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Sökning: L773:1792 1074 OR L773:1792 1082

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1.
  • Al-Ramadan, Afkar, et al. (författare)
  • Analysis of radiation effects in two irradiated tumor spheroid models
  • 2018
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 15:3, s. 3008-3016
  • Tidskriftsartikel (refereegranskat)abstract
    • Multicellular spheroids have proven suitable as three-dimensional in vivo-like models of non-vascularized micrometastases. Unlike monolayer-based models, spheroids mirror the cellular milieu and the pathophysiological gradients inside tumor nodules. However, there is limited knowledge of the radiation effects at the molecular level in spheroids of human origin. The present study is a presentation of selected cell biological processes that may easily be analyzed with methods available at routine pathology laboratories. Using gamma irradiated pancreatic neuroendocrine BON1 and colonic adenocarcinoma HCT116 spheroids as model systems, the present study assessed the radiobiological response in these models. Spheroid growth after irradiation was followed over time and molecular responses were subsequently assessed with immunohistochemistry (IHC) staining for descriptive analyses and semi-automatic grading of apoptosis, G(2)-phase and senescence in thin sections of the spheroids. Growth studies demonstrated the BON1 spheroids were slower growing and less sensitive to radiation compared with the HCT116 spheroids. IHC staining for G2-phase was primarily observed in the outer viable P-cell layers of the spheroids, with the 6 Gy irradiated HCT116 spheroids demonstrating a very clear increase in staining intensity compared with unirradiated spheroids. Apoptosis staining results indicated increased apoptosis with increasing radiation doses. No clear association between senescence and radiation exposure in the spheroids were observed. The present results demonstrate the feasibility of the use of multicellular spheroids of human origin in combination with IHC analyses to unravel radiobiological responses at a molecular level. The present findings inspire further investigations, including other relevant IHC-detectable molecular processes in time-and radiation dose-dependent settings.
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2.
  • Algaber, Anwar, et al. (författare)
  • Targeting FHL2-E-cadherin axis by miR-340-5p attenuates colon cancer cell migration and invasion
  • 2021
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 22:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Convincing data has suggested that four and a half LIM domain 2 protein (FHL2) serves a key function in cancer cell metastasis and that microRNA (miR)-340-5p can regulate cancer cell migration. The current study hypothesized that targeting FHL2 expression by miR-340-5p in colon cancer may attenuate colon cancer cell migration and invasion. FHL2 expression was therefore assessed in colon cancer microarray datasets using Qlucore omics explorer as well as in HT-29 and AZ-97 colon cancer cell lines via reverse transcription-quantitative PCR (RT-qPCR). Colon cancer cell migration and invasion were evaluated in the presence of miR-340-5p mimic, mimic control or mimic with a target site blocker. Confocal microscopy and RT-qPCR were subsequently performed to assess FHL2, E-cadherin (E-cad) protein and mRNA expression in colon cancer cells. Microarray dataset analysis revealed that FHL2 expression was lower in primary colon cancer cells compared with normal colonic mucosa. It was revealed that the expression of miR-340-5p and FHL2 were inversely related in serum-grown and low-serum conditions in HT-29 and AZ-97 cells. Short-time serum exposure to low-serum grown cells induced FHL2 expression. Transfection of HT-29 cells with miR-340-5p mimic not only decreased serum-induced expression of FHL2 but also decreased cancer cell migration and invasion. Bioinformatics analysis revealed that FHL2 mRNA had one putative binding site for miR-340-5p at the 3-untranslated region. Blocking of the target site using a specific blocker reverted miR-340-5p mimic-induced inhibition of FHL2 expression and cancer cell migration and invasion. Confocal microscopy confirmed that the reduction of FHL2 expression by miR-340-5p mimic also reversed serum-induced E-cad disruption and that the target site blocker abrogated the effect of miR-340-5p. The current results suggested that miR-340-5p could be used to antagonize colon cancer cell metastasis by targeting the FHL2-E-cad axis.
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3.
  • Andersson, Carola, et al. (författare)
  • Primary spinal intradural mesenchymal chondrosarcoma with detection of fusion gene HEY1-NCOA2 : a paediatric case report and review of the literature
  • 2014
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 8:4, s. 1608-1612
  • Forskningsöversikt (refereegranskat)abstract
    • Mesenchymal chondrosarcoma is an extremely rare malignant tumour that most commonly originates in the bone, but is also present in extraskeletal sites. The tumour is morphologically characterized by a biphasic pattern of small round cells and islands of cartilage. Spinal mesenchymal chondrosarcomas are even rarer and, therefore, few investigations exist regarding the biological behaviour of the tumours. In the present study, we report a case of a 10-year-old female presenting with 9 months of back pain and radiographic findings of an intradural lesion measuring 1.5 cm at the level of Th4. The tumour was completely excised and subjected to pathological analyses. Following detection of the HEY1-NCOA2 fusion gene, the tumour was morphologically and immunohistochemically defined as an intradural mesenchymal chondrosarcoma attached to the dura mater. In this study, we validate the recent identification of the fusion gene HEY1-NCOA2 in paediatric extraskeletal mesenchymal chondrosarcomas: The relevant literature is reviewed and further discussed in relation to our findings.
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4.
  • Andersson, Jennie, et al. (författare)
  • Imaging of HER2 may improve the outcome of external irradiation therapy for prostate cancer patients
  • 2015
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 9:2, s. 950-954
  • Tidskriftsartikel (refereegranskat)abstract
    • Prostate cancer (PCa) is the most common type of cancer among males. Human epidermal growth factor receptor type 2 (HER2) expression in PCa has been reported by several studies and its involvement in the progression towards androgen-independent PCa has been discussed. External irradiation is one of the existing therapies, which has been demonstrated to be efficient in combination with androgen deprivation therapy for the treatment of advanced PCa. However, 20-40% of patients develop recurrent and more aggressive PCa within 10 years. The current study investigates the involvement of HER2 in survival and radioresistance in PCa cells and we hypothesized that, by monitoring HER2 expression, treatment may be personalized. The PCa cell lines, LNCap, PC3 and DU-145, received a 6 Gy single dose of external irradiation. The number of PC3 cells was not affected by a single dose of radiation, whereas a 5-fold decrease in cell number was detected in LNCap (P<0.00001) and DU-145 (P<0.0001) cells. The HER2 expression in PC3 exhibited a significant increase post irradiation, however, the expression was stable in the remaining cell lines. The administration of trastuzumab post-irradiation resulted in a 2-fold decrease in the PC3 cell number, while the drug did not demonstrate additional effects in LNCap and DU-145 cells, when compared with that of irradiation treatment alone. The results of the present study demonstrated that an increase in membranous HER2 expression in response to external irradiation may indicate cell radioresistance. Furthermore, imaging of HER2 expression prior to and following external irradiation may present a step towards personalized therapy in PCa.
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5.
  • Andersson, Sonia, et al. (författare)
  • Age, margin status, high-risk human papillomavirus and cytology independently predict recurrent high-grade cervical intraepithelial neoplasia up to 6 years after treatment
  • 2021
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 22:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study aimed to identify the factors that independently contribute to disease recurrence among women first-time treated for high-grade cervical intraepithelial neoplasia (CIN) during 4-6 years of follow-up. Overall, 529 of 530 eligible patients participated; these patients all attended a 1st follow-up appointment similar to 6 months post-conization, at which time high-risk human-papillomavirus (HPV) testing, liquid-based cytology and colposcopy were performed. Full data on margin excision status, other aspects of initial treatment and comorbidity were obtained. At least one subsequent follow-up was attended by 88% of patients. A total of 22 recurrent cases were detected during follow-up. Detected recurrence was the outcome of focus for multiple logistic regression analysis, with odds ratios (OR) and 95% confidence intervals (CI) computed. Four significant independent risk factors were identified: Age 45 years or above (OR=3.5, 95% CI=1.3-9.9), one or both unclear or uncertain margins (OR=5.3, 95% CI=2.0-14.2), positive HPV at 1st follow-up (OR=5.8, 95% CI=2.0-16.8), and abnormal cytology at 1st follow-up (OR=3.9, 95% CI=1.4-11.0). Bivariate analysis revealed that persistent HPV positivity was associated with recurrence (P<0.01). These findings indicated that incomplete excision of the CIN lesion may warrant more intensive subsequent screening, regardless of early post-conization HPV findings. Although early post-conization positive HPV was a powerful, independent predictor of recurrent high-grade CIN, over one-third of the patients with detected recurrence had a negative early post-conization HPV finding. These patients returned for routine screening, at which time, in most cases, HPV status was positive, thus indicating the need for repeated HPV evaluation. Especially during the on-going pandemic, home vaginal self-sampling is recommended. Particular attention is required for women aged >= 45 years. In addition, although not statistically significant, relevant comorbidities, especially autoimmune conditions, warrant consideration in clinical decision-making. Women who have been treated for high-grade CIN are at risk for recurrent disease and progression to cervical cancer; therefore, they require careful, individualized follow-up to avoid these adverse consequences.
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6.
  • Andersson, Sonia, et al. (författare)
  • Results of cytology and high-risk human papillomavirus testing in females with cervical adenocarcinoma in situ
  • 2013
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 6:1, s. 215-219
  • Tidskriftsartikel (refereegranskat)abstract
    • The incidence rates of cervical adenocarcinoma have been increasing over the last two decades, contrary to those of squamous cell carcinoma. This trend is particularly evident among females aged <40 years and has occurred despite extensive cytology-based screening programs. The aim of the present retrospective database study was to investigate adenocarcinoma in situ (AIS) with respect to previous cytological results, high-risk (HR) human papillomavirus (HPV) infections and histological results from AIS-adjacent squamous mucosa. Databases were used to identify 32 female patients with AIS treated for various conditions between 2009 and 2012 at the Department of Gynecology, Uppsala University Hospital (Uppsala, Sweden) and previous cytological, HPV and histological results. Of the individuals in the study, 64.3% had a previously recorded cytological result showing squamous cell abnormalities; five had glandular cell abnormalities (18%) and two had AIS (7.1%). Among the patients with available HPV results, 95% were HR-HPV-positive; HPV18/45 predominated (77%), followed by HPV16 (27%). The patients with multiple HPV infections were aged <= 32 years, while patients aged >= 38 years were only infected with HPV18/45. All but three patients had cervical intraepithelial neoplasia (CIN) in the AIS-adjacent squamous mucosa, 79% of which was CIN2 or worse. The present retrospective database study suggests that AIS is detected at screening mainly due to simultaneous squamous precursor lesions and that HPV18/45 infection is an increasing co-factor for AIS in older patients. HPV analyses of glandular precursor lesions aid in the identification of female individuals at risk of progression to invasive disease, and thus have a favorable effect on adenocarcinoma prevention, together with vaccination.
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7.
  • Andersson, Sonia, et al. (författare)
  • Uneven distribution of human papillomavirus 16111 cervical carcinoma in situ and squamous cell carcinoma in older females : A retrospective database study
  • 2014
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 8:4, s. 1528-1532
  • Tidskriftsartikel (refereegranskat)abstract
    • Human papillomavirus (HPV) 16 is the dominant cofactor in cervical cancer development. The present report investigated the age-specific prevalence of HPV16 in cervical carcinoma in situ (CIS) in females attending organised cervical cancer screening. A retrospective observational study was performed based on individual data from two databases. A total of 162 females aged between 20 and 65 years from Uppsala County, Sweden with CIS and an HPV test conducted between 2010 and 2011, preceding or concomitant to CIS diagnosis, were included. Females with cervical squamous cell carcinoma (SCC; n=35) were used for comparison. In total, 96% (n=156) of females with CIS were positive for high-risk HPV; HPV16 was the most prevalent (44.5%), followed by HPV33/52/58 (19.5%), HPV31 (13.1%) and HPV18145 (9.5%). HPV16 was most frequently detected in females with CIS aged between 20 and 29 years (73.6%) and least frequently detected in those aged between 50 and 65 years (33.3%), with a statistically significant age-specific difference (P=0.001). Among the HPV16-positive females, multiple infections were most frequent in the younger age groups. The prevalence of HPV16 in females with CIS decreased with age, whereas a high prevalence of HPV16 remained in females with SCC. These results may indicate that HPV16 has increased oncogenic potential in older females.
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8.
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9.
  • Attaran, Nima, et al. (författare)
  • Antigen peptide transporters are upregulated in squamous cell carcinoma of the oral tongue and show sex‑specific associations with survival
  • 2022
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 24:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Transporter associated with antigen processing 1 (TAP1) and TAP2 serve pivotal roles in adaptive immunity. Tumor cells often show reduced antigen presentation on their surface as one mechanism to escape immune recognition. Whether downregulation of TAPs is a common mechanism of tumor immune evasion in squamous cell carcinoma of the oral tongue (SCCOT) is unclear. In the present study, samples from 78 patients with SCCOT and 17 patients with benign hyperplastic tongue lesions were analyzed for TAP1 and TAP2 expression by immunohistochemistry. The percentage of positive cells and staining intensity were scored. Associations with clinicopathological variables and survival outcome were also investigated. The results demonstrated that TAP1 and TAP2 levels were highly associated with each other in individual samples and were upregulated in SCCOT compared with benign lesions (P<0.001). The proportion of TAP1‐ or TAP2‐positive tumor cells was >80% in all but two of the tumors, whereas 25.6 and 23.0% of the tumors showed weak intensity of TAP1 and TAP2, respectively. There were no significant associations with clinicopathological variables or survival outcomes between TAP‐intermediate/strong and TAP‐weak tumors. However, in patients <70 years old and with early stage SCCOT, male patients had better outcomes than female patients (log‐rank P<0.05), and the best outcome was observed in male patients with intermediate/strong TAP expression. In conclusion, loss of TAP was not a frequent event in SCCOT and stronger TAP expression in male patients was associated with improved survival, providing further evidence for sex‐specific immune modulation in cancer.
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10.
  • Basic, Vladimir, et al. (författare)
  • Integrative meta-analysis of gene expression profiles identifies FEN1 and ENDOU as potential diagnostic biomarkers for cervical squamous cell carcinoma
  • 2021
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 22:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Cervical carcinoma is a global public health burden. Given that it is usually asymptomatic at potentially curative stages, the development of clinically accurate tests is critical for early detection and individual risk stratification. The present study performed an integrative meta-analysis of the transcriptomes from 10 cervical carcinoma cohorts, with the aim of identifying biomarkers that are associated with malignant transformation of cervical epithelium, and establish their clinical applicability. From among the top ranked differentially expressed genes, flap structure-specific endonuclease 1 (FEN1) and poly (U)-specific endoribonuclease (ENDOU) were selected for further validation, and their clinical applicability was assessed using immunohistochemically stained microarrays comprising 110 tissue cores, using p16 and Ki67 staining as the comparator tests. The results demonstrated that FEN1 expression was significantly upregulated in 65% of tumor specimens (P=0.0001), with no detectable expression in the non-tumor tissues. Furthermore, its expression was significantly associated with Ki67 staining in tumor samples (P<0.0001), but no association was observed with p16 expression or the presence of human papilloma virus types 16/18, patient age, tumor grade or stage. FEN1 staining demonstrated lower sensitivity than p16 (69.3 vs. 96.8%) and Ki67 (69.3 vs. 76.3%); however, the specificity was identical to p16 and higher than that of Ki67 (100 vs. 71.4%).ENDOU staining was consistent with the microarray results, demonstrating 1% positivity in tumors and 40% positivity in non-tumor tissues. Gene set enrichment analysis of cervical tumors overexpressing FEN1 revealed its association with enhanced growth factor signaling, immune response inhibition and extracellular matrix remodeling, whereas tumors with low ENDOU expression exhibited inhibition of epithelial development and differentiation processes. Taken together, the results of the present study demonstrate the feasibility of the integrative meta-analysis approach to identify relevant biomarkers associated with cervical carcinogenesis. Thus, FEN1 and ENDOU may be useful diagnostic biomarkers for squamous cervical carcinoma. However, further studies are required to determine their diagnostic performance in larger patient cohorts and validate the results presented here.
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11.
  • Belkić, Karen, et al. (författare)
  • Predictors of treatment failure for adenocarcinoma in situ of the uterine cervix : Up to 14 years of recorded follow-up
  • 2022
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 24:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The incidence of adenocarcinoma-in-situ (AIS) of the uterine cervix is rising, with invasive adenocarcinoma becoming increasingly common relative to squamous cell carcinoma. The present study reviewed a cohort of 84 patients first-time treated by conization for histologically-confirmed AIS from January 2001 to January 2017, to identify risk factors associated with recurrent/persistent AIS as well as progression to invasive cervical cancer. Nearly 80% of the patients were age 40 or younger at conization. Endocervical and ectocervical margins were deemed clear in 42 of the patients. All but two patients had ≥1 follow-up, with post-conization high-risk human papilloma virus (HPV) results documented in 52 patients. Altogether, 12 histopathologically-confirmed recurrences (14.3%) were detected; two of these patients had microinvasive or invasive carcinoma. In three other patients cytology showed AIS, but without recorded histopathology. Eight patients underwent hysterectomy for incomplete resection very soon after primary conization; they were not included in bivariate or multivariate analyses. Having ≥1 post-follow-up positive HPV finding yielded the highest sensitivity for histologically-confirmed recurrence: 87.5 [95% confidence interval (CI) 47.4-99.7]. Current or historical smoking status provided highest specificity: 94.4 (95% CI 72.7-99.9) and overall accuracy: 88.0 (95% CI 68.8-97.5) for histologically-confirmed recurrence. With multiple logistic regression (MLR), adjusting for age at conization and abnormal follow-up cytology, positive HPV18 was the strongest predictor of histologically-confirmed recurrence (P<0.005). Having ≥2 positive HPV results also predicted recurrence (P<0.02). Any unclear margin yielded an odds ratio 7.21 (95% CI 1.34-38.7) for histologically-confirmed recurrence adjusting for age, but became non-significant when including abnormal cytology in the MLR model. The strong predictive value of HPV, particularly HPV18 and persistent HPV positivity vis-à-vis detected recurrence indicated that regular HPV testing for patients treated for AIS is imperative. In conclusion, furthering a participatory approach, including attention to smoking with encouragement to attend needed long-term follow-up, can better protect these patients at high risk for cervical cancer.
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12.
  • Boldrup, Linda, et al. (författare)
  • Levels of MUC1 in tumours and serum of patients with different sub-types of squamous cell carcinoma of the head and neck
  • 2020
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 20:2, s. 1709-1718
  • Tidskriftsartikel (refereegranskat)abstract
    • Mucin 1 (MUC1) is a membrane-bound and secreted glycoprotein that has a protective role in surface epithelia. We recently demonstrated that MUC1 mRNA expression was upregulated in tumour-free tongue tissues adjacent to squamous cell carcinoma of the oral tongue (SCCOT) compared with that in the tumour tissues. The present study investigated MUC1 protein in SCCOT tissue and serum from patients with squamous cell carcinoma of the head and neck (SCCHN) at different sub-sites. The results from immunohistochemistry demonstrated that all SCCOT tissues expressed MUC1; however, the protein levels were not correlated with MUC1 mRNA levels in the same tumours. Furthermore, serum MUC1 level was lower in patients with SCCOT, tonsil SCC and gingival SCC compared with that in healthy subjects; however, the difference was only significant for patients with SCCOT (P=0.0421). No correlation was seen between MUC1 level in tumour tissues and MUCI level in serum from the same patients. The absence of correlation between MUC1 protein and mRNA levels in SCCOT tissues emphasized the importance of validating genomic data in clinical samples. Although significant MUC1 downregulation was observed in the serum of patients with SCCOT, there was a large variation within the groups, suggesting that MUC1 may not be used as a biomarker for these types of tumors.
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13.
  • Carlsson, J., et al. (författare)
  • Tendencies for higher co-expression of EGFR and HER2 and downregulation of HER3 in prostate cancer lymph node metastases compared with corresponding primary tumors
  • 2013
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 5:1, s. 208-214
  • Tidskriftsartikel (refereegranskat)abstract
    • The epidermal growth factor receptor (EGFR) family members are potential targets for therapy using extracellular domain receptor binding agents, such as the antibodies trastuzumab and cetuximab, or antibodies labeled with therapeutically useful radionuclides or toxins. This is especially the case when the tumor cells are resistant to chemotherapy and tyrosine kinase inhibitors. Studies concerning the expression of these receptors in prostate cancer vary in the literature, possibly due to differences in patient inclusion, sample preparations and scoring criteria. In our study, EGFR, HER2 and HER3 expression was analyzed in prostate cancer samples from primary tumors and corresponding lymph node metastases from 12 patients. The expression of HER2 and EGFR was scored from immunohistochemical preparations and the HercepTest criteria (0, 1+, 2+ or 3+), while HER3 expression was scored as no, weak or strong staining. There were 5 EGER-positive (2+ or 3+) primary tumors and 6 EGFR-positive lymph node metastases, and there was EGFR upregulation in one metastasis. Only 4 of the 12 patients had marked HER2 expression (2+ or 3+) in their primary tumors and there was one downregulation and 5 cases of upregulation in the metastases. Thus, a total of 8 out of 12 analyzed metastases were HER2-positive. Of the 12 primary tumors, 9 expressed HER3 while only 2 of the lymph node metastases expressed recognizable HER3 staining, so 7 metastases appeared to have downregulated HER3 expression. In one of the primary tumors there was positive co-expression of EGFR and HER2, while this co-expression was observed in 4 of the metastases. Thus, there were tendencies for upregulation of HER2, increased co-expression of EGFR and HER2 and downregulation of HER3 in the prostate cancer lymph node metastases in comparison to the primary tumors. The results are encouraging for studies involving more patients. Possible strategies for EGFR- and HER2-targeted therapy are briefly discussed in the present study, especially with regard to the expression and co-expression of EGFR and HER2 in metastases.
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14.
  • Carlsson, Jessica, 1984-, et al. (författare)
  • The potential role of miR-126, miR-21 and miR-10b as prognostic biomarkers in renal cell carcinoma
  • 2019
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 17:5, s. 4566-4574
  • Tidskriftsartikel (refereegranskat)abstract
    • Renal cell carcinoma (RCC) is the most commonly diagnosed renal tumor, consisting of ~3% of all malignancies worldwide. The prognosis of RCC can vary widely, and detecting patients at risk of recurrence at an early stage of disease may improve patient outcome. The factors presently used in a clinical setting cannot reliably predict the natural history of the disease. Therefore, there is a requirement to identify novel biomarkers that can aid in predicting patient outcome. Previous studies have indicated that microRNAs (miRNAs/miRs) are potential candidates as prognostic biomarkers for patients suffering from RCC. Consequently, the aims of the present study were to validate the potential of 3 of these miRNAs to predict the prognosis of patients with RCC, and to investigate the stability of endogenous control genes for miRNA studies in RCC tissues. The expression of 7 endogenous controls was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in formalin-fixed paraffin-embedded tumor and benign tissues from patients suffering from clear cell RCC (ccRCC). The analyses identified RNU48 and U47 as the most stable endogenous controls. The expression of miR-126, miR-21 and miR-10b was analyzed using RT-qPCR in renal tissues from 116 patients diagnosed with ccRCC. All three investigated miRNAs were differentially expressed between malignant and benign tissues. miR-126 and miR-10b were also differentially expressed between grades and stages of ccRCC. In a univariate, but not in a multivariate model, low expression of miR-126 was associated with shorter time to recurrence of the disease. The results of the present study indicate that of the 3 miRNAs investigated, the expression of miR-126 has the strongest potential as a prognostic biomarker for patients suffering from ccRCC.
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15.
  • Cervantes-Madrid, Diana Lizeth, 1987, et al. (författare)
  • FosB transcription factor regulates COX-2 expression in colorectal cancer cells without affecting PGE2 expression
  • 2017
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 13:3, s. 1411-1416
  • Tidskriftsartikel (refereegranskat)abstract
    • The expression levels of cyclooxygenase (COX)-2 and the prostaglandin E2 (PGE2) content have been associated with poor prognosis in patients with colorectal cancer (CRC). There is a strong correlation between COX-2 expression and PGE2 production in tissues from CRC patients, suggesting an important role for COX-2 on the regulation of PGE2 production. Previous studies by the present authors, where CRC patients were divided into high-or low-COX-2 expressing tumors, displayed important differences in the expression levels of several transcription factors involved in carcinogenesis. Among them, FBJ murine osteosarcoma viral oncogene homolog B (FosB), which is a member of the activator protein-1 complex, was the highest upregulated transcription factor in patients with high expression levels of COX-2. The present study aimed to investigate the role of FosB on the COX-2/PGE2 axis in CRC cells with high COX-2 expression levels. Interference RNA technology was used to knockdown FosB expression in HCA-7 cells, and 72 h later the messenger (m) RNA expression levels of COX-1 and COX-2, as well as the PGE2 content, were measured. The results indicated that FosB knockdown decreased the expression levels of COX-2 but did not affect the PGE2 content or the mRNA expression levels of COX-1. The present findings suggest an important role for FosB on the regulation of COX-2 expression, but no effect on the regulation of the PGE2 levels. In addition, the present results imply independent regulatory mechanisms for COX-2 expression and PGE2 content.
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16.
  • Dimberg, Jan, et al. (författare)
  • Analysis of APC and IGFBP7 promoter gene methylation in Swedish and Vietnamese colorectal cancer patients
  • 2013
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 5:1, s. 25-30
  • Tidskriftsartikel (refereegranskat)abstract
    • The tumour suppressor gene adenomatous polyposis coli (APC) is a key component that drives colorectal carcinogenesis. The reported DNA methylation in the promoter of APC varies greatly among studies of colorectal cancer (CRC) in different populations. Insulin-like growth factor binding protein 7 (IGFBP7), also known as IGFBP‑related protein 1 (IGFBP-rP1), is expressed in various tissue types, including the lung, brain, prostate and gastrointestinal tract, and has been suggested to play a tumour suppressor role against colorectal carcinogenesis. Studies have indicated that IGFBP7 is inactivated by DNA methylation in human colon, lung and breast cancer. In the present study, we used the methylation‑specific polymerase chain reaction to study the methylation status of the APC and IGFBP7 gene promoters in cancerous and paired normal tissue to evaluate its impact on clinical factors and association with ethnicity, represented by Swedish and Vietnamese CRC patients. We also investigated the distribution of CpG islands and the CpG dinucleotide density of each CpG island in the regions which were the subject of our investigation. Overall, normal tissue from Swedish patients exhibited a significantly higher frequency of IGFBP7 gene methylation in comparison with that of Vietnamese patients. Moreover, a significantly higher number of cancer tissues from Vietnamese individuals showed higher levels of methylation versus the paired normal tissue compared with that of Swedish patients. When we studied the methylation in cancer compared with the matched normal tissue in individuals, we found that a significantly higher number of Vietnamese patients had a higher degree of IGFBP7 gene methylation in cancer versus matched normal tissue in comparison with Swedish patients. Taken together, our results suggest that the methylation of the APC and IGFBP7 gene promoter region in cancerous tissue, in combination with the predominance of methylation in normal tissue, may serve as a prognostic factor in CRC patients.
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17.
  • Dimberg, Jan, et al. (författare)
  • Expression of the serine protease inhibitor serpinA3 in human colorectal adenocarcinomas
  • 2011
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 2:3, s. 413-418
  • Tidskriftsartikel (refereegranskat)abstract
    • Proteases facilitate a number of steps in cancer progression. The serine protease inhibitors (serpins) are a protein superfamily with inhibitory activity against proteases. One of these proteases, serpinA3, appears to have a multifaceted role and is associated with inflammatory reactions, Alzheimer's disease, malignant melanoma and gastric cancer. To gain insight into the potential effect of serpinA3 on colorectal cancer (CRC) we determined whether serpinA3 is altered in colorectal tissue or plasma in CRC patients. Collectively, by using ELISA we noted a significantly lower serpinA3 level in cancer tissue compared to paired normal tissue. Moreover, the tumour serpinA3 level tended to be higher in disseminated disease as compared to localised disease. No significant difference in the plasma levels of serpinA3 was noted in the patients when compared to the controls. However, plasma serpinA3 and C-reactive protein (marker of inflammation) in the CRC patients and controls were significantly positively correlated. To confirm and detect localization of serpinA3 expression, immunohistochemistry was performed. Immunohistochemistry showed heterogeneous immunoreactivity in epithelial cells in the cancer and normal tissue and extracellular staining within bands of stroma as well as in some stromal cells. A Taq Man system was used to investigate a single nucleotide polymorphism (rs4934) in the serpinA3 signal sequence gene with supposed effect on serpinA3 secretion and expression. No significant difference was observed between CRC and control subjects regarding genotype and allelic distributions, nor were associations noted between clinical characteristics and serpinA3 levels. In conclusion, an altered serpinA3 concentration in CRC tissue may be a potential biomarker in CRC progression. SerpinA3 concentrations in plasma appear to be correlated with systemic inflammation, but do not appear to be specific to CRC patients. Further studies are warranted to improve our understanding of the role of serpinA3 in CRC.
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18.
  • Dimberg, Jan, et al. (författare)
  • Polymorphism of the p38 beta gene in patients with colorectal cancer
  • 2014
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 8, s. 1093-1095
  • Tidskriftsartikel (refereegranskat)abstract
    • The p38 mitogen‑activated protein kinase (MAPK) signaling pathways have been proposed to participate in the pathological process of cancer by affecting inflammation, proliferation, metastasis and cell survival. A single nucleotide polymorphism (SNP; rs2235356, ‑1628A→G) in the promoter region of the p38β gene has been proposed as a genetic modifier for colorectal cancer (CRC) in a Chinese population. The present study evaluated the susceptibility of patients possessing this SNP to CRC, in addition to determining its association with clinical parameters in Swedish patients with CRC. Using the LightSNiP genotyping assay, this SNP was screened in 389 patients with CRC and 517 control subjects. No significant difference in the genotype distribution or in the allelic frequencies was identified between the two groups nor was any association identified with the clinical parameters. These findings indicate that the ‑1628A→G polymorphism of the p38β gene is not significantly associated with a susceptibility to CRC in a Swedish population.
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19.
  • Ellegård, Sander, et al. (författare)
  • ERBB2 and PTPN2 gene copy numbers as prognostic factors in HER2-positive metastatic breast cancer treated with trastuzumab
  • 2019
  • Ingår i: Oncology Letters. - Athens, Greece : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 17:3, s. 3371-3381
  • Tidskriftsartikel (refereegranskat)abstract
    • Trastuzumab has markedly improved the treatment and long-term prognosis of patients with HER2-positive breast cancer. A frequent clinical challenge in patients with relapsing and/or metastatic disease is de novo or acquired trastuzumab resistance, and to date no predictive biomarkers for palliative trastuzumab have been established. In the present study, the prognostic values of factors involved in the HER2-associated PI3K/Akt signalling pathway were explored. The first 46 consecutive patients treated at the Department of Oncology, Linkoping University Hospital between 2000 and 2007 with trastuzumab for HER2-positive metastatic breast cancer were retrospectively included. The gene copy number variation and protein expression of several components of the PI3K/Akt pathway were assessed in the tumour tissue and biopsy samples using droplet digital polymerase chain reaction and immunohistochemistry. Patients with tumours displaying a high-grade ERBB2 (HER2) amplification level of amp;gt;= 6 copies had a significantly improved overall survival hazard ratio [(HR)=0.4; 95%, confidence interval (CI): 0.2-0.9] and progression-free survival (HR=0.3; 95% CI: 0.1-0.7) compared with patients with tumours harbouring fewer ERBB2 copies. High-grade ERBB2 amplification was significantly associated with the development of central nervous system metastases during palliative treatment. Copy gain (amp;gt;= 3 copies) of the gene encoding the tyrosine phosphatase PTPN2 was associated with a shorter overall survival (HR=2.0; 95% CI: 1.0-4.0) and shorter progression-free survival (HR=2.1; 95% CI: 1.0-4.1). In conclusion, high ERBB2 amplification level is a potential positive prognostic factor in trastuzumab-treated HER2-positive metastatic breast cancer, whereas PTPN2 gain is a potential negative prognostic factor. Further studies are warranted on the role of PTPN2 in HER2 signalling.
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20.
  • Fagman, Johan Bourghardt, 1980, et al. (författare)
  • EGFR, but not COX-2, protein in resected pancreatic ductal adenocarcinoma is associated with poor survival.
  • 2019
  • Ingår i: Oncology letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 17:6, s. 5361-5368
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of EGFR and COX-2 protein overexpression on clinical outcomes in pancreatic ductal adenocarcinoma (PDAC) patients remains unclear. Therefore, the aim of the present study was to evaluate the protein expression of epithelial growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in tumor cells in surgically resected PDAC, in comparison with clinicopathological characteristics and clinical outcomes. Immunohistochemical staining of formalin-fixed paraffin-embedded tissue derived from surgically resected tumors was performed. Tissue slides were evaluated for membrane wild-type EGFR and cytoplasmic COX-2 staining using a histoscore system. Statistical associations between EGFR and COX-2 staining and clinicopathological characteristics were examined to predict survival. In a cohort of 32 resected PDAC patients, high EGFR protein expression in tumor cells was significantly associated with shorter median overall survival (7.9 vs. 39.2 months, P=0.0038). The corresponding hazard ratio (HR) for patients with high EGFR protein expression in tumor cells was 3.12 [95% confidence interval (CI): 1.39-7.00, P=0.006]. COX-2 protein expression was not associated with survival (22.6 vs. 24.5 months P=0.60; HR 1.22 95% CI: 0.59-2.51, P=0.60). Following multivariate Cox regression analysis, high EGFR protein expression in tumor cells (P=0.043) remained as significant independent prognostic factor for survival. In conclusion, high wild-type EGFR protein expression, but not COX-2 protein expression, in tumor cells is a prognostic factor for reduced overall survival following pancreatic tumor resection, supporting a role for EGFR in identifying resected patients that may benefit from EGFR-targeted therapy.
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21.
  • Fohlin, Helena, 1979-, et al. (författare)
  • RAB6C is an independent prognostic factor of estrogen receptor-positive/progesterone receptor-negative breast cancer
  • 2020
  • Ingår i: Oncology Letters. - : SPANDIDOS PUBL LTD. - 1792-1074 .- 1792-1082. ; 19:1, s. 52-60
  • Tidskriftsartikel (refereegranskat)abstract
    • The majority of breast cancer tumors are estrogen receptor-positive (ER+) and can be treated with endocrine therapy. However, certain patients may exhibit a good prognosis without systemic treatment. The aim of the present study was to identify novel prognostic factors for patients with ER breast cancer tumors using gene copy data, and to investigate if these factors have prognostic value in subgroups categorized by progesterone receptor status (PR). Public data, including the whole genome gene copy data of 199 systemically untreated patients with ER+ tumors, were utilized in the present study. To assess prognostic value, patients were divided into two groups using the median gene copy number as a cut-off for the SNPs that were the most variable. One SNP was identified, which indicated that the Ras-related protein Rab-6C (RAB6C) gene may exhibit prognostic significance. Therefore, RAB6C protein expression was subsequently investigated in a second independent cohort, consisting of 469 systematically untreated patients (of which 310 were ER+) who received long term follow-up. In the public data set, a distant recurrence risk reduction of 55% was determined for copy numbers above the median value of RAB6C compared with numbers below [multivariable adjusted hazard ratio (HR), 0.45; 95% CI 0.28-0.72; P=0.001)]. It was also more pronounced in the ER+/PR- subgroup (HR, 0.15; 95% CI, 0.05-0.46; P=0.001). In the second cohort, patients of the ER+/PR- subgroup who exhibited high RAB6C expression had a reduced distant recurrence risk (HR, 0.17; 95% CI, 0.05-0.60; P=0.006). However, this was not identified among ER+/PR- tumors (HR, 1.31; 95% CI, 0.69-2.48; P=0.41). The results of the present study indicated that RAB6C serves as an independent prognostic factor of distant recurrence risk in systemically untreated patients with an ER+/PR- tumor.
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22.
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23.
  • Green, Caroline, et al. (författare)
  • Combined treatment with radiotherapy, chemotherapy and avelumab results in regression of metastatic Merkel cell carcinoma and improvement of associated Lambert‑Eaton myasthenic syndrome : a case report
  • 2022
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 24:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy arising from mecha‑ noreceptors in the basal epidermis. Due to a pronounced risk of spread and a high propensity for recurrence after treatment, immediate treatment is of utmost importance. Lambert‑Eaton myasthenic syndrome (LEMS) is a paraneoplastic phenom‑ enon affecting the muscles with autoimmune pathophysiology, and >50% of known cases are associated with an underlying malignancy. In the present report, the case of a 67‑year‑old man presenting with progressive proximal muscle weakness, auto‑ nomic dysfunction and involuntary weight loss is described. Symptoms and detection of voltage‑gated calcium channel antibodies were consistent with LEMS. Distant metastases were found in the inguinal and iliac lymph nodes, and these were immunohistochemically confirmed to be of epithelial and neuroendocrine origin, consistent with MCC. Local radio‑ therapy and chemotherapy improved the symptoms; however, a change of treatment was required due to the side effects of the chemotherapy. Avelumab, an immune checkpoint inhibitor, was therefore introduced, and within a year the patient did not only experience tumor remission but also exhibited marked improvements in muscle strength and mobility. At present, 2 years later, the MCC is still in remission. To the best of our knowledge, the present report is the first to describe MCC with associated LEMS, which was successfully treated with avelumab after previous radiotherapy and chemotherapy, with both improved functional motor recovery and tumor reduc‑ tion. In conclusion, the present case report demonstrated that the present treatment strategy is a potential treatment option and could thus be considered in similar cases.
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24.
  • Gustafsson Asting, Annika, et al. (författare)
  • Host knockout of E-prostanoid 2 receptors reduces tumor growth and causes major alterations of gene expression in prostaglandin E2-producing tumors
  • 2017
  • Ingår i: Oncology Letters. - : SPANDIDOS PUBL LTD. - 1792-1074 .- 1792-1082. ; 13:1, s. 476-482
  • Tidskriftsartikel (refereegranskat)abstract
    • Prostaglandin E-2 (PGE(2)) is elevated in a variety of malignant tumors and has been shown to affect several hallmarks of cancer. Accordingly, the PGE, receptor, E-prostanoid 2 (EP2), has been reported to be associated with patient survival and reduced tumor growth in EP2-knockout mice. Thus, the aim of the present study was to screen for major gene expression alterations in tumor tissue growing in EP2-knockout mice. EP2-knockout mice were bred and implanted with EP2 receptor-expressing and PGE(2)-producing epithelial-like tumors. Tumor tissue and plasma were collected and used for analyses with gene expression microarrays and multiplex enzyme-linked immunosorbent assays. Tumor growth, acute phase reactions/systemic inflammation and the expression of interleukin-6 were reduced in EP2-knockout tumor-bearing mice. Several hundreds of genes displayed major changes of expression in the tumor tissue when grown in EP2-knockout mice. Such gene alterations involved several different cellular functions, including sternness, migration and cell signaling. Besides gene expression, several long non-coding RNAs were downregulated in the tumors from the EP2-knockout mice. Overall, PGE(2) signaling via host EP2 receptors affected a large number of different genes involved in tumor progression based on signaling between host stroma and tumor cells, which caused reduced tumor growth.
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25.
  • Göstring, L., et al. (författare)
  • 17AAG-induced internalisation of HER2-specific Affibody molecules
  • 2016
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082 .- 1021-335X .- 1791-2431. ; 12:4, s. 2574-2580
  • Tidskriftsartikel (refereegranskat)abstract
    • The geldanamycin derivative 17-allylamino- 17-demethoxygeldanamycin (17-AAG) is known to induce internalisation and degradation of the otherwise internalisation-resistant human epidermal growth factor receptor 2 (HER2) receptor. In the present study, 17-AAG was used to increase internalisation of the HER2-specific Affibody molecule ABY-025. The cellular redistribution of halogen-labelled211At-ABY-025 and radiometal-labelled111In-ABY-025 following treatment with 17-AAG was studied. 17-AAG treatment of SKOV-3 human ovarian carcinoma and SKBR-3 human breast carcinoma cells to some extent shifted the localisation of 111In-ABY-025 from the cell surface to intracellular compartments in the two cell lines. ABY-025 labelled with the high-linear energy transfer α emitter211At was also internalised to a higher degree; however, due to its physiological properties, this nuclide was excreted faster. The results indicate that 17-AAG may be used to facilitate cell-specific intracellular localisation of a suitable cytotoxic or radioactive agent coupled to ABY-025 in HER2-overexpressing cells. © 2016, Spandidos Publications. All rights reserved.
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26.
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27.
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28.
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29.
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30.
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31.
  • Jonsson, Eva Lindell, et al. (författare)
  • Effect of radiotherapy on expression of hyaluronan and EGFR and presence of mast cells in squamous cell carcinoma of the head and neck
  • 2012
  • Ingår i: ONCOL LETT. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 4:6, s. 1177-1182
  • Tidskriftsartikel (refereegranskat)abstract
    • Head and neck squamous cell carcinoma is a common form of cancer, and despite improvements in treatment during the last decades, survival rates have not significantly increased. There is therefore a need to better understand how these tumours and the adjacent tissues react to radiotherapy, the most common type of treatment for this group of tumours. In order to improve this understanding, the expression of hyaluronan (HA) and epidermal growth factor receptor (EGFR) and the presence of mast cells were mapped before and after radiotherapy using immunohistochemistry. The results showed HA and EGFR to have similar expression patterns in tumour tissue and histologically normal squamous epithelium prior to radiotherapy. Following radiotherapy, EGFR increased in histologically normal epithelium. An increased number of mast cells were also observed as a result of radiotherapy. No expression of EGFR was observed in the connective tissue either prior to or following radiotherapy.
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32.
  • Kamat, Nasir, et al. (författare)
  • Microsatellite instability and loss of heterozygosity detected in middle-aged patients with sporadic colon cancer : A retrospective study
  • 2013
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 6:5, s. 1413-1420
  • Tidskriftsartikel (refereegranskat)abstract
    • Microsatellite instability (MSI) is a mutator phenotype that results from a defective mismatch repair (MMR) pathway. The present study examined the incidence of MSI and loss of heterozygosity (LOH) according to five markers from the panel of the National Cancer Institute (NCI) in 38 colorectal cancer (CRC) patients from the United Arab Emirates (UAE). MSI and LOH were analyzed using fragment analyses in a multiplex PCR setting on a capillary array electrophoresis platform. The expression of the MMR proteins, hMLH1 and hMSH2, was analyzed using immunohistochemistry. The cohort consisted of 17 females (44.7%) and 21 males (55.3%) with mean ages of 59.9 and 63.3 years, respectively. The overall MSI incidence was 31.3% (95% CI, 16.1-50.0), and included three patients with high MSI (MSI-H; 9.4%; 95% CI, 2.0-25.0) and seven patients with low MSI (MSI-L; 21.9%; 95% CI, 10.7-39). LOH was detected in three patients, while the remaining 25 patients (65.8%) showed no instability and were therefore classified as microsatellite stable (MSS). MSI was detected in the following screened markers: Bat25 in seven patients, Bat26 in three patients, adenomatous polyposis coli (APC; D5S346) in five patients, AFM093xh3 (D2S123) in two patients and Mfd15 (D17S250) in three patients. Of the five MSI-positive patients, four (80%) were evidently younger, aged 38, 48, 49 and 59 years, respectively. The MSI-H incidence (9.4%) was lower compared with that of other ethnic groups. In terms of the MMR proteins, hMLH1 expression was deficient in seven patients, of whom three were MSI-H patients, and hMSH2 was deficient in three patients. Fisher's exact test showed significant associations between hMLH1 and MSI when classified as MSS, MSI-L or MSI-H (P=0.0003). No such association was observed with abnormal MMR protein expression, age, cancer stage or gender.
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33.
  • Karlsson, Henning, et al. (författare)
  • Selective radiosensitization by nitazoxanide of quiescent clonogenic colon cancer tumour cells
  • 2022
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 23:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Nitazoxanide is a Food and Drug Administration-approved antiprotozoal drug recently demonstrated to be selectively active against quiescent and glucose-deprived tumour cells. This drug also has several characteristics that suggest its potential as a radiosensitizer. The present study aimed to investigate the interaction between nitazoxanide and radiation on human colon cancer cells cultured as monolayers, and to mimic key features of solid tumours in patients, as spheroids, as well as in xenografts in mice. In the present study, colon cancer HCT116 green fluorescent protein (GFP) cells were exposed to nitazoxanide, radiation or their combination. Cell survival was analysed by using total cell kill and clonogenic assays. DNA double-strand breaks were evaluated in the spheroid experiments, and HCT116 GFP cell xenograft tumours in mice were used to investigate the effect of nitazoxanide and radiation in vivo. In the clonogenic assay, nitazoxanide synergistically and selectively sensitized cells grown as spheroids to radiation. However, this was not observed in cells cultured as monolayers, as demonstrated in the total cell kill assays, and much less with the clinically established sensitizer 5-fluorouracil. The sensitizing effect from nitazoxanide was confirmed via spheroid gamma-H2A histone family member X staining. Nitazoxanide and radiation alone similarly inhibited the growth of HCT116 GFP cell xenograft tumours in mice with no evidence of synergistic interaction. In conclusion, nitazoxanide selectively targeted quiescent glucose-deprived tumour cells and sensitized these cells to radiation in vitro. Nitazoxanide also inhibited tumour growth in vivo. Thus, nitazoxanide is a candidate for repurposing into an anticancer drug, including its use as a radiosensitizer.
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34.
  • Kuphal, Silke, et al. (författare)
  • UVB radiation represses CYLD expression in melanocytes
  • 2017
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 14:6, s. 7262-7268
  • Tidskriftsartikel (refereegranskat)abstract
    • CYLD lysine 63 deubiquitinase (CYLD) was originally identified as a tumor suppressor that is mutated in familial cylindromatosis. Unlike in cylindromatosis, downregulation of the deubiquitinase CYLD in melanoma, a highly aggressive tumor, is not caused by mutations in the CYLD gene, but rather by a constitutive and high expression of the snail family transcriptional repressor 1 (SNAIL1). A reduced CYLD level leads to B-cell lymphoma-3/p50/p52-dependent nuclear factorκB activation, which in turn triggers the expression of genes such as cyclin D1 and N-cadherin. Elevated levels of cyclin D1 and N-cadherin promote melanoma proliferation and invasion. By analyzing the regulation of CYLD expression in melanocytes, the present study identified a signaling pathway that is regulated in response to ultraviolet B (UVB) radiation in melanocytes. UVB light leads to an extracellular signal-regulated kinase-mediated induction of SNAIL1 and subsequent downregulation of CYLD expression in normal human epithelial melanocytes. The UVB-mediated suppression of CYLD in melanocytes may have a key role in the reaction to UV stimuli, and may also potentially be involved in the early malignant transformation processes.
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35.
  • Li, Yifei, et al. (författare)
  • Expression and clinical significance of FXYD3 in endometrial cancer
  • 2014
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 8:2, s. 517-522
  • Tidskriftsartikel (refereegranskat)abstract
    • FXYD3 expression is upregulated in numerous cancer cell types. The present study compared the FXDY3 expression in normal endometrium, premalignant lesion and endometrial cancer tissue samples, and investigated the correlation between FXDY3 expression and clinicopathological features. FXYD3 expression was analyzed by streptavidin-peroxidase immunohistochemistry in 21 normal endometrial tissue samples, 18 atypical endometrial hyperplasia samples and 50 tissues obtained from patients diagnosed with endometrial cancer. The percentage of FXYD3-positive cell expression in the normal endometrium, atypical hyperplasia and endometrial cancer tissues samples was 0, 22, and 26%, respectively. The differences between the atypical hyperplasia and endometrial cancer groups were statistically significant when compared with the normal group (P=0.007 and P=0.037, respectively). There was no significant difference between the atypical hyperplasia and endometrial cancer groups. The percentage of FXYD3-positive cells correlated with the fertility frequency (Pless than0.05). In conclusion, FXYD3 is a potential biomarker for endometrial cancer, and its upregulation may be an early event in endometrial carcinoma progression. In addition, FXYD3 expression in endometrial carcinoma correlates with fertility frequency.
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36.
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37.
  • Loizou, Christos, et al. (författare)
  • Incidence of tonsillar cancer in northern Sweden : Impact of human papilloma virus
  • 2015
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 10:6, s. 3565-3572
  • Tidskriftsartikel (refereegranskat)abstract
    • The incidence rate of tonsillar cancer is increasing worldwide. The current study identifies a parallel increase in the incidence of tonsillar cancer, human papilloma virus (HPV) and p16 expression among a population from northern Sweden, a sparsely populated area, confirming the strong association between p16 and HPV infection in tonsillar tissue. Data from the Swedish Cancer Registry was assessed to identify cases of tonsillar cancer in the northern territorial area of Sweden. HPV DNA was extracted from paraffin embedded diagnostic biopsies and detected by polymerase chain reaction using general primers Gp5+/6+ and CpI/IIG. Expression of p16 was identified by immunochemistry. Patients were grouped into urban or rural residence categories. A total of 214 cases were identified, comprising 155 (72.4%) men and 59 (27.6%) women, and 65 of these patients, who presented between 2000 and 2012, were analyzed. The overall median age for the analyzed patients was 58 years; 48 (74%) were males (median age, 57.5 years) and 17 (26%) were females (median age, 65 years). Of the 65 specimens, 59 (91%) were positive for HPV, and 62 (95%) expressed p16. The incidence of tonsillar cancer in the cohort demonstrated a 2-fold increase between 1990 and 2013; specifically, a 2.7-fold increase was observed in men whilst the female group exhibited only a small increase. These findings demonstrate a strong association between p16 expression and HPV infection in tonsillar malignancies. The incidence of HPV-positive tonsillar cancer has increased in recent years, even in sparsely populated regions, as demonstrated in northern Sweden.
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38.
  • Matic, Natasa, et al. (författare)
  • In vitro measurement of glucose uptake after radiation and cetuximab treatment in head and neck cancer cell lines using 18F-FDG, gamma spectrometry and PET/CT
  • 2019
  • Ingår i: Oncology Letters. - : SPANDIDOS PUBL LTD. - 1792-1074 .- 1792-1082. ; 18:5, s. 5155-5162
  • Tidskriftsartikel (refereegranskat)abstract
    • The standard treatment for head and neck squamous cell carcinoma (HNSCC) is radiotherapy, often in combination with chemotherapy or surgery. However, a novel monoclonal antibody, cetuximab (Erbitux (R)), has also been approved for patient therapy. The aim of present study was to develop an in vitro method for the measurement of 18F-fluoro-2deoxy-D-glucose (FDG) to determine if cellular 18F-FDG uptake is associated with response to radiotherapy or cetuximab treatment. In the current study, HNSCC cell lines were treated with radiation or with cetuximab. Next, the uptake of 18F-FDG was measured using a gamma spectrometer (GS). Thereafter, uptake after radiation was measured first with GS and then compared with positron emission tomography (PET)/computed tomography (CT) imaging. Furthermore, the mRNA expression of glucose transporter 1 (GLUT1) was measured following cetuximab treatment via reverse transcription-quantitative PCR. A study protocol was developed to measure the cellular uptake of 18F-FDG via gamma-ray spectrometry and comparable results were obtained with those of clinical PET/CT. The results revealed a decrease in 18F-FDG after radiation and cetuximab treatment. The uptake of 18F-FDG following cetuximab treatment was significantly lower in the cetuximab-sensitive cell line UT-SCC-14 compared with the cetuximab-resistant cell lines UT-SCC-2 and UT-SCC-45. Furthermore, after treatment with cetuximab for 24 and 48 h, a significant increase in GLUT1 expression was detected in the sensitive cell line compared with the two resistant cell lines. In conclusion, a novel yet reliable method for the measurement of intracellular 18F-FDG via GS has been developed, and our results indicate that 18F-FDG uptake is associated with radiation and cetuximab response in HNSCC.
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39.
  • Memon, Ashfaque A., et al. (författare)
  • Soluble HER3 predicts survival in bladder cancer patients
  • 2018
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 15:2, s. 1783-1788
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of soluble human epidermal growth factor receptor (sHER3) in bladder cancer remains unclear. In the present study, an ELISA was developed for the quantification of sHER3 and its role was investigated in patients with bladder cancer (n=82) followed for 10 years. Furthermore, the effects of sHER3 on bladder cancer cell growth and migration were also investigated. The results demonstrated that plasma sHER3 levels were significantly higher in non-invasive tumours (Ta) compared with muscle-invasive tumours (T2-T4). Higher sHER3 levels were associated with a more improved survival rate. However multivariate Cox regression analysis, adjusted for clinical stage, grade, type and size of the tumour, demonstrated that sHER3 was not an independent biomarker of survival. Exogenous sHER3 significantly inhibited bladder cancer cell growth and migration. These results suggest that high sHER3 levels are associated with improved survival rates in patients with bladder cancer, and that sHER3 inhibits bladder cancer cell growth and migration.
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40.
  • Mikkelsen, L. H., et al. (författare)
  • Genomic and immunohistochemical characterisation of a lacrimal gland oncocytoma and review of literature
  • 2017
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 14:4, s. 4176-4182
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the present study was to report the genetic and immunohistochemical profile of a rare case of lacrimal gland oncocytoma. A 20-year-old male underwent magnetic resonance imaging (MRI) due to viral encephalitis. Notably, the MRI revealed a multicystic tumor in the left lacrimal gland. A lateral orbitotomy was performed and the tumor was completely excised. Four months following surgery, the patient was free of symptoms. Histopathologically, the tumor was composed of large, eosinophilic and polyhedral cells with small round nuclei. The tumor cells stained strongly for antimitochondrial antibody MU213-UC, cytokeratin (CK) 5/6, CK 7, CK 17, CK 8/18 and CK 19. The final diagnosis was an oncocytoma of the lacrimal gland without any signs of malignancy. Array-based comparative genomic hybridisation demonstrated a gain of one copy of chromosome 8 and loss of one copy of chromosome 22 as the sole genomic imbalances. These chromosomal alterations have not previously been identified in oncocytoma and may be specific to lacrimal gland oncocytoma. Sequencing of the mitochondrial genome demonstrated multiple alterations of the NADH-ubiquinone oxidoreductase chain 5 (ND5) gene involved in mitochondrial oxidative phosphorylation. This may support the notion of a common genetic background of oncocytic lesions in the lacrimal gland and other anatomical sites. © 2017, Spandidos Publications. All rights reserved.
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41.
  • Mörth, Charlott, et al. (författare)
  • Validation and optimization of a predictive model for radiation pneumonitis in patients with lung cancer
  • 2016
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 12:2, s. 1144-1148
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the current retrospective study was to validate a predictive model for radiation pneumonitis (STRIPE) in an independent dataset and to investigate whether the addition of other potential risk factors could strengthen the accuracy of the model. Consecutive patients with non-small cell lung carcinoma (NSCLC; n=71) treated with definitive concurrent chemotherapy and radiotherapy were retrospectively assessed for radiation pneumonitis (RP). The results identified that 16 (23%) patients developed grade >= 2 RP. Furthermore, STRIPE score (intermediate vs. low risk) was independently associated with the development of RP [odds ratio (OR), 3.72; 95% confidence interval (CI), 1.00-13.89], whereas current smoking status was found to be protective against RP (OR, 0.09; 95% CI, 0.01-0.78). Similar discriminatory power of the STRIPE score was observed as in the original study. The addition of smoking status strengthened the model's discriminatory ability to predict RP. Thus, the addition of smoking status as a risk factor may strengthen the accuracy of the model for predicting RP in patients with NSCLC.
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42.
  • Nilsson, Jonas, et al. (författare)
  • Incidence trends in high-grade primary brain tumors in males and females
  • 2017
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 13:4, s. 2831-2837
  • Tidskriftsartikel (refereegranskat)abstract
    • The focus of the present review is to investigate whether there is a variation in the incidence rates between male and female patients with high-grade primary brain tumors and if there are altered incidence rates associated with the time at which they were diagnosed. Previous studies identified in internationally peer-reviewed journals were identified using a systematic search of the PubMed database. Due to the difficulties in data interpretation, studies that exclusively included patient data classified prior to the 2nd edition of the World Health Organization histological classification system of brain tumors were excluded. The overall incidence rates and incidence trends of male and female patients were analyzed separately. The mean age-adjusted overall incidence rate in the male population was 1.27 per 100,000 compared with 0.89 per 100,000 in the female population. The variance between the two genders differed and a Wilcoxon rank-sum test indicated that there was no significant difference in the incidence rate of high-grade primary brain tumors between males and females (P=0.3658). Furthermore, there was no significant difference in incidence rate trend between 1996-2004 and 2005-2010 for male or female populations (P=0.101 and P=0.472, respectively). The results from the present systematic review did not demonstrate a significant difference in incidence rate between the two genders. Therefore, the results from the current study are considered to be preliminary and further studies are required to elucidate this issue.
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43.
  • Nilsson, Johan S., et al. (författare)
  • Dendritic cell subpopulations in nasopharyngeal cancer
  • 2019
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 17:2, s. 2557-2561
  • Tidskriftsartikel (refereegranskat)abstract
    • Nasopharyngeal cancer (NPC) is associated with Epstein-Barr virus (EBV) and EBV antigen may be utilized for therapeutic purposes, including targeting of dendritic cells (DCs). Although DCs may be present in NPC, the information is limited and not up-to-date with current knowledge on DC subsets. In the present study, biopsies from untreated NPC were obtained and subjected to multicolor flow-cytometry focusing on DC subtype markers: CD123 for plasmacytoid DCs (pDCs); and CD1c and CD141 for myeloid DCs (mDCs). Furthermore, subset-specific expression of the C-lectin receptor (CLR) CD207 (also termed langerin) was assessed. pDCs and mDCs were detected in the NPC lesions, contributing to a frequency mean average of 0.78% of CD45+ leukocytes in situ. Different subpopulations, previously not described in NPC, were observed, including: CD123+ pDCs; CD1c+ mDCs; CD141+ mDCs; and CD1c-CD141- mDCs. A high frequency of CD1c+ mDCs expressing CD207 was observed, compared with other subsets. In conclusion, different DC subsets are present in NPC lesions. The CLR CD207, a selective endocytic marker on CD1c+ mDCs, may be targeted for therapeutic purposes to facilitate cross-presentation of antigens and aid cell-mediated antitumor effects.
  •  
44.
  •  
45.
  • Prosén, Sara, 1980-, et al. (författare)
  • Decreased expression of the mitochondrial solute carrier SLC25A43 in basal cell carcinoma compared with healthy skin
  • 2017
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 14:2, s. 2218-2222
  • Tidskriftsartikel (refereegranskat)abstract
    • Basal cell carcinoma is the most common type of cancer in fair-skinned individuals, and its incidence is rapidly increasing. The aim of the present study was to investigate the gene and protein expression of the mitochondrial solute carrier family 25 member 43 (SLC25A43) in basal cell carcinoma. SLC25A43 has previously been identified to be genetically altered and associated with cell proliferation in human epidermal growth factor receptor 2-positive breast cancer. However, the knowledge about SLC25A43 is limited, and its role in other cancers is unknown. The SLC25A43 gene and protein expression was analysed in 14 basal cell carcinomas and healthy skin samples from the same individuals by quantitative polymerase chain reaction and immunohistochemistry, respectively. The results demonstrated a significantly lower (>= 50%) SLC25A43 gene expression in all carcinomas compared with that in healthy skin. In addition, SLC25A43 protein expression was absent in >90% of all visual fields in the basal cell carcinomas, and the H-score was significantly lower in tumours compared with the adjacent epidermis. These results demonstrate that SLC25A43 expression is altered at the gene and protein levels in basal cell carcinoma. The underlying mechanisms and the clinical relevance of these data must be elucidated in additional experimental and clinical studies.
  •  
46.
  • Ranhem, Cecilia, et al. (författare)
  • Evaluation of dyskerin expression and the Cajal body protein WRAP53 beta as potential prognostic markers for patients with primary vaginal carcinoma
  • 2022
  • Ingår i: Oncology Letters. - : SPANDIDOS PUBL LTD. - 1792-1074 .- 1792-1082. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Primary vaginal cancer (PVC) is a rare gynaecological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53 beta), both of which exert their functions in the telomerase holoenzyme complex, have been shown to be upregulated in different cancer types. These proteins have also been proposed as prognostic markers in some types of cancer. The aim of the present study was to examine the expression patterns of dyskerin and WRAP53 beta in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prognosis in PVC, the expression of these two proteins and their potential association with clinical variables and survival were also evaluated. The expression of dyskerin and WRAP53 beta was assessed in PVC tumour samples from 68 patients using immunohistochemistry. The majority of tumour samples showed low and moderate expression levels of dyskerin. Upregulation of dyskerin in tumour samples was significantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53 beta was also expressed in most of the cells but was not significantly associated with clinical variables or survival. This study demonstrates that upregulation of dyskerin is significantly associated with poor prognosis. Thus, dyskerin may serve as a promising prognostic marker and a potential putative therapeutic target in PVC.
  •  
47.
  • Ranhem, Cecilia, et al. (författare)
  • Evaluation of dyskerin expression and the Cajal body protein WRAP53β as potential prognostic markers for patients with primary vaginal carcinoma
  • 2022
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Primary vaginal cancer (PVC) is a rare gynaecological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53β), both of which exert their functions in the telomerase holoenzyme complex, have been shown to be upregulated in different cancer types. These proteins have also been proposed as prognostic markers in some types of cancer. The aim of the present study was to examine the expression patterns of dyskerin and WRAP53β in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prognosis in PVC, the expression of these two proteins and their potential association with clinical variables and survival were also evaluated. The expression of dyskerin and WRAP53β was assessed in PVC tumour samples from 68 patients using immunohistochemistry. The majority of tumour samples showed low and moderate expression levels of dyskerin. Upregulation of dyskerin in tumour samples was significantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53β was also expressed in most of the cells but was not significantly associated with clinical variables or survival. This study demonstrates that upregulation of dyskerin is significantly associated with poor prognosis. Thus, dyskerin may serve as a promising prognostic marker and a potential putative therapeutic target in PVC.
  •  
48.
  • Ranhem, Cecilia, et al. (författare)
  • Evaluation of dyskerin expression and the Cajal body protein WRAP53β as potential prognostic markers for patients with primary vaginal carcinoma
  • 2022
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Primary vaginal cancer (PVC) is a rare gynae- cological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53β), both of which exert their functions in the telomerase holoenzyme complex, have been shown to be upregulated in different cancer types. These proteins have also been proposed as prognostic markers in some types of cancer. The aim of the present study was to examine the expression patterns of dyskerin and WRAP53β in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prog- nosis in PVC, the expression of these two proteins and their potential association with clinical variables and survival were also evaluated. The expression of dyskerin and WRAP53β was assessed in PVC tumour samples from 68 patients using immunohistochemistry. The majority of tumour samples showed low and moderate expression levels of dyskerin. Upregulation of dyskerin in tumour samples was signifi- cantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53β was also expressed in most of the cells but was not significantly associated with clinical variables or survival. This study demonstrates that upregulation of dyskerin is significantly associated with poor prognosis. Thus, dyskerin may serve as a promising prognostic marker and a potential putative therapeutic target in PVC.
  •  
49.
  • Salehi, Amir M., et al. (författare)
  • Patients with oral tongue squamous cell carcinoma and co‑existing diabetes exhibit lower recurrence rates and improved survival : implications for treatment
  • 2024
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 27:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Locoregional recurrences and distant metastases are major problems for patients with squamous cell carcinoma of the head and neck (SCCHN). Because SCCHN is a heterogeneous group of tumours with varying characteristics, the present study concentrated on the subgroup of squamous cell carcinoma of the oral tongue (SCCOT) to investigate the use of machine learning approaches to predict the risk of recurrence from routine clinical data available at diagnosis. The approach also identified the most important parameters that identify and classify recurrence risk. A total of 66 patients with SCCOT were included. Clinical data available at diagnosis were analysed using statistical analysis and machine learning approaches. Tumour recurrence was associated with T stage (P=0.001), radiological neck metastasis (P=0.010) and diabetes (P=0.003). A machine learning model based on the random forest algorithm and with attendant explainability was used. Whilst patients with diabetes were overrepresented in the SCCOT cohort, diabetics had lower recur‑ rence rates (P=0.015 after adjusting for age and other clinical features) and an improved 2‑year survival (P=0.025) compared with non‑diabetics. Clinical, radiological and histological data available at diagnosis were used to establish a prognostic model for patients with SCCOT. Using machine learning to predict recurrence produced a classification model with 71.2% accuracy. Notably, one of the findings of the feature importance rankings of the model was that diabetics exhibited less recur‑ rence and improved survival compared with non‑diabetics, even after accounting for the independent prognostic variables of tumour size and patient age at diagnosis. These data imply that the therapeutic manipulation of glucose levels used to treatdiabetes may be useful for patients with SCCOT regardless of their diabetic status. Further studies are warranted to investigatethe impact of diabetes in other SCCHN subtypes.
  •  
50.
  • Sgaramella, Nicola, et al. (författare)
  • Ethnicity based variation in expression of E-cadherin in patients with squamous cell carcinoma of the oral tongue
  • 2018
  • Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 16:5, s. 6603-6607
  • Tidskriftsartikel (refereegranskat)abstract
    • The oral tongue is the most common site for tumours within the oral cavity. Despite intense research, there has been no improvement in the survival rate for patients with oral tongue squamous cell carcinoma (OTSCC) during the last decades. Differences between oral cancer patients based on ethno-geographical distribution have been reported. The present study used immunohistochemistry to evaluate commonly used markers of cancer cell phenotypes, E-cadherin, -catenin and cytokeratins 5 and 19, in 120 patients with OTSCC. To evaluate the impact of ethnicity, patients from Sweden and Italy were included. A higher proportion of Swedish patients exhibited high expression of E-cadherin in their tumours (P=0.039), and high levels of E-cadherin in Swedish OTSCC patients that had succumbed to their disease were associated with poor prognosis. These data demonstrated differences in the pathological characteristics of OTSCC between two different European populations. The findings emphasise the need to take ethnicity/geographical location of patients into account when comparing results from different studies of OTSCC.
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