The Therapeutic Application of Hydrogen in Cancer: The Potential and Challenges.

Hydrogen therapy has emerged as a possible approach for both preventing and treating cancer. Cancers are often associated with oxidative stress and chronic inflammation. Hydrogen, with its unique physiological functions and characteristics, exhibits antioxidant, anti-inflammatory, and anti-apoptotic properties, making it an attractive candidate for cancer treatment. Through its ability to mitigate oxidative damage, modulate inflammatory responses, and sustain cellular viability, hydrogen demonstrates significant potential in preventing cancer recurrence and improving treatment outcomes. Preclinical studies have shown the efficacy of hydrogen therapy in several cancer types, highlighting its ability to enhance the effectiveness of conventional treatments while reducing associated side effects. Furthermore, hydrogen therapy has been found to be safe and well-tolerated in clinical settings. Nonetheless, additional investigations are necessary to improve a comprehensive understanding of the mechanisms underlying hydrogen's therapeutic potential and refine the administration and dosage protocols. However, further clinical trials are still needed to explore its safety profile and capacity. In aggregate, hydrogen therapy represents an innovative and promising treatment for several malignancies.

Comparison of skin cancer risk between renal transplant recipients and patients with glomerular diseases in rural Queensland.

INTROUDCTION: There is increased risk of skin cancer in patients with gloermular disease or those with renal transplant. OBJECTIVES: To compare the risk of skin cancer between kidney recipients (KTRs) and patients with glomerular disease (GD). DESIGN: The cohort comprised patients with KTRs (n = 61) and GD (n = 51) in Central and Central West Queensland, Australia. A quantitative cohort study was undertaken to study the risk of skin cancer in rural communities between two subgroups of patients with kidney diseases in relationship to immunosuppression. Statistical analyses of the differences in incidence of skin cancers between the two groups were done by chi-square test, Fisher's exact test, independent t-test and McNemar's test. FINDINGS: KTRs with non-melanoma skin carcinoma (NMSC) increased significantly after treatment with immunosuppressants (pre-transplantation, n = 11 [18.0%], post-transplantation, n = 28 [45.9%]; p < 0.001). There were no differences in number of patients with NMSC observed in the GD group (pre-diagnosis, n = 6 [11.8%], post-diagnosis, n = 7 [13.7%]; p = 1.000). Compared to the risks at 1 year post-immunosuppressants, the incidence of NMSC of KTRs increased significantly at 3 years (20.3% vs. 35.4%, p < 0.001) and 5 years (20.3% vs. 62.2%, p < 0.001) post-immunosuppressants, whereas the increased incidence of NMSC was observed only at 5 years (2.1% vs. 11.8%, p = 0.012) in the GD cohort. The mean cumulative number of NMSC in KTRs increased significantly at 3 years (p = 0.011), and 5 years (p = 0.001) post-immunosuppressants, compared to the risks at 1 year post-immunosuppressants, however, no differences were noted in the GD cohort. DISCUSSION: Immunosuppressants increased the risk of NMSC in KTRs. The increased risk is likely dependent on the intensity and duration of immunosuppressants. CONCLUSION: In patients with a high risk of NMSC, reducing skin cancer risk should be considered in conjunction with the optimisation of treatment.

G-Protein Signaling Modulator 2 as a Potential Biomarker in Colorectal Cancer: Integrative Analysis Using Genetic Profiling and Pan-Cancer Studies.

Colorectal cancer (CRC) imposes a significant healthcare burden globally, prompting the quest for innovative biomarkers to enhance diagnostic and therapeutic strategies. This study investigates the G-protein signaling modulator (GPSM) family across several cancers and presents a comprehensive pan-cancer analysis of the GPSM2 gene across several gastrointestinal (GI) cancers. Leveraging bioinformatics methodologies, we investigated GPSM2 expression patterns, protein interactions, functional enrichments, prognostic implications, genetic alterations, and immune infiltration associations. Furthermore, the expression of the GPSM2 gene was analyzed using real-time analysis. Our findings reveal a consistent upregulation of GPSM2 expression in all GI cancer datasets analyzed, suggesting its potential as a universal biomarker in GI cancers. Functional enrichment analysis underscores the involvement of GPSM2 in vital pathways, indicating its role in tumor progression. The prognostic assessment indicates that elevated GPSM2 expression correlates with adverse overall and disease-free survival outcomes across multiple GI cancer types. Genetic alteration analysis highlights the prevalence of mutations, particularly missense mutations, in GPSM2. Furthermore, significant correlations between GPSM2 expression and immune cell infiltration are observed, suggesting its involvement in tumor immune evasion mechanisms. Collectively, our study underscores the multifaceted role of GPSM2 in GI cancers, particularly in CRC, emphasizing its potential as a promising biomarker for prognosis and therapeutic targeting. Further functional investigations are warranted to elucidate its clinical utility and therapeutic implications in CRC management.

Surface Markers for the Identification of Cancer Stem Cells.

Cancer stem cells have genetic and functional characteristics which can turn them resistant to standard cancer therapeutic targets. Identification of these cells is challenging and is done mainly by detecting the expression of antigens specific to stem cells. Currently, there is a significant number of surface markers available which can detect cancer stem cells by directly targeting the specific antigens present in cells. These markers possess differential expression patterns and sub-localizations in cancer stem cells compared to nonneoplastic and somatic cells. In addition to these biomarkers, multiple analytical methods and techniques, including functional assays, cell sorting, filtration approaches, and xenotransplantation methods, are used to identify cancer stem cells. This chapter will overview the functional significance of cancer stem cells, their biological correlations, specific markers, and detection methods.

Pegylated nanoliposomal cisplatin ameliorates chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse effect of cisplatin. The current study aimed to determine whether PEGylated nanoliposomal cisplatin can limit CIPN in an animal model. METHODS: Cisplatin-loaded PEGylated liposome nanoparticles (Cis-PL) were produced as a combination of lecithin, cholesterol, and DSPE-mPEG2000 in a molar ratio of 50:45:5 and were characterized by polydispersity index (PDI), zeta potential, Field emission scanning electron microscopy (FESEM) analysis, as well as encapsulation efficiency (EE). Fifteen male rats were provided and randomly divided into 3 groups including Cis-PL group, cisplatin group, and control group. Behavioural tests (hot-plate test and acetone drop test) were used for evaluating CIPN. Moreover, oxidative stress markers and histopathological analysis were applied. Treatment-related toxicity was assessed by haematological analysis as well as liver and renal function tests. RESULTS: Cis-PL had an average particle size of 125.4, PDI of 0.127, and zeta potential of -40.9 mV. Moreover, the Cis-PL exhibited a high EE as well as low levels of leakage rate at 25 °C. In a hot-plate test, paw withdrawal latency was longer in Cis-PL group in comparison to rats treated with cisplatin. A lower number of withdrawal responses was detected during acetone drop test in Cis-PL group than in cisplatin-treated rats. Assessment of oxidative stress markers showed that Cis-PL could improve oxidative stress. Additionally, histopathological assessment demonstrated that the number of satellite cells was significantly reduced in the dorsal root ganglion (DRG) of Cis-PL-treated rats compared with those treated with cisplatin. The cisplatin group had elevated white blood cells counts, reduced platelet counts, and higher levels of bilirubin, ALT (alanine aminotransferase, and AST (aspartate aminotransferase), and creatinine compared with the control group, which was ameliorated in Cis-PL group. CONCLUSIONS: Data from the current study support the previous hypothesis that Cisplatin-loaded PEGylated liposome could be a promising solution for CIPN in the future by modulating oxidative stress and preventing glial cell activation in DRG, suggesting further clinical studies to investigate the efficacy of this agent and its potential application in clinical practice.

Non-Calcifying/Langerhans Cell-Rich Calcifying Epithelial Odontogenic Tumour: A Critical Review of the Rare and Distinctive Entity.

BACKGROUND: The study aims to analyse the non-calcifying/Langerhans cell rich (NCLC) subtype of calcifying epithelial odontogenic tumour (CEOT).  METHOD: The features of cases of the NCLC subtype of CEOT noted in the English literature by PubMed as well as 3 new cases were reviewed. RESULTS: Overall, twenty-one cases were noted. Many were women in the fourth to sixth decades (male-to-female ratio =1 to 2). Radiologically, the lesion is often unilocular with resorption of the affected teeth. Nineteen of the 21 cases occurred in the maxilla, especially the anterior portion. On pathological examination, epithelial cells are noted in non-calcifying amyloid-rich fibrous stroma. The main differential diagnosis is the amyloid subtype of central odontogenic fibroma. Immunohistochemical studies revealed the tumour epithelial cells were positive for cytokeratins and p63 and contained CD1a, S-100, and langerin-positive Langerhans cells. On a median follow-up of 2 years, one patient had a recurrence one year after curettage. CONCLUSION: The NCLC subtype of CEOT is unique as it contains significant numbers of Langerhans cells and has clinicopathological features distinctive from classic CEOT.

Down regulation of Cathepsin W is associated with poor prognosis in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is associated with a very poor prognosis. Therefore, there has been a focus on identifying new biomarkers for its early diagnosis and the prediction of patient survival. Genome-wide RNA and microRNA sequencing, bioinformatics and Machine Learning approaches to identify differentially expressed genes (DEGs), followed by validation in an additional cohort of PDAC patients has been undertaken. To identify DEGs, genome RNA sequencing and clinical data from pancreatic cancer patients were extracted from The Cancer Genome Atlas Database (TCGA). We used Kaplan-Meier analysis of survival curves was used to assess prognostic biomarkers. Ensemble learning, Random Forest (RF), Max Voting, Adaboost, Gradient boosting machines (GBM), and Extreme Gradient Boosting (XGB) techniques were used, and Gradient boosting machines (GBM) were selected with 100% accuracy for analysis. Moreover, protein-protein interaction (PPI), molecular pathways, concomitant expression of DEGs, and correlations between DEGs and clinical data were analyzed. We have evaluated candidate genes, miRNAs, and a combination of these obtained from machine learning algorithms and survival analysis. The results of Machine learning identified 23 genes with negative regulation, five genes with positive regulation, seven microRNAs with negative regulation, and 20 microRNAs with positive regulation in PDAC. Key genes BMF, FRMD4A, ADAP2, PPP1R17, and CACNG3 had the highest coefficient in the advanced stages of the disease. In addition, the survival analysis showed decreased expression of hsa.miR.642a, hsa.mir.363, CD22, BTNL9, and CTSW and overexpression of hsa.miR.153.1, hsa.miR.539, hsa.miR.412 reduced survival rate. CTSW was identified as a novel genetic marker and this was validated using RT-PCR. Machine learning algorithms may be used to Identify key dysregulated genes/miRNAs involved in the disease pathogenesis can be used to detect patients in earlier stages. Our data also demonstrated the prognostic and diagnostic value of CTSW in PDAC.

The Prognostic Value of ASPHD1 and ZBTB12 in Colorectal Cancer: A Machine Learning-Based Integrated Bioinformatics Approach.

Introduction: Colorectal cancer (CRC) is a common cancer associated with poor outcomes, underscoring a need for the identification of novel prognostic and therapeutic targets to improve outcomes. This study aimed to identify genetic variants and differentially expressed genes (DEGs) using genome-wide DNA and RNA sequencing followed by validation in a large cohort of patients with CRC. Methods: Whole genome and gene expression profiling were used to identify DEGs and genetic alterations in 146 patients with CRC. Gene Ontology, Reactom, GSEA, and Human Disease Ontology were employed to study the biological process and pathways involved in CRC. Survival analysis on dysregulated genes in patients with CRC was conducted using Cox regression and Kaplan-Meier analysis. The STRING database was used to construct a protein-protein interaction (PPI) network. Moreover, candidate genes were subjected to ML-based analysis and the Receiver operating characteristic (ROC) curve. Subsequently, the expression of the identified genes was evaluated by Real-time PCR (RT-PCR) in another cohort of 64 patients with CRC. Gene variants affecting the regulation of candidate gene expressions were further validated followed by Whole Exome Sequencing (WES) in 15 patients with CRC. Results: A total of 3576 DEGs in the early stages of CRC and 2985 DEGs in the advanced stages of CRC were identified. ASPHD1 and ZBTB12 genes were identified as potential prognostic markers. Moreover, the combination of ASPHD and ZBTB12 genes was sensitive, and the two were considered specific markers, with an area under the curve (AUC) of 0.934, 1.00, and 0.986, respectively. The expression levels of these two genes were higher in patients with CRC. Moreover, our data identified two novel genetic variants-the rs925939730 variant in ASPHD1 and the rs1428982750 variant in ZBTB1-as being potentially involved in the regulation of gene expression. Conclusions: Our findings provide a proof of concept for the prognostic values of two novel genes-ASPHD1 and ZBTB12-and their associated variants (rs925939730 and rs1428982750) in CRC, supporting further functional analyses to evaluate the value of emerging biomarkers in colorectal cancer.

Extracellular vesicles: Emerging mediators of cell communication in gastrointestinal cancers exhibiting metabolic abnormalities.

There is a complex interaction between pro-tumoural and anti-tumoural networks in the tumour microenvironment (TME). Throughout tumourigenesis, communication between malignant cells and various cells of the TME contributes to metabolic reprogramming. Tumour Dysregulation of metabolic pathways offer an evolutional advantage in the TME and enhance the tumour progression, invasiveness, and metastasis. Therefore, understanding these interactions within the TME is crucial for the development of innovative cancer treatments. Extracellular vesicles (EVs) serve as carriers of various materials that include microRNAs, proteins, and lipids that play a vital role in the communication between tumour cells and non-tumour cells. EVs are actively involved in the metabolic reprogramming process. This review summarized recent findings regarding the involvement of EVs in the metabolic reprogramming of various cells in the TME of gastrointestinal cancers. Additionally, we highlight identified microRNAs involved in the reprogramming process in this group of cancers and explained the abnormal tumour metabolism targeted by exosomal cargos as well as the novel potential therapeutic approaches.

Therapeutic Potential of Targeting the Cytochrome P450 Enzymes Using Lopinavir/Ritonavir in Colorectal Cancer: A Study in Monolayers, Spheroids and In Vivo Models.

Cytochrome P450 (CYP450) enzyme has been shown to be expressed in colorectal cancer (CRC) and its dysregulation is linked to tumor progression and a poor prognosis. Here we investigated the therapeutic potential of targeting CYP450 using lopinavir/ritonavir in CRC. The integrative systems biology method and RNAseq were utilized to investigate the differential levels of genes associated with patients with colorectal cancer. The antiproliferative activity of lopinavir/ritonavir was evaluated in both monolayer and 3-dimensional (3D) models, followed by wound-healing assays. The effectiveness of targeting CYP450 was examined in a mouse model, followed by histopathological analysis, biochemical tests (MDA, SOD, thiol, and CAT), and RT-PCR. The data of dysregulation expressed genes (DEG) revealed 1268 upregulated and 1074 down-regulated genes in CRC. Among the top-score genes and dysregulated pathways, CYPs were detected and associated with poor prognosis of patients with CRC. Inhibition of CYP450 reduced cell proliferation via modulating survivin, Chop, CYP13a, and induction of cell death, as detected by AnnexinV/PI staining. This agent suppressed the migratory behaviors of cells by induction of E-cadherin. Moreover, lopinavir/ritonavir suppressed tumor growth and fibrosis, which correlated with a reduction in SOD/thiol levels and increased MDA levels. Our findings illustrated the therapeutic potential of targeting the CYP450 using lopinavir/ritonavir in colorectal cancer, supporting future investigations on this novel therapeutic approach for the treatment of CRC.

Correction: Aktar et al. Gene Expression Analysis of Immune Regulatory Genes in Circulating Tumour Cells and Peripheral Blood Mononuclear Cells in Patients with Colorectal Carcinoma. Int. J. Mol. Sci. 2023, 24, 5051.

Faysal Bin Hamid was not included as an author in the original publication [...].

Gene Expression Analysis of Immune Regulatory Genes in Circulating Tumour Cells and Peripheral Blood Mononuclear Cells in Patients with Colorectal Carcinoma.

Information regarding genetic alterations of driver cancer genes in circulating tumour cells (CTCs) and their surrounding immune microenvironment nowadays can be employed as a real-time monitoring platform for translational applications such as patient response to therapeutic targets, including immunotherapy. This study aimed to investigate the expression profiling of these genes along with immunotherapeutic target molecules in CTCs and peripheral blood mononuclear cells (PBMCs) in patients with colorectal carcinoma (CRC). Expression of p53, APC, KRAS, c-Myc, and immunotherapeutic target molecules PD-L1, CTLA-4, and CD47 in CTCs and PBMCs were analysed by qPCR. Their expression in high versus low CTC-positive patients with CRC was compared and clinicopathological correlations between these patient groups were analysed. CTCs were detected in 61% (38 of 62) of patients with CRC. The presence of higher numbers of CTCs was significantly correlated with advanced cancer stages (p = 0.045) and the subtypes of adenocarcinoma (conventional vs. mucinous, p = 0.019), while being weakly correlated with tumour size (p = 0.051). Patients with lower numbers of CTCs had higher expression of KRAS. Higher KRAS expression in CTCs was negatively correlated with tumour perforation (p = 0.029), lymph node status (p = 0.037), distant metastasis (p = 0.046) and overall staging (p = 0.004). CTLA-4 was highly expressed in both CTCs and PBMCs. In addition, CTLA-4 expression was positively correlated with KRAS (r = 0.6878, p = 0.002) in the enriched CTC fraction. Dysregulation of KRAS in CTCs might evade the immune system by altering the expression of CTLA-4, providing new insights into the selection of therapeutic targets at the onset of the disease. Monitoring CTCs counts, as well as gene expression profiling of PBMCs, can be helpful in predicting tumour progression, patient outcome and treatment.

Current Status of Circulating Tumor Cells in Head and Neck Squamous Cell Carcinoma: A Review.

OBJECTIVE: Circulating tumor cells (CTCs) are found in the blood of patients with cancer, including head and neck squamous cell carcinomas (HNSCCs). The aim is to review the most up-to-date status of CTCs for applications in patients with HNSCC. DATA SOURCES: English articles in PubMed. REVIEW METHODS: All the studies on CTCs in HNSCCs in the literature were reviewed. CONCLUSIONS: There is emerging information on the diagnostic and prognostic value of CTCs in HNSCCs. Evidence also highlights the advantages of various downstream analysis approaches over circulating tumor DNA (ctDNA), such as single-CTC analysis, ex vivo, and in vivo expansion of CTCs. Multiple phenotypic surface markers (cytokeratins, EpCAM, vimentin, etc.), used for CTCs characterization using different immunoassays, could predict disease progression as well as patients' response to treatment efficacy. Immune checkpoint inhibitors' status in CTCs could also provide better insight into treatment. Clonal expansion of CTCs and single-cell analysis of CTCs are the most emerging fields nowadays which may offer an understanding of the mechanism of tumor evolution as well as therapeutic efficacy. Although several clinical trials are ongoing, limitations still exist in the detection and characterization of CTCs. Due to the lack of a gold standard protocol, the sensitivity and specificity of CTC enumeration methods vary. IMPLICATIONS FOR PRACTICE: Prospective clinical trials are still needed before CTCs can be employed as diagnostic and prognostic markers in the clinical management of patients with HNSCC.

A diagnostic pitfall; Small cell carcinoma-like features in basaloid squamous cell carcinoma of the esophagus.

Esophageal basaloid squamous cell carcinoma may resemble small cell carcinoma biopsy specimens and cause difficulties in pathology diagnosis. We aimed to clarify the clinicopathological significance of small cell carcinoma-like morphologies in basaloid squamous cell carcinoma. Thirty biopsy specimens of esophageal basaloid squamous cell carcinoma were reviewed and compared with 13 matched surgical specimens. Small cell carcinoma-like features, such as diffuse growth, nuclear molding, or nuclear crush artifact, were identified in 80% (24/30) of the biopsies and in 77% (10/13) of the surgery specimens, but in a proportionally much smaller area in the surgical specimens than in the biopsy samples. The presence of a small cell carcinoma-like feature had no impact on patients´ outcome. Immunohistochemically, synaptophysin and chromogranin A were consistently negative, while CD56 was expressed in 42% (10/24) of basaloid squamous cell carcinomas with small cell carcinoma-like features. p16, a highly sensitive marker for small cell carcinoma, was also expressed in 8% (2/24). p40 was expressed in all cases of basaloid squamous cell carcinoma. In conclusion, small cell carcinoma-like features are frequent and conspicuous in biopsies, which are probably caused by exogenous factors such as friction and external pressure that occur in biopsy procedure and in the tumor environment. Small cell carcinoma-like features may lead to a misinterpretation of a true small cell carcinoma, if CD56 is the only neuroendocrine marker expressed. p16 expression may also be detected in basaloid squamous cell carcinoma.

Lipopolysaccharide-binding protein as a biomarker in oral and maxillofacial tumors.

Oral and maxillofacial tumors (OMTs), such as oral squamous cell carcinoma (SCC), pleomorphic adenoma, and ameloblastoma, are common head and neck tumors. Lipopolysaccharide-binding protein (LBP) is a type I acute reactive protein, which participates in body inflammatory response modulation through lipopolysaccharide (LPS)-induced signaling pathway by targeting macrophages (expressing cluster of differentiation 204 [CD204]). Although it is well established that LBP is associated with the development of multiple types of cancer, little is known about the role of LBP in OMTs. This study aims to explore the expression of LBP in OMTs. Here, immunohistochemical (IHC) double staining of LBP and CD204 and enzyme-linked immunosorbent assay (ELISA) were conducted to explore the LBP expression in OMTs. The findings demonstrated that the LBP expression in OMTs was significantly elevated (p < 0.001). In addition, the LBP expression was associated with the clinical stage (p < 0.001), T classification (p < 0.001), and lymph node metastasis (p < 0.001, except ELISA) but independent of histological grade of SCC, gender, and age in patients with SCC. The optional cutoff of the LBP serum level is 0.721 µg/ml. To conclude, LBP contributes to the development of OMTs and could be a biomarker in the screening and predicting metastasis in patients with OMTs.

Analysis of metabolomics and transcriptomics data in head and neck squamous cell carcinoma.

OBJECTIVE: Studies have shown that cancer progression of head and neck squamous cell carcinoma (HNSCC) is related with metabolic alterations. The aim of this study is to identify the clinical roles of metabolic alterations in HNSCC. MATERIALS AND METHODS: Metabolism-related genes associated with HNSCC were searched in public databases. A predictive and efficacious LASSO model was fabricated to optimize the diagnosis that was based on these genes. Meantime, ultra-performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used to compare patients with HNSCC (n = 73) with healthy controls (n = 51) for serum metabolites. Potential biomarkers and alterations in serum metabolites were analysed and evaluated using t test analysis, principal component analysis and orthogonal partial least square-discrimination analysis. RESULTS: Overall, 21 differential metabolites were probed in serum, of which eight metabolites had potential for clinical uses. Transcriptome analysis showed that four genes in the constructed LASSO model were found to be associated with seven differential metabolites. Metabolic pathway analysis by MetaboAnalyst showed that the biomarkers that were related with HNSCC were closely related to four metabolism pathways (p < 0.05). CONCLUSION: To conclude, future research on HNSCC should be directed towards multi-omics to provide treatment, intervention or diagnosis of the disease.

An integrated skin cancer education program in renal transplant recipients and patients with glomerular disease.

Sun-protective strategies focusing on skin cancer awareness are needed in immunosuppressed patients at risk of skin cancers. The study aims to determine the effect of an integrated skin cancer education program on skin cancer awareness and sun-protective behaviours in renal transplant recipients (RTRs) and patients with glomerular disease (GD) treated with long-term immunosuppressants. A pilot prospective cohort study in Central Queensland, Australia was undertaken among adult RTRs and patients with GD, who completed survey questionaries on skin cancer and sun-health knowledge (SCSK), sun-protection practices and skin examination pre- and post-education. Fifty patients (25 RTRs, 25 patients with GD) participated in the study. All of them completed questionnaires at pre-, 3-month post-education and 92%(n = 46) at 6-month post-education. There was a significant increase in SCSK scores from baseline at 3-months (p < 0.001) and 6-months post-intervention (p < 0.01). Improved knowledge was retained for 6 months after education. There were changes in 2 of 8 photoprotective behaviours at 6 months. Interventional education enhanced regular self-skin examination rate (p < 0.001) as well as the frequency of full skin checks by general practitioners (GPs) (p < 0.001). Overall, RTRs had better compliance with sun-protective methods and higher skin examination rates by themselves and/ or GPs before and after the intervention of education compared to patients with GD. To conclude, an integrated skin cancer education program improved knowledge of skin cancer and skin health as well as the frequency of self-skin examination and formal skin assessments. However, improvement in patient compliance did not extend to other sun-protective practices.

Comprehensive assessment of actionable genomic alterations in primary colorectal carcinoma using targeted next-generation sequencing.

BACKGROUND: The clinical utility of comprehensive genomic profiling (CGP) for guiding treatment has gradually become the standard-of-care procedure for colorectal carcinoma (CRC). Here, we comprehensively assess emerging targeted therapy biomarkers using CGP in primary CRC. METHODS: A total of 575 primary CRCs were sequenced by ACTOnco® assay for genomic alterations, tumour mutational burden (TMB), and microsatellite instability (MSI). RESULTS: Eighteen percent of patients were detected as MSI-High (MSI-H), and the remaining cases were classified as microsatellite stable (MSS). Driver mutation prevalence in MSS CRCs were APC (74%), TP53 (67%), KRAS (47%), PIK3CA (21%) and BRAF (13%). The median TMBs for MSI-H and MSS patients were 37.8 mutations per mega base (mut/Mb) and 3.9 mut/Mb, respectively. Forty-seven percent of MSI-H CRC harboured at least one loss-of-function mutations in genes that may hamper immune checkpoint blockade. Among MSS RAS/RAF wild-type CRCs, 59% had at least one actionable mutation that may compromise the efficacy of anti-EGFR therapy. For late-stage CRC, 51% of patients are eligible for standard care actionability and the remaining 49% could be enrolled in clinical trials with investigational drugs. CONCLUSIONS: This study highlights the essential role of CGP for identifying rational targeted therapy options in CRC.

An update on the current epidemiological status of metastatic neoplasms to the thyroid.

Secondary tumours to the thyroid gland are uncommon with an overall prevalence of 5.9% in autopsy studies. In recent clinical series, secondary thyroid cancer is seen in only 1.9% of malignant thyroids. There is no gender predominance both overall (female to male 1.07:1) and when stratified by common histological subtypes (renal cell carcinoma, lung adenocarcinoma and colorectal adenocarcinoma). The median age of patients diagnosed with metastatic thyroid tumours in major studies ranges from 54 to 68 years. Metastases are more frequent in patients with pre-existing or concurrent thyroid pathology. In autopsy studies, the most common primary sites are breast carcinoma and lung carcinoma. Renal cell carcinoma, lung carcinoma and breast carcinoma predominate in clinical series. Upper aerodigestive tract primaries often directly infiltrate the thyroid gland. The underlying frequency of a histological subtype, geographic prevalence and aggressiveness of primary cancer likely contributes to the incidence of metastasis in the thyroid gland. This is seen in case series from Asia where gastric and oesophageal primary cancers predominate. Secondary thyroid cancer can present metachronously (60%), synchronously (34%), or as the first presentation of the underlying cancer (6%). Late metastases and first clinical presentations of disease often originate from renal cell carcinomas while synchronous cases tend to originate from the lungs. Other common primary sites for first presentation of secondary thyroid cancer include the lung and oesophagus. Although rare, secondary thyroid cancer should be considered as a differential particularly in patients with previous malignancy, such as from the kidney, lung, or breast.