Several tumors exhibit pH gradient reversal, with acidification of extracellular pH (pHe) and alkalinization of intracellular pH (pHi). The pH gradient reversal is evident even during the preliminary stages of tumorigenesis and is crucial for survival and propagation of tumors, irrespective of their pathology, genetics and origins. Moreover, this hallmark seems to be present ubiquitously in all malignant tumors. Based on these facts, we propose a new emerging hallmark of cancer “pH gradient reversal”. Normalizing pH gradient reversal through inhibition of various proton transporters such as Na⁺-H⁺ exchanger (NHE), Vacuolar-type H⁺-ATPase (V-ATPase), H⁺/K⁺-ATPases and carbonic anhydrases (CAs) has demonstrated substantial therapeutic benefits. Indeed, inhibition of NHE1 is now being regarded as the latest concept in cancer treatment. A recent patent deals with the utilization of cis-Urocanic acid to acidify the pHi and induce apoptosis in tumors. Another patent reports therapeutic benefit by inhibiting Lactate Dehydrogenase - 5 (LDH-5) in various cancers. Several patents have been formulated by designing drugs activated through acidic pHe providing a cancer specific action. The purpose of this review is to analyze the available literature and help design selective therapies that could be a valuable adjunct to the conventional therapies or even replace them.

Background and Objectives: Plants as sources of medicinal compounds have continued to play a predominant role in the maintenance of human health since ancient times. Even though several effective antifungal agents are available for oral candida infections, the failure is not uncommon because isolates of Candida albicans may exhibits resistance to the drug during therapy. The present study was conducted to evaluate the antimicrobial effects of few plant extracts on Candida albicans. An additional objective was to identify an alternative, inexpensive, simple, and effective method of preventing and controlling Candida albicans. Materials and Methods: Fine texture powder or paste form of leaves was soaked in sterile distilled water and 100% ethyl alcohol, which were kept in refrigerator at 4°C for 24 h. Then filtrates were prepared and kept in a hot air oven to get a black shining crystal powder/paste form. Stock solutions of plant extracts were inoculated on petri plates containing species of Candida albicans and incubated at 25 ± 2°C for 72 h. Results: Alcoholic curry leaves showed the maximum zone of inhibition on Candida albicans followed by aqueous tea leaves. The other plant extracts like alcoholic onion leaves, alcoholic tea leaves, alcoholic onion bulb, alcoholic aloe vera, and alcoholic mint leaves also inhibited the growth of Candida albicans but lesser extent. Conclusion: The present study renders few medicinal plants as an alternative medicines to the field of dentistry which can be used adjunct to conventional therapy of oral candidasis.

Objectives: The purpose of this paper is to systematically review the various studies and case reports on the morphology and prevalence of middle canals in the mandibular molars. Methodology: Electronic databases such as MEDLINE, PubMed, EBSCOhost, ScienceDirect and various journals were screened to identify published literature till March 2017 and earlier for articles related to middle canals in the human permanent mandibular molars. Obtained articles were categorized as original researches, case reports and review articles. Well-defined review questions were developed using the patient population, intervention, comparison and outcome framework to summarize the objectives: “Does middle canal vary in morphology and anatomic location? What is the prevalence of middle canals in mandibular molars? Does ethnicity affect the prevalence of middle canals in mandibular molars?” Morphology was studied and prevalence rates were determined from the evaluation of data extracted from the articles. Results: The search strategy resulted in 87 articles, of which 36 were original research papers and 51 were case reports. The prevalence of middle canals in the various populations ranged from 0.26% to 53.8%. Middle canals were reported in Europeans, Asians, Africans and South and North American populations. The prevalence of middle mesial canal and middle distal canal in various races was reported as up to 53.8% and 10%, respectively. The orifice of middle canal exists below a dentinal projection in the groove between the two main canals. They were observed in fin, confluent and independent configuration. Out of these, confluent configuration was more prevalent. Conclusion: Middle canal varies in morphology and anatomic location. Ethnicity affects the prevalence of middle canals in the mandibular molars.

Context: Significant increase in vascularity occurs during the transition from normal oral mucosa, through differing degrees of dysplasia, to invasive squamous cell carcinoma (SCC). Aims: To evaluate microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in oral tumorigenesis and correlate it with the clinicopathological characteristics. Settings and Design: VEGF expression and MVD were quantified immunohistochemically using anti-VEGF and anti-CD34 antibody. Materials and Methods: For this study we used a total of 60 archival specimens, including 10 normal oral mucosa (NOM), 7 mild epithelial dysplasia (Mild ED), 8 moderate epithelial dysplasia (Mod ED), 5 severe epithelial dysplasia (SED), 14 well-differentiated SCC, 11 moderately-differentiated SCC, and 5 poorly-differentiated SCC. VEGF expression was assessed in relation to the localization, intensity, and area of the immunohistochemically stained cells. MVD was evaluated using the Image-Pro^® Plus software. Statistical Analysis: One-way ANOVA (F test) was carried out for comparing the parameters for multiple groups such as different histopathological grades of dysplasia and carcinoma. Comparison between groups was carried out using the Student's 't' test. Correlations between VEGF score and MVD were estimated using the Karl Pearson coefficient of correlation. Results: VEGF and MVD appeared to increase with disease progression and were statistically higher in oral SCC than in epithelial dysplasia and normal buccal mucosa. There was significant correlation between VEGF expression and MVD. Conclusions: These findings indicate that VEGF expression is upregulated during head and neck tumorigenesis.

Background. Cyclin D1 regulates the G1 to S transition of cell cycle. Its deregulation or overexpression may lead to disturbance in the normal cell cycle control and tumour formation. Overexpression of cyclin D1 has been reported in various tumors of diverse histogenesis. This case control retrospective study was carried out to study the immunohistochemical reactivity and expression of cyclin D1 and its association with site, clinical staging, and histopathological differentiation of oral squamous cell carcinoma (OSCC).Methods. Forty formalin-fixed paraffin-embedded tissue blocks of biopsy specimens of oral squamous cell carcinoma were immunohistochemically evaluated for expression of cyclin D1.Results. Cyclin D1 expression was seen in 45% cases of OSCC. It did not correlate with site and clinical staging. Highest expression was seen in well-differentiated, followed by moderately differentiated, and poorly differentiated squamous cell carcinomas, with a statistically significant correlation.Conclusion. Cyclin D1 expression significantly increases with increase in differentiation.

The etiology of oral squamous cell carcinoma (OSCC) is complex and involves many factors. The most clearly defined risk factors are smoking and alcohol, which substantially increase the risk of oral SCC. However, despite this clear association, a substantial proportion of patients develop OSCC without exposure to them, emphasizing the role of other risk factors such as genetic susceptibility and oncogenic viruses. Some viruses are strongly associated with OSCC while the association of others is less frequent and may depend on co-factors for their carcinogenic effects. Therefore, the exact role of viruses must be evaluated with care in order to improve the diagnosis and treatment of OSCC.