Head and neck squamous cell cancer

Top PDF Head and neck squamous cell cancer:

Biomarker driven treatment of head and neck squamous cell cancer

Biomarker driven treatment of head and neck squamous cell cancer

Abstract: Treatment modalities of head and neck squamous cell cancer include surgery, radiation, chemotherapy, targeted agents and immune checkpoint inhibition. Treatment is often toxic and can affect long-term function and quality of life. In this context, identification of biomarker data that can help tailor therapy on an individualized basis and reduce treatment-related toxicity would be highly beneficial. A variety of predictive biomarkers have been discovered and are already utilized in clinical practice, while many more are being explored. We will review p16 overexpression as a surrogate biomarker in HPV-associated head and neck cancer and plasma EBV DNA as a biomarker in nasopharyngeal carcinoma, the two established biomarkers currently utilized in clinical practice. We will also examine novel predictive biomarkers that are in clinical development and may shape the future landscape of targeted head and neck cancer therapy. These emerging biomarkers include the tyrosine kinases and their signaling pathway, immune checkpoint biomarkers, tumor suppressor abnormalities, and molecular predictors of hypoxia-targeted therapy. We will also look at futuristic biomarkers including detection of circulating DNA from clinical specimens and rapid tumor profiling. We will highlight the ongoing effort that will see a shift from prognostic to predictive biomarker development in head and neck cancer with the goal of delivering individualized cancer therapy.
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Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck.

Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck.

Patient-reported outcomes, including symp- toms and health-related quality of life, were ex- ploratory end points and were evaluated with the use of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire–Core 30 module (QLQ-C30) and the head-and-neck–specific module (QLQ-H&N35). Scores for these modules range from 0 to 100, with higher scores indicating better functioning or well-being or higher symptom burden, although scales measuring symptom burden were reverse- scored to facilitate presentation. The propor- tion of patients reporting health problems was assessed with the use of the three-level version of the European Quality of Life–5 Dimensions (EQ-5D-3L) questionnaire. Patients also com- pleted the EQ-5D-3L visual-analogue scale, for which scores range from 0 to 100 and higher scores indicate better perceived health status.
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ONCOGENICITY OF TOBACCO-SMOKING: A REVIEW ON SQUAMOUS CELL CARCINOMA OF THE TONGUE, DIAGNOSIS AND TREATMENT

ONCOGENICITY OF TOBACCO-SMOKING: A REVIEW ON SQUAMOUS CELL CARCINOMA OF THE TONGUE, DIAGNOSIS AND TREATMENT

Squamous cell carcinoma (SCC) of the tongue is the commonest type of tongue cancer affecting young smokers and older men (over 45 years of age) than women. It represents more than ninety percent of all head and neck cancers, and occurs mainly in the lateral posterior border that may extend to the dorsum of the tongue. The major risk factors for SCC of the tongue are tobacco-smoking (to a greater extent) and frequent consumption of large amounts of alcohol (to a smaller extent). Minor risk factors for SCC of the tongue include irritation induced by chewing tobacco, dental caries, overuse of mouthwash, chewing betel nut and oral human papillomavirus (HPV) acquired via genito-oral route. The early stages of SCC of the tongue are usually asymptomatic, but later stages may present as lesions that appear as areas of erythroplakia or leukoplakia, with ulceration and pain usually at the base of the tongue, and consequently a lump or an induration on the tongue. Diagnosis of SCC of the tongue involves taking a medical history and physical examination of the tongue for unhealed ulcers and nearby lymph nodes for swelling. If SCC of the tongue is suspected, a biopsy of affected areas of the tongue is made, followed by processing of the biopsied tissue and preparation of smears on clean grease-free glass slides. Finally, the smears are stained with the „„Haematoxylin and Eosin (H & E) stain‟‟, and then examined under the microscope. The presence of intense pleomorphism, nuclear hyperchromatism, increased nuclear to cytoplasmic ratio, and increased proliferation of epithelial cells is diagnostic of SCC of the tongue. Treatment of this disease involves glossectomy, with postoperative radiation or chemo-radiation. It is not new that tobacco-smoking via cigarettes and shishas, as well as regular consumption of large volumes of alcohol among the elderly and especially young people is rapidly on the increase. Thus, this review was aimed at discussing the consequence of tobacco-smoking with focus on Squamous Cell Carcinoma of the Tongue, its diagnosis and treatment. It is therefore highly recommended that tobacco-smoking, as well as chronic consumption of alcohol be avoided, and that these artisans (smokers and alcoholics) should get themselves examined medically.
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PDGF AA mediates mesenchymal stromal cell chemotaxis to the head and neck squamous cell carcinoma tumor microenvironment

PDGF AA mediates mesenchymal stromal cell chemotaxis to the head and neck squamous cell carcinoma tumor microenvironment

It is now believed that bone marrow derived MSCs serve a significant source of differentiated CAFs in the tumor microenvironment [2–4]. In models of gastric can- cer, 20% of CAFs were shown to originate from the bone marrow and derived of MSCs [4]. In this model, bone marrow derived MSCs are thought to home to tumors via paracrine signals generated by the tumor itself [2, 5, 6], and once resident within the local microenvironment MSCs serve as important precursors for CAFs, together enhancing tumor growth through autocrine and parac- rine signaling pathways [2, 7]. Co-culture of bone mar- row derived MSCs, either direct or indirect via transwell culture, with breast cancer cells has been shown to signif- icantly increase aldehyde dehydrogenase (ALDH) expres- sion, a CSC marker [2]. The conditioned media alone from MSC was not enough to induce increased ALDH expression on the breast cancer cells, suggesting that the paracrine signaling feedback loop between the breast cancer cells and MSCs is necessary to drive the increase in ALDH expression [2].
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The role of interleukin-18 in glioblastoma pathology implies therapeutic potential of two old drugs—disulfiram and ritonavir

The role of interleukin-18 in glioblastoma pathology implies therapeutic potential of two old drugs—disulfiram and ritonavir

IL-18–mediated increase in centrifugal migration was observed in gastric cancer cells [8,40] similar to what Yeh et al. [5] found in glioblastoma. Increased circulating IL- 18 was observed in patients with gastric cancer [41], head and neck squamous cell carcinoma [10], esophageal can- cer [41], epithelial ovarian cancer [42], and non–small cell lung cancer [15,43] where higher levels of IL-18 were as- sociated with poorer overall survival [13], in patients with breast cancer [44] where levels of IL-18 in metastatic dis- ease were also higher than those in non-metastatic disease [45], and in patients with prostate cancer [14], small cell lung cancer [15], and pancreatic cancer where higher levels of IL-18 predicted poorer overall survival [46]. The common theme in these studies is that IL-18 increases most with metastatic disease. These findings, combined with IL-18–stimulated centrifugal migration in gastric cancer cells [8,40] and glioblastoma cells [5], point to IL-18 as a general mobility-enhancing signaling mol- ecule for cancers.
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Original Article Appraising microRNA-99a as a novel prognostic biomarker across 21 human cancer types based on data from the cancer genome atlas

Original Article Appraising microRNA-99a as a novel prognostic biomarker across 21 human cancer types based on data from the cancer genome atlas

In this study, we employed an integrated analy- sis approach to analyze the prognostic value of miR-99a across 21 human cancer types derived from TCGA datasets. The downregulat- ed miR-99a were significantly associated with poorer survival in lung adenocarcinoma, cervi- cal cancer, esophageal cancer and head and neck squamous cell carcinoma, which was con- sistent with the results of the previous study [24, 26, 27]. Nonetheless, the significant cor- relation was also found between low level of miR-99a expression and better outcome in urothelial bladder cancer and cutaneous mela- noma. Interestingly, we further confirmed that lower levels of miR-99a expression significantly reduced overall survival through TCGA data and the published studies. In the contrary to our result, Zhou et al. analyzed the miR-99a expres- sion profile of 84 paired bladder cancer through TCGA data and identified the prognostic value of miR-99a that predicted patient survival [28]. Moreover, with data identified from TCGA data-
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Role of cancer stem cells in breast and prostate cancer

Role of cancer stem cells in breast and prostate cancer

Within the stem cell niche there is a cellular hierarchy based on the morphology, proliferation and differentiation potential of the cells and the clones of cells formed in the hierarchy are known as: holoclones, meroclones and paraclones (Barrandon and Green 1987). Holoclones are the least abundant colony forming cells within the hierarchy, but are the most proliferative and can differentiate into both meroclone and paraclone, whereas paraclones are terminally differentiated cells and can divide a limited number of times by symmetrical cell division. Meroclones are said to be in a transitional state between holoclones and paraclones and have some proliferative capacity although not as great as holoclones, and can differentiate into meroclones and paraclones (Barrandon and Green 1987). The hierarchy within stem cells has also been identified in many cancer cell lines including head and neck squamous carcinoma, oral squamous carcinoma and prostate cancer (Felthaus et al. 2011, Li et al. 2008, Locke et al. 2005, Doherty et al. 2011, Beaver, Ahmed and Masters 2014). It is apparent that holoclones may contain the CSC population, or the CSC form holoclones. Whichever concept it may be, holoclones have the ability to differentiate into meroclones and paraclones and upon terminal differentiation these colony forming cells lose the ability to transdifferentiate (Doherty et al. 2011), although in epithelial to mesenchymal transition phenotypic plasticity is observed (Baum, Settleman and Quinlan 2008, Lin et al. 2012) .
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Head and Neck Cancer: Closer Look at Patients Quality of Life

Head and Neck Cancer: Closer Look at Patients Quality of Life

A prospective clinical study that enrolled 87 patients with HNSCC that presented to the Radiation therapy de- partment of the National Cancer Institute, Cairo University, it started from March 2012 and ended in December 2013. The patients had received RT or chemo-radiotherapy (CRT) treatment with or without surgical resection. The inclusion criteria were: Histopathologically confirmed squamous cell carcinoma of head and neck cancer (HNSCC) with any of the following subsites: oropharynx, hypopharynx, larynx, oral cavity, no evidence of dis- tant metastases, performance status ECOG (0-1), the prescribed radiation dose fraction was 2 Gy with a maxi- mum total dose of 70 Gy in case of radical radiotherapy. Clinical factors such as the site of the tumor, clinical stage, treatment modality (RT, CRT), and social factors (age, gender, smoking habit) were evaluated. The pa- tients’ characteristics are presented in Table 1. The standardized EORTC-QLQ-C30 (version 3.0) questionnaire and QLQ-H&N35 module were used for the evaluation of QOL. The items covered in QLQ-C30 questionnaire are focused on evaluating general health, physical, emotional and social aspects. It comprises 30 questions grouped into the 5 functional scales. The questionnaire also includes 3 symptomatic scales—fatigue, nausea and pain—as well as 6 single questions evaluating the intensity of the following symptoms: dyspnea, sleeplessness, lack of appetite, constipation, diarrhea and financial problems. The last two questions deal with the overall health assessment. There is a four-degree scale in the answers to the questions in the questionnaire (never 1, sometimes 2, often 3, very often 4). The QLQ-H&N35 questionnaire deals with specific symptoms related to tumors of the head and neck, and effects of treatment. It has 35 questions grouped into 7 scales: pain, swallow- ing, senses, speaking, eating in the company of others, social contacts, sexuality, and 11 individual questions concerning teeth problems, difficulties with opening the mouth, oral cavity dryness, the presence of thick saliva, coughing, illness awareness, taking pain killers, using food supplements, and losing or gaining weight. Similarly, to the core questionnaire, a patient gave one answer to each question, and the answers had a four-degree scale.
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Enhanced cell migration and apoptosis resistance may underlie the association between high SERPINE1 expression and poor outcome in head and neck carcinoma patients

Enhanced cell migration and apoptosis resistance may underlie the association between high SERPINE1 expression and poor outcome in head and neck carcinoma patients

High SERPINE1 expression is a common event in head and neck squamous cell carcinoma (HNSCC); however, whether it plays a role in determining clinical outcome remains still unknown. We studied SERPINE1 as a prognostic marker in two HNSCC patient cohorts. In a retrospective study (n = 80), high expression of SERPINE1 was associated with poor progression-free (p = 0.022) and cancer-specific (p = 0.040) survival. In a prospective study (n = 190), high SERPINE1 expression was associated with poor local recurrence-free (p = 0.022), progression-free (p = 0.002) and cancer- specific (p = 0.006) survival. SERPINE1 expression was identified as an independent risk factor for progression-free survival in patients treated with chemo-radiotherapy or radiotherapy (p = 0.043). In both patient cohorts, high SERPINE1 expression increased the risk of metastasis spread (p = 0.045; p = 0.029). The association between SERPINE1 expression and survival was confirmed using the HNSCC cohort included in The Cancer Genome Atlas project (n = 507). Once again, patients showing high expression had a poorer survival (p < 0.001). SERPINE1 over-expression in HNSCC cells reduced cell proliferation and enhanced migration. It also protected cells from cisplatin-induced apoptosis, which was accompanied by PI3K/AKT pathway activation. Downregulation of SERPINE1 expression had the opposite effect.
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Understanding Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Critical Update in Development of New Approaches

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Cancer Stem Cells (CSCs) have an important role in Head and Neck Squamous Cell Carcinoma (HNSCC). HNSCC is considered as one of the major health problems throughout the world. These self-renewing cells are responsible for resistance to conventional anti-cancer therapy. CSCs have the ability of cancer recurrence; metastasis and can form a heterogeneous tumour. The idea of 'CSCs' has led the scientific community to a new era in the field of research and possibly effective treatment modalities for cancer in the future. This paper aims primarily to review the recent advancements made in the use of stem cells in the treatment of cancer. Secondly, this review presents a discussion on the consideration of CSCs being the backbone in the development of cancer and, precisely the role played by the CSCs in carcinogenesis and its outcome leading to development of possible cancer treatment in the future.
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Combating head and neck cancer metastases by targeting Src using multifunctional nanoparticle-based saracatinib

Combating head and neck cancer metastases by targeting Src using multifunctional nanoparticle-based saracatinib

enzyme of CTSB, an overexpressed and secreted enzyme in tumor endothelial and epithelial cells, is one of targets that are frequently used in the development of enzyme-triggered nanomedicine. The expression of CTSB has been reported to be increased along with the cancerization in oral squamous cell carcinoma [38, 51], which is also positively associated with highly invasive and metastatic phenotypes [52]. We collected 19 pri- mary HNSCC tissues with paired adjacent normal tis- sues and determined the expression levels of CTSB by real-time RT-PCR. More than tenfold higher levels of CTSB were observed in HNSCC tissues compared with paired adjacent normal tissues (data not shown), provid- ing a strong rational basis for the design of CTSB-sensitive NP for saracatinib delivery. Given that solid tumors have an acidic extracellular environment and an altered pH gradient across their cell compart- ments [53, 54], the formulations of Nano-sar were de- signed to exploit the pH gradients that exist in tumor microenvironments. Therefore, Nano-sar can be select- ively activated and release the loaded saracatinib into head and neck tumors in order to maintain effective drug levels at tumor tissues.
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MicroRNA Deregulations in Head and Neck Squamous Cell Carcinomas

MicroRNA Deregulations in Head and Neck Squamous Cell Carcinomas

microRNA alteration. To identify microRNAs associated with HNSCC metastasis, Liu et al. [108] examined the differential expression of microRNAs in a panel of HNSCC cell lines with different metastatic potential. Their result showed that miR-138 is consistently down- regulated in highly metastatic cell lines. Restoring miR- 138 led to suppression of cell invasion, cell cycle arrest and induced apoptosis. In contrast, knockdown of miR- 138 enhanced cell invasion and suppressed apoptosis. The fact that highly metastatic cells often showed reduced expression of miR-138 suggests the potential role of miR-138 as a metastatic suppressor, and may serve as a potential therapeutic target for HNSCC patients at risk of metastasis. The same group of investigators later validated the down-regulation of miR-138 in tongue SCC tissue samples [148], and down-regulation of miR-138 was also reported in HNSCC by different labs [27,148,149]. Recent functional analysis demonstrated that miR-138 regulates cell migration and invasion by concurrently targeting RhoC and ROCK2, leading to the down-regulation of the Rho GTPase signalling pathway that is essential for actin cytoskeleton remodelling [150]. Tumour cells can dedifferentiate through activation of specific biological pathways associated with epithelial- mesenchymal-transition (EMT), thereby gaining the ability to migrate and invade. EMT is characterized by the loss of epithelial-cell markers (e.g., E-cadherin) and the gain of mesenchymal-cell markers (e.g., Vimentin). Previous studies suggested that members of the miR- 200 family regulate EMT by targeting the Zinc finger E-box-binding homeobox (ZEB) family of transcription repressors (ZEB1 and ZEB2) which control E-cadherin expression [151]. Furthermore, down-regulation of miR-101 leads to the overexpression of polycomb group protein EZH2 [152,153], which also acts as a transcription suppressor to inhibit the expression of E-cadherin and induce EMT [154]. Both bioinformatics analysis and in vitro experimental results indicated that miR-138 targets ZEB and EZH repressors, and other molecular regulators that control E-cadherin expression, such as FOSL1. Interestingly, miR-138 also controls Vim expression by interacting with its targeting sequences located in both the 3’-UTR and coding region of the Vim gene. As such, these studies suggested that miR-138 is an essential EMT regulator that controls EMT through multiple pathways. Taken together, these observations suggest that miR-138 is a multi-functional molecular regulator, and the down-regulation of miR- 138 in HNSCC plays essential roles in the neoplastic progression of HNSCC in terms of enhancing the metastatic potential of the HNSCC cells by promoting EMT and enhancing cell migration and invasion. The ability for the cancer cells to survive under hypoxic conditions or in the presence of chemotherapeutic
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Epidemiological profile of oral cancers in Benin

Epidemiological profile of oral cancers in Benin

Results: With a rate of 19.8%, oral cavity cancer was the most frequent cancer localization in the ENT, head and neck sphere in Benin. The most frequent sites of cancers in the oral cavity were the palate (32.2%) followed by the tongue (25.4%) and the inner face of the cheeks (16.9%). The average age of the patients was 53.18±20.60 years with extremes of 1 year and 90 years. The sex ratio was 0.90. Squamous cell carcinoma was the most common histological type with 67.80%.

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Original Article Association of PIN1 promoter polymorphisms with colorectal carcinoma risk and clinicopathological parameters

Original Article Association of PIN1 promoter polymorphisms with colorectal carcinoma risk and clinicopathological parameters

and alleles were not significantly different between the colorectal cancer patients and controls. In the study of breast cancer [13], squamous cell carcinoma of the head and ne- ck [12] and lung cancer [15], -842GC heterozy- gote had a significantly decreased cancer risk comparing to -842GG homozygote. Yet, no sig- nificant difference on the frequency of -842G>C genotype was observed in a study of breast cancer [16] and a study of hepatocellular carci- noma [12]. Furthermore, there was no evidence that -667C>T polymorphism was significantly associated with cancer risk in the study of breast cancer [13, 16], squamous cell carcino- ma of the head and neck [14] and lung cancer [15]. However, decreased risk of cancer was found to be associated with the -842C variant allele in the study of breast cancer [13] and the study of squamous cell carcinoma of the head and neck [14]. The SNP -667T allele increased in the patients group of hepatocellular carci- noma with HBV and HCV co-infection [12]. Table 3. Association between the genotype
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Cancer stem cell related markers of radioresistance in head and neck squamous cell carcinoma

Cancer stem cell related markers of radioresistance in head and neck squamous cell carcinoma

In this study we aimed to investigate the potential role of CSC marker expression in HNSCC radiosensitivity and their regulation upon radiotherapy. We showed an up-regulation of stem cell markers in HNSCC cells after irradiation including expression of CD133, ALDH activity, as well as expression of the proteins involved in the regulation of survival, stemness and self-renewal, such as Akt, Oct4, and BMI1. Irradiation of FaDu and Cal33 cells with multiple 4 Gy fractions led to an acquisition of long term moderate radioresistance in FaDu cells and substantially increased radioresistance in Cal33 cells compared to their parental lines. As shown before by Yaromina et al. parental Cal33 cells exhibit high radioresistance. Nevertheless the IR derivatives of Cal33 are even more radioresistant. In contrast parental FaDu cells are only moderately resistant to radiotherapy and their IR daughters only slightly increased their radioresistant properties [5]. This acquired cellular radioresistance might be attributed to the selection of the pre-existing minor cellular clones or to de-novo mutations or epigenetic changes that occur in the cells during or after irradiation. Indeed, recent investigations demonstrated that cancer therapy represents a strong selection pressure for tumor cells and that high intra-tumor genetic diversity correlates with only partial or no therapy response and worse treatment outcome in HNSCC cancer patients [26, 27]. This suggests that high heterogeneity within one tumor may be attributed to various mutations within tumor progenitor cells that could favor their survival during cancer therapy and increase the possibility of tumor regrowth. Other studies also reported that anti-cancer therapy can effect clonal evolution and lead to the emergence of minor mutated clones, which are therapy resistant, and associated with tumor relapse [28]. Moreover, clonal expansion of tumor cells with advantageous mutations leading to therapy resistance and poor survival has been demonstrated to be clinically relevant in different types of cancer [29, 30]. In addition to the treatment-related clonal selection, recent evidence suggests that radiotherapy can directly sustain cancer cell de-differentiation to a stem cell phenotype that can potentially impact tumor curability [31]. However, the question whether the emergence of radioresistant HNSCC sublines is an induced or selective response to irradiation requires further investigation. Future studies utilizing in vivo tracking of CSCs will clarify the effect of irradiation on the induction and selection of radioresistant clones.
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<p>CD44-Targeted Magnetic Nanoparticles Kill Head And Neck Squamous Cell Carcinoma Stem Cells In An Alternating Magnetic Field</p>

<p>CD44-Targeted Magnetic Nanoparticles Kill Head And Neck Squamous Cell Carcinoma Stem Cells In An Alternating Magnetic Field</p>

were obtained by coprecipitation and reacted with carboxy- methyl dextran to obtain a carboxyl terminal (-COOH), and an amide bond (-CO-NH-) was covalently coupled with the amino terminus (-NH2) of the CD44 antibody. Biosafety eva- luation of the CD44-SPIONPs showed good biocompatibility. In recent years, some studies have con fi rmed that CD44- positive cells account for less than 10% of all head and neck tumor cells, but these cells have a strong ability to clone and self-renew, as well as the ability to initiate tumors. 15 CD44 on the surface of many cells is in a relatively static state, while CD44 on the surface of CSCs is in an overexpression state, which can bind to its ligand, leading to the immune escape of cancer cells, and can promote the occurrence, development, invasion and metastasis of tumors. 17,34 Western blot results showed that CSCs overexpressed CD44 compared to Cal-27 cells. Therefore, we selected the CD44 antibody receptor on the surface of CSCs as a target and labeled the CD44 antibody with FITC fl uorescence. After coculture with cells, it was observed by confocal microscopy that CD44-SPIONPs pene- trated into the cytoplasm through the cell membrane.
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Impaired light detection of the circadian clock in a zebrafish melanoma model

Impaired light detection of the circadian clock in a zebrafish melanoma model

A reduction in circadian clock amplitude has been reported in other types of cancer such as breast, prostate, non-small cell lung cancer, and head and neck squamous cell carcinoma. 37-40 In par- ticular, a study on human melanoma tumor biopsies has reported a significant down regulation of clock genes compared to adja- cent healthy tissues. 33 However, human skin contains different cell types displaying a range of amplitudes in clock gene rhythms, with keratinocyte and dermal fibroblast cultures showing a more robust clock compared to melanocyte cultures. 28 To ensure that the difference in amplitude we observed between normal skin and melanoma tumors in our study is not due to a higher num- ber of melanocytes in tumor samples, we analyzed clock gene expression in zebrafish dysplastic naevi (Fig. S2). Dysplastic naevi appear during the radial growth phase of melanoma development and lack alterations in certain pathways, such as phosphoinositide 3-kinase (PI3K)-AKT signaling, required for the vertical growth phase and formation of a melanoma tumor. 35 Naevi, therefore, provide a melanocyte-rich environment, which has not yet pro- gressed to a malignant melanoma (Fig. S1). Analysis of per1, clock1 and bmal1a expression across one LD cycle showed no down regulation in naevus samples compared to healthy skin (Fig. S2). This result indicates that the decreased amplitude in clock gene expression seen in melanoma tumors is most likely due to malignant transformation itself and not to the abundance of melanocytes.
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Sensitizing mucoepidermoid carcinomas to chemotherapy by targeted disruption of cancer stem cells

Sensitizing mucoepidermoid carcinomas to chemotherapy by targeted disruption of cancer stem cells

example, tumors cells with squamous and intermediate differentiation are commonly acetylated, but hypoacetylated tumor cells are also present within the tumor mass. Interestingly, mucous-like tumor cells are also hypoacetylated. Indeed, the level of histone acetylation correlates with the transcriptional activity of the cell [61, 62]. Histone acetylation is associated with increased transcription of genes involved in differentiation, and histone deacetylation is associated with reduced gene transcription and/or activation of stem cell-associated genes. Changes in the levels of histone acetylation has been observed in various processes, including the initiation and progression of cancer, cellular plasticity, inflammation, maintenance of CSCs, and activation of tumor resistance pathways [12, 21, 56]. We have observed that certain head and neck tumor cell lines are prone to histone deacetylation upon administration of chemotherapy [12]. Moreover, these cells are characterized by increased resistance to chemotherapy. Given that histone deacetylases are involved in transcriptional repression, we hypothesize that histone deacetylation in tumor cells selectively activates stem cell-associated genes, resulting in chemoresistance. If true, pharmacological inhibition of histone deacetylases in all tumors cells would disrupt signaling programs associated with maintenance of CSCs, thereby reducing the resistance of MEC to Cisplatin. Evidence of the efficacy of such combined therapy has been demonstrated in Hodgkin’s Lymphoma, cervical cancer, ovarian cancer, head and neck squamous cell carcinoma, and pancreatic cancer [12, 57-60, 63]; however, the mechanism of action remain elusive. Our work focuses on the response of CSCs to chemotherapy. Interestingly, we found that CSCs derived from MEC cell lines show variable responses to Cisplatin. While CSCs derived from UM-HMC3A did not respond to Cisplatin, CSCs derived from a metastatic MEC (UM-HMC3B) were sensitive to this drug. Perhaps the most interesting result came from UM-HNC5 cells, in which Cisplatin induced an abrupt accumulation of CSCs. Although unexpected, CSCs in other tumors accumulate in response to chemotherapy [64-66]. Unlike Cisplatin, SAHA reduced the number of tumor spheres and ALDH +
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The molecular pathogenesis of head and neck squamous cell carcinoma

The molecular pathogenesis of head and neck squamous cell carcinoma

Recent advances in our understanding of the molecular pathogenesis of HNSCC were provided by whole-exome sequencing (i.e., sequenc- ing exons of all known protein-coding genes) conducted on a total of approximately 100 HNSCC specimens independently by two groups (10, 11). While the two studies analyzed etiologically similar tumors with related sequencing platforms, there was a five-fold difference in the average number of mutations reported per tumor. This differ- ence likely reflects distinct bioinformatic and validation approaches used in the studies, and therefore a subset of identified changes may represent “passenger” mutations (as a result of increased mutation rates in cancer cells, or even mutation “miscalls”) rather than true “driver” mutations with an etiologic role in HNSCC. Nevertheless, several key findings were shared by these studies. This work, together with a large body of previous genomic and functional analyses of HNSCC, highlights the relatively small number of oncogenes tar- geted by activating mutations and supports the fundamental roles of tumor suppressor pathways including p53, Rb/INK4/ARF, and Notch in disease pathogenesis. These and other bona fide HNSCC cancer genes play major roles in at least four key functional path- ways: cellular proliferation, squamous epithelial differentiation, cell survival, and invasion/metastasis, with many of the genes impacting more than a single pathway (Figure 1). These pathways are critical to the pathogenesis of HNSCC and, not surprisingly, reflect normal developmental programs within the stratified squamous epithelium. Given the paucity of driver oncogenes in HNSCC, targeting these pathways therapeutically represents a substantial and critical chal- lenge for improving outcomes of this disease.
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PROGNOSTIC ROLE OF HUMAN PAPILLOMA VIRUS IN ORAL SQUAMOUS CELL CARCINOMA: A REVIEW

PROGNOSTIC ROLE OF HUMAN PAPILLOMA VIRUS IN ORAL SQUAMOUS CELL CARCINOMA: A REVIEW

HPV associated OSCC are related with better prognosis than HPV-negative tumors in the most of the studies. [11,31,36] Moreover, According to the results of retrospective analyses, the patients with HPV-positive oropharyngeal cancer have higher response rates to chemotherapy and radiation and increased survival. [35,37,39] In addition , in 2008 , a prospective clinical trial , in patients with head and neck squamous cell carcinoma showed that the response to treatment , survival rate and other related outcomes were better in HPV positive types versus HPV negative ones. [40] The good survival rates imply the increased sensitivity to chemotherapy and radiotherapy in HPV- positive patients.
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