A Plausible Proposition of CCL20-Related Mechanism in Fusobacterium nucleatum-Associated Oral Carcinogenesis

Objective: The objective of this prospective observational case–control study is to evaluate the prevalence of Fusobacterium nucleatum in the tissues of oral squamous cell carcinoma (OSCC). Reconnoitering the CCL20-related mechanism of carcinogenesis in Fusobacterium nucleatum-positive OSCC is another objective. Methodology: Tissues from 50 OSCC patients and 30 healthy oral tissues were collected. The prevalence of Fusobacterium nucleatum was evaluated in both tumour and healthy tissue by polymerase chain reaction. The immunohistochemistry of OSCC tissues was conducted to evaluate the difference in the expression of CCL20 between Fusobacterium nucleatum-positive and -negative OSCC tissues. Results: Fusobacterium nucleatum was significantly (p < 0.001) prevalent in OSCC tissues (74%), compared to healthy tissues (26%). No association of Fusobacterium nucleatum or CCL20 immuno-expression with any clinical or histopathological features of OSCC was observed. While the intensity of CCL20 immuno-expression did not differ (p = 0.053), the CCL20-positive cell population was significantly different (p = 0.034) between Fusobacterium nucleatum-positive and -negative OSCC. Conclusion: Fusobacterium nucleatum is possibly prevalent in oral cancer tissues in the Indian population. By using immunohistochemistry, this is the first study to propose that the carcinogenesis in Fusobacterium nucleatum-positive OSCC may be CCL20-related. The findings enrich the knowledge of mechanisms involved in Fusobacterium nucleatum-mediated oral carcinogenesis.

SPIRULINA – A WONDER NUTRACEUTICAL AGAINST CANCER: A REVIEW

Spirulina, a filamentous and spiral-shaped blue-green alga, contains an array of bioactive compounds and has emerged to be a nutraceutical. It has a unique blend of around 70 biologically active compounds which enhances its therapeutic significance. Its role against carcinogenesis can be attributed to its antioxidant and anti-inflammatory properties due to the presence of ingredients like C-Phycocyanin, ?-Carotene, Calcium Spirulan, Linoleic and Linolenic acids. Spirulina extracts were shown to enhance endonuclease activity, DNA repair and induction of apoptosis in cells. Some studies also reported myelosuppression and enhanced immune function. Murine studies indicated there was a possibility of reversing the mechanism of carcinogenesis, particularly in oral, stomach, breast and skin cancers as well as in doxorubicin, cyclophosphamide and DBMA-induced tumours. Spirulina also appeared to reduce cardio-, nephro- and hepato-toxicity in rodents. The chemo and radioprotective effect of Spirulina was also observed in various carcinogenic human cell lines. The C-phycocyanin component was shown to induce apoptosis in HeLa cells in vitro. Commercially available Spirulina is administered as an adjunct to chemotherapy. The evidence of effectiveness of Spirulina in cancer is extremely limited as far as the clinical trials are concerned. The Spirulina studies conducted on various types of carcinogenesis show a degree of similitude but are in a haphazard state. The current anatomization is an attempt on part of the authors to coalesce all the contemporaneous data and create a systematic review.

Advances in Rodent Models for Breast Cancer Formation, Progression, and Therapeutic Testing

Breast cancer is a highly complicated disease. Advancement in the treatment and prevention of breast cancer lies in elucidation of the mechanism of carcinogenesis and progression. Rodent models of breast cancer have developed into premier tools for investigating the mechanisms and genetic pathways in breast cancer progression and metastasis and for developing and evaluating clinical therapeutics. Every rodent model has advantages and disadvantages, and the selection of appropriate rodent models with which to investigate breast cancer is a key decision in research. Design of a suitable rodent model for a specific research purpose is based on the integration of the advantages and disadvantages of different models. Our purpose in writing this review is to elaborate on various rodent models for breast cancer formation, progression, and therapeutic testing.

Cytogenomic Changes in Sporadic Colorectal Cancer and Surrounding Nonneoplastic Tissues: The Relevance of Subtelomeric Copy Number Variations

The purpose of this study was to investigate the relevance of subtelomeric cytogenomic changes in patients with sporadic colorectal cancer (CRC) using multiplex ligation-dependent probe amplification (MLPA) and single nucleotide polymorphism arrays. The results revealed pathogenic genomic alterations in the TNFRS18 (1p), CHL1 (3p), TRIML2 (4q), FBXO25 (8p), NKX3-1 (8p), RECQL4 (8q), DOCK8 (9p), ZMYND11 (10p), KDM5A (12p), PSPC1 (13q), ADPRTL2 (14q), MTA1 (14q), DECR2 (16p), GAS8 (16q), THOC1 (18p), CTDP1 (18q), SOX12 (20p), ADRM1 (20q), UCKL1 (20q), OPRL1 (20q), IL17RA (22q), and SYBL1 (Xq) genes. We detected copy number variations (CNVs) with frequencies greater than 40% in the probes located in 20q, which contains very important genes in the study of tumors. These findings showed instability in the tumor genome and altered regions associated with cell migration, transcription activation, apoptosis, and immune system deregulation. Unexpectedly, we detected concomitant pathogenic CNVs in tumors and surrounding tissues. Our data suggest that characterizing the genomic CRC profile is an important contribution to better understanding instability as a mechanism of carcinogenesis in CRC patients.

Progress in the Understanding of the Immune Microenvironment and Immunotherapy in Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a remarkably aggressive thoracic malignancy with a limited survival of only 5-12 months. However, MPM still remains unresponsive to conventional standards of treatment, including pleurectomy and decortication, extrapleural pneumonectomy for resectable disease with or without chemotherapy, and/or radiation therapy. The mechanism of carcinogenesis has not been fully elucidated, although approximately 80% of cases can still be linked to asbestos exposure. The tumor immune microenvironment (TME) has been proven to play an important role in MPM pathogenesis and treatment outcomes. Several molecular pathways have been implicated in the MPM tumor microenvironment, such as angiogenesis, apoptosis, cell cycle regulation, and stromal processes. Immunotherapy has already shown promising results in other thoracic solid tumors, such as non-small-cell lung cancer (NSCLC). However, immunotherapy has shown less convincing results in MPM than in melanoma and NSCLC. A multicenter, randomized trial (DETERMINE) proved that immune checkpoint inhibition using tremelimumab, an anti-cytotoxic T lymphocyteassociated protein 4 (CTLA-4) antibody, failed to improve median overall survival. Therefore, it is important to explore the relationship between the characteristics of the tumor microenvironment and immunotherapy. Here, we review the heterogeneity of the TME and the progress in the understanding of the immune microenvironment and immunotherapy in MPM to explore the mechanisms of resistance to immunotherapy.

Pepsin and laryngeal and hypopharyngeal carcinomas

Laryngeal and hypopharyngeal carcinomas are common malignant tumors of the head and neck, which are both exhibiting increasing incidences. Laryngopharyngeal reflux is the retrograde flow of gastric contents into the larynx, oropharynx, and/or nasopharynx. There remains controversy regarding whether laryngopharyngeal reflux is a risk factor for laryngeal and hypopharyngeal cancers. The refluxing substances mainly include hydrochloric acid, pepsin, and occasionally bile acids and bile salts, as well as bacteria that colonize the gastrointestinal tract. Loss of epithelium in the mucous membrane of the throat is presumably caused by pepsin. Here, we review the relationships between laryngopharyngeal reflux and both laryngeal and hypopharyngeal carcinomas, as well as the significance of pepsin, methods of clinical detection, and the mechanism of carcinogenesis.