Skeletal Divergence and Condylar Asymmetry in Patients with Temporomandibular Disorders (TMD): A Retrospective Study

Introduction. This study was aimed at evaluating the association between vertical skeletal patterns, condylar height symmetry, and temporomandibular disorders in adults. Methods. The study sample consisted of 200 patients (ages 18-30 years old) retrospectively recruited: 100 with temporomandibular disorders (TMD) and 100 without TMD (control), diagnosed by Diagnostic Criteria for the Temporomandibular Disorders (DC/TMD). For each subject, skeletal divergence was assessed on lateral cephalograms, and condylar height symmetry was evaluated by orthopantomography (Habets' method). Results. Subjects with temporomandibular disorders showed a strong association with condylar asymmetry (p0.29). Conclusions. Although it does not imply a direct cause-and-effect relationship, the present study suggests condylar asymmetry and hyperdivergent skeletal pattern are more likely to be associated with a higher risk of temporomandibular disorder joint diseases in adult patients

Topical administration of a doxorubicin-specific monoclonal antibody prevents drug-induced mouth apoptosis in mice

One of the most severe side effects of anti-tumour chemotherapy is mucositis due to drug toxicity for rapidly dividing cells. We show here that anti-DXR monoclonal antibodies can prevent DXR-induced damage. Indeed, apoptosis, confined to the proliferative compartment of the basal mucosa, observed in the tongue of DXR-treated mice was completely inhibited by topical application of the anti-DXR antibodies. © 2001 Cancer Research Campaign http://www.bjcancer.co

The lung microbiota: role in maintaining pulmonary immune homeostasis and its implications in cancer development and therapy

Like other body districts, lungs present a complex bacteria community. An emerging function of lung microbiota is to promote and maintain a state of immune tolerance, to prevent uncontrolled and not desirable inflammatory response caused by inhalation of harmless environmental stimuli. This effect is mediated by a continuous dialog between commensal bacteria and immune cells resident in lungs, which express a repertoire of sensors able to detect microorganisms. The same receptors are also involved in the recognition of pathogens and in mounting a proper immune response. Due to its important role in preserving lung homeostasis, the lung microbiota can be also considered a mirror of lung health status. Indeed, several studies indicate that lung bacterial composition drastically changes during the occurrence of pulmonary pathologies, such as lung cancer, and the available data suggest that the modifications of lung microbiota can be part of the etiology of tumors in lungs and can influence their progression and response to therapy. These results provide the scientific rationale to analyze lung microbiota composition as biomarker for lung cancer and to consider lung microbiota a new potential target for therapeutic intervention to reprogram the antitumor immune microenvironment. In the present review, we discussed about the role of lung microbiota in lung physiology and summarized the most relevant data about the relationship between lung microbiota and cancer

TLR3 expression induces apoptosis in human non‐small‐cell lung cancer

The prognostic value of Toll\u2010like receptor 3 (TLR3) is debated in cancer, differing between tumor types, methods, and cell types. We recently showed for the first time that TLR3 expression on early stage non\u2010small\u2010cell lung cancer (NSCLC) results associated with a good prognosis. Here, we provide experimental evidences explaining the molecular reason behind TLR3\u2019s favorable prognostic role. We demonstrated that TLR3 activation in vitro induces apoptosis in lung cancer cell lines and, accordingly, that TLR3 expression is associated with caspase\u20103 activation in adenocarcinoma NSCLC specimens, both evaluated by immunohistochemistry. Moreover, we showed that TLR3 expression on cancer cells contributes to activate the CD103+ lung dendritic cell subset, that is specifically associated with processing of antigens derived from apoptotic cells and their presentation to CD8+ T lymphocytes. These findings point to the relevant role of TLR3 expression on lung cancer cells and support the use of TLR3 agonists in NSCLC patients to re\u2010activate local innate immune response

Exploiting poly(I:C) to induce cancer cell apoptosis

TLR3 belong to the Toll-like receptors family, it is mainly expressed on immune cells where it senses pathogen-associated molecular patterns and initiates innate immune response. TLR3 agonist poly(I:C) was developed to mimic pathogens infection and boost immune system activation to promote anti-cancer therapy. Accordingly, TLR agonists were included in the National Cancer Institute list of immunotherapeutic agents with the highest potential to cure cancer. Besides well known effects on immune cells, poly(I:C) was also shown, in experimental models, to directly induce apoptosis in cancer cells expressing TLR3. This review presents the current knowledge on the mechanism of poly(I:C)-induced apoptosis in cancer cells. Experimental evidences on positive or negative regulators of TLR3-mediated apoptosis induced by poly(I:C) are reported and strategies are proposed to successfully promote this event in cancer cells. Cancer cells apoptosis is an additional arm offered by poly(I:C), besides activation of immune system, for the treatment of various type of cancer. A further dissection of TLR3 signaling would contribute to greater resolution of the critical steps that impede full exploitation of the poly(I:C)-induced apoptosis. Experimental evidences about negative regulator of poly(I:C)-induced apoptotic program should be considered in combinations with TLR3 agonists in clinical trials

Equivalent Fixed-Points in the Effective Average Action Formalism

Starting from a modified version of Polchinski's equation, Morris' fixed-point equation for the effective average action is derived. Since an expression for the line of equivalent fixed-points associated with every critical fixed-point is known in the former case, this link allows us to find, for the first time, the analogous expression in the latter case.Comment: 30 pages; v2: 29 pages - major improvements to section 3; v3: published in J. Phys. A - minor change

Poly(I:C) and CpG-ODN combined aerosolization to treat lung metastases and counter the immunosuppressive microenvironment

The immunostimulatory ability of synthetic oligonucleotides containing CpG motifs (CpG-ODN), agonists of Toll-like receptor 9 (TLR9), can be harnessed to promote antitumor immunity by their application at the tumor site to stimulate local activation of innate immunity; however, particularly in the lung, tumor-associated immunosuppression can subvert such antitumor innate immune responses. To locally maintain continuous activation of innate subpopulations while inhibiting immunosuppressive cells, we evaluated aerosol delivery CpG-ODN combined with Poly(I:C), a TLR3 agonist able to convert tumor-supporting macrophages to tumoricidal effectors, in the treatment of B16 melanoma lung metastases in C57BL/6 mice. Aerosolization of CpG-ODN with Poly(I:C) into the bronchoalveolar space reduced the presence of M2-associated arginase- and IL-10-secreting macrophages in tumor-bearing lungs and increased the antitumor activity of aerosolized CpG-ODN alone against B16 lung metastases without apparent signs of toxicity or injury of the bronchial-bronchiolar structures and alveolar walls. Moreover, CpG-ODN/Poly(I:C) aerosol combined with dacarbazine, a therapeutic agent used in patients with inoperable metastatic melanoma able to exert immunostimulatory effects, led to a significant increase in antitumor activity as compared to treatments with aerosolized CpG-ODN/Poly(I:C) or dacarbazine alone. This effect was related to an enhanced recruitment and cytotoxic activity of tumor-infiltrating NK cells in the lung. Our results point to aerosol delivery as a convenient approach for repeated applications of immunostimulants in patients with lung metastases to maintain a continuous local activation of innate immune cells while suppressing polarization of tumor-infiltrating macrophages to an M2 phenotype

Extracellular matrix features discriminate aggressive HER2-positive breast cancer patients who benefit from trastuzumab treatment

We previously identified an extracellular matrix (ECM) gene expression pattern in breast cancer (BC), called ECM3, characterized by a high expression of genes encoding structural ECM proteins. Since ECM is reportedly implicated in response to therapy of BCs, the aim of this work is to investigate the prognostic and predictive value of ECM3 molecular classification in HER2-positive BCs. ECM3 resulted in a robust cluster that identified a subset of 25-37% of HER2-positive tumors with molecular aggressive features. ECM3 was significantly associated with worse prognosis in two datasets of HER2-positive BCs untreated with adjuvant therapy. Analyses carried out on two of our cohorts of patients treated or not with adjuvant trastuzumab showed association of ECM3 with worse prognosis only in patients not treated with trastuzumab. Moreover, investigating a dataset that includes gene profile data of tumors treated with neoadjuvant trastuzumab plus chemotherapy or chemotherapy alone, ECM3 was associated with increased pathological complete response if treated with trastuzumab. In the in vivo experiments, increased diffusion and trastuzumab activity were found in tumors derived from injection of HER2-positive cells with Matrigel that creates an ECM-rich tumor environment. Taken together, these results indicate that HER2-positive BCs classified as ECM3 have an aggressive phenotype but they are sensitive to trastuzumab treatment

FOXP3 expression in tumor cells and its role in cancer progression

Deep insight on FOXP3 expression in tumor cells and its role in cancer progression

Anti-tumor activity of CpG-ODN aerosol in mouse lung metastases

Studies in preclinical models have demonstrated the superior anti-tumor effect of CpG oligodeoxynucleotides (CpG-ODN) when administered at the tumor site rather than systemically. We evaluated the effect of aerosolized CpG-ODN on lung metastases in mice injected with immunogenic N202.1A mammary carcinoma cells or weakly immunogenic B16 melanoma cells. Upon reaching the bronchoalveolar space, aerosolized CpG-ODN activated a local immune response, as indicated by production of IL-12p40, IFN-γ and IL-1β and by recruitment and maturation of DC cells in bronchoalveolar lavage fluid of mice. Treatment with aerosolized CpG-ODN induced an expansion of CD4+ cells in lung and was more efficacious than systemic i.p. administration against experimental lung metastases of immunogenic N202.1A mammary carcinoma cells, whereas only i.p. delivery of CpG-ODN provided anti-tumor activity, which correlated with NK cell expansion in the lung, against lung metastases of the poorly immunogenic B16 melanoma. The inefficacy of aerosol therapy to induce NK expansion was related to the presence of immunosuppressive macrophages in B16 tumor-bearing lungs, as mice depleted of these cells by clodronate treatment responded to aerosol CpG-ODN through expansion of the NK cell population and significantly reduced numbers of lung metastases. Our results indicate that tumor immunogenicity and the tumor-induced immunosuppressive environment are critical factors to the success of CpG therapy in the lung, and point to the value of routine sampling of the lung immune environment in defining an optimal immunotherapeutic strategy