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The aims of this study were to explore the involvement of Aurora kinase A (AURKA) gene single nucleotide polymorphisms (SNPs) in uterine cervical cancer that has not yet been investigated. One hundred and six patients with cervical invasive cancer and 94 patients with precancerous lesions, and 302 Taiwanese female individuals were included. AURKA SNPs rs2273535, rs6024836, rs2064863 and rs1047972 were analyzed for genotypic distributions using real-time polymerase chain reaction. There were no statistically significant differences in the genetic frequencies of AURKA SNPs among patients with invasive cancer and those with precancerous lesions of uterine cervix and control women. There were no associations among AURKA SNPs and clinicopathologcal variables and recurrence and survival events. However, in a multivariate analysis, cervical cancer patients with adenocarcinoma (HR: 3.18, 95% CI: 1.23-8.23; p=0.017) and larger tumor (HR: 5.61, 95% CI: 2.10-14.95; p=0.001) had poorer recurrence-free survival. In conclusion, tumor size and pelvic lymph node status rather than AURKA SNPs were the most obvious independent parameter that could significantly predict 5 years survival rate in Taiwanese women with cervical cancer.

Background: Tumor mutation burden (TMB) was correlated with the immunotherapeutic response in various malignancies. We aimed to evaluate the TMB immune signature in colon adenocarcinoma (COAD). Methods: Gene expression profile, mutation and clinical data of COAD patients were obtained from The Cancer Genome Atlas (TCGA) database. The samples were divided into high and low TMB level groups to identify differentially expressed genes (DEGs). Functional enrichments analyzes were performed to identify the biological functions of the DEGs. Then, immune cell infiltration signatures were calculated by the CIBERSORT algorithm. Finally, Cox proportional hazard model was constructed to estimate the prognostic value of the identified immune-related genes. Results: Gene set enrichment analysis in the high-TMB level group showed that DEGS were enriched in immune-related pathways, such as antigen processing and presentation, Toll-like receptor signaling and natural killer cell-mediated cytotoxicity. A higher infiltration level of CD8+ T cells, CD4+ T cells, activated NK cells , M1 Macrophages and T follicular helper cells was observed in the high-TMB level group. Furthermore, a Cox regression model combined with survival analysis based on the expression level of four identified prognostic genes was constructed, validated anf revealed that higher risk-score levels conferred poor survival outcomes in COAD patients. Conclusions: Our data demonstrate that the high TMB levels are associated with an immune signature in COAD and deepen the molecular understanding of TMB function in tumor immunotherapy.

CD151 impacts various signaling pathways in different cancers, and promotes colorectal cancer (CRC) cell malignancy by yet undefined mechanisms. This study aimed to comprehensively assess CD151's function in CRC. CD151 levels were significantly higher in CRC tissues and cells compared with controls in the tissue microarray. Cell viability, migration and invasion were suppressed by CD151 downregulation in CRC cells. Consistently, mouse xenografts were inhibited by CD151 silencing. RNA-seq revealed that multiple genes were significantly altered by CD151 knockdown in cultured CRC cells and xenografts. Particularly, transforming growth factor β1 (TGFβ1), carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) alongside CD151 were downregulated both in vitro and in vivo. Co-immunoprecipitation and mass spectrometry results were validated by qRT-PCR and immunoblot. Moreover, pull-down assay and immunofluorescence confirmed the associations of TGFβ1, CEACAM6 and LGR5 with CD151. This study demonstrated CEACAM6, LGR5 and Wnt pathway suppression by CD151 silencing might occur through TGFβ1 regulation, offering a comprehensive view of CD151's roles in colorectal carcinogenesis. Our findings provide an insight into the CD151-involved signaling network in CRC oncogenesis, which could be utilized to design novel targeted therapies against CD151-based signaling in treatment for CRC.

Lung adenocarcinoma (LUAD) is the predominant subtype of lung cancer with a relatively poor prognosis. The dramatic improvements of new immunotherapy strategies have shown promising results in lung cancer patients. This study aimed to elucidate the functions of immune-associated genes in LUAD prognosis and pathogenesis by analyzing public databases. We obtained expression profiles of LUAD patients from The Cancer Genome Atlas (TCGA) database and applied the ESTIMATE algorithm to calculate immune scores and stromal scores. A series of microenvironment-related genes with prognostic value was then identified. Of note, heat shock factor 5 (HSF5) was found to be decreased in LUAD patients and positively correlated with overall survival, which was further confirmed in the Gene Expression Omnibus (GEO) database. Moreover, Gene Ontology (GO) analysis based on the correlated genes of HSF5 demonstrated that HSF5 expression was significantly associated with the immune response and inflammatory activities. Based on the Tumor IMmune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) datasets, HSF5 expression showed strong correlations with various immune cell infiltration and diverse immune marker sets. These findings suggest that HSF5 can be used as a promising biomarker for determining prognosis and immune infiltration in LUAD patients.

Rationale: Accumulating evidence indicates that long noncoding RNAs (lncRNAs) play crucial roles in cancer progression; however, only few have been characterized in detail. The current study aimed to identify a novel cancer driver lncRNA in glioblastoma and colon adenocarcinoma. Methods: We performed whole transcriptome analysis of TCGA pan-cancer datasets to compare the lncRNA expression profiles of tumor and paired normal tissues. In situ hybridization of tissue sections was performed to validate the expression data and determine the localization of lncRNAs that may be linked to glioblastoma and colon adenocarcinoma. Chromatin isolation by RNA purification (ChIRP), chromatin immunoprecipitation (ChIP), and Co-immunoprecipitation (Co-IP) assays were performed to assess the interaction between lncRNA, proteins, and chromatin. The functional significance of the identified lncRNAs was verified in vitro and in vivo by knockdown or exogenous expression experiments. Results: We found a lncRNA ENST00000449248.1 termed PRC2 and DDX5 associated lncRNA (PRADX) that is highly expressed in glioblastoma and colon adenocarcinoma cells and tissues. PRADX, mainly located in the nucleus of tumor cells, could bind to EZH2 protein via the 5' terminal sequence. Moreover, PRADX increased the trimethylation of H3K27 in the UBXN1 gene promoter via PRC2/DDX5 complex recruitment and promoted NF-κB activity through UBXN1 suppression. Knockdown of PRADX significantly inhibited tumor cell viability and clonogenic growth in vitro. In xenograft models, PRADX knockdown suppressed tumor growth and tumorigenesis and prolonged the survival of tumor-bearing mice. Conclusions: PRADX acts as a cancer driver and may serve as a potential therapeutic target for glioblastoma and colon adenocarcinoma.

Background: Acyl-CoA dehydrogenase short-chain (ACADS) is a crucial enzyme in the fatty acid metabolism pathway located in mitochondria. However, the expression level and prognostic value of ACADS in colorectal cancer (CRC) remain unclear. Methods: The mRNA and protein expression data of ACADS was obtained from The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Oncomine. Prognostic values of ACADS were calculated using Kaplan-Meier survival analysis. Correlations between ACADS and immune infiltration were estimated using TIMER, CIBERSORT, EPIC, quanTIseq, and xCell. The UALCAN and MEXPRESS databases were utilized for Methylation analysis. The co-expression analysis based on mRNA expression and interaction network of ACADS were performed via several online tools. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on ACADS co-expressed genes were performed using the Metascape. Results: The expression analysis demonstrated that ACADS was down-regulated in CRC tissues compared with paired normal tissue. Expression of ACADS was found to be significantly associated with clinical cancer stages and the consensus molecular subgroups (CMS) constituent ratio in CRC patients. Besides, lower ACADS expression was found to predict poor prognosis and be significantly associated with common immune checkpoint genes and MMR genes in CRC. ACADS expression levels were positively related to B cells, CD4+ T cells, CD8+ T cells, M1 macrophages, neutrophils, and Tregs, while negatively correlated with M0 macrophages, M2 macrophages. The methylation level of ACADS in normal tissues was significantly higher than that in tumor tissues, and several methylation sites were identified. The enrichment analysis suggested the co-expressed genes mainly enriched in cell mitochondrial metabolism. Conclusions: The present study provided multilevel evidences for expression of ACADS in CRC and the function of ACADS in prognostic prediction, immune infiltration, and methylation. ACADS might have the potential as the novel biomarker and therapeutic target in CRC patients.

Background and aim: The molecular signatures of lung adenocarcinoma (LUAD) are not well understood. Centromere protein F (CENPF) has been shown to promote oncogenesis in many cancers; however, its role in LUAD has not been illustrated. We explored the role of CENPF in LUAD. Methods: CENPF expression level was investigated in public online database firstly, the prognosis of CENPF in LUAD were also assessed by Kaplan-Meier analysis. Then quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed using 13 matched pairs of clinical LUAD tissue samples. Subsequently, the impact of CENPF expression on cell proliferation, cell cycle, apoptosis, colony formation was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometric analysis and colony formation assay, respectively. Finally, experimental xenograft lung cancer model of nude mice armpit of right forelimb to determine the effect of CENPF on LUAD tumorigenesis. Results: CENPF mRNA expression was significantly elevated in LUAD tissues compared with adjacent non-tumor lung tissues in Gene Expression Profiling Interactive Analysis (GEPIA) (P < 0.001). Up-regulated CENPF was remarkably positively associated with pathological stage, relapse free survival (RFS) as well as overall survival (OS) of LUAD patients. Besides, CENPF knockdown greatly suppressed A549 cell proliferation, induced S phase arrest, promoted apoptosis and decreased colony numbers of LUAD cells. Furthermore, knockdown of CENPF significantly inhibited the tumor growth of the LUAD cells in an experimental xenograft lung cancer model of nude mice armpit of right forelimb. Conclusion: Taken together, these results demonstrated that CENPF may serve as a potential biomarker of prognostic relevance and a potential therapeutic target for LUAD.

Lung adenocarcinoma (LUAD) is a common type of lung cancer with high frequent metastasis and a high death rate. However, genes responsible for LUAD metastasis are still largely unknown. Here, we identify an important role of ras homolog family member V (RHOV) in LUAD metastasis using a combination of bioinformatic analysis and functional experiments. Bioinformatic analysis shows five hub LUAD metastasis driver genes (RHOV, ZIC5, CYP4B1, GPR18 and TCP10L2), among which RHOV is the most significant gene associated with LUAD metastasis. High RHOV expression predicted shorter overall survival in LUAD patients. RHOV overexpression promotes proliferation, migration, and invasion of LUAD cells, whereas RHOV knockdown inhibits these biological behaviors. Moreover, knockdown of RHOV suppresses LUAD tumor growth and metastasis in nude mice. Mechanistically, RHOV activates Jun N-terminal Kinase (JNK)/c-Jun signalling pathway, an important pathway in lung cancer development and progression, and regulates the expression of markers of epithelial-to-mesenchymal transition, a process involved in cancer cell migration, invasion and metastasis. RHOV-induced malignant biological behaviors are inhibited by pyrazolanthrone, a JNK inhibitor. Our findings indicate a critical role of RHOV in LUAD metastasis and may provide a biomarker for prognostic prediction and a target for LUAD therapy.

Background: Teashirt homolog 2 (TSHZ2) is essential for maintaining cellular homeostasis and regulating transcription on neoplasia development. However, the regulation of TSHZ2 in lung tumorigenesis and the underlying mechanisms remain unclear. Objective: To evaluate the relationship between TSHZ2 expression in patients' tumor tissue and prognosis in lung adenocarcinoma. Methods: TSHZ2 expression in different lung adenocarcinoma cell lines and human tissue were detected by Western blotting. The effect of TSHZ2 on cell proliferation, apoptosis and migration in lung adenocarcinoma cells was measured by CCK8, colony formation, flowcytometric analyses and wound-healing, respectively. TSHZ2 expression in different lung adenocarcinoma cell lines and human tissue from patients was detected using Western blotting and immunohistochemical staining. We also retrospectively analyzed 226 lung adenocarcinoma patients after surgical resection using immunohistochemical staining, and the association of TSHZ2 expression with the patient survival was evaluated. Results: TSHZ2 was lowly expressed in certain lung adenocarcinoma cell lines (PC9 and B203L), but other cells showed a high expression. Low expression of TSHZ2 was also observed in most lung adenocarcinoma tissues compared with adjacent tissues. Furthermore, we found that the overexpression of TSHZ2 plasmids led to the dramatic inhibition of cell proliferation, colony formation ability, migration and apoptosis induction in PC9 lung adenocarcinoma cells. In contrast, no obvious effect was found when the TSHZ2 expression was down-regulated by si-TSHZ2. An elevated TSHZ2 expression was observed in 155(68.6%) tumor tissues samples of lung adenocarcinoma patients. Notably, the lung adenocarcinoma patients with a high TSHZ2 expression tended to have EGFR mutations less frequently and a preferable prognosis to those with a lower expression. Conclusion: A high TSHZ2 expression inhabited cell proliferation and predicted a better prognosis of lung adenocarcinoma, possibly representing a useful therapeutic target for lung adenocarcinoma.

This study is a subset analysis of a retrospective multicenter study performed in Japan and its purpose was to investigate the effectiveness of stereotactic body radiotherapy (SBRT) for pulmonary oligometastases from colorectal cancer. Local control (LC), freedom from further metastases, relapse-free survival and overall survival (OS) after SBRT were retrospectively analyzed. The Kaplan–Meier method was used to estimate lifetime data and the log-rank test was performed as univariate analyses. The Cox proportional hazards model was applied in multivariate analyses. Data for 330 patients with 371 tumors were used for analyses. The median follow-up period was 25.0 months. The 3-year LC, freedom from further metastases, relapse-free survival and OS rates were 64.9, 34.9, 24.9 and 63.4%, respectively. The results of multivariate analyses showed that a higher LC rate was associated with no history of local therapy for oligometastases (P = 0.01), SBRT without concurrent chemotherapy (P

Smoking accounts for almost 80–90% of lung cancer cases, which is also the most frequent cause of cancer-related deaths in humans. With over 60 carcinogens in tobacco smoke, cells dividing at the time of carcinogen exposure are at particular risk of neoplasia. The present study aimed to investigate global gene expression differences in lung adenocarcinoma (LUAD) tumour samples of current smokers and non-smokers, in an attempt to elucidate biological mechanisms underlying divergent smoking effects. Current and non-smoker tumour samples were analysed using bioinformatics tools, examining differences in molecular drivers of cancer initiation and progression, as well as evaluating the effect of smoking and sex on epithelial mesenchymal transition (EMT). As a result, we identified 1150 differentially expressed genes showing visible differences in the expression profiles between the smoking subgroups. The genes were primarily involved in cell cycle, DNA replication, DNA repair, VEGF, GnRH, ErbB and T cell receptor signalling pathways. Our results show that smoking clearly affected E2F transcriptional activity and DNA repair pathways including mismatch repair, base excision repair and homologous recombination. We observed that sex could modify the effects of PLA2G2A and PRG4 in LUAD tumour samples, whereas sex and smoking status might possibly have a biological effect on the EMT-related genes: HEY2, OLFM1, SFRP1 and STRAP. We also identified potential epigenetic changes smoking solely might have on EMT-related genes, which may serve as potential diagnostic and prognostic biomarkers for LUAD patients.

Detection rate of de novo EGFR T790 M mutation was increased up to 80% through recent ultrasensitive detection methods. Here, we investigated the clinical significance and its usefulness of detecting de novo EGFR T790 M using ultrasensitive droplet-digital polymerase chain reaction (ddPCR) method. In total, 102 cases diagnosed as lung adenocarcinoma with EGFR-tyrosine kinase inhibitor (TKI) sensitizing mutations (mEGFR) and had been treated with 1(st) ~ 2(nd) generation EGFR-TKI alone were enrolled for this study. De novo T790 M status was tested using the tissues at the initial diagnosis and positivity was defined as the ratio of T790 M/wild-type copies over 0.00294 by ddPCR. Seventy patients (68.6%) harbored the de novo T790 M. De novo T790 M was more frequently detected in cases with EGFR L858 R mutation than those with EGFR exon 19 deletion (E19d) mutations (P = 0.024). Forty-three patients underwent rebiopsy due to disease progression. The cases who experienced progression due to acquired T790 M were more likely to have E19d at initial diagnosis and the presence of de novo T790 M and the ratio of T790 M/wild-type copies did not relate to the emergence of acquired T790 M. On the other hand, the cases with a longer duration of disease-control by EGFR-TKI had higher change to get acquired T790 M mutation (P-value = 0.040). The presence of de novo T790 M has limitation in predicting disease progression by acquired T790 M, suggesting that identifying de novo T790 M through the ultrasensitive methods may not be necessary identifying patients who would be beneficial by 3rd-generation EGFR-TKI as the 1st line treatment.

Salivary gland neoplasms of the buccal mucosa are relatively rare and often present with an unusual histopathologic profile when compared with other intraoral locations. We present a series of minor salivary gland neoplasms of the buccal mucosa and discuss demographics, clinical presentation, and histologic findings. An IRB approved retrospective search of University of Florida Oral Pathology Biopsy Service archive from 1994 to 2018 for all salivary gland neoplasms of the buccal mucosa was undertaken. Data related to age, gender, clinical presentation, diagnosis, and category of neoplasm recorded. Review for consensus of diagnosis and immunohistochemical (IHC) testing on current diagnostic standards was performed and diagnoses updated based on results. Of 66 cases identified majority were females (72.7%) and age mean was 63 years. Benign tumors were 56.06% and 43.94% malignant, with Mucoepidermoid carcinoma (MEC) being commonest (26/66, 39.4%), followed by canalicular adenoma (CLA) (14/66, 21.2%), ductal papilloma (DP) (10/66, 15.2%), cystadenoma (CA) (8/66, 12.1%), basal cell adenoma (BCA) (4/66, 6.1%), and 1(1.5%) each for pleomorphic adenoma (PA), secretory carcinoma (SC), adenoid cystic carcinoma (ACC) and adenocarcinoma not otherwise specified (ACNOS). This study with respect to demographics and percentage of benign and malignant buccal mucosal salivary gland neoplasms is in conformity with the literature. It underscores the fact that both benign and malignant salivary gland neoplasms should be included in the differential diagnosis of submucosal buccal masses. Future larger multicenter studies with detailed treatment and outcomes data may aid and assist in further understanding the behavior, diverse histomorphology and prognosis of these neoplasms.

Myeloma Overexpressed (MYEOV) is closely related to cell growth and differentiation in many cancer types. However, the role of this protein-coding gene in pancreatic ductal adenocarcinoma (PDAC) has rarely been investigated. In this study, we demonstrated that MYEOV was higher expressed in tumor tissues compared with adjacent normal pancreas tissues (ANPTs) both in mRNA and protein levels. We also performed bioinformatic analysis and found high MYEOV expression was positively correlated with tumor differentiation (P = 0.004), lymph node metastasis (P = 0.016) and TNM stage (P = 0.001). Moreover, Kaplan-Meier and Cox proportional-hazards analyses indicated that high MYEOV expression was significantly associated with poor survival in patients with PDAC and that MYEOV was an independent prognostic factor for overall survival in patients with PDAC. Geneset Enrichment Analysis (GSEA) result showed that high expression of MYEOV facilitates glycolysis of tumor cells in PDAC and validated in cellular assays. In conclusion, our results suggest that MYEOV acts as an oncogene in PDAC and can therefore serve as a biomarker for the prognosis of patients with PDAC.

Surgery is the standard modality for early-stage I–II non-small-cell lung cancer (NSCLC). Generally, patients who are >80 years old tend to have more comorbidities and inferior physical status than younger patients. Stereotactic body radiation therapy (SBRT) may provide an alternative treatment for this group of patients. Here, we report our experience using SBRT to in the management of early-stage NSCLC in patients >80 years old. Patients aged ≥80 years old who were diagnosed with early-stage NSCLC and treated with definitive lung SBRT from January 2000 to January 2018 were retrospectively analysed. Local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), cancer-specific survival (CSS), progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were analysed for patients >80 years old. A total of 153 patients were included, with a median age of 85 years (range, 80–94). The median follow-up period and OS was 39.8 months (range, 10–101 months) and 76 months, respectively. The 3-year OS, PFS, CSS, RRFS and LRFS were 65.3, 58.0, 75.7, 73.9 and 85.3%, respectively. Radiation pneumonitis grade 0–1, grade 2, grade 3 and grade 4 was observed in 135 (88.2%), 13 (8.5%), 4 (2.61%) and 1 (0.6%) patient(s), respectively. On multivariate analyses, tumor size, pretreatment C-reactive protein (CRP) value, histology and pretreatment physical state were significantly associated with OS. Definitive lung SBRT appears to have high LRFS and OS without causing high-grade radiation-related toxicities in early-stage NSCLC patients who were >80 years old.

Raman spectroscopy is a fast and sensitive technique able to identify molecular changes in biological specimens. Herein, we report on three cases where Raman microspectroscopy was used to distinguish normal vs. oesophageal adenocarcinoma (OAC) (case 1) and Barrett’s oesophagus vs. OAC (cases 2 and 3) in a non-destructive and highly accurate fashion. Normal and OAC tissues were discriminated using principal component analysis plus linear discriminant analysis (PCA-LDA) with 97% accuracy (94% sensitivity and 100% specificity) (case 1); Barrett’s oesophagus vs. OAC tissues were discriminated with accuracies ranging from 98 to 100% (97–100% sensitivity and 100% specificity). Spectral markers responsible for class differentiation were obtained through the difference-between-mean spectrum for each group and the PCA loadings, where C–O–C skeletal mode in β-glucose (900 cm−1), lipids (967 cm−1), phosphodioxy (1296 cm−1), deoxyribose (1456 cm−1) and collagen (1445, 1665 cm−1) were associated with normal and OAC tissue differences. Phenylalanine (1003 cm−1), proline/collagen (1066, 1445 cm−1), phospholipids (1130 cm−1), CH2 angular deformation (1295 cm−1), disaccharides (1462 cm−1) and proteins (amide I, 1672/5 cm−1) were associated with Barrett’s oesophagus and OAC tissue differences. These findings show the potential of using Raman microspectroscopy imaging for fast and accurate diagnoses of oesophageal pathologies and establishing subtle molecular changes predisposing to adenocarcinoma in a clinical setting. Graphical abstract Graphical abstract demonstrating how oesophageal tissue is processed through Raman mapping analysis in order to detect spectral differences between stages of oesophageal transformation to adenocarcinoma Electronic supplementary material The online version of this article (10.1007/s00216-020-02637-1) contains supplementary material, which is available to authorized users.

We retrospectively reviewed the effect of stereotactic body radiation therapy (SBRT) in patients with stage I lung cancer whose lung tumor showed a nodular appearance of ground glass opacity, so-called ground glass nodule (GGN). A total of 84 patients (42 men, 42 women; mean age, 75 years) with stage I lung cancer with GGN accompanying a solid component

Background: Barrett's oesophagus (BO), a precursor to oesophageal adenocarcinoma, requires long-term endoscopic surveillance. The rising incidence of this chronic disease has implications for service provision and patient burden. Few studies have explored BO patients’ personal burden, care delivery experience and participation in health-care delivery decisions. Objective: To identify and explore factors impacting BO patients’ health-related quality of life, follow-up needs and views on new models of follow-up care. Design: An exploratory qualitative approach was adopted using semi-structured, in-depth, one-to-one interviews, audio-recorded and transcribed verbatim. Patients undergoing BO surveillance, at a single NHS hospital, were recruited using purposive sampling with the aim of achieving maximum variation. Data were analysed using framework analysis approach, supported by NVivo Pro 11. Results: Data saturation occurred after 20 participant interviews. Ten subthemes and three main themes emerged from the analysis: (a) burden of disease—symptom control, worry of oesophageal cancer and surveillance endoscopy; (b) follow-up experiences—follow-up care, at this NHS hospital, was found to be inconsistent and often inadequate to meet patients’ needs, in particular a lack of disease-specific information; and (c) follow-up needs—participants sought enhanced communication, organization and structure of care. They highly valued face-to-face interaction with a specialist, and the concept of direct secondary care access in-between endoscopies was reassuring to participants. Conclusions: This qualitative research provides an in-depth account of the patients’ perspective of BO, the effectiveness of follow-up care and patient opinion on new follow-up systems.

The current study aimed to evaluate the outcomes of patients with adenocarcinoma (AC) of the uterine cervix after definitive radiotherapy (RT) and to evaluate prognostic factors, including immunity-related molecules. A total of 71 patients with AC of the uterine cervix from multiple Japanese institutions were retrospectively analysed. Histological subtypes were diagnosed according to the 2014 World Health Organization classification. All patients underwent definitive RT comprising external beam RT and intracavitary brachytherapy with or without concurrent chemotherapy. Immunohistochemical studies were performed to detect the expression of programmed cell death-ligand 1(PD-L1) and CD8. The 5-year locoregional control (LC), overall survival (OS) and progression-free survival (PFS) rates for all patients were 61.8, 49.7 and 36.1%, respectively. The LC, OS and PFS rates were not significantly different among the histological subtypes. Membranous PD-L1 expression was not significantly associated with prognosis. Patients with CD8-positive tumor-infiltrating lymphocytes (CD8+TILs) in the tumor nests had significantly better OS than patients without CD8+TILs in the tumor nests (5-year OS: 53.8 vs 23.8%, P = 0.038). As expected, the International Federation of Gynecology and Obstetrics (FIGO) stage (2008) III–IVA and maximum tumor diameter > 40 mm were significantly associated with worse prognosis. In summary, the presence of CD8+TILs in the tumor nests has the potential to be an independent favorable prognostic factor for patients with AC of the uterine cervix after definitive RT.

Utilizing genomic data to predict cancer prognosis was insufficient. Proteomics can improve our understanding of the etiology and progression of cancer and improve the assessment of cancer prognosis. And the Clinical Proteomic Tumor Analysis Consortium (CPTAC) has generated extensive proteomics data of the vast majority of tumors. Based on CPTAC, we can perform a proteomic pan-carcinoma analysis. We collected the proteomics data and clinical features of cancer patients from CPTAC. Then, we screened 69 differentially expressed proteins (DEPs) with R software in five cancers: hepatocellular carcinoma (HCC), children’s brain tumor tissue consortium (CBTTC), clear cell renal cell carcinoma (CCRC), lung adenocarcinoma (LUAD) and uterine corpus endometrial carcinoma (UCEC). GO and KEGG analysis were performed to clarify the function of these proteins. We also identified their interactions. The DEPs-based prognostic model for predicting over survival was identified by least absolute shrinkage and selection operator (LASSO)-Cox regression model in training cohort. Then, we used the time-dependent receiver operating characteristics analysis to evaluate the ability of the prognostic model to predict overall survival and validated it in validation cohort. The results showed that the DEPs-based prognostic model could accurately and effectively predict the survival rate of most cancers.

Introduction Colorectal cancer (CRC) is traditionally regarded as the most commonly diagnosed gastrointestinal malignant disease. Nevertheless, despite advances in diagnosis and novel therapeutic options, the clinical outcomes of patients are still not satisfactory. Aim To investigate the clinicopathological and prognostic roles of Notch1 expression, the immunohistochemical investigation was performed in samples of CRC tumour tissues, adjacent non-pathological mucosa, and metastatic foci in regional lymph nodes in Caucasian patients. Material and methods Paraffin-embedded adenocarcinoma samples were assessed immunohistochemically for Notch1 protein and scored according to the percentage of cells with a positive reaction combined with staining intensity. Connections between Notch1 immunoexpression and clinicopathological factors including the 5-year overall survival (OS) were evaluated. Results The level of the Notch1 immunohistochemical reactivity was correlated with the grade of the histological differentiation, size of the primary tumour, regional lymph node involvement, and perineural invasion (all p < 0.001). Kaplan-Meier survival analysis showed that the survival time for patients with a low expression of Notch1 was significantly longer than that for patients with moderate or strong level of Notch1 immunoreactivity (p < 0.001). Conclusions The enhanced level of Notch1 immunoexpression was significantly associated with malignancy-related clinicopathological factors and reduced the 5-year overall survival in CRC patients.

Introduction It is generally accepted that the gastrointestinal tract, and especially the colon, is constantly exposed to reactive oxygen species (ROS) that may be responsible for the appearance of genetic mutations. To keep a steady-state control over ROS production-detoxification, organisms have evolved a defensive system. Nevertheless, many reports have described decreased level of antioxidant enzymes, especially catalase (CAT), in cancer tissues. Aim In this work we try to assess the immunohistochemical expression of CAT protein in colorectal adenoma and adenocarcinoma samples. Material and methods This study was performed on resected specimens obtained from 122 patients who had undergone surgical resection for colorectal cancer, and from 120 patients who had undergone colonoscopy. Paraffin- embedded, 4 µm-thick tissue sections were stained for rabbit polyclonal anti CAT antibody obtained from GeneTex (cat. no. GTX110704). Results In adenoma strong immunoexpression was detected mainly in infiltrating mononuclear cells within lamina propria. High expression of CAT was significantly associated with grade of dysplasia (high grade vs. low grade, p = 0.037). In adenocarcinoma samples, the high level of CAT immunoexpression was significantly correlated with histological grade of tumour (G1 vs. G2 vs. G3, p = 0.001) and depth of invasion (T1 vs. T2 vs. T3 vs. T4, p = 0.003). Conclusions Development of colorectal cancer is associated with increased expression of CAT in the stage of adenoma and decreased expression in the stage of adenocarcinoma.

Lung cancer patients with lymph node metastasis usually had short overall survival and occurred distant metastases at the early stage. However, some of these people did have more prolonged survival. The underlying reason is still unclear. In this study, we found a novel molecule, family with sequence similarity 136, member A gene (FAM136A). First, we performed immunohistochemistry for FAM136A in 177 lung carcinoma tissues. Second, we carried out in vitro studies by using A549 and PC-9. We detected FAM136A immunoreactivity in 79 out of 177 (44.6%) lung carcinoma tissues, and the FAM136A status was significantly associated with tumor T stage, lymph node metastasis, and the Tumor-Node-Metastasis (TNM) staging system in these cases. Importantly, it was significantly associated with the overall survival of the patients with lymph node metastasis, especially FAM136A positive patients, who had worse outcomes. Subsequent in vitro experiments revealed that the proliferation activity and migration property decreased both A549 and PC-9 lung carcinoma cells transfected with siRNA-FAM136A, and apoptosis reduced. Meanwhile, the expression of CDK4 and CDK6 decreased. FAM136A status would be a potent, worse prognostic factor in lung cancer patients with lymph node metastasis. It would play a vital role in the proliferation, apoptosis, and migration properties of A549 and PC-9. In the future, We will focus on the uncovered signal mechanism between FAM136A and lung cancer., Graphical Abstract Abbreviation: FAM136A: family with sequence similarity 136 member A; NSCLC: non-small-cell lung cancer; SCC: squamous cell carcinoma; IHC: immunohistochemistry; PBS: phosphate-buffered saline; CDK: cyclin-dependent kinase.

Introduction Cholelithiasis is most common disease of the gallbladder and cholecystectomy is the one of the most performed surgical procedure worldwide. Aim To assess the relationship between the demographic, biochemical, and histopathological variables of patients who underwent cholecystectomy. Material and methods Demographic, biochemical, and histopathological data of 5077 patients undergoing cholecystectomy were compared in terms of two different aspects: open cholecystectomy (OC group; n = 2090) versus laparoscopic cholecystectomy (LC group; n = 2987), and an elective group (n = 4814) versus an emergency group (n = 263). Results A total of 5077 patients aged between 13 and 97 years were included in the study. Aspartate aminotransferase (AST) levels, alanine aminotransferase (ALT) levels, mean platelet volume, and prevalence of acute/chronic cholecystitis were significantly higher in the LC group than in the OC group. On the other hand, age, direct bilirubin level, thrombocyte count, and prevalence of gallbladder cancer/gangrenous cholecystitis were significantly higher in the OC group than in the LC group. Levels of AST, ALT, white blood cells, neutrophils, and some prevalence of acute/chronic active cholecystitis were higher in the emergency group than in the elective group. On the other hand, the lymphocyte count and prevalence of chronic cholecystitis/hyperplastic polyps were higher in the elective group than in the emergency group. Histopathological analysis identified 32 patients with malignant gallbladder cancer as follows: adenocarcinoma (n = 21), mucinous adenocarcinoma (n = 3), papillary adenocarcinoma (n = 3), adenosquamous carcinoma (n = 1), clear cell adenocarcinoma (n = 2), squamous carcinoma (n = 1), and hepatocellular carcinoma metastasis (n = 1). Conclusions Even when the appearance of gallbladder specimens is normal, histopathological assessment allows for early diagnosis of many unusual findings such as gallbladder cancer.

Current data shows there are differences in factors associated with colorectal neoplasia based on geographical location and cultural settings. There are no studies focusing on the association between environmental factors and colorectal polyps in Australia. The aim of this study was to prospectively evaluate the association of various factors with different colorectal neoplasia histology. We utilized a simplified one-page questionnaire for patients undergoing colonoscopy for information on age; gender; comorbidities; family history of colorectal cancer; physical activity; smoking; diet; alcohol intake; and body mass index. Factors were then evaluated for association with the presence of: (1) neoplastic lesions; (2) conventional adenomas; (3) neoplastic serrated polyps; (4) any lesions (past and present); and (5) hyperplastic polyps. 291 procedures and 260 patients were included. Factors with a p-value < 0.2 in a univariate regression were included in an initial multivariable regression model. Backwards elimination was then performed, removing one predictor at a time until only significant predictors remained. In the final multivariable model, age≥65, male gender, type-2 diabetes mellitus, active smoking and family history of colorectal cancer were found to be statistically significant predictors for the presence of colorectal neoplasia. However, the significant predictors found for conventional adenomas (older age, male gender and smoking) were different from the significant predictors for neoplastic serrated polyps (type-2 diabetes mellitus and family history of colorectal cancer). Older age, male gender, type-2 diabetes mellitus, and smoking were significantly associated with the presence of colorectal neoplasia. The factors associated with conventional adenomas differed from those associated with neoplastic serrated polyps.

Purpose The goal of this study was to assess the effectiveness of dysphagia relief and overall survival in patients with advanced esophageal cancer treated with palliative high-dose-rate (HDR) brachytherapy (BT) without computed tomography-based planning. Material and methods Palliative 2D HDR-BT was used to treat 93 patients with advanced or incurable esophageal cancer in a regional cancer center from October 2010 to December 2016. Before the treatment patients presented the following grades of dysphagia: 0 - 0%, I - 57%, II - 33.3%, III - 6.5%, IV - 3.2%. The planned dose was 22.5 Gy in 3 fractions. The median age of patients was 65 years (45-88). Squamous cell carcinoma was diagnosed in 59.4%, adenocarcinoma in 22.6%, and other histological types of tumors in 6.7% of cases. The histopathological report was unknown in 11.3% of patients. Results The mean follow-up was 5.0 months (range 1-43). The median tumor length was 72.5 mm. Due to BT dysphagia was significantly decreased: grade 0 - 38.7%, I - 31.2%, II - 20.4%, IV - 1.1% (p < 0.001). Dysphagia relief was achieved in 55% of patients and lasted for a mean time of 4.6 months; stabilization occurred in 31% and deterioration in 14%. The patients with partial or complete dysphagia relief lived longer (5.8 vs. 4.1 months, p = 0.02). The patients with a length of the tumor less than 72.5 mm, histopathologically confirmed adenocarcinoma or after dilatation with a metal stent subsequently to BT had improved overall survival as well (7.1 vs. 3.6; 8.0 vs. 4.1; 6.5 vs. 4.0 months, respectively; p < 0.05). The primary localization and primary grade of dysphagia were not factors that influenced the survival of patients. The logistic regression model did not reveal any predictors for treatment response. Conclusions 2D HDR-BT reduces dysphagia and prolongs survival in patients who respond to the treatment. It meets the assumption of palliative treatment for advanced esophageal cancer because of its simplicity and effectiveness.

Objective: To investigate the clinicopathologic features and immunophenotype of invasive-stratified mucin-producing carcinoma (ISMC). Methods: We retrospectively analyzed three patients who underwent surgery for pathologically confirmed ISMC from January 2017 to December 2017 in Anyang Tumor Hospital. The pathological features, immunophenotype, and prognosis were discussed. Results: Clinical symptoms and imaging were atypical. Microscopically, the arrangement of tumor cells is close to that of squamous cell carcinoma, showing flake or nested growth. Morphologically, tumor cells were reminiscent of adenocarcinoma. The tumor cells showed abundant intracytoplasmic mucus which routinely created spacing between adjacent nuclei. The nuclei was round or oval with irregular karyotypes, thick nuclear membrane, staining empty light, rough chromatin, visible small nucleoli. Mucous vacuoles or pink-stained foam were visible in the cytoplasm. Mitotic features and apoptotic bodies were seen in the invasive component of all three cases, whereas all but one of these showed a neutrophil-dominant inflammatory cells infiltration. A large number of histocytes were found in the stroma of two cases. Special staining of mucus confirmed the presence of mucus in cytoplasm. Immunohistochemical results showed that tumor cells were strongly and diffusely positive for p16 and CK7 and had high Ki-67 expression. Conclusions: ISMC is a rare tumor in female genital tract and is often misdiagnosed as squamous cell carcinoma and other cervical cancers. The diagnosis mainly depends on the unique clinicopathologic features together with the immunophenotype. Treatment and prognosis, like other cervical cancer, are mainly based on clinical stages.

Cancer consists of heterogeneous cells that contain a small population of cells that possess stem cell properties; these cells, referred to as cancer stem cells (CSCs) or tumor-initiating cells, are involved in tumor progression and metastasis. Using a sphere-forming assay, canine mammary CSCs were found to be similar to human breast CSCs. Metabolic reprogramming has been recognized as a hallmark of various cancers. However, the significance of cellular metabolism in CSCs remains unclear. The aim of this study was to define the metabolic characteristics of CSCs derived from canine mammary tumors and gain an understanding of the maintenance of stemness. We identified metabolite profiles of canine mammary adenocarcinoma cell lines using gas chromatography-mass spectrometry. Metabolites were extracted from both adherent and sphere-forming cells derived from three cell lines. Sphere-forming cells were separated from adherent cells using an orthogonal, partial least-squares discriminant analysis. Sphere-forming cells were found to contain high levels of the amino acids alanine, glycine and proline compared with adherent cells. They also had high levels of palmitoleate, palmitate and dihomo-gamma-linolenic acid compared with adherent cells. In a sphere-forming assay, palmitate increased the number of spheres for all cell lines. These results indicate that the sphere-forming cells derived from canine mammary adenocarcinoma cell lines have specific metabolic profiles that may be useful for the development of CSC-specific therapies targeting metabolic pathways and potential stemness biomarkers; these results also clarify the maintenance of stemness in canine mammary CSCs.

Circular RNA (circRNA) is a new class of non-coding RNA that plays a pivotal role in carcinogenesis. Recently, circ-MTO1 (hsa_circ_0007874) was shown to be a cancer-related circRNA. However, its role in lung adenocarcinoma (LUAD) has not been reported. Here, we found that circ-MTO1 was significantly down-regulated in LUAD, which was closely associated with malignant features and dismal prognosis. Enforced expression of circ-MTO1 suppressed the growth of LUAD cells both in vitro and in vivo. Subsequent mechanism experiments showed that circ-MTO1 served as a sponge of oncogenic miR-17 to increase the expression of RNA-binding protein QKI-5, leading to the inactivation of Notch signaling pathway, thereby restraining the growth of LUAD. Importantly, increased QKI-5 expression caused by circ-MTO1 overexpression in turn promoted circ-MTO1 expression. Clinically, circ-MTO1 expression was strongly positively correlated with QKI-5 expression, but negatively correlated with miR-17 expression. Taken together, our data suggest that circ-MTO1 is a critical negative regulator of LUAD and elucidate the potential molecular mechanism of a novel circ-MTO1/miR-17/QKI-5 feedback loop in inhibiting LUAD progression.

Purpose Despite extensive biological and clinical studies, including comprehensive genomic and transcriptomic profiling efforts, pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease, with a poor survival and limited therapeutic options. The goal of this study was to assess co-expressed PDAC proteins and their associations with biological pathways and clinical parameters. Methods Correlation network analysis is emerging as a powerful approach to infer tumor biology from omics data and to prioritize candidate genes as biomarkers or drug targets. In this study, we applied a weighted gene co-expression network analysis (WGCNA) to the proteome of 20 surgically resected PDAC specimens (PXD015744) and confirmed its clinical value in 82 independent primary cases. Results Using WGCNA, we obtained twelve co-expressed clusters with a distinct biology. Notably, we found that one module enriched for metabolic processes and epithelial-mesenchymal-transition (EMT) was significantly associated with overall survival (p = 0.01) and disease-free survival (p = 0.03). The prognostic value of three proteins (SPTBN1, KHSRP and PYGL) belonging to this module was confirmed using immunohistochemistry in a cohort of 82 independent resected patients. Risk score evaluation of the prognostic signature confirmed its association with overall survival in multivariate analyses. Finally, immunofluorescence analysis confirmed co-expression of SPTBN1 and KHSRP in Hs766t PDAC cells. Conclusions Our WGCNA analysis revealed a PDAC module enriched for metabolic and EMT-associated processes. In addition, we found that three of the proteins involved were associated with PDAC survival.

The cell block (CB) technique is a generalized method utilized for the diagnostic evaluation of body cavity fluids. Ascites cytology is one of the most important diagnostic processes for epithelial ovarian cancer. However, in clinical practice, the usefulness of the CB method to diagnose this tumor remains unelucidated. Between 2008 and 2017, 15 peritoneal or pleural fluid samples obtained from patients with ovarian or peritoneal carcinoma or other gastrointestinal malignancies were preoperatively subjected to a diagnostic evaluation to predict the histological type and original organ. The CBs were made from 10% formalin neutral buffer solution fixed sediments of fluid samples after cytological smears were made by conventional method. Four-μm thickness sections were prepared from the cell blocks and stained with immunohistochemical method, using 16 kinds of antibodies and hematoxylin eosin staining method. The cellularity, architectural patterns, and morphological details were also studied. The median (range) age of patients was 73 (35–87) years. The clinical features were identified as follows: pleural effusion in 4, ovarian mass in 7, peritoneal dissemination in 12, para-aortic nodal swelling in one, and liver tumor in one (some overlapping). Five patients had a history of prior malignancy. Finally, we could accurately diagnose the histological type in 9 patients based on subsequent biopsy, surgery, and autopsy. In all 9 women, the clinical diagnosis, CB diagnosis and final pathological diagnosis were consistent. The CB technique may be a helpful modality for evaluating fluid cytology to obtain a final histopathologic diagnosis.

Lung cancer is one of the most malignant cancers worldwide, and lung adenocarcinoma (LUAD) is the most common histologic subtype. Thousands of biomarkers related to the survival and prognosis of patients with this cancer type have been investigated through database mining; however, the prediction effect of a single gene biomarker is not satisfactorily specific or sensitive. Thus, the present study aimed to develop a novel gene signature of prognostic values for patients with LUAD. Using a data-mining method, we performed expression profiling of 1145 mRNAs in large cohorts with LUAD (n = 511) from The Cancer Genome Atlas database. Using the Gene Set Enrichment Analysis, we selected 198 genes related to GLYCOLYSIS, which is the most important enrichment gene set. Moreover, these genes were identified using Cox proportional regression modeling. We established a risk score staging system to predict the outcome of patients with LUAD and subsequently identified four genes (AGRN, AKR1A1, DDIT4, and HMMR) that were closely related to the prognosis of patients with LUAD. The identified genes allowed us to classify patients into the high-risk group (with poor outcome) and low-risk group (with better outcome). Compared with other clinical factors, the risk score has a better performance in predicting the outcome of patients with LUAD, particularly in the early stage of LUAD. In conclusion, we developed a four-gene signature related to glycolysis by utilizing the Cox regression model and a risk staging model for LUAD, which might prove valuable for the clinical management of patients with LUAD.

Background In patients with resectable colorectal liver metastases (CRLM), distinct histopathological growth patterns (HGPs) develop at the interface between the tumour and surrounding tissue. The desmoplastic (d) HGP is characterised by angiogenesis and a peripheral fibrotic rim, whereas non-angiogenic HGPs co-opt endogenous sinusoidal hepatic vasculature. Evidence from previous studies has suggested that patients with dHGP in their CRLM have improved prognosis as compared to patients with non-desmoplastic HGPs. However, these studies were relatively small and applied arbitrary cut-off values for the determination of the predominant HGP. We have now investigated the prognostic effect of dHGP in a large cohort of patients with CRLM resected either with or without neoadjuvant chemotherapy. Methods All consecutive patients undergoing a first partial hepatectomy for CRLM between 2000 and 2015 at a tertiary referral centre were considered for inclusion. HGPs were assessed in archival H&E stained slides according to recently published international consensus guidelines. The dHGP was defined as desmoplastic growth being present in 100% of the interface between the tumour and surrounding liver. Results In total, HGPs in CRLMs from 732 patients were assessed. In the chemo-naive patient cohort (n = 367), the dHGP was present in 19% (n = 68) and the non-dHGP was present in 81% (n = 299) of patients. This dHGP subgroup was independently associated with good overall survival (OS) (HR: 0.39, p

Outcomes for patients with Stage IB1–IVA cervical cancer treated with computed tomography (CT)-based image-guided brachytherapy (IGBT) were examined in this study. A total of 84 patients were analyzed between March 2012 and June 2015. Whole-pelvic radiotherapy with a central shield was performed for each patient, and the total pelvic sidewall dose was 50 Gy. IGBT was delivered in 2–4 fractions. The initial prescription dose (6.8 Gy) was delivered at Point A, and the dose distribution was modified manually by graphical optimization. The total dose was calculated as the biologically equivalent dose in 2 Gy fractions (EQD2). Concurrent chemotherapy was administered to 64 patients (76%). The median follow-up period was 36 months (range 2–62 months). The 3-year overall survival, local control, and progression-free survival rates were 94%, 89% and 81%, respectively. The mean EQD2 for HR-CTV D90 was 73.4 Gy, and the EQD2 for HR-CTV D90 was not significantly associated with the local control rate. In multivariate analysis, adenocarcinoma (P = 0.03) and tumor size ≥45 mm (P = 0.06) were risk factors for local control. The patients were divided into four groups based on histology (squamous cell carcinoma vs adenocarcinoma) and tumor size (

Introduction Colorectal cancer (CRC) is traditionally regarded as the most commonly diagnosed gastrointestinal malignant disease. Nevertheless, despite advances in diagnosis and novel therapeutic options, the clinical outcomes of patients are still unsatisfactory. Aim To investigate the clinicopathological and prognostic roles of GRP94 expression, the immunohistochemical investigation was performed on samples of CRC tumour tissues, adjacent non-pathological mucosa, and metastatic foci in regional lymph nodes in Caucasian patients. Material and methods Paraffin-embedded adenocarcinoma samples were assessed immunohistochemically for GRP94 protein and scored according to the percentage of cells with positive reaction combined with staining intensity. Connections between GRP94 immunoexpression and clinicopathological factors including the overall survival (OS) were evaluated. Results The level of the GRP94 immunohistochemical reactivity was correlated with the grade of the histological differentiation (H (2.92) = 25.906; p < 0.001), size of the primary tumour (Z = –4.010; p < 0.001), regional lymph node involvement (Z = –6.547; p < 0.001), and perineural invasion (Z = –6.235; p < 0.001). Kaplan-Meier survival analysis showed that the survival time for patients with a low expression of GRP94 was significantly longer than that for patients with a moderate or strong level of GRP94 immunoreactivity (p < 0.001). Conclusions An enhanced level of GRP94 immunoexpression was significantly associated with malignancy-related clinicopathological factors and reduced the 5-year overall survival in CRC patients. However, a multivariate analysis demonstrated that GRP94 was not revealed as an independent risk factor for CRC prognosis.

Aim of the study The main purpose of this study was to assess detection of mutations in the epidermal growth factor receptor (EGFR) gene in circulating tumor DNA (ctDNA) as a tool for EGFR tyrosine kinase inhibitor (TKI) monitoring therapy. Material and methods The study was conducted using 20 samples from 7 adenocarcinoma patients treated with TKIs. Blood samples for ctDNA analysis were collected in 2015-2016. ctDNA was isolated using the QIAamp Circulating Nucleic Acid Kit (Qiagen) and analyzed using the ctEGFR Mutation Detection Kit (EntroGen). Results The most common exon 19 deletion and p.Leu858Arg mutation in exon 21 of the EGFR gene were detected. We observed a correlation between stabilization of patient condition and the lack of p.Thr790Met mutation detection in ctEGFR during TKI treatment (2 out of 7 patients). We also observed a correlation between progression of the disease and p.Thr790Met mutation detection in ctEGFR (3 out of 7 cases). We did not detect ctDNA p.Thr790Metp in two patients in whom progression occurred shortly thereafter. Last but not least, we noticed that good organization during plasma collection and transportation (average time of 6 minutes and 30 seconds) allows to use K2EDTA tubes. Conclusions When tissue is limited or insufficient, analysis of the ctEGFR mutational status can be considered as an alternative tool for qualifying patients with non-small cell lung cancer (NSCLC) for TKI therapy, also as a potential monitoring tool. The plasma p.Thr790Met-negative result needs to be verified for the presence of p.Thr790Met-positive tumor tissue.

Lung adenocarcinoma (LA) is the most common cause of cancer-related death worldwide. Despite the advances over last decade in new targeted therapies, cancer genetics, diagnostics, staging, and surgical techniques as well as new chemotherapy and radiotherapy protocols, the death rate from LA remains high. The tumour microenvironment is composed of several cytokines, one of which is transforming growth factor b1 (TGF-β1), which modulates and mediates the expression of epithelial-mesenchymal transition (EMT), correlated with invasive growth in LAs, and exhibits its pleiotropic effects through binding to transmembrane receptors TbR-1 (also termed activin receptor-like kinases – ALKs) and TbR-2. Accordingly, there is an urgent need to elucidate the molecular mechanisms associated with the tumoural spreading process and therapeutic resistance of this serious pathology. In this review, we briefly discuss the current role of contextual signal TGF-β1 inducer of epithelial mesenchymal transition in metastatic lung adenocarcinoma patients with brain metastases, and give an overview of our current mechanistic understanding of the TGF-β1-related pathways in brain metastases progression, TGF-β1 pathway inhibitors that could be used for clinical treatment, and examination of models used to study these processes. Finally, we summarise the current progress in the therapeutic approaches targeting TGF-β1.

Purpose To investigate the safety and feasibility of endovascular brachytherapy using iodine-125 (125I) seed strand for locally advanced pancreatic ductal adenocarcinoma (PDAC) with vascular invasion. Material and methods From January 2010 to January 2015, 12 patients diagnosed with locally advanced, inoperable PDAC with splenic or superior mesenteric vein invasion were enrolled in the present study and received endovascular brachytherapy combined with regional intra-arterial infusion chemotherapy. Standardized software was used for dose calculation. Procedure-related and radiation complications were documented and assessed. Overall survival was calculated with the Kaplan-Meier approach. Results The technical success rate of 125I seed strand implantation and stent placement was 100%. During follow-up with a mean duration of 17.00 ±6.07 months (range, 6~24 months), the mean and median survival times were 12.0 ±2.4 months (95% CI: 7.4~16.6 months) and 10.7 ±1.4 months (95% CI: 8.0~13.5 months), respectively. One month after the treatment, the disease control and objective rates were 83.8% and 58.3%, respectively. The 6-, 12-, and 15-month cumulative survival rates were 66.7%, 47.6%, and 9.5%, respectively. Conclusions Endovascular brachytherapy using 125I seed strand and stent placement may be a safe and effective treatment option for locally advanced pancreatic duct adenocarcinoma with vascular invasion.

Aim of the study The objective of the study was to analyse the survival rate of women with malignant ovarian tumours in the years 1990-2015 in the Podkarpacie province. Material and methods The database used for calculations covered 2399 cancer incidences verified at the end of 2014. The estimated relative survival rates were calculated by means of the Hakulinen method. Results The number of recorded cases amounted to 196 in 2015 and was higher by 86.7% than in 1990. The rates of one-year, three-year, and five-year survival was 72.5%, 51.2%, and 42.4%, respectively. Conclusions Survival rates of women with ovarian cancer in the Podkarpacie province are comparable to survivals calculated for the entire Poland region. Despite the low risk factor, women suffering from ovarian adenocarcinoma have lower survival rates than others, and as many as 42.5% of patients with adenocarcinoma were diagnosed in stage IV. Steps aimed at improvement of detectability of ovarian cancers in the earliest possible stage should be taken. This should increase survival rates in each age group.

The inositol polyphosphate-4-phosphatase type II (INPP4B) has been mostly proposed to act as a tumor suppressor whose expression is frequently dysregulated in numerous human cancers. To date, little is unveiled about whether and how INPP4B will exert its tumor suppressive function on the turnover of cadherin-based cell-cell adhesion system in pancreatic ductal adenocarcinomas (PDACs) in vitro. Here we provide the evidence that INPP4B manipulates cadherin switch in certain PDAC cell lines through a phosphorylated AKT-inactivation manner. The knockdown of INPP4B in AsPC-1 results in a more invasive phenotype, and overexpression of it in PANC-1 leads to partial reversion of mesenchymal status and impediment of in vitro invasion but not migration. More importantly, E-cadherin (Ecad) is enriched in the early and sorting endosomes containing INPP4B by which its recycling rather than degradation is enabled. Immunohistochemical analysis of 39 operatively resected PDAC specimens reveals it is poorly differentiated, non-cohesive ones in which the INPP4B and Ecad are partially or completely compromised in expression. We therefore identify INPP4B as an tumor suppressor in PDAC which attenuates AKT activation and participates in preservation of Ecad in endocytic pool and cellular membrane.

Background With a less than 5% overall survival rate, esophageal adenocarcinoma (EAC) is one of the leading causes of death in the United States. Epithelial cell adhesion molecule (EpCAM) is a cancer stem cell (CSC) marker that is expressed in various epithelial carcinomas, including EAC. Accumulating evidence indicates that CSC subpopulations can initiate cancer development and, in addition, drive metastasis, recurrence and drug resistance. It has also been reported that EpCAM up-regulation in EAC may lead to an aggressive behavior and, thus, an adverse clinical outcome. Here, we aimed to determine whether treatment with standard chemotherapeutic agents may induce EpCAM expression and, concomitantly, increases in malignant potential and drug resistance in EAC. Methods EpCAM expression was assessed in 20 primary human EAC/adjacent normal tissues, as well as in a human EAC-derived cell line (OE-19), in a pre-malignant Barrett’s Esophagus cell line (Bar-T) and in a benign esophageal cell line (HET 1-A), using immunohistochemistry, Western blotting and qRT-PCR, respectively. Drug-induced resistance was investigated in OE-19-derived spheres treated with (a combination of) adriamycin, cisplatin and 5-fluorouracil (ACF) using survival, adhesion and flow cytometric assays, respectively, and compared to drug resistance induced by standard chemotherapeutic agents (CTA). Finally, ACF treatment-surviving cells were evaluated for their tumor forming capacities both in vitro and in vivo using spheroid formation and xenograft assays, respectively. Results High EpCAM expression was observed in esophageal cancer tissues and esophageal cancer-derived cell lines, but not in adjacent benign esophageal epithelia and benign esophageal cell lines (HET 1-A and Bar-T). The OE-19 cell spheres were drug resistant and EpCAM expression was significantly induced in the OE-19 cell spheres compared to the non-sphere OE-19 cells. When OE-19 cell spheres were challenged with ACF, the EpCAM mRNA and protein levels were further up-regulated up to 48 h, whereas a decreased EpCAM expression was observed at 72 h. EpCAM down-regulation by RNA interference increased the ACF efficacy to kill OE-19 cells. Increased EpCAM expression coincided with the CSC marker CD90 and was associated with an aggressive growth pattern of OE-19 cell spheres in vivo. Conclusions From our data we conclude that an ACF-induced increase in EpCAM expression reflects the selection of a CSC subpopulation that underlies tumor development and drug resistance in EAC.

Introduction: Pancreatic cancers are often an aggressive type of malignancy, with a 5-year survival rate estimated at around 5%. The main purpose of our study was to determine whether or not tumor dimensions influence the presence of jaundice and the diameters of the CBD and Wirsung duct. Material and methods: The study group included 32 patients (19 males, 13 females) diagnosed with various histological types of pancreatic head cancers who were hospitalized in the Surgery Department of the County Clinical Emergency Hospital of Craiova during 2016-2018. All 32 patients underwent an initial abdominal ultrasonography (US), followed by an abdominal computed tomography (CT) scan and an abdominal magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) sequences. Results: Based on tumor dimensions, 19 (59.38%) were equal to or larger than 30mm, while 13 (40.62%) were smaller than 30mm. The average age of male patients was 65.15 years, while the average age of female patients was 60.07 years. Tumor dimensions ranged between 22mm and 52mm (33.53mm on average). Furthermore, the diameter of the CBD ranged from 5mm to 20mm (13.40mm on average), while the diameter of the Wirsung duct ranged from 3mm to 12mm (5.75 mm on average). Conclusion: In conclusion, our study reached its’ initial purpose and revealed a significant association between the tumor dimensions and the diameter of the Wirsung duct and also between the diameter of the CBD and the presence of jaundice.

Classical anti-inflammatory cytokines are known to play a role in both cancer progression as well as cancer elimination. We evaluated the anti-inflammatory cytokines IL-10 and TGF-β in patients with colon adenocarcinoma and metastatic colon adenocarcinoma using immunohistochemical assays to determine the expression of the cytokines between various malignant tissues. We found tissues stained with TGF-β showed no significant upregulation within malignant tumors when compared with normal tissue controls. We observed high levels of TGF-β presence in most tissues similar to GAPDH expression. Within both colon adenocarcinoma and metastatic carcinomas there was a significant variability among patients in the expression of IL-10. While some patients experienced insignificant increases in the cytokine compared with controls, other patients had a clear upregulation of the protein within their tissue. In addition, there was an increase in the number of patients positive for IL-10 upregulation within metastatic tumors when compared with primary tumors. These data indicate that there is substantial variability between patients in regards to IL-10 expression, which may further aid in characterizing tumors and evaluating metastatic potential.