Tumor Biology - Volume 43, issue 1

Article Type: Correction

DOI: 10.3233/TUB-219008

Citation: Tumor Biology, vol. 43, no. 1, pp. 261-262, 2021

Authors: Aguiar, Graziela de Moura | Ramão, Anelisa | Plaça, Jessica Rodrigues | Simões, Sarah Capelupe | Scaraboto, Natália Volgarine | Freitas-Castro, Felipe | Cardoso, Cibele | Sousa, Josane de Freitas | Silva Jr , Wilson Araújo

Article Type: Research Article

Abstract: BACKGROUND: Expression dysregulation of HOX homeobox genes has been observed in several cancers, including head and neck squamous cell carcinoma (HNSC). Although characterization of HOX gene roles in HNSC development has been reported, there is still a need to better understand their real contribution to tumorigenesis. OBJECTIVE: The present study aimed to evaluate the contribution of the protein-coding HOX genes (HOXA10 , HOXC9 , HOXC10 , and HOXC13 ) in cellular processes related to carcinogenesis and progression of the HNSC. METHODS: Expression of HOX genes was analyzed in HNSC RNA-Seq data from …The Cancer Genome Atlas (TCGA) and by RT-qPCR in different tumor cell lines. siRNA-mediated knockdown of HOXA10 , HOXC9 , HOXC10 or HOXC13 was performed in HNSC cell lines, and predicted transcriptional targets HOX genes was analyzed by bioinformatic. RESULTS: Thirty-one out of the 39 mammalian HOX genes were found upregulated in HNSC tissues and cell lines. The HOXC9 , HOXC10 or HOXC13 knockdown attenuated cell migration, and lead to downregulation of epithelial-mesenchymal transition (EMT) markers, which were predicted as transcriptional targets of these three HOX genes. Diminished colony formation and cell cycle arrest after HOXC10 or HOXC13 knockdown were also observed, corroborating the fact that there was an enrichment for genes in proliferation/cell cycle pathways. CONCLUSIONS: In summary, we revealed roles for HOXC9 , HOXC10 , and HOXC13 in cell migration and proliferation/cell cycle progression in HNSC cells and suggested that those HOX members contribute to HNSC development possibly by regulating tumor growth and metastasis. Show more

Keywords: HOX genes, head and neck cancer, bioinformatics, migration, proliferation

DOI: 10.3233/TUB-211525

Citation: Tumor Biology, vol. 43, no. 1, pp. 263-278, 2021

Article Type: Correction

DOI: 10.3233/TUB-219005

Citation: Tumor Biology, vol. 43, no. 1, pp. 279-279, 2021

Article Type: Correction

DOI: 10.3233/TUB-219007

Citation: Tumor Biology, vol. 43, no. 1, pp. 281-281, 2021

Article Type: Addendum

DOI: 10.3233/TUB-219006

Citation: Tumor Biology, vol. 43, no. 1, pp. 283-283, 2021

Authors: Patel, Deep A. | Blay, Jonathan

Article Type: Review Article

Abstract: Peripheral human blood is a readily-accessible source of patient material in which circulating tumour cells (CTCs) can be found. Their isolation and characterization holds the potential to provide prognostic value for various solid cancers. Enumeration of CTCs from blood is becoming a common practice in informing prognosis and may guide therapy decisions. It is further recognized that enumeration alone does not capture perspective on the heterogeneity of tumours and varying functional abilities of the CTCs to interact with the secondary microenvironment. Characterizing the isolated CTCs further, in particular assessing their functional abilities, can track molecular changes in the disease progress. …As a step towards identifying a suite of functional features of CTCs that could aid in clinical decisions, developing a CTC isolation technique based on extracellular matrix (ECM) interactions may provide a more solid foundation for isolating the cells of interest. Techniques based on size, charge, density, and single biomarkers are not sufficient as they underutilize other characteristics of cancer cells. The ability of cancer cells to interact with ECM proteins presents an opportunity to utilize their full character in capturing, and also allows assessment of the features that reveal how cells might behave at secondary sites during metastasis. This article will review some common techniques and recent advances in CTC capture technologies. It will further explore the heterogeneity of the CTC population, challenges they experience in their metastatic journey, and the advantages of utilizing an ECM-based platform for CTC capture. Lastly, we will discuss how tailored ECM approaches may present an optimal platform to capture an influential heterogeneous population of CTCs. Show more

Keywords: CTC, metastasis, EMT, integrins, ECM adhesion

DOI: 10.3233/TUB-210001

Citation: Tumor Biology, vol. 43, no. 1, pp. 285-306, 2021

Article Type: Correction

DOI: 10.3233/TUB-219009

Citation: Tumor Biology, vol. 43, no. 1, pp. 307-307, 2021

Authors: Takeba, Yuko | Ohta, Yuki | Ootaki, Masanori | Kobayashi, Tsukasa | Kida, Keisuke | Watanabe, Minoru | Koizumi, Satoshi | Otsubo, Takehito | Iiri, Taroh | Matsumoto, Naoki

Article Type: Research Article

Abstract: BACKGROUND: Cytokines play an important role in the immune response, angiogenesis, cell growth, and differentiation in hepatocellular carcinoma (HCC). OBJECTIVE: We performed a comprehensive study to identify tumor-related cytokines and pathways involved in HCC pathogenesis. METHODS: Cytokine production was evaluated in human HCC tissues and adjacent non-tumor tissues using an antibody-based protein array technique. We compared cytokine expression in HCC tissues with that of hepatic hemangioma (HH), liver metastasis of colorectal cancer, and noncancerous liver tissues from transplantation donors. The protein levels and localization of the candidate cytokines were analyzed by western blotting and immunohistochemistry. …RESULTS: Increased expression of interleukin (IL)-1 receptor antagonist, macrophage migration inhibitory factor, and IL-16 was observed in HCC and paired adjacent non-tumor tissues compared with noncancerous livers. In addition, there were increased IL-16 levels in HCC tissues compared with HH. IL-16 treatment significantly increased cell proliferation in vitro . The expression of extracellular signal-regulated kinase (ERK)1/2 and cyclin D1 was markedly increased in cells from two HCC cell lines, Huh7 and HepG2, in a dose- and time-dependent manner. Phosphorylated to total ERK1/2 ratio was increased in Huh7 cells following IL-16 50 ng/ml, but not HepG2 cells. ERK phosphorylation have occurred earlier than protein accumulation at 48 h. Pretreatment with the ERK inhibitor, FR18024, or an anti-IL-16 antibody reduced the increase in IL-16 production in HCC cells. CONCLUSIONS: These results suggest that cell proliferation induced by IL-16 is mediated through the ERK pathway, thus, we identified a new factor associated with HCC tumor growth. Show more

Keywords: Antibody-based protein array, IL-16, Cyclin D1, ERK, hepatocellular carcinoma

DOI: 10.3233/TUB-211507

Citation: Tumor Biology, vol. 43, no. 1, pp. 309-325, 2021

Authors: Andrade da Mota, Tales Henrique | Reis Guimarães, Ana Flávia | Silva de Carvalho, Amandda Évelin | Saldanha- de Araujo, Felipe | Pinto de Faria Lopes, Giselle | Pittella-Silva, Fábio | do Amaral Rabello, Doralina | Madureira de Oliveira, Diêgo

Article Type: Research Article

Abstract: BACKGROUND: The inhibition of the enzyme telomerase (TERT) has been widely investigated as a new pharmacological approach for cancer treatment, but its real potential and the biochemical consequences are not totally understood. OBJECTIVE: Here, we investigated the effects of the telomerase inhibitor MST-312 on a human glioma cell line after both short- and long-term (290 days) treatments. METHODS: Effects on cell growth, viability, cell cycle, morphology, cell death and genes expression were assessed. RESULTS: We found that short-term treatment promoted cell cycle arrest followed by apoptosis. Importantly, cells with telomerase knock-down revealed that the …toxic effects of MST-312 are partially TERT dependent. In contrast, although the long-term treatment decreased cell proliferation at first, it also caused adaptations potentially related to treatment resistance and tumor aggressiveness after long time of exposition. CONCLUSIONS: Despite the short-term effects of telomerase inhibition not being due to telomere erosion, they are at least partially related to the enzyme inhibition, which may represent an important strategy to pave the way for tumor growth control, especially through modulation of the non-canonical functions of telomerase. On the other hand, long-term exposure to the inhibitor had the potential to induce cell adaptations with possible negative clinical implications. Show more

Keywords: Glioma, telomerase, TERT, MST-312, long-term treatment

DOI: 10.3233/TUB-211515

Citation: Tumor Biology, vol. 43, no. 1, pp. 327-340, 2021

Authors: Meirovitz, Amichay | Baider, Lea | Peretz, Tamar | Stephanos, Samir | Barak, Vivian

Article Type: Research Article

Abstract: BACKGROUND: Cancer progression is associated with significant systemic clinical manifestations including cachexia induced weight loss and anorexia. Pentoxifylline (PTX) is a drug that has been shown to have multiple beneficial effects in cancer patients through its anti-inflammatory properties. MAIN OBJECTIVE: To evaluate PTX effects on colon cancer patients treated with chemotherapy. PATIENTS and METHODS: Forty metastatic colon cancer patients receiving chemotherapy were enrolled in this randomized study. 17 patients were treated with a full dose of PTX (400 mg TID), 9 patients with a reduced dose PTX (200 mg TID) and 23 served as controls (no PTX). …RESULTS: Follow-up evaluations of patients included the following: physical examination; leukopenia determination; weight determination; stomatitis determination; and survival rate. Patients treated with PTX (both full and reduced doses), experienced a significant increase in weight and a reduction in stomatitis relative to the control group. Treatment with PTX also significantly increased patient survival rate. All patients treated with PTX, had a median overall survival (OS) rate of 20.4 months as compared to 13.2 months in the control group. CONCLUSIONS: PTX treatment of colon cancer patients, in addition to chemotherapy, significantly improved survival rates, induced weight gain and reduced stomatitis occurrence –all important parameters of cachexia. Show more

Keywords: Pentoxifylline, colon cancer, cachexia, weight gain, stomatitis, survival

DOI: 10.3233/TUB-211533

Citation: Tumor Biology, vol. 43, no. 1, pp. 341-349, 2021