Background: BRAF V600E mutation is proved critical in the progression and invasion of thyroid cancer, and as a prognostic biomarker. As anaplastic thyroid cancer (ATC) is a rare and aggressive form of thyroid cancer, this study was conducted to provide a view on prevalence of BRAF V600E as well as the best molecular diagnostic method in ATC patients. Methods: A comprehensive literature search was performed from their inception to Oct 2022 in PubMed, Scopus, Google Scholar, and Web of Science (WoS). The data of the prevalence of ATC were extracted. Moreover, the diagnostic feature of the available diagnostic tools was extracted to measure the sensitivity and specificity. To pool the prevalence data, we used meta-proportion analysis and diagnostic meta-analysis was conducted to determine the specificity and sensitivity of the immunohistochemistry method in detecting BRAF V600E mutation among patients with ATC. Results: Overall, 34 studies were included in this meta-analysis. The incidence of BRAF V600E was shown 33% in the 978 patients. The sensitivity and specificity of IHC in detecting BRAF V600E were detected 78.9% (95%CI: 60.1-97.2), and 69.7% (95%CI: 41.2-98.1), respectively. Conclusion: IHC had an acceptable prognostic profile for detecting BRAF V600E in ATC patients. The diagnosis of BRAF mutation is critical in clinical trials and may be helpful for choosing proper-targeted therapy strategies in ATC patients.

Different immunomodulation strategies have been used to manage COVID-19 due to the complex immune-inflammatory processes involved in the pathogenesis of this infection. Curcumin with its powerful anti-inflammatory and antiviral properties could serve as a possible COVID-19 therapy. In this study, a randomized, double-blinded, placebo-controlled trial was performed to investigate the effectiveness and safety of nano-curcumin oral soft gels as a complementary therapy in moderate-severe COVID-19 patients. Hydroxychloroquine (HCQ) plus sofosbuvir was routinely administered to all 42 COVID-19 patients, who were randomly assigned to receive 140 mg of nano-curcumin or placebo for 14 days. CT scans of the chest were taken, and blood tests were run for all patients at time points of 0, 7, and 14 days. Our results indicated that C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels significantly decreased from baseline in the nano-curcumin-treated group on day 7. Furthermore, blood levels of D-dimer, CRP, serum ferritin, ESR, and inflammatory cytokines including IL-6, IL-8, and IL-10 decreased more significantly in the nano-curcumin-treated group after 14 days. Additionally, the nano-curcumin group showed significant improvements in chest CT scores, oxygen saturation levels, and hospitalization duration. Based on our data, oral administration of nano-curcumin may be regarded as a promising adjunct treatment for COVID-19 patients due to its ability to speed up chest clearance and recovery.

BACKGROUND:We aimed to analyze the prognostic power of CT-based radiomics models using data of 14,339 COVID-19 patients. METHODS:Whole lung segmentations were performed automatically using a deep learning-based model to extract 107 intensity and texture radiomics features. We used four feature selection algorithms and seven classifiers. We evaluated the models using ten different splitting and cross-validation strategies, including non-harmonized and ComBat-harmonized datasets. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were reported. RESULTS:In the test dataset (4,301) consisting of CT and/or RT-PCR positive cases, AUC, sensitivity, and specificity of 0.83 ± 0.01 (CI95%: 0.81-0.85), 0.81, and 0.72, respectively, were obtained by ANOVA feature selector + Random Forest (RF) classifier. Similar results were achieved in RT-PCR-only positive test sets (3,644). In ComBat harmonized dataset, Relief feature selector + RF classifier resulted in the highest performance of AUC, reaching 0.83 ± 0.01 (CI95%: 0.81-0.85), with a sensitivity and specificity of 0.77 and 0.74, respectively. ComBat harmonization did not depict statistically significant improvement compared to a non-harmonized dataset. In leave-one-center-out, the combination of ANOVA feature selector and RF classifier resulted in the highest performance. CONCLUSION:Lung CT radiomics features can be used for robust prognostic modeling of COVID-19. The predictive power of the proposed CT radiomics model is more reliable when using a large multicentric heterogeneous dataset, and may be used prospectively in clinical setting to manage COVID-19 patients.

Abstract In this paper, we use a simple and cheap approach for the synthesis of herceptin-conjugated graphene biosensor to detect the HER2-positive breast cancer cells. The bifunctional graphene-herceptin nanosheets are prepared from graphite by a simple ultrasonic-mediated technique. The prepared protein-mediated graphene is fully characterized. The results show the exfoliation of graphene layers in herceptin solution. Moreover, herceptin is effectively conjugated into the surface of graphene nanosheets. The synthesized herceptin-conjugated graphene is applied for breast cancer detection. The linear range of this biosensor is 1–80 cells, which is significant. The biosensor shows an excellent selectivity performance for detection of HER2-positive cancer cells. Likewise, the stability and functionality of the biosensor is about 40 days. Based on the results, this device is a promising candidate for rapid and selective detection of cancer cells.

Background: The outbreak of coronavirus disease 2019 (COVID-19) has become a major threat to all humans. Objectives: To assess the association between the patients’ clinical and laboratory records, computed tomography (CT) findings, and epidemiological features of COVID-19 with the severity of the disease. Patients and Methods: In this retrospective case-control study conducted on the medical records of confirmed COVID-19 pneumonia patients on admission, we investigated the CT manifestations and clinical and laboratory risk factors for progression to severe COVID-19 pneumonia. The medical records and radiological CT features of confirmed COVID-19 patients were reviewed in one public hospital and one respiratory clinic in Qom, Iran, from August 1 to September 30, 2020. Results: Of 236 confirmed COVID-19 cases, 62 were infected with moderate to severe COVID-19 and required hospital admission, and 174 were followed-up on an outpatient basis. A significant difference was found in the mean age of the outpatient and hospitalized groups. The incidence of bilateral lung involvement, consolidations, linear opacities, crazy-paving pattern, air bronchogram, and number of lobes involved were significantly higher in the hospitalized group compared to the outpatient group. However, the crazy-paving pattern was only significantly associated with an oxygen saturation (SpO2) level < 90% and, coughing. Our findings indicated that the crazy-paving pattern was significantly associated with the inflammatory phase. The presence of this pattern on admission, SpO2 < 90%, older age, and diabetes were independent risk factors for progression to severe COVID-19. Conclusion: The crazy-paving pattern can predict the severity of COVID-19, which is of great importance in the management and follow-up of COVID-19 pneumonia patients. Clinical factors, such as aging, male gender, and diabetes, may be risk factors for the crazy-paving pattern. Severe cough is the most important clinical sign related to this pattern, along with an SpO2 < 90%, which is an important sign of COVID-19 severity.

Background: With the growing rate of tumors, cancer has become one of the most important health concerns in Iran. The urgency with which Iranian researchers and health professionals address this challenge leads to a load of scientific materials. Methods: To reveal gaps in produced knowledge and suggest future research directions, applying well-validated scientometric tools, we assessed the trends of Iranian published scientific articles and citations in the field of oncology. The inclusion criteria consisted of all oncology-related articles that were data-based, and peer-reviewed; with at least an abstract published in English; and authored by at least one researcher affiliated with Iranian institutions. Results: Amongst 5063525 oncology research records indexed in at least one of PubMed, Scopus, or Web of Science Core Collection (WoS) from the start to February 2019, Iranian researches accounted for about 24867 (0.49%). Published articles on all cancers by Iranian researchers had a sharp continuously ascending trend, with the same pattern for citations received. Some important topics such as complementary and alternative medicine (CAM) therapies have been missing and some such as diagnostic and pharmaceutical innovations have been less investigated. The most collaborative country was the United States, while no close collaboration was observed with China that was introduced as the most productive country in the field of oncology over the past decades. Conclusion: Despite the progressive trend in most oncology fields, some significant practical topics are still missing. Systematic reviews of produced theoretical innovations and translating them to functional knowledge can be of importance to fulfill the mentioned gaps.

Background: Long non-coding RNAs (lncRNAs) have several important functions in the regulation of cell homeostasis and cell fate. Consequently, abnormal transcription of lncRNAs has been correlated with malignant transformation of cells. These human transcripts have been shown to participate in the progression of gastric cancer. Methods: In the current project, we evaluated expression of a panel of lncRNAs including HULC, MALAT1, FAS-AS1, GAS5, PVT1, OIP5-AS1 and THRIL in 30 gastric cancer tissues and paired adjacent non-cancerous tissues (ANCTs) using quantitative real-time PCR. Results: HULC, OIP5-AS1 and THRIL transcription quantities were significantly lower in gastric tumors compared to ANCTs (P values = .02, 0.02 and 0.007, respectively). Relative transcription quantities of HULC, MALAT1, OIP5-AS1, PVT1, FAS-AS1 and THRIL were associated with the site of the primary tumor (P values = .002, 0.003, 0.002, 0.002, 0.002, and 0.001, respectively). Moreover, relative expression levels of PVT1 were associated with history of smoking (P value = .04). Correlations were identified between transcript quantities of these lncRNAs in both tumor samples and ANCTs. Receiver operating characteristic curve assessment demonstrated that THRIL had the highest diagnostic power among the mentioned lncRNAs (area under curve (AUC) = 0.72, P value = .001). HULC and OIP5-AS1 ranked afterwards (AUC values of 0.69 and 0.68; P values = .005 and 0.007, respectively). Conclusion: The current investigation underscores the dysregulation of these transcripts in gastric cancer specimens and suggests a number of these transcripts for further assessments of their suitability as cancer biomarkers.

Abstract Background: The outbreak of coronavirus disease 2019 (COVID-19) becomes an enormous threat to all human beings. Via this retrospective study conducted on medical records of confirmed COVID-19 pneumonia patients on admission, we investigate the CT manifestation and clinical and laboratory risk factors associated with progression to severe COVID-19 pneumonia and assessed the association among clinical and laboratory records, CT findings, and epidemiological features. The medical records and radiological CT Features of 236 confirmed COVID-19 patients were reviewed at one public hospital and one respiratory clinic in Quom, from 1 August to 30 September 2020. Results: Among a total of 236 confirmed Covid-19 cases, 62 were infected with moderate to severe COVID-19 disease and required hospital admission, and 174 were followed up on outpatient bases. A significant difference was verified in the mean age between outpatients and hospitalized groups. The incidences of bilateral lung involvement, consolidation, linear opacities, crazy-paving pattern, air bronchogram sign, and the number of lobe involvement were significantly higher in hospitalized groups. However, only the crazy-paving pattern was significantly associated with an SpO2 level lower than 90%, with clinical sign of cough severity. Our data indicate that this pattern is also significantly associated with inflammatory levels and the presence of this pattern along with SpO2 level lower than 90%, older age, diabetes, on admission are independent risk factors for COVID-19 progression to severe level.Conclusions: The crazy-paving pattern can predict the severity of COVID-19, which is of great significance for the management and follow-up of COVID-19 pneumonia patients. The clinical factors of aging, male gender, and diabetes, may be risk factors for the crazy-paving pattern, whereas severe coughing is considered to be the most important clinical symptom related to this pattern, and SpO2 level lower than 90%, which is a matter of more severity.

INTRODUCTION:Long non-coding RNAs (lncRNAs) have fundamental roles in cell migration, proliferation, invasion and metastasis.METHODS:In the current study, we evaluated expression of a panel of lncRNAs in bladder cancer tissues, adjacent non-cancerous tissues (ANCTs) and normal bladder tissues to evaluate their diagnostic power.RESULTS:PV1 was down-regulated in tumor tissues compared with both ANCTs and normal controls (Expression ratios of 0.48 and 0.14; P values of 0.4 and <0.001 respectively). HOTAIR, NEAT1, TUG1 and FAS-AS1 were significantly down-regulated in tumor tissues compared with normal controls (Expression ratios of 0.4, 0.68, 0.54 and 0.11; P values of 0.04, 0.02, 0.02 and <0.001 respectively).CONCLUSION:Combination of transcript levels of seven lncRNAs improved both sensitivity and specificity values to 100%. The current study shows dysregulation of lncRNAs in bladder cancer and implies their role as diagnostic markers in this malignancy.

Quantitative reverse transcription polymerase chain reaction (qRT-PCR) in thyroid tumors require accurate data normalization, however, there are no sufficient studies addressing the suitable reference genes for gene expression analysis in malignant and normal thyroid tissue specimens. The purpose of this study was to identify valid internal control genes for normalization of relative qRT-PCR studies in human papillary thyroid carcinoma tissue samples. The expression characteristics of 12 candidate reference genes (GAPDH, ACTB, HPRT1, TBP, B2M, PPIA, 18SrRNA, HMBS, GUSB, PGK1, RPLP0, and PGM1) were assessed by qRT-PCR in 45 thyroid tissue samples (15 papillary thyroid carcinoma, 15 paired normal tissues and 15 multinodular goiters). These twelve candidate reference genes were selected by a systematic literature search. GeNorm, NormFinder, and BestKeeper statistical algorithms were applied to determine the most stable reference genes. The three algorithms were in agreement in identifying GUSB and HPRT1 as the most stably expressed genes in all thyroid tumors investigated. According to the NormFinder software, the pair of genes including 'GUSB and HPRT1' or 'GUSB and HMBS' or 'GUSB and PGM1' were the best combinations for selection of pair reference genes. The optimal number of genes required for reliable normalization of qPCR data in thyroid tissues would be three according to calculations made by GeNorm algorithm. These results suggest that GUSB and HPRT1 are promising reference genes for normalization of relative qRT-PCR studies in papillary thyroid carcinoma.

PURPOSE:This study aims to investigate the expression level of mir-let7b-3p and mir-548, which are involved in PTEN expression in tissue samples of prostate cancer patients versus benign prostate hyperplasia (BPH) and normal adjacent tissue.MATERIALS AND METHODS:Prostate cancer tissues were obtained from patients after receiving informed consent. Total RNA extraction and cDNA synthesis were performed for determining gene expression.RESULTS:Ten patients were determined to have high Gleason scores (> 7), 36 and seven samples had intermediate Gleason scores (7?) and BPH, respectively, and 40 samples were derived from normal adjacent tissue. Downreg-ulation of mir-let7b and upregulation of mir-548 expression significantly correlated with high-risk Gleason scores.CONCLUSION:The present study showed that miR-let7b and/or mir-548 can be considered as potential targets in prostate cancer therapy.

To evaluate the diagnostic potential of 23 candidate genes, belonging to a category of tumor-specific antigens known as cancer-testis antigens (CTAs), in transitional cell carcinoma (TCC) patients. The expression of 16 known candidate CTAs and seven testis restricted/selective genes, predominantly expressed in the testis, was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). Urinary exfoliated cells (UECs) and cancerous tissues of 73 TCC patients were used as cases, while 25 tumor-free adjacent bladder tissue specimens along with bladder tissue specimens and UECs of five non-TCC individuals were analyzed as controls. Among the known CTAs only MAGEA3, MAGEB4, TSGA10, PIWIL2, OIP5, and ODF4 were expressed specifically in TCC tissues and UEC samples. ACTL7A, AURKC, and CGB2 were testis-restricted/selective genes that indicated specific expression in cases in comparison to controls. MAGEA3, MAGEB4, and ODF4 mRNA was detectable in more than 50% of both TCC tissues, and UEC samples. Slight differences were detected in the mRNA expression pattern of candidate genes between the UEC samples and tumor tissues. Different panels formed by combinations of these genes can show up to 95.9% and 94.5% of positivity in TCC tissues and UEC samples, respectively, suggesting their diagnostic and surveillance potential. Meanwhile the RT-PCR assay of at least MAGEA3, MAGEB4, and ODF4 may be particularly useful for diagnostic and surveillance of TCC in the form of a multi-biomarker panel.

The article's abstract is no available.

Background: This study aimed to evaluate the diagnostic value of outer dense fiber 4 (ODF4), melanomaassociated antigen A3 (MAGEA3), and MAGEAB4 mRNAs in transitional cell carcinoma (TCC), using a small amount of cell reverse transcriptase-polymerase chain reaction (RT-PCR) on urinary exfoliated cells. Methods: We recruited a total of 105 suspected TCC patients and 54 sexand age-matched non-TCC controls. The candidates’ genetic expression patterns were investigated with RT-PCR, while reverse transcription quantitative PCR was applied to quantify and compare each mRNA level between cases and control groups. Results: The sensitivity of ODF4, MAGEA3, and MAGEAB4 RT-PCR was 54.8%, 63%, and 53.4%, whereas the specificity was 73.7%, 86%, and 94.7%, respectively. Combining ODF4, MAGEA3, and MAGEAB4 RT-PCR offered a relatively higher sensitivity (83.6%). Conclusion: RT-PCR with ODF4, MAGEA3, and MAGEAB4 on urinary exfoliated cells could provide clinicians with a promising method to improve TCC diagnosis, especially in the case of gross hematuria and catheterization. The method used here is non-invasive, simple and convenient, and unlike cytology, it does not rely directly on expert professional opinions. These features can be of particular importance to the management of TCC patients in whom regular and lifelong surveillance is required. DOI: 10.22034/ibj.22.3.160

AIM:Cancer-testis antigens (CTAs) have specific expression in gametogenic tissues and aberrant expression in cancers. Materials & methods: We assessed expression of five testis-specific genes namely KIF2B, CST8, TMEM225, RBM46, OAZ3 in bladder cancer tissues, adjacent non-neoplastic tissues and urinary cell pellets (UCPs) of bladder cancer patients compared with nonmalignant conditions.RESULTS:Expressions of all CTAs were higher in UCPs of bladder cancer patients compared with nonmalignant conditions. RBM46 expression in UCPs was higher in patients with recurrent tumors compared with primary tumors and in patients without hematuria compared with those having hematuria. TMEM225 expression in tumoral tissues was higher in high-grade tumors compared with low-grade tumors.CONCLUSION:Expression analysis of CTAs in UCP might provide diagnostic information about bladder cancer.

AIM:miRNAs have been suggested as biomarkers for bladder cancer. We aimed to find a diagnostic panel of miRNAs based on differential expression of miRNAs in urine specimens of patient with bladder cancer compared with control group.METHODS:miR-141, miR-10b, miR-34b and miR-103 were selected to assess their expression in urine samples of 66 bladder cancer patients and 53 matched controls using quantitative real time PCR.RESULTS:miR-10b and miR-34b were upregulated in cases compared with controls. The combination of four miRNAs showed a sensitivity of 75% and specificity of 63.5% with a diagnostic power of 72%.CONCLUSION:Certain miRNAs can be used as biomarkers for early diagnosis of bladder cancer.

Background Exosomes have been regarded as emerging tools for cancer diagnosis. Tumor-derived exosomes contain molecules that enhance cancer progression and affect immune responses. Material and methods In the present study, we evaluated expression of seven cancer-testis antigens (CTAs) that are regarded as putative biomarkers and immunotherapeutic targets along with NMP22 in urinary exosomes of bladder cancer patients, healthy subjects and patients affected with nonmalignant urinary disorders. Results Exosomal expression of MAGE-B4 was significantly higher in bladder cancer patients compared with normal samples (expression ratio=2.68, P=0.01). However, its expression was lower in bladder cancer patients compared with benign prostate hyperplasia (BPH) patients (expression ratio=0.17, P=0.01). Exosomal expression of NMP22 was significantly higher in bladder cancer patients compared with BPH patients (expression ratio=9.22, P=0.02). Expressions of other genes were not significantly different between bladder cancer patients and normal/nonmalignant samples. We found significant correlation between MAGE-A3 and MAGE-B4 expressions in exosomes obtained from controls. In addition, TSGA10 expression was correlated with expression of NMP22 in both cancer patients and controls. Conclusion The present study provides evidences for differential expression of CTAs in urinary exosomes of bladder cancer patients and urogenital disorders and warrants further studies for assessment of their significance in cancer diagnosis and immunotherapeutic approaches.

Deregulation of key signaling pathways is one of the primary phenomena in carcinogenesis. DAB2IP and SPRY2 are regulatory elements, which act as feedback inhibitors of receptor tyrosine kinases signaling in mitogen-activated protein kinase pathway. These elements have also been implicated in the pathophysiology of cancer. Therefore, this study is aimed to investigate the expression of all known splice variants of DAB2IP and SPRY2 in prostate tissue. Fresh Prostate tissue samples (50 prostate cancer/matched normal tissue and 30 BPH) were collected and total RNA was extracted followed by cDNA synthesis. The expression of DAB2IP and SPRY2 transcript variants were evaluated using RT-PCR and quantitative Real-time PCR. The results indicated significant down-regulation of DAB2IP transcript variant 1 in cancerous tissues compared to paired normal tissues (P = 0.001) as well as SPRY2 transcript variant 2 in cancerous tissues in comparison with the normal counterparts and BPH (P = 0.008 and P = 0.025, respectively). In addition, there was a significant negative correlation between DAB2IP.1 and SPRY2.2 expression with PSA levels in prostate cancer (P = 0.039 rho = -0.24 and P = 0.045 rho = -0.3, respectively). Interestingly, the down-regulation of DAB2IP.1 mRNA and SPRY2.2 mRNA was positively correlated in tumor samples (P = 0.002 rho = 0.434). For the first time, this experiment highlights the deregulation of DAB2IP and SPRY2 transcript variants in human prostate cancer. The present study confirms and extends the previous reports through indicating transcript-specific down-regulation and significant association of DAB2IP and SPRY2 in prostate tumorigenesis.

Background: Bladder cancer (BC) is a frequent cancer with high morbidity and mortality. Method: We assessed expression of NMP22, BAG3, BCL2 and BAX in BC samples, adjacent non-neoplastic tissues (ANNTs), urinary cell pellets (UCP) of the same patients and non-malignant conditions (NM). Results: NMP22 was up-regulated in tumoral tissues compared with ANNTs and in UCP of BC patients compared with UCP of NM. BCL2 and BAX were down-regulated in BC tissues compared with ANNTs. BAG3 and BAX were down-regulated in UCP of BC compared with NM. The combination of all four genes had 100% sensitivity and specificity for detection of BC in urine. Conclusion: Expression analysis of these genes in tumor or urine is a tool for detection of BC.

BACKGROUND:Long non-coding RNAs (lncRNAs) and exosomes have been regarded as components of cell signal transmission that modulate indigenous cellular microenvironments. Exosomes also participate in relocation of functional lncRNAs between cells.METHODS:In the present study, we evaluated expression of LINC00355, LINC00958, UCA1-201, UCA1-203, and MALAT1 lncRNAs in urinary exosomes isolated from transitional cell carcinoma (TCC) of bladder, non-malignant urinary disorders, and normal subjects.RESULTS:LINC00355, UCA1-203, and MALAT1 expression was significantly higher in TCC patients compared to controls (non-malignant or normal samples). However, UCA1-201 expression was significantly decreased in TCC patients compared with controls. LINC00355 and MALAT1 expression was significantly lower in cigarette smokers and opium-addicted TCC patients, respectively. On the other hand, LINC00355 expression tended to be higher in opium-addicted TCC patients. The proposed panel of lncRNAs (composed of UCA1-201, UCA1-203, MALAT1, and LINC00355) had 92% sensitivity and 91.7% specificity for diagnosis of bladder cancer from normal samples.CONCLUSION:Transcript levels of lncRNAs in urinary exosomes are potential diagnostic bio-markers in bladder cancer.