Protein Profile of Human Saliva as a Predictive and Prognostic Tool for OSCC in Tamol Chewer's Population in Assam.

OBJECTIVE: To identify potential proteomic salivary biomarker in tamol chewers and comparing it to healthy and Oral squamous cell carcinoma cases. METHODS: A total of fifty unstimulated saliva samples were collected from the healthy volunteers, tamol chewers (without tobacco), and OSCC patients referred to North-East cancer Hospital, Jorabat, Assam, India. The 2-D gel analysis and western blotting were performed to analyze protein profiling. RESULTS: The identified proteins were serum albumin, HSP (Heat shock protein) 27, gamma actin, SCC (Squamous cell carcinoma) 1, and Annexin A4. All the proteins were associated with OSCC development when their values were compared with those of normal healthy subjects. HSP27 was subjected to further validation using western blotting methods. An increase of 18.39% (Serum Albumin), 15.04% (gamma actin), 14.01% (SSC 1), and 20.22% (ANX4) were observed in Tamol chewers when compared with healthy control subjects. CONCLUSION: Our results revealed that the identified salivary proteins have a positive association with OSCC development. Profiling of these saliva proteomes especially HSP (Heat shock protein) 27 as a potential biomarker for OSCC detection in the high-risk population is recommended.

Effect of corticosteroid ointment on radiation induced dermatitis in head and neck cancer patients: A prospective study.

BACKGROUND: Almost all the patients receiving curative radiotherapy for head and neck cancer develop radiation dermatitis, which many a times leads to treatment interruption and reduce patient compliance. In this study, we evaluated the effect of potent topical steroid (Betamethasone Valerate 0.1%) cream on acute radiation dermatitis in head and neck cancer patients receiving curative radiotherapy. METHODS: A total 106 patients of head and neck cancers were randomly divided into arm A (52 patients) and arm B (54 patients). The patient in study arm A were treated with topical betamethasone 0.1% twice daily during radiotherapy/chemo-radiotherapy and arm B was kept as control. The radiation reaction in both the groups was monitored weekly according to Radiation Therapy Oncology Group (RTOG) acute radiation dermatitis grading. RESULTS: Out of 106 patients, 85 (80.2%) patients completed treatment. Patient in control arm had earlier onset of grade 1 reaction (5.7% in arm A vs 16.7 % in arm B at 2nd week, P value 0.157 and 28.8% in arm A vs 50% in arm B at 3rd week, P value 0.028) and progression of radiation dermatitis. In 7th week patient in arm A had higher grade 1 reaction (17.3% in arm A vs 0% in arm B), while arm B had higher grade 2 reaction (66.7% arm B vs 55.8% in arm A). There was no difference in incidence of grade 3 and 4 reaction. No difference was observed in time taken for reaction to heal. CONCLUSION: Topical Betamethasone can delay the onset and progression of radiation dermatitis in head and neck cancer, without significant delay in wound healing.

MYC Regulates the HIF2α Stemness Pathway via Nanog and Sox2 to Maintain Self-Renewal in Cancer Stem Cells versus Non-Stem Cancer Cells.

Cancer stem cells (CSC) maintain both undifferentiated self-renewing CSCs and differentiated, non-self-renewing non-CSCs through cellular division. However, molecular mechanisms that maintain self-renewal in CSCs versus non-CSCs are not yet clear. Here, we report that in a transgenic mouse model of MYC-induced T-cell leukemia, MYC, maintains self-renewal in Sca1+ CSCs versus Sca-1- non-CSCs. MYC preferentially bound to the promoter and activated hypoxia-inducible factor-2α (HIF2α) in Sca-1+ cells only. Furthermore, the reprogramming factors, Nanog and Sox2, facilitated MYC regulation of HIF2α in Sca-1+ versus Sca-1- cells. Reduced expression of HIF2α inhibited the self-renewal of Sca-1+ cells; this effect was blocked through suppression of ROS by N-acetyl cysteine or the knockdown of p53, Nanog, or Sox2. Similar results were seen in ABCG2+ CSCs versus ABCG2- non-CSCs from primary human T-cell lymphoma. Thus, MYC maintains self-renewal exclusively in CSCs by selectively binding to the promoter and activating the HIF2α stemness pathway. Identification of this stemness pathway as a unique CSC determinant may have significant therapeutic implications. SIGNIFICANCE: These findings show that the HIF2α stemness pathway maintains leukemic stem cells downstream of MYC in human and mouse T-cell leukemias. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/79/16/4015/F1.large.jpg.

Identification and Validation of Fibroblast Growth Factor 12 Gene as a Novel Potential Biomarker in Esophageal Cancer Using Cancer Genomic Datasets.

Esophageal squamous cell carcinoma (ESCC) has a complex, multifactorial etiology in which environmental, geographical, and genetic factors play major roles. It is the second most common cancer among men and the fourth most common among women in India, with a particularly high prevalence in Northeast India. In this study, an integrative in silico [DAVID, NCG5.0, Oncomine, Cancer Cell Line Encyclopedia, and The Cancer Genome Atlas (TCGA)] approach was used to identify the potential biomarkers by using the available three genomic datasets on ESCC from Northeast India followed by its in vitro functional validation. Fibroblast Growth Factor 12 (FGF12) gene was overexpressed in ESCC. The upregulation of FGF12 was also observed on ESCC of TCGA OncoPrint portal, whereas very low expression of FGF12 gene was mapped in normal esophageal tissue on the GTEx database. Silencing of FGF12 showed significant inhibition in activity of tumor cell proliferation, colony formation, and cell migration. The upregulation of FGF12 showed significantly reduced survival in ESCC patients. The protein interaction analysis of FGF12 found the binding with MAPK8IP2 and MAPK13. High expression of FGF12 along with MAPK8IP2, and MAPK13 proteins correlate with poor survival in ESCC patients. Tissue microarray also showed expression of these proteins in patients with ESCC. These results indicate that FGF12 has a potential role in ESCC and suggest that cancer genomic datasets with application of in silico approaches are instrumental for biomarker discovery research broadly and specifically, for the identification of FGF12 as a putative biomarker in ESCC.

Evaluation of Tongue Cancer Using High-Resolution Sonography: Comparison With Magnetic Resonance Imaging.

OBJECTIVES: To evaluate the role of sonography in assessing tongue cancer compared with magnetic resonance imaging (MRI). METHODS: A randomized prospective study was performed on 40 cases of tongue cancer. Magnetic resonance imaging and sonography of the tongue were performed, tumor spreading to particular sites was recorded in all cases. Sonographic and MRI findings were correlated with histopathologic findings in 18 operable cases. In 22 inoperable cases, sonography was compared only with MRI. RESULTS: In operable patients, sonography achieved sensitivity of 61.1%, whereas MRI achieved sensitivity of 94.4%. The difference was statistically significant (P < .05). The results for detection of individual site involvement on sonography and MRI were as follows: intrinsic muscles only, 0 and 6, respectively; tongue base, 5 and 5; genioglossus muscle, 34 and 34; mylohyoid muscle, 9 and 8; sublingual space, 12 and 14; sublingual neurovascular bundle, 12 and 12; submandibular gland, 3 and 3; spread across the lingual septum, 17 and 17; and alveolar involvement, 0 and 1. There was no significant difference (P> .05) between sonography and MRI in detecting involvement of the above-mentioned sites except for cases with only intrinsic muscles and alveolar involvement. Tumors involving intrinsic tongue muscles only were not visualized on sonography. They all underwent surgery, resulting in reduced sensitivity of sonography in operable cases. CONCLUSIONS: Even though small tumors were difficult to visualize, sonography can play an important role in assessment of tumor extension in large growths, especially when MRI is unavailable, contraindicated, or unaffordable, and for posttreatment follow-up.

Status of epigenetic chromatin modification enzymes and esophageal squamous cell carcinoma risk in northeast Indian population.

Esophageal cancer incidence is reported in high frequency in northeast India. The etiology is different from other population at India due to wide variations in dietary habits or nutritional factors, tobacco/betel quid chewing and alcohol habits. Since DNA methylation, histone modification and miRNA-mediated epigenetic processes alter the gene expression, the involvement of these processes might be useful to find out epigenetic markers of esophageal cancer risk in northeast Indian population. The present investigation was aimed to carryout differential expression profiling of chromatin modification enzymes in tumor and normal tissue collected from esophageal squamous cell carcinoma (ESCC) patients. Differential mRNA expression profiling and their validation was done by quantitative real time PCR and tissue microarray respectively. Univariate and multiple logistic regression analysis were used to analyze the epidemiological data. mRNA expression data was analyzed by Student t-test. Fisher exact test was used for tissue microarray data analysis. Higher expression of enzymes regulating methylation (DOT1L and PRMT1) and acetylation (KAT7, KAT8, KAT2A and KAT6A) of histone was found associated with ESCC risk. Tissue microarray done in independent cohort of 75 patients revealed higher nuclear protein expression of KAT8 and PRMT1 in tumor similar to mRNA expression. Expression status of PRMT1 and KAT8 was found declined as we move from low grade to high grade tumor. Betel nut chewing, alcohol drinking and dried fish intake were significantly associated with increased risk of esophageal cancer among the study subject. Study suggests the association of PRMT1 and KAT8 with esophageal cancer risk and its involvement in the transition process of low to high grade tumor formation. The study exposes the differential status of chromatin modification enzymes between tumor and normal tissue and points out that relaxed state of chromatin facilitates more transcriptionally active genome in esophageal carcinogenesis.

Cutaneous metastasis from squamous carcinoma of the base of tongue.

CONTEXT: Cutaneous metastasis from head and neck cancer is uncommon and it is seen from laryngeal cancer. Cutaneous metastasis from the base of tongue is relatively rare. CASE REPORT: A 55-year-old male, who was a treated case of squamous carcinoma of the base of tongue presented with metastatic nodule on the skin of face and thigh. But, there was complete resolution of the tumor at the primary site. In the present case, clinically obvious cutaneous nodules with metastasis appeared soon after the completion of treatment with concurrent chemo-radiotherapy. The metastasis to the skin of face clinically appeared like an inflammatory lesion. Fine needle aspiration cytology confirmed the diagnosis of metastasis to skin at both the sites. CONCLUSION: Our case has highlighted that there could be associated occult skin metastasis at the time of diagnosis in squamous carcinoma of the base of tongue.

Basaloid Squamous Carcinoma of Skin Associated with Xeroderma Pigmentosum in an 8-year-old Child: A Rare Entity.

Xeroderma pigmentosum (XP) is a rare autosomal recessive genodermatosis associated with hypersensitivity to ultraviolet (UV) light, due to defects in deoxyribonucleic acid (DNA) repair. Basaloid squamous cell carcinoma is a rare aggressive variant of squamous cell carcinoma. Patients with XP are at increased risk of developing cutaneous malignancy and are commonly associated with squamous carcinoma. We report an extremely rare case of 8-year-old child with XP along with basaloidsquamous carcinoma of skin; and review of literature related to it.

Evaluation of hypopharyngeal carcinoma using high-resolution ultrasound: comparison with CT.

BACKGROUND: To evaluate the role of sonography (US) in assessing hypopharyngeal carcinoma when compared with CT. METHODS: A randomized prospective study was performed on 40 biopsy-proven cases of hypopharyngeal carcinoma.Contrast-enhanced CT of the neck was performed in all patients, followed by US. Sonographic identification of any tumor extension into the extralaryngeal soft tissues, postcricoid space, subglottis, thyroid gland, esophagus, and across the midline was recorded. US observations and CT findings were compared and then correlated with the histopathologic findings in 14 operative cases. In the remaining 26 inoperable cases, US was compared only with CT. RESULTS: Our cohort was composed of 38 men and 2 women ranging in age from 36 to 59 years. In a subset of 14 operative patients, US had a sensitivity of 71.4% (10/14), while CT achieved a sensitivity of 92.8% (13/14), and the difference was not statistically significant (p > 0.05). US and CT findings concurred in 67.5% (27/40) of cases. CONCLUSIONS: Even though small tumors are difficult to visualize, US can play a significant role in the assessment of tumor extension within and beyond the larynx, especially when cross-sectional imaging is either unavailable or unaffordable.

Inflammatory myofibroblastic tumor of the upper alveolus: A rare entity presenting as a jaw swelling.

Inflammatory myofibroblastic tumor (IMT) is a rare tumor of borderline nature that can clinically present as a malignant neoplasm. It commonly occurs in the lungs, and a very few oral IMTs have been reported in the literature. IMT consists of inflammatory cells and myofibroblastic spindle cells. The diagnosis of IMT requires histopathological examination with immunohistochemical staining to look for the expression of smooth-muscle actin for confirmation of the diagnosis. The objective of this paper is to report an IMT on the upper alveolus with clinic-a pathological similarity with a malignant lesion and its management. Though oral IMTs are rare, it should be considered in the differential diagnosis of tumors of the upper jaw. Complete surgical excision of alveolar IMT is the treatment of choice because of its unpredictable clinical behavior. The patients with oral IMTs require periodic post-surgical follow-up for recurrence.

Population-based incidence and patterns of cancer in Kamrup Urban Cancer Registry, India.

BACKGROUND: Cancer is not a notifiable disease in India. The Indian Council of Medical Research (ICMR) initiated the National Cancer Registry Programme in 1982 to measure the burden and pattern of cancer in India. However, no data were available from the northeastern region till 2001 when a WHO- sponsored, ICMR project showed a relatively high frequency of microscopically diagnosed cases of cancer in the region. A population-based cancer registry was established in January 2003 in Guwahati to cover the Kamrup Urban district in the northeastern region of India. We report the data generated in the first 6 years of the registry (2003-08). METHODS: Information on cancer was obtained by voluntary participation of different sources including major hospitals, diagnostic centres, state referral board and birth and death registry centres within the registry area. A total of 6608 cases were registered during the 6-year period (1 January 2003- 31 December 2008); 3927 were men and 2681 women. RESULTS: The age-adjusted incidence rates were 167.9 per 100000 among men and 133.8 per 100000 among women. The oesophagus was the leading site of cancer among men, comprising 18.3% of all cancers with an age-adjusted rate of 30.7 per 100000. Among women, the breast followed by the cervix uteri were the leading sites of cancer. These two cancers comprised 30% of all cancers among women. Tobacco-related cancers accounted for 58.2% of cancers among men and 26.9% of cancers among women. CONCLUSION: The patterns observed from the analysis of data from the cancer registry at Guwahati provide comprehensive information on occurrence of cancer and can be valuable for planning cancer control programmes in the region.

ADP-ribose polymer--a novel and general biomarker of human cancers of head & neck, breast, and cervix.

BACKGROUND: Poly-ADP-ribosylation, a reversible post-translational modification of primarily chromosomal proteins, is involved in various cellular and molecular processes including carcinogenesis. ADP-ribose polymer or poly-ADP-ribose adducts are enzymatically added onto or stripped off the target chromosomal proteins during this metabolic process. Due to this, the chromatin superstructure is reversibly altered, which significantly influences the pattern of gene expression. We hypothesize that a decrease in the concentration of total poly-ADP-ribose adducts of peripheral blood lymphocyte (PBL) proteins strongly correlates with the incidence of human cancer. RESULTS: Using a novel immunoprobe assay, we show a statistically significant (P ≤ 0.001) reduction (~ 42 to 49%) in the level of poly-ADP-ribose adducts of PBL proteins of patients with advanced cancers of head & neck (H & N) region (comprising fourteen distinct cancers at different sites), breast and cervix in comparison to healthy controls. CONCLUSIONS: These findings imply potential utility of the poly-ADP-ribose adducts of PBL proteins as a novel and general biomarker of human cancers with potentials of significant clinical and epidemiological applications.