Gastric-type gene expression and phenotype in non-terminal respiratory unit type adenocarcinoma of the lung with invasive mucinous adenocarcinoma morphology.

AIMS: We sought to determine if non-terminal respiratory unit (TRU) type adenocarcinoma of lung with invasive mucinous adenocarcinoma (IMA) morphology shows gastric differentiation. METHODS AND RESULTS: We reviewed whole-section images of 489 cases of lung adenocarcinoma from The Cancer Genome Atlas (TCGA). TCGA data were classified into 426 TRU type adenocarcinoma, 49 IMA and 14 unclassifiable. Their RNA sequencing data was analysed by DESeq2 and WGCNA R packages. Gene expression in patients' samples was measured by NanoString assay. Overexpression of genes including REG4, TFF2, MUCL3, FER1L6, B3GALT5, ANXA10 was observed by TCGA analysis in IMA compared to TRU type adenocarcinoma. Many of these genes are those expressed in normal gastric glands and selected for NanoString experiment on 14 IMA and 10 TRU type adenocarcinoma cases. The expression of genes, including ANXA10, FER1L6, HNF4a, MUC5AC, REG4, TFF1, TFF2 and VSIGI, was increased> 15-fold in IMA. Immunohistochemistry of ANXA10, TFF2 and FER1L6 performed on 31 IMA and 135 TRU type adenocarcinomas showed a predominant expression in IMA, but are not in TRU type adenocarcinoma. CONCLUSION: Our results showed the level of genes expressed in stomach mucosa was increased in IMA compared to TRU type adenocarcinoma, supporting gastric differentiation of IMA. This finding may help the understanding of the pathogenesis of IMA and discovery of therapeutic targets.

Vesical Imaging-Reporting and Data System for Multiparametric MRI to Predict the Presence of Muscle Invasion for Bladder Cancer.

BACKGROUND: The Vesical Imaging-Reporting and Data System (VI-RADS) is a newly developed system of bladder cancer staging with multiparametric MRI (mpMRI), which can be used to predict the presence of muscle invasion for bladder cancer. PURPOSE: To evaluate the accuracy of three mpMRI series (T2 WI, diffusion-weighted imaging [DWI], and dynamic contrast-enhanced image [DCEI]) and VI-RADS for diagnosing the muscle invasive bladder cancer (MIBC). STUDY TYPE: Retrospective. POPULATION: In all, 66 pathologically proven bladder cancers in 32 patients. FIELD STRENGTH/SEQUENCE: Before the diagnostic MRI with an intramuscular antispasmodic agent, optimal bladder distension was confirmed. 3.0T MRI with T2 WI, DWI, and DCEI. ASSESSMENT: Three reviewers independently assessed and scored the bladder cancers in T2 WI, DWI, and DCEI using a five-point score system. Based on the scores in the three sequences, reviewers scored each bladder cancer with reference to VI-RADS categories. We evaluated the diagnostic performance of each of three mpMRI sequences and the final VI-RADS categorization for diagnosing MIBC. STATISTICAL TESTS: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the curve (AUC) of each of three sequences separately and VI-RADS categorization for diagnosing the MIBC. RESULTS: The diagnostic performances of each of the three mpMRI series and VI-RADS for diagnosing MIBC were excellent. Especially using the optimal cutoff score >3 for predicting MIBC on DWI, DCEI, and VI-RADS, the sensitivity, specificity, PPV, NPV, and AUC values were 90% (95% confidence interval [CI]: 0.56, 1.00), 100% (95% CI: 0.94, 1.00), 100% (95% CI: 0.66. 1.00), 98.3% (95% CI: 0.91, 1.00), and 0.95, respectively. DATA CONCLUSION: mpMRI based on VI-RADS can stratify patients with bladder cancer according to the presence of muscle invasion. LEVEL OF EVIDENCE: 3. TECHNICAL EFFICACY STAGE: 2. J. Magn. Reson. Imaging 2020;52:1249-1256.

Is it worth carrying out ultrasound-magnetic resonance imaging fusion targeted biopsy on Prostate Imaging Reporting and Data System score 3 prostate lesions?

OBJECTIVES: To evaluate the use of ultrasound-magnetic resonance imaging fusion targeted biopsy for Prostate Imaging Reporting and Data System 3 prostate lesions. METHODS: We identified 227 patients with prostate-specific antigen levels ≥4 ng/mL who underwent concurrent transrectal ultrasound-guided systemic biopsy and fusion biopsy. Suspicious prostatic lesions were assessed in accordance with Prostate Imaging Reporting and Data System version 2.0. We compared ultrasound-magnetic resonance imaging fusion targeted biopsy and ultrasound-guided biopsy cancer detection rates in Prostate Imaging Reporting and Data System 3 lesions with those in other Prostate Imaging Reporting and Data System score lesions. In Prostate Imaging Reporting and Data System 3 patients, we identified clinically significant prostate cancer risk factors by logistic regression analysis. RESULTS: In total, 2770 transrectal ultrasound-guided and 867 fusion biopsy cores were obtained; where 332 (12.0%) and 194 (22.4%) cores were prostate cancer-positive, respectively (P < 0.001). The fusion biopsy cancer detection rate (8.0%) in Prostate Imaging Reporting and Data System 3 lesions was similar to that in Prostate Imaging Reporting and Data System 1-2 lesions, but was lower than that of Prostate Imaging Reporting and Data System 4 (30.0%; P < 0.001) and 5 lesions (65.2%; P < 0.001), and ultrasound-guided biopsy (12.0%; P = 0.023). For clinically significant prostate cancer detection, fusion biopsy in Prostate Imaging Reporting and Data System 3 lesions was inferior to that in Prostate Imaging Reporting and Data System 4 and 5 lesions, and non-superior to ultrasound-guided biopsy. Cancer detection rate trends were similar in biopsy-naïve patients. In Prostate Imaging Reporting and Data System 3 patients, prostate-specific antigen density was the only significant predictor of clinically significant prostate cancer. CONCLUSIONS: The present findings do not support the use of ultrasound-magnetic resonance imaging fusion targeted biopsy for Prostate Imaging Reporting and Data System 3 lesions. Thus, we recommend the use of transrectal ultrasound-guided systemic biopsy for patients with Prostate Imaging Reporting and Data System 3 index lesions.

E2F1 Promotes Progression of Bladder Cancer by Modulating RAD54L Involved in Homologous Recombination Repair.

DNA repair defects are important factors in cancer development. High DNA repair activity can affect cancer progression and chemoresistance. DNA double-strand breaks in cancer cells caused by anticancer agents can be restored by non-homologous end joining (NHEJ) and homologous recombination repair (HRR). Our previous study has identified E2F1 as a key gene in bladder cancer progression. In this study, DNA repair genes related to E2F1 were analyzed, and RAD54L involved in HRR was identified. In gene expression analysis of bladder cancer patients, the survival of patients with high RAD54L expression was shorter with cancer progression than in patients with low RAD54L expression. This study also revealed that E2F1 directly binds to the promoter region of RAD54L and regulates the transcription of RAD54L related to the HRR pathway. This study also confirmed that DNA breaks are repaired by RAD54L induced by E2F1 in bladder cancer cells treated with MMC. In summary, RAD54L was identified as a new target directly regulated by E2F1. Our results suggest that, E2F1 and RAD54L could be used as diagnostic markers for bladder cancer progression and represent potential therapeutic targets.

TFE3 translocation and protein expression in renal cell carcinoma are correlated with poor prognosis.

AIMS: Since Xp11.2 translocation-associated renal cell carcinoma (TRCC) was first recognised, its morphological features and the clinical significance of TFE3 expression, frequency of gene translocation and diagnostic criteria have been the subject of limited studies. The present retrospective analysis aimed to evaluate the correlation between TFE3 immunoreactivity and its gene translocation status using fluorescence in-situ hybridisation (FISH) and determine how TFE3 translocation and expression affect patient prognosis differently. METHODS AND RESULTS: We enrolled 303 consecutive renal cell carcinoma cases. Immunohistochemical staining for TFE3 was performed in 303 cases, and FISH analysis was performed for molecular testing. The TCGA data set of renal cell carcinoma was evaluated to validate TFE3 expression and survival analysis. TFE3 expression was associated significantly with the nested alveolar pattern, papillary pattern, eosinophilic cytoplasm, voluminous expansile cytoplasm, nuclear grade, tumour necrosis, sarcomatoid pattern and picket fence appearance. FISH analysis showed break-apart signals in 26 of 32 (81.25%) cases expressing strong or moderate nuclear TFE3 immunoreactivity. Thirteen of 56 samples that showed no or weak TFE3 expression with morphologically suspicious cases were translocation-positive in the FISH assay. The TFE3-translocation group (harbouring TFE3 translocation regardless of TFE3 expression) showed the poorest progression-free survival (PFS), and the TFE3-expressing group (expressing TFE3 but negative for translocation) was correlated significantly with decreased PFS. CONCLUSION: Increased TFE3 expression in RCC was associated with poor PFS regardless of the gene translocation status. Moreover, morphological analysis should help to select candidates who would benefit from TFE3 staining and FISH analysis.

The cumulative incidence and risk factors of postoperative inguinal hernia in patients undergoing radical prostatectomy.

BACKGROUND: The aim of this study is to investigate the cumulative incidence and risk factors of postoperative inguinal hernia (PIH) in patients undergoing radical prostatectomy, i.e., laparoscopic prostatectomy (LRP) and robot-assisted laparoscopic prostatectomy (RARP). METHODS: This study included 1124 patients who had undergone radical prostatectomy or transurethral resection of bladder tumor from 2011-2016. We compared the cumulative incidence of PIH in the radical prostatectomy groups (460; LRP 341, RARP 119) and the control group (664; transurethral resection of bladder tumor), and we then analyzed the risk factors (age, operative methods, previous abdominal operative history, thickness and width of external oblique muscle and rectus muscle, thickness of abdominal subcutaneous fat layer at Hesselbach's triangle level, body mass index, prostate-specific antigen, operative time, specimen weight, Gleason score, and pathology T-stage) of PIH in the radical prostatectomy groups. RESULTS: The median follow-up period in this study was 39.6 months. In Kaplan-Meier curve analysis, the cumulative incidence of PIH was 5.3, 4.2, and 0.5% for the LRP, RARP, and control groups, respectively (p < 0.001). Multiple logistic regressions showed that thickness of external oblique muscle and width of rectus muscle were significant risk factors (p < 0.001 and p = 0.027). CONCLUSIONS: PIH is considered to be one of the complications of LRP and RARP. Moreover, we suggest that if the thickness of the muscle is <7.3 mm, thoughtful surgical manipulation is needed for radical prostatectomy, and care should be taken to determine whether hernia occurs during follow-up.

Tumor necrosis could reflect advanced disease status in patients with diffuse large B cell lymphoma treated with R-CHOP therapy.

Tumor necrosis (TN) can lower responsiveness to chemotherapy and confer basic resistance to anti-cancer therapy. We investigated the association of TN with poor clinical features and outcome in diffuse large B cell lymphoma (DLBCL). We examined the presence or absence of TN in 476 DLBCL patients of who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Eighty-nine (18.7 %) patients had TN at diagnosis. Patients with TN had a progression-free survival (PFS) and overall survival (OS) of 39.3 and 46.7 %, whereas patients without TN had a PFS and OS of 73.4 and 82.6 %. Adverse clinical factors of poor Eastern Cooperative Oncology Group performance status ≥ grade 2 (p = 0.005), elevated lactate dehydrogenase ratio >1 (p < 0.001), advanced Ann Arbor stage (p = 0.002), and bulky disease (p = 0.026) were more prevalent in the TN group than the non-TN group. Cox regression model analysis revealed TN as an independent prognostic factor for PFS and OS in DLBCL (PFS, hazard ratio [HR] = 1.967, 95 % confidence interval [CI] = 1.399-2.765, p < 0.001; OS, HR = 2.445, 95 % CI = 1.689-3.640, p < 0.001). The results indicate that TN could reflect adverse clinical features and worse prognosis in DLBCL patients receiving R-CHOP therapy.

Would Lipophilic Statin Therapy as a Prognostic Factor Improve Survival in Patients With Uterine Cervical Cancer?

OBJECTIVES: In vitro studies showed that lipophilic statins inhibit cell growth, adhesion, and invasion and induce apoptosis in cancer cell lines. In uterine cervical cancer, several important factors including age, stage, anemia, lymphovascular invasion, lymph node metastases, and parametrial spread were known to significantly predict survival. We investigated whether statin therapy as a prognostic factor would significantly predict survival in cervical cancer. METHODS: Patients with stages IB to IV cervical cancer who received radical hysterectomy and/or para-aortic lymph node dissection were included. The statin-use group was identified as patients who were continuously prescribed with lipophilic statins from prediagnostic period of the cancer. RESULTS: The baseline characteristics of both statin-use group and control group were comparable. During a median follow-up of 36.6 months, progression-free survival and overall survival of the statin-use group were significantly higher than the control group (P < 0.001 and P = 0.004, respectively). In multivariate analysis, the statin-use group had an independent prognostic significance compared with other prognostic factors (progression-free survival: hazards ratio = 0.062, 95% confidence interval = 0.008-0.517, P = 0.010; overall survival: hazards ratio = 0.098, 95% confidence interval = 0.041-0.459, P = 0.032). CONCLUSIONS: In the present study, continuous lipophilic statin therapy from the prediagnostic period of uterine cervical cancer could reflect favorable outcome, independently.

IDH1 R132C mutation is detected in clear cell hepatocellular carcinoma by pyrosequencing.

BACKGROUND: Isocitrate dehydrogenase 1 (IDH1) mutation is common in low-grade glioma (approximately 80%) and acute myeloid leukemia (approximately 10%). Other than brain tumor or hematologic malignancies, intrahepatic cholangiocarcinoma (iCC) is a well-known solid tumor with IDH1 mutation (6.8-20%). Histologically, poor differentiation and clear cell change are associated with IDH1 mutation in iCC. Since hepatocellular carcinoma (HCC) shares histologic features with iCC, some specific subtypes of HCC might show a higher IDH1 mutation rate than reported before (0.5-1.5%). METHODS: Forty-six cases of iCC and 48 cases of HCC (including 20 cases of clear cell type and 13 cases of pseudoglandular pattern) were tested for IDH1 mutation by pyrosequencing. RESULTS: Three cases in iCC (6.5%) and five cases in HCC (10.4%) had IDH1 mutation, all of which were Arg132Cys. IDH1 mutant HCCs were all clear cell type. Although the IDH1 mutation rate between iCC and HCC demonstrated no significant difference, clear cell HCC revealed statistically increased mutation rate compared to that of HCC without clear cell change (P = 0.009). Presence of IDH1 mutation was related with poor survival in clear cell HCC patients (P = 0.004). CONCLUSIONS: Clear cell HCC showed higher frequency of IDH1 mutation rate than other variants of HCC. This result consolidates the assumption that morphological features of tumors reflect molecular alterations.

Three cases of adrenocortical tumors mistaken for hepatocellular carcinomas/diagnostic pitfalls and differential diagnosis.

Adrenocortical adenomas and carcinomas in other parenchyma are extremely rare, with few cases reported and because of the rarity of these tumors, they occasionally cause problems during diagnosis. Adrenal cortical neoplasms in liver parenchyma can be present in 3 forms, including direct invasion or adhesion to liver parenchyma, tumors arising in adrenohepatic fusion tissue or in ectopic adrenal gland tissue. We report 3 cases of adrenal cortical tumors that were misdiagnosed as hepatocellular carcinoma in the preoperative state. The first case involved an adrenocortical adenoma arising in adrenohepatic fusion tissue. The remaining 2 cases involved an adrenocortical carcinoma and an adrenocortical oncocytoma arising in ectopic adrenal tissue in the liver. We describe the clinical presentations, gross, microscopic findings, immunohistochemical findings with respect to each case, with emphasis on differential diagnosis from hepatocellular carcinoma.

Tissue response to implanted Ahmed glaucoma valve with adjunctive amniotic membrane in rabbit eyes.

AIMS: To investigate the histopathology of the fibrous capsule around Ahmed glaucoma valves (AGVs) implanted with adjunctive amniotic membranes in rabbits. METHODS: AGV implantation with or without adjunctive amniotic membrane was performed in a single eye of 20 albino rabbits. The upper surface of the AGV body was covered with amniotic membrane in the study group. After 2 months, histology was used to compare the thickness and characteristics of the fibrous capsule, transdifferentiation of myofibroblasts, and density of blood vessels and leukocytes between the study and control groups. RESULTS: The fibrous capsule along the roof of the bleb was composed of compact collagen fibers with minimal vascularization in the control group. In contrast, in the study group, the fibrous capsule was looser and had a more disorganized collagen architecture. The thickness of the fibrous capsule and the myofibroblast layer was significantly thinner in the study group than in the control group (p < 0.001). The number of CD31-positive blood vessels did not differ between the two groups (p = 0.235). CD45-positive inflammatory cells were more frequently observed in the study group than the control group (p = 0.001). The groups did not differ in the thickness of the fibrous capsule or myofibroblast layer, or the density of blood vessels and leukocytes along the floor of the bleb. CONCLUSIONS: Adjunctive amniotic membranes could reduce the risk of encapsulation and aqueous outflow resistance by altering the tissue response to implanted AGVs and subsequent formation of a loose thin capsule.

Significant simultaneous changes in serum CA19-9 and CA125 due to prolonged torsion of mature cystic teratoma of the ovary.

Mature cystic teratoma is a common benign neoplasm of the ovary. Complications occur in approximately 20% of cases. Clinical manifestations, laboratory findings, and imaging studies can assist in making a diagnosis of ovarian torsion of mature cystic teratoma. Furthermore, serum tumor markers may be helpful for diagnosing mature cystic teratoma and its torsion and, thus, can lead to early surgical intervention. A 56-year-old woman presented with a huge pelvic mass and pelvic pain. Serum CA19-9, CA125, and carcinoembryonic antigen levels were abnormally elevated at >700 U/ml, 282.5 U/ml, and 3.94 U/ml, respectively. The tumor was surrounded by extensive adhesions and showed inflammatory changes. The serum levels of these markers returned to normal levels after surgery.

Ciliated adenocarcinomas of the lung: a tumor of non-terminal respiratory unit origin.

Whereas most carcinomas occur through a sequential step, atypical adenomatous hyperplasia and bronchioloalveolar carcinoma pathway is known for pulmonary adenocarcinoma. This type is known as terminal respiratory unit adenocarcinoma. Based on our observation of transitions from normal ciliated columnar cells to adenocarcinoma via dysplastic mucous columnar cells, we reviewed our archive of pulmonary adenocarcinoma. Terminal respiratory unit type adenocarcinoma was defined as adenocarcinoma with type II pneumocyte, Clara cell, or bronchiolar cell morphology according to previous reports. Among 157 cases, 121 cases have been identified as terminal respiratory unit type adenocarcinoma and 36 cases as non-terminal respiratory unit type adenocarcinoma. Among non-terminal respiratory unit type adenocarcinoma, 24 cases revealed mucous columnar cell changes that were continuous with bronchial ciliated columnar cells. The mucous columnar cells became dysplastic showing loss of cilia, disorientation, and enlarged nuclei. Adenocarcinoma arose from these dysplastic mucous columnar cells and, characteristically, this type of adenocarcinoma showed acute inflammation, and honeycombing changes in the background. TTF1 immunostaining was consistently negative. In a case study with 14 males and 10 females, including 12 smokers or ex-smokers, EGFR and KRAS mutations were detected in 3 and 6 patients, respectively. We think that this kind of adenocarcinoma arising through mucous columnar cell change belongs to non-terminal respiratory unit type adenocarcinoma, and mucous columnar cell change is a precursor lesion of pulmonary adenocarcinoma.

Comparative Analysis of Proteomes and Phosphoproteomes in Patients with Prostate Cancer Using Different Surgical Conditions.

PURPOSE: To establish the standard of procedure in preparing benign and cancerous prostate tissues and evaluate the quality of proteomics and phosphoproteomics during transurethral resection of the prostate (TUR-P) with different surgical conditions. MATERIALS AND METHODS: TUR-P tissue samples from three patients, two diagnosed with prostate cancer and one with benign prostatic hyperplasia, were each analyzed under three different conditions, based on differences in energy values, tissue locations, and surgical techniques. Global- and phosphorylated proteomic profiles of prostate tissues were analyzed by liquid chromatography-tandem mass spectrometry. RESULTS: A total of 6,019 global proteins and 4,280 phosphorylated peptides were identified in the nine tissues. The quantitative distributions of proteins and phosphorylation in tissues from the same patient were not affected by changes in the surgical conditions, but indirect relative comparisons differed among patients. Phosphorylation levels, especially of proteins involved in the androgen receptor pathway, important in prostate cancer, were preserved in each patient. CONCLUSIONS: Proteomic profiles of prostate tissue collected by TUR-P were not significantly affected by energy levels, tissue location, or surgical technique. In addition, since protein denaturation of samples through TUR-P is rarely confirmed in this study, we think that it will be an important guide for tissue samples in castration resistant prostate cancer patients, where it is difficult to obtain tissue. This result is the first report about proteomic and phosphoproteomic results with TUR-P samples in prostate cancer and will be theoretical basis in protein analysis research with prostate cancer tissues.

Chemical control of receptor kinase signaling by rapamycin-induced dimerization.

Membrane-localized leucine-rich repeat receptor kinases (LRR-RKs) sense diverse extracellular signals, and coordinate and specify cellular functions in plants. However, functional understanding and identification of the cellular signaling of most LRR-RKs remain a major challenge owing to their genetic redundancy, the lack of ligand information, and subtle phenotypes of LRR-RK overexpression. Here, we report an engineered rapamycin-inducible dimerization (RiD) receptor system that triggers a receptor-specific LRR-RK signaling independent of their cognate ligands or endogenous receptors. Using the RiD-receptors, we demonstrated that the rapamycin-mediated association of chimeric cytosolic kinase domains from the BRI1/BAK1 receptor/co-receptor, but not the BRI1/BRI1 or BAK1/BAK1 homodimer, is sufficient to activate downstream brassinosteroid signaling and physiological responses. Furthermore, we showed that the engineered RiD-FLS2/BAK1 could activate flagellin-22-mediated immune signaling and responses. Using the RiD system, we also identified the potential function of an unknown orphan receptor in immune signaling and revealed the differential activities of SERK co-receptors of LRR-RKs. Our results indicate that the RiD method can serve as a synthetic biology tool for precise temporal manipulation of LRR-RK signaling and for understanding LRR-RK biology.

Inflammatory Endobronchial Myofibroblastic Tumor: A Case Report.

Inflammatory myofibroblastic tumor is a rare benign lesion that accounts for 0.04-1% of all lung tumors and usually appears as a solitary pulmonary nodule or mass. Here, we report the case of an endobronchial inflammatory myofibroblastic tumor in a 21-year-old man with a focus on the imaging findings and a review of previous literature.

Beating Thermal Coarsening in Nanoporous Materials via High-Entropy Design.

Controlling the feature sizes of 3D bicontinuous nanoporous (3DNP) materials is essential for their advanced applications in catalysis, sensing, energy systems, etc., requiring high specific surface area. However, the intrinsic coarsening of nanoporous materials naturally reduces their surface energy leading to the deterioration of physical properties over time, even at ambient temperatures. A novel 3DNP material beating the universal relationship of thermal coarsening is reported via high-entropy alloy (HEA) design. In newly developed TiVNbMoTa 3DNP HEAs, the nanoporous structure is constructed by very fine nanoscale ligaments of a solid-solution phase due to enhanced phase stability by maximizing the configuration entropy and suppressed surface diffusion. The smallest size of 3DNP HEA synthesized at 873 K is about 10 nm, which is one order of magnitude smaller than that of conventional porous materials. More importantly, the yield strength of ligament in 3DNP HEA approaches its theoretical strength of G/2π of the corresponding HEA alloy even after thermal exposure. This finding signifies the key benefit of high-entropy design in nanoporous materials-exceptional stability of size-related physical properties. This high-entropy strategy should thus open new opportunities for developing ultrastable nanomaterials against its environment.

Differences in immune-related gene expressions and tumor-infiltrating lymphocytes according to chemotherapeutic response in ovarian high-grade serous carcinoma.

BACKGROUND: High-grade serous carcinoma (HGSC) of the ovary is the most common subtype of epithelial ovarian cancer (EOC) and has an overall poor prognosis. There is increasing awareness of the importance of immune cell populations and tumor-infiltrating lymphocytes (TILs) in various immune pathways in the tumor microenvironment. The present study evaluated immune-related gene expressions and TIL levels, as well as associated chemotherapeutic responses, to elucidate the correlation between gene expression and TIL levels in HGSC. MATERIALS AND METHODS: Fresh tissue samples from 12 HGSC patients were included in this study. Depending on their response to adjuvant chemotherapy, the patients were divided into two groups: chemosensitive (CS) or chemoresistant (CR). The expression levels of 770 genes were analyzed using the nCounter® PanCancer Immune Profiling Panel of the NanoString nCounter® Analysis System. Quantitative real-time polymerase chain reaction (qPCR) was performed to validate the NanoString data obtained. The TIL levels in representative sections were examined via hematoxylin and eosin staining. Gene and TIL levels were subsequently correlated with the chemotherapeutic response. RESULTS: Several genes were differentially expressed in the two study groups. Eleven representative genes were selected for further evaluation. Of those, 9 genes (IRF1, CXCL9, LTB, CCL5, IL-8, GZMA, PSMB9, CD38, and VCAM1) were significantly overexpressed in the CS group; whereas expressions of 2 genes (CD24 and CD164) were increased in the CR group. Results of qPCR were consistent with those of the NanoString nCounter® analysis. Stromal TIL levels were significantly associated with adjuvant chemotherapeutic response (p = 0.001). CONCLUSIONS: Significant differences between the CS and CR groups were observed in the expression levels of immune-related genes. Immune-related gene expressions were significantly higher in the CS group, which also had higher levels of TILs. We, therefore, suggest that, in patients with HGSC, immune-related gene expressions and TIL levels may be associated with chemotherapeutic sensitivity.

Comparison of the accuracy of multiparametric magnetic resonance imaging (mpMRI) results with the final pathology findings for radical prostatectomy specimens in the detection of prostate cancer.

AIMS: To assess the accuracy of multiparametric magnetic resonance imaging (mpMRI), used in conjunction with the Prostrate Imaging Reporting and Data System (PI-RADS), version 2, in the detection of prostate cancer (PCa), and to determine the extent of the efficacy of mpMRI as a screening test in biopsy-naïve patients. METHODS: Retrospective analysis was conducted in 107 patients who underwent mpMRI prior to radical prostatectomy (RP) at a single institution. The mpMRI findings were reassessed using PI-RADS, version 2. A comparison was made between the histological findings for the RP specimens and the mpMRI results. RESULTS: Unique histologically confirmed PCa foci (237) were identified in 107 patients. Overall, mpMRI sensitivity of 46% was found for PCa detection (110/237). The sensitivity, specificity and negative predictive value of mpMRI was 75.5%, 77.0% and 79.8%, respectively, for clinically significant cancer, and 75.7%, 77.7% and 79.5%, for pathological index tumors. A moderate and significant correlation was observed between a high PI-RADS score and a high pathological grade, tumor volume, index tumor status and clinically significant cancer status (all, P < 0.001, respectively). Pathological tumor volume was a significant predictor of PCa detection using mpMRI according to multivariate analysis. Using a cut-off value of 0.89 cc, the sensitivity and specificity of mpMRI for PCa detection were 0.87 and 0.65, respectively. CONCLUSION: The mpMRI, used in conjunction with PI-RADS, was useful in detecting PCa and in predicting tumor aggressiveness. However, the detection of 20% of clinically significant cancer was missed using mpMRI. Thus, its inclusion in a triage test should be limited to selected biopsy-naïve patients.

Effects of pre-applied orthodontic force on the regeneration of periodontal tissues in tooth replantation.

OBJECTIVE: This study aimed to investigate the effect of pre-applied orthodontic force on the regeneration of periodontal ligament (PDL) tissues and the underlying mechanisms in tooth replantation. METHODS: Orthodontic force (50 cN) was applied to the left maxillary first molars of 7-week-old male Sprague-Dawley rats (n = 32); the right maxillary first molars were left untreated to serve as the control group. After 7 days, the first molars on both sides were fully luxated and were immediately replanted in their original sockets. To verify the effects of the pre-applied orthodontic force, we assessed gene expression by using microarray analysis and real-time reverse transcription polymerase chain reaction (RT-PCR), cell proliferation by using proliferating cell nuclear antigen (PCNA) immunofluorescence staining, and morphological changes by using histological analysis. RESULTS: Application of orthodontic force for 7 days led to the proliferation of PDL tissues, as verified on microarray analysis and PCNA staining. Histological analysis after replantation revealed less root resorption, a better arrangement of PDL fibers, and earlier regeneration of periodontal tissues in the experimental group than in the control group. For the key genes involved in periodontal tissue remodeling, including CXCL2, CCL4, CCL7, MMP3, PCNA, OPG, and RUNX2, quantitative RT-PCR confirmed that messenger RNA levels were higher at 1 or 2 weeks in the experimental group. CONCLUSIONS: These results suggest that the application of orthodontic force prior to tooth replantation enhanced the proliferation and activities of PDL cells and may lead to higher success rates with fewer complications.