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Aberrant expression of serine/arginine-rich splicing factor 2 (SRSF2) can lead to tumorigenesis, but its molecular mechanism in colorectal cancer is currently unknown. Herein, we found SRSF2 to be highly expressed in human colorectal cancer (CRC) samples compared with normal tissues. Both in vitro and in vivo, SRSF2 significantly accelerated the proliferation of colon cancer cells. Using RNA-seq, we screened and identified 33 alternative splicing events regulated by SRSF2. Knockdown of SLMAP-L or CETN3-S splice isoform could suppress the growth of colon cancer cells, predicting their role in malignant proliferation of colon cancer cells. Mechanistically, the in vivo crosslinking immunoprecipitation assay demonstrated the direct binding of the RNA recognition motif of SRSF2 protein to SLMAP and CETN3 pre-mRNAs. SRSF2 activated the inclusion of SLMAP alternative exon 24 by binding to constitutive exon 25, while SRSF2 facilitated the exclusion of CETN3 alternative exon 5 by binding to neighboring exon 6. Knockdown of SRSF2, its splicing targets SLMAP-L, or CETN3-S caused colon cancer cells to arrest in G1 phase of the cell cycle. Rescue of SLMAP-L or CETN3-S splice isoform in SRSF2 knockdown colon cancer cells could effectively reverse the inhibition of cell proliferation by SRSF2 knockdown through mediating cell cycle progression. Importantly, the percentage of SLMAP exon 24 inclusion increased and CETN3 exon 5 inclusion decreased in CRC samples compared to paired normal samples. Collectively, our findings identify that SRSF2 dysregulates colorectal carcinoma proliferation at the molecular level of splicing regulation and reveal potential splicing targets in CRC patients., Competing Interests: Conflict of interest All the authors declare that they have no conflicts of interest with the contents of the article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Secretory carcinoma of the breast (SCB) is a rare low-grade often triple-negative breast carcinoma. We aim to analyze the pathological and molecular features of 21 SCBs, especially the SCBs with axillary lymph node metastasis., Methods: The clinicopathological characteristics of 21 SCBs were reviewed. Breast biomarkers, Pan-TRK and ETV6 break, and ETV6-NTRK3 fusion were performed on all cases. Next-Generation Sequencing (NGS) was performed on two cases with lymph node metastasis., Results: 21 SCBs consisted of 2 men and 19 women aged 5～73 years (median 43 years), with a mean 2.1 cm (range 0.5～3.5 cm) tumor size. 90.1% (19/21) cases had mixed microcystic, solid, tubular, and papillary patterns. Pan-TRK and S100 are positive in 95% (20/21) and 90% (19/21) of cases, respectively. Tumor markers ER, PR, and HER2 expressions were 62% (13/21), 33% (7/21), and 0% (0/21). All cases showed ETV6 (21/21) rearrangement and ETV6-NTRK3 (11/11) fusion. 57% (12/21) of the cases had a balanced translocation and 38% (8/21) with unbalanced signals of ETV6. There was no clinical difference between balanced and unbalanced translocations in histological morphology and other prognosis factors. Furthermore, one case (#4) had a duplication of the ETV6 gene and presented axillary lymph node metastasis. NGS analysis revealed simple genomes, low tumor mutation burden, stable microsatellite sites, and single nucleotide polymorphism (SNP) heterozygous mutation in both SCBs with nodal metastasis., Conclusion: SCB is an indolent invasive carcinoma, even the cases with axillary lymph node metastasis, presenting simple genomes. Duplication of ETV6 cases may indicate lymph node metastasis., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Importance: A higher incidence of pancreatic cancer has been reported in the Chinese population compared with the White population, but genetic differences are unknown to date. Large-sample germline testing for both familial and sporadic pancreatic cancers has been conducted predominantly in White populations, whereas similar studies in Chinese populations are limited., Objective: To assess the prevalence of germline sequence variations in patients with pancreatic diseases in China., Design, Setting, and Participants: This genetic association study was a case series that included genetic data from patients with pancreatic ductal adenocarcinoma (PDAC) or non-PDAC pancreatic diseases seen at The First Affiliated Hospital of Nanjing Medical University in Nanjing, China, between January 2006 and December 2017 (Nanjing cohort). Comparator group data were obtained for a US cohort from Johns Hopkins Hospital (JHH), a population from East Asia from the Exome Aggregation Consortium (ExAC) database, and the larger population from China from the ChinaMAP database. Data were updated and analyzed in July 2021., Main Outcomes and Measures: Next-generation sequencing technology was used to examine the prevalence of deleterious variations in 59 genes of the included Chinese patients with DNA extracted from peripheral blood samples. The Fisher exact test was used to assess differences among the frequencies of germline variations in the study patients vs the comparator groups., Results: A total of 1009 patients with PDAC (627 [62.1%] male; mean [SD] age, 62.8 [10.2] years) and 885 with non-PDAC diseases (477 [53.9%] male; mean [SD] age, 52.0 [15.9] years) from the Nanjing cohort were included for genetic analysis; all were Han Chinese individuals. Pathogenic variations were detected in 63 patients with PDAC (6.2%; 95% CI, 4.7%-7.7%). Variations in BRCA2 (odds ratio [OR], 3.2; 95% CI, 1.4-7.7; P = .008) and PALB2 (OR, 5.2; 95% CI, 1.6-17.0; P = .007) were significantly associated with pancreatic risk in the Nanjing cohort. Pathogenic variants of genes associated with homologous recombination DNA damage repair, including ATM, BRCA1/2, PALB2, BRIP1, FANCA, FANCC, RAD51D, and XRCC2, were found in 34 patients with PDAC (3.4%). No Ashkenazi Jewish-specific BRCA2 variation (p.Ser1982fs) was detected. The odds ratio of a SPINK1 variation in patients with PDAC was 3.2 (95% CI, 1.8-5.7; P < .001) in the Nanjing cohort compared with the ExAC cohort. Variations in the pancreatic secretory enzyme genes CPA1 and CPB1 were not detected in the Nanjing cohort., Conclusions and Relevance: In this genetic association study, sporadic pancreatic cancer was associated with pathogenic germline variations in a cohort from China. These findings provide insights into the genetic background of pancreatic cancer in the Han Chinese population with PDAC.

The aim of this study was to evaluate renal hemodynamics, routine clinical and laboratory parameters used to estimate renal function, and clinical evolution during six months in bitches with mammary carcinomas that underwent mastectomy and were treated (TG) or not (CG) with carprofen for three months after surgery. Twenty-six bitches with mammary carcinoma were equally distributed into TG that received carprofen 4.4 mg/kg/day for 90 days and CG that did not receive anti-inflammatory medication. Renal artery Doppler flowmetry, contrast-enhanced ultrasound (CEUS) of renal parenchyma, haematological, biochemical and clinical analyses were obtained once a month. These data were compared between groups and time via analysis of variance (ANOVA) in a completely randomized design with repeated measures (P < 0.05). On B-mode ultrasound, the area of the renal artery was greater (P = 0.0003) in the TG. Regarding laboratory findings, haematocrit and haemoglobin were similar in both groups, showing a significant and gradual increase after three months of treatment; MCV, MHC, and MCHC were increased (P < 0.05) and lymphocyte and band counts decreased (P < 0.05) in the TG. Regarding biochemical tests, ALT was the only parameter with a significant difference, being higher (P = 0.0272) in the treated group. It can be concluded that the use of carprofen for 90 days causes minimal changes in renal perfusion, erythrocyte parameters and ALT activity, and reduces the proportion of blood inflammatory cells. Therefore, use of this medication can be carried out safely in patients who require auxiliary cancer treatment., (© 2021. The Author(s).)

This retrospective study investigated the clinicopathological characteristics of secretory carcinoma of salivary glands (SCSG) in 23 patients with histopathologically confirmed SCSG between January 2010 and December 2020. In total, 13 males and 10 females (ratio, 1.3:1) aged 10 - 69 years (median, 45 years) were enrolled in this study; the average disease duration was 2.44 years (0.25-20 years). Twenty-one patients (91.3%) had SCSG in the parotid gland, and two (8.7%) in the submandibular gland. All patients had single nodules of diameters 0.8-4.8 cm (average 2.6 cm); five with lymph node metastases, and two with distant metastases. Immunohistochemically, tumors stained positive for S-100, mammaglobin, CK7, GATA3 and pan-Trk, and negative for DOG1, P63, and calponin, with Ki-67 positivity from 1 to 50%. ETV6 gene rearrangement was confirmed in 15 patients. All patients underwent oncological resection, four had radioactive particles implanted postoperatively, one received chemotherapy, and seven underwent chemoradiotherapy. Six patients had regional recurrences, two distant metastases, and one died before the last follow-up. SCSGs are typically indolent, with a low locoregional recurrence rate and excellent survival. Prognosis is correlated to clinical stage, pathological grade, and surgical procedures., (© 2021. The Author(s).)

Background: Gall bladder carcinoma (GBC) is a multi-factorial disease, involving multiple genetic alterations. The present pilot study aims to explore some of the molecular pathways, by studying immunohistochemical (IHC) expression of biomarkers (HER2/neu, KRAS, and VEGF) in GBC with their correlation with various clinicopathological parameters., Aim of the Study: To study the expression of prognostic biomarkers (HER2/neu, KRAS and VEGF-A) in GBC and their correlation with clinico-morphological parameters. Materials and., Methods: This prospective study was conducted over a period of 2 years. The study group included tissue of GBC (29) reported as malignant on histopathology and cholecystitis as a control group (29) for histopathological evaluation and IHC expression of above markers., Results: HER2/neu was expressed in 27.5% cases, and KRAS in 51.6%; however, both showed no association with tumor type, stage and grade. No association was found in KRAS expression and dysplasia. Vascular Endothelial Growth Factor - A (VEGF-A) was expressed in 86.1% cases, of which strong positivity was seen in 48.27%; it showed significant association with tumor stage (P value-0.027, Fishers' exact test), hence possibly suggesting its role in tumor progression; though no association was found in VEGF expression with tumor type and grade. No significant association was seen with vascular and tumor invasion also., Conclusion: The results suggest that the VEGF-A expression may be used as a potential prognostic biomarker in GBC.

Objective: To analyze the clinicopathological features of metastatic bone tumors over a period of two decades and identify the primary site of malignancy in metastasis of unknown origin., Materials and Methods: A total number of 365 cases were included in the study. The clinical features and location of the tumors were noted. The histopathological features of all the cases were studied. Immunohistochemistry (IHC) was done either to categorize or confirm the primary diagnosis using organ specific/organ restricted markers., Results: A total 712 bony sites were involved by metastasis in 365 patients, of which spine was the most commonly affected. Metastasis was the initial presentation in 69.5% patients. The primary site was known in 220 patients and almost half of them were detected after the diagnosis of metastasis. IHC was used as adjunct to suggest the possible origin in cases with unknown primary in 27.4%. Among the metastatic carcinoma, adenocarcinoma was the most common histological subtype with thyroid being the most frequent primary site of origin followed by lung and breast., Conclusion: More than two-third of cases in surgical pathology practice present as initial manifestations. Detection rate of primary depends on extent of metastatic work-up and IHC with organ specific/organ restricted markers to facilitate treatment with bone targeting agents.

Introduction: Pancreaticobiliary subtype of Periampullary carcinoma (PAC) has a poor prognosis in comparison to the intestinal subtype. We assessed the potential of cytokeratins and mucin markers to classify the sub-types of periampullary tumors and compared them with the survival data to identify markers that may predict prognosis., Methodology: PAC tumor tissues were obtained from 94 patients undergoing Whipples Pancreaticoduodenectomy. Paraffin-embedded tissues were immunostained with cytokeratins CK7, CK20), mucins (MUC1, MUC2, MUC5Ac), and CDX2 antibodies. The survival status of patients was obtained as follow-up up to 5-years of surgery. The Receiver Operating Character Curve (ROC) analysis was used for detecting sensitivity and specificity. The survival data were analyzed using the Kaplan-Meier survival curve., Results: Tumors were initially categorized on the basis of histological classification as pancreaticobiliary (n = 46), intestinal (n = 35) and indeterminate (n = 13). Further, using immunohistochemical markers (MUC1, CK20, and CDX2), we gave systematic classification of IHC-PB (n = 51), IHC-Int (n = 30) and IHC-Mixed (n = 13). The interobserver analysis showed good agreement between histologic and IHC type with a kappa value of 0.554. Combined expression of CK20, MUC1 and CDX2 accurately classify the mixed type of tumor. Overall survival rate and duration were 74.4% and 44.95 ± 2.29 months. Survival analysis for subtypes reveal, pancreaticobiliary tumors have low survival (27.9 ± 1.63 months) than mixed type (35.5 ± 0.45 months) and intestinal-type (52.92 ± 2.18 months). Among these, intestinal-type have better survival. Only TNM Stage III (tumor staging as per American Joint Committee on Cancer classification) and perineural invasion have been associated with predicting poor survival in PAC patients., Conclusion: Our results suggest that the combined expression of MUC1, CK20 and CDX2 could serve as markers to diagnose histological inconclusive specimens as mixed subtype tumors.

Objectives: To investigate the effect of surgical stabilization for patients with metastatic spinal disease on objective mobility metrics., Methods: A retrospective chart review identified patients who had mechanical back pain from metastatic spinal disease and underwent spinal stabilization during 2017. Mobility metrics, the Activity Measure for Post-Acute Care (AM-PAC) inpatient mobility short form (IMSF) and the Johns Hopkins Highest Level of Mobility (JH-HLM), were reviewed., Results: A total of 26 patients were included in the analysis with median hospital stay of 8 days. Preoperative JH-HLM scores were available for 17 patients with a mean score of 5.4, increasing to mean score of 6.6 at last follow-up (P = 0.036). Preoperative AM-PAC IMSF scores were available for 14 patients with a mean score of 19.4, decreasing slightly to a mean score of 18.7 at last follow-up (P = 0.367). Last follow-up with mobility metrics occurred a median of 6.5 days postoperatively (range: 3-66 days). Multivariable analysis showed that American Spinal Injury Association and Karnofsky Performance Status scores were significantly associated with both JH-HLM and AM-PAC mobility scores at last follow-up. A higher JH-HLM or AM-PAC score was significantly associated with direct home discharge and a higher AM-PAC score was associated with shorter hospital stay., Conclusions: Surgical stabilization for patients with mechanical back pain secondary to metastatic spinal disease might lead to an objective improvement in JH-HLM score. JH-HLM and AM-PAC scores may be correlated with length of hospital stay and discharge disposition. Future studies are encouraged to further characterize the role of these mobility metrics in the management plan of these patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Nova Circular RNA (circRNA) of non-coding RNA has gradually become an important regulatory factor, and it has made people attach great concern over the occurrence and development of many diseases, particularly carcinomas. circ&#95;RPPH1 is a newly discovered circRNA. Gene Expression Omnibus (GEO) analysis showed that there are high contents of circ&#95;RPPH1 in breast cancer (BC), but the mechanism of circRNA in BC remains unclear., Methods: Real-time quantitative PCR (qRT-PCR) was applied to test the role of circ&#95;RPPH1 in BC patients, and functional experiments were applied to test the role of circ&#95;RPPH1 on BC tumor. Fluorescence in situ hybridization, double luciferase reporter gene analysis, RNA pull-down and RNA immunoprecipitation experiments were performed to explore the correlation of circ&#95;RPPH1 with miR-146b-3p/E2F2 in BC., Results: circ&#95;RPPH1 was evidently enhanced in BC, and its content was related to the clinical stage and pathological grade. circ&#95;RPPH1 can accelerate the proliferation, migration and invasion, and promote tumorigenesis and metastasis. Mechanism exploration indicated that circ&#95;RPPH1 acted as ceRNA (competing endogenous RNA) of miR-146b-3p, so as to reduce the inhibitory role of miR-146b-3p on its target E2F2., Conclusion: Circ&#95;RPPH1/miR-146b-3p/E2F2 axis can promote the progression of BC, and it might be a latent therapeutic target for clinical BC.

Laryngeal carcinomas are the most common upper respiratory tract cancers and most commonly involve the glottic region. The aim of this study is to evaluate the voice quality after radiotherapy (RT) and microsurgical cordectomy (MC) treatments using Voice Handicap Index (VHI) and Grade, Roughness, Breathiness, Astenicity, and Strain (GRBAS) perceptual evaluation scale in patients with early-stage glottic carcinoma. A total of 37 patients with early-stage glottic carcinomas, 19 patients had RT and 18 patients with MC, were included in our study. The patients were evaluated in terms of their sound quality by using VHI-10 and GRBAS perceptual assessment scale 3 months after the treatment was completed. Although the findings were better in favor of RT according to GRBAS perceptual assessment scale of patients who received RT (n = 19) and MC (n = 18), no statistically significant difference was found between the 2 groups ( P = .613). Patients in both groups were evaluated with VHI-10, emotional ( P = .036) and physiological ( P = .038) scores were significantly higher in MC group and no significant difference was found in functional scores ( P = .192). However, there was no statistically significant difference between the 2 groups in terms of voice quality ( P = .185). In early-stage (Tis, T1a, T1b) glottic carcinoma, there was no significant difference between RT and MC in terms of voice quality. Therefore, the choice of treatment modality in patients with early-stage glottic carcinoma should be taken into account in terms of the patient's occupation, comorbid diseases, cost of treatment, hospital stay, and, most importantly, patient preference.

Serrated adenocarcinoma (SAC) and colorectal carcinomas showing histological and molecular features of high-level of microsatellite instability (hmMSI-H) are both end points of the serrated pathway of colorectal carcinogenesis. Despite common features (right-sided location, CpG island methylation phenotype and BRAF mutation) there are no studies comparing the microRNA (miRNA) expression profiles in SACs and hmMSI-H. The microtranscriptome from 12 SACs and 8 hmMSI-H were analysed using Affymetrix GeneChip miRNA 3.0 arrays and differentially enriched functions involving immune response were observed from this comparison. miR-181a-2* was found significantly more expressed in hmMSI-H than in SAC and higher expression of this miRNA in microsatellite unstable colorectal cancer were corroborated by Real-Time PCR in an extended series (61 SAC, 21 hmMSI-H). An analysis of genes possibly regulated by miR-181a-2* was carried out and, amongst these, an inverse correlation of NAMPT with miR-181a-2* expression was observed, whereas, for TRAF1 and SALL1, additional regulation mechanisms involving CpG island methylation were observed. miR-181a-2* is associated with particular histological and molecular features of colorectal carcinomas within the serrated pathological pathway and might play a role in the immune responses of microsatellite instability carcinomas., (© The Author(s) 2019. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Adrenocortical neoplasms are rare in childhood. Unlike their adult counterparts, they are often hormonally active and malignant. Despite being uncommon, adrenocortical neoplasms in children have significant associated morbidity and require complete surgical resection for effective management. Furthermore, the clinical overlap between adrenocortical neoplasms, adrenal medullary neoplasms, and functional disorders of the adrenal cortex requires that the practicing pediatric surgeon have a solid working knowledge of the presentation, diagnostic workup, and management of these anatomically related yet disparate pathologies., (Copyright © 2020. Published by Elsevier Inc.)

The aim of this prospective study was to analyze the voice and quality-of-life outcomes of microscopic diode laser surgery (MDLS). The study was conducted on a series of 46 patients with Tis-T1a glottic carcinoma treated with microscopic endolaryngeal diode laser surgery. Patients were asked to complete the Voice Handicap Index and quality-of-life questionnaires of the European Organization for Research and Treatment of Cancer. When comparing the pre- and postoperative scores, there were significant difference on the physical scores ( P = .014) of the patients who underwent type III cordectomy and functional ( P = .022), emotional ( P = .002), and overall scores ( P = .005) of the patients who underwent type IV cordectomy, in the direction of better quality of voice after MDLS. The postoperative functional, physical, emotional, and overall scores of groups were significantly increased with the extension of resection.

Surgery for esophageal cancer is associated with high morbidity and mortality. Reduced pulmonary functions and exercise capacity are known as risk factors for complications after esophagectomy. The 6-minute walk distance (6MWD) measured by the 6-minute walk test (6MWT) is a simple field test that can be used to evaluate the functional exercise capacity of patients who undergo thoracic surgery. The aim of this study was to evaluate the association of the preoperative 6MWD with postoperative complications in patients with esophageal cancer. Records of a total of 111 patients who underwent thoracic surgery followed by postoperative rehabilitation from January 2013 to December 2015 were retrospectively reviewed. Data of patients who experienced Clavien-Dindo grade II or severer (grade ≥ II) complications were compared with those who experienced grade ≤I complications. The 6MWD was significantly correlated with age, serum albumin concentration, hemoglobin concentration, and hand grip strength. A total of 42 patients experienced grade ≥II. The 6MWD of patients with grade ≥ II complications was significantly shorter than that of those with grade ≤I complications. In receiver operating characteristic analysis, 6MWD ≤ 454 m was a threshold for predicting grade ≥II complications with 71.0% sensitivity and 54.8% specificity. The incidence of grade ≥II complications led to delayed ambulation and longer stays in hospital. In the multiple regression analysis, the preoperative risk factors for incidence of grade ≥II complications included lower levels of preoperative 6MWD and % of the predicted value of forced expiratory volume in 1 second. Our results indicate that the 6MWT is useful to assess preoperative physical status in patients with esophageal cancer., (© The Author(s) 2019. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Median age at diagnosis of lung cancer is 70 years. Its presentation in patients 40 or younger is uncommon and it has been proposed that maybe it is a different disease due to its clinical characteristics and genetic makeup. There are a limited number of studies in this population and they report different clinic-pathological characteristics in comparison with older patients., Methods: We described the incidence of lung cancer patients diagnosed at age 40 or younger at the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima-Peru; from 2009 to 2017 and evaluated the characteristic of NSCLC. Epidemiologic and clinic-pathological data was collected from clinical files. Analysis was carried out using SPSSvs19 software., Results: We identified 3823 patients with lung cancer seen at INEN during the study period. Among these, 166 (4.3%) patients were 40 years or younger, and 137/166 (82.5%) were NSCLC. Median age at diagnosis was 36 years (range 14-40 years) and 59.1% of patients were female. A smoking history was present in 14.4% of patients. Frequent symptoms at diagnosis were cough (62.0%), chest pain (51.8%) and dyspnea (40.9%). Adenocarcinoma was the most common histological type (63.3%). Most patients had advanced disease at diagnosis (84.7%). The median overall survival was 8.2 months., Conclusions: The proportion of young patients with lung cancer in our population is higher than that reported in the most recent literature. Lung cancer in the young is mostly sporadic, more frequent in women, usually adenocarcinoma type and it presents with advanced disease, resulting in a very poor survival.

Background: Cervical cancer is the second-leading cause of cancer-related mortality in females. Coix lacryma-jobi L. var. ma-yuen (Rom.Caill.) Stapf ex Hook. f. is the most widely recognized medicinal herb for its remedial effects against inflammation, endocrine system dysfunctions, warts, chapped skin, rheumatism, and neuralgia and is also a nourishing food., Methods: To investigate the activity of Coix lacryma-jobi sprout extract (CLSE) on cell proliferation in human cervical cancer HeLa cells, we conducted a Cell Counting Kit-8 (CCK-8) assay. Flow-cytometric analysis and western blot analysis were performed to verify the effect of CLSE on the regulation of the cell cycle and apoptosis in HeLa cells., Results: We observed that CLSE significantly inhibited cell proliferation. Furthermore, CLSE dose-dependently promoted cell cycle arrest at the sub-G1/ S phase in HeLa cells, as detected by bromodeoxyuridine (BrdU) staining. The cell-cycle-arrest effects of CLSE in HeLa cells were associated with downregulation of cyclin D1 and cyclin-dependent kinases (CDKs) 2, 4, and 6. Moreover, CLSE induced apoptosis, as determined by flow-cytometric analysis and nuclear DNA fragmentation with Annexin V/propidium iodide (PI) and 4'6'-diamidino-2-phenylindole (DAPI) staining. Induction of apoptosis by CLSE was involved in inhibition of the antiapoptotic protein B-cell lymphoma 2 (Bcl-2) and upregulation of the apoptotic proteins p53, cleaved poly (ADP-ribose) polymerase (PARP), cleaved caspase-3, and cleaved caspase-8. Finally, we observed that CLSE inactivated the phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) pathways., Conclusions: CLSE causes cell cycle arrest and apoptotic cell death through inactivation of the PI3K/AKT pathway in HeLa cells, suggesting it is a viable therapeutic agent for cervical cancer owing to its anticancer effects.

MicroRNAs were known to play very important roles in human diseases, and have attracted great interests of research scientists in medicine, toxicology and functional foods. Gastric carcinoma (GC) remains one of the most common and lethal types of malignancy worldwide. However, the molecular mechanism of GC and the role of microRNAs in GC development remain unclear. The expression of extracellular matrix protein 1 (ECM1) is up-regulated in many cancer types, but its functional role is inconstant. In the present study, we aimed to investigate the correlation between GC development and ECM1 expression, along with its regulation by microRNAs. Immunohistochemical results showed that ECM1 was up-regulated in GC tissues and ECM1 expression level was negatively correlated with the prognosis of GC. ECM1 was found to promote gastric cancer cell metastasis in cell migration assays by facilitating the expression of proteins involved in epithelial-mesenchymal transition (EMT). MiR-92a was recognized for the first time to suppress the migration of human GC cells by directly targeting to the 3'UTR of ECM1 gene in a dual-luciferase reporter assay. These results highlighted the antagonistic roles of ECM1 and miR-92a in GC development, which may serve as a new target for gastric cancer., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

T-2 toxin is a major pollutant in crops and feedstuffs. Due to its high toxicity in a variety of organisms, T-2 toxin is of great concern as a threat to humans and to animal breeding. Overexpression of CYP1A1 may contribute to carcinogenesis, and CYP1A1 may be a promising target for the prevention and treatment of human malignancies. Therefore, it is essential to understand the regulatory mechanism by which T-2 toxin induces CYP1A1 expression in human cells. In this study, we confirmed that T-2 toxin (100 ng/mL) induced the expression of CYP1A1 in HepG2 cells through NRF1 and Sp1 bound to the promoter instead of through the well-recognized Aromatic hydrocarbon receptors (AhR). In cells treated with T-2 toxin, Sp1, but not NRF1, was significantly upregulated. However, T-2 toxin apparently promoted the interaction between NRF1 and Sp1 proteins, as revealed by IP analysis. Furthermore, in T-2 toxin-treated HepG2 cells, nuclear translocation of NRF1 was enhanced, while knockdown of Sp1 ablated NRF1 nuclear enrichment. Our results revealed that the upregulation of CYP1A1 by T-2 toxin in HepG2 cells depended on enhanced interaction between Sp1 and NRF1. This finding suggests the tumorigenic features of T-2 toxin might be related to the CYP1A1, which provides new insights to understand the toxicological effect of T-2 toxin., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Liver-X-receptor (LXR) agonists are known to bear anti-tumor activity. However, their efficacy is limited and additional insights regarding the underlying mechanism are necessary. By performing transcriptome analysis coupled with global polar metabolite screening, we show that LXR agonists, LXR623 and GW3965, enhance synergistically the anti-proliferative effect of BH3 mimetics in solid tumor malignancies, which is predominantly mediated by cell death with features of apoptosis and is rescued by exogenous cholesterol. Extracellular flux analysis and carbon tracing experiments (U- 13 C-glucose and U- 13 C-glutamine) reveal that within 5 h, activation of LXRβ results in reprogramming of tumor cell metabolism, leading to suppression of mitochondrial respiration, a phenomenon not observed in normal human astrocytes. LXR activation elicits a suppression of respiratory complexes at the protein level by reducing their stability. In turn, energy starvation drives an integrated stress response (ISR) that up-regulates pro-apoptotic Noxa in an ATF4-dependent manner. Cholesterol and nucleotides rescue from the ISR elicited by LXR agonists and from cell death induced by LXR agonists and BH3 mimetics. In conventional and patient-derived xenograft models of colon carcinoma, melanoma, and glioblastoma, the combination treatment of ABT263 and LXR agonists reduces tumor sizes significantly stronger than single treatments. Therefore, the combination treatment of LXR agonists and BH3 mimetics might be a viable efficacious treatment approach for solid malignancies., (© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)

Breast cancer (BC) is a complex and heterogeneous disease whose evolution depends on the tumor-host interaction. This type of cancer occurs when the mammary cells begin to grow wildly and become able to invade nearby tissues and/or promote metastases. Mouse mammary tumor virus (MMTV) is the accepted etiological agent of mammary tumors in mice. The identification of MMTV-like sequences and antigens in human mammary carcinoma has supported the theory that a virus homologous to MMTV (namely, HMTV) may be involved in human BC, but the role of retroviral elements in this disease remains elusive, as results from different research groups were contradictory. In the present review we present works for and against the involvement of HMTV in BC and discuss possible causes of divergences among studies. In the final section we fit current data regarding this issue to stablished causality criteria. We conclude that there is convincing data supporting the association of HMTV with BC, however there is still a need for epidemiological and basic research studies focusing on carcinogenic mechanisms for this virus in humans to fully understand its role in BC. This knowledge may open the way for the development of new preventive and therapeutic approaches in human BC., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Gallbladder carcinoma (GBC) is a rare pathology. We reviewed our hospital database for prognosticating the patients with post-cholecystectomy abdominal wall nodule. On reviewing the database we could find 7 patients who were diagnosed with GBC after simple cholecystectomy. Three of those patients were diagnosed after evaluation of a scar site nodule. Two patients were females and one patient was male. The mean age of the patients was 55 years. Two patients underwent laparoscopic cholecystectomy and one patient underwent open cholecystectomy. The average time of detection of malignancy was 10.6 months. The gallbladder was not subjected to histopathological examination in all three patients. The patients had the unresectable disease on restaging workup. Two patients had adenocarcinoma while one patient had a neuroendocrine tumor. abdominal wall nodule is a rare marker of occult gallbladder carcinoma. Subjecting every gallbladder specimen to histopathology should help in improving the survival in these patients.

Background: Pituitary carcinomas are rare and aggressive neoplasms that despite current treatment regimens continue to have a poor prognosis. Adrenocorticotrophic hormone pituitary tumors have been shown to alter their clinical manifestations with conversion to Cushing disease and silent types., Case Description: The purpose of this paper is to present the first documented case of an adrenocorticotrophic hormone-secreting pituitary adenoma with Cushing disease that differentiated into a silent corticotroph pituitary carcinoma with metastases to distant sites in the central nervous system., Conclusions: This patient was later treated with radiotherapy, temozolomide, and bevacizumab, with 8 years of progression-free survival., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) in distal common bile duct (CBD) is a rare entity., Case Report: This case report describes a 45-year-old male with a history of a choledochal cyst status post partial excision and cholecystectomy who presented with a mass in the remaining distal/intrapancreatic common bile duct. It was initially mistaken for post-surgery hematoma; however, the rapid growth raised concern for malignancy, and prompted a pancreaticoduodenectomy (Whipple) procedure. Macroscopic examination revealed a 5.5 cm polypoid mass grossly confined in the lumen of the distal CBD. Histology was consistent with UC-OGC, with minimal invasion into the polyp stalk and adjacent CBD wall. Immunohistochemistry demonstrated co-expression of CK7 and p40, normal/wild-type p53, and retained SMAD4 expression in tumor cells. Next-generation sequencing detected mutations at p.Q61H (c.183A>C) of KRAS and p.E545K (c.1633G>A) of PIK3CA, keeping in line with similarity to conventional cholangiocarcinoma. The patient remained disease-free after two years of follow-up without chemotherapy., Conclusion: To our knowledge, this is the first case report of UC-OGC presented as a polypoid mass in the distal CBD. It highlights the complex dynamism and controversial pathogenesis of this unique entity, which should be made aware to avoid diagnostic pitfalls., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Up to 20% of patients with pancreatic cancer have a family history of the disease. Familial pancreatic cancer is defined as at least two first-degree relatives with pancreatic cancer that occurs without being part of a cancer syndrome. Although this does not follow a specific Mendelian pattern of inheritance, research is underway to better understand this cohort of patients. Recent expert opinion/recommendations encourage physicians treating patients with pancreatic cancer to ask them to consider having germline testing. Herein, we summarize the current peer-reviewed literature on the most common syndromes associated with pancreatic cancer, associated genetic mutations, and recommendations from various consortia regarding screening strategies. Lastly, we describe the economic impact of pancreatic cancer and the impact of screening tools in high-risk populations.

Gastric cancer has reduced prevalence, but poor prognoses. To improve treatment, better knowledge of carcinogenesis and cells of origin should be sought. Stomach cancers are typically localized to one of the three mucosae; cardial, oxyntic and antral. Moreover, not only the stem cell, but the ECL cell may proliferate and give rise to tumours. According to Laurén, the classification of gastric carcinomas seems to reflect biological important differences and possible different cell of origin since the two subtypes, intestinal and diffuse, do not transform into the other and show different epidemiology. The stem cell probably gives rise to the intestinal type, whereas the ECL cell may be important in the diffuse type. Elevation of gastrin may be the carcinogenic factor for Helicobacter pylori as well as the recently described increased risk of gastric cancer due to proton pump inhibitor treatment. Therefore, it is essential to determine the role of the gastrin target cell, the ECL cell, in gastric carcinogenesis. Clinical trials with gastrin antagonists could improve prognoses in those with gastrin receptor positive tumours. However, further studies on gastric carcinomas applying relative available methods and with the highest sensitivity are warranted to improve our knowledge of gastric carcinogenesis.

Background: Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare tumors considered to be benign although 10% to 15% of SPNs have been reported to be aggressive. Due to its rarity, there have only been a few cases reported regarding the clinical course of patients with aggressive SPNs. The goal of this study is to describe the clinical course of patients diagnosed with aggressive SPNs., Methods: A PubMed search was done looking for articles describing the clinical course of patients diagnosed with SPN that locally invaded, recurred, or metastasized. Institutional experience was also added to the pooled data. Patient information was extracted from the articles. Survival and recurrence curves were plotted and factors associated with survival and recurrences were analyzed., Results: A total of 59 patients were identified to have aggressive SPN. Seven patients were males and 52 were females and the mean age was 37.44 ± 2.21 years. Systemic metastasis constituted 81.4% while recurrence and deep tissue invasion were found in 11.9% and 6.8% of the patients, respectively. Disease-free survival was 45 ± 6.28 months and disease-specific survival was 152.67 ± 12.8 months. In survival analysis, age, gender, tumor size, tumor location, combined resection, type of recurrence, and stage IV on diagnosis were not significant factors in predicting survival. However, an unresectable tumor (hazards ratio [HR] = 4.871, 95% confidence interval [CI] 1.480-16.03, P = .009), and metastasis within 36 months (HR = 6.399, 95% CI: 1.390-29.452, P = .017) were identified as independent variables in predicting survival., Conclusion: SPNs of the pancreas carry a favorable course. Despite having aggressive properties, patients can still survive for more than 10 years as long as the tumor can be resected completely.

The aim of this study was to evaluate hypoxia level at various tumor developmental stages and to compare various methods of hypoxia evaluation in pre-clinical CT26 tumor model. Using three methods of hypoxia determination, we evaluated hypoxia levels during CT26 tumor development in BALB/c mice from day 4 till day 19, in 2-3 days intervals. Molecular method was based on the analysis of selected genes expression related to hypoxia (HIF1A, ANGPTL4, TGFB1, VEGFA, ERBB3, CA9) or specific for inflammation in hypoxic sites (CCL2, CCL5) at various time points after CT26 cancer cells inoculation. Imaging methods of hypoxia evaluation included: positron-emission tomography (PET) imaging using [18F]fluoromisonidazole ([18F]FMISO) and a fluorescence microscope imaging of pimonidazole (PIMO)-positive tumor areas at various time points. Our results showed that tumor hypoxia at molecular level was relatively high at early stage of tumor development as reflected by initially high HIF1A and VEGFA expression levels and their subsequent decrease. However, imaging methods (both PET and fluorescence microscopy) showed that hypoxia increased till day 14 of tumor development. Additionally, necrotic regions dominated the tumor tissue at later stages of development, decreasing the number of hypoxic areas and completely eliminating normoxic regions (observed by PET). These results showed that molecular methods of hypoxia determination are more sensitive to show changes undergoing at cellular level, however in order to measure and visualize hypoxia in the whole organ, especially at later stages of tumor development, PET is the preferred tool. Furthermore we concluded, that during development of tumor, two peaks of hypoxia occur., Competing Interests: The authors have declared that no competing interests exist.

Uterine serous carcinoma (USC) is closely associated with advanced age in patients. The p53 signature (p53S) is considered the earliest indication for the presence of carcinogenesis of USC. Based on our previous studies, the presence of p53Ss have almost always been found in elderly women and are suspected of being responsible for the imbalance between the proliferation and apoptosis of endometrial epithelial cells with advanced age. We have summarized the current state of knowledge regarding the association between age and cancer and propose an age-related type of endometrial cancer instead of Type II estrogen-independent endometrial cancer.

The biosynthesis of endogenous androgenic anabolic steroids (EAAS) in males varies with age. Knowledge of the general urinary EAAS profile's dependence from aging - not reported up to now - may represents a prerequisite for its exploitation in the screening and diagnostic support for several pathologies. Extended urinary EAAS profiles were obtained from healthy and pathological individuals, using a GC-MS method which was fully validated by a stepwise, analyst-independent scheme. Seventeen EAAS and five of their concentration ratios were determined and investigated using multivariate statistical methods. A regression model based on Kernel partial least squares algorithm was built to correlate the chronological age of healthy male individuals with their "physiological age" as determined from their urinary EAAS profile. Strong correlation (R 2  = 0.75; slope = 0.747) and good prediction ability of the real chronological age was inferred from EAAS data. In contrast, patients with recent diagnosis (not pharmacologically treated) of prostatic carcinoma (PCa) exhibited a comprehensive EAAS profile with strong negative deviation from the model, corresponding a younger predicted age. This result is possibly related to the activation of anomalous steroid biosynthesis induced from PCa. Over a restricted 60-80 years-old population, PLS-discriminant analysis (DA) was used to distinguish healthy subjects from patients with untreated PCa. PLS-DA yielded excellent discrimination (sensitivity and specificity >90%) between healthy and pathological individuals. This proof-of-concept study provides a preliminary evaluation of multivariate DA on wide EAAS profiles as a screening method to distinguish PCa from non-pathological conditions, overcoming the potentially interfering effect of ageing., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Choroid plexus carcinoma (CPC) is a rare, malignant tumor occurring more commonly in children than adults. This case report describes the clinical course of a 3-year-old boy with a rare case of metastatic CPC with a novel TP53 mutation., Case Description: A 3-year-old boy presented with postconcussive symptoms after a fall. Computed tomography and magnetic resonance imaging revealed lesions in the suprasellar cistern, left lateral ventricle, and cauda equina. The tumor was diagnosed as choroid plexus carcinoma with a novel TP53 V216M somatic mutation. The patient underwent resection of the left lateral ventricle lesion., Conclusion: We describe a case of CPC with highly metastatic characteristics and a novel TP53 mutation. Our report implicates TP53 in the pathogenesis of pediatric CPC, and we emphasize that CPC in children should prompt careful consideration of TP53 status to inform prognosis and clinical treatment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Although PIWI-interacting RNAs (piRNAs) have recently been linked to human diseases, their roles and functions in malignancies remain unclear. This study aimed to investigate the significance of some piRNAs in colorectal cancer (CRC). Methods: We first analyzed the expression profile of piRNAs in CRC using the TCGA and GEO databases. The top 20 highly expressed piRNAs were selected and tested in our CRC tumor and non-tumor tissue samples. We then examined the relevance of the significantly differentially expressed piRNA to the CRC outcomes in 218 patients receiving postoperative chemotherapy and 317 patients receiving neoadjuvant chemotherapy. A series of biochemical and molecular biological assays were conducted to elucidate the functional mechanism of a piRNA of interest in CRC. Furthermore, experiments with mice xenografts were performed to evaluate the therapeutic effect of an inhibitor specific to the piRNA. Results: We found that among the examined 20 piRNAs, only piRNA-54265 was overexpressed in CRC compared with non-tumor tissues and higher levels in tumor or in serum were significantly associated with poor survival in patients. Functional assays demonstrated that piRNA-54265 binds PIWIL2 protein and this is necessary for the formation of PIWIL2/STAT3/phosphorylated-SRC (p-SRC) complex, which activates STAT3 signaling and promotes proliferation, metastasis and chemoresistance of CRC cells. Treatment with a piRNA-54265 inhibitor significantly suppressed the growth and metastasis of implanted tumors in mice. Conclusion: These results indicate that piRNA-54265 is an oncogenic RNA in CRC and thus might be a therapeutic target., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: We examined survival and time until recurrence of disease by multivariant analysis in patients treated for papillary thyroid carcinoma (PTC)., Patients and Methods: In the period from January 2003 to January 2018, we analyzed 102 patients with PTC in Public Health Institution-Hospital "Sveti Vracevi" in Bijeljina. Survival and time until recurrence of the disease were analyzed using patients' general data and factors based on preoperative, intraoperative and postoperative examinations. Many prognostic factors were analyzed together; the AGES prognostic score, consisting of age, grade, extent and size, and the AMES prognostic score, consisting of age, metastases, extent and size., Results: We analyzed 102 patients with PTC. Out of these 87 patients had AGES p.s ≤ 3.99 and 15 patients had AGES p.s> 4. The survival of patients was affected by the presence of distant metastases at the time of diagnosis p = 0.00109 and age p = 0.0436. Recurrence of the disease was recorded in 14 patients. Most patients had recurrence of the disease in the first 5 years after initial surgery. Analyzing the time until recurrence, we concluded that, statistically speaking, AGES p.s> 4 affect recurrence of the disease p = 0.0355 in a significant way, while distant metastases affect it in a very significant way (p = 0.008)., Conclusions: Prognostic factors of papillary thyroid carcinoma can be divided into 4 categories, patients' general data and factors based on preoperative, intraoperative and postoperative examinations.

Rationale: Carotid sinus hypersensitivity (CSH) is traditionally classified into 3 subgroups: cardioinhibitory, vasodepressor, and mixed subtypes. However, the underlying mechanism of CSH in head and neck cancer is controversial. Several pathological mechanisms of CSH have been proposed: atherosclerotic noncompliance, sternocleidomastoid proprioceptive denervation, and generalized autonomic dysfunction., Patient Concerns: We reported a 75-year-old man who had recurrent syncope attacks secondary to hypotension and reduced plasma norepinephrine (NE) levels. CSH was suspected when carotid massage induced syncope-like symptom., Diagnoses: Nasopharynx carcinoma with regional lymph node involvement and CSH., Interventions: On admission, dopamine was administered to maintain the blood pressure. When NE deficiency was confirmed, intravenous NE combined with oral midodrine replaced the dopamine treatment., Outcomes: The syncopal episodes completely resolved with periodic occurrence of hypertension., Lessons: Our case suggests a potential role of carotid sinus in regulating the release of NE in adrenal gland and that the monitoring of catecholamine level is recommended in the CSH cases either from head and neck tumors or other mechanical manipulation of carotid sinus.

Rationale: Primary malignant mixed mullerian tumors of the fallopian tube is very rare and has only 1 case in the current literature with cervix metastasis., Patient Concerns: We reported a 49-year-old woman sufferring from primary malignant mixed mullerian tumors of the fallopian tube with cervix metastasis, and the imaging examination found a strip of solid mass in the right fallopian tube and a nodular mass in cervical canal, which were both hyperintense on T2 weighted image (T2WI) and diffusion weighted image (DWI) and continuous moderate enhancement on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)., Diagnoses: The diagnosis was confirmed according to the specific anatomical location and pathological examination which was proved as primary malignant mixed mullerian tumors of the fallopian tube with cervix metastasis., Interventions: The patient underwent radical hysterctomy, bilateral adnexectomy, pelvic lymph node dissection, omentum majus excision and intravenous chemotherapy., Outcomes: Her posttreatment condition was good., Lessons: Primary malignant mixed mullerian tumors of the fallopian tube can be located by magnetic resonance image examination, which may also offer several diagnostic tips according to changes in signal and enhancement. When combined with pathological findings, qualitative diagnosis can be determined. Surgery and adjuvant chemotherapy are considered as effective methods. Our paper discussed its epidemiology, clinical symptoms, pathologic characters, therapeutic method as well as magnetic resonance imaging findings suggesting the diagnosis and differential diagnosis, including precontrast scan, contrast scan and diffusion weighted image and provided magnetic resonance imaging characteristics of primary malignant mixed mullerian tumors of the fallopian tube described in other literatures.

Background: The aim was to compare health-related quality-of-life (HRQOL) and cost-effectiveness between cytoreductive surgery with intraperitoneal chemotherapy (CRS + IPC) and systemic chemotherapy for patients with colorectal peritoneal metastases., Methods: Patients included in the Swedish Peritoneal Trial comparing CRS + IPC and systemic chemotherapy completed the EORTC QLQ-C30 and SF-36 questionnaires at baseline, 2, 4, 6, 12, 18, and 24 months. HRQOL at 24 months was the primary endpoint. EORTC sum score, SF-36 physical and mental component scores at 24 months were calculated and compared for each arm and then referenced against general population values. Two quality-adjusted life-year (QALY) indices were applied (EORTC-8D and SF-6D) and an incremental cost-effectiveness ratio (ICER) per QALY gained was calculated. A projected life-time ICER per QALY gained was calculated using predicted survival according to Swedish population statistics., Results: No statistical differences in HRQOL between the arms were noted at 24 months. Descriptively, survivors in the surgery arm had higher summary scores than the general population at 24 months, whereas survivors in the chemotherapy arm had lower scores. The projected life-time QALY benefit was 3.8 QALYs in favor of the surgery arm (p=0.06) with an ICER per QALY gained at 310,000 SEK (EORTC-8D) or 362,000 SEK (SF-6D) corresponding to 26,700-31,200 GBP., Conclusion: The HRQOL in patients with colorectal peritoneal metastases undergoing CRS + IPC appear similar to those receiving systemic chemotherapy. Two-year survivors in the CRS + IPC arm have comparable HRQOL to a general population reference. The treatment is cost-effective according to NICE guidelines., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Rationale: Myelodysplastic syndrome (MDS) is a heterogeneous malignant hematologic disease with median overall survival ranging from six months to more than ten years. Solid tumor rarely occurs in combination with MDS and the underlying pathogenesis and prognostic significance still remain controversial., Patient Concerns: Here we report a relative low risk myelodysplastic syndrome-refractory cytopenia with multilineage dysplasia (MDS-RCMD) patient, with a rare t(1; 19)chromosome translocation. This patient also suffered from gastric carcinoma., Diagnoses: Gastric carcinoma, Myelodysplastic syndrome with t (1; 19) chromosome translocation., Interventions: This patient received radical operation for gastric carcinoma and erythropoietin infusion., Outcomes: The patient took follow up visits every 2 to 3 months in past years and now he is in stable disease without further treatment., Lessons: We reviewed the mechanism of MDS complicated by solid tumor and concluded the potential mechanisms of this patient. The interactions between potential factors may play a role in oncogenesis which, however, need an in-depth study of its operating mechanism.

Rationale: Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland carcinoma that histologically resembles in situ and invasive ductal carcinoma of the breast. We present the first case of advanced SDC of the minor salivary gland arising from the supraglottis and review the literature on the clinicopathologic characteristics and prognosis of SDC., Patient Concerns: A 59-year-old male patient with progressive difficulty in swallowing and a muffled voice for 2 months., Diagnoses: The patient was diagnosed with SDC arising from the supraglottis with extensive tumor invasion into the subsites of the larynx and pharynx., Interventions: Due to impending airway obstruction, the patient underwent CO2 laser debulking surgery. In addition to local disease, lymph node and distant metastases were also noted at diagnosis and concurrent chemoradiation therapy was arranged., Outcomes: Laryngeal function was preserved and tracheostomy was avoided. The patient has survived for >1 year after the initial diagnosis., Lessons: SDC is a rare and aggressive subtype of salivary gland carcinoma that histologically resembles in situ and invasive ductal carcinoma of the breast. Here we presented the first case of advanced SDC of the minor salivary gland arising from the supraglottis that was treated with CO2 laser debulking surgery followed by concurrent chemoradiation therapy. Due to their rarity, further studies are required to establish the most effective treatment protocol for advanced SDC.

Differentiating between malignant phyllodes tumors and metaplastic spindle cell carcinomas could be problematic, especially on core biopsies. Immunohistochemical staining for cytokeratin cocktail and p63 has been utilized to differentiate between these tumor types. Forty-three phyllodes tumors (27 benign, 6 borderline, and 10 malignant) and 22 metaplastic carcinomas, consisting at least 80% of spindle cells, were identified. At least 4 tissue blocks from each phyllodes tumor were subjected to immunohistochemical staining for cytokeratin cocktail and p63. The immunohistochemical profiles for the spindle cells in metaplastic carcinoma were reviewed. Phyllodes tumor was diagnosed in the younger age group (mean age 41 y) with a larger tumor size (mean size 6.6 cm), compared with metaplastic spindle cell carcinoma (mean age 62.7 y, mean size 3.4 cm). Focal expression (5% of the tumor cells) of cytokeratin cocktail and p63 was identified in the stroma of 2 of 10 malignant phyllodes tumors in a scattered/patchy pattern. The stroma of benign and borderline phyllodes tumors was negative for these markers. In metaplastic spindle cell carcinomas, cytokeratin cocktail was negative in 2 of 15 cases and very focally positive in another 3 cases, whereas p63 was negative in one case and focally positive in another case. There can be anomalous, focal expression of cytokeratin and p63 in the stroma of malignant phyllodes tumors, whereas metaplastic spindle cell carcinoma can occasionally have cytokeratin and/or p63-negative staining or have very focal positivity. Caution should be exercised when relying on these markers for confirming a diagnosis, especially on core biopsies.

Endometrium cancer is the most common invasive gynecologic malignancy in developed countries. Succinic acid (CO2HCH2-CH2CO2H) is a type of dibasic acid that has uncolored crystal. Succinic acid is used in bakery products and aromatized products. It is naturally found in some vegetables. Succinic acid has no adverse effects because it is metabolized by body cells and has a role in the tricarboxylic acid cycle (TCA) as a cycle media component. The TCA cycle and its enzyme components have some crucial roles for basal cell metabolism. Any mistakes, concentration differences in product, or enzyme deficiencies are important within the cell this cycle. In this proposal project, we aimed to investigate the effect of succinic acid at different doses and at different times in an endometrial cancer cell line. The study was performed using methods that determine for apoptosis (for cytotoxicity, WST-1, for caspase enzyme activity, Caspase 3/BCA; apoptotic determination using flow cytometry; Annexin V; to understand mitochondrial membrane potential; JC-1). The results showed that 5 and 10 µM concentration of succinic acid resulted in apoptosis in endometrium cancer; no such effect was seen in the control cell line, which comprised healthy lung cells.  According to our results, it is thought that succinic acid would be effective for the treatment of endometrial cancer cell lines, thus providing new data for other areas of cancer research.

Background: The available studies concerning the influence of age on the phenotypical expression of differentiated thyroid carcinoma (DTC) have hitherto compared DTC presentation either between pre-pubertal and pubertal children or between pediatric patients and aged adults; aim of this study was to ascertain for the first time whether presentation of DTC may significantly vary according to age, even within a peculiar study population covering only young patients aged less than 30 years., Methods: The main clinical, biochemical and pathologic data at DTC diagnosis were retrospectively recorded in 2 selected cohorts including, respectively, 18 children and adolescents aged less than 18 years (Group A) or 45 young adults aged between 20 and 29.8 years (Group B)., Results: The statistical distribution of DTC cases in the different age ranges was found to progressively increase with increasing age; furthermore, the patients of Group A exhibited at diagnosis a more severe clinical involvement and a higher rate of extra-regional metastases; finally, also the association with both autoimmune thyroid diseases (AITDs) and a biochemical hypothyroid pattern was more common in Group A patients., Conclusions: In a study population younger than 30 years: a) the risk of developing DTC increases with age, achieving its zenith during the 3rd decade of life; b) clinical presentation is more severe in children and adolescents younger than 18 years than in the patients aged between 20 and 30; c) in the cohort of children and adolescents DTC is more often associated with AITDs, which might play some role in conditioning the more aggressive phenotypical presentation of DTC in this patient group.

Radiation therapy, a major method of treatment for brain cancer, may cause severe brain injuries after many years. We used a rare and unique cohort of nasopharyngeal carcinoma patients with normal-appearing brains to study possible early irradiation injury in its presymptomatic phase before severe, irreversible necrosis happens. The aim is to detect any structural or functional imaging biomarker that is sensitive to early irradiation injury, and to understand the recovery and progression of irradiation injury that can shed light on outcome prediction for early clinical intervention. We found an acute increase in local brain activity that is followed by extensive reductions in such activity in the temporal lobe and significant loss of functional connectivity in a distributed, large-scale, high-level cognitive function-related brain network. Intriguingly, these radiosensitive functional alterations were found to be fully or partially recoverable. In contrast, progressive late disruptions to the integrity of the related far-end white matter structure began to be significant after one year. Importantly, early increased local brain functional activity was predictive of severe later temporal lobe necrosis. Based on these findings, we proposed a dynamic, multifactorial model for radiation injury and another preventive model for timely clinical intervention. Hum Brain Mapp 39:407-427, 2018. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Laryngeal carcinoma (LC) is one of the most prevalent malignant tumors in the head and neck area. Due to its high morbidity and mortality, LC poses a serious threat to human life and health. Even with surgical removal, some patients were not sensitive to radiotherapy or experienced transfer or recurrence. 20(s)-Protopanaxadiol (PPD), a natural product from Panax ginseng, has been reported to have cytotoxic effects against several cancer cell lines. However, whether it can improve the radiation sensitivity and the underlying mechanism of PPD's sensitization effect is still unknown. Herein, from in vitro and in vivo experiments, we found that the combination of PPD and radiation not only significantly inhibited proliferation and induced apoptosis, but also suppressed the tumor growth in mouse models. These findings confirmed the role of PPD in enhancing the sensitivity of radiotherapy. Moreover, our work showed that the expression levels of mTOR and its downstream effectors decreased remarkably after PPD addition when compared to radiation only. This result suggested that PPD's excellent synergistic effects with radiation might be associated with the down-regulation of the mTOR signaling pathway in Hep-2 cells.

Skin fibroblasts and tumor fibroblasts were extracted from a 64-year old male patient clinically diagnosed with laryngeal carcinoma. Control and tumor specific induced pluripotent stem cells were reprogrammed with 5 reprogramming factors, Klf-4, c-Myc, Oct-4, Sox-2, and Lin-28, using the messenger RNA reprogramming system. The transgene-free iPSC lines showed pluripotency, confirmed by immunofluorescence staining. The iPSC lines also showed normal karyotype, and could form embryoid bodies in vitro and differentiate into the 3 germ layers in vivo. This in vitro cellular model can be used to study the oncogenesis and pathogenesis of laryngeal carcinoma., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: C-reactive protein (CRP) has been shown to be associated with several tumors. However, its association with nasopharyngeal carcinoma (NPC) is not well characterized. We performed a literature review and meta-analysis to assess the prognostic relevance of elevated CRP levels in patients with NPC., Methods: A literature search for relevant studies was performed on PubMed (Medline), the Cochrane Library, and Web of Science databases. Hazard ratios (95% confidence intervals) were calculated to assess the association between elevated CRP levels and survival outcomes., Results: Five studies with a combined study population of 5215 patients with NPC were included. Pooled hazard ratios for overall survival and distant metastasis-free survival were 1.84 (95% CI = 1.57-2.17) and 1.81 (95% CI = 1.53-2.14), respectively. Subgroup analyses showed that types of indicators and treatment before inclusion had no significant impact on the observed association., Conclusion: Elevated serum CRP levels in patients with NPC were associated with worse prognosis.

The worst complication of cancer is represented by its spread to distant sites. In particular, bone provides a fertile soil for several cancer types, especially those derived from breast, prostate and lung tumours. Despite the progress in diagnostic and therapeutic strategies, bone metastases (BM) still impact on quality of life and overall survival, making it necessary to identify the "high-risk" patients at an earlier stage. Since BM affect physiological bone turnover, measurement of bone turnover markers (BTM) has been widely investigated for diagnostic and prognostic purposes, as well as to support the development of anti-cancer drugs. Furthermore, biomarkers are still under intensive investigation for their potential BM predictive role. The review summarises the current knowledge on BM development and the most recent advances in biomarker research, focusing on breast, prostate and lung malignancies., (© 2017 John Wiley & Sons Ltd.)

Human papillomaviruses (HPVs) infect the cutaneous or mucosal epithelia and are classified phylogenetically as genera and species. Persistent infections by the mucosal high-risk (HR) HPV types from genus alpha are associated with cancer development of the genital and upper respiratory tracts. The products of two early genes, E6 and E7, are the major HR HPV oncoproteins, being essential in all steps of the carcinogenic process. Cutaneous beta HPV types are proposed, together with ultraviolet (UV) radiation, to promote non-melanoma skin cancer development. However, in contrast to the HR HPV types, beta HPV types appear to be required only at an early stage of carcinogenesis, facilitating the accumulation of UV-induced DNA mutations. Although findings in experimental models also suggest that beta HPV types and other carcinogens may synergize in the induction of malignancies, these possibilities need to be confirmed in human studies., (Copyright © 2017 Elsevier B.V. All rights reserved.)