Tumour Biology[JOURNAL]
Sun
200 papers
The component changes of lysophospholipid mediators in colorectal cancer.
Kitamura C, Sonoda H, Nozawa H … +13 more , Kano K, Emoto S, Murono K, Kaneko M, Hiyoshi M, Sasaki K, Nishikawa T, Shuno Y, Tanaka T, Hata K, Kawai K, Aoki J, Ishihara S
Tumour Biol · 2019 May · PMID 31106679 · Publisher ↗
Although lysophospholipids are known to play an important role in the development and progression of several kinds of cancers, their role in human colorectal cancer is as yet unclear. In this study, we aim to investigate...
Although lysophospholipids are known to play an important role in the development and progression of several kinds of cancers, their role in human colorectal cancer is as yet unclear. In this study, we aim to investigate lysophospholipid levels in colorectal cancer tissues to identify lysophospholipids, the levels of which change specifically in colorectal cancers. We used liquid chromatography-tandem mass spectrometry to measure lysophospholipid levels in cancerous and normal tissues from 11 surgical specimens of sigmoid colon cancers, since recent advances in this field have improved detection sensitivities for lysophospholipids. Our results indicate that, in colon cancer tissues, levels of lysophosphatidylinositol and lysophosphatidylserine were significantly higher ( p = 0.025 and p = 0.01, respectively), whereas levels of lysophosphatidic acid were significantly lower ( p = 0.0019) than in normal tissues. Although levels of lysophosphatidylglycerol were higher in colon cancer tissues than in normal tissues, this difference was not found to be significant ( p = 0.11). Fatty acid analysis further showed that 18:0 lysophosphatidylinositol and 18:0 lysophosphatidylserine were the predominant species of lysophospholipids in colon cancer tissues. These components may be potentially involved in colorectal carcinogenesis.
Radotinib inhibits mitosis entry in acute myeloid leukemia cells via suppression of Aurora kinase A expression.
Heo SK, Noh EK, Jeong YK … +8 more , Ju LJ, Sung JY, Yu HM, Cheon J, Koh S, Min YJ, Choi Y, Jo JC
Tumour Biol · 2019 May · PMID 31074363 · Publisher ↗
Aurora kinases play critical roles in regulating several processes pivotal for mitosis. Radotinib, which is approved in South Korea as a second-line treatment for chronic myeloid leukemia, inhibits the tyrosine kinase BC...
Aurora kinases play critical roles in regulating several processes pivotal for mitosis. Radotinib, which is approved in South Korea as a second-line treatment for chronic myeloid leukemia, inhibits the tyrosine kinase BCR-ABL and platelet-derived growth factor receptor. However, the effects of radotinib on Aurora kinase expression in acute myeloid leukemia are not well studied. Interestingly, the cytotoxicity of acute myeloid leukemia cells was increased by radotinib treatment. Radotinib significantly decreased the expression of cyclin-dependent kinase 1 and cyclin B1, the key regulators of G2/M phase, and inhibited the expression of Aurora kinase A and Aurora kinase B in acute myeloid leukemia cells. In addition, radotinib decreased the expression and binding between p-Aurora kinase A and TPX2, which are required for spindle assembly. Furthermore, it reduced Aurora kinase A and polo-like kinase 1 phosphorylation and suppressed the expression of α-, β-, and γ-tubulin in acute myeloid leukemia cells. Furthermore, radotinib significantly suppressed the key regulators of G2/M phase including cyclin B1 and Aurora kinase A in a xenograft animal model. Therefore, our results suggest that radotinib can abrogate acute myeloid leukemia cell growth both in vitro and in vivo and may serve as a candidate agent or a chemosensitizer for treating acute myeloid leukemia.
Corrigendum.
Tumour Biol · 2019 May · PMID 31044657 · Publisher ↗
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Mesenchymal stem cells targeting PI3K/AKT pathway in leukemic model.
Ahmed ESA, Ahmed NH, Medhat AM … +3 more , Said UZ, Rashed LA, Abdel Ghaffar ARB
Tumour Biol · 2019 Apr · PMID 31018830 · Publisher ↗
Mesenchymal stem cells have therapeutic properties that are related to their potentials for trans-differentiation, immunomodulation, anti-inflammatory, inhibitory effect on tumor proliferation, and induction of apoptosis...
Mesenchymal stem cells have therapeutic properties that are related to their potentials for trans-differentiation, immunomodulation, anti-inflammatory, inhibitory effect on tumor proliferation, and induction of apoptosis. This study was performed to analyze the role of mesenchymal stem cells as an alternative for cellular signaling growth factors involved in the pathogenesis of leukemogenesis in rats. Treatment of rats with 7,12-dimethyl benz [a] anthracene induced leukemogenesis appeared as a significant decrease in hematological parameters with concomitant significant increase in bone marrow oxidative and inflammatory indices (transforming growth factor beta and interleukin-6) in comparison with normal groups. On the contrary, Western immunoblotting showed a significant increase in the signaling growth factors: PI3K, AKT, mTOR proteins and a significant decrease in PTEN in 7,12-dimethyl benz [a] anthracene-treated group. In addition, a significant increase in the transcript levels of B cell lymphoma-2 protein gene in the 7,12-dimethyl benz [a] anthracene group, while that of C-X-C motif chemokine receptor-4 and B cell lymphoma-2 protein associated x-protein were significantly downregulated compared to controls. Meanwhile, therapeutic mesenchymal stem cells treatment predict a significant improvement versus 7,12-dimethyl benz [a] anthracene group through the modulation of growth factors that confront bone marrow dysplasia. In the same direction treatment of 7,12-dimethyl benz [a] anthracene group with mesenchymal stem cells, it induced apoptosis and increased the homing efficacy to bone marrow. In conclusion, mesenchymal stem cells improve hematopoiesis and alleviate inflammation, and modulated PI3K/AKT signaling pathway contributed to experimental leukemogenesis.
Common matrix metalloproteinase-2 gene variants and altered susceptibility to breast cancer and associated features in Tunisian women.
Habel AF, Ghali RM, Bouaziz H … +8 more , Daldoul A, Hadj-Ahmed M, Mokrani A, Zaied S, Hechiche M, Rahal K, Yacoubi-Loueslati B, Almawi WY
Tumour Biol · 2019 Apr · PMID 31014197 · Publisher ↗
A role for matrix metalloproteinase polymorphisms in breast cancer development and progression was proposed, but with inconclusive results. We assessed the relation of matrix metalloproteinase-2 variants with breast canc...
A role for matrix metalloproteinase polymorphisms in breast cancer development and progression was proposed, but with inconclusive results. We assessed the relation of matrix metalloproteinase-2 variants with breast cancer and related phenotypes in Tunisians. This case-control retrospective study involved 430 women with breast cancer and 498 healthy controls. Genotyping of matrix metalloproteinase-2 rs243866, rs243865, rs243864, and rs2285053 was analyzed by allelic exclusion. The minor allele frequency of rs2285053 was significantly lower in women with breast cancer cases as compared to control women; minor allele frequencies of the remaining single-nucleotide polymorphisms were similar between cases and control women. The distribution of rs243865 and rs2285053 genotypes was significantly different between breast cancer patients and control subjects. This persisted when key covariates were controlled for. None of the matrix metalloproteinase-2 variants were associated with estrogen receptor positivity, progesterone receptor positivity, or with double estrogen receptor-progesterone receptor positivity in breast cancer patients. Matrix metalloproteinase-2 rs243866, rs243865, and rs243864 were positively associated with menstrual irregularity and histological type, while rs243866 and rs2285053 were negatively associated with menarche and nodal status. In addition, rs2285053 was negatively associated with triple negativity, tumor size, distance metastasis, molecular type, and chemotherapy. Haploview analysis revealed high linkage disequilibrium between matrix metalloproteinase-2 variants. Four-locus Haploview analysis identified haplotypes GCTT and GTTC to be negatively associated with breast cancer, which remained statistically after controlling for key covariates. Matrix metalloproteinase-2 alleles and genotypes, along with four-locus haplotypes, are related to reduced susceptibility to breast cancer in Tunisian women, suggesting a protective effect.
Association of expression of inflammatory response genes and DNA repair genes in colorectal carcinoma.
Germini DE, Franco MIF, Fonseca FLA … +6 more , de Sousa Gehrke F, da Costa Aguiar Alves Reis B, Cardili L, Oshima CTF, Theodoro TR, Waisberg J
Tumour Biol · 2019 Apr · PMID 30973070 · Publisher ↗
Inflammation is an important etiological factor of colorectal carcinoma and may be related to colorectal carcinoma growth and proliferation. This study aimed to verify whether the presence of chronic inflammation represe...
Inflammation is an important etiological factor of colorectal carcinoma and may be related to colorectal carcinoma growth and proliferation. This study aimed to verify whether the presence of chronic inflammation represented by tumor necrosis factor-α, interleukin-2, interleukin-6, and interleukin-10 gene expression is related to hMLH1, hMSH2, hMSH6, and PMS2 gene expression and the corresponding protein levels of these genes from the DNA repair system. A total of 83 patients were operated on for curative or palliative colorectal carcinoma. Expression of the inflammatory response genes tumor necrosis factor-α, interleukin-2, interleukin-6, and interleukin-10 as well as expression of the hMLH1, hMSH2, hMSH6, and PMS2 genes of the DNA repair system (mismatch repair) and the expression levels of the corresponding mismatch repair proteins were measured in neoplastic tissue by reverse transcription polymerase chain reaction and immunohistochemistry, respectively. Associations were observed between hMSH6 mRNA expression and interleukin-2 mRNA expression (p = 0.026) as well as between hMLH1 and hMSH2 gene expression and tumor necrosis factor-α gene expression (p = 0.042). Higher tissue levels of interleukin-2 and tumor necrosis factor-α gene expression were associated with lower hMSH6, hMLH1, and hMSH2 gene expression.
CXC chemokine ligand 1 mediates adiponectin-induced angiogenesis in ovarian cancer.
Ouh YT, Cho HW, Lee JK … +3 more , Choi SH, Choi HJ, Hong JH
Tumour Biol · 2019 Apr · PMID 30967059 · Publisher ↗
OBJECTIVES: Adiponectin is a cytokine secreted from adipose tissue that regulates energy homeostasis, inflammation, and cell proliferation. Obesity is associated with increased risk of various cancers, including ovarian...
OBJECTIVES: Adiponectin is a cytokine secreted from adipose tissue that regulates energy homeostasis, inflammation, and cell proliferation. Obesity is associated with increased risk of various cancers, including ovarian cancer. Adipokines, including adiponectin, have been implicated as a factor linking obesity and carcinogenesis. The oncogenic role of adiponectin is not known with regard to various cancer types. We sought to determine the role of adiponectin in angiogenesis in ovarian cancer in vitro. METHODS: We transfected SKOV3 cells with vascular endothelial growth factor small interfering RNA in order to identify the independent angiogenic role of adiponectin in ovarian cancer. The vascular endothelial growth factor knockdown SKOV3 cell lines were treated with adiponectin for 48 h. The cytokines involved in adiponectin-mediated angiogenesis were explored using the human angiogenesis cytokine array and were verified with the enzyme-linked immunosorbent assay. The angiogenic effect of adiponectin was evaluated using the human umbilical vein endothelial cell tube formation assay. We also investigated the effects of adiponectin treatment on the migration and invasion of SKOV3 cells. RESULTS: The number of tubes formed by human umbilical vein endothelial cell decreased significantly after knockdown of vascular endothelial growth factor (via transfection of vascular endothelial growth factor small interfering RNA into SKOV3 cells). When these vascular endothelial growth factor knockdown SKOV3 cells were treated with adiponectin, there was an increase in the number of tubes in a tube formation assay. Following adiponectin treatment, the CXC chemokine ligand 1 secretion increased in a cytokine array. This was confirmed by both enzyme-linked immunosorbent assay and Western blot. The increased secretion of CXC chemokine ligand 1 by adiponectin occurred regardless of vascular endothelial growth factor knockdown. In addition, the induction of migration and invasion of SKOV3 cells were significantly stronger with adiponectin treatment than they were without. CONCLUSION: Adiponectin treatment of ovarian cancer cells induces angiogenesis via CXC chemokine ligand 1 independently of vascular endothelial growth factor. These findings suggest that adiponectin may serve as a novel therapeutic target for ovarian cancer.
The metabolic milieu in melanoma: Role of immune suppression by CD73/adenosine.
Passarelli A, Tucci M, Mannavola F … +2 more , Felici C, Silvestris F
Tumour Biol · 2019 Apr · PMID 30957676 · Publisher ↗
The mechanisms leading to immune escape of melanoma have been largely investigated in relation to its tumour immunogenicity and features of inflamed microenvironment that promote the immune suppression during the disease...
The mechanisms leading to immune escape of melanoma have been largely investigated in relation to its tumour immunogenicity and features of inflamed microenvironment that promote the immune suppression during the disease progression. These findings have recently led to advantages in terms of immunotherapy-based approaches as rationale for overcoming the immune escape. However, besides immune checkpoints, other mechanisms including the adenosine produced by ectonucleotidases CD39 and CD73 contribute to the melanoma progression due to the immunosuppression induced by the tumour milieu. On the other hand, CD73 has recently emerged as both promising therapeutic target and unfavourable prognostic biomarker. Here, we review the major mechanisms of immune escape activated by the CD39/CD73/adenosine pathway in melanoma and focus potential therapeutic strategies based on the control of CD39/CD73 downstream adenosine receptor signalling. These evidences provide the basis for translational strategies of immune combination, while CD73 would serve as potential prognostic biomarker in metastatic melanoma.
Clinical-pathological characteristics and short-term follow-up associated with proliferation, apoptosis and angiogenesis in a prospective cohort of patients with colorectal tumours.
Redondo M, Abitei C, Téllez T … +16 more , Fúnez R, Pereda T, Rodrigo I, Betancourt AM, García-Aranda M, Rueda A, Martínez García RC, Morales Suarez-Varela MM, Zabalza I, Sánchez Del Charco M, Borrero Martín JJ, García Del Moral R, Escobar A, Quintana J, Rivas-Ruiz F, REDISSEC-CARESS/CCR group
Tumour Biol · 2019 Apr · PMID 30957671 · Publisher ↗
We investigate the clinical and pathological features related to variations in colorectal tumour apoptosis, proliferation and angiogenesis and the influence of the latter in short-term mortality (2 years); 551 tumour sam...
We investigate the clinical and pathological features related to variations in colorectal tumour apoptosis, proliferation and angiogenesis and the influence of the latter in short-term mortality (2 years); 551 tumour samples from a prospective cohort of patients with colorectal cancer were examined and tumour biology markers were determined as follows: percentage of apoptotic cells, by the terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling technique; Ki-67 antigen, as a cell proliferation marker and density of microvessels (as a marker of angiogenesis). An increase in the percentage of cellular apoptosis is significantly related to the presence of poorly differentiated tumours, with vascular invasion (p < 0.001). The CD105 angiogenesis marker is not related to any clinical-pathological parameter except that of higher frequency in older patients (p = 0.03). Ki-67 is more frequently expressed in tumours with less nervous invasion (p = 0.05). Neither apoptosis nor angiogenesis present any significant association with short-term survival. The only marker clearly related to 2-year survival is Ki-67, which is shown to be a good prognostic factor in the multivariate analysis (hazard ratio = 0.49; 95% confidence interval = 0.27-0.90). Therefore, in a prospective cohort of colorectal cancer patients, only Ki-67 is a marker of good prognosis in short-term follow-up.
The expression and prognostic value of stem cell markers Bmi-1, HESC5:3, and HES77 in human papillomavirus-positive and -negative oropharyngeal squamous cell carcinoma.
Mohamed H, Hagström J, Jouhi L … +4 more , Atula T, Almangush A, Mäkitie A, Haglund C
Tumour Biol · 2019 Mar · PMID 30915904 · Publisher ↗
Human papillomavirus is detected in over 50% of oropharyngeal squamous cell carcinomas. Human papillomavirus-positive oropharyngeal squamous cell carcinomas differ from human papillomavirus-negative tumors, and both expr...
Human papillomavirus is detected in over 50% of oropharyngeal squamous cell carcinomas. Human papillomavirus-positive oropharyngeal squamous cell carcinomas differ from human papillomavirus-negative tumors, and both expression patterns are classified as distinct entities. The Bmi-1 oncogene is a well-known member of the mammalian polycomb-group family. HESC5:3 and HES77 are newly developed monoclonal antibodies produced against undifferentiated embryonic stem cells. Our aim was to explore their roles in both human papillomavirus-positive and -negative oropharyngeal squamous cell carcinomas. Our cohort comprised 202 consecutive oropharyngeal squamous cell carcinoma patients diagnosed and treated with curative intent. We used tissue microarray tumor blocks to study the immunohistochemical expression of Bmi-1, HESC5:3, and HES77. We compared the expressions of these stem cell markers with p16 immunoexpression and human papillomavirus status, as well as with other characteristics of the tumor, and with patients' clinical data and follow-up data. Human papillomavirus- and p16-positive tumors expressed less Bmi-1 and more HESC5:3 than the negative tumors. HES77 expression was high in human papillomavirus-positive oropharyngeal squamous cell carcinoma, but it did not correlate with p16 positivity. In our multivariable model, Bmi-1 and HESC5:3 were still associated with human papillomavirus, but the association between human papillomavirus and HES77 remained absent. In conclusion, Bmi-1, HESC5:3, and HES77 may have a different role in human papillomavirus-positive and human papillomavirus-negative tumors. There was no correlation between Bmi-1, HESC5:3, and HES77 expression and survival.
Investigation on core-fucosylated prostate-specific antigen as a refined biomarker for differentiation of benign prostate hyperplasia and prostate cancer of different aggressiveness.
Lang R, Rolny V, Leinenbach A … +7 more , Karl J, Swiatek-de Lange M, Kobold U, Schrader M, Krause H, Mueller M, Vogeser M
Tumour Biol · 2019 Mar · PMID 30907281 · Publisher ↗
Prostate cancer represents a major cause of cancer death in men worldwide. Novel non-invasive methods are still required for differentiation of non-aggressive from aggressive tumors. Recently, changes in prostate-specifi...
Prostate cancer represents a major cause of cancer death in men worldwide. Novel non-invasive methods are still required for differentiation of non-aggressive from aggressive tumors. Recently, changes in prostate-specific antigen glycosylation pattern, such as core-fucosylation, have been described in prostate cancer. The objective of this study was to evaluate whether the core-fucosylation determinant of serum prostate-specific antigen may serve as refined marker for differentiation between benign prostate hyperplasia and prostate cancer or identification of aggressive prostate cancer. A previously developed liquid chromatography-mass spectrometry/mass spectrometry-based strategy was used for multiplex analysis of core-fucosylated prostate-specific antigen (fuc-PSA) and total prostate-specific antigen levels in sera from 50 benign prostate hyperplasia and 100 prostate cancer patients of different aggressiveness (Gleason scores, 5-10) covering the critical gray area (2-10 ng/mL). For identification of aggressive prostate cancer, the ratio of fuc-PSA to total prostate-specific antigen (%-fuc-PSA) yielded a 5%-8% increase in the area under the curve (0.60) compared to the currently used total prostate-specific antigen (area under the curve = 0.52) and %-free prostate-specific antigen (area under the curve = 0.55) tests. However, our data showed that aggressive prostate cancer (Gleason score > 6) and non-aggressive prostate cancer (Gleason score ≤ 6) could not significantly (p-value = 0.08) be differentiated by usage of %-fuc-PSA. In addition, both non-standardized fuc-PSA and standardized %-fuc-PSA had no diagnostic value for differentiation of benign prostate hyperplasia from prostate cancer. The %-fuc-PSA serum levels could not improve the differentiation of non-aggressive and aggressive prostate cancer compared to conventional diagnostic prostate cancer markers. Still, it is unclear whether these limitations come from the biomarker, the used patient cohort, or the imprecision of the applied method itself. Therefore, %-fuc-PSA should be further investigated, especially by more precise methods whether it could be clinically used in prostate cancer diagnosis.
Circulating miRNA-1290 as a potential biomarker for response to chemoradiotherapy and prognosis of patients with advanced oral squamous cell carcinoma: A single-center retrospective study.
Nakashima H, Yoshida R, Hirosue A … +11 more , Kawahara K, Sakata J, Arita H, Yamamoto T, Toya R, Murakami R, Hiraki A, Shinohara M, Ito T, Kuwahara Y, Nakayama H
Tumour Biol · 2019 Mar · PMID 30887897 · Publisher ↗
MicroRNAs are a class of small, endogenous, noncoding 18- to 24-nucleotide-long RNAs that can regulate multiple processes related to cancer progression. However, their clinical value in patients with oral squamous cell c...
MicroRNAs are a class of small, endogenous, noncoding 18- to 24-nucleotide-long RNAs that can regulate multiple processes related to cancer progression. However, their clinical value in patients with oral squamous cell carcinoma has not yet been fully explored. Therefore, the aim of this study was to investigate the clinical significance of circulating microRNAs in oral squamous cell carcinoma patients. The expression levels of circulating miR-1246 and miR-1290 in healthy volunteers and oral squamous cell carcinoma patients were examined by quantitative real-time polymerase chain reaction. The expression levels of both microRNAs in the radioresistant oral squamous cell carcinoma cell line (SAS-R) and the parent cell line (SAS) and in the conditioned medium obtained from these cell lines were also examined by quantitative real-time polymerase chain reaction. In addition, the correlations between circulating microRNA status and various clinicopathological features in 55 oral squamous cell carcinoma patients with locally advanced oral squamous cell carcinoma who underwent surgery following 5-fluorouracil-based chemoradiotherapy were examined. The expression level of miR-1290 was significantly lower in the plasma of oral squamous cell carcinoma patients than in that of healthy volunteers (p < 0.01). The expression levels of microRNAs in the conditioned medium and in the cells varied from cell to cell. In the clinicopathological analyses, the frequency of patients with low miR-1290 levels was significantly higher among cases with lower pathological differentiation and among those with a poor pathological response for preoperative chemoradiotherapy (p = 0.030 each). Furthermore, Cox regression analysis based on the 5-year overall survival and disease-free survival revealed that miR-1290 status was a significant prognostic factor for patients with oral squamous cell carcinoma (hazard ratio = 0.169, p = 0.008, and hazard ratio = 0.186, p = 0.008, respectively). Circulating miR-1290 status could be a valuable biomarker for predicting the clinical response to chemoradiotherapy as well as overall survival in patients with oral squamous cell carcinoma.
Genetic polymorphisms in CDH1 and Exo1 genes elevate the prostate cancer risk in Bangladeshi population.
Imtiaz H, Afroz S, Hossain MA … +6 more , Bellah SF, Rahman MM, Kadir MS, Sultana R, Mazid MA, Rahman MM
Tumour Biol · 2019 Mar · PMID 30880589 · Publisher ↗
The polymorphisms of invasion suppressor gene CDH1 and DNA mismatch repair gene Exo1 have been reported to play critical role in the development, tumorigenesis, and progression of several kinds of cancers including prost...
The polymorphisms of invasion suppressor gene CDH1 and DNA mismatch repair gene Exo1 have been reported to play critical role in the development, tumorigenesis, and progression of several kinds of cancers including prostate cancer. This study was designed to analyze the contribution of single-nucleotide polymorphisms of the CDH1 (-160C/A) and Exo1 (K589E) to prostate cancer susceptibility in Bangladeshi population. The study included 100 prostate cancer cases and age-matched 100 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to determine the genetic polymorphisms. A significant association was found between CDH1 -160C/A (rs16260) and Exo1 (rs1047840, K589E) polymorphisms and prostate cancer risk. In case of CDH1 -160C/A polymorphism, the frequencies of the three genotypes C/C,C/A, and A/A were 45%, 48%, and 7% in cases and 63%, 32%, and 5% in controls, respectively. The heterozygote C/A genotype and combined C/A + A/A genotypes showed 2.10-fold (odds ratio = 2.1000, 95% confidence interval = 1.2956-4.0905, p = 0.013) and 2.08-fold (odds ratio = 2.0811, 95% confidence interval = 1.1820-3.6641, p = 0.011) increased risk of prostate cancer, respectively, when compared with homozygous C/C genotypes. The variant A allele also was associated with increased risk of prostate cancer (odds ratio = 1.6901, 95% confidence interval = 1.0740-2.6597, p = 0.0233). In case of Exo1 (K589E) polymorphism, G/A heterozygote, A/A homozygote, and combined G/A + A/A genotypes were found to be associated with 2.30-, 4.85-, and 3.04-fold higher risk of prostate cancer, respectively (odds ratio = 2.3021, 95% confidence interval = 2.956-4.0905, p = 0.0031; odds ratio = 4.8462, 95% confidence interval = 1.0198-23.0284, p = 0.0291; OR = 3.0362, 95% confidence interval = 1.7054-5.4053, p = 0.0001, respectively). The "A" allele showed significant association with increased susceptibility (2.29-fold) to prostate cancer (odds ratio = 2.2955, 95% confidence interval = 1.4529-3.6270, p = 0.0004). Our results suggest that CDH1 -160C/A and Exo1 K589E polymorphisms are associated with increased susceptibility to prostate cancer in Bangladeshi population.
Gallium nanoparticles along with low-dose gamma radiation modulate TGF-β/MMP-9 expression in hepatocellular carcinogenesis in rats.
Moawed FS, El-Sonbaty SM, Mansour SZ
Tumour Biol · 2019 Mar · PMID 30859905 · Publisher ↗
Combining chemotherapy with radiotherapy potentiates the outcome of cancer treatment for the more comprehensive attack. In the current study, we continued to assess the therapeutic efficaciousness of the newly synthesize...
Combining chemotherapy with radiotherapy potentiates the outcome of cancer treatment for the more comprehensive attack. In the current study, we continued to assess the therapeutic efficaciousness of the newly synthesized gallium nanoparticles (GaNPs) combined with low level of gamma radiation (IR), on the incidence of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. Oral administration of GaNPs (1 mg/Kg b.wt.) 5 times per week for 6 weeks combined with IR to rats treated with DEN (20 mg/Kg b.wt. 5 times per week for 6 weeks) significantly reduced serum levels of alpha-fetoprotein (AFP), aspartate transferase (AST), alanine transferase (ALT), and gamma-glutamyltransferase (GGT). In addition, the immunoblotting results of matrix metalloproteinase-9 (MM-9) showed a marked downregulation of protein expression along with a significant decrease in the hepatic level of transforming growth factor β (TGF-β). Furthermore, GaNPs and/or low dose of radiation significantly elevated the level of caspase-3 gene transcript accompanied with evoked DNA fragmentation in rats treated with DEN. The ameliorative effect of GaNPs and IR well appreciated with the histopathological alteration finding in DEN groups. It can be concluded that the combination of GaNPs and/or IR can serve as a good therapeutic agent for the treatment of HCC, which ought to attract more studies.
Progesterone receptor expression in proliferating cancer cells of hormone-receptor-positive breast cancer.
Ueno T, Saji S, Chiba T … +9 more , Kamma H, Isaka H, Itoh H, Imi K, Miyamoto K, Tada M, Sasano H, Toi M, Imoto S
Tumour Biol · 2018 Nov · PMID 30841783 · Publisher ↗
Breast cancer has been suggested to have two distinct driving mechanisms: the hormone receptor and the growth factor receptor pathways. We hypothesized that each driving system produces a different expression pattern of...
Breast cancer has been suggested to have two distinct driving mechanisms: the hormone receptor and the growth factor receptor pathways. We hypothesized that each driving system produces a different expression pattern of estrogen-regulated genes, such as progesterone receptor, in proliferating cells. Progesterone receptor and Ki67 expressions were assessed by dual-fluorescence immunohistochemistry in estrogen-receptor-positive breast cancer tissues. Two distinct proliferating cell populations were observed: progesterone-receptor-positive and progesterone-receptor-negative. In the training cohort, tissues with progesterone-receptor-positive proliferating cells were associated with lower grade and better disease-free survival (p = 0.0055 and 0.0026, respectively). These associations were confirmed in the validation cohort from the neoadjuvant endocrine trial JFMC34 (p = 0.033 and 0.0003, respectively). In the validation cohort, patients with progesterone-receptor-positive proliferating cells responded better to endocrine therapy and had a lower Oncotype DX Recurrence Score. In the multivariate analysis, progesterone receptor status of proliferating cells, but not progesterone receptor or Ki67 alone, was an independent predictor of disease-free survival in both cohorts (p = 0.0043 and 0.0026). In conclusion, the progesterone receptor status of proliferating cancer cells was associated with histological grade and Recurrence Score, and a potent prognostic factor in estrogen-receptor-positive breast cancers. Results suggest that different driving systems generate different expression patterns of progesterone receptor in proliferating cancer cells. Further studies are warranted to validate the findings.
NADPH oxidase 4 expression in the normal endometrium and in endometrial cancer.
Degasper C, Brunner A, Sampson N … +6 more , Tsibulak I, Wieser V, Welponer H, Marth C, Fiegl H, Zeimet AG
Tumour Biol · 2019 Feb · PMID 30813866 · Publisher ↗
The aim of this study was to explore the role of NOX4 in the biology of the normal endometrium and endometrial cancer. NOX4 plays a key role in other adenocarcinomas and has been implicated in the pathogenesis of diabete...
The aim of this study was to explore the role of NOX4 in the biology of the normal endometrium and endometrial cancer. NOX4 plays a key role in other adenocarcinomas and has been implicated in the pathogenesis of diabetes and obesity, which are important risk factors for endometrial cancer. NOX4 expression was assessed in 239 endometrial cancer and 25 normal endometrium samples by quantitative real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry. DNA methylation of the NOX4 promoter was determined by means of MethyLight PCR. Data were correlated with clinicopathological parameters and analyzed in the context of diabetes and body mass index. In the normal endometrium, NOX4 microRNA expression was significantly higher in the secretory transformed compared with proliferative endometrium ( p = 0.008). In endometrial cancer specimens, NOX4 expression did not differ between diabetic and non-diabetic patients, but was the highest in patients with a body mass index ≤ 26 ( p = 0.037). The lowest NOX4 expression was found in carcinosarcomas ( p = 0.007). High NOX4 expression predicted poorer clinical outcome with regard to overall survival, especially in non-diabetic patients and those with a body mass index > 20. Independent prognostic significance of NOX4 transcripts was retained in type I endometrial cancer and was the most meaningful in patients with a body mass index > 20. No prognostic impact was shown for NOX4 promoter methylation in endometrial cancer. For the first time, we demonstrate that NOX4 plays a considerable role in the cycle-dependent changes in the normal endometrium and in the biology of endometrial cancer.
Role of discoidin domain receptor 2 (DDR2) and microRNA-182 in survival of women with high-grade serous ovarian cancer.
Ramalho S, Andrade LAA, Filho CC … +6 more , Natal RA, Pavanello M, Ferracini AC, Sallum LF, Sarian LO, Derchain S
Tumour Biol · 2019 Jan · PMID 30810094 · Publisher ↗
The objective of this study is to evaluate the relationship between discoidin domain receptor 2 (DDR2) and miR-182 expression with response to platinum-based chemotherapy and survival in women with high-grade serous ovar...
The objective of this study is to evaluate the relationship between discoidin domain receptor 2 (DDR2) and miR-182 expression with response to platinum-based chemotherapy and survival in women with high-grade serous ovarian cancer (HGSOC). We evaluated 78 women with HGSOC stages I-IV, diagnosed between 1996 and 2013, and followed up until 2016. DDR2 expression was assessed using immunohistochemistry on tissue microarray slides. The microRNAs were evaluated by qRT-PCR. DDR2 expression was high in 11 (14.1%) women. PFS was significantly lower in women with FIGO stage I/II - versus III/IV, post-surgery residual disease and high expression of DDR2. Women with postsurgery residual disease, FIGO stage I/II - versus III/IV and DDR2 expression had worse OS, but only post-surgery residual disease remained an independent prognostic factor for worse OS in multivariable analysis. miR-182 expression levels were significantly lower in patients harboring tumors with higher expression of DDR2 (p < 0.001). In this relatively large cohort of women with HSGOC, higher DDR2 expression was associated with lower miR-182 levels and worse PFS, suggesting that these molecules may be associated with mechanisms of HGSOC progression.
Feasibility of single-cell analysis of model cancer and foetal cells in blood after isolation by cell picking.
Smith J, Mathisen AF, Funch Richardt N … +4 more , Vander Plaetsen AS, Van Nieuwerburgh F, Stender H, Hillig T
Tumour Biol · 2019 Feb · PMID 30808252 · Publisher ↗
The objective of the present feasibility study was to transfer single cell line cells to either microscopy slides for downstream immune characterization or to polymerase chain reaction tubes for downstream DNA quantitati...
The objective of the present feasibility study was to transfer single cell line cells to either microscopy slides for downstream immune characterization or to polymerase chain reaction tubes for downstream DNA quantitation. Tumour cell lines, SKBR3 and MCF7 and trophoblast cell line JEG-3 were spiked in healthy donor blood. The CytoTrack system was used to scan the spiked blood samples to identify target cells. Individual target cells were identified, picked by use of a CytoPicker and deposited to either a microscopic slide or a polymerase chain reaction tube (PCR). Single tumour cells on microscopic slides were further immunostained with human epidermal growth factor receptor 2 (Her2) and epithelial cell adhesion molecule (EpCAM). From the picked cells in polymerase chain reaction tubes, DNA was amplified, quantified and used for Short Tandem Repeat genotyping. Depositing rare cells to microscopy slides was laborious with only five cells per hour. In this study with a trained operator, the picked cells had an 80.5% recovery rate. Depositing single trophoblast cells in PCR tubes was a faster process with 10 cells in 5 min. Immunostaining of isolated cells by both Her2 and EpCAM was possible but showed varying staining intensity. Presence of trophoblasts and contaminating white blood cells in PCR tubes after cell picking was confirmed based on DNA yield and mixed Short Tandem Repeat profiles in five out of eight samples. Using the CytoPicker tool, single tumour and trophoblast cells were successfully isolated and moved from blood samples, allowing subsequent immunostaining or Short Tandem Repeat genotyping.
Metformin diminishes the unfavourable impact of Nrf2 in breast cancer patients with type 2 diabetes.
Urpilainen E, Kangaskokko J, Puistola U … +1 more , Karihtala P
Tumour Biol · 2019 Jan · PMID 30803422 · Publisher ↗
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a major regulator of the oxidative stress response and it is negatively regulated by Kelch-like ECH-associated protein 1 (Keap1). The Keap1-Nrf2 axis has a fundamenta...
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a major regulator of the oxidative stress response and it is negatively regulated by Kelch-like ECH-associated protein 1 (Keap1). The Keap1-Nrf2 axis has a fundamental role in carcinogenesis. In previous studies, the widely used diabetes drug metformin has appeared to have a critical role in the regulation of Nrf2 function. In this study, we assessed the expression of Nrf2 and Keap1 immunohistochemically in 157 patients with type 2 diabetes who underwent breast cancer surgery with curative intent. In total, 78 (49.7%) of these patients were taking metformin alone or combined with other oral anti-diabetic medication at the time of breast cancer diagnosis. We found that high-level cytoplasmic Nrf2 expression predicted dismal overall survival and breast cancer-specific survival, but only in the patients who were not taking metformin at the time of diagnosis. Similarly, low-level nuclear Keap1 expression had an adverse prognostic value in terms of overall survival and breast cancer-specific survival in patients without metformin. On the other hand, high-level nuclear Keap1 expression was associated with prolonged overall survival and breast cancer-specific survival. The results may be explained in terms of non-functioning or displaced Keap1, although more mechanistic pre-clinical and prospective clinical studies are warranted.
Total cell-free DNA, carcinoembryonic antigen, and C-reactive protein for assessment of prognosis in patients with metastatic colorectal cancer.
Spindler KG, Demuth C, Sorensen BS … +6 more , Johansen JS, Nielsen D, Pallisgaard N, Hoegdall E, Pfeiffer P, Vittrup Jensen B
Tumour Biol · 2018 Nov · PMID 30486767 · Publisher ↗
In late-stage metastatic colorectal cancer, difficult treatment decisions should incorporate a thorough evaluation of the patient's general condition and subject for shared decision making. Assessment of the individual p...
In late-stage metastatic colorectal cancer, difficult treatment decisions should incorporate a thorough evaluation of the patient's general condition and subject for shared decision making. Assessment of the individual patients' prognosis is valuable in this setting. The aim was to analyze the prognostic value of plasma levels of total cell-free DNA, carcinoembryonic antigen and C-reactive protein in 97 heavily pretreated patients with metastatic colorectal cancer. Patients received irinotecan, cetuximab, and everolimus in a phase-2 clinical trial ( clinicaltrials.gov NCT01387880). Plasma samples were used for DNA purification and quantification of total cell-free DNA by droplet digital polymerase chain reaction. Serum carcinoembryonic antigen and C-reactive protein were analyzed by routine methods. Clinical endpoints were overall survival and progression-free survival. A total of 82 patients had blood samples available for quantification of total cell-free DNA. Patients with pre-treatment cell-free DNA levels higher than the median total cell-free DNA (9800 alleles per milliliter plasma) had a significantly shorter overall survival of 4.3 months (95% confidence interval: 3.6-5.8) compared to patients with cell-free DNA levels below the median with an overall survival of 11.3 months (95% confidence interval: 8.0-14.8, p < 0.0001). When using the upper normal limit from a previously analyzed normal control group, the median overall survival was 11.3 (95% confidence interval: 7.3-14.8) and 4.3 (95% confidence interval: 3.7-6.1) months, respectively (p < 0.0001). Serum carcinoembryonic antigen and C-reactive protein had similar prognostic value with short overall survival and progression-free survival in patients with elevated levels compared to those within normal range. A high-risk profile of elevated cell-free DNA, carcinoembryonic antigen, and C-reactive protein was described, but in combined Cox regression multivariate analysis, only total cell-free DNA preserved a strong prognostic value. In conclusion, total cell-free DNA in plasma, carcinoembryonic antigen, and C-reactive protein could all contribute to assessment of patients' prognosis and potentially aid in clinical decision making in patients with metastatic colorectal cancer.
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