Patterns of Cancer Incidence and Mortality in North- Eastern India: The First Report from the Population Based Cancer Registry of Tripura.

BACKGROUND: There is, till date no population-based data regarding cancer patterns in North- Eastern India, dictating the need to understand the epidemiology of cancer in this population for its effective management. METHODS: This is the first report of the Population Based Cancer Registry (PBCR) in Tripura (2010-2014). The protocol involves active collection of data on all cancer cases from Tripura through staff visit in more than 150 sources of incident and mortality registration, government and private hospitals, municipal corporation, etc. and scrutiny, corroboration with existing records. Data was analyzed statistically to understand cancer trends in terms of incidence and mortality across different sites, age groups affected and gender. RESULTS: A total of 10,251 cases were registered during the period, with overall age-adjusted incidence rates of 75.7 and 54.9 per 100,000 males and females respectively. Crude Incidence Rate (CR) and Age- Adjusted Rate (AAR) was among the lowest reported in India, probably due to associated socio-economic factors. The most prevalent cancers were lung (18.1%), esophageal (8.3%) for men and cervix uteri (17.6%), breast (13.8%) for females. Gall bladder cancer in females was one of the highest in the country. Rate of cancer mortality in the population was quite high and significantly increased with time, probably accounting for dearth in early detection and feasible treatment alternatives. CONCLUSION: The data suggests that high cancer incidence and mortality are prevalent in the population of Tripura, dictating the need of active tobacco control measures, early detection and awareness drives for effective cancer control.

Secondary Structure-Dependent Physicochemical Interaction of Oligonucleotides with Gold Nanorod and Photothermal Effect for Future Applications: A New Insight.

We investigate the physicochemical interactions of gold nanorod (GNR) with single-stranded, double-stranded, and hairpin DNA structures to improve the biological compatibility as well as the therapeutic potential, including the photothermal effect of the conjugates. Studies have demonstrated that different DNA secondary structures, containing thiol group, have different patterns of physicochemical interaction. Conjugation efficiency of paired oligonucleotides are significantly higher than that of oligonucleotides with naked bases. Furthermore, hairpin-shaped DNA structures are most efficient in terms of conjugation and increased dispersion, with least interference on GNR near-infrared absorbance and photothermal effect. Our conjugation method can successfully exchange the overall coating of the GNR, attaching the maximum number of DNA molecules, thus far reported. Chemical mapping depicted uniform attachment of thiolated DNA molecules without any topological preference on the GNR surface. Hairpin DNA-coated GNR are suitable for intracellular uptake and remain dispersed in the cellular environment. Finally, we conjugated GNR with 5-fluoro-2'-deoxyuridine-containing DNA hairpin and the conjugate demonstrated significant cytotoxic activity against human cervical cancer cell line (KB). Thus, hairpin DNA structures could be utilized for optimal dispersion and photothermal effect of GNR, along with the delivery of cytotoxic nucleotides, developing the concept of multimodality approach.

Differential transmission of the molecular signature of RBSP3, LIMD1 and CDC25A in basal/ parabasal versus spinous of normal epithelium during head and neck tumorigenesis: A mechanistic study.

Head and neck squamous cell carcinoma (HNSCC) is a global disease and mortality burden, necessitating the elucidation of its molecular progression for effective disease management. The study aims to understand the molecular profile of three candidate cell cycle regulatory genes, RBSP3, LIMD1 and CDC25A in the basal/ parabasal versus spinous layer of normal oral epithelium and during head and neck tumorigenesis. Immunohistochemical expression and promoter methylation was used to determine the molecular signature in normal oral epithelium. The mechanism of alteration transmission of this profile during tumorigenesis was then explored through additional deletion and mutation in HPV/ tobacco etiological groups, followed byclinico-pathological correlation. In basal/parabasal layer, the molecular signature of the genes was low protein expression/ high promoter methylation of RBSP3, high expression/ low methylation of LIMD1 and high expression of CDC25A. Dysplastic epithelium maintained the signature of RBSP3 through high methylation/ additional deletion with loss of the signatures of LIMD1 and CDC25A via deletion/ additional methylation. Similarly, maintenance and / or loss of signature in invasive tumors was by recurrent deletion/ methylation. Thus, differential patterns of alteration of the genes might be pre-requisite for the development of dysplastic and invasive lesions. Etiological factors played a key role in promoting genetic alterations and determining prognosis. Tobacco negative HNSCC patients had significantly lower alterations of LIMD1 and CDC25A, along with better survival among tobacco negative/ HPV positive patients. Our data suggests the necessity for perturbation of normal molecular profile of RBSP3, LIMD1 and CDC25A in conjunction with etiological factors for head and neck tumorigenesis, implying their diagnostic and prognostic significance.

Analytical Study on the Efficacy of Neoadjuvant Chemotherapy Using a Combination of Methotrexate, Bleomycin, and Cisplatin in the Management of Advanced Squamous Cell Carcinoma of the Buccal Mucosa.

CONTEXT: Cancers of the buccal mucosa (CaBM) predominate in India with late- stage diagnosis and poor survival, necessitating optimal management. Aim: Our study aimed at testing the efficacy of combination neoadjuvant chemotherapy (NACT) using cisplatin (CIS), bleomycin (BL) and methotrexate (MTX) for reducing tumour volume prior to surgery. METHODOLOGY: Patients with advanced CaBM (stage III, IV, n = 100) were administered 6 rounds of NACT with CIS, BL and MTX. Responses, toxicity and 6-month follow-up was monitored statistically to determine persistence of response. RESULTS: A significant number of patients showed objective response as either complete or partial tumour regression with subjective response as reduced trismus, pain, salivation and foul odour. Moreover, there was mild associated toxicity and tumour regression continued in most patients even after 6-month follow-up. CONCLUSION: Our study indicates that NACT with CIS, BL and MTX offers a good therapeutic alternative in terms of significant objective and subjective responses, low toxicity, affordable costs and persistent responses.

Human papilloma virus (HPV) infection leads to the development of head and neck lesions but offers better prognosis in malignant Indian patients.

Head and neck cancers constitute a multifactorial global disease burden and are associated with human papilloma virus (HPV) as a possible risk factor. The aim of the study is to understand the relationship between HPV and the development of head and neck lesions in Indian patients. To this end, frequency of HPV was assessed in relation to different demographic and etiological features and correlated with patient survival. The prevalence of HPV significantly increased from mild dysplastic lesions (43.6%) to head and neck squamous cell carcinoma (HNSCC) stage IV (68.5%) with HPV 16 being pre-dominant in both dysplasia (43.8%) and HNSCC (61.5%). Similar trend was observed in increasing grades of the tumour. In invasive lesions, patients aged below the median age of onset showed significantly higher occurrence of HPV than those above it. Patients harbouring HPV showed a significantly better survival irrespective of age of onset. Likewise, better survival was observed in tobacco habit negative/HPV-positive patients, and as reflected in both univariate and multivariate analysis. Majority of the HPV 16-positive samples showed moderate/high nuclear expression of HPV E6 and E7 proteins in tumours and respective basal layer of adjacent normal tissues. Thus, our data indicate that frequent HPV infection, along with tobacco habit, is a pre-requisite factor for the development of HNSCC of Indian patients but offers a better survival even during tobacco usage, implicating its diagnostic and prognostic importance.

WITHDRAWN: Differential molecular signature alterations of RBSP3, LIMD1 and CDC25A in normal oral epithelium during oral tumorigenesis.

The Accepted Manuscript version of this article (published on 1 June 2016) was withdrawn on 24 November 2017 at the request of the authors.