Dysregulation of miR-21-5p, miR-93-5p, miR-200c-3p and miR-205-5p in Oral Squamous Cell Carcinoma: A Potential Biomarkers Panel?

Oral squamous cell carcinoma (OSCC) is considered the sixth most common cancer worldwide. To reduce the high mortality of the disease, sensitive and specific diagnostic and prognostic biomarkers are urgently needed. Non-coding RNA, microRNAs (miRNAs), which are short length non-coding transcripts, or long non-coding RNA (lncRNA) seem to be potential biomarkers, considering that they have an important role in regulation of cell fate being involved in a wide range of biological processes. Literature data emphasized the important role of these transcripts as a biomarker for diagnosis and prognosis in oral squamous cell carcinoma. Therefore, we have evaluated the expression levels of a panel of four miRNAs (miR-21-5p, miR-93-5p, miR-200c-3p and miR-205-5p) and H19, MALAT1 by quantitative real-time PCR (qRT-PCR) from 33 fresh frozen tissues and 33 normal adjacent tissues. Our date revealed miR-21-5p and miR-93-5p to be upregulated, while miR-200c-3p and miR-205-5p to be downregulated. Regarding the long non-coding RNAs, H19 and MALAT1, were also downregulated. We also investigated the expression of BCL2, which is another important gene correlated to non-coding RNAs investigated by as, and it was also under-expressed. Additional validation step at protein level was done for KI67, TP53 and BCL2. In our patient cohort no correlation with clinical stage and smoking status was observed. The results of the present study indicated the important role of miR-21-5p, miR-93-5p, miR-200c-3p, miR-205-5p and H19 in OSCC. Differential expression of these transcripts at sub-sites, may serve as a diagnostic marker with further elaboration on a larger sample size. Additional studies should be conducted to confirm the results, particularly the interconnection with coding and non-coding genes.

Nanoscale delivery systems for microRNAs in cancer therapy.

Concomitant with advances in research regarding the role of miRNAs in sustaining carcinogenesis, major concerns about their delivery options for anticancer therapies have been raised. The answer to this problem may come from the world of nanoparticles such as liposomes, exosomes, polymers, dendrimers, mesoporous silica nanoparticles, quantum dots and metal-based nanoparticles which have been proved as versatile and valuable vehicles for many biomolecules including miRNAs. In another train of thoughts, the general scheme of miRNA modulation consists in inhibition of oncomiRNA expression and restoration of tumor suppressor ones. The codelivery of two miRNAs or miRNAs in combination with chemotherapeutics or small molecules was also proposed. The present review presents the latest advancements in miRNA delivery based on nanoparticle-related strategies.

Differentiation of Endometriomas from Ovarian Hemorrhagic Cysts at Magnetic Resonance: The Role of Texture Analysis.

Background and Objectives: To assess ovarian cysts with texture analysis (TA) in magnetic resonance (MRI) images for establishing a differentiation criterion for endometriomas and functional hemorrhagic cysts (HCs) that could potentially outperform their classic MRI diagnostic features. Materials and Methods: Forty-three patients with known ovarian cysts who underwent MRI were retrospectively included (endometriomas, n = 29; HCs, n = 14). TA was performed using dedicated software based on T2-weighted images, by incorporating the whole lesions in a three-dimensional region of interest. The most discriminative texture features were highlighted by three selection methods (Fisher, probability of classification error and average correlation coefficients, and mutual information). The absolute values of these parameters were compared through univariate, multivariate, and receiver operating characteristic analyses. The ability of the two classic diagnostic signs ("T2 shading" and "T2 dark spots") to diagnose endometriomas was assessed by quantifying their sensitivity (Se) and specificity (Sp), following their conventional assessment on T1-and T2-weighted images by two radiologists. Results: The diagnostic power of the one texture parameter that was an independent predictor of endometriomas (entropy, 75% Se and 100% Sp) and of the predictive model composed of all parameters that showed statistically significant results at the univariate analysis (100% Se, 100% Sp) outperformed the ones shown by the classic MRI endometrioma features ("T2 shading", 75.86% Se and 35.71% Sp; "T2 dark spots", 55.17% Se and 64.29% Sp). Conclusion: Whole-lesion MRI TA has the potential to offer a superior discrimination criterion between endometriomas and HCs compared to the classic evaluation of the two lesions' MRI signal behaviors.

Analysis of Clinical-Pathological Data with Impact on Overall Survival in Male Breast Carcinoma: An International Multi-Institutional Study of 217 Cases.

Background: The aim of this study was to evaluate clinical-pathological parameters with impact on overall survival (OS) in male breast carcinoma (MBC). Methodology: We assessed OS at 5 years and at 10 years respectively, as well as OS according to age, tumor size, microscopic type, histological grade, axillary lymph node status, and molecular profile. Results:Two hundred seventeen cases, with a mean age of 62 (range: 18- 85), right breast involvement (52.53%), invasive carcinoma of no special type (86.63%), G2 histological grade (55.4%), T2 (54.41%), N+ (65.89%) and Luminal A molecular subtype (85.29%) were identified. ER, PR and AR were positive in 89.71%, 83.82% and 93.29% of cases, respectively. HER2 was overexpressed in 8.33% of cases and a high Ki67 proliferation index was present in 75% of cases. The 5-year OS was 67.2%, whereas 10-year OS was 48.5%; OS was 92.7% at 5 years and 73.8% at 10 years in axillary lymph node (LN) negative cases, while OS was 59.7% at 5 years and 41.3% at 10 years in axillary LN positive cases (p=0.003). Conclusions: Age at diagnosis ( 60 years), larger tumor size, presence of LN metastases and absence of oncological treatment are negative factors influencing prognosis, with only axillary LN status (p=0.005) and triple negative molecular profile (p=0.05) being statistically significant unfavorable independent prognostic parameters in a multivariate analysis.

The decrease of some serum free amino acids can predict breast cancer diagnosis and progression.

This study was targeted on a metabolomic approach to compare the blood serum free amino acid profiles and concentration of confirmed breast cancer (stages I-III) patients to healthy controls in order to establish reliable biomarkers of early detection and prediction of breast cancer. The ultra-high-performance liquid chromatography coupled with mass spectrometry using positive ionization electrospray was applied for the picoline-derivatized serum free amino acids using the EZ:faastTM kit. Multivariate statistical analysis principal component analysis, partial least squares discrimination analysis and univariate analysis were applied in order to discriminate between patient groups and putative amino acid biomarkers for breast cancer. A significant decrease of amino acid concentrations between the breast cancer group and the control group was positively correlated with breast cancer progression. Arginine, Alanine, Isoleucine, Tyrosine and Tryptophan were identified as being good potential discriminants (AUROC ≥0.85) and suitable candidates to diagnose and predict the breast cancer progression.

Progress in Research on the Role of Flavonoids in Lung Cancer.

Lung cancer is the leading cause of cancer deaths worldwide. Therefore, for the prevention, diagnosis, prognosis and treatment of lung cancer, efficient preventive strategies and new therapeutic strategies are needed to face these challenges. Natural bioactive compounds and particular flavonoids compounds have been proven to have an important role in lung cancer prevention and of particular interest is the dose used for these studies, to underline the molecular effects and mechanisms at a physiological concentration. The purpose of this review was to summarize the current state of knowledge regarding relevant molecular mechanisms involved in the pharmacological effects, with a special focus on the anti-cancer role, by regulating the coding and non-coding genes. Furthermore, this review focused on the most commonly altered and most clinically relevant oncogenes and tumor suppressor genes and microRNAs in lung cancer. Particular attention was given to the biological effect in tandem with conventional therapy, emphasizing the role in the regulation of drug resistance related mechanisms.

Non-Small Cell Lung Cancer in Countries of Central and Southeastern Europe: Diagnostic Procedures and Treatment Reimbursement Surveyed by the Central European Cooperative Oncology Group.

This article analyzes the availability of different diagnostic procedures of non-small cell lung cancer (NSCLC) and the reimbursement landscape of drugs for NSCLC in countries of central and southeastern Europe (CEE). A survey was conducted by the Central European Cooperative Oncology Group. Results of the survey show that both availability and reimbursement of diagnoses of molecular alterations in NSCLC, the detection of which is essential for therapeutic decisions, varies widely between countries of CEE. Not only is "reflex" testing often substituted by analyses performed only "on demand," but reimbursement of such assessments varies widely between unavailability and payments by the health care system or even pharmaceutical companies. It was concluded that a structured access to testing and reimbursement should be the aim in order to provide patients with appropriate therapeutic options. IMPLICATIONS FOR PRACTICE: This article provides an overview of the limitations in lung cancer treatment in countries of central and southeastern Europe, as well as the reimbursement status of various lung cancer treatment regimens in these countries, which directly impacts treatment options.

Follicle-stimulating hormone receptors: A comparison of commercially-available monoclonal and polyclonal antibodies as immunohistochemical markers for cancer research.

PURPOSE: In recent studies, follicle-stimulating hormone receptors (FSHRs) have been reported in a wide range of malignant and benign tumours, depending on the type of antibody used. Using two commercially available antibodies (monoclonal and polyclonal), the current research attempted to demonstrate the usefulness of each antibody for investigating FSHRs in non-canonical tissues. Further, we sought to replicate the results of a major study which demonstrated the presence of FSHRs in the endothelial cells of perineoplastic blood vessels. METHODS: Immunostaining was performed on 16 surgically excised benign and malignant tumor tissue samples using both monoclonal and polyclonal anti-FSHR antibodies. RESULTS: Positive staining of FSHRs was heterogeneous among the tissue samples used for analysis, and was confirmed not only in tumour and endothelial cells of perineoplastic blood vessels, but also in benign and normal cells. Based on our findings, FSHR staining using a polyclonal antibody appeared to be highly sensitive, but with a relatively low specificity. Comparatively, immunoreactivity using a monoclonal antibody appeared to show high specificity, but relatively low sensitivity. Although the selected monoclonal antibody for FSHRs seemed to be more specific than the polyclonal variant, neither exhibited a high overall specificity. Neither of the antibodies assessed in the present research could replicate the results of the aforementioned major study. CONCLUSIONS: In conclusion, neither of the two commercially available antibodies seem to be appropriate for investigating FSHRs in non-canonical tissues and, by extension, their role in carcinogenesis.

Follicle-stimulating hormone receptors: a new immunohistochemical marker in cancers?

PURPOSE: Follicle-stimulating hormone receptors (FSHR) have been reported in ovarian cancer and prostate cancer cells, but recent studies have highlighted their presence in the endothelium of blood vessels belonging to multiple neoplasias. Current research attempts to determine the role of FSHR in neoplastic proliferation and possible therapeutic or diagnostic implications. This paper aimed to analyze articles that have revealed the presence and/or role of FSHR in various neoplasms in humans. METHODS: After performing an extensive search of MEDLINE/ PubMed using MeSH terms "follicle-stimulating hormone receptors" and "cancer", 22 original articles were found relevant for the subject proposed for analysis. RESULTS: FSHR were found in all neoplasms studied, being present in both tumor cells and endothelial cells of intraand perineoplasic blood vessels. Although, the presence of these receptors seemed to be ubiquitary, conclusion and the exact role of these receptors could not be stated due to heterogeneous nature of the existing studies. CONCLUSIONS: Although extensive research studies are needed in order to elucidate the exact role of FSHRs and their utility in clinical practice, joint efforts in studying their implication in neoplastic processes can lead to the use of new diagnostic and therapeutic strategies for cancer patients.

Biomarkers for the early detection of relapses in metastatic colorectal cancers.

PURPOSE: To assess prognostic/predictive value of carcinoembryonic antigen (CEA), transthyretin (TRT), αenolase (NNE), ß2-microglobulin (ß2-micro), B-cell activating factor (BAFF) and circulating tumor cells (CTCs) in metastatic colorectal cancer (mCRC) patients treated with chemotherapy with or without bevacizumab. METHODS: 72 histologically confirmed mCRC patients treated at Oncology Institute Cluj were included. Biomarker levels were measured through validated methods. A manual method was used for CTCs, involving hemolysis, cytospin centrifugation and immunocytochemical staining for pan-cytokeratin. Statistical endpoints were response, progression- free survival (PFS) and overall survival (OS). RESULTS: Initial chemotherapy was fluoropyrimidine/oxaliplatin-based in 93.1%; bevacizumab was added in 58.3% of the patients. Median PFS and OS were 16.4 and 24.4 months. Two-year OS for CR & PR vs SD vs PD were 90% vs 48% vs 12%, respectively (p<0.01). Two-year OS for chemo/ bevacizumab vs chemotherapy: 65% vs 42% (p=0.09). Baseline CEA ≥5 ng/ml had a negative prognostic impact on OS and PFS (p<0.01). High baseline CEA was predictive of improved OS when adding bevacizumab (2-year OS chemo/bevacizumab vs chemo: 60% vs 17%, p<0.01); adding bevacizumab in patients with normal CEA did not improve OS (p=0.29). Higher than cut-off values for TRT had a positive OS prognostic value (p<0.01); higher levels for NNE, ß2-microglobulin and BAFF had a negative impact (p<0.01). Two-year OS for baseline <1 CTC/ml vs ≥1 CTC/ ml was 74% vs 64% respectively (p=0.15). CONCLUSIONS: The evaluated biomarkers could be useful prognostic factors for survival. Baseline CEA also has predictive value, suggesting that patients with low levels do not benefit from bevacizumab. A non-statistically significant correlation was observed between the number of CTCs and outcome.