MyMedR

Fulltext Spectrum of surgical presentation of eosinophilic enteritis

Shetty SS, Shetty CK

Case Rep Surg, 2015;2015:691904.

PMID: 25960910 DOI: 10.1155/2015/691904

Eosinophilic enteritis is a rare disorder presenting mostly with diarrhea, malabsorption, abdominal pain, weight loss, and hypersensitivity. Surgical manifestation of eosinophilic gastrointestinal disorders depends on the site and extent of involvement. In our case series of four patients two of them had ileocaecal masses with recurrent subacute intestinal obstruction with past history of intake of antitubercular drugs for 9 months. On histopathological examination both of them proved to have eosinophilic enterocolitis. Thus it is a clinical dilemma to differentiate between these two conditions. The other two patients presented as acute abdomen with perforation and intussusception. All four patients were treated surgically. Postoperatively they recovered well with no symptoms on one year follow-up. In Indian setup tuberculosis being rampant there may be under reporting or wrongly diagnosed cases of eosinophilic enteritis. Thus a strong clinical suspicion and awareness of this clinical entity are essential among surgical community.

Novel Pathways and Mechanism of Nicotine-Induced Oral Carcinogenesis

Sharma M, Shetty SS, Radhakrishnan R

Recent Pat Anticancer Drug Discov, 2021 08 06.

PMID: 34365933 DOI: 10.2174/1574892816666210806161312

BACKGROUND: Smokeless Tobacco (SLT) contains 9 times more nicotine than Smoked Tobacco (SMT). The carcinogenic effect of nicotine is intensified by converting nicotine-to-nicotine-derived Nitrosamines (NDNs).

METHODS: A review of the literature was conducted with a tailored search strategy to unravel the novel pathways and mechanisms of nicotine-induced oral carcinogenesis.

RESULTS: Nicotine and NDNs act on nicotinic Acetylcholine Receptors (nAChRs) as agonists. Nicotine facilitates cravings through α4β2nAChR and α7nAChR, via enhanced brain dopamine release. Nicotine binding to nAChR promotes proliferation, migration, invasion, chemoresistance, radioresistance, and metastasis of oral cancer cells. Nicotine binding to α7nAChR on keratinocytes triggers Ras/Raf-1/MEK1/ERK cascade promoting anti-apoptosis and pro-proliferative effects. Furthermore, the nicotine-enhanced metastasis is subdued on nAChR blockade through reduced nuclear localization of p-EGFR.

CONCLUSION: Protracted exposure to nicotine/NDN augments cancer-stimulatory α7nAChR and desensitizes cancer inhibitory α4β2nAChR. Since nAChRs dictate both addictive and carcinogenic effects of nicotine, it seems counterintuitive to designate nicotine just as an addictive agent devoid of any carcinogenicity.

Fulltext Clinical and conceptual comments on "Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis"

Jayaraj R, Kumarasamy C, Shetty SS, Ram M R, Shaw P

J Infect, 2020 10;81(4):647-679.

PMID: 32407756 DOI: 10.1016/j.jinf.2020.05.011

Fulltext 10 "C" in COVID19

Shetty SS, Merchant Y, Shabadi N, Aljunid ST

Oral Surg, 2020 May 29.

PMID: 32837534 DOI: 10.1111/ors.12527

World war "C"1 has set in against an invisible virus. The routes of transmission include *Contact of contaminated objects,*Circulating droplets in the air called aerosols disseminated through *Cough, sneeze, ocular secretions2 from an infected individual.

Clinical interpretation of findings from a systematic review and a comprehensive meta-analysis on clinicopathological and prognostic characteristics of oral squamous cell carcinomas (OSCC) arising in patients with oral lichen planus (OLP)

Jayaraj R, Shetty SS, Kumaraswamy C, Gothandam KM, Ram MR, Shaw P

Oral Oncol, 2020 09;108:104974.

PMID: 32798186 DOI: 10.1016/j.oraloncology.2020.104974

Fulltext Signaling pathways promoting epithelial mesenchymal transition in oral submucous fibrosis and oral squamous cell carcinoma

Shetty SS, Sharma M, Fonseca FP, Jayaram P, Tanwar AS, Kabekkodu SP, et al.

Jpn Dent Sci Rev, 2020 Nov;56(1):97-108.

PMID: 32874377 DOI: 10.1016/j.jdsr.2020.07.002

Epithelial-mesenchymal transition (EMT) is a critical process that occurs during the embryonic development, wound healing, organ fibrosis and the onset of malignancy. Emerging evidence suggests that the EMT is involved in the invasion and metastasis of cancers. The inflammatory reaction antecedent to fibrosis in the onset of oral submucous fibrosis (OSF) and the role of EMT in its malignant transformation indicates a hitherto unexplored involvement of EMT. This review focuses on the role of EMT markers which are regulators of the EMT mediated complex network of molecular mechanisms involved in the pathogenesis of OSF and OSCC. Further the gene enrichment analysis and pathway analysis supports the association of the upregulated and downregulated genes in various EMT regulating pathways.

Role of Yes-associated protein and transcriptional coactivator with PDZ-binding motif in the malignant transformation of oral submucous fibrosis

Sharma M, Hunter KD, Fonseca FP, Shetty SS, Radhakrishnan R

Arch Oral Biol, 2021 Aug;128:105164.

PMID: 34044344 DOI: 10.1016/j.archoralbio.2021.105164

OBJECTIVE(S): The objective of the present manuscript is to elucidate the role of matrix stiffness in the malignant transformation of oral submucous fibrosis.

DESIGN: The role of matrix stiffness in several cancers including oral cancer was reviewed with a tailored search strategy using relevant keywords as per the Medline format. The role of molecular mediators, Yes-associated protein 1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) was weighed in the context of OSF along two distinct pathways.

RESULTS: Increased matrix stiffness activates the transcriptional coactivators, YAP and TAZ shuttling between the nucleus and cytoplasm. YAP and TAZ, serve as mechanical transducers in promoting cell migration, invasion and epithelial-mesenchymal transition (EMT). The hypoxic microenvironment in the advanced stage of OSF promotes the migratory phenotype through mechanical memory.

CONCLUSIONS: Reprogramming of a stiff matrix has the potential to restore the Hippo-YAP/TAZ tumor suppressor pathway and reverse fibrosis-associated tumor development.

Fulltext Understanding the molecular mechanism associated with reversal of oral submucous fibrosis targeting hydroxylysine aldehyde-derived collagen cross-links

Shetty SS, Sharma M, Kabekkodu SP, Kumar NA, Satyamoorthy K, Radhakrishnan R

J Carcinog, 2021;20:9.

PMID: 34526855 DOI: 10.4103/jcar.JCar_24_20

Fibrosis is a pathological state characterized by excessive deposition of the extracellular matrix components leading to impaired tissue function in the affected organ. It results in scarring of the affected tissue akin to an over-healing wound as a consequence of chronic inflammation and repair in response to injury. Persistent trauma of susceptible oral mucosa due to habitual chewing of betel quid resulting in zealous healing of the mucosal tissue is one plausible explanation for the onset of oral submucous fibrosis (OSF). The irreversibility and resistance of collagen to degradation and its high potential to undergo malignant change are a major reason for morbidity in OSF. Hence, early diagnosis and timely treatment are crucial to prevent the progression of OSF to malignancy. This review focuses on the mechanistic insight into the role of collagen cross-links in advancing fibrosis and possible therapeutic targets that bring about a reversal of fibrosis. These options may be beneficial if attempted as a specific therapeutic modality in OSF as is in organ fibrosis. The upregulation of lysyl oxidase and lysyl hydroxylase has been shown to exhibit the higher levels of the hydroxylysine aldehyde-derived cross-links in fibrosis and tumor stroma promoting the tumor cell survival, resistance, and invasion. The in silico analysis highlights the potential drugs that may target the genes regulating collagen crosslinking.

Biological implications of the immune factors in the tumour microenvironment of oral cancer

Shetty SS, Padam KSR, Hunter KD, Kudva A, Radhakrishnan R

Arch Oral Biol, 2021 Oct 24;133:105294.

PMID: 34735925 DOI: 10.1016/j.archoralbio.2021.105294

OBJECTIVE: The objective of this review is to decipher the biological implications of the immune factors in the tumour microenvironment in oral cancer. The restoration of balance between tumour tolerance and tumour eradication by the host immune cells is critical to provide effective therapeutic strategies.

DESIGN: The specific role of the stromal and the immune components in oral cancer was reviewed with a tailored search strategy using relevant keywords. The articles were retrieved from bibliometric databases indexed in PubMed, Scopus, and Embase. An in silico analysis was performed to identify potential drug candidates for immunotherapy, by accessing the Drug-Gene Interactions Database (DGIdb) using the rDGIdb package.

RESULTS: There is compelling evidence for the role of the cellular and extracellular components of the tumour microenvironment in inducing immunosuppression and progression of oral cancer. The druggable candidates specifically targeting the immune system are a viable option in the treatment of oral cancer as they can regulate the tumour microenvironment.

CONCLUSION: A complex interaction between the tumour and the immunological microenvironment influences the disease outcome in oral cancer. Targeting specific components of the immune system might be relevant, as immunotherapy may become the new standard of care for oral cancer.

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