Oral Mucosa Of Patients Research Articles

Immediate Analgesic Effect of 8% Lidocaine Applied to the Oral Mucosa in Patients with Trigeminal Neuralgia

Trigeminal nerve block is widely used for trigeminal neuralgia (TN), though with much painful procedure and potential serious complications. The pain of TN occurs most frequently in the second and the third divisions of the trigeminal nerve, which are distributed in intraoral mucous membrane as well as face skin. Here, we examined the response to intraoral application of 8% lidocaine (LDC) in patients with oral TN pain in a double-blind, placebo (PBO)-controlled crossover study. Twenty-four outpatients with oral TN pain were randomized to receive intraoral application of either 8% LDC or saline PBO to the painful area. Following 7-days period, patients were crossed over to receive the alternative treatment. The pain was assessed with a numerical rating scale (NRS) before and 15 minutes after treatment. Patients used a descriptive scale to grade pain outcome and were asked to note any recurrence and the latency for recurrence after therapy. Intraoral LDC, but not PBO, significantly decreased the NRS from 5 (4, 8) (median [25, 75 percentiles]) to 1 (0, 4) (P = 0.001). Of the 24 patients, 19 described marked or moderate relief of pain after LDC but only three described the same after PBO application. The effect of LDC and PBO persisted for 2.8 (0.3, 3.0) and 0 (0, 0) hours, respectively. Intraoral application of 8% LDC produced prompt analgesia without serious side effects in patients with TN who presented with severe intraoral pain.

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Investigation of contact allergy to dental materials by patch testing.

Background:Dental products are widely used by patients and dental personnel alike and may cause problems for both. Dental materials could cause contact allergy with varying manifestations such as burning, pain, stomatitis, cheilitis, ulcers, lichenoid reactions localized to the oral mucosa in patients, and hand dermatitis in dental personnel. Patch testing with the dental series comprising commonly used materials can be used to detect contact allergies to dental materials.Aim:This study aimed to identify contact allergy among patients who have oral mucosal lesions after dental treatment and among dental personnel who came in contact with these materials.Materials and Methods:Twenty patients who had undergone dental procedures with symptoms of oral lichen planus, oral stomatitis, burning mouth, and recurrent aphthosis, were included in the study. Dental personnel with history of hand dermatitis were also included in the study. Patch testing was performed using Chemotechnique Dental Series and results interpreted as recommended by the International Contact Dermatitis Research Group (ICDRG).Results:Out of 13 patients who had undergone dental treatment/with oral symptoms, six patients with stomatitis, lichenoid lesions, and oral ulcers showed positive patch tests to a variety of dental materials, seven patients with ulcers had negative patch tests, seven dental personnel with hand dermatitis showed multiple allergies to various dental materials, and most had multiple positivities.Conclusion:The patch test is a useful, simple, noninvasive method to detect contact allergies among patients and among dental personnel dealing with these products. Long term studies are necessary to establish the relevance of these positive patch tests by eliminating the allergic substances, identifying clinical improvement, and substituting with nonallergenic materials.

Langerhans Cells in Oral Mucosa from Patients with Acquired Immunodeficiency Syndrome

Background: Oral manifestations are common in patients with acquired immunodeficiency syndrome (AIDS). Objectives: Compare the number of Langerhans cells and intensity of anti-CD1a expression in the mucous membranes of the oral cavities of the same patients with AIDS and HIV-negative individuals. Materials and methods: Sixteen autopsied adults were investigated, including 11 with AIDS, and 5 HIV negative. We identified Langerhans cells in three oral regions of the same subject using an anti-CD1a antibody and quantified them in cells/mm2. Were applied normality tests and Mann-Whitney. Results: The numbers of Langerhans cells in the AIDS patient group were less than in the control group, but didn't differ significantly between the two groups. The intensity of anti-CD1a expression was lower in patients with AIDS. Of the three areas, the greater intensity of CD1a cells were found in the masticatory mucosa. Discussion: We observed a reduction of Langerhans cells in the oral mucosa of patients with AIDS and this is the first report, to our knowledge, that evaluate three different oral mucosal membranes in the same subject. Conclusion: Our study suggests that AIDS influences on the depletion of Langerhans’ cells, particularly in the specialized mucosa, and the intensity of expression of anti- CD1a regardless of the type of oral mucosa.

Familial Mastocytosis: Identification Of KIT K509I Mutation and Its In Vitro Sensitivity To Imatinib, Dasatinib and PKC412

BackgroundMast cell diseases are myeloproliferative neoplasms characterized by an abnormal proliferation and accumulation of mast cells in different tissues. The clinical presentation of mastocytosis is heterogeneous, ranging from skin-limited disease to more aggressive variants that may be associated with multiorgan dysfunction/failure and shortened survival. In a relatively high proportion of cases, the clonal nature of the disease can be established on the basis of the demonstration of gain-of-function mutations involving the tyrosine kinase (TK) domain of KIT in skin lesions and BM cells and by the factor-independent proliferation and transforming abilities of these mutations. The tyrosine kinase inhibitor Imatinib is a treatment available for mastocytosis patients; however, some KIT mutations, specially KIT D816V, confer resistance to this drug. AimsTo characterize the clinical phenotype and molecular mutations of 2 relatives with diagnosis of systemic mastocytosis (WHO 2008). We also aimed to test the in vitro sensitivity of primary bone marrow (BM) cells from both patients to tyrosine kinase inhibitors. Patients and methodsFour individuals were included in the study; two patients (case 1 [mother], and case 2 [daughter]), and the parents of case 1. DNA samples were obtained from total BM cells, CD3+ BM cells and oral mucosa of patients, and from peripheral blood of all individuals. KIT (exons 1 to 21) was submitted for Sanger sequencing analysis. Primary bone marrow cells (5X104) from the 2 patients were cultured and treated with Imatinib (5uM), Dasatinib (80nM) and PKC 412 (100nM) or with vehicle only (control cells) and submitted for proliferation (MTT) and apoptosis assays (Annexin-V/PI) at days 4, 8 and 12 of culture. ResultsCase 1 was a 33 year-old woman with a chronic history of pruritic skin rash who was referred to our outpatient service for evaluation of massive splenomegaly (25 centimeters in length) and pancytopenia. She had neither comorbidities nor any familial history of hematological malignancies. The patient had no siblings and had only one daughter (case 2). At biopsy, she showed extensive skin and bone marrow infiltration by mast cells. During follow up, the patient presented with spontaneous splenic rupture and had to undergo splenectomy, which led to the resolution of pancytopenia. She was diagnosed with Aggressive Systemic Mastocytosis. Her daughter (case 2), a 17 year-old woman, was also evaluated for an insidious history of diffuse skin rash. Skin and bone marrow biopsies showed massive infiltration by atypical mast cells and a diagnosis of Indolent Systemic Mastocytosis was made. The rare KIT K509I mutation was found in all DNA samples obtained from both patients, but not from the parents of case 1. This suggests that the KIT K509I was a germ line mutation acquired de novo by patient 1 that was subsequently transmitted to her daughter (patient 2). In vitro treatment of primary bone marrow cells harboring the KIT K509I mutation from patients 1 and 2 resulted in variable clinical response rates according to the drug used and the treatment duration. Imatinib treatment resulted in a significant reduction in proliferation (days 4, 8 and 12 of culture) and an increase in apoptosis (days 8 and 12) in cases 1 and 2 (all p≤0.03). Although Dasatinib resulted in decreased proliferation in both patients at day 12 (all p≤0.008), a significantly higher apoptosis ratio was observed only for patient 1 at day 12 of culture (p=0.03). PKC412 had a negative effect over cell growth in patient 1 (days 4 and 8) and in patient 2 (day 4) (all p≤0.03); however, no effect in apoptosis ratio was seen. ConclusionsWe herein provide a report of a KIT K509I mutation in familial mastocytosis. This mutation has been previously described in the literature in one case of familial mastocytosis. Although rare, the screening for KIT K509I mutation should be considered in all cases of familial mastocytosis. Based on in vitro studies, mastocytosis patients harboring the KIT K509I mutation could benefit from treatment with Imatinib, Dasatinib and PKC 412. However, Imatinib may be more effective in inducing neoplastic mast cells apoptosis. Both patients described were started on Imatinib in June 2013. Disclosures:No relevant conflicts of interest to declare.

Oral HPV infection and persistence in patients with head and neck cancer

To investigate the presence and persistence of human papillomavirus (HPV) infection in the oral mucosa of patients with head and neck squamous cell carcinoma (HNSCC), and its correlation with prognosis. HPV infection was characterized in tumors and pre and posttreatment oral scrapings in 51 patients with HNSCC and matched controls using the SPF10 LiPA Extra assay. p16INK4A immunostain and in situ hybridization for high-risk HPV genotypes recognized transcriptionally active infection in tumor samples. The risk of infection was compared in patients and controls. The association of pretreatment HPV status with recurrence and survival and with posttreatment HPV persistence was assessed. Oral HPV infection risk was significantly higher in patients with HNSCC than in controls (P < .001). Oral HPV infection was associated with infection in the first posttreatment scrapings (P = .015), but did not affect recurrence or prognosis. Oral HPV infection is frequent in patients with HNSCC and has no prognostic implications, suggesting that posttreatment polymerase chain reaction monitoring on oral cells is not effective to monitor patient recurrence risk.

Patterns of oral mucosa lesions in patients with epidermolysis bullosa: comparison and agreement between oral medicine and dermatology

The oral mucosa in patients with epidermolysis bullosa (EB) can be affected with different lesions and degrees of severity. However, patterns of oral lesions in distinct types of EB are still unclear. The purpose of this study was to determine the frequency and distribution of four types of lesions (erythema, erosion, atrophy, and blister) for each oral site and to calculate the interobserver reliability for each type of lesion in each site. Ninety-two patients with different EB types were assessed independently by an oral medicine specialist and a dermatologist. The degree of agreement was calculated by the intraclass correlation coefficient (ICC). The most affected oral site was the tongue, with the most frequent lesion being erythema and atrophy [54(58.7%) patients] for the oral medicine specialist and erosion [54(58.7%) patients] for the dermatologist. Patients with recessive dystrophic EB-severe generalized (RDEB-sev gen) showed the highest mean of sites involved by each lesion for both oral medicine and dermatology. The interobserver reliability on the total of lesions was excellent on only 3 sites: lower lip (ICC: 0.89; 95%CI:0.83-0.92), hard palate (ICC:0.85; 95%CI:0.72-0.91), and tongue (ICC:0.89; 95%CI:0.84-0.92), whereas the interobserver reliability calculated for each single oral lesion showed a lower agreement. Total distribution of sites involved by four types of lesions was higher in RDEB-sev gen than in the rest of EB types, with a predominance of erythema followed by erosion. The agreement on the type of lesion was found to be poor-moderate for many oral sites.

Heterotopic gastrointestinal mucosa in the oral cavity of adults

Heterotopic gastrointestinal mucosa (HGM) is a rare entity observed in the head and neck region and occurs more frequently in male infants and children. The floor of the mouth and anterior aspects of the tongue are the most commonly affected sites. Histologically, HGM resembles gastric, intestinal or colonic mucosa with areas of squamous epithelium, which can be cystic or solid. In the current report, 2 cases of HGM affecting the oral mucosa in patients over 35years of age are presented, and one of these cases presented 2 nodules in different locations. Both cases represented solid lesions instead of the more common cystic presentation showing gastric glandular-type tissue that was lined with pseudostratified columnar epithelium containing crypts and fundic glands. Immunohistochemical analysis revealed positive expression of cytokeratins 7, 8 and 18 and smooth muscle actin (SMA). In both cases, the final diagnosis was HGM, and conservative surgical excision was performed.

Histology of the Oral Mucosa in Patients With BRONJ at III Stage: A Microscopic Study Proves the Unsuitability of Local Mucosal Flaps

BackgroundBisphosphonate Osteonecrosis of the Jaw (BRONJ) is a newly recognized condition reported in patients treated with aminobisphosphonates (BF). BRONJ is defined as the presence of exposed necrotic alveolar bone that does not resolve over a period of 8 weeks in a patient taking bisphosphonates who has not had radiotherapy to the jaw. Treatment protocols have been outlined, but trials and outcomes of treatment and long-term follow-up data are not yet available. In 2004 an expert panel outlined recommendations for the management of bisphosphonate-associated osteonecrosis of the jaws. Through the histological study of the oral mucosa over the bone necrosis and around the osteonecrosis area in 8 patients affected by BRONJ at III stage, the authors highlight the inappropriateness of the local mucosal flaps to cover the losses of substance of the jaw, BF-related.MethodsMucosa tissue was taken from 8 patients, affected by BRONJ, III stage. The samples taken from the mucosa around and over the osteonecrosis area were fixed with formalin and an ematossilina-eosin dichromatic coloring was carried out.ResultsThe samples of mucosa showed pathognomonic signs of cell suffering that prove that in these patients using local mucosa flaps is inappropriate.ConclusionsThe authors suggest that only a well vascularized flap as free flap must be used to cover the osteonecrosis area in patients with BRONJ stage III. Because of the structural instability of the mucosa in patients suffering of osteonecrosis Bf related the local flaps are prone to ulceration and to relapse.

Cytological picture of the oral mucosa in patients with gastric and colon cancer

The incidence of malignant gastrointestinal cancers in Poland has been constantly growing, which has led to an intensification of the search for new markers of the early clinical stage of this disease. The oral cavity,as the first part of the gastrointestinal tract, has a very important role. The oral cavity presents symptoms of both typically stomatological and systemic diseases. Oral cancers, benign or malignant, may originate and grow in any of the tissues of the mouth, and within this small area they may be of varied clinical, histological and biological features. These can be lesions typically observed in the oral cavity, but also characteristic of cases where the symptoms occur both in the mouth and in other body parts. The aim of this study was to present a cytological picture of the oral mucosa in patients with gastric and colon cancer and to compare the cytological picture with that obtained from a group of patients with no cancer, using the Papanicolaou classification and the Bethesda system. The study was conducted in 126 patients treated surgically in the II General and Gastroenterological Surgery Clinic between 2006 and 2008. All patients were divided into two groups based on the type of lesions. In both of the studied groups, more than half of the patients did not present any abnormalities in the mucosa of the mouth, lips and cheeks in the physical examination. None of the patients had erosion, ulceration or lesions typical of leukoplakia or lichen planus. No malignant cells were detected in either of the studied groups, and there were no well-defined lesions found in the oral cavity that would distinguish the patients with gastrointestinal cancer.

Cytological picture of the oral mucosa in patients with gastric and colon cancer

The incidence of malignant gastrointestinal cancers in Poland has been constantly growing, which has led to an intensification of the search for new markers of the early clinical stage of this disease. The oral cavity, as the first part of the gastrointestinal tract, has a very important role. The oral cavity presents symptoms of both typically stomatological and systemic diseases. Oral cancers, benign or malignant, may originate and grow in any of the tissues of the mouth, and within this small area they may be of varied clinical, histological and biological features. These can be lesions typically observed in the oral cavity, but also characteristic of cases where the symptoms occur both in the mouth and in other body parts. The aim of this study was to present a cytological picture of the oral mucosa in patients with gastric and colon cancer and to compare the cytological picture with that obtained from a group of patients with no cancer, using the Papanicolaou classification and the Bethesda system. The study was conducted in 126 patients treated surgically in the II General and Gastroenterological Surgery Clinic between 2006 and 2008. All patients were divided into two groups based on the type of lesions. In both of the studied groups, more than half of the patients did not present any abnormalities in the mucosa of the mouth, lips and cheeks in the physical examination. None of the patients had erosion, ulceration or lesions typical of leukoplakia or lichen planus. No malignant cells were detected in either of the studied groups, and there were no well-defined lesions found in the oral cavity that would distinguish the patients with gastrointestinal cancer. (

Protecting the oral mucosa in patients with oral tongue squamous cell carcinoma treated postoperatively with intensity‐modulated radiotherapy: A randomized study

Is the severity of acute oral mucositis in patients who receive postoperative intensity-modulated radiotherapy (PO-IMRT) for oral tongue squamous cell carcinoma (SCC) reduced by sparing the oral mucosa outside of the planning target volume (PTV)? Prospective, randomized trial. Forty-eight patients with oral tongue SCC who received PO-IMRT at our institution were randomized to two groups: the oral-sparing (OR-SP) group and oral-unsparing (OR-USP) group. For the OR-SP group (n = 24), the oral mucosa outside of the PTV was spared. Furthermore, the mucosa including the bilateral cheeks, upper lip, and lower lip was defined as the united site and given <32 Gy. For the OR-USP group (n = 24), none of the oral mucosa was protected. The severity of clinical acute mucositis in each patient was assessed weekly during PO-IMRT until completely healed. Oral mucositis was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Dosimetry and therapeutic measures related to acute mucositis between the two groups were compared. During PO-IMRT, no patient experienced grade 4+ acute mucositis in any oral site. Compared to the OR-USP group, there was less grade 2 and 3 mucositis in the united site of the OR-SP group (0% and 25% vs. 45.8% and 54.2%, respectively; P = .000). Also, the mean dose to the united site was significantly lower with OR-SP compared to OR-USP (41.8 ± 7.4 Gy vs. 58.8 ± 2.2 Gy; P = .000). The OR-SP group was associated with significant reductions in the use of analgesics (P = .043) and intravenous antibiotics (P = .039). No recurrences were detected in the vicinity of the spared oral mucosa (the united site) during a median follow-up time of 30 months. OR-SP PO-IMRT for patients with oral tongue SCC resulted in a significant decrease in the severity of acute mucositis and improved quality of life. The sparing of the oral mucosa outside of the PTV is safe and does not compromise oncologic outcomes.

Heat-shock protein 60 kDa and atherogenic dyslipidemia in patients with untreated mild periodontitis: a pilot study

Identification of predictors of cardiovascular risk can help in the prevention of pathologic episodes and the management of patients at all stages of illness. Here, we investigated the relationships between serum levels of Hsp60 and dyslipidemia in patients with periodontitis by performing a cross-sectional study of 22 patients with mild periodontitis without any prior treatment for it (i.e., drug naïve) and 22 healthy controls, matched for age and body mass index (BMI). All subjects were evaluated for periodontal status, gingival inflammation, and oral hygiene. Levels of circulating Hsp60, C-reactive protein (CRP), and plasma lipids were measured, and small, dense low-density lipoproteins (LDL) were indirectly assessed by determining the triglycerides/high-density lipoproteins (HDL) cholesterol ratio. We also assessed by immunohistochemistry Hsp60 levels in oral mucosa of patients and controls. No difference was found in CRP levels or plasma lipids between the two groups, but subjects with periodontitis showed, in comparison to controls, higher levels of small, dense LDL (p = 0.0355) and circulating Hsp60 concentrations (p < 0.0001). However, levels of mucosal Hsp60 did not change significantly between groups. Correlation analysis revealed that circulating Hsp60 inversely correlated with HDL-cholesterol (r = -0.589, p = 0.0039), and positively with triglycerides (r = +0.877, p < 0.0001), and small, dense LDL (r = +0.925, p < 0.0001). Serum Hsp60 significantly correlated with the degree of periodontal disease (r = +0.403, p = 0.0434). In brief, untreated patients with mild periodontitis had increased small, dense LDL and serum Hsp60 concentrations, in comparison to age- and BMI-matched controls and both parameters showed a strong positive correlation. Our data indicate that atherogenic dyslipidemia and elevated circulating Hsp60 tend to be linked and associated to periodontal pathology. Thus, the road is open to investigate the potential value of elevated levels of circulating Hsp60 as predictor of risk for cardiovascular disease when associated to dyslipidemia in periodontitis patients.

Scanning electron microscopy study on mandibular human bone and immunofluorescence study on oral mucosa in patients treated with bisphosphonates

Bisphosphonates are stable analogues of pyrophosphate with a P-C-P structure and 2 side chains attached to the carbon atom. Intravenous bisphosphonates are primarily used and effective in the management of cancer-related conditions in the context of solid tumors, such as breast cancer, prostate cancer, and lung cancer. Moreover bisphosphonates are subministrated to patients with metabolic bone diseases such as osteoporosis and Paget disease. Bisphosphonate-associated osteonecrosis of the jaws (BONJ) is a really complication of intravenous bisphosphonate therapy in patients with cancer. It is common knowledge that the jaws have a greater blood supply than other bones and a fasterbone turnover rate, related both to their daily activity and presence of teeth which mandates daily bone remodeling around the periodontal ligament; moreover bisphosphonates toxicity to epithelial cells has been well documented. On this basis, the aim of this study is to evaluate the pathological changes of the mandibular bone and oral mucosa in patients treated with bisphosphonates, during osteoporosis treatment and during chemotherapy from solid cancer. In details we have analyzed, by immunohistochemical and scanning electron microscopic methods, intrasurgical biopsy of mandibular bone and of gingival mucosa in patients treated with bisphosphonates both intravenous and oral via after 24 and 36 months from assumption of drugs. Our results show in all patients great area demineralization bone mixed to normal bone, moreover in the demineralization bone it’s possible to observe numerous micro lacunae. In the correspondence samples of gingival epithelium we observe important lesions of histological structure and the disappearance of protein adhesion system cells to cells and cells to matrix. On this basis it is intriguing to speculate that the adverse effects of BP on oral epithelium may play a critical role in the initiation of BONJ an “outside-in” hypothesis.

8568 POSTER Protection of Oral Mucosa in Patients With Oral Tongue Squamous Cell Carcinoma Treated Postoperatively With Intensity Modulated Radiotherapy

8568 POSTER Protection of Oral Mucosa in Patients With Oral Tongue Squamous Cell Carcinoma Treated Postoperatively With Intensity Modulated Radiotherapy

Zmiany patologiczne na błonie śluzowej jamy ustnej w przebiegu choroby Leśniowskiego-Crohna – opis dwóch przypadków

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Ślebioda Z, Szponar E, Linke K. Pathological lesions on the oral mucosa in patients with Crohn’s disease: a report of two cases. Gastroenterology Review/Przegląd Gastroenterologiczny. 2011;6(5):334-337. doi:10.5114/pg.2011.25385. APA Ślebioda, Z., Szponar, E., & Linke, K. (2011). Pathological lesions on the oral mucosa in patients with Crohn’s disease: a report of two cases. Gastroenterology Review/Przegląd Gastroenterologiczny, 6(5), 334-337. https://doi.org/10.5114/pg.2011.25385 Chicago Ślebioda, Zuzanna, Elżbieta Szponar, and Krzysztof Linke. 2011. "Pathological lesions on the oral mucosa in patients with Crohn’s disease: a report of two cases". Gastroenterology Review/Przegląd Gastroenterologiczny 6 (5): 334-337. doi:10.5114/pg.2011.25385. Harvard Ślebioda, Z., Szponar, E., and Linke, K. (2011). Pathological lesions on the oral mucosa in patients with Crohn’s disease: a report of two cases. Gastroenterology Review/Przegląd Gastroenterologiczny, 6(5), pp.334-337. https://doi.org/10.5114/pg.2011.25385 MLA Ślebioda, Zuzanna et al. "Pathological lesions on the oral mucosa in patients with Crohn’s disease: a report of two cases." Gastroenterology Review/Przegląd Gastroenterologiczny, vol. 6, no. 5, 2011, pp. 334-337. doi:10.5114/pg.2011.25385. Vancouver Ślebioda Z, Szponar E, Linke K. Pathological lesions on the oral mucosa in patients with Crohn’s disease: a report of two cases. Gastroenterology Review/Przegląd Gastroenterologiczny. 2011;6(5):334-337. doi:10.5114/pg.2011.25385.

P7 p63, K14 and p53 expression in epithelial layers of tumor-distant oral mucosa in patients with oral squamous cell carcinoma

P7 p63, K14 and p53 expression in epithelial layers of tumor-distant oral mucosa in patients with oral squamous cell carcinoma

P8 Mutagen sensitivity and p53 in suprabasal layers of tumor-distant oral mucosa in patients with oral squamous cell carcinoma

the rest were used as test data set to valid the predicted “AminoIndex”. Results: Plasma concentrations of several amino acids were significantly changed in breast cancer patients compared to control subjects in study data set. Finally, “AminoIndex” for breast cancer composed with six amino acids (Gln, Ala, ABA, Trp, Orn, and Arg) was predicted. To evaluate the performance, the ROC curve was calculated, and this gave an AUC of ROC of 0.832 using the study data. Validation of predicted “AminoIndex” using test data set resulted same discriminating performance (AUC of ROC of 0.822), suggesting the robustness of the predicted classifier. Furthermore, predicted AminoIndex showed notably features. 1. The index could discriminate breast cancer patients in early stages. 2. The index showed higher discrimination performance than those of existing tumor markers especially in stages 0, I, and II patients. 3. The index could equally discriminate breast cancer patients of any histological types. Therefore, predicted “AminoIndex” would be suitable for screening and early detection of breast cancer patients. Conclusion and Perspectives: In this study, we demonstrated that change of plasma amino acid profile would be a helpful tool for early detection of breast cancer patients. “AminoIndex” would be useful to concentrate and inspire the candidates for further survey such as mammography. To evaluate the efficacy of this method, cohort studies are ongoing.

Microcirculation and intravascular coagulopathy in patients with severe sepsis and septic shock

Sidestream darkfield imaging (SDF) technology is a new method to visualize directly microcirculation. In this study we examined the perfusion of the oral mucosa in patients with severe sepsis and septic shock in order to evaluate the link between the severity of illness, microcirculation and intravascular coagulopathy.

TW-37, a small-molecule inhibitor of Bcl-2, mediates S-phase cell cycle arrest and suppresses head and neck tumor angiogenesis

Members of the Bcl-2 family play a major role in the pathobiology of head and neck cancer. We have shown that Bcl-2 orchestrates a cross talk between tumor cells and endothelial cells that have a direct effect on the progression of head and neck squamous cell carcinoma (HNSCC). Notably, Bcl-2 is significantly up-regulated in the tumor-associated endothelial cells compared with the endothelial cells of normal oral mucosa in patients with HNSCC. Here, we evaluated the effect of TW-37, a small-molecule inhibitor of Bcl-2, on the cell cycle and survival of endothelial cells and HNSCC and on the progression of xenografted tumors. TW-37 has an IC50 of 1.1 micromol/L for primary human endothelial cells and averaged 0.3 micromol/L for head and neck cancer cells (OSCC3, UM-SCC-1, and UM-SCC-74A). The combination of TW-37 and cisplatin showed enhanced cytotoxic effects for endothelial cells and HNSCC in vitro, compared with single drug treatment. Notably, whereas cisplatin led to an expected G2-M cell cycle arrest, TW-37 mediated an S-phase cell cycle arrest in endothelial cells and in HNSCC. In vivo, TW-37 inhibited tumor angiogenesis and induced tumor apoptosis without significant systemic toxicities. Combination of TW-37 and cisplatin enhanced the time to tumor failure (i.e., 4-fold increase in tumor volume), compared with either drug given separately. Collectively, these data reveal that therapeutic inhibition of Bcl-2 function with TW-37 is sufficient to arrest endothelial cells and HNSCC in the S phase of the cell cycle and to inhibit head and neck tumor angiogenesis.