Here, we present the case of a 74-year-old woman with clinically prominent hirsutism and a large adrenal mass where the clinical diagnosis was inconsistent with the histological appearance. Her hormonal evaluation showed normal androgens with slightly inadequate cortisol suppression upon dexamethasone test but normal 24-h urinary free cortisol. Abdominal computed tomography (CT) imaging showed a large inhomogeneous mass of the left adrenal and the FDG PET/CT scan revealed hypermetabolic foci in the right upper lobe of the lung, in hilum lymph nodes, and in the soft tissue in proximity to the right femoral neck. The cytological examination of a biopsy from the pulmonary lesion showed a highly malignant neoplasm of unknown origin, and left adrenalectomy, nephrectomy, and splenectomy were performed. The pathologists reported infiltration of the adrenal by an undifferentiated carcinoma of unknown origin. Due to the clinical suspicion of adrenocortical carcinoma (ACC), a mitotane therapy along with hydrocortisone substitution was directly initiated, and the patient also received 6 cycles of chemotherapy. However, the patient’s condition deteriorated quickly, and she died. Upon availability of steroidogenic factor-1 staining, the positivity of the resected tumor could be documented postmortem, confirming the diagnosis of an ACC. Taken together, this case underlines the difficulties in the differential diagnosis of aggressive adrenal masses.

Soft tissue sarcoma is a heterogeneous disease and treatment options are limited in advanced stage settings. Brivudine is a thymidine-nucleoside analog and inhibits DNA polymerase in VZV infection. We demonstrated a case of a patient who was diagnosed with both VZV infection and advanced stage sarcoma, and unexpected anti-tumoral response after brivudine therapy.

Microtubule-targeting agents often have limitations to the development of resistance. Colchicine binding site (CBS) agents have several advantages compared with other tubulin inhibitors. Numerous medications in this class are less susceptible to multidrug resistance that restricts the viability of different inhibitors. In the present study, molecules that bind to the CBS of tubulin are collected from PubMed literature against the A549 cancer cell line. Regression models were established between the descriptor and IC50 value of all the compounds present in the training set based on significant molecular fingerprints using multiple linear regression (MLR). Fifteen most significant descriptors selected include Burden modified eigenvalue descriptors, PaDEL-weighted path descriptor, autocorrelation descriptor, topological distance matrix descriptor, MLFER descriptor, Barysz matrix descriptor, chi path cluster descriptor, and validated using internal and external validation parameters. The selected MLR-GA model has R2adjusted = 0.7895, Q2 CV = 0.76577, R2 pred = 0.7419, and R2 tes = 0.77373. An applicability domain is also defined so that it defines the chemical space that the model can predict. The above details suggest a good predictive model for CBS inhibitors that can predict the IC50 value of the unknown chemical compound.

Objectives: Analysis of multi-molecular interactions and detection of combinatorial transcriptomic signatures are emerging as important research topics in disease analytics. Currently, a combination of gene and miRNA expression profiling in bioinformatic analysis enables us to comprehensively detect molecular changes in cancer and thereafter to identify integrated signatures and pathways that exist in the miRNA and gene interaction networks. Although many methodologies and applications have been suggested in recent literature, efficient techniques that can integrate the complex gene as well as miRNA expression profiles, and identify the most relevant signatures are required. Methods: In this article, we presented a new framework of multi-molecular data integration to identify combinatorial transcriptomic signatures through the strategy of unsupervised learning and target detection. Later, we evaluated their utility in survival analysis through a multi-variate Cox regression study. We used a cervical cancer data repository to conduct our experiment. To construct the miRNA-mRNA interaction network, we selected the downregulated mRNAs that were negatively correlated with the upregulated miRNAs. Thereafter, we identified dense modules by using an unsupervised learning technique. The silhouette index value was computed for each cluster. Results: By considering the network centrality of each molecule belonging to each cluster we identified top 3 combined signatures We also highlighted cluster-2 (hsa-mir-944, CFTR, GABRB2, HNF4G, TAC1, and C7orf57) for its high cohesiveness and contained a combined signature. We then applied three well-known classifiers (viz., SVM, KNN, and random forest) using 10-fold cross-validation, and obtained a high AUC score for cluster-2. Finally, we conducted a survival study with each molecule of the same cluster. Conclusion: Finally, we conducted a survival study with each molecule of the same cluster. Our proposed combined signature detection strategy can determine the signature(s) for any microarray or RNA-Seq profile. The code is available at https://github.com/sahasuparna/DeMoS

Objectives: To investigate the immune inflammatory profile in patients affected by benign salivary gland tumors (SGTs) by evaluating the blood inflammatory biomarkers. Methods: A retrospective chart review was performed between January 2015 and April 2020, collecting the data of all patients admitted for benign SGTs in our maxillofacial surgery unit. A total of 191 patients were divided into two groups: 94 with Warthin’s tumor (WT group) and 97 with pleomorphic adenoma (PA group) at histological diagnosis. The third group consisted of 90 patients randomly selected as the control group (C group). Results: The most relevant correlations were found by analyzing the values of some inflammatory biomarkers among the three groups. The neutrophil-to-lymphocyte ratio was found significantly higher in patients in the PA (p<0.005) and WT (p<0.001) groups than in patients in the C group. Similarly, the systemic immune-inflammation index was found significantly higher in patients in the PA and WT (p<0.005) groups than in patients in the C group. The platelet-tolymphocyte ratio was significantly higher in patients in the PA group than in patients in the WT (p<0.05) and C groups (p<0.05). Conclusion: In both WT and PA groups, the inflammatory status of the patients was found altered. Thus, inflammation and the immune system seem to have a role in the genesis of these benign salivary neoplasms whose etiopathogenesis is still debated.

Objectives: Breast cancer (BCa) remains the world’s second biggest cause of cancer death. This occurs as a result of unregulated cell development and can be metastasized to other parts of the human. Estrogen receptor alpha is the renowned target that has piqued the interest of researchers to target BCa. FlexX molecular docking technique was used to predict the aspects of interaction, affinities energy, and orientation of natural compounds in the protein site. Phytoconstituents have a vital role in anticancer activities due to their important scaffolds, which may offer more effective and reduced costs and side effects than synthetic drugs. The present study aims to identify new anticancer agents from natural and dietary compounds with lesser adverse effects. Methods: To accomplish this, we implemented with the help of molecular docking approaches using FlexX for predicting the features of bioactive phytocompounds from natural products and evaluating targeted binding affinity energy. Results: Our results confirm that among various natural compounds, daidzein has the best docking score in the ten compounds compared with the standard drug cytarabine. Conclusion: Our study suggests that daidzein is a potent ligand for ERα BCa among all and can be further investigated through in vitro and in vivo studies.

Objectives: The objective of the study is to evaluate the expression of CD10 in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC) and to determine its role as a potential biomarker in OSCC. Methods: Immunohistochemical evaluation of 40 archival paraffin-embedded tissue specimens grouped into oral epithelial dysplasia and early invasive, well-differentiated, and moderately differentiated OSCC was conducted to determine and compare the CD10 expression among the groups. Stromal positivity of the CD10 expression was calculated and statistically analyzed at p<0.05. Results: The results of the study showed that there was a statistically significant increase in the mean CD10 expression among the four groups. Intergroup comparison showed a statistically significant difference between oral epithelial dysplasia and OSCC while statistical significance was not observed in the various grades of OSCC. Conclusion: CD10 expression could be used as an important biomarker for determining the progression of oral epithelial dysplasia and the overall prognosis of OSCC.

Objectives: Composite lymphomas (CL), which are a combination of different types of lymphomas in a single patient can occur simultaneously or sequentially. Diagnosis and treatment of CL require a full range of modern approaches. Methods: The study included 37 cases of CL (M:F=2:1), the median age of patients was 64 (38-83 years). All patients underwent a full range of diagnostic procedures, including histopathological, immunohistochemical/immunophenotypic (flow cytometry), cytogenetic/FISH, and molecular tests at the National Research Centre for Hematology, Moscow. Results: Metachronous CL were observed in 17 cases and the most common type of the second lymphoma was diffuse large B-cell lymphoma (DLBCL) or Hodgkin's lymphoma (HL). In 30% of cases, DLBCL developed after HL therapy, and in 30% - after therapy of angioimmunoblastic T-cell lymphoma (AITL). In 20 cases of synchronous CL the most common was B-cell chronic lymphocytic leukemia (B-CLL) combined with hairy cell leukemia (HCL) - 54.5%, large granular lymphocytic leukemia, marginal zone lymphoma (MZL), follicular lymphoma, multiple myeloma, or mycosis fungoides. A combination of HL with other lymphoma was observed in 25% of cases (HL+MZL represent 60% of cases). Conclusion: CL are excellent models for studying the complex process of tumor cells evolution during the course of the disease. Treatment of CL is a non-trivial task and aims to control both diseases.

Objectives: Worldwide, Non-Muscle-Invasive Bladder Cancer (NMIBC) patients are characterized by a high rate of recurrence and progression highlighting the need for a valuable prognostic estimation for better management of this disease. Thus, the present preliminary study was planned to evaluate the validation of the European Organization for Research and Treatment of Cancer (EORTC) and the Spanish Urological Club for Oncological Treatment (CUETO) risk tables to predict recurrence and progression in Moroccan patients with NMIBC. Methods: A total of 56 NMIBC patients that have undergone transurethral resection of bladder tumor (TURBT), between January 2017 and May 2021, were recruited. The recurrence and progression rates at 1 and 5 years were calculated for each patient using EORTC and CUETO scoring models and compared to EORTC and CUETO risk tables. KaplanMeier was performed to validate stratification and difference between the four groups obtained. A univariate analysis using the Cox regression test was realized to evaluate the association between prognostic factors with recurrence and progression of the disease. Results: For the 56 NMIBC patients, the median follow-up duration was 49.68 months. In this cohort, 43 patients had recurrent tumors, and 27 showed progression to an advanced stage and/or grade. At 1-year progression and recurrence rates were higher than the values predicted by the EORTC and CUETO risk tables, while both tables overestimate the long-term risk probabilities of recurrence and progression. Only the CUETO model successfully stratified our patients with statistically significant differences between the four groups of recurrence (p=0.005). Of particular interest, univariate Cox analysis indicated that only prior recurrence rate had a significant effect on both recurrence-free survival (p=0.04) and progression-free survival (p=0.037). Conclusion: CUETO scoring model is better than EORTC for recurrence stratification in Moroccan patients with NMIBC. Both models overestimate risk in 1-year and underestimate risk in 5-years. A prospective study should be realized in large cohorts to establish an ideal prognosis model for Moroccan NMIBC patients.

Objectives: Human Papillomavirus (HPV) is the main contributor to the development of cervical cancer. This study aimed to investigate the biological significance of changes in the expression of lncRNAs induced by HPV oncoproteins in cervical oncogenesis mechanisms. Methods: We performed a review using online databases. The alterations were associated with some molecular and/or cellular characteristics that could be involved in the pathogenesis of cervical cancer. The molecular targets of the RNAs were identified using the Gene Expression Profiling Interactive Analysis (GEPIA) bioinformatics sites/tools, GeneCards®, OMIM, and Lnc2Cancer 3.0. Results: Sixty-one altered lncRNAs were identified. The alterations contribute to the higher staging of cervical cancer and a worse prognosis. These lncRNAs can act by competing for miRNAs for response elements, influencing the regulation of target genes and, ultimately, participating in the cancer regulation process and exhibit multiple biological functions, such as chromatin modification, transcription, translation, splicing, and epigenetic regulation. Conclusion: Changes in lncRNA expression have been associated with the onset, progression, and prognosis of cervical cancer. These changes can contribute to several features of cervical oncogenesis, and their identification has the potential to provide new biomarkers and therapeutic targets for the treatment of this cancer.

Currently, cancer is an important health problem, and virus-related infections have a large share among the factors that have been confirmed to play a role in the etiology of cancer. Until now, virus-associated cancers and nonvirusassociated cancers are treated with the same therapeutic agents. The answer to the question of whether the treatment of virus-associated tumors should be different from the treatment of other tumors has not yet been clearly answered. In addition to protective methods such as vaccination and pretransfusion serological tests, the immune system also plays an important role in eliminating the virus from the body. Besides, viruses escape from the immune system in various ways. Immunotherapies, which have been used in recent years, have brought a different dimension to cancer treatment by eliminating the inhibition of the immune checkpoint and activating T lymphocytes, thus showing an immunostimulating effect. The data showing that these agents, which are used in many types of cancer, may also be effective in virus-related cancers are increasing day by day. In this review, we aimed to evaluate the results of immunotherapies in randomized controlled trials in virus-associated cancers. Immunotherapies can play a role in many issues such as treatment of premalignant lesions and elimination of suppression or immunity after malignancy develops. As we summarized in our study, many randomized controlled clinical studies are ongoing to investigate the effectiveness of immunotherapies in virus-related cancers, and the results of these studies will answer many questions.

While humanity has not been able to end the fight against the COVID-19 pandemic, newly reported cases of monkeypox have caused unease. The current review sheds light on the transmission routes, pathogenesis, clinical presentation, treatment, and prevention of the disease in this early stage of the ongoing monkeypox epidemic.

Sarcoid like reaction is an interesting entity in cases treated by checkpoint inhibitor treatment and suggests a good response to therapy. Here a case with granulomatous reaction has been reported in a case with malignant mesothelioma treated by nivolumab. This entity may simulate disease progression by imaging modalities especially in PET/CT.

Objectives: Breast cancer is among the most commonly diagnosed cancers and one of the main causes of cancerrelated deaths in females. Long noncoding RNAs (lncRNA) are vital regulators of both oncogenesis and tumor suppression involved in crucial cancer pathways. Recent studies have demonstrated that LINC01296 and LINC00152 were aberrantly upregulated in different tumor types. In this study, we aimed to assess the expression levels of LINC01296 and LINC00152 in breast cancer and its adjacent tissues. Methods: Sample tissues were collected from 49 women with breast cancer referred to Shahid Faghihi Hospital in Shiraz for surgery from 2017 to 2018. Total RNA was extracted from fresh tumor and normal breast cancer tissues and expression of lncRNAs was assessed using real-time polymerase chain reaction. Results: A significant upregulation of LINC01296 and LINC00152 in breast cancer tissues compared with the adjacent normal tissues was observed (p<0.01). The Mann–Whitney analysis showed a significant relationship between the upregulation of LINC01296 and the use of oral contraceptives in luminal B breast cancer subjects (p=0.028). No significant relationship was found between the expression of LINC01296 and quantitative variables. Conclusion: This study showed an upregulation of LINC01296 and LINC00152 in breast cancer tissues compared with the adjacent normal tissues.

Objectives: Cancer patients were found to be at higher risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and experienced more adverse outcomes. The objective of this meta-analysis was to estimate the prevalence of lung cancer patients with SARS-CoV-2 infection during the COVID-19 pandemic. Methods: A comprehensive search was carried out on PubMed, Web of Science, Scopus, MedRxiv, SciELO, SID, CNKI, and Wanfang databases to retrieve all relevant publications. All cross-sectional studies and consecutive case series on cancer patients with SARS-CoV-2 infection were selected. A total of 28 studies including 5400 infected cancer patients and 767 lung cancer patients with COVID-19 were included. Results: Combined data indicated that the prevalence of lung cancer patients with SARS-CoV-2 infection was 15.2% (95% CI, 0.111–0.205) overall. Stratified analysis by ethnicity showed that the prevalence was 16.4% and 15.4% in Asian and Caucasian lung cancer patients with COVID-19, respectively. Moreover, subgroup analysis by country of origin showed that the prevalence was highest in China (19.3.0%) followed by France (12.6%), the UK (10.7%), and the USA (8.3%). Conclusion: This meta-analysis revealed that the prevalence of lung cancer patients with SARS-CoV-2 infection during the COVID-19 pandemic was 15.2%.

Objectives: Radio-resistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment. Due to individual variations in radio-sensitivity, biomarkers are needed to tailor radiation treatment. Within this frame, the identification of series of genetic signatures mainly SNPs for NPC patients treated with radiotherapy may help to predict treatment outcome and deliver personalized therapy. The aim of this study was to evaluate the possible association between the GSTP1 Ile105Val and GPX1 Pro198Leu polymorphisms and response to radiotherapy in NPC patients. Methods: From September 2016 to October 2018, a total of 101 patients with confirmed NPC, recruited at Mohammed IV Center for Treatment of Cancer of Casablanca, underwent radiotherapy. DNA was extracted from peripheral blood. Genotyping of the GPX1 Pro198Leu and GPX1 Val105Leu polymorphisms was carried out by PCR amplification and DNA sequencing. SPSS was used to analyse the association of GSTP1 and GPX1 genotypes with clinico-pathological features and response to radiotherapy. Results: The genotyping data revealed the presence of only two genotypes namely Pro/Pro (57.4%) and Pro/Leu (40.6%) for GPX1 gene. The allelic frequencies of C and T alleles were 78.7% and 21.3% respectively. For GSTP gene, the homozygous genotypes Val/Val and Leu/Leu were detected in 35.6% and 12.9% of patients respectively. The heterozygous genotype Val/Leu prevailed (51.5%). Allelic frequencies showed the presence of the two alleles A and G in 57.1% and 42.9% patients respectively. Statistical analysis failed to find any significant association between GSTP Val105Ile and GPX1 Pro198Leu genetic polymorphisms and socio-demographic and clinico-pathological features as well as response to radiotherapy (p>0.05). Conclusion: Further research is warranted on the potential role of SNPs within antioxidant defines genes in radiotherapy response and to identify reliable predictive and non-invasive biomarkers for radio-resistance among NPC patients for personalised therapies.

Objectives: Although immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment. In this group, a few of the patients with a hyperprogressive disease (HPD) have shorter overall survival (OS) compared with those having a progressive disease (PD). Therefore, biomarkers are needed to differentiate HPD and PD. Methods: Ninety-five patients treated with ICIs with progression according to response evaluation criteria ın solid tumors criteria in the first control imaging were included. HPD was defined according to Russo's work. The PILE scoring system, which includes pan-immune-inflammation value, lactate dehydrogenase, and Eastern Cooperative Oncology Group PS, was followed. The relationship between PILE score and HPD was analyzed. Results: The median OS of all cohorts was 11.18 months. The patients in the HPD group had decreased OS (4.77 vs. 13.94 months, p<0.001) and progression-free survival (PFS) (1.89 vs. 3.16 months, p<0.001) compared with those in the PD group. The risk of HPD was higher than the risk of PD in patients with a high PILE score (p=0.001). Conclusion: In this study, we showed that patients treated with ICI with a higher PILE score are at greater risk for HPD. The PILE score may be a biomarker to differentiate HPD from PD.