title: Reduction of proliferation and induction of apoptosis are associated with shrinkage of head and neck squamous cell carcinoma due to neoadjuvant chemotherapy.
abstract: BACKGROUND
  Neoadjuvant chemotherapy (NACT) is a treatment modality whereby chemotherapy is used as the initial treatment of HNSCC in patients presenting with advanced cancer that cannot be treated by other means. It leads to shrinkage of tumours to an operable size without significant compromise to essential oro-facial organs of the patients. The molecular mechanisms behind shrinkage due to NACT is not well elucidated.
  
  
  METHODS
  Eleven pairs of primary HNSCCs and adjacent normal epithelium, before and after chemotherapy were screened for cell proliferation and apoptosis. This was followed by immunohistochemical analysis of some cell cycle (LIMD1, RBSP3, CDC25A, CCND1, cMYC, RB, pRB), DNA repair (MLH1, p53) and apoptosis (BAX, BCL2) associated proteins in the same set of samples.
  
  
  RESULTS
  Significant decrease in proliferation index and increase in apoptotic index was observed in post-therapy tumors compared to pre-therapy. Increase in the RB/ pRB ratio, along with higher expression of RBSP3 and LIMD1 and lower expression of cMYC were observed in post-therapy tumours, while CCND1 and CDC25A remained unchanged. While MLH1 remained unchanged, p53 showed higher expression in post-therapy tumors, indicating inhibition of cell proliferation and induction of apoptosis. Increase in the BAX/BCL2 ratio was observed in post-therapy tumours, indicating up-regulation of apoptosis in response to therapy.
  
  
  CONCLUSIONS
  Thus, modulation of the G1/S cell cycle regulatory proteins and apoptosis associated proteins might play an important role in tumour shrinkage due to NACT.
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata, India E-mail : ckpanda.cnci@gmail.com.
authors.forename: Shreya
authors.initials: S
authors.lastname: Sarkar
authors.forename: Guru Prasad
authors.initials: GP
authors.lastname: Maiti
authors.forename: Jayesh
authors.initials: J
authors.lastname: Jha
authors.forename: Jaydip
authors.initials: J
authors.lastname: Biswas
authors.forename: Anup
authors.initials: A
authors.lastname: Roy
authors.forename: Susanta
authors.initials: S
authors.lastname: Roychoudhury
authors.forename: Tyson
authors.initials: T
authors.lastname: Sharp
authors.forename: Chinmay Kumar
authors.initials: CK
authors.lastname: Panda
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D004260:DNA Repair; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D000077195:Squamous Cell Carcinoma of Head and Neck; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins