the gel containing PV-Pd-NLCs could be beneficial in the local treatment of gingival cancer.

We report a case of cavernous sinus metastasis following postoperative maxillary gingival squamous cell carcinoma. An 83-year-old man was referred to our hospital due to pain in the left maxillary gingiva. Contrast-enhanced computed tomography imaging showed a mass lesion with bone destruction in the left maxillary gingiva. Biopsy indicated the presence of squamous cell carcinoma(T4bN1M0, Stage ⅣB), and the tumor was resected under general anesthesia. Four months after surgery, the patient experienced headache, and orbital pain, failing vision, and movement disorder of the left eye appeared. Magnetic resonance imaging revealed a tumor invading the cavernous sinus and orbit. The lesion was clinically diagnosed as metastatic cavernous sinus following postoperative left maxillary gingival carcinoma. Although the patient underwent chemotherapy, he died from multiple organ failure about 5 months after surgery.

Background: To elucidate the role of iPLA2/PLA2G6 in gingivobuccal squamous cell carcinoma (GB-SCC) and to ascertain the synthetic lethality-based chemoprevention role of aspirin in arachidonic acid metabolism (AAM) pathway down-regulated GB-SCC., Methods: The in vitro efficacy of aspirin on GB-SCC cells (ITOC-03 and ITOC-04) was assessed by cell proliferation, colony formation, apoptosis, cell migration, cell cycle assay and RNA-seq, while inhibition of PLA2G6 and AAM pathway components was affirmed by qPCR, Western blot and immunofluorescence staining. The in vivo effect of aspirin was evaluated using NOD-SCID mice xenografts and immunohistochemical analysis., Results: We found that aspirin, which has been reported to act through the COX pathway, is inhibiting PLA2G6, and thereby the COX and LOX components of the AAM pathway. The findings were validated using PLA2G6 siRNA and immunohistochemical marker panel. Moreover, a pronounced effect in ITOC-04 cells and xenografts implied aspirin-induced synthetic lethality in the AAM pathway down-regulated GB-SCC., Conclusions: This study reveals that aspirin induces the anti-tumor effect by a previously unrecognized mechanism of PLA2G6 inhibition. In addition, the effect of aspirin is influenced by the baseline AAM pathway status and could guide precision prevention clinical trials of AAM pathway inhibitors.

Gingival squamous cell carcinoma (GSCC) is responsible fora large proportion of oral cavity malignancies. GSCC is characterized by rapid cell growth, and progressive invasion and migration. P21 is a widely recognized tumor suppressor, which is induced by P53 activation; however, drugs that aim to promote P21‑mediated tumor suppression remain to be identified. A natural compound library was used to perform broad‑spectrum screening of drugs that could promote P21 expression. Subsequently, the effects of the screened drug on GSCC cell proliferation and apoptosis were evaluated. The results of the present study suggested that lapiferin was the most effective natural compound that promoted the expression of P21 at both mRNA and protein levels. Lapiferin inhibited proliferation and enhanced apoptosis of YD‑38 GSCC cells in a dose‑dependent manner. Furthermore, following treatment with lapiferin, the critical cell cycle regulators cell division cycle 25C and cyclin B1 and tumor cell proliferation markers proliferating cell nuclear antigen and Ki67 were markedly decreased. In addition, pro‑apoptotic proteins were promoted following treatment of YD‑38 cells with lapiferin. Following the depletion ofP21 expression, lapiferin‑mediated inhibition of cell proliferation and enhancement of cell apoptosis were significantly reduced. These results indicated that lapiferin may exert potent antitumor effects on GSCC via regulation of P21; therefore, lapiferin may be considered a potential, natural therapeutic agent for the treatment of GSCC.

Background: Canine malignant melanoma is highly aggressive and generally chemoresistant. Toceranib is a kinase inhibitor drug that inhibits several tyrosine kinases including the proto-oncogene receptor tyrosine kinase KIT. Although canine malignant melanoma cells often express KIT, a therapeutic effect for toceranib has yet to be reported for this tumor, with only a small number of patients studied to date. This is a case report of a dog with malignant melanoma that experienced a transient response to toceranib. Furthermore, the KIT expressed in the tumor of this case was examined using molecular analysis., Case Presentation: A Shiba Inu dog presented with a gingival malignant melanoma extending into surrounding structures with metastasis to a submandibular lymph node. The dog was treated with toceranib (Palladia®; 2.6-2.9 mg/kg, orally, every other day) alone. Improvement of tumor-associated clinical signs (e.g., halitosis, tumor hemorrhage, trismus, and facial edema) with reduced size of the metastatic lymph node was observed on Day 15. The gingival tumor and associated masses in the masseter and pterygoid muscles decreased in size by Day 29 of treatment. Toceranib treatment was terminated on Day 43 due to disease progression and the dog died on Day 54. The tumor of this dog had a novel deletion mutation c.1725_1733del within KIT and the mutation caused ligand-independent phosphorylation of KIT, which was suppressed by toceranib. This mutation was considered to be an oncogenic driver mutation in the tumor of this dog, thereby explaining the anti-tumor activity of toceranib., Conclusions: This is the first report that presents a canine case of malignant melanoma that responded to toceranib therapy. KIT encoded by KIT harboring a mutation c.1725_1733del is a potential therapeutic target for toceranib in canine malignant melanoma. Further investigation of the KIT mutation status and toceranib therapy in canine malignant melanoma will need to be undertaken.

Arsenic is a well‑documented environmental toxicant that can induce neurotoxicity and peripheral vascular diseases. In fact, arsenic trioxide has been used to treat various cancer types. Oral cancer has been in the top ten common cancers for decades in Taiwan, and the incidence rate is continuously increasing. The majority of oral cancers are associated with excessive tobacco, alcohol consumption and betel chewing. To the best of our knowledge, no study has revealed the effect of arsenic compounds on oral cancers. Thus, the present study used OEC‑M1 oral squamous carcinoma cells treated with sodium arsenite (NaAsO2) and dimethylarsenic acid (DMA) to determine whether both arsenic compounds could exert anticancer effects on oral cancer. The results demonstrated that NaAsO2 and DMA induced rounding up and membrane blebbing in OEC‑M1 cells, which are morphological characteristics of apoptosis. Annexin V/PI double staining analysis further confirmed that both arsenic compounds induced apoptosis of OEC‑M1 cells. In addition, NaAsO2 and DMA significantly decreased the survival rate and increased the percentage of OEC‑M1 cells in the subG1 and G2/M phases (P<0.05). Furthermore, both arsenic compounds significantly activated the cleavage of caspase‑8, ‑9, ‑3 and PARP, and the phosphorylation of JNK, ERK1/2 and p38 in OEC‑M1 cells (P<0.05). Collectively, the findings of the present study indicated that NaAsO2 and DMA stimulate extrinsic and intrinsic apoptotic pathways through the activation of the MAPK pathways to induce apoptosis of OEC‑M1 cells, suggesting that NaAsO2 and DMA may be used as novel anticancer drugs for oral cancers.

Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC)., Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n = 66; SCRT group: n = 18)., Results: The median follow-up time was 24 (range: 1-124) months. The median prescribed dose was 60 (6-70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8, 95% confidence interval [CI]: 66.0-87.6; SCRT: 50.4, 95% CI: 27.6-73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6, 95% CI: 62.7-85.2; SCRT: 42.0, 95% CI: 17.7-70.9; P = 0.028) and local control rates (LC; IACRT: 77.2, 95% CI: 64.2-86.4; SCRT: 42.0, 95% CI: 17.7-70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups., Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

Background: Heteronemin, a marine sesterterpenoid-type natural product, possesses an antiproliferative effect in cancer cells. In addition, heteronemin has been shown to inhibit p53 expression. Our laboratory has demonstrated that the thyroid hormone deaminated analogue, tetrac, activates p53 and induces antiproliferation in colorectal cancer. However, such drug mechanisms are still to be studied in oral cancer cells., Methods: We investigated the antiproliferative effects by Cell Counting Kit-8 and flow cytometry. The signal transduction pathway was measured by Western blotting analyses. Quantitative PCR was used to evaluate gene expression regulated by heteronemin, 3,3',5,5'-tetraiodothyroacetic acid (tetrac), or their combined treatment in oral cancer cells., Results: Heteronemin inhibited not only expression of proliferative genes and Homo Sapiens Thrombospondin 1 ( THBS-1 ) but also cell proliferation in both OEC-M1 and SCC-25 cells. Remarkably, heteronemin increased TGF-β1 expression in SCC-25 cells. Tetrac suppressed expression of THBS-1 but not p53 expression in both cancer cell lines. Furthermore, the synergistic effect of tetrac and heteronemin inhibited ERK1/2 activation and heteronemin also blocked STAT3 signaling. Combined treatment increased p53 protein and p53 activation accumulation although heteronemin inhibited p53 expression in both cancer cell lines. The combined treatment induced antiproliferation synergistically more than a single agent., Conclusions: Both heteronemin and tetrac inhibited ERK1/2 activation and increased p53 phosphorylation. They also inhibited THBS-1 expression. Moreover, tetrac suppressed TGF-β expression combined with heteronemin to further enhance antiproliferation and anti-metastasis in oral cancer cells.

Background: The aim of this study was to evaluate the prognostic factors and treatment outcomes of advanced maxillary gingival squamous cell carcinoma (SCC) treated with intra-arterial infusion chemotherapy concurrent with radiotherapy., Methods: A total of 46 patients were reviewed retrospectively in this study. The treatment schedule comprised intra-arterial chemotherapy (total, 60 mg/m 2 docetaxel and 150 mg/m 2 cisplatin) and three-dimensional computed tomography based, daily conventional radiotherapy (total, 60 Gy/30 fr) for 6 weeks., Results: The median follow-up period was 40 months (range, 3-110 months). The 3-year overall survival and locoregional control rates for all patients were 64.3% and 84.3%, respectively. The OS rate of the patients with N0-1 was significantly higher than that of the patients with N ≥ 2 (P < .05). No grade 5 toxicities were observed., Conclusions: Intra-arterial infusion chemotherapy concurrent with radiotherapy was effective for advanced maxillary gingival SCC., (© 2019 Wiley Periodicals, Inc.)

Disseminated carcinomatosis of the bone marrow (DCBM) is characterized by diffuse metastasis to bone marrow and sudden mortality. To the best of our knowledge, no studies to date have reported progression of oral squamous cell carcinoma to DCBM. Herein, we report a case of squamous cell carcinoma in the maxillary gingiva suspected of progressing to DCBM. A 64-year-old woman presented with white lesions on the left maxillary gingiva. The lesions were diagnosed as squamous cell carcinoma (T2, N0, M0), and partial maxillectomy performed. Two years and 5 months after surgery, metastasis was noted in the left cervical lymph node and left radical neck dissection carried out. The subsequent diagnosis was right cervical lymph node metastasis and multiple bone metastases. The patient also presented with thrombocytopenia, anemia, and elevated levels of alkaline phosphatase, probably due to metastatic bone disease. Although various antitumor therapies were administered, the patient died 6 months after diagnosis of multiple bone metastases.

Competing Interests: Competing interests: None declared.

BACKGROUND Ocular Kaposi's sarcoma (KS) involving the conjunctiva and ocular adnexa is uncommon and is usually treated with cryotherapy or surgical excision. We report a case of ocular KS successfully treated with HAART combined with 8 cycles of weekly docetaxel. CASE REPORT Our patient was a 24-year-old, treatment-naïve, HIV-positive (CD4 cell count 198 cells/mm3), homosexual man treated as having atypical hordeolum and subconjunctival hemorrhage, and later confirmed with pathology to have ocular KS with immunohistochemistry study showing KS with positive HHV8, CD34, CD31, and focal positive staining with Factor VIIIRA. HAART therapy was initiated combined with weekly docetaxel. With 2-month treatment of HAART and 8 cycles of weekly docetaxel, the KS of the bulbar conjunctiva and the eyelid partially resolved. CONCLUSIONS HAART combined with weekly docetaxel is an effective and well-tolerated option for ocular KS, which could be considered before cryotherapy or surgical excision.

Oral mucosal melanoma is rare and more aggressive than cutaneous melanoma. Hard palate and maxillary alveolar crest are most commonly involved. Multidisciplinary team approach is necessary for successful management of this tumor. The main treatment modality is surgical resection, which usually results in impaired mastication, deglutition, speech, oral competence and significant cosmetic deformity. Here, a rare case of oral mucosal melanoma of mandibular gingiva in a 44-year man is reported, who was treated by en-block mandibular resection followed by adjuvant therapy with high dose interferons (IFN) - 2b. Following two weeks of healing period, prosthetic rehabilitation of the patient was done with an interim removable denture prosthesis, which effectively limited the unfavourable effects of surgery and helped him in resocialisation.

Gingival squamous cell carcinoma is a rare form of cancer that accounts for less than 10% of all head and neck cancers. Targeted therapies with natural compounds are of interest because they possess high efficacy with fewer side-effects. Methylsulfonylmethane (MSM) is an organic sulfur-containing compound with anticancer activities. The main goal of this study was to induce proliferation inhibition and apoptosis in the metastatic YD-38 cell line. MSM up-regulated expression of P21 Waf1/Cip1 and P27 Kip1 genes and down-regulated expression of cyclin D1 (CCND1) and CDK4. Moreover, treatment with MSM induced apoptosis and up-regulation of BAX in YD-38 cells. In accordance, the expression of the BCL-2 and BCL-XL, were inhibited, indicating the role of mitochondria in MSM-induced apoptosis. Analysis of mitochondrial integrity showed a loss of mitochondrial potential with an increased level of cytochrome c in the cytosol compared to mitochondria. Active CASPASE-3 (CASP3) was also observed, confirming that MSM-induced apoptosis is caspase-mediated., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The purpose of this study was to evaluate the clinical efficacy of initial periodontal therapy in gingival pregnancy tumors. Thirty-nine patients diagnosed with gingival tumors of pregnancy between 2007 and 2015 were enrolled in this study. The patients received initial periodontal therapy, then supportive periodontal therapies at 3- to 6-month intervals. The patients underwent follow up for 6 months to 8 years after treatment. After plaque control, supragingival scaling, and root planning, the tumors in 25 patients were gradually eliminated without the necessity of surgery. In 3 patients, tumors <5 mm in size disappeared in a mean time of 3.6 months, 4 patients with tumors 5-10 mm disappeared in a time of 7.5 months, 11 patients with tumors 10-15 mm disappeared in 10.2 months, 6 patients with tumors 15-20 mm disappeared in 15 months, and one patient with a tumor >20 mm disappeared in 20 months. No recurrence of gingival pregnancy tumors was noted during subsequent follow-up. Initial periodontal therapy combined with oral hygiene maintenance is efficacious in treating gingival pregnancy tumors of patients with normal hormone levels, which can potentially serve as an option to avoid surgery.

Tannic acid (TA), is a potent anti-oxidant, showing anti-proliferative effects on numerous cancers. The ability of TA to induce proliferation inhibition on the rare tumor, gingival squamous cell carcinoma (GSCC), comprising <10% of all head and neck squamous cell carcinomas was studied in the YD-38 cell line. The main goal was to modulate the Jak2/STAT3 pathway using TA and to induce cell cycle arrest and apoptosis in GSCC. TA treatment induced G1 arrest and apoptosis in YD-38 cells. Molecular analysis revealed that TA inhibits Jak2/STAT3 pathway by preventing their expression as well as phosphorylation. This inhibition of STAT3 phosphorylation prevented the nuclear translocation and DNA binding capability of STAT3. Together with the inhibition of transcriptional regulatory function of STAT3, TA inhibited the expression of G1 phase modulators CDK-4, CDK-6, cyclin D1 and cyclin E. It is also evidenced that TA exerted an intense activation of p21Waf1/Cip1, p27Kip1 and p53 genes confirming its role in G1 phase inhibition. Additionally, upon treatment with TA, the expression of mitochondrial pore factors Bax, Bcl-2 and Bcl-XL were changed. We observed inhibition of Bcl-2 and an increase in mitochondrial localization of Bax leading to the loss of mitochondrial membrane potential, resulting in the release of cytochrome c to the cytosol. In addition, we perceived the activation of caspases upon TA treatment. Specific inhibition of caspase protected the cells from TA induced apoptosis. Taken together, this study reveals that TA significantly inhibits the Jak2/STAT3 signaling pathway and induces G1 arrest and mitochondrial apoptosis in YD-38 cells.

The use ofa central venous(CV)port system has become common for the treatment of patients with tumors. We report on the failure to remove CV catheters in 2 patients. The first patient was a 50 years woman with acute myeloid leukemia. She underwent CV port implantation via the left brachial approach 11 years previously. The second patient was an 80 years man with a lower gingival carcinoma. He underwent CV port implantation via the left brachial approach 6 years previously. CV catheter removal was attempted in both patients, but was unsuccessful because of strong adhesion to the vessel wall. Based on our experience, if catheter removal is impossible, its retention is more suitable.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare neoplastic process constituting 15% to 20% of peripheral T-cell lymphomas. We report the clinicopathologic and molecular characteristics of an unusual intraoral manifestation of AITL. A 35-year-old white man with a history of AITL presented with a 2.5-cm, poorly circumscribed, erythematous, exophytic lesion occupying the free and attached buccal gingiva of the right maxillary lateral incisor and canine. Histopathologically, the tumor showed diffuse and intense polymorphic infiltration by small to medium-sized lymphocytes admixed with numerous eosinophils. The neoplastic cells showed strong and diffuse reactivity for CD2, CD3, CD4, CD10, and PD-1 (programmed cell death 1 [PDCD1]). Rare immunopositivity was seen with BCL6 (B-cell CLL/lymphoma 6) and CXCL13 (chemokine [C-X-C motif] ligand 13). Neoplastic cells were negative for CD7 and EBER ISH (Epstein-Barr virus-encoded small RNA in situ hybridization). CD21 did not show any increased follicular dendritic cell component. Polymerase chain reaction-based assay found monoclonal T-cell receptor γ (TRG) gene rearrangements. Diagnosis of recurrent/residual AITL was rendered. Chemotherapy was administered, with the intraoral tumor resolving completely 3 months later., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Many red algae-derived natural products are known to have anticancer effects. The biological functions of the red alga Solieria robusta from the Karachi coast (Pakistan) remain unclear. Here, we prepared a methanolic extracts of S. robusta (MESR) to examine its possible anti-oral cancer effects and the corresponding mechanism of action. Cell viability of MESR-incubated oral cancer Ca9-22 cells was dose-responsively decreased (p<0.001). According to a propidium iodide (PI)-based assay the cell cycle distribution was dramatically changed, especially for subG1 accumulation. Annexin V/PI assay of apoptosis using flow cytometry also showed that MESR-incubated Ca9-22 cells were dose-responsively increased (p<0.001). For evaluation of oxidative stress in MESR-incubated Ca9-22 cells, we found that reactive oxygen species (ROS) were overexpressed dose- and time-responsively and mitochondrial depolarization was also increased (p<0.001). Taken together, MESR showed inhibitory effects on oral cancer proliferation coupled with apoptosis and oxidative stress.

Introduction: Lymphomatoid granulomatosis is an uncommon Epstein-Barr virus-positive B-cell lymphoma, an angiocentric-destructive process with a predominant T-cell background. Lymphomatoid granulomatosis is listed among rare diseases. Common localization is in the lungs. Lymphomatoid granulomatosis with oral involvement is described in only two reports. In this report, we describe a third case of oral lymphomatoid granulomatosis., Case Presentation: A 65-year-old Caucasian man with a gingival ulceration underwent a biopsy. The histological pattern was compatible with a grade III lymphomatoid granulomatosis. The staging revealed a nodular lesion in the lower lobe of his right lung. Our patient also presented with hemoptysis, an unusual and not reported clinical sign. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy was performed every three weeks for six cycles., Conclusions: The pulmonary nodule and the gingival lesion disappeared. At eight-month follow-up, our patient is disease-free. We wish to emphasize that the oral manifestation described was the first sign of the disease and allowed for diagnosis. This case report adds to the medical literature for the particular clinical presentation of this rare disease.

The patient was a 73-year-old male who came to our hospital with a chief complaint of pain and swelling of the left side of his jaw. Computed tomography revealed a mass in his left gingiva but no bone destruction. No lesions were observed at any other sites, and an incisional biopsy was performed on the gingival mass on the left side. Histologically, the mass was a diffuse large B-cell lymphoma (DLBCL), and it was CD20-positive, and CD5-negative, CD10-negative, surface immunoglobulin-negative, and Epstein-Barr virus-encoded RNA (EBER)-negative. A serum Human immunodeficiency virus (HIV)-antibody test was negative. A complete remission was achieved after 6 courses of systemic combination chemotherapy, and the complete remission has been maintained for approximately 3 years. According to the literature, primary gingival DLBCL have a high Ki-67-positive rate and many of the cases are stage I and international prognostic index low-risk. However, HIV patients have a high EBER-positive rate and a high risk of developing a CD20-negative, CD138-positive plasmablastic lymphoma, and they have a poor prognosis. By contrast, limited-stage primary gingival lymphomas whose data can be used have been rare in human immunodeficiency virus-negative patients, and only 12 cases, including our own, have ever been reported. Many of the patients have been around 65 years of age, and all of the cases have been CD20-positive, CD138-negative DLBCLs, and the CD5-negative, Epstein-Barr virus-positive rate has been low, with most cases having been non-germinal-center B-cell-like. The prognosis for relapse-free survival has been favorable.

Interleukin-4 receptor α (IL-4Rα) is highly expressed on the surface of various human solid tumors including head and neck squamous cell carcinoma (HNSCC). We designed a novel IL-4Rα-lytic hybrid peptide composed of a binding peptide to IL-4Rα and a cell-lytic peptide. In the present study, we evaluated the antitumor activity of the IL-4Rα-lytic hybrid peptide as a novel molecular-targeted therapy in HNSCC. Immunoblot analysis revealed that IL-4Rα was expressed in all tested HNSCC cell lines (HSC-2, HSC-3, HSC-4, Ca9-22 and OSC-19), but not in a human normal keratinocyte (HaCaT) cell line. Immunohistochemical expression levels of IL-4Rα in HNSCC tissues were higher compared to those in normal epithelial tissue. The IL-4Rα-lytic hybrid peptide showed cytotoxic activity in all five cancer cell lines with a concentration that killed 50% of all cells (IC50) as low as 10 µM. HaCaT cells were less sensitive to this peptide with an IC50 of >30 µM. In addition, intratumoral administration of IL-4Rα-lytic hybrid peptide significantly inhibited tumor growth in a xenograft model of human HNSCC in vivo. These results indicate that the IL-4Rα-lytic hybrid peptide may serve as a potent agent to provide a novel therapy for patients with HNSCC.

Central giant cell granuloma (CGCG) is a benign jaw lesion predominantly found in the mandible of young female patients with a variable clinical behavior. Although surgical management is regarded as the main treatment modality for this lesion, the use of intralesional injections of steroids has been recently advocated for its treatment. In addition to this conservative management, the use of fine needle aspiration cytology (FNAC) for diagnosing CGCGs has been proven a safe and efficient approach, especially useful in cases with lesions located in esthetic regions. Herein, it is described a case of CGCG extending to the overlying gingiva of a 15-year-old male patient diagnosed by FNAC and subsequently treated with intralesional injections of a solution of triamcinolone acetonide and ethanolamine oleate that led to an important clinical remission, allowing a more conservative surgical procedure for preservation of gingival esthetics. Therefore, both procedures can be considered as management options for CGCG of the jaws.

Lymphomatoid granulomatosis (LYG) represents a B cell lymphoproliferative disorder that appears to be driven by infection of the lesional cells by Epstein-Barr virus (EBV). Although not a common condition, the overwhelming majority of cases affect the lungs and mediastinal lymph nodes. Oral mucosal involvement has been documented in only one other report. We describe an 82-year-old man who developed a chronic oral ulcer following extraction of a mandibular molar tooth. Biopsy of the ulcer identified large atypical mononuclear cells that had a B cell immunophenotype and were associated with the walls of several arterioles in the sample. In situ probes for EBV-encoded small RNA showed prominent labeling of these large cells, suggesting the possibility of LYG. Imaging studies identified mediastinal and hilar lymphadenopathy on CT imaging, while PET scans showed hypermetabolic activity in the lymph nodes as well as the left mandible. Based on these findings, a diagnosis of LYG was made and the patient was treated with rituximab, an anti-CD20 monoclonal antibody, combined with a chemotherapeutic regimen consisting of etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin. After three cycles of therapy, the oral ulcer resolved significantly, as well as the areas of hypermetabolic nodal activity. Remission continued for 3 years, however the patient eventually developed non-small cell carcinoma of the lung and expired as a result of that tumor.

Angiosarcoma is a rare and highly malignant mesenchymal tumor. Similar to other soft tissue sarcomas, it may arise in any organ, although it occurs more frequently within skin structures like the scalp. Angiosarcoma has a characteristic pattern of local and distant relapse involving primary site, regional lymph nodes, and lung. Patients affected by unresectable relapses or metastases have a dismal prognosis with a median overall survival of less than 9 months. We present the case of a 74-year-old woman who previously underwent total mastectomy for a radiotherapy-induced angiosarcoma of the breast. She subsequently developed a rapidly growing gingival tumor lesion that was in fact a unique distant metastasis of her angiosarcoma. In general, surgery is the mainstay of angiosarcoma treatment, and even metastases are aggressively resected whenever feasible. We describe the successful multidisciplinary treatment that avoided a likely mutilating surgery and review the literature regarding primary and metastatic gingival angiosarcoma.

When treating head and neck cancer of an advanced stage, additional therapy modalities are often combined with surgery. This sets new challenges for the reconstructive surgery, especially after segmental mandibulectomy. There is continuous discussion considering the optimal timing of the surgery with relation to other treatment methods such as radiation therapy and chemotherapy. In this work, we have analyzed a series of 10 patients treated with segmental mandibulectomy and preoperative irradiation or chemoradiation in our institute between 1999 and 2006. Surgery was scheduled within 5 weeks from the radiation therapy. 9 out of 10 reconstruction flaps were vital at the last follow-up. In general the outcome of these patients was consistent with the results published earlier by other institutes using postoperative irradiation or chemoradiation. We conclude that preoperative irradiation does not have negative impact on microvascular reconstruction with free bone flap and this procedure offers an equal option for the treatment of these patients.

Kaposi's sarcoma is a common malignancy associated with HIV/AIDS. Herein, we describe the case of a 26-year-old man who presented with bilateral neck and inguinal lymphadenopathy, a massive tumor on the gum, and a nodule over the left eye. A series of tests, including tumor biopsies, were performed, and disseminated Kaposi's sarcoma with human herpesvirus 8 infection was diagnosed. To test for HIV, we used enzyme-linked immunosorbent assay and real-time polymerase chain reaction, but the results were negative. The patient was treated by biweekly intravenous infusion of pegylated liposomal doxorubicin (25 mg/m(2)), and this treatment resulted in a partial response., (Copyright © 2011. Published by Elsevier B.V.)

Previous investigations have shown that areca nut extracts (ANE) or arecoline (ARE) causes DNA damage, which in turn contributes to oral cell carcinogenesis. To understand the role of microRNA (miRNA) in ANE-associated carcinogenesis, miRNA expression profile was examined in ANE-treated normal human oral fibroblasts. Among the miRNAs changed by ANE exposure, we found that ANE-induced miR-23a overexpression was correlated with an increase of γ-H2AX, a DNA damage marker. In addition, DNA double-strand breaks (DSB) repair that was determined by an in vivo plasmid-based assay was reduced in ANE-treated or miR-23a-overexpressed cells, suggesting the role of miR-23a in DSB repair. FANCG is one of Fanconi anemia susceptibility genes that participate in DSB repair pathway to prevent chromosomal aberrations. FANCG was predicted as a candidate target of miR-23a by TargetScan algorithm. This was confirmed by ectopic overexpression or knockdown of miR-23a. The correlation between miR-23a overexpression and areca nut-chewing habit could also be found in oral cancer patients. Finally, we showed that ANE-induced/ARE-induced miRNAs were significantly associated with the functional categories of "genetic disorders" and "cancer" using network-based analyses. In conclusion, our data showed for the first time that ANE-induced miR-23a was correlated with a reduced FANCG expression and DSB repair, which might contribute to ANE-associated human malignancies.

The occurrence of angiosarcoma in the oral cavity is extremely rare, and optimal management of this tumor is undefined. These tumors are aggressive, with a high propensity for local recurrence. We present here a case of primary gingival angiosarcoma successfully treated by intra-arterial chemotherapy concurrent with radiation therapy. A 69-year-old female with a primary angiosarcoma in the right maxillary gingiva was admitted to our hospital. The diagnosis of angiosarcoma was established by immunohistochemistry. The patient refused surgical treatment, and so intra-arterial cisplatin and concurrent radiation were given. The gingival tumor disappeared after completion of the therapeutic regimen. However, the patient died 8 months after initial treatment because of multiple lung metastases. Locoregional control was achieved up to her death. To our knowledge, this is the first report of this treatment for angiosarcoma of the oral cavity.

PERIOD (PER) proteins are transcriptional regulators that are involved in circadian rhythms, sleep homeostasis, cell proliferation and tumour progression. We previously showed that the expression of PER1 was related to the regulation of apoptosis in human pancreatic cancer and hepatocellular carcinoma cells. However, the significance of PER in oral cancer has not been reported, and the detailed molecular mechanisms by which anti-tumour drug induces apoptosis in gingival cancer cells are not well understood. We examined whether PER1 and PER3 are involved in the regulation of apoptosis in human gingival cancer CA9-22 cells. The expression of PER1 and PER3 was upregulated and downregulated, respectively, by cis-diamminedichloroplatinum (II) (cisplatin: CDDP) treatment in CA9-22 cells, whereas CDDP treatment had little effects on the expression of PER1 and PER3 in human gingival fibroblasts (HGF-1). We found that short interference RNA (siRNA)-mediated knockdown of PER1 enhanced apoptosis of CA9-22 cells, and that PER1 regulated the amount of Bim, an apoptosis-related molecule. On the other hand, PER3 knockdown had an inhibitory effect on the apoptosis of CA9-22 cells induced by CDDP treatment. These results suggest that the alternation of expression of PER1 and PER3 was related to the apoptosis of CA9-22 cells. Furthermore, PER1 was intensely stained in the gingival cancer tissues, whereas PER3 was significantly stained in the non-tumour tissues by immunohistochemistry. These findings suggest that PER1 and PER3 have anti-apoptotic and pro-apoptotic effects in human gingival cancer CA9-22 cells, respectively. The balance of PER1 and PER3 may modulate apoptotic reactions in gingival cancer cells., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Choriocarcinoma is a rare neoplasia with a tendency of distant metastasis although highly sensitive to chemotherapy renders a good prognosis and outcome. Lungs, liver and cerebral metastasis are commonly implicated with maxillofacial region rarely involved. We illustrate a case of overwhelming metastatic choriocarcinoma to lungs, liver, brain and to the extreme of gum metastasis. Decompressive craniectomy for intracranial bleeding, multiple transfusions to correct anaemia and coagulopathy were done before high-risk-regime chemotherapy. Despite this, due to fulminant multi-organs involvement she finally succumbed to death. In conclusion, gum bleeding in choriocarcinoma may suggest metastasis and poor prognosis., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We report a case of advanced upper gingival carcinoma with a contralateral metastatic lymph node invading the maxillary sinus (T4aN2cM0). An 83-year-old man was treated concurrently with chemoradiotherapy and S-1. S-1 (80 mg/body/day) was administered for 2 weeks followed by a 1-week rest period as one course. Radiation therapy involved a total of 60 Gy (2 Gy/day; 5 days/week). There were side effects of mild leucopenia and a grade 2 stomatitis. After the completion of 2 courses and radiation therapy, the primary tumor disappeared, and the patient achieved a pathologically complete response. The metastatic lymph node also completely disappeared. S-1 was then administered in the same regimen for 1 year. Neither local recurrence nor distant metastasis has been detected 2 years after the completion of the concurrent chemoradiotherapy with S-1.

We report a 53-year-old female patient with an unresectable metastasis to the supraclavicular lymph node from a primary gingival carcinoma of the mandible. The patient had a history of tongue carcinoma and had undergone a radical neck dissection for the treatment of gingival carcinoma. She underwent combined chemotherapy consisting of S-1 (80 mg on days 1-14, followed by a 7-day rest), docetaxel (35mg/m2 by intravenous infusion on days 1 and 8), and CDDP (10mg/m2 by intravenous infusion on days 1 and 8) every 3 weeks. After three courses of the above chemotherapy regimen, a computerized tomography examination revealed a complete response. The patient did not experience any severe side effects during the course of chemotherapy. Combined S-1, docetaxel, and CDDP chemotherapy can thus be effective for unresectable recurrences of oral cancer in lymph nodes.

Introduction: The association between malignant tumors and HIV infection is well known. We report a rare case of gingival granulocytic sarcoma (GS) associated to HIV infection., Observation: A 31 year-old HIV patient consulted for left maxillary tumefaction. His viral load was high (40,112 copies/ml) and CD4 count low (287cells/mm(3)). After biopsy-exeresis, histology and an immunohistochemical study confirmed the diagnosis of GS. Chemotherapy similar to that of acute myeloid leukemia (AML) completed the treatment. The remission was complete at 5 years., Discussion: Only one case of intra-oral GS associated to HIV infection has been reported so far. The clinical and radiological presentation is unspecific. Histology proves the diagnosis. The treatment is comparable to that of AML. The prognosis is usually bad., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

Acanthomatous ameloblastoma (AA) is a benign gingival tumour that often invades bone. This retrospective study evaluated the efficacy of intralesional (IL) bleomycin as a treatment for AA. Six dogs received weekly or bimonthly IL bleomycin injections (dose range, 10-20 U m(-2)). A seventh dog presented with advanced, nonresectable AA was treated palliatively. One to sixteen treatments were administered (median, 5). Six of the seven dogs had a complete response within 4 months from initial IL injection (median, 1.5 months), whereas the palliative case had approximately 25% decrease in tumour volume 14 days from initial injection. Local recurrence was not observed during the study period, with a median follow-up time of 842 days. Adverse effects were limited to wound formation with bone exposure (n = 4), mild tissue reactions (n = 3), local swelling (n = 2) and local infection (n = 1). The conclusions of this study show IL bleomycin is an effective treatment for canines with AA.

Angiosarcoma is a rare malignant neoplasm and primary angiosarcoma is extremely rare. This study reports clinico-pathological features and CT image finding of a case of primary angiosarcoma in the upper gingival and a review of previously reported cases of primary gingival angiosarcomas including the present case.

Gingival epulis represents a family of benign tumors and tumorlike masses of the gingiva. A spectrum of inflammatory and other reactive changes can be observed pathologically as granulation, fibrous or vascular tissue. It may occur at any age, but most commonly found in patients at their twenties and sixties. Women are more frequently affected than men. Surgical excision or removal is the treatment of choice, and wider resection including extraction of the involved teeth and adjacent tissues is often required in order to prevent recurrence. However, wider resection may result in cosmetic and functional problems. Epulis bears some similarities with hemangioma both clinically and histopathologically. Therefore, we hypothesize that intralesional injection of Pingyangmycin may be a safe and effective treatment for epulis. The efficacy of this treatment modality is worthy of further investigation.

Burkitt lymphoma (BL) is an aggressive form of non-Hodgkin B-cell lymphoma with 3 variants: endemic, sporadic, and immunodeficiency-associated types. The sporadic form, most commonly involving the abdomen and ileocecal region, presents as an abdominal mass, rarely presenting in the orofacial region. A 36-year-old Indian female presented to the Hospital of the University of Pennsylvania for evaluation of a persistent intraoral swelling ulceration of the lower right mandibular alveolar ridge with minimal bony invasion. Progressive systemic symptoms of fatigue, weakness, and fever developed without resolution following treatment for a presumed odontogenic infection in the 4 weeks before presentation. An incisional biopsy revealed a diffuse proliferation of intermediate- to large-sized lymphocytes with multiple small peripheral nucleoli, scant cytoplasm, and nuclear pleomorphism. Nearly all cells displayed Ki67 expression. A final diagnosis of BL was rendered following confirmation of a cMYC translocation by fluorescence in situ hybridization. This article presents a case of the sporadic form of BL with atypical presentation clinically and morphologically, primarily involving the oral soft tissue.

Background: Non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of lymphoproliferative malignancies that may be associated with acquired immunodeficiency syndrome (AIDS). NHL can disseminate to extranodal sites; however, its dissemination to the jaws and mouth is not common. This report presents and discusses two unusual cases of gingival primary extranodal non-Hodgkin's lymphoma (PE-NHL) as the first manifestation of AIDS., Methods: Two males presented with asymptomatic gingival swelling. They were examined clinically. Biopsies of the gingival tissue were evaluated using routine histologic techniques and immunohistochemistry. The patients were tested for human immunodeficiency virus (HIV) infection., Results: The clinicopathological evaluation and the serological HIV examination of the patients led us to the final diagnosis of gingival PE-NHL as the first manifestation of AIDS. Both patients were referred to an oncologist and to an infectious disease specialist and were given antineoplastic chemotherapy and highly active antiretroviral therapy. Only one patient presented a favorable clinical evolution., Conclusion: The present case reports have important clinical implications; the two unusual presentations of gingival PE-NHL contribute to information about the differential diagnosis of rapidly progressing gingival swelling.

Severe advanced head and neck carcinoma which can not be removed via surgical procedure combined with a large lymph node metastasis has a poor prognosis. We administered concurrent chemoradiotherapy with S-1 for a lower gingival carcinoma. As a direct result, we discovered that the treatment greatly reduced the size of tumor, and we consider that this treatment prolonged the patient.s life. The treatment results suggest that the so-called dormancy state of the tumor was continued. In this case study, radiotherapy with S-1 showed a highly effective response from the viewpoint of QOL improvement.

Coupling anticancer drugs to synthetic polymers is a promising approach to improve the efficacy and reduce the side effects of these drugs. The pH-activated polymer has been demonstrated to be a successful drug delivery vehicle system, whereas the photochemical internalization (PCI) was invented for site-specific delivery of membrane impermeable macromolecules from endocytic vesicles into the cytosol. In this study, doxorubicin (DOX) was conjugated to polyamidoamine (PAMAM) dendrimers via pH-sensitive and -insensitive linkers and was combined with different PCI strategies to evaluate the cytotoxic effects. Our results showed that both PCI strategies significantly improved the cytotoxicity of free DOX on Ca9-22 cells at higher concentrations. The 'light after' PCI treatment was efficient in releasing DOX from the PAMAM-hyd-DOX conjugates, resulted in more nuclear accumulation of DOX and more cell death through synergistic effects. On the other hand, antagonism was observed when 'light before' PCI combined with PAMAM-hyd-DOX conjugate. The distribution of PAMAM-amide-DOX was mainly cytosolic with or without PCI treatments. Both PCI strategies failed to improve the cytotoxicity of PAMAM-amide-DOX conjugates. Our results provide invaluable information in the future design of drug-polymer complexes for multi-modality cancer treatments.