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1.
Ann Oncol ; 28(3): 597-603, 2017 03 01.
Article in English | MEDLINE | ID: mdl-27998968

ABSTRACT

Background: Lung cancer is the leading cause of cancer-related deaths across the world. In this study, we present therapeutically relevant genetic alterations in lung adenocarcinoma of Indian origin. Materials and methods: Forty-five primary lung adenocarcinoma tumors were sequenced for 676 amplicons using RainDance cancer panel at an average coverage of 1500 × (reads per million mapped reads). To validate the findings, 49 mutations across 23 genes were genotyped in an additional set of 363 primary lung adenocarcinoma tumors using mass spectrometry. NIH/3T3 cells over expressing mutant and wild-type FGFR3 constructs were characterized for anchorage independent growth, constitutive activation, tumor formation and sensitivity to FGFR inhibitors using in vitro and xenograft mouse models. Results: We present the first spectrum of actionable alterations in lung adenocarcinoma tumors of Indian origin, and shows that mutations of FGFR3 are present in 20 of 363 (5.5%) patients. These FGFR3 mutations are constitutively active and oncogenic when ectopically expressed in NIH/3T3 cells and using a xenograft model in NOD/SCID mice. Inhibition of FGFR3 kinase activity inhibits transformation of NIH/3T3 overexpressing FGFR3 constructs and growth of tumors driven by FGFR3 in the xenograft models. The reduction in tumor size in the mouse is paralleled by a reduction in the amounts of phospho-ERK, validating the in vitro findings. Interestingly, the FGFR3 mutations are significantly higher in a proportion of younger patients and show a trend toward better overall survival, compared with patients lacking actionable alterations or those harboring KRAS mutations. Conclusion: We present the first actionable mutation spectrum in Indian lung cancer genome. These findings implicate FGFR3 as a novel therapeutic in lung adenocarcinoma.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Drug Resistance, Neoplasm/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Receptor, Fibroblast Growth Factor, Type 3/genetics , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Adult , Aged , Animals , Cell Proliferation/drug effects , Female , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/pathology , Male , Mice , Middle Aged , Mutation , NIH 3T3 Cells , Proto-Oncogene Proteins p21(ras)/genetics , Pyrimidines/administration & dosage , Receptor, Fibroblast Growth Factor, Type 3/antagonists & inhibitors , Xenograft Model Antitumor Assays
2.
Int J Clin Pediatr Dent ; 8(2): 163-5, 2015.
Article in English | MEDLINE | ID: mdl-26379389

ABSTRACT

Duchenne muscular dystrophy (DMD) is an recessive X-linked mediated, musculoskeletal disorder that affects only males. It is the most common and severe form of muscular dystrophy where there is failure to manufacture dystrophin. Clinically, it is characterized by progressive muscle wasting eventually leading to premature death. This case report describes the genetic, oral and systemic findings in two cases of DMD in male siblings. How to cite this article: Suneja B, Suneja ES, Adlakha VK, Chandna P. A Rare Case Report of Neurodegenerative Disease: Duchenne Muscular Dystrophy in Two Male Siblings. Int J Clin Pediatr Dent 2015;8(2):163-165.

3.
J Indian Soc Pedod Prev Dent ; 29(1): 71-3, 2011.
Article in English | MEDLINE | ID: mdl-21521924

ABSTRACT

Clefts of the palate, alveolus and lip are some of the most frequently encountered anomalies of the face. This article presents a case report of a neonate with cleft lip and palate in whom a feeding obturator was delivered. This article demonstrates the indications, construction, and benefits of a palatal obturator in an 11-day-old infant with a bilateral cleft lip and palate.


Subject(s)
Cleft Lip/rehabilitation , Cleft Palate/rehabilitation , Dental Prosthesis Design , Palatal Obturators , Biocompatible Materials , Dental Impression Materials , Dental Impression Technique , Humans , Infant, Newborn , Polyethylene , Polyvinyls , Siloxanes
4.
J Indian Soc Pedod Prev Dent ; 28(4): 293-6, 2010.
Article in English | MEDLINE | ID: mdl-21273719

ABSTRACT

Peripheral giant cell granuloma is a benign reactive lesion of gingiva. It manifests as a firm, soft, bright nodule or as a sessile or pedunculate mass. This article reports the management of peripheral giant cell granuloma in a 12-year-old boy by surgical excision.


Subject(s)
Gingival Diseases/surgery , Granuloma, Giant Cell/surgery , Child , Diagnosis, Differential , Diastema/etiology , Gingival Diseases/complications , Gingival Diseases/pathology , Granuloma, Giant Cell/complications , Granuloma, Giant Cell/pathology , Humans , Male , Maxilla
5.
J Environ Sci Eng ; 49(1): 51-3, 2007 Jan.
Article in English | MEDLINE | ID: mdl-18472560

ABSTRACT

The physico-chemical and bacteriological analysis was carried out to assess the water quality of a sacred water tank "Sannihit Sarovar" in Kurukshetra (India) and the results are presented in this paper. Water quality of this holy tank found impaired with mass bathing and offerings made in this Sarovar, which cause organic pollution. Different parameters measured are temperature, pH, colour, turbidity, D.O., B.O.D., C.O.D., acidity, total alkalinity, sulphate, total hardness, total solids, suspended solids, dissolved solids, chloride, nitrate, total bacterial count, coliform and E. coli. From the obtained data, it is found that parameters like, colour, turbidity, acidity, DO, BOD, COD, total bacterial count, coliform and E. coli exceed the permissible values for organized outdoor bathing use of waters in this tank, whereas other parameters were found within the limits or below limit.


Subject(s)
Baths , Fresh Water/analysis , Water Pollutants/analysis , Chlorides/analysis , Colony Count, Microbial , Color , Enterobacteriaceae/isolation & purification , Environmental Monitoring , Escherichia coli/isolation & purification , Hydrogen-Ion Concentration , India , Nephelometry and Turbidimetry , Nitrates/analysis , Oxygen/analysis , Sulfates/analysis , Temperature , Water Microbiology
6.
Proc Natl Acad Sci U S A ; 102(36): 12962-7, 2005 Sep 06.
Article in English | MEDLINE | ID: mdl-16123131

ABSTRACT

The central problem in cancer chemotherapy is the severe toxic side effects of anticancer drugs on healthy tissues. Invariably the side effects impose dose reduction, treatment delay, or discontinuance of therapy. To limit the adverse side effects of cancer chemotherapy on healthy organs, we proposed a drug delivery system (DDS) with specific targeting ligands for cancer cells. The proposed DDS minimizes the uptake of the drug by normal cells and enhances the influx and retention of the drug in cancer cells. This delivery system includes three main components: (i) an apoptosis-inducing agent (anticancer drug), (ii) a targeting moiety-penetration enhancer, and (iii) a carrier. We describe one of the variants of such a system, which utilizes camptothecin as an apoptosis-inducing agent and poly(ethylene glycol) as a carrier. Luteinizing hormone-releasing hormone (LHRH) was used as a targeting moiety (ligand) to LHRH receptors that are overexpressed in the plasma membrane of several types of cancer cells and are not expressed detectably in normal visceral organs. The results showed that the use of LHRH peptide as a targeting moiety in the anticancer DDS substantially enhanced the efficacy of chemotherapy, led to amplified apoptosis induction in the tumor, and minimized the side effects of the anticancer drug on healthy organs. The LHRH receptor targeting DDS did not show in vivo pituitary toxicity and did not significantly influence the time course or the plasma concentration of luteinizing hormone and its physiological effects on the reproductive functions of mice.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Drug Delivery Systems/methods , Gonadotropin-Releasing Hormone/pharmacokinetics , Neoplasms/drug therapy , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Cell Line, Tumor , Disease Models, Animal , Female , Gene Expression Regulation, Neoplastic , Humans , Mice , Mice, Nude , Molecular Structure , Neoplasms/genetics , Neoplasms/pathology , Organ Specificity , Receptors, LHRH/genetics , Receptors, LHRH/metabolism , Xenograft Model Antitumor Assays
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