•The role of NACT in T4 oral cancers remains a contentious issue with sparse evidence in literature.•cT4b oral cancers performed better when they received NACT prior to surgery in comparision to cT4a ...oral cancers.•Results of our matched pair analysis are hypothesis generating which needs to be tested in a randomized trial.
Noradrenaline can modulate multiple cellular functions important for cancer progression; however, how this single extracellular signal regulates such a broad array of cellular processes is unknown. ...Here we identify Src as a key regulator of phosphoproteomic signalling networks activated in response to beta-adrenergic signalling in cancer cells. These results also identify a new mechanism of Src phosphorylation that mediates beta-adrenergic/PKA regulation of downstream networks, thereby enhancing tumour cell migration, invasion and growth. In human ovarian cancer samples, high tumoural noradrenaline levels were correlated with high pSrc(Y419) levels. Moreover, among cancer patients, the use of beta blockers was significantly associated with reduced cancer-related mortality. Collectively, these data provide a pivotal molecular target for disrupting neural signalling in the tumour microenvironment.
Noradrenaline can modulate multiple cellular functions important for cancer progression; however, how this single extracellular signal regulates such a broad array of cellular processes is unknown. ...Here we identify Src as a key regulator of phosphoproteomic signalling networks activated in response to beta-adrenergic signalling in cancer cells. These results also identify a new mechanism of Src phosphorylation that mediates beta-adrenergic/PKA regulation of downstream networks, thereby enhancing tumour cell migration, invasion and growth. In human ovarian cancer samples, high tumoural noradrenaline levels were correlated with high pSrc(Y419) levels. Moreover, among cancer patients, the use of beta blockers was significantly associated with reduced cancer-related mortality. Collectively, these data provide a pivotal molecular target for disrupting neural signalling in the tumour microenvironment.
Purpose
Thyroid nodules are of common occurrence in the general population. About a fourth of these nodules are indeterminate on aspiration cytology placing many a patient at risk of unwanted ...surgery. The purpose of this review is to discuss various molecular markers described to date and place their role in proper perspective. This review covers the fundamental role of the signaling pathways and genetic changes involved in thyroid carcinogenesis. The current literature on the prognostic significance of these markers is also described.
Methods
PubMed was used to search relevant articles. The key terms “thyroid nodules”, “thyroid cancer papillary”, “carcinoma papillary follicular”, “carcinoma papillary”, “adenocarcinoma follicular” were searched in MeSH, and “molecular markers”, “molecular testing”, mutation, BRAF, RAS, RET/PTC, PAX 8, miRNA, NIFTP in title and abstract fields. Multiple combinations were done and a group of experts in the subject from the International Head and Neck Scientific Group extracted the relevant articles and formulated the review.
Results
There has been considerable progress in the understanding of thyroid carcinogenesis and the emergence of numerous molecular markers in the recent years with potential to be used in the diagnostic algorithm of these nodules. However, their precise role in routine clinical practice continues to be a contentious issue. Majority of the studies in this context are retrospective and impact of these mutations is not independent of other prognostic factors making the interpretation difficult.
Conclusion
The prevalence of these mutations in thyroid nodule is high and it is a continuously evolving field. Clinicians should stay informed as recommendation on the use of these markers is expected to evolve.
Based on the identified stress-independent cellular functions of activating transcription factor 4 (ATF4), we reported enhanced ATF4 levels in MCF10A cells treated with TGFβ1. ATF4 is overexpressed ...in triple negative breast cancer (TNBC) patients, but its impact on patient survival and the underlying mechanisms remain unknown. We aimed to determine
effects on breast cancer patient survival and TNBC aggressiveness, and the relationships between TGFβ and ATF4. Defining the signaling pathways may help us identify a cell signaling-tailored gene signature.
Patient survival data was determined by Kaplan-Meier analysis. Relationship between TGFβ and ATF4, their effects on aggressiveness (tumor proliferation, metastasis, and stemness), and the underlying pathways were analyzed in three TNBC cell lines and
using patient-derived xenografts (PDXs).
overexpression correlated with TNBC patient survival decrease and a SMAD-dependent crosstalk between ATF4 and TGFβ was identified.
expression inhibition reduced migration, invasiveness, mammosphere-forming efficiency, proliferation, epithelial-mesenchymal transition, and antiapoptotic and stemness marker levels. In PDX models,
silencing decreased metastases, tumor growth, and relapse after chemotherapy. ATF4 was shown to be active downstream of SMAD2/3/4 and mTORC2, regulating TGFβ/SMAD and mTOR/RAC1-RHOA pathways independently of stress. We defined an eight-gene signature with prognostic potential, altered in 45% of 2509 breast cancer patients.
ATF4 may represent a valuable prognostic biomarker and therapeutic target in TNBC patients, and we identified a cell-signaling pathway-based gene signature that may contribute to the development of combinatorial targeted therapies for breast cancer.
Abstract
Context:
Head and neck surgeries are complex. Wound complications are associated with considerable morbidity and can result in delay in the adjuvant treatment. Identification of factors will ...help in formulating preventive guidelines.
Aims:
The aim of this study is to identify perioperative factors responsible for wound complications.
Settings and Design:
Prospective study of 186 head and neck patients. Subjects and Methods: Pre-operative, intraoperative and post-operative factors were recorded. Each patient was evaluated for minor and major wound complications twice daily during the hospital stay.
Statistical Analysis:
Chi-square test was used for univariate and log regression test was used for multivariate analysis.
Results:
The overall wound complication rate was 29% with 7% major and 22% minor complications. On univariate analysis, laryngeal and hypopharyngeal location, advanced T stage, poor oral hygiene, clean-contaminated surgery, low Karnofsky performance status (KPS), flap reconstruction, blood loss more than 1000 ml, perioperative blood transfusion, duration of surgery greater than 4.3 h and post-operative hemoglobin lesser than 11 g%, post-operative tracheostomy and resection of mandible were statistical significant factors. On multivariate analysis, post-operative tracheostomy, low KPS, post-operative serum albumin less than 3.7 g/dl and duration of surgery greater than 4.3 h were significant factors.
Conclusion :
Apart from unavoidable factors, it is essential to take care of certain factors viz nutrition, haemoglobin, oral hygiene, asepsis and repeating antibiotics in prolonged surgery.
E X E C U T I V E S U M M A R Y
The document is based on consensus among the experts and best available evidence pertaining to Indian population and is meant for practice in India. Early diagnosis is ...imperative in improving outcomes and preserving quality of life. High index of suspicion is to be maintained for leukoplakia (high risk site). Evaluation of a patient with newly diagnosed tongue cancer should include essential tests: Magnetic resonance imaging (MRI) is investigative modality of choice when indicated. Computed tomography (CT) scan is an option when MRI is unavailable. In early lesions when imaging is not warranted ultrasound may help guide management of the neck. Early stage cancers (stage I & II) require single modality treatment - either surgery or radiotherapy. Surgery is preferred. Adjuvant radiotherapy is indicated for T3/T4 cancers, presence of high risk features lymphovascular emboli (LVE), perineural invasion (
P
NI), poorly differentiated, node +,close margins). Adjuvant chemoradiation (CTRT) is indicated for positive margins and extranodal disease. Locally advanced operable cancers (stage III & IVA) require combined multimodality treatment - surgery + adjuvant treatment. Adjuvant treatment is indicated in all and in the presence of high risk features as described above. Locally advanced inoperable cancers (stage IVB) are treated with palliative chemo-radiotherapy, chemotherapy, radiotherapy, or symptomatic treatment depending upon the performance status. Select cases may be considered for neoadjuvant chemotherapy followed by surgical salvage. Metastatic disease (stage IVC) should be treated with a goal for palliation. Chemotherapy may be offered to patients with good performance status. Local treatment in the form of radiotherapy may be added for palliation of symptoms. Intense follow-up every 3 months is required for initial 2 years as most recurrences occur in the first 24 months. After 2 nd year follow up is done at 4-6 months interval. At each follow up screening for local/ regional recurrence and second primary is done. Imaging is done only when indicated.
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