Chemoprevention of Head and Neck Cancer by Green Tea Extract: EGCG—The Role of EGFR Signaling and “Lipid Raft”

Over the past decade dose-intensified chemo-radiotherapy or molecular targeted therapy has been introduced into the treatments of head and neck squamous cell carcinoma (HNSCC) to improve the outcomes of this dismal disease. However, these strategies have revealed only limited efficacy so far. Moreover, the frequent occurrences of second primary tumor further worsen the prognosis of patients. In this context, early detection and chemoprevention appear to be a realistic and effective method to improve the prognosis as well as quality of life in patients with HNSCC. In this short paper, we discuss the potential of green tea extract, (-)-epigallocatechin-3-galate (EGCG) in HNSCC chemoprevention, focusing on two aspects that are provided recently: (1) evidence of clinical efficacy and (2) unique biological effects on “lipid raft” that emerged as an important platform of numerous biophysical functions, for example, receptor tyrosin kinases (RTKs) signalings including epidermal growth factor receptor (EGFR), which play critical roles in HNSCC carcinogenesis

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

Background and purposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] https://doi.org/10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals

A case of hypopharyngeal cancer with stenosis, perforation, and pyogenic spondylitis development after chemoradiotherapy

Introduction: Chemoradiotherapy plays an important role in preserving function and morphology in head and neck cancer. However, in a few cases, chemoradiotherapy has been shown to result in late complications, such as hypopharyngeal perforation, which is very rare. Presentation of case: A 65-year-old man, who had undergone chemoradiotherapy for hypopharyngeal cancer 30 months previously, presented with high fever and neck pain. He subsequently developed hypopharyngeal stenosis, hypopharyngeal perforation, and a retropharyngeal abscess followed by pyogenic spondylitis. He underwent surgical treatment (resection with reconstruction) and was administered an antibacterial agent and steroids for an extended period. This treatment regimen was successful, and the patient has survived disease-free without symptoms. Discussion: Chemoradiotherapy-induced hypopharyngeal perforation is an extremely rare condition. In the present case, the perforation was large (2 cm), and the hypopharyngeal cavity was originally constricted. Pharyngeal reconstruction with a jejunal autograft was therefore necessary. Through the present case, we reconfirmed that although the primary purpose of chemoradiotherapy is organ preservation, it can also lead to organ destruction and fatal complications. It is important that physicians be aware of the possibility of hypopharyngeal perforation so as to avoid delayed diagnosis and treatment of similar rare cases. Conclusion: Hypopharyngeal perforation can sometimes be fatal because it can lead to pyogenic spondylitis. Suitable surgical techniques and appropriate doses of antibacterial agents for long-term use were appropriate treatments for the patient in this case

Chemoprevention of Head and Neck Cancer by Green Tea Extract: EGCG-The Role of EGFR Signaling and "Lipid Raft

Over the past decade dose-intensified chemo-radiotherapy or molecular targeted therapy has been introduced into the treatments of head and neck squamous cell carcinoma (HNSCC) to improve the outcomes of this dismal disease. However, these strategies have revealed only limited efficacy so far. Moreover, the frequent occurrences of second primary tumor further worsen the prognosis of patients. In this context, early detection and chemoprevention appear to be a realistic and effective method to improve the prognosis as well as quality of life in patients with HNSCC. In this short paper, we discuss the potential of green tea extract, (-)-epigallocatechin-3-galate (EGCG) in HNSCC chemoprevention, focusing on two aspects that are provided recently: (1) evidence of clinical efficacy and (2) unique biological effects on "lipid raft" that emerged as an important platform of numerous biophysical functions, for example, receptor tyrosin kinases (RTKs) signalings including epidermal growth factor receptor (EGFR), which play critical roles in HNSCC carcinogenesis

A Critical Role of c-Cbl-Interacting Protein of 85 kDa in the Development and Progression of Head and Neck Squamous Cell Carcinomas through the Ras-ERK Pathway12

Activation of the transforming growth factor (TGF) α/epidermal growth factor receptor (EGFR)-mediated signaling pathway is a common mechanism for dysregulated growth of head and neck squamous cell carcinoma (HNSCC). c-Cbl-interacting protein of 85 kDa (CIN85) is an adaptor protein that facilitates EGFR internalization. Little is known, however, about a role of CIN85 in EGFR signaling as well as its relevance to tumor development and progression of HNSCC. Here, we demonstrate that CIN85 is highly expressed in HNSCC tumor samples compared with adjacent normal tissues, and this overexpression is significantly correlated with advanced clinical stage. The experiments using CIN85-overexpressing and knockdown HNSCC cell lines showed that CIN85 promotes HNSCC growth and facilitates EGFR internalization without apparently affecting phosphorylation of EGFR. Moreover, CIN85 promoted TGF-α-induced activation of Ras and phosphorylation of downstream molecules such as c-Raf, MEK, and extracellular signal-regulated kinase, leading to expression of c-Myc that is critical for sustained proliferation of HNSCC. Taken together, these findings suggest that CIN85 not only controls EGFR internalization but also promotes the EGFR-mediated tumor development and progression, and thus, CIN85 may serve as a potential therapeutic target in a subset of HNSCC