Immunotherapy: The Fourth Domain in Oral Cancer Therapeutics.

Owing to high global prevalence, incidence and associated mortality, cancer of head and neck particularly oral cancer remains a cardinal domain for research and trials. Immune-modulatory therapies that employ patients own immune system for therapeutic benefits in oral cancer seems promising. The aim of this review is to gauge the potential of immunotherapy as fourth domain of Oral cancer therapeutics. Articles were searched using suitable search terms in MEDLINE and Google Scholar database to include clinical trials, meta-analyses, and research in humans/animals/cell lines published in peer reviewed journals. A total of 97 articles were included in this review. Literature has several studies and trials where different types of immunotherapies has been attempted but it is crucial to identify precise biomarkers of genome based targeted agents and to find parameters to select patients who might benefit from immunotherapy. Also further research is required to estimate predictive value of tumor mutational burden and mutational signatures so as to aid in personalized prediction of oral cancer therapeutic response.

Unraveling the Genetic Web: H-Ras Expression and Mutation in Oral Squamous Cell Carcinoma-A Systematic Review.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a commonly occurring malignancy with complex genetic alterations contributing to its development. The H-Ras, a proto-oncogene, becomes an oncogene when mutated and has been implicated in various cancers. This systematic review aims to research to what extent H-Ras expression and mutation contribute to the development and progression of OSCC, and how does this molecular alteration impacts the clinical characteristics and prognosis in patients with OSCC. METHODS: A thorough electronic scientific literature search was carried out in PUBMED, SCOPUS, and GOOGLE SCHOLAR databases from 2007 to 2021. The search strategy yielded 120 articles. Following aggregation and filtering all results through our inclusion and exclusion criteria total 9 articles were included in our literature review. It has also been registered with PROSPERO (CRD42023485202). RESULTS: It was found that mutations in the Ras gene commonly reported in hotspots at codons 12, 13, and 61 resulting in the activation of downstream signaling pathways causing abnormal and uncontrolled cell growth. This systematic review has shown an increased prevalence of H-Ras mutation in well-differentiated OSCC and also the prevalence of H-Ras mutation in individuals engaging in multiple risk behaviors, particularly chewing tobacco, demonstrated a significant association with a higher prevalence of H-Ras positivity. CONCLUSION: This review sheds light on the prevalence of H-Ras mutations, their association with clinical characteristics, and their potential implications for OSCC prognosis. It also enhances our comprehension of the molecular mechanisms that underlie OSCC and paves the way for further research into targeted treatments based on H-Ras alterations.

Dendritic cell-based immunotherapy: a potential player in oral cancer therapeutics.

Background & aim: Dendritic cell (DC)-based immunotherapy modulates a patient's immune system for recognition and subsequent removal of tumor cells. DC-mediated anticancer therapy has been considered in several studies/ongoing trials for multiple types of cancer. Our aim is to describe the potential and current status of DC-based immunotherapy in oral cancer therapeutics. Materials & methods: An internet-based literature search with relevant search terms from 2012 to 2022 post-screening resulted in 58 articles that were considered for systematic review. Results & conclusion: Evaluation of DC based immunotherapy exploiting the critical immune cells in well-equipped laboratories with adequately trained and skilled experts along with a synergistic approach that is affordable and approachable to the patients can prove as an efficient anticancer therapy.

Considering the grave scenario of cancer, several studies/ongoing trials have focused on dendritic cell (DC)-mediated anticancer therapy in many types of cancer, including oral cancer. DC-based immunotherapy is a personalized/customized treatment protocol that modulates a patient's immune system to recognize and remove tumor cells by identifying them as foreign. DCs process antigens (present in tumor cells) and present them on MHC class I molecules to CD8+ T cells or MHC class II molecules to CD4+ T cells for an immune response. The literature has evidence exhibiting activation of antigen-specific T cells after injection of antigen-pulsed DCs. In addition, DC-based vaccines have been attempted with successful outcomes in various cancer types. A combination of DCs and other treatment modalities such as immune checkpoint inhibitors appears quite promising. Evaluation of DC based immunotherapy exploiting the critical immune cells in well-equipped laboratories with adequately trained and skilled experts along with a synergistic approach that is affordable and approachable to the patients can prove as an effective anticancer therapy.

Auricular reconstruction via 3D bioprinting strategies: An update.

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Potential of Internet of Medical Things (IoMT) applications in building a smart healthcare system: A systematic review.

Sudden spurting of Corona virus disease (COVID-19) has put the whole healthcare system on high alert. Internet of Medical Things (IoMT) has eased the situation to a great extent, also COVID-19 has motivated scientists to make new 'Smart' healthcare system focusing towards early diagnosis, prevention of spread, education and treatment and facilitate living in the new normal. This review aims to identify the role of IoMT applications in improving healthcare system and to analyze the status of research demonstrating effectiveness of IoMT benefits to the patient and healthcare system along with a brief insight into technologies supplementing IoMT and challenges faced in developing a smart healthcare system. An internet-based search in PUBMED, Google Scholar and IEEE Library for english language publications using relevant terms resulted in 987 articles. After screening title, abstract, and content related to IoMT in healthcare and excluding duplicate articles, 135 articles published in journal with impact factor ≥1 were eligible for inclusion. Also relevant articles from the references of the selected articles were considered. The habituation of IoMT and related technology has resolved several difficulties using remote monitoring, telemedicine, robotics, sensors etc. However mass adoption seems challenging due to factors like privacy and security of data, management of large amount of data, scalability and upgradation etc. Although ample knowledge has been compiled and exchanged, this structured systematic review will help the healthcare practitioners, policymakers/decision makers, scientists and researchers to gauge the applicability of IoMT in healthcare more efficiently.

A Systematic Review of Potential Immunotherapies Targeting PRAME in Retinoid Resistant Oral Potentially Malignant Disorders and Oral Cancer.

Backgound and objective: Early chemoprevention in Oral Potentially Malignant Disorders (OPMDs) and Oral Cancer (OC) has been extensively researched in order to mitigate the malignant transformation and progression of the lesion. Many agents have been attempted, but their cost inefficacy and inadequate outcomes posed a major hindrance in their successful adoption. Retinoid Based Therapy (RBT) though a cheap and effective treatment option, could not achieve much clinical usage because of variable responsiveness in clinical outcomes. Such clinical response variability may be attributed to the repression of retinoid receptors by Preferentially Expressed Antigen of Melanoma (PRAME) protein molecule. Therefore, in order to make RBT successful, targeting PRAME by various immunotherapies is an exciting area of research investigation. This review provides an insight into the various immunotherapeutic strategies targeting PRAME and their usefulness in retinoid-resistant OPMD and OC. Method of data collection: An exhaustive internet-based literature search following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was carried out in PUBMED and Google SCHOLAR database using terms 'Anti-PRAME' OR 'PRAME Immunotherapy' OR 'PRAME Vaccines' AND 'Cancer' AND 'Retinoid resistance'. Only articles in the English language with at least 1 citation, published in a journal with impact factor ≥ 1, having relevance to the context and availability of full text were considered. Results: After an initial search, 342 articles were yielded on the basis of inclusion criteria and, by reading the abstract and availability of full text, a total of 124 articles were selected. Further reading the full texts and considering articles from the references of the selected articles, a total of 65 articles were finally included in the review. Conclusion: Our analysis of the literature suggests that PRAME screening in OC and OPMDs prior to RBT should be done. In PRAME positive cases, approaches like PRAME based immunotherapy in the form of Cancer vaccine therapy [Acellular PRAME vaccine, PRAME pulsed Dendritic Cells (DC)]; Adoptive T Cell therapy/T Cell Receptor-T Cell therapy, Antibody therapy/Chimeric Antigen Receptor-T Cell therapy along with Presented antigen modulation Therapies employing histone deacetylase inhibitors and demethylation agents seem plausible. In the future, a combination therapy employing either PRAME vaccines or antibodies or Adoptive T cell Therapy and ATRA could be used in retinoid resistant OC and OPMDs.

From injectable to 3D printed hydrogels in maxillofacial tissue engineering: A review.

INTRODUCTION: This review aims at describing different types of hydrogels in context to their composition, fabrication techniques and other specific features along with an insight into the latest advancements including smart hydrogels, 3D printed, programmable, shape memory and self-healing hydrogels for their applicability as scaffold in maxillofacial bone and cartilage tissue regeneration. METHODS: Electronic database searches were undertaken on PubMed, Ovid, Medline, Embase, ProQuest and science direct for English language literature, published for application of hydrogels in maxillofacial bone and cartilage tissue engineering. The search items used in this article were hydrogel, bone and cartilage tissue engineering, maxillofacial, clinical trials. Reviews and in vitro studies were excluded. RESULTS: Search for injectable hydrogel showed 4955 articles, when restricted to bone tissue engineering results were reduced to 463 and for cartilage engineering to 335; when we limited it to maxillofacial bone and cartilage tissue engineering, search results showed 49 articles to which 9 additional articles were included from references, after exclusion of in-vitro studies and duplicates 16 articles were obtained for our study. Similarly, for 3D printed hydrogels, result showed 1126 articles, which got restricted to 19 when searched for maxillofacial bone and cartilage engineering, then 2 additional articles were included directly from references, and finally after exclusion of the invitro studies and duplicates, a total of 5 articles were obtained. CONCLUSION: Modifications in hydrogel can improve the mechanical properties, biocompatibility and unique chemistries for its use in bone and cartilage tissue engineering for future research.

3D bioprinting and craniofacial regeneration.

BACKGROUND: Considering the structural and functional complexity of the craniofacial tissues, 3D bioprinting can be a valuable tool to design and create functional 3D tissues or organs in situ for in vivo applications. This review aims to explore the various aspects of this emerging 3D bioprinting technology and its application in the craniofacial bone or cartilage regeneration. METHOD: Electronic database searches were undertaken on pubmed, google scholar, medline, embase, and science direct for english language literature, published for 3D bioprinting in craniofacial regeneration. The search items used were 'craniofacial regeneration' OR 'jaw regeneration' OR 'maxillofacial regeneration' AND '3D bioprinting' OR 'three dimensional bioprinting' OR 'Additive manufacturing' OR 'rapid prototyping' OR 'patient specific bioprinting'. Reviews and duplicates were excluded. RESULTS: Search with above described criteria yielded 476 articles, which reduced to 108 after excluding reviews. Further screening of individual articles led to 77 articles to which 9 additional articles were included from references, and 18 duplicate articles were excluded. Finally we were left with 68 articles to be included in the review. CONCLUSION: Craniofacial tissue and organ regeneration has been reported a success using bioink with different biomaterial and incorporated stem cells in 3D bioprinters. Though several attempts have been made to fabricate craniofacial bone and cartilage, the strive to achieve desired outcome still continues.

Predicting transition from oral pre-malignancy to malignancy via Bcl-2 immuno-expression: Evidence and lacunae.

Bcl-2 (B cell Lymphoma -2) family comprises of both anti-apoptotic and pro-apoptotic proteins whose altered expression or change in ratio inhibits apoptosis, and promotes tumor progression. The aim of this study is to assess the usefulness of Bcl-2 in distinguishing dysplastic or malignant epithelium from non-dysplastic or normal epithelium to aid in prediction of malignant transformation potential. MATERIAL AND METHOD: Study group comprised of 30 cases of clinically diagnosed leukoplakia (OPMD), 15 cases of Oral Squamous Cell Carcinoma (OSCC) and 5 normal tissue samples. The labeling index of Bcl-2 was analyzed in immunohistochemically stained sections. Different statistical tools were used to analyze the data and to compare Bcl-2 expression qualitatively and quantitatively among all the groups. RESULTS: An increasing trend of Bcl-2 immunoexpression was observed from normal epithelium to non-dysplastic and from non-dysplastic to dysplastic lesions. In OSCC, the peripheral cells in the differentiating epithelial islands (within the connective tissue) showed Bcl-2 immuno-reactivity, which gradually decreased towards the center. In contrast, intense and diffuse Bcl-2 immuno-reactivity was seen in poorly differentiated carcinoma. But the overall Bcl-2 positivity was less in OSCC as compared to dysplastic lesions. CONCLUSION: Increased expression of Bcl-2 oncoprotein in sequentially progressing epithelial dysplasia and down-regulation in differentiating carcinoma (well and moderately differentiating OSCC) unveils the clinical relevance of Bcl-2 in early stages of OSCC tumorigenesis. The heterogenous expression of Bcl-2 in carcinoma with different grades of differentiation renders them unable to be used as an independent tool for predicting transition from oral pre-malignancy to malignancy.

Apoptosis and genes involved in oral cancer - a comprehensive review.

Oral cancers needs relentless research due to high mortality and morbidity associated with it. Despite of the comparable ease in accessibility to these sites, more than 2/3rd cases are diagnosed in advanced stages. Molecular/genetic studies augment clinical assessment, classification and prediction of malignant potential of oral lesions, thereby reducing its incidence and increasing the scope for early diagnosis and treatment of oral cancers. Herein we aim to review the role of apoptosis and genes associated with it in oral cancer development in order to aid in early diagnosis, prediction of malignant potential and evaluation of possible treatment targets in oral cancer. An internet-based search was done with key words apoptosis, genes, mutations, targets and analysis to extract 72 articles after considering inclusion and exclusion criteria. The knowledge of genetics and genomics of oral cancer is of utmost need in order to stop the rising prevalence of oral cancer. Translational approach and interventions at the early stage of oral cancer, targeted destruction of cancerous cells by silencing or promoting involved genes should be the ideal intervention.

Poly hydroxyalkanoates (PHA): Role in bone scaffolds.

Polyhydroxyalkanoates (PHA) are prokaryotic macromolecules accumulated within the cytoplasm as granules. Due to their suitable mechanical properties, biocompatibility, degradation time, ability to be blended, surface modified, and form copolymers, it is widely used in medical devices and as scaffolds in bone tissue engineering. This review describes in brief the production and extraction sources, physico-chemical characteristic, mechanical properties, degradation rate and applications of various PHAs and its copolymers with special emphasis to its role as scaffolds in bone tissue engineering.

Polycaprolactone as biomaterial for bone scaffolds: Review of literature.

Bone tissue engineering using polymer based scaffolds have been studied a lot in last decades. Considering the qualities of all the polymers desired to be used as scaffolds, Polycaprolactone (PCL) polyester apart from being biocompatible and biodegradable qualifies to an appreciable level due its easy availability, cost efficacy and suitability for modification. Its adjustable physio-chemical state, biological properties and mechanical strength renders it to withstand physical, chemical and mechanical, insults without significant loss of its properties. This review aims to critically analyse the efficacy of PCL as a biomaterial for bone scaffolds.

Assessment of Root Resorption and Root Shape by Periapical and Panoramic Radiographs: A Comparative Study.

INTRODUCTION: One of the common findings encountered by the clinician at the end of orthodontic treatment is the apical root resorption. Root resorption occurs to various degrees. A severe form of root resorption is characterized by shortening of root for more than 4 mm or more than one-third of the total tooth length. A low incidence rate of resorption is observed based on radiographic findings for the diagnosis of root resorption, panoramic radiography, and periapical radiography. Hence, we evaluated the accuracy of panoramic radiographic films for assessing the root resorption in comparison with the periapical films. MATERIALS AND METHODS: This study included the assessment of all the cases in which pre- and post-treatment radiographs were available for analysis of the assessment of the amount of root resorption. Complete records of 80 patients were analyzed. Examination of a total of 900 teeth was done. Mean age of the patients in this study was 21 years ranging from 11 to 38 years. The majority of the patients in the present study were females. All the treatments were carried out by registered experienced orthodontists having minimum experience of more than 10 years. All the cases were divided into two study groups. Group I comprised panoramic radiographic findings, while group II consisted of periapical radiographic findings. For the measurement of crown portion, root portion, and the complete root length, magnification loops of over 100 powers with parallax correction with inbuilt grids were used. Assessment of the tooth length and the crown length was done by the same observers. All the results were analyzed by Statistical Package for the Social Sciences software version 6.0. RESULTS: Maximum amount of root resorption was observed in case of maxillary central incisors and canines among group I and II cases respectively. However, nonsignificant difference was obtained while comparing the mean root resorption in relation to maxillary incisors and canines among the two study groups. While comparing the overall value of root resorption among the two study groups, a significant difference was obtained. The maximum value of tooth length in both the groups was observed in cases of maxillary canines. Significant differences were observed while comparing the tooth length of various teeth among the two study groups. Among the deviated forms of root shape, dilacera-tion was the most common form of root shape detected in both the study groups. CONCLUSION: Periapical radiographs are more efficient in the assessment of the shape and resorption of the root. CLINICAL SIGNIFICANCE: Thorough evaluation of periapical radiographs is necessary for detection of even minute levels of root resorption.

Expression of p63 in potentially malignant and malignant oral lesions.

BACKGROUND: p63, a member of p53 family, known to be expressed in embryonic tissues and basal regenerative layers of many epithelial tissues in the adult, is also expressed in various benign and malignant lesions of body including lesions of oral cavity. To evaluate the expression of p63 and compare the expression qualitatively and quantitatively in normal buccal mucosa, epithelial dysplasia, oral submucous fibrosis (OSMF), and oral squamous cell carcinoma (OSCC). METHODS: The study material consisted of 45 archival cases which were divided into Group I with 5 cases of normal buccal mucosa, Group II with 15 cases of epithelial dysplasia, and Group III with 10 cases of OSMF and 15 cases of OSCC. Immunohistochemical expression of p63 was assessed by using mean, standard deviation, and analysis of variance. RESULTS: Overexpression of p63 was seen in epithelial dysplasia, OSMF, and squamous cell carcinoma with an increased suprabasal expression in cases of epithelial dysplasia. The mean labeling index (LI) of p63 was found to be in increasing order from normal oral mucosa (33.75%), OSMF (57.37%), epithelial dysplasia (63.87%) to squamous cell carcinoma (69.76%). CONCLUSION: The results suggest a possible role of p63 in oral carcinogenesis, and an increased LI as well as increased suprabasal expression of this gene in dysplastic lesions may have a potential to be utilized as a marker for premalignancy.

Keratoameloblastoma: Report of a rare variant with review of literature.

Ameloblastoma has intrigued clinicians as well as pathologists due to its diverse clinical behavior and histomorphologic presentations. Keratoameloblastoma is a rare histologic sub type, characterized by extensive keratin formation within ameloblastic epithelium, with only a handful number of cases described in the literature. Here, we report a case of this uncommon sub type of ameloblastoma in a young female patient presenting as an extensive lesion in mandibular ramus area. The radiological and fine needle aspiration findings suggested of a keratinizing cystic lesion and incisional biopsy showed features of ameloblastoma. Patient underwent segmental mandibulectomy and histological examination of excisional specimen revealed features of ameloblastoma with abundant keratinization leading to a diagnosis of keratoameloblastoma. The diagnostic pitfalls related with the lesion have been discussed along with a short review of the literature.