BackgroundExosomes are extracellular vesicles released by almost all cell types, including cancer cells, into bodily fluids such as saliva, plasma, breast milk, semen, urine, cerebrospinal fluid, amniotic fluid, synovial fluid and sputum. Their key function being intercellular communication with both neighbouring as well as distant cells. Cancer exosomes have been shown to regulate organ-specific metastasis. However, little is known about the functional differences and molecular consequences of normal cells responding to exosomes derived from normal cells compared to those derived from cancer cells.MethodsHere, we characterised and compared the transcriptome profiles of primary human normal oral keratinocytes (HNOK) in response to exosomes isolated from either primary HNOK or head and neck squamous cell carcinoma (HNSCC) cell lines.ResultsIn recipient HNOK cells, we found that regardless of normal or cancer derived, exosomes altered molecular programmes involved in matrix modulation (MMP9), cytoskeletal remodelling (TUBB6, FEZ1, CCT6A), viral/dsRNA-induced interferon (OAS1, IFI6), anti-inflammatory (TSC22D3), deubiquitin (OTUD1), lipid metabolism and membrane trafficking (BBOX1, LRP11, RAB6A). Interestingly, cancer exosomes, but not normal exosomes, modulated expression of matrix remodelling (EFEMP1, DDK3, SPARC), cell cycle (EEF2K), membrane remodelling (LAMP2, SRPX), differentiation (SPRR2E), apoptosis (CTSC), transcription/translation (KLF6, PUS7). We have also identified CEP55 as a potential cancer exosomal marker.ConclusionsIn conclusion, both normal and cancer exosomes modulated unique gene expression pathways in normal recipient cells. Cancer cells may exploit exosomes to confer transcriptome reprogramming that leads to cancer-associated pathologies such as angiogenesis, immune evasion/modulation, cell fate alteration and metastasis. Molecular pathways and biomarkers identified in this study may be clinically exploitable for developing novel liquid-biopsy based diagnostics and immunotherapies.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0846-5) contains supplementary material, which is available to authorized users.

BACKGROUND: Epigenetic reprogramming of the methylome has been implicated in all stages of cancer evolution. It is now well accepted that cancer cells exploit epigenetic reprogramming, a mechanism that regulates stem/progenitor cell renewal and differentiation, to promote cancer initiation and progression. The oncogene FOXM1 has been implicated in all major forms of human cancer. METHODS: We have recently shown that aberrant upregulation of FOXM1 orchestrated a DNA methylation signature that mimics the cancer methylome landscape, from which we have identified a number of FOXM1-induced epigenetic markers. Differential promoter methylation and gene expression in clinical specimens were measured using commercially available bisulfite conversion kits and absolute quantitative PCR, respectively. RESULTS: Here, we investigated 8 FOXM1-induced differentially methylated genes, SPCS1, FLNA, CHPF, GLT8D1, C6orf136, MGAT1, NDUFA10, and PAFAH1B3, using human head and neck tissue specimens donated by 2 geographically independent patient cohorts from Norway and the United Kingdom. Two genes (GLT8D1 and C6orf136) were found to be differentially expressed in head and neck squamous cell carcinomas (HNSCCs). Using methylationspecific quantitative PCR, we confirmed that the promoters of GLT8D1 and C6orf136 were hypo-and hypermethylated, respectively, in HNSCC tissues. CONCLUSIONS: Given that epigenetic change precedes gene expression, methylation status of candidate genes identified from this study may represent a signature of premalignancy, rendering them potentially useful predictive biomarkers for precancer screening and/or therapeutic targets for cancer prevention. Cancer 2013;119:4249-58.

Background The concept of head and neck cancers (HNSCC) having unique molecular signatures is well accepted but relating this to clinical presentation and disease behaviour is essential for patient benefit. Currently the clinical significance of HNSCC molecular subtypes is uncertain therefore personalisation of HNSCC treatment is not yet possible. Methods We performed meta-analysis on 8 microarray studies and identified six significantly up- (PLAU, FN1, CDCA5) and down-regulated (CRNN, CLEC3B and DUOX1) genes which were subsequently quantified by RT-qPCR in 100 HNSCC patient margin and core tumour samples. Results Retrospective correlation with sociodemographic and clinicopathological patient details identified two subgroups of opposing molecular signature (+q6 and -q6) that correlated to two recognised high-risk HNSCC populations in the UK. The +q6 group were older, male, and excessive alcohol users whilst the –q6 group were younger, female, paan-chewers and predominantly Bangladeshi. Additionally, all patients with tumour recurrence were in the latter subgroup. Conclusions We provide the first evidence linking distinct molecular signatures in HNSCC with clinical presentations. Prospective trials are required to determine the correlation between these distinct genotypes and disease progression or treatment response. This is an important step towards the ultimate goal of improving outcomes by utilising personalised molecular-signature-guided treatments for HNSCC patients.

Introduction: Thyroid function disorders are among the most common endocrine diseases. Females are affected more than males, especially during the reproductive age. Hypothyroidism is the most prevalent type with a reported frequency of 2–5% worldwide. Thyroid hormones are essential for virtually all body tissues. So deficiency may affect hematopoiesis in bone marrow and eventually hematopoietic cells. Hematological abnormalities have frequently been reported in thyroid disorders. Anemia is frequently observed in patients with primary hypothyroidism. Objectives: To study the hematological changes and pattern of anemia in primary hypothyroid patients. Materials & Methods: This is a cross sectional study conducted on newly diagnosed 100 patients with primary hypothyroidism, between 18 –60 years. They were categorized as 35 patients of subclinical and 65 patients of overt hypothyroidism based on TSH level. Patients’ who fulfills the inclusion exclusion criteria were evaluated for thyroid function tests (T3, T4 and TSH) and hematological parameters (CBC and PBF). Results: Our analysis revealed an overall prevalence rate of anemia was 56% in patients with hypothyroidism which is higher than the WHO reported data of prevalence of anemia throughout the world. Our results showed that prevalence of normocytic normochromic anemia was significantly higher, microcytic anemia had the second rank, while macrocytic anemia had the lowest prevalence rate. On subgroup analysis, there was no statistical difference between subclinical hypothyroid and overt hypothyroid, in term of hematological parameters and type of anemia. Conclusion: Without proper diagnosis and effective treatment of the underlying thyroid disease, it is often difficult to achieve a complete correction of the anemia. The high prevalence of anemia in patients with hypothyroidism suggests screening for hypothyroidism during the differential diagnosis of cases presenting with anemia. Keywords: Hypothyroidism, subclinical, overt, anemia, hematological, thyroid, blood.

Skin is the largest organ of the body and many types of tumor arises from different part of skin layer. A leiomyoma is an uncommon, benign tumour of smooth muscle of skin derived from the arrector pili muscle of skin. These lesions can develop wherever smooth muscle is present, but malignant transformation probably does not occur. Cutaneous leiomyomas or piloleiomyomas appear as small (0.5-2 cm) firm skin coloured nodules. They arise from the arrector pili muscles which are responsible for making your hairs stand on end. Multiple lesions may develop, often in clusters and commonly in a segmental distribution. These nodules are benign, so are only of concern because of their appearance or their tendency to be tender if knocked. Female patients with cutaneous leiomyomas may also develop uterine leiomyomas (fibroids), and very rarely leiomyomas can be associated with renal cell carcinoma (hereditary leiomyomatosis and renal cell cancer). We report a case cutaneous leiomyoma of scalp in a 22 year old male who present with the complaints of scalp swelling.