Tumour Biology[JOURNAL]
Sun
200 papers
Attempts to use statins in cancer therapy: An update.
Matusewicz L, Czogalla A, Sikorski AF
Tumour Biol · 2020 Jul · PMID 32662332 · Publisher ↗
Although it could be speculated that almost everything has been said concerning the use of statins in cancer therapy, statins as anticancer drugs have both committed supporters and opponents, for whom the dispute about t...
Although it could be speculated that almost everything has been said concerning the use of statins in cancer therapy, statins as anticancer drugs have both committed supporters and opponents, for whom the dispute about the legitimacy of statin use in cancer treatment seems never to be clearly resolved; every year more than 300 reports which deepen the knowledge about statins and their influence on cancer cells are published. In this mini-review, we focus on the latest (since 2015) outcomes of cohort studies and meta-analyses indicating statin effectiveness in cancer treatment. We discuss attempts to improve the bioavailability of statins using nanocarriers and review the effectiveness of statins in combined therapies. We also summarise the latest results regarding the development of mechanisms of resistance to statins by cancer cells and, on the other hand, give a few examples where statins could potentially be used to overcome resistance to commonly used chemotherapeutics. Finally, special attention is paid to new reports on the effect of statins on epithelial-mesenchymal transition.
Characterization of Chilean patients with sporadic colorectal cancer according to the three main carcinogenic pathways: Microsatellite instability, CpG island methylator phenotype and Chromosomal instability.
Wielandt AM, Hurtado C, Moreno C M … +8 more , Villarroel C, Castro M, Estay M, Simian D, Martinez M, Vial MT, Kronberg U, López-Köstner F
Tumour Biol · 2020 Jul · PMID 32635826 · Publisher ↗
Molecular classification of colorectal cancer is difficult to implement in clinical settings where hundreds of genes are involved, and resources are limited. This study aims to characterize the molecular subtypes of pati...
Molecular classification of colorectal cancer is difficult to implement in clinical settings where hundreds of genes are involved, and resources are limited. This study aims to characterize the molecular subtypes of patients with sporadic colorectal cancer based on the three main carcinogenic pathways microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and chromosomal instability (CIN) in a Chilean population. Although several reports have characterized colorectal cancer, most do not represent Latin-American populations. Our study includes 103 colorectal cancer patients who underwent surgery, without neoadjuvant treatment, in a private hospital between 2008 and 2017. MSI, CIN, and CIMP status were assessed. Frequent mutations in KRAS, BRAF, and PIK3CA genes were analyzed by Sanger sequencing, and statistical analysis was performed by Fisher's exact and/or chi-square test. Survival curves were estimated with Kaplan-Meier and log-rank test. Based on our observations, we can classify the tumors in four subgroups, Group 1: MSI-high tumors (15%) are located in the right colon, occur at older age, and 60% show a BRAF mutation; Group 2: CIN-high tumors (38%) are in the left colon, and 26% have KRAS mutations. Group 3: [MSI/CIN/CIMP]-low/negative tumors (30%) are left-sided, and 39% have KRAS mutations; Group 4: CIMP-high tumors (15%) were more frequent in men and left side colon, with 27% KRAS and 7% presented BRAF mutations. Three percent of patients could not be classified. We found that CIMP-high was associated with a worse prognosis, both in MSI-high and MSI stable patients (p = 0.0452). Group 3 (Low/negative tumors) tend to have better overall survival compared with MSI-high, CIMP-high, and CIN-high tumors. This study contributes to understanding the heterogeneity of tumors in the Chilean population being one of the few characterizations performed in Latin-America. Given the limited resources of these countries, these results allow to improve molecular characterization in Latin-American colorectal cancer populations and confirm the possibility of using the three main carcinogenic pathways to define therapeutic strategies.
and variations in outcomes of tobacco- and alcohol-related head and neck squamous cell carcinoma patients.
Costa EFD, Lima TRP, Lopes-Aguiar L … +12 more , Nogueira GAS, Visacri MB, Quintanilha JCF, Pincinato EC, Calonga L, Mariano FV, Altemani AMAM, Altemani JMC, Moriel P, Chone CT, Ramos CD, Lima CSP
Tumour Biol · 2020 Jul · PMID 32628088 · Publisher ↗
Radiotherapy and cisplatin lead to cell killing in head and neck squamous cell carcinoma patients, but adverse events and response to treatment are not the same in patients with similar clinicopathological aspects. The a...
Radiotherapy and cisplatin lead to cell killing in head and neck squamous cell carcinoma patients, but adverse events and response to treatment are not the same in patients with similar clinicopathological aspects. The aim of this prospective study was to evaluate the roles of c.215G > C, c.-671A > G, c.-1378G > A, c.-844 C > T, c.-1191A > G, and c.-182-247G > T single nucleotide variants in toxicity, response rate, and survival of cisplatin chemoradiation-treated head and neck squamous cell carcinoma patients. Genomic DNA was analyzed by polymerase chain reaction for genotyping. Differences between groups of patients were analyzed by chi-square test or Fisher's exact test, multiple logistic regression analysis, and Cox hazards model. One hundred nine patients with head and neck squamous cell carcinoma were enrolled in study. All patients were smokers and/or alcoholics. Patients with c.-671GG genotype, c.-671AG or GG genotype, and c.-844CC genotype had 5.52 (95% confidence interval (CI): 1.42-21.43), 4.03 (95% CI: 1.51-10.79), and 5.77 (95% CI: 1.23-27.04) more chances of presenting chemoradiation-related anemia of grades 2-4, lymphopenia of grade 3 or 4, and ototoxicity of all grades, respectively, than those with the remaining genotypes. c.-671GG genotype was also seen as an independent predictor of shorter event-free survival (hazard ratio (HR): 2.05; 0.007) and overall survival (HR: 1.83; 0.02) in our head and neck squamous cell carcinoma patients. These findings present, for the first time, preliminary evidence that inherited abnormalities in apoptosis pathway, related to c.-671A > G and c.-844 C > T single nucleotide variants, can alter toxicity and survival of tobacco- and alcohol-related head and neck squamous cell carcinoma patients homogeneously treated with cisplatin chemoradiation.
Label-free proteomics reveals serum proteins whose levels differ between pancreatic ductal adenocarcinoma patients with short or long survival.
Holm M, Saraswat M, Joenväärä S … +3 more , Seppänen H, Renkonen R, Haglund C
Tumour Biol · 2020 Jun · PMID 32586207 · Publisher ↗
Pancreatic ductal adenocarcinoma is the most common and aggressive type of pancreatic cancer, with a 5-year survival rate that is less than 10%. New biomarkers to aid in predicting the prognosis of pancreatic ductal aden...
Pancreatic ductal adenocarcinoma is the most common and aggressive type of pancreatic cancer, with a 5-year survival rate that is less than 10%. New biomarkers to aid in predicting the prognosis of pancreatic ductal adenocarcinoma patients are needed. Previous proteomic studies have to a great extent focused on finding proteins of value for the diagnosis of pancreatic ductal adenocarcinoma. There is a lack of studies that have profiled the serum or plasma proteome in order to discover candidates for new prognostic biomarkers. In this study, we have used ultra-performance liquid chromatography-ultra-definition mass spectrometry to analyze the serum samples of 21 pancreatic ductal adenocarcinoma patients with short or long survival. Statistical analysis discovered 31 proteins whose expression differed significantly between pancreatic ductal adenocarcinoma patients with short or long survival. Pathway analysis discovered multiple canonical pathways enriched in this data set, with several pathways having roles in inflammation and lipid metabolism. The serum proteins identified here, which include complement components and several enzymes, could be of value as candidates for new noninvasive prognostic markers.
Genomic profiling of microRNA target genes in colorectal cancer.
Fadaka AO, Bakare OO, Pretorius A … +1 more , Klein A
Tumour Biol · 2020 Jun · PMID 32552466 · Publisher ↗
Colorectal cancer is the second and third most common cancer in men and women, respectively, worldwide. Alterations such as genetic and epigenetic are common in colorectal cancer and are the basis of tumor formation. The...
Colorectal cancer is the second and third most common cancer in men and women, respectively, worldwide. Alterations such as genetic and epigenetic are common in colorectal cancer and are the basis of tumor formation. The exploration of the molecular basis of colorectal cancer can drive a better understanding of the disease as well as guide the prognosis, therapeutics, and disease management. This study is aimed at investigating the genetic mutation profile of five candidate microRNAs (hsa-miR-513b-3p, hsa-miR-500b-3p, hsa-miR-500a-3p, hsa-miR-450b-3p, hsa-miR-193a-5p) targeted by seven genes (APC, KRAS, TCF7L2, EGFR, IGF1R, CASP8, and GNAS)) using in silico approaches. Two datasets (dataset 1 from our previous study and dataset two (The Cancer Genome Atlas, Nature 2012) were considered for this study. Protein-protein interaction, expression analysis, and genetic profiling were carried out using STRING, FireBrowse, and cBioPortal, respectively. Protein-protein interaction network showed that epidermal growth factor receptor has the highest connection among the target genes and this can be considered as the hub gene. Relative to other solid tumors, in colorectal cancer, six of the target genes were downregulated and only CASP8 was upregulated. Genes with protein tyrosine kinases domain were frequently altered in colorectal cancer and the most common alteration in these genes/domain are missense mutation. These results could serve as a lead in the identification of driver genes responsible for colorectal cancer initiation and progression. However, the intense mechanism of these results remains unclear and further experimental validation and molecular approaches are the focal points in the nearest future.
Evaluating macrophage migration inhibitory factor 1 expression as a prognostic biomarker in colon cancer.
Olsson L, Lindmark G, Hammarström ML … +2 more , Hammarström S, Sitohy B
Tumour Biol · 2020 Jun · PMID 32515296 · Publisher ↗
OBJECTIVE: Several studies indicate that macrophage migration inhibitory factor 1 plays a role for tumor progression in colon cancer. We investigated whether determination of migration inhibitory factor 1 mRNA expression...
OBJECTIVE: Several studies indicate that macrophage migration inhibitory factor 1 plays a role for tumor progression in colon cancer. We investigated whether determination of migration inhibitory factor 1 mRNA expression levels in lymph nodes of colon cancer patients could be used as a prognostic marker. METHODS: Expression levels of migration inhibitory factor 1 and carcinoembryonic antigen mRNAs were assessed in primary tumors and regional lymph nodes of 123 colon cancer patients (stages I-IV), and in colon cancer- and immune cell lines using quantitative reverse transcriptase-polymerase chain reaction. Expression of migration inhibitory factor 1 protein was investigated by two-color immunohistochemistry and immunomorphometry. RESULTS: Migration inhibitory factor 1 mRNA was expressed at 60 times higher levels in primary colon cancer tumors compared to normal colonic tissue (medians 8.2 and 0.2 mRNA copies/18S rRNA unit; p < .0001). A highly significant difference in mRNA expression levels was found between hematoxylin-eosin positive lymph nodes and hematoxylin-eosin negative lymph nodes (p < .0001). Migration inhibitory factor 1 and carcinoembryonic antigen proteins were simultaneously expressed in many colon cancer-tumor cells. Kaplan-Meier survival model and hazard ratio analysis, using a cutoff level at 2.19 mRNA copies/18S rRNA unit, revealed that patients with lymph nodes expressing high levels of migration inhibitory factor 1 mRNA had a 3.5-fold (p = .04) higher risk for recurrence, associated with a small, but significant, difference in mean survival time (7 months, p = .03) at 12 years of follow-up. CONCLUSION: Although migration inhibitory factor 1 mRNA expression levels were related to severity of disease and lymph node analysis revealed that colon cancer patients with high levels had a shorter survival time after surgery than those with low levels, the difference was small and probably not useful in clinical practice.
ΔKi67 proliferation index as independent predictive and prognostic factor of outcome in luminal breast cancer: data from neoadjuvant letrozole-based treatment.
Ianza A, Giudici F, Pinello C … +15 more , Corona SP, Strina C, Bernocchi O, Bortul M, Milani M, Sirico M, Allevi G, Aguggini S, Cocconi A, Azzini C, Dester M, Cervoni V, Bottini A, Cappelletti M, Generali D
Tumour Biol · 2020 Jun · PMID 32489146 · Publisher ↗
A key tool for monitoring breast cancer patients under neoadjuvant treatment is the identification of reliable predictive markers. Ki67 has been identified as a prognostic and predictive marker in ER-positive breast canc...
A key tool for monitoring breast cancer patients under neoadjuvant treatment is the identification of reliable predictive markers. Ki67 has been identified as a prognostic and predictive marker in ER-positive breast cancer. Ninety ER-positive, HER2 negative locally advanced breast cancer patients received letrozole (2.5 mg daily) and cyclophosphamide (50 mg daily) with/without Sorafenib (400 mg/bid daily) for 6 months before undergoing surgery. Ki67 expression and tumor size measured with caliber were determined at baseline, after 30 days of treatment and at the end of treatment. Patients were assigned to a clinical response category according to Response Evaluation Criteria in Solid Tumors, both at 30 days and before surgery and further classified as high-responder and low-responder according to the median variation of Ki67 values between biopsy and 30 days and between biopsy and surgery time. The predictive role of Ki67 and its changes with regard to clinical response and survival was analyzed. No differences in terms of survival outcomes emerged between the arms of treatment, while we observed a higher percentage of women with progression or stable disease in arm with the combination containing Sorafenib (20.5% vs 7.1%, = 0.06). Clinical complete responders experienced a greater overall variation in Ki67 when compared with partial responders and patients with progressive/stable disease (66.7% vs 30.7%, = 0.009). High responders showed a better outcome than low responders in terms of both disease-free survival ( = 0.009) and overall survival ( = 0.002). ΔKi67 score evaluated between basal and residual tumor at definitive surgery showed to be highly predictive of clinical complete response, and a potential parameter to be used for predicting disease-free survival and overall survival in luminal breast cancer treated with neoadjuvant endocrine-based therapy.
gene polymorphisms and related indel as predictor biomarkers of treatment response for colorectal cancer - toward a personalized medicine.
Barbirou M, Sghaier I, Bedoui S … +9 more , Ben Abderrazek R, Kraiem H, Farah A, Hassiki R, Mokrani A, Mezlini A, Almawi WY, Loueslati-Yacoubi B, Bouhaouala-Zahar B
Tumour Biol · 2020 Jun · PMID 32484056 · Publisher ↗
The gene variants were differentially associated with cancers. However, their association with colorectal cancer has not yet been explored. We investigated the contribution of the gene variants rs3331, rs1051295, and i...
The gene variants were differentially associated with cancers. However, their association with colorectal cancer has not yet been explored. We investigated the contribution of the gene variants rs3331, rs1051295, and indel (insertion/deletion) rs11468831 Polymorphism as predictors of the treatment response in colorectal cancer patients. A retrospective study, which involved 291 Tunisian colorectal cancer patients (aged 60.0 ± 13.1 years), who were stratified into responder and non-responder groups, according to TNM stages and their responsiveness to chemotherapy based on fluorouracil. genotyping was performed with amplification-refractory mutation system-polymerase chain reaction, and was confirmed by Sanger sequencing. Sex-specific response was found and colorectal cancer females are less likely to achieve a positive response during the chemotherapy strategy, compared to males. Weight and body mass index, tumor size, and tumor localization are considered as predictive factors to treatment responsiveness. Carriage of rs11468831 Ins allele was significantly associated with successful therapy achievement ( < 0.001). Stratification of colorectal cancer patients' response according to tumor localization and TNM stages reveals negative association of rs3331 Major allele to treatment response among the patients with advanced cancer stages (subgroup G2). The presence of rs3331 (homozygous minor) C/C genotype was positively associated with decline in carcino-embryonic antigen ( = 0.043) and CA19-9 ( = 0.014) serum levels. On the other hand, the presence of rs1051295 (homozygous minor) A/A genotype was correlated with marked decline in CA19-9 serum levels. haplotype did not reveal any association between haplotypes and treatment response. The results obtained suggest that gender-specific strategies for screening treatment and prevention protocols as well as variants may constitute an effective model for ongoing personalization medicine.
Contributions of HOX genes to cancer hallmarks: Enrichment pathway analysis and review.
Brotto DB, Siena ÁDD, de Barros II … +9 more , Carvalho SDCES, Muys BR, Goedert L, Cardoso C, Plaça JR, Ramão A, Squire JA, Araujo LF, Silva WAD
Tumour Biol · 2020 May · PMID 32456563 · Publisher ↗
Homeobox genes function as master regulatory transcription factors during development, and their expression is often altered in cancer. The HOX gene family was initially studied intensively to understand how the expressi...
Homeobox genes function as master regulatory transcription factors during development, and their expression is often altered in cancer. The HOX gene family was initially studied intensively to understand how the expression of each gene was involved in forming axial patterns and shaping the body plan during embryogenesis. More recent investigations have discovered that HOX genes can also play an important role in cancer. The literature has shown that the expression of HOX genes may be increased or decreased in different tumors and that these alterations may differ depending on the specific HOX gene involved and the type of cancer being investigated. New studies are also emerging, showing the critical role of some members of the HOX gene family in tumor progression and variation in clinical response. However, there has been limited systematic evaluation of the various contributions of each member of the HOX gene family in the pathways that drive the common phenotypic changes (or "hallmarks") and that underlie the transformation of normal cells to cancer cells. In this review, we investigate the context of the engagement of HOX gene targets and their downstream pathways in the acquisition of competence of tumor cells to undergo malignant transformation and tumor progression. We also summarize published findings on the involvement of HOX genes in carcinogenesis and use bioinformatics methods to examine how their downstream targets and pathways are involved in each hallmark of the cancer phenotype.
The association of a single-nucleotide variant in the microRNA-146a with advanced colorectal cancer prognosis.
Santos JSD, Zunta GL, Negrini AB … +5 more , Ribeiro MSG, Martinez CAR, Ribeiro ML, Lourenço GJ, Ortega MM
Tumour Biol · 2020 May · PMID 32438863 · Publisher ↗
The aim of this study was to evaluate the association of single-nucleotide variant n.60G>C (rs2910164) of microRNA (miR)-146a, related to suppressing of BRCA1/2 DNA repair protein, with the risk and survival of colorecta...
The aim of this study was to evaluate the association of single-nucleotide variant n.60G>C (rs2910164) of microRNA (miR)-146a, related to suppressing of BRCA1/2 DNA repair protein, with the risk and survival of colorectal cancer patients, as well as miR-146a and levels and miR binding efficiency. The genotypes were identified in 125 colorectal cancer patients and 276 controls using TaqMan polymerase chain reaction assay. The miR-146a and levels were assessed by quantitative-polymerase chain reaction protocols. Primary precursor of miR-146a containing G (wild-type) and C (variant) allele were cloned into pcDNA.3.3 vector and co-transfected in HT-29 colorectal cancer cell line. Luciferase reporter assay was performed to assess miR-146a binding to 3'-untranslated region in HT-29. The differences between groups were calculated using chi-square or Fisher's exact test, logistic regression, and Mann-Whitney test. The prognostic impact of single-nucleotide variant genotypes on overall survival was evaluated by Kaplan-Meier estimate and Cox regression. The GC or CC genotypes prevalence was similar in patients and controls (50.4% vs 50.7%, = 0.74). However, patients with tumors in advanced stage with miR-146a GG genotype had 2.41 more chance of dying than GC or CC genotypes. In addition, tumor tissues of patients with GG genotype presented higher miR-146a ( = 0.02) and lower ( = 0.01) and ( < 0.0001) levels when compared to those with GC or CC genotypes. In fact, pcDNA.3.3-miR-146a-G presented increased binding capacity to the 3'-untranslated region of ( = 0.001) compared to pcDNA.3.3-miR-146a-C. In addition, the G allele altered the binding affinity between miR-146a and its 3'-untranslated region target ( < 0.001), thus enhancing suppression of expression. Our results suggest that single-nucleotide variant rs2910164 does not influence the colorectal cancer risk in Brazilian patients; however, the GG genotype could act as a factor of worse prognosis in patients with advanced disease due to suppression of modulated by miR-146a.
Evaluation of cytotoxic and anticancer effect of methanolic extract on cancer cell lines.
Hegazy MG, Imam AM, Abdelghany BE
Tumour Biol · 2020 May · PMID 32367771 · Publisher ↗
We aimed to assess the antitumor activity of methanolic extract and evaluate its cytotoxic effect on different cancer cell lines to develop an effective natural anticancer drug. Components of methanolic extract were an...
We aimed to assess the antitumor activity of methanolic extract and evaluate its cytotoxic effect on different cancer cell lines to develop an effective natural anticancer drug. Components of methanolic extract were analyzed using gas chromatography-mass spectrometry. The extract's antioxidant activity was assessed by 2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power procedures and cytotoxicity of the extract was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase assays. Caspase-3 activity was also estimated. methanolic extract shows powerful antioxidant activity. The extract inhibited the propagation of human hepatocellular carcinoma (HepG2), human prostate cancer (PC3), human breast adenocarcinoma (MCF-7), and human colon carcinoma (HCT-116) in a dose-dependent manner. treated cells displayed obvious morphological structures distinctive of apoptosis. MTT assay exposed that the extract presented prevention of cell persistence in a dose-dependent means and revealed extremely cytotoxic activity against HepG2, PC3, MCF-7, and HCT-116 with 50% inhibitory concentration values 30.3, 111, 89.6, and 28.6 µg/mL, respectively, after 24 h of incubation. In addition, treatment of HCT-116 with various concentrations of the extract caused the release of lactate dehydrogenase and induction of caspase-3 activity in a dose-dependent way. In conclusion, our findings suggested that the extract possesses potent antioxidant, cytotoxic activity, and anticancer properties which are possibly due to the principal bioactive phytochemical composites existing in this plant. These results can be used to develop new drugs for cancer treatment.
Overexpression of associated with altered genome and poor survival in selected types of human cancer.
Tran OT, Tadesse S, Chu C … +1 more , Kidane D
Tumour Biol · 2020 May · PMID 32364878 · Publisher ↗
Base excision repair, which is initiated by the DNA -glycosylase proteins, is the frontline for repairing potentially mutagenic DNA base damage. Several base excision repair genes are deregulated in cancer and affect cel...
Base excision repair, which is initiated by the DNA -glycosylase proteins, is the frontline for repairing potentially mutagenic DNA base damage. Several base excision repair genes are deregulated in cancer and affect cellular outcomes to chemotherapy and carcinogenesis. Endonuclease VIII-like 3 (NEIL3) is a DNA glycosylase protein that is involved in oxidative and interstrand crosslink DNA damage repair. Our previous work has showed that NEIL3 is required to maintain replication fork integrity. It is unknown whether overexpression could contribute to cancer phenotypes, and its prognostic value and use as potential drug target remain unexplored. Our analysis of cancer genomics data sets reveals that frequently undergoes overexpression in several cancers. Furthermore, patients who exhibited NEIL3 overexpression with pancreatic adenocarcinoma, lung adenocarcinoma, lower grade glioma, kidney renal clear cell carcinoma, and kidney papillary cell carcinoma had worse overall survival. Importantly, overexpressed tumors accumulate mutation and chromosomal variations. Furthermore, overexpressed tumors exhibit simultaneous overexpression of homologous recombination genes (BRCA1/2) and mismatch repair genes (). However, overexpression is negatively correlated with tumor overexpressing nucleotide excision repair genes (/). Our results suggest that NEIL3 might be a potential prognosis marker for high-risk patients, and/or an attractive therapeutic target for selected cancers.
Increased circulating tumor DNA as a noninvasive biomarker of early treatment response in patients with metastatic ovarian carcinoma: A pilot study.
Alves MC, Fonseca FLA, Yamada AMTD … +6 more , Barros LADR, Lopes A, Silva LCFF, Luz AS, Melo Cruz FJS, Del Giglio A
Tumour Biol · 2020 May · PMID 32364828 · Publisher ↗
Detection of circulating tumor DNA is a new noninvasive technique with potential roles in diagnostic, follow-up, and prognostic evaluation of patients with many types of solid tumors. We aimed to evaluate the role of cir...
Detection of circulating tumor DNA is a new noninvasive technique with potential roles in diagnostic, follow-up, and prognostic evaluation of patients with many types of solid tumors. We aimed to evaluate the role of circulating tumor DNA in the setting of metastatic ovarian carcinoma. A prospective cohort of patients with metastatic ovarian cancer who were referred to systemic therapy was enrolled. Blood samples were collected before the start of treatment and monthly thereafter for 6 months. Circulating tumor DNA was quantified by real-time quantitative reverse transcription polymerase chain reaction of different lengths of elements as described by Umetani et al. A total of 11 patients were included, 2 for primary disease and 9 for recurrent disease. After the first cycle of chemotherapy, patients whose circulating tumor DNA levels increased from baseline were more likely to respond to chemotherapy than those whose circulating tumor DNA levels did not increase (p = 0.035). Furthermore, patients whose circulating tumor DNA levels rose after the first cycle of chemotherapy also had improved disease-free survival compared to those whose circulating tumor DNA levels did not increase (p = 0.0074). We conclude that the increase in circulating tumor DNA values collected in peripheral blood after the first cycle of systemic treatment in patients with advanced ovarian cancer is associated with an early response to systemic treatment and correlates with superior disease-free survival in this population. Circulating tumor DNA might be a specific, noninvasive, and cost-effective new biomarker of early response to systemic treatment in these patients.
Knockdown of A-kinase anchor protein 4 inhibits proliferation of triple-negative breast cancer cells and .
Jagadish N, Devi S, Gupta N … +2 more , Suri V, Suri A
Tumour Biol · 2020 Apr · PMID 32342732 · Publisher ↗
Triple-negative breast cancers are the most aggressive subtypes with poor prognosis due to lack of targeted cancer therapy. Recently, we reported an association of A-kinase anchor protein 4 expression with various clinic...
Triple-negative breast cancers are the most aggressive subtypes with poor prognosis due to lack of targeted cancer therapy. Recently, we reported an association of A-kinase anchor protein 4 expression with various clinico-pathological parameters of breast cancer patients. In this context, we examined the effect of knockdown of A-kinase anchor protein 4 on cell cycle, apoptosis, cellular proliferation, colony formation, migration, and invasion in triple-negative breast cancer cells. We also examined the synergistic cytotoxic effect of paclitaxel on A-kinase anchor protein 4 downregulated triple-negative breast cancer cells. Knockdown of A-kinase anchor protein 4 resulted in significant reduction in cellular growth and migratory abilities. Interestingly, we also observed enhanced cell death in A-kinase anchor protein 4 downregulated cells treated with paclitaxel. Knockdown of A-kinase anchor protein 4 in cell cycle resulted in G0/G1 phase arrest. Knockdown of A-kinase anchor protein 4 also led to increased reactive oxygen species generation as a result of upregulation of NOXA and CHOP. In addition, levels of cyclins, cyclin-dependent kinases, anti-apoptotic molecules, and mesenchymal markers were reduced in A-kinase anchor protein 4 downregulated cells. Moreover, downregulation of A-kinase anchor protein 4 also caused tumor growth reduction in studies. These data together suggest that A-kinase anchor protein 4 downregulation inhibits various malignant properties and enhances the cytotoxic effect of paclitaxel, and this combinatorial approach could be useful for triple-negative breast cancer treatment.
Comparison of methods for the isolation of cell-free DNA from cell culture supernatant.
Bronkhorst AJ, Ungerer V, Holdenrieder S
Tumour Biol · 2020 Apr · PMID 32338581 · Publisher ↗
In vitro characterization of cell-free DNA using two-dimensional cell culture models is emerging as an important step toward an improved understanding of the physical and biological characteristics of cell-free DNA in hu...
In vitro characterization of cell-free DNA using two-dimensional cell culture models is emerging as an important step toward an improved understanding of the physical and biological characteristics of cell-free DNA in human biology. However, precise measurement of the cell-free DNA in cell culture medium is highly dependent on the efficacy of the method used for DNA purification, and is often a juncture of experimental confusion. Therefore, in this study, we compared six commercially available cell-free DNA isolation kits for the recovery of cell-free DNA from the cell culture supernatant of a human bone cancer cell line (143B), including two magnetic bead-based manual kits, one automated magnetic bead-based extraction method, and three manual spin-column kits. Based on cell-free DNA quantitation and sizing, using the Qubit dsDNA HS assay and Bioanalyzer HS DNA assay, respectively, the different methods showed significant variability concerning recovery, reproducibility, and size discrimination. These findings highlight the importance of selecting a cell-free DNA extraction method that is appropriate for the aims of a study. For example, mutational analysis of cell-free DNA may be enhanced by a method that favors a high yield or is biased toward the isolation of short cell-free DNA fragments. In contrast, quantitative analysis of cell-free DNA in a comparative setting (e.g. measuring the fluctuation of cell-free DNA levels over time) may require the selection of a cell-free DNA isolation method that forgoes a high recovery for high reproducibility and minimal size bias.
Polo-like kinase 1 as a promising diagnostic biomarker and potential therapeutic target for hepatocellular carcinoma.
Yousef EH, El-Mesery ME, Habeeb MR … +1 more , Eissa LA
Tumour Biol · 2020 Apr · PMID 32252611 · Publisher ↗
Hepatocellular carcinoma is a major cause of cancer mortality worldwide. The outcome of hepatocellular carcinoma depends mainly on its early diagnosis. To date, the performance of traditional biomarkers is unsatisfactory...
Hepatocellular carcinoma is a major cause of cancer mortality worldwide. The outcome of hepatocellular carcinoma depends mainly on its early diagnosis. To date, the performance of traditional biomarkers is unsatisfactory. Polo-like kinase 1 is a serine/threonine kinase that plays essential roles in cell cycle progression and deoxyribonucleic acid damage. Moreover, polo-like kinase 1 knockdown decreases the survival of hepatocellular carcinoma cells; therefore, polo-like kinase 1 is an attractive target for anticancer treatments. Nobiletin, a natural polymethoxy flavonoid, exhibits a potential antiproliferative effect against a wide variety of cancers. This study targets to identify a reliable diagnostic biomarker for hepatocellular carcinoma and provide a potential therapeutic target for its treatment. Polo-like kinase 1 levels were analyzed in 44 hepatocellular carcinoma patients, 33 non-hepatocellular carcinoma liver cirrhosis patients and 15 healthy controls using the enzyme-linked immunosorbent assay method. Receiver operating characteristics curve analysis was used to establish a predictive model for polo-like kinase 1 relative to α-fetoprotein in hepatocellular carcinoma diagnosis. Furthermore, in the in vitro study, gene expressions were assessed by quantitative polymerase chain reaction in two human hepatocellular carcinoma cell lines after treatment with doxorubicin and polo-like kinase 1 inhibitor volasertib (Vola) either alone or in combination with nobiletin. Cell viability was also determined using the crystal violet assay.: Serum polo-like kinase 1 levels in hepatocellular carcinoma patients were significantly higher than liver cirrhosis and control groups (p < 0.0001). Polo-like kinase 1 showed a reasonable sensitivity, specificity, positive predictive value, and negative predictive value in hepatocellular carcinoma diagnosis. Moreover, nobiletin improved inhibition of cell growth induced by Vola and doxorubicin. Regarding reverse transcription polymerase chain reaction results, nobiletin suppressed expressions of polo-like kinase 1 and proliferating cell nuclear antigen and elevated expressions of P53, poly (ADPribose) polymerase 1, and caspase-3. Nobiletin/doxorubicin and nobiletin/Vola showed a significant increase in caspase-3 activity indicating cell apoptosis. Polo-like kinase 1 may be a potential biomarker for hepatocellular carcinoma diagnosis and follow-up during treatment with chemotherapies. In addition, nobiletin synergistically potentiates the doxorubicin and Vola-mediated anticancer effect that may be attributed partly to suppression of polo-like kinase 1 and proliferating cell nuclear antigen expression and enhancement of chemotherapy-induced apoptosis.
Samarium enriches antitumor activity of ZnO nanoparticles via downregulation of CXCR4 receptor and cytochrome P450.
Nabeel AI
Tumour Biol · 2020 Mar · PMID 32129155 · Publisher ↗
Cancer is the leading cause of death and exhausts human and economic resources for treatment and protection. Zinc oxide nanoparticles play an effective role in tumor treatment but with some cautions, such as overexpressi...
Cancer is the leading cause of death and exhausts human and economic resources for treatment and protection. Zinc oxide nanoparticles play an effective role in tumor treatment but with some cautions, such as overexpression of cytochrome P450, hepatic overload, and the mammalian target of rapamycin pathway resistance. Although lanthanides have antitumor activity, their use is limited. Therefore, the current study aims to improve the effectiveness of zinc oxide nanoparticle via doping with lanthanides, such as samarium. In vitro study revealed that samarium doped with zinc oxide showed more antitumor activity than the other lanthanides, and the antitumor activity depends on the concentration of samarium in the nanocomposite. The in vivo experiment on mice bearing Ehrlich solid tumor revealed that intramuscular injection of samarium/zinc oxide downregulates the expressions of CXCR4 and PI3K/Akt/mammalian target of rapamycin pathway in respect to Ehrlich solid tumor group. Regarding the apoptotic biomarkers, samarium/zinc oxide upregulates the apoptotic biomarker; Bax accompanied with the mitotic catastrophe which was indicated by cell cycle arrest in G2 phase. Moreover, samarium:zinc oxide nanoparticles exhibited minimum toxicity which was indicated by suppressed activities of cytochrome P450 and hepatic enzymes, including alanine transaminase and aspartate transaminase. In addition, the histopathological finding, as well as immunophenotyping results, appreciated the biochemical finding. Therefore, samarium:zinc oxide might be offered a new approach to improve the effectiveness of zinc oxide nanoparticles along with lower toxic effect. Also, samarium:zinc oxide nanoparticles can be a candidate as a new antitumor compound to detect its mode of action.
Commentary: Cancer research quality and tumour classification.
Cree IA, Indave BI
Tumour Biol · 2020 Feb · PMID 32098581 · Publisher ↗
Cancer researchers require accurate diagnoses for the samples, cell lines, patients or populations that they study. These diagnoses are underpinned by an internationally accepted taxonomy - the World Health Organization...
Cancer researchers require accurate diagnoses for the samples, cell lines, patients or populations that they study. These diagnoses are underpinned by an internationally accepted taxonomy - the World Health Organization Classification of Tumours. This is still largely based on the histopathological examination of biopsy specimens, but increasingly also molecular methods and radiological examination of patients. Classifications evolve as new evidence arises, and for tumours that evidence is available in a quantity that is both remarkable and daunting. Evaluating this deluge of new information and incorporating it into the World Health Organization Classification of Tumours is now the responsibility of an editorial board, and up to 200 editors and authors work on each system to update it within the new 5th edition. Just as cancer researchers depend on the classification for diagnoses, so too the classification depends on the generation of high-quality, trustworthy data by cancer researchers. It is not just a case of quantity but quality too. Scientific fraud is thankfully rare, but high-profile cases are damaging and standards need to improve, not least to ensure that accurate information enters the classification.
Antiproliferative and proapoptotic effects of extract on Burkitt lymphoma cell line.
Virdis P, Migheli R, Galleri G … +13 more , Fancello S, Cadoni MPL, Pintore G, Petretto GL, Marchesi I, Fiorentino FP, di Francesco A, Sanges F, Bagella L, Muroni MR, Fozza C, De Miglio MR, Podda L
Tumour Biol · 2020 Feb · PMID 32013807 · Publisher ↗
Burkitt lymphoma is a very aggressive B-cell non-Hodgkin lymphoma. Although remarkable progress has been made in the therapeutic scenario for patients with Burkitt lymphoma, search and development of new effective antica...
Burkitt lymphoma is a very aggressive B-cell non-Hodgkin lymphoma. Although remarkable progress has been made in the therapeutic scenario for patients with Burkitt lymphoma, search and development of new effective anticancer agents to improve patient outcome and minimize toxicity has become an urgent issue. In this study, the antitumoral activity of , a traditional herb obtained from plants collected on the Asinara Island, Italy, was evaluated in order to explore potential antineoplastic effects of its metabolites on Burkitt lymphoma. Raji human cell line was treated with increasing extract concentration for cytotoxicity screening and subsequent establishment of cell cycle arrest and apoptosis. Moreover, gene expression profiles were performed to identify molecular mechanisms involved in the anticancer activities of this medical plant. The extract exhibited powerful antiproliferative and cytotoxic activities on Raji cell line, showing a dose- and time-dependent decrease in cell viability, obtained by cell cycle arrest in the G2/M phase and an increase in cell apoptosis. The treatment with caused downregulation of genes involved in cell cycle and proliferation (c-MYC, CCND1) and inhibition of cell apoptosis (BCL2, BCL2L1, BCL11A). The extract causes strong anticancer effects on Burkitt lymphoma cell line. The molecular mechanisms underlying such antineoplastic activity are based on targeting and downregulation of genes involved in cell cycle and apoptosis. Our data suggest that natural metabolites should be further exploited as potential antineoplastic agents against Burkitt lymphoma.
Identification of an immune-suppressed subtype of feline triple-negative basal-like invasive mammary carcinomas, spontaneous models of breast cancer.
Dagher E, Simbault L, Abadie J … +3 more , Loussouarn D, Campone M, Nguyen F
Tumour Biol · 2020 Jan · PMID 31959092 · Publisher ↗
Feline invasive mammary carcinomas are characterized by their high clinical aggressiveness, rare expression of hormone receptors, and pathological resemblance to human breast cancer, especially triple-negative breast can...
Feline invasive mammary carcinomas are characterized by their high clinical aggressiveness, rare expression of hormone receptors, and pathological resemblance to human breast cancer, especially triple-negative breast cancer (negative to estrogen receptor, progesterone receptor, and epidermal growth factor receptor type 2). Recent gene expression studies of triple-negative breast cancers have highlighted their heterogeneity and the importance of immune responses in their biology and prognostic assessment. Indeed, regulatory T cells may play a crucial role in producing an immune-suppressed microenvironment, notably in triple-negative breast cancers. Feline invasive mammary carcinomas arise spontaneously in immune-competent animals, in which we hypothesized that the immune tumor microenvironment also plays a role. The aims of this study were to determine the quantity and prognostic value of forkhead box protein P3-positive peritumoral and intratumoral regulatory T cells in feline invasive mammary carcinomas, and to identify an immune-suppressed subgroup of triple-negative basal-like feline invasive mammary carcinomas. One hundred and eighty female cats with feline invasive mammary carcinomas, treated by surgery only, with 2-year follow-up post-mastectomy, were included in this study. Forkhead box protein P3, estrogen receptor, progesterone receptor, Ki-67, epidermal growth factor receptor type 2, and cytokeratin 14 expression were assessed by automated immunohistochemistry. Peritumoral regulatory T cells were over 300 times more abundant than intratumoral regulatory T cells in feline invasive mammary carcinomas. Peritumoral and intratumoral regulatory T cells were associated with shorter disease-free interval and overall survival in both triple-negative (ER-, PR-, HER2-, N = 123 out of 180) and luminal (ER+ and/or PR+, N = 57) feline invasive mammary carcinomas. In feline triple-negative basal-like (CK14+) mammary carcinomas, a regulatory T-cell-enriched subgroup was associated with significantly poorer disease-free interval, overall survival, and cancer-specific survival than regulatory T-cell-poor triple-negative basal-like feline invasive mammary carcinomas. High regulatory T-cell numbers had strong and negative prognostic value in feline invasive mammary carcinomas, especially in the triple-negative basal-like subgroup, which might contain a "basal-like immune-suppressed" subtype, as described in triple-negative breast cancer. Cats with feline invasive mammary carcinomas may thus be interesting spontaneous animal models to investigate new strategies of cancer immunotherapy in an immune-suppressed tumor microenvironment.
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