Psychological Stress and Cancer: New Evidence of An Increasingly Strong Link.

To date stress, a highly complex process that disrupts homeostasis and involves environmental and psychosocial factors, is considered as one of the most crucial factor that affects our daily life, especially urban dweller's life. Clinical and experimental studies widely support the notion that adrenergic stimulation due to chronic stress affects inflammation and metabolism. In this work, supported by several recent scientific evidences, we show how stress plays a positive role in cancer initiation, progression and cancer metastasis, a negative role for anti-tumor immune function and therapy response. Understanding the intricacies of this interaction could provide an additional help on how act in cancer prevention and therapy.

Medical Cannabis: A plurimillennial history of an evergreen.

The history of Cannabis goes along that of humankind, as speculated based on geographical and evolutionary models together with historic data collected to date. Its medical use is several thousand years old, as attested both by archeobotanical evidence of Cannabis remains and written records found in ancient texts from the sacred Vedic foundational texts of Ayurvedic medicine (about 800 before current era [BCE]) to the first known Pharmacopoea, the Chinese "Shen Nung Pen Ts'ao Ching" (1 century BCE). In this paper, we retrace the history of Cannabis traveling through the key stages of its diffusion among the most important ancient cultures up to our days, when we are facing a renaissance of its medical employment. We report through the centuries evidence of its use in numerous pathologic conditions especially for its anti-inflammatory, antiseptic, and anticonvulsing properties that support the requirement to direct our present research efforts into the definitive understanding of its efficacy.

Dental care and dentistry practice in the Medieval Medical School of Salerno.

Even though dental care is sometimes erroneously considered a modern practice, written records from major ancient civilisation all around the world date back to several millennia BC. In particular, in the Middle Ages, among the tenth and thirteenth centuries, the illustrious Medical School of Salerno in Italy, the most important institution in the Western world for the diffusion of medical knowledge, disseminated through its precepts the importance of oral hygiene and practiced specific dental therapies for tooth decay, gingivitis, paradentosis and halitosis among others. Interestingly, several of the officinal plants and natural ingredients proposed for oral care by the school's most famous physicians recipes, notably those of the legendary Trotula De Ruggiero, considered the first female physician in history, are still in vogue in the twenty-first century.

p53 regulates the mevalonate pathway in human glioblastoma multiforme.

The mevalonate (MVA) pathway is an important metabolic pathway implicated in multiple aspects of tumorigenesis. In this study, we provided evidence that p53 induces the expression of a group of enzymes of the MVA pathway including 3'-hydroxy-3'-methylglutaryl-coenzyme A reductase, MVA kinase, farnesyl diphosphate synthase and farnesyl diphosphate farnesyl transferase 1, in the human glioblastoma multiforme cell line, U343 cells, and in normal human astrocytes, NHAs. Genetic and pharmacologic perturbation of p53 directly influences the expression of these genes. Furthermore, p53 is recruited to the gene promoters in designated p53-responsive elements, thereby increasing their transcription. Such effect was abolished by site-directed mutagenesis in the p53-responsive element of promoter of the genes. These findings highlight another aspect of p53 functions unrelated to tumor suppression and suggest p53 as a novel regulator of the MVA pathway providing insight into the role of this pathway in cancer progression.

Anandamide inhibits breast tumor-induced angiogenesis.

Breast cancer is one of the most frequently diagnosed malignancies and a leading cause of cancer death in women. Great advances in the treatment of primary tumors have led to a significant increment in the overall survival rates, however recurrence and metastatic disease, the underlying cause of death, are still a medical challenge. Breast cancer is highly dependent on neovascularization to progress. In the last years several anti-angiogenic drugs have been developed and administered to patients in combination with chemotherapeutic drugs. Collected preclinical evidence has proposed the endocannabinoid system as a potential target in cancer. The endocannabinoid anandamide has been reported to affect breast cancer growth at multiple levels, by inhibiting proliferation, migration and invasiveness in vitro and in vivo and by directly inhibiting angiogenesis. Aim of the present work is to investigate if anandamide is able to affect the proangiogenic phenotype of the highly invasive and metastatic breast cancer cells MDA-MB-231. We found that following anandamide treatment, MDAMB-231 cells lose their ability to stimulate endothelial cells proliferation in vitro, due to a significant inhibition of all the pro-angiogenic factors produced by these cells. This finding adds another piece of evidence to the anti-tumor efficacy of anandamide in breast cancer.

Rimonabant (SR141716) exerts anti-proliferative and immunomodulatory effects in human peripheral blood mononuclear cells.

BACKGROUND AND PURPOSE: Rimonabant (SR141716) is the first selective cannabinoid receptor CB(1) antagonist described. Along with its anti-obesity action, emerging findings show potential anti-proliferative and anti-inflammatory action of SR141716 in several in vitro and in vivo models. In this study we have investigated the anti-proliferative and immunomodulatory effects of SR141716 in human peripheral blood mononuclear cells (PBMCs). EXPERIMENTAL APPROACH: We have evaluated in vitro the effect of SR141716 in human PBMCs stimulated with different mitogens. Cell proliferation was assessed by (3)H-thymidine incorporation. Cell cycle, cell death and apoptosis were analysed by flow cytometry. Protein expression was investigated by Western blot. KEY RESULTS: SR141716 significantly inhibited the proliferative response of PBMCs and this effect was accompanied by block of G(1)/S phase of the cell cycle without induction of apoptosis and cell death. SR141716 used in combination with 2-methyl-arachidonyl-2'-fluoro-ethylamide (Met-F-AEA), a stable analogue of the endogenous cannabinoid anandamide, showed synergism rather than antagonism of the inhibition of cell proliferation. The immunomodulatory effects of SR141716 were associated with increased expression of IkappaB, phosphorylated AKT (p-AKT) and decreased expression of NF-kappaB, p-IkappaB, p-ERK, COX-2 and iNOS. CONCLUSIONS AND IMPLICATIONS: Our findings suggest SR141716 is a novel immunomodulatory drug with anti-inflammatory properties.

Interaction between natural killer and dendritic cells: the role of CD40, CD80 and major histocompatibility complex class i molecules in cytotoxicity induction and interferon-gamma production.

This study focuses on the differential role of CD40 and CD80 costimulatory molecules and major histocompatibility complex class I (MHC-I) antigens in the regulation of the interplay between dendritic cells (DCs) and interleukin (IL)-2-activated human natural killer (NK) lymphocytes. Our data indicate that CD40 and CD80 molecules might play a preferential role in the induction of cytotoxic function but not in the interferon-gamma(IFN-gamma) production by human IL-2-activated NK effectors in the presence of autologous and allogeneic DCs. In addition, a critical role of CD94-dependent MHC-I recognition in the regulation of both IFN-gamma production and target cell lysis was shown in the functional interaction between NK and DCs.

Levels of cytokines and collagen type I and type III as a function of age in human gingivitis.

The objective of this study was to examine the age-dependent relationships between levels of inflammatory cytokines and collagen in human gingival inflammation. The gingival biopsies were obtained from 142 patients, divided into the following age groups: 6 to 14 years (prepubertal children); 18 to 35 years (young adults); 36 to 54 years (mature adults); and 55 years or above. The patients were also divided according to the severity of gingivitis. The tissues were analyzed for the contents of the inflammatory cytokines interleukin (IL)-1 beta, IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) using specific ELISA kits, and interstitial collagen type I and type III using the ELISA method and specific antibodies. We found that in young adults, levels of IL-1 beta and IL-6 were significantly higher in inflamed than in non-inflamed gingiva. Total collagen in the young adults, however, was lower in inflamed than in non-inflamed gingiva. There was no significant difference in the levels of either IL-8 or TNF-alpha between inflamed and non-inflamed gingiva independent of age. No difference in the level of collagen type I between the inflamed and non-inflamed gingiva was found in any age groups. The level of collagen type III was lower in inflamed than in non-inflamed gingiva in both children and > or = 55 year group. The results indicate a disparity in the effect of age on the levels of cytokines and of collagen type I and type III in both clinically normal and inflamed gingiva.

Serologic and molecular analysis of the HLA system in Israeli Jewish patients with oral erosive lichen planus.

Oral erosive lichen planus is a distinct subtype of the common dermatosis lichen planus. Although the etiology of lichen planus is still obscure, it is known that cell-mediated immune mechanisms and genetic factors underlie its pathogenesis. Previous studies have found an association between lichen planus and HLA-DR3 or DR9 in different population groups. The present work was designed to elucidate, at the serologic and molecular levels, whether and which HLA genes are associated with oral erosive lichen planus in Israeli Jewish patients. A significant association with HLA-DR2 (RR = 4.7; pc < 0.0013) and a decrease in DR4 (RR = 0.3; p < 0.03) among the patients were noted. Oligotyping of DR2 alleles showed the presence of all three common variants (DRB1*1501, DRB1*1502 and DRB1*1601) in the patients, although none of the variants was overrepresented significantly. Three possible explanations for the role of HLA genes in the predisposition to oral erosive lichen planus are discussed. The most attractive theory for the pathogenesis of the disease seems to include the involvement of non-classical HLA genes.

Oral mucosal lesions among elderly in Israel.

The prevalence of ulcerative or proliferative oral mucosal lesions (OML) is an important parameter in evaluating the oral health of an elderly population. This paper relates the prevalence of OML in an elderly population to possible risk factors and defined high-risk groups. The second objective was to examine whether effective prediction of OML was possible from interview data alone. The elderly population of a Jerusalem neighborhood was surveyed in 1981: 456 elderly were interviewed by trained interviewers, and their oral cavities were examined by an oral epidemiologist. Specific diagnoses were confirmed by an independent senior clinician. Almost 40% of the elderly presented ulcerative or proliferative oral mucosal lesions. The prevalence of these OML was strongly related to the condition and age of dentures. The association between these OML and oral hygiene disappeared after controlling for the condition of the denture. Two variables ascertained by interview--age of denture and self-reported suitability of denture--turned out to be strong predictors of denture condition.

Epidemiological study of oral health among the elderly of Baka, a Jerusalem neighborhood.

This epidemiological study of the elderly in a Jerusalem neighborhood assessed oral health using five indicators: prevalence of oral mucosal conditions, denture condition, the age of dentures, oral hygiene status and periodontal condition. The utilization by the elderly of dental services and their awareness of their oral problems were also surveyed. Ninety-six percent of the elderly population were assessed as needing oral care. The capacity of the subsidized dental services in Jerusalem covers only about 15% of the elderly in need of such services.

The syndrome of oral complaints: etiology and therapy.

Many patients who were examined at the oral medicine clinic have had almost no findings, despite their severe complaints, and we propose to diagnose their condition as SOC (syndrome of oral complaints). It is more frequent in middle-aged postmenopausal women who thereby tend to express all three determinants of illness--the biologic, the psychological, and the social. Such a triple assessment of the determinants, together with a thorough physical examination, brings the SOC into the diagnostic category of hypochondria. Therefore, it should be treated by the family dentist or by the general internist, with reassurance, local measures, and minor tranquilizers.

Comparison and evaluation of fluorescent antibody techniques in the detection of herpes simplex virus in oral infection.

This article deals with the reliability and applicability of fluoroscopy in the diagnosis of herpetic lesions of the oral cavity. The reported results are based on a clinical experiment performed on fifty-two lesions suspected to be of herpetic origin. Three different methods were compared for detection of the possible presence of the virus--cytologic, virologic, and immunofluorescent. The greater reliability and speed of the last technique are demonstrated by our findings. Such features acquire special importance in the differential diagnosis of a number of diseases.