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Gliomatosis peritonei (GP), almost exclusively linked to mature or immature ovarian teratoma, is a very rare disease. To the best of our knowledge, reports on the complete clinical course and imaging features of ovarian mature teratoma with GP are extremely rare. We present a case of ovarian mature teratoma with GP in a 9-year-old girl admitted to the emergency department for a 2-month history of a large abdominal mass found accidentally. Carcinoembryonic antigen and cancer antigen 125 levels were elevated. CT scans suggested a large mass with mild enhancement, and an immature teratoma derived from the left ovary with ascites was diagnosed by ultrasound. Subsequently, left ovarian tumor resection and omentectomy were performed, and a solid cystic mass accompanied by massive ascites and numerous white to grayish nodules was identified on the left ovary. The pathology results revealed a mature teratoma with GP. The patient had good postoperative recovery, and her serum tumor marker levels decreased to normal at the 3-month follow-up.

An aptamer is a short oligonucleotide chain that can specifically recognize targeting analytes. Due to its high specificity, low cost, and good biocompatibility, aptamers as the targeting elements of biosensors have been applied widely in non‐invasive tumor imaging and treatment in situ to replace traditional methods. In this review, we will summarize recent advances in using aptamer‐based biosensors in tumor diagnosis. After a brief introduction of the advantage of aptamers compared with enzyme sensors and immune sensors, the different sensing designs and mechanisms based on 3 signal transduction modes will be reviewed to cover different kinds of analytical methods, including: electrochemistry analysis, colorimetry analysis, and fluorescence analysis. Finally, the prospective advantages of aptamer‐based biosensors in tumor theranostics and post‐treatment monitoring are also evaluated in this review., This review introduces the advantages of aptamer sensors in disease diagnosis compared with traditional biosensors. It also shows the design strategies of the 3 most studied aptamer sensors: fluorescent aptasensors, electrochemical aptasensors, and colorimetric aptasensors, and their application in early tumor diagnosis. Moreover, taking the fluorescent aptasensor as an example, the design of aptasensors combined with nanomaterials can not only be used for tumor imaging, but also has important significance in tumor treatment and efficacy evaluation. The design provides a new idea for the integration of tumor theranostics.

A 45-year-old multiparous woman with a STK11 mutation and a history of Peutz-Jeghers syndrome underwent radical hysterectomy and bilateral salpingo-oophorectomy for a gastric-type cervical mucinous carcinoma. Four and a half years later, blood tests revealed elevations in CEA and CA125 tumor marker levels, and computed tomography showed multiple calcifications in the peritoneum. Peritoneal dissemination was suspected, and a laparoscopic biopsy was performed. Histopathology showed a high-grade serous carcinoma, and the patient was diagnosed with a metachronous stage IIIC primary peritoneal carcinoma. She had no BRCA1/2 mutation. After chemotherapy with docetaxel, carboplatin, and bevacizumab, she achieved complete remission.

Objective To investigate the clinical features and computed tomography (CT) findings of pediatric ovarian torsion. Methods A retrospective analysis of the clinical and CT data of 61 newborns, infants, children, and adolescents with ovarian torsion confirmed by histopathology was performed. Results Clinical features included abdominal mass, abdominal pain, nausea and vomiting, and fever. The tumor marker α-fetoprotein was increased in five cases. Ovarian enlargement was found in 26 cases, and follicles were detected in the peripheral region of the ovary in 21 cases. Twenty-one cases presented as solid mixed-density masses on CT images. A total of 30 cases of ovarian torsion were associated with a benign ovarian mass. Among 27 cases of cystic or predominantly cystic masses, the mass had a thickened wall in 26 cases and showed an uneven density in 23 cases. Among all 61 patients, a torsed pedicle was detected in 47 cases. A torsed ovary or mass exhibited mild contrast enhancement in seven cases. Uterine deviation toward the involved side, blurred fat space around lesions, and pelvic free fluid were also found. Conclusion Pediatric ovarian torsion presents a relatively characteristic CT appearance. Correct diagnosis can be established based on clinical and imaging features.

OBJECTIVE To evaluate the relationship between plasma levels of the inflammatory markers tumor necrosis factor-alpha (TNF-α), C reactive protein (CRP), and interlukin-6 (IL-6) with insulin resistance in Saudi women with polycystic ovaries syndrome (PCOS). METHODS One hundred eighty Saudi women with and without PCOS, aged 22-38 years, were randomly recruited in this age and body mass index matched case-control study. Clinical assessment, anthropometric measurements, and biochemical parameters were determined for all study participants. RESULTS Levels of TNF-α, IL-6, hs-CRP, insulin, and insulin resistance indices were significantly higher among PCOS group than their age and BMI matched controls (p

Lung cancer remains incurable; therefore, novel therapeutical approaches are of great demand. This study was designed to investigate the effectiveness of cisplatin nanoparticles combined with vitamin-D3 on urethane-induced early lung cancer in rats and to clarify the underlying signaling mechanisms. Early lung cancer was induced in male Wistar rats by urethane. Rats were divided into six groups: I-control, II-cancer untreated, III-cancer + free cisplatin, IV-cancer + cisplatin nanoparticles, V-cancer + free cisplatin + vitamin-D3 , VI-cancer + cisplatin nanoparticles + vitamin-D3 . Inflammation, proliferation, and apoptosis were evaluated together with the levels of tumor marker CK-19 along with histological assessment. Treatment of lung cancer with either free or nanoparticles of cisplatin alone demonstrated significant suppression in the expression of inflammatory, anti-apoptotic and tumor markers compared to rats with lung cancer. Moreover, vitamin-D3 supplementation with either cisplatin forms lead to a further decrease of all markers, markedly with cisplatin nanoparticles. The present study shows the synergistic effect of cisplatin-nanoparticles combined with vitamin-D3 as a new therapy regimen against lung cancer. Further studies with larger sample sizes and longer duration are needed to confirm these results.

Objectives To identify whether delirium biomarkers aligned with the National Institute on Aging-Alzheimer's Association (NIA-AA) research framework, a conceptual model that describes the use of diagnostic biomarkers for Alzheimer's disease and other related dementias (ADRD). Design Systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Setting Acute care and outpatient settings. Participants Adults diagnosed with delirium. Methods and measurements MEDLINE, PsycInfo, Embase, and the Cochrane Library were searched for English-language studies published from January 2010 to February 2020. Studies included adults older than 18 years, identified delirium with a standardized assessment tool, and measured an ADRD biomarker. Independent reviewers determined whether an association between delirium and ADRD biomarker was found, the quality of biomarker data based on the REMARK (REporting recommendations for tumor MARKer prognostic studies) checklist, and the study bias based on the Newcastle-Ottawa Scale. Results A total of 61,256 citations were identified; 113 studies were included. Most studies did not examine amyloid, tau, or neurodegeneration biomarkers. Delirium may be associated with neurodegeneration biomarkers, but few to no studies found an association with amyloid and tau biomarkers. Delirium was not consistently associated with inflammatory biomarkers. The quality of biomarker data was moderate, and the risk of bias was moderate to high. Studies often did not collect prehospital and posthospital cognitive data. Conclusion Most delirium diagnostic biomarker studies did not measure amyloid, tau, and/or neurodegenerative biomarkers, making characterization of the relationship between delirium and ADRD difficult. Future delirium biomarker diagnostic studies could improve the understanding of pathophysiologic links between delirium with other conditions affecting cognition.

Background Lung cancer serum tumor markers including carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21‐1), and carbohydrate antigen 125(CA125) as prognostic predictors is controversial. Therefore, this study aimed to evaluate the association between these markers and the survival of patients with postoperative stage III‐N2 non‐small cell lung cancer (NSCLC). Methods We enrolled 1011 patients with pathologically confirmed stage III‐N2 NSCLC who underwent resection and whose pretreatment serum tumor marker levels were available. Patients were categorized according to their serum levels into low‐, medium‐, and high‐risk groups. Overall survival (OS), progression‐free survival (PFS), local regional relapse‐free survival (LRFS), and distant metastasis‐free survival (DMFS) were calculated from the date of resection. Their association with each serum tumor marker was assessed using the log‐rank test. Results Abnormal CEA levels were associated with worse five‐year OS, PFS and DMFS; abnormal CYFRA21‐1 levels were associated with worse five‐year OS and LRFS; and abnormal CA125 levels were associated with worse five‐year OS, PFS, LRFS and DMFS. Among the risk groups, there were significant differences in five‐year OS, PFS, LRFS and DMFS (P = 0.000). In propensity score matching analysis, the model also achieved prognostic significance for all four survival classifications (P = 0.001–0.004) among the three risk groups. Conclusions The combined model achieved prognostic significance for all survival outcome types. The serum tumor markers tested are useful prognostic predictors for postoperative NSCLC patients but not for all survival outcomes. The combination of the three indices is more reliable in predicting all four of the survival outcomes. Key points Significant findings of the study Serum CEA, CYFRA21‐1, and CA125 levels can be used as prognostic factors of postoperative N2 non‐small cell lung cancer patients but not for all survival outcomes, suggesting that combinative detection of all three indices would be more reliable. What this study adds Our model utilizes available technology, with conventional cutoff values, inexpensive costs, and simple mathematics methods and, thus, can be feasibly employed by clinicians or oncologists., From a large number of patients' analysis, we achieved a neat model to be able to predict the OS, PFS, LRFS and DMFS of postoperative III‐N2 NSCLC.

Tumor cell‐surface markers are usually overexpressed or mutated protein receptors for which spatiotemporal regulation differs between and within cancers. Single‐molecule fluorescence imaging can profile individual markers in different cellular contexts with molecular precision. However, standard single‐molecule imaging methods based on overexpressed genetically encoded tags or cumbersome probes can significantly alter the native state of receptors. We introduce a live‐cell points accumulation for imaging in nanoscale topography (PAINT) method that exploits aptamers as minimally invasive affinity probes. Localization and tracking of individual receptors are based on stochastic and transient binding between aptamers and their targets. We demonstrated single‐molecule imaging of a model tumor marker (EGFR) on a panel of living cancer cells. Affinity to EGFR was finely tuned by rational engineering of aptamer sequences to define receptor motion and/or native receptor density., Localization and tracking of individual membrane receptors on living cells was achieved upon transient binding of aptamer probes through minimally invasive solution diffusion. Probe affinity was modulated by rational engineering of the aptamer sequence. Detection of single molecules is linked to binding affinity, so probes with different affinity provide readouts on different properties, such as diffusive dynamics and receptor density levels.

Objective Owing to variations in the exterior appearances of noncancerous diseases in the oral cavity, clinicians may have difficulty diagnosing oral squamous cell carcinoma (OSCC). Tissue biopsy is confirmatory, but invasive. Therefore, reliable tumor markers for OSCC are required. Here, exosomal Alix (exoAlix) levels were measured in serum/salivary samples from patients with OSCC and healthy controls (HCs). Methods Fifty-seven patients admitted to Nagoya University Hospital from 2017 through 2019 were enrolled, and serum samples (OSCC, n = 29; HC, n = 21) and/or saliva samples (OSCC, n = 23; HC, n = 20) were collected. Exosomal fractions were isolated using ultracentrifugation. ExoAlix levels were measured using enzyme-linked immunosorbent assay. Results Serum/salivary exoAlix levels were significantly higher in patients with OSCC than in HCs. Receiver operating characteristic analyses revealed that sensitivity, specificity, positive predictive value, and area under the curve were 0.345, 1.000, 1.000, and 0.685, respectively, for serum exoAlix and 0.348, 1.000, 1.000, and 0.712, respectively, for salivary exoAlix at optimal cut-off values (serum, 0.205; saliva, 0.193). All tested OSCC tissue sections (n = 21) were immuno-reactive for Alix. Conclusion Serum and salivary exoAlix were identified as potential diagnostic OSCC biomarkers. Serum exoAlix was suitable for prediction of therapeutic responses.

Currently, a reliable serum biomarker for hepatocellular carcinoma (HCC) has not been established, particularly for early‐stage HCC (single tumor 0.8. In our validation study, serum exo‐miR‐4661‐5p could diagnose HCC in all stages (AUROC = 0.917), even in early stage (AUROC = 0.923), with a greater accuracy than other candidate serum exo‐miRs and serum AFP. The panel composed of exo‐miR‐4661‐5p and exo‐miR‐4746‐5p was identified as the most accurate biomarker for early‐stage HCC (AUROC = 0.947, 95% confidence interval = 0.889‐0.980, sensitivity = 81.8%, and specificity = 91.7%). In conclusion, exo‐miR‐4661‐5p–based serum panel is a promising diagnostic marker for early‐stage HCC., The present study derived potential serum exosomal microRNA panels for hepatocellular carcinoma (HCC) using a systematic, genome‐wide biomarker discovery approach. Serum exosomal microRNA‐4661‐5p–based panel is a potent diagnostic biomarker for early stage HCC and could also be used as a prognostic indicator in patients with HCC.

Endometrial cancer is the most common genital cancer in high-resource countries. Treatment is essentially surgical, but the role of lymphadenectomy in the treatment of low-stage and low-grade tumors has not been defined. Although no tumor factors have been validated for use as preoperative prognostic markers of endometrial cancer at yet, human epididymis protein 4 (HE4) has received much interest as a potential diagnostic and prognostic tumor marker. Since 2008, several studies have explored its utility in the management of endometrial cancer: HE4 may be a useful preoperative prognostic marker because it is associated with lymphatic metastasis and other unfavorable factors in endometrial cancer. In addition, some studies have explored a HE4 cutoff value to classify patients according to lymph node involvement. HE4 might be beneficial as a serum marker that helps clinicians in the decision-making algorithm for treatment of endometrial cancer, enabling them to perform individualized operations and decrease the adverse effects of unnecessary surgery.

Introduction Surgery for postchemotherapy residual nonseminomatous germ cell tumors may be difficult due to exceptional lesion size and location. Case presentation A 47-year-old man presented with swelling and pain in the left scrotum. Computed tomography revealed a solid occupied lesion in the left scrotum with huge metastases in the left lung and pleura. Results of a left high inguinal orchiectomy indicated a pathological diagnosis of germ cell tumors of several histological types. The patient declined postoperative chemotherapy but returned to our department 10 months later with dyspnea. Serum tumor marker levels were restored to normal range by adjuvant chemotherapy. Thereafter, an extrapleural pneumonectomy was performed for the remaining tumors. He has since been asymptomatic without recurrence or dyspnea for over 5 years. Conclusion Extrapleural pneumonectomy is a valid treatment option for the management of huge pleural and pulmonary metastases of nonseminomatous germ cell tumors.

Objectives To analyze predictors associated with viable cells in pulmonary residual lesions after chemotherapy for metastatic testicular nonseminomatous germ cell tumors and to develop models to prioritize pulmonary resection. Methods Between 2008 and 2017, 40 patients underwent pulmonary metastasectomy after chemotherapy for nonseminomatous germ cell tumors. We evaluated these patients, and 326 pulmonary residual lesions were confirmed using computed tomography and pathological evaluations. Relationships with outcomes were analyzed using logistic regression analyses. Risk prediction models were developed, and predictive probabilities for the risk of viable cells were estimated. Results Histological examinations showed that 73 (22%) pulmonary residual lesions contained viable cells: teratomas, 46 (14%); and cancer cells, 37 (11%). Multivariate analyses showed that the predictors associated with cancer cells in the residual lesions were elevated tumor marker levels, multiregimen chemotherapy, increased tumor size 6 months before surgery and the histological composition of the primary lesion, including yolk sac tumors. Additional predictors associated with teratomas were aspect ratio and histological composition of the primary lesion, including teratomas. Conclusions Intratumoral heterogeneity contributes to nonseminomatous germ cell tumor chemoresistance, and primary lesion site yolk sac tumors and teratomas are associated with greater risks of viable cells. Increased residual lesion size during chemotherapy could also be a predictor. Our simple model can predict the presence of viable cells in residual lesions after chemotherapy, and it might assist in decision-making and prioritizing pulmonary residual lesion resection.

BACKGROUND Lichen planus (LP) is an autoinflammatory mucocutaneous skin disorder with a multifactorial pathogenesis. Squamous cell carcinoma antigen (SCCA) is a tumor marker recognized as a part of the ovalbumin-serpin family. In patients' serum and skin, SCCA expression is increased with inflammatory skin diseases as psoriasis. AIM This study aimed to estimate serum SCCA2 levels in patients with LP and to assess its relationship with disease severity and types. PATIENTS AND METHODS We included 34 adult patients with LP and 20 healthy adults as control. The total score of LP activity, area, and severity index was calculated for all patients, whereas serum SCCA2 levels were measured in all participants using enzyme-linked immunosorbent assay. RESULTS The mean serum SCCA2 levels were significantly higher in patients than their healthy controls (P

BACKGROUND Currently, prostate-specific membrane antigen-radioligand therapy (PSMA-RLT) is considered a last-line treatment option in advanced castration-resistant prostate cancer. Despite these patients' poor prognosis, accurate estimation of their overall survival (OS) is essential to determine whether benefits exist from the treatment and whether the loss of valuable time and unnecessary side effects can be avoided. The aim of the present study is to evaluate whether various biochemical markers can predict OS in men undergoing PSMA-RLT and whether the changes assessed after PSMA-RLT correlate with the OS. METHODS The tested tumor markers in this retrospective analysis were alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BAP), prostate-specific antigen (PSA), lactate dehydrogenase (LDH), chromogranin A, and pro-gastrin-releasing peptide (pro-GRP). For the evaluation, we performed blood tests before each PSMA-RLT cycle and during follow-up visits (which were 2-3 months apart). All patients were followed up until their deaths. To test the correlations between the tumor markers and survival, we conducted the logrank tests and the multivariate Cox proportional-hazards regression model. The significance level was set at P

BACKGROUND: The purpose of this study was to determine the additional diagnostic value of squamous cell carcinoma antigen (SCC-Ag) in cervical lymph node fine needle aspiration (FNA) samples for the detection of regional metastases of head and neck squamous cell carcinoma (HNSCC).METHODS: In 149 FNA samples of 114 patients, SCC-Ag concentration was retrospectively analyzed and associated with diagnosis to establish a cutoff concentration in relation to sensitivity and specificity of HNSCC detection.RESULTS: SCC-Ag was elevated in lymph nodes from patients with HNSCC compared to lymph nodes from other patients (P CONCLUSIONS: SCC-Ag in FNA is a reliable test for detecting HNSCC in cervical lymph nodes.

Background There are several studies describing the correlation between unsatisfactory tumor marker decline and a poor prognosis for adult patients treated for germ cell tumors. In pediatric patients, the data are limited. Therefore, this study retrospectively analyzed data from Children's Oncology Group (COG) protocol AGCT0132 to determine whether a relationship exists between α-fetoprotein (AFP) decline and outcome. Methods One hundred thirty-one patients with germ cell tumors who were enrolled in COG protocol AGCT0132 were eligible for this analysis of AFP decline. The serum AFP half-life was calculated from levels collected postoperatively as a baseline and after the start of chemotherapy. AFP decline was defined as automatically satisfactory (AFP normalized within the first 2 AFP measures after the start of chemotherapy), calculated satisfactory (AFP half-life ≤7 days after the start of chemotherapy), and unsatisfactory. Results The 3-year cumulative incidence of relapse was 11% (95% confidence interval [CI], 6.0%-18%) for patients with a satisfactory decline and 38% (95% CI, 13%-64%) for patients with an unsatisfactory decline (P = .006). In stratified analyses, this effect was limited to patients who were 11 years of age or older and had standard risk 2 (SR2) disease (P = .004 and P = .007, respectively). Three-year overall survival (OS) for patients with a satisfactory decline versus an unsatisfactory decline was not statistically significant. Conclusions This study is the first to show an association between AFP decline and the cumulative incidence of relapse in pediatric patients treated for germ cell tumors. Recognition of patients at high risk for relapse may allow for early intensification of therapy, which could affect future clinical trial design.

Aim To evaluate the clinical characteristics and outcome of ovarian Sertoli-Leydig cell tumors (SLCTs) managed at a single institution. Methods The hospital records of 17 patients with the diagnosis of ovarian SLCT between 1994 and 2018 were reviewed retrospectively. Results The median age of the patients was 30 years (range, 18-67 years). All the patients had unilateral tumors. All of the 17 were stage 1 tumors. Two (11.8%) patients were stage 1C1 and two (11.8%) patients were stage 1C2. Thirteen (76.5%) patients were stage 1A. Three (17.6%) of the tumors were well differentiated, 11 (64.7%) were intermediately differentiated, 1 (5.9%) was poorly differentiated, and the degree of the differentiation was not identified for 2 (11.8%) patients. One showed retiform pattern and one had heterologous elements at the histopathologic evaluation. Among the 17 patients, we identified structural/vascular renal and ureteral anomalies in 3 (17.6%) patients. Eight patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, seven underwent unilateral salpingo-oophorectomy or oophorectomy and two underwent cystectomy with or without additional surgical staging procedures. Four patients received adjuvant chemotherapy. All the 17 patients were alive and free of disease for 1-287 months after the diagnosis. Median follow-up time was 78 months. None of the patients recurred. Conclusion Sertoli-Leydig cell tumors are rare ovarian malignancies with low recurrence rates and have a favorable outcome compared to malignant epithelial tumors of the ovary. Main treatment is surgical resection and it is appropriate to prefer fertility sparing conservative surgeries for young patients.

Non-small cell lung cancer (NSCLC) is the most common cause of cancer mortality worldwide. NSCLC has an aggressive phenotype and poor prognosis, and is quite heterogeneous without effective and specific targeted therapies. Therefore, exploring new tumor markers and drug targets for NSCLC is crucial towards individualized treatment. Here, we demonstrate that enkurin domain containing 1 (ENKD1), a protein with unknown structure and function, is significantly downregulated in NSCLC tumor tissues compared with their non-tumor counterparts. We also show that ENKD1 expression is decreased in NSCLC cells compared to normal human lung epithelial cells. EdU incorporation, wound healing, and transwell invasion assays reveal that ENKD1 regulates the proliferation, migration, and invasion of NSCLC cells. Collectively, these results suggest that ENKD1 plays an important role in NSCLC progression and that ENKD1 is a tumor marker and a potential molecular drug target for the treatment of NSCLC patients.

Breast cancer (BC) is one of the most common malignancies among women in the world. There is a global attempt to diagnose breast cancer (BC) as early as possible. Long non-coding RNAs (lncRNAs) are emerging as novel targets and biomarkers for BC diagnosis and prognosis. Aberrant expression of lncRNAs is associated with BC development, making them a potential tumor marker for BC. To investigate this possibility, we determined the expression levels of Down Syndrome Cell Adhesion Molecule-Antisense RNA-1 (DSCAM-AS1) and Mitotically-Associated Long Non-Coding RNA (MANCR) lncRNAs in BC tissues. This case-control study was included 50 paired tumor and adjacent non-tumor tissues from female BC patients. The total RNA was isolated and the expression levels of MANCR and DSCAM-AS1 lncRNAs were assessed using quantitative real-time reverse transcription-PCR. Potential correlations between lncRNA levels and clinicopathological characteristics were also analyzed. DSCAM-AS1 and MANCR lncRNAs were significantly up-regulated in BC tumor tissues compared with the adjacent non-tumor tissues. We also found the significant up-regulation of DSCAM-AS1 in advanced tumor-node-metastasis stage (TNM III) of BC tumor tissues. Furthermore, the expression of DSCAM-AS1 and MANCR in HER-2 positive patients was significantly higher than HER-2 negative affected individuals. Receiver operating characteristic curve analysis showed a satisfactory diagnostic efficacy (P-value < 0.0001) which means that DSCAM-AS1 and MANCR lncRNAs can potentially serve as a biomarker. The present study might provide further approval for the clinical diagnostic significance of DSCAM-AS1 and MANCR lncRNAs that their high expressions were associated with aggressive clinical parameters of BC. This article is protected by copyright. All rights reserved.

Background Many tumor‐derived endothelial cells (TECs) are shed into the blood and turn into circulating TECs (CTECs). Rare circulating non‐hematologic aneuploid cells contain CTCs and CTECs, which are biologically and functionally different from each other. CD31 is one of the most representative endothelial cell (EC) markers, yet CD31 alone is not sufficient to detect malignant CTECs due to the existence of abundant normal ECs in circulation. Aneuploidy of chromosome 8 (CEP8) is an important criterion for the identification of malignant cells. Combined in situ phenotypic and karyotypic characterization, which includes an examination of both protein expression and aneuploid chromosomes, has demonstrated its unique advantage for both effective distinguishing and comprehensive detection of CTCs and CTECs. Methods A total of 98 subjects were recruited in the current study, including healthy donors and patients with benign disease and early‐stage non‐small‐cell lung cancer (NSCLC). SE‐iFISH was performed to quantitatively analyze diverse subtypes of aneuploid CD31+ CTECs and CD31− CTCs classified upon the ploidy of chromosome 8 and tumor marker expression in the specimens collected from the recruited subjects. Results CD31− CTCs primarily consist of triploid CTCs with a small cell size (≤5 µm) and large hyperploid CTCs (≥ pentaploid), whereas CD31+ CTECs are mainly comprised of large hyperploid cells. Enumeration of the total numbers of both CTCs and CTECs might help identify malignant nodules with a high sensitivity, whereas quantification of tetraploid CTCs and CTECs specifically exhibited a high specificity for the identification of malignant nodules. Conclusions Combined detection of the specific subtypes of aneuploid CD31+ CTECs and CD31− CTCs may help to effectively identify malignant nodules with a higher sensitivity and specificity in early stage NSCLC patients., CTCs primarily consist of triploid CTCs with a small cell size (≤5 µm) and large hyperploid CTCs (≥pentaploid); CTECs are mainly composed of large hyperploid cells; quantification of tetraploid CTCs and CTECs had the potential of identification of malignant nodules.

Cell-free DNA (cfDNA), which are small DNA fragments in blood derived from dead cells including tumor cells, could serve as useful biomarkers and provide valuable genetic information about the tumors. cfDNA is now used for the genetic analysis of several types of cancers, as a surrogate for tumor biopsy, designated as "liquid biopsy." Rhabdomyosarcoma (RMS), the most frequent soft tissue tumor in childhood, can arise in any part of the body, and radiological imaging is the only available method for estimating the tumor burden, because no useful specific biological markers are present in the blood. Because tumor volume is one of the determinants of treatment response and outcome, early detection at diagnosis as well as relapse is essential for improving the treatment outcome. A 15-year-old male patient was diagnosed with alveolar RMS of prostate origin with bone marrow invasion. The PAX3-FOXO1 fusion was identified in the tumor cells in the bone marrow. After the diagnosis, cfDNA was serially collected to detect the PAX3-FOXO1 fusion sequence as a tumor marker. cfDNA could be an appropriate source for detecting the fusion gene; assays using cfDNA have proved to be useful for the early detection of tumor progression/recurrence. Additionally, the fusion gene dosage estimated by quantitative polymerase chain reaction reflected the tumor volume during the course of the treatment. We suggest that for fusion gene-positive RMSs, and other soft tissue tumors, the fusion sequence should be used for monitoring the tumor burden in the body to determine the diagnosis and treatment options for the patients.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide and the need for novel biomarkers and therapeutic strategies to improve diagnosis and surveillance is obvious. This study aims to identify β6 -integrin (ITGB6) as a novel serum tumor marker for diagnosis, prognosis, and surveillance of CRC. ITGB6 serum levels were validated in retro- and prospective CRC patient cohorts. ITGB6 serum levels were analyzed by ELISA. Using an initial cohort of 60 CRC patients, we found that ITGB6 is present in the serum of CRC, but not in non-CRC control patients. A cut-off of ≥2 ng/mL ITGB6 reveals 100% specificity for the presence of metastatic CRC. In an enlarged study cohort of 269 CRC patients, ITGB6 predicted the onset of metastatic disease and was associated with poor prognosis. Those data were confirmed in an independent, prospective cohort consisting of 40 CRC patients. To investigate whether ITGB6 can also be used for tumor surveillance, serum ITGB6-levels were assessed in 26 CRC patients, pre- and post-surgery, as well as during follow-up visits. After complete tumor resection, ITGB6 serum levels declined completely. During follow-up, a new rise in ITGB6 serum levels indicated tumor recurrence or the onset of new metastasis as confirmed by CT scan. ITGB6 was more accurate for prognosis of advanced CRC and for tumor surveillance as the established marker carcinoembryonic antigen (CEA). Our findings identify ITGB6 as a novel serum marker for diagnosis, prognosis, and surveillance of advanced CRC. This might essentially contribute to an optimized patient care.

The increase in glycolytic flux in cancer, known as aerobic glycolysis, is one of the most important hallmarks of cancer. Therefore, glycolytic enzymes have importance in understanding the molecular mechanism of cancer progression. Triosephosphate isomerase (TPI) is one of the key glycolytic enzymes. Furthermore, it takes a part in gluconeogenesis, pentose phosphate pathway and fatty acid biosynthesis. To date, it has been shown altered levels of TPI in various cancer types, especially in metastatic phenotype. According to other studies, TPI might be considered as a potential therapeutic target and a cancer-related biomarker in different types of cancer. However, its function in tumor formation and development has not been fully understood. Here, we reviewed the relationship between TPI and cancer for the first time.

Specific microRNAs (miRNAs) are packaged in exosomes that regulate processes in tumor development and progression. The current study focuses on the influence of exosomal miRNAs in the pathogenesis of epithelial ovarian cancer (EOC). MiRNA profiles were determined in exosomes from plasma of 106 EOC patients, eight ovarian cystadenoma patients, and 29 healthy women by TaqMan real-time PCR-based miRNA array cards containing 48 different miRNAs. In cell culture experiments, the impact of miR-200b and miR-320 was determined on proliferation and apoptosis of ovarian cancer cell lines. We report that miR-21 (P = 0.0001), miR-100 (P = 0.034), miR-200b (P = 0.008), and miR-320 (P = 0.034) are significantly enriched, whereas miR-16 (P = 0.009), miR-93 (P = 0.014), miR-126 (P = 0.012), and miR-223 (P = 0.029) are underrepresented in exosomes from plasma of EOC patients as compared to those of healthy women. The levels of exosomal miR-23a (P = 0.009, 0.008) and miR-92a (P = 009, 0.034) were lower in ovarian cystadenoma patients than in EOC patients and healthy women, respectively. The exosomal levels of miR-200b correlated with the tumor marker CA125 (P = 0.002) and patient overall survival (P = 0.019). MiR-200b influenced cell proliferation (P = 0.0001) and apoptosis (P < 0.008). Our findings reveal specific exosomal miRNA patterns in EOC and ovarian cystadenoma patients, which are indicative of a role of these miRNAs in the pathogenesis of EOC.

Ovarian cancer (OC) is the fifth leading cause of cancer-related death among women. The high mortality rate is due to lack of early symptoms, late diagnosis, limited treatment options, and also emerging of drug resistance. Todays, molecular markers have become promising in tumor-targeted therapy. Several molecular markers have been known in OC immunotherapy. Identification of the specific molecular markers with prognostic significance is interested. CD24 is a small sialoglycoprotein which is localized in lipid rafts through its glycosylphosphatidylinositol (GPI) anchor. It has been reported that CD24 is overexpressed in many cancers including OC. Also, CD24 is identified as a cancer stem cell marker in OC. The CD24 expression is associated with the development, invasion, and metastasis of cancer cells. The exact role of CD24 in cancer cells is not clearly understood. Recently, CD24 has been identified as an independent prognostic marker of survival in patients with OC. In this study, we reviewed the molecular targets in OC immune-targeted therapy and also presented an overview of the new molecular marker CD24 and its association with the OC by reviewing the recent literature.

Background and aim A high yield of biopsy is mandatory to perform molecular genetic research with endoscopically obtained gastric cancer tissues. We evaluated whether probe-based confocal laser endomicroscopy (pCLE) can increase the yield of endoscopic biopsy for gastric cancer compared with white light endoscopy (WLE). Methods All lesions in the pCLE and WLE groups were initially evaluated through WLE. In the pCLE group, lesions were further examined through pCLE. In the pilot study, five and three biopsy specimens were obtained for histopathological examination and tumor marker analysis, respectively. In the confirmatory study, six biopsy specimens for histopathological evaluation were obtained. Results A total of 30 gastric cancers and 61 undifferentiated-type gastric cancers were analyzed in the pilot and confirmatory studies, respectively. The proportion of cancer cells in biopsy samples of poorly differentiated adenocarcinoma or signet ring cell carcinoma was higher in the pCLE group than in the WLE group in both the pilot and confirmatory studies (pilot: median proportion, 65% vs 30%, P = 0.010; confirmatory: mean ± standard deviation, 49.5 ± 29.3 vs 29.3 ± 13.7, P = 0.002). The expression ratio of tumor markers including carcinoembryonic antigen, GW112, HOX transcript antisense RNA, and H19 tended to be higher in the pCLE group than in the WLE group. Conclusion Probe-based confocal laser endomicroscopy-targeted biopsy provided superior results in terms of the proportion of cancer cells in biopsy samples compared with WLE-targeted biopsy in gastric cancer with undifferentiated histology.

Long non-coding RNA (lncRNA) is one of the focuses and hotspots of biological research in recent years. At the same time, tumors have become the main disease that endangers human health. In recent years, a large number of researchers have explored the relationship between lncRNA and tumors. HOXA11-AS is one of these lncRNAs. The long non-coding RNA HOXA11 antisense RNA (HOXA11-AS) is a novel lncRNA recently discovered. It is found in a variety of tumors such as ovarian cancer, glioma, and gastric cancer (GC) and so on, and is defined as an oncogene. It promotes tumor proliferation and metastasis by interacting with proteins such as miRNA and EZH2. In this paper, we review the mechanism of interaction between HOXA11-AS and various tumors in recent years, and believe that it can be a potential tumor marker and therapeutic target in the future prevention and treatment of tumors.

The focus of this study was to investigate the expression status of Circ-vimentin (VIM) and further analyze its pathogenesis and clinical significance in acute myeloid leukemia (AML) patients. Real-time quantitative polymerase chain reaction was carried on Circ-VIM in 113 AML patients and 42 healthy controls. Circ-VIM was significantly upregulated in AML compared with control and was positively correlated with white blood cells (WBC) count. Receiver operating characteristic curve analysis indicated that the performance of Circ-VIM expression could serve as a promising biomarker for differentiating AML patients from controls. Significant correlations of Circ-VIM expression were found with WBC and French-American-British classifications. Survival analyses further showed that over-expressed Circ-VIM were associated with markedly shorter overall survival (OS) and leukemia-free survival (LFS) in whole-cohort AML, nonacute promyelocytic leukemia AML and cytogenetically normal-AML patients. Multivariate analysis also disclosed that Circ-VIM over-expression was an independent poor prognostic factor for OS and LFS in AML patients. Remarkably, Pearson correlation analysis evidenced that the expression of Circ-VIM was positively correlated with VIM expression in all AML patients. These results indicated that overexpression Circ-VIM could serve as a significant biomarker.

Preclinical studies have shown positive effects of statins against specific cancers. This study aimed to determine the therapeutic effect of simvastatin in 12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer. Female albino mice were divided into two groups, with or without DMBA administration. After tumor appearance, DMBA-treated group was further divided into four groups (D1-D4) as control (D1), treated with simvastatin at 80 and 40 mg/kg/day, orally (D2 and D3) and tamoxifen (50 mg/kg/day, orally) treated group (D4). After 4 weeks, animals were sacrificed, serum samples were collected and tumors were dissected for histopathological study and determination of selected parameters. The tumor marker carcinoma antigen 15-3 (CA15-3), oxidative stress parameters and prostaglandin E2 (PGE2) levels were analyzed in serum and tumors in experimental groups. Tamoxifen and high dose of simvastatin improved parameters of mammary carcinogenesis including mean tumor volume, body weight and percent of mortality as compared to mice with breast tumors without treatment (D1). Additionally, simvastatin usage increased total antioxidant capacity (TAC) level, paraoxonase 1 (PON1) activity in serum and decreased total oxidant status (TOS) and malondialdehyde (MDA) levels in tumors similar to tamoxifen. No significant decrease was found in serum CA 15-3 and tumor PGE2 levels in simvastatin and tamoxifen treated groups as compared to D1 group. These data suggest that simvastatin has anticancer effects which are relatively similar to that of tamoxifen in an animal model of breast cancer.

Objectives To assess clinicopathological data and oncological outcomes focused on metastatic testicular cancer patients, who received chemotherapy as the initial treatment, in the nationwide multi-institutional study by the Cancer Registration Committee of the Japanese Urological Association. Methods A testicular cancer survey was carried out by the Japanese Urological Association in 2011 to register newly diagnosed testicular cancers in 2005 and 2008. Among 1121 registered patients, 278 patients with metastases who received chemotherapy as the initial treatment and could be categorized by the Japanese Urological Association classification were eligible for the analysis. Results As first-line chemotherapy, bleomycin, etoposide and cisplatin, and etoposide and cisplatin therapies were chosen for 260 patients (93.5%). As second-line therapy, vinblastine, ifosfamide and cisplatin/etoposide, ifosfamide and cisplatin; and paclitaxel, ifosfamide and cisplatin/paclitaxel, ifosfamide and nedaplatin therapies were carried out in 23 out of 63 (36.5%) and 29 out of 63 (46.0%) patients, respectively. The response rate and serum tumor marker normalization rate were 93.4% and 81.3% at first line, 75.4% and 60.7% at second line, and 41.7% and 16.7% at third line, respectively. The Japanese Urological Association classification (≥IIIB2 vs ≤IIIB1) and choriocarcinoma component in primary histology were independent prognostic factors of overall survival before starting chemotherapy. Furthermore, in patients with non-seminomatous germ cell tumors, serum tumor marker normalization was an independent factor that was associated with better outcome of overall survival after completion of the initial series of chemotherapies. Conclusions The initial accurate diagnosis and risk stratification is an important prognostic factor to achieve better oncological outcomes. In patients with non-seminomatous germ cell tumors, aiming for serum tumor marker normalization with continuous sequential chemotherapy could improve overall survival.

Background and objectives To identify surrogate markers for prognosis of breast cancer patients with non-pathological complete response (non-pCR) to neoadjuvant chemotherapy (NAC), our investigation focused on the serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA15-3) as well as clinicopathological factors both before and after NAC. Methods A total of 185 breast cancer patients treated with NAC were recruited. Serum carcinoembryonic antigen and CA15-3 were measured at baseline and at completion of NAC. Results Among the non-pCR cancers (n = 142), the disease-free survival (DFS) of patients with CA15-3-low at baseline (3-year DFS: 0.908, n = 73) was significantly better than of those with CA15-3-high (3-year DFS: 0.681, n = 69, P = .0134). Multivariable analysis demonstrated that baseline CA15-3 levels (hazard ratio: 3.31, 95% confidence interval: 1.28-10.23; P = .0122) and residual invasive size (hazard ratio: 4.47, 1.26-28.39; P = .0171) were significant independent factors for DFS. The combination of these factors proved to be an accurate predictor for DFS regardless of breast cancer subtypes. Conclusions The combination of residual invasive size and serum CA15-3 levels at baseline seems to be a significant and independent surrogate marker of poor outcome for patients with non-pCR. These findings suggest that these markers may be useful for identifying patients with inferior prognosis and candidates for additional adjuvant treatments.