• Issue

    Cancer Science: Volume 108, Issue 4

    543-804
    April 2017

ISSUE INFORMATION

Free Access

Issue Information

  • Pages: 543-545
  • First Published: 26 April 2017
Issue Information

Cover of this issue. Mosaic expression of SMARCB1/INI1 in schwannomatosis. See also Kohashi et al. (pages 547–552 of this issue).

IN THIS ISSUE

Free Access

In This Issue

  • Page: 546
  • First Published: 26 April 2017

REVIEW ARTICLES

Open Access

Oncogenic roles of SMARCB1/INI1 and its deficient tumors

  • Pages: 547-552
  • First Published: 21 January 2017
Oncogenic roles of SMARCB1/INI1 and its deficient tumors

Target genes and pathways implicated in the tumor suppressor activity of SMARCB1/INI1.

Open Access

Epigenetics in normal and malignant hematopoiesis: An overview and update 2017

  • Pages: 553-562
  • First Published: 18 January 2017
Epigenetics in normal and malignant hematopoiesis: An overview and update 2017

In this review, we provide an overview of genetic alterations within epigenetic genes in various types of hematopoietic neoplasms. We also summarize the physiologic roles of these epigenetic modifiers during hematopoiesis, and describe therapeutic approaches targeting the epigenetic modifications.

Open Access

Impact of senescence-associated secretory phenotype and its potential as a therapeutic target for senescence-associated diseases

  • Pages: 563-569
  • First Published: 06 February 2017
Impact of senescence-associated secretory phenotype and its potential as a therapeutic target for senescence-associated diseases

We provide the latest insight into the impact of senescence-associated secretory phenotype (SASP) on age-related diseases by reviewing and discussing its functional and regulatory mechanisms. SASP could have beneficial or detrimental outcomes in physiological and pathological processes during aging, and emerging therapeutic strategies targeting senescent cells and SASP are promising for future clinical translation controlling aging and aging-associated diseases, including cancer.

Open Access

Molecular-targeting therapies against quantitative abnormalities in gene expression with malignant tumors

  • Pages: 570-573
  • First Published: 08 February 2017
Molecular-targeting therapies against quantitative abnormalities in gene expression with malignant tumors

In this manuscript, we focused on the quantitative abnormalities in gene expression with carcinogenesis, and discussed the importance of normalizing the quantitative abnormalities in gene expression by molecular-targeting agents.

Open Access

Suppressors of cytokine signaling: Potential immune checkpoint molecules for cancer immunotherapy

  • Pages: 574-580
  • First Published: 11 February 2017
Suppressors of cytokine signaling: Potential immune checkpoint molecules for cancer immunotherapy

Inhibition of immune-checkpoint molecules, PD-1 and CTLA4, has been shown to be a promising cancer treatment. SOCS proteins are the third immune-checkpoint molecules that inhibit cytokine signaling. This review is focusing on the mechanism of inhibition of cytokine signaling by CIS, SOCS1 and SOCS3, and their relationship to T cell biology and anti-tumor immunity.

ORIGINAL ARTICLES

BASIC AND CLINICAL IMMUNOLOGY

Open Access

Novel pegylated interferon-β as strong suppressor of the malignant ascites in a peritoneal metastasis model of human cancer

  • Pages: 581-589
  • First Published: 27 January 2017
Novel pegylated interferon-β as strong suppressor of the malignant ascites in a peritoneal metastasis model of human cancer

Malignant ascites manifests as an end-stage event during the progression of a number of cancers and is associated with significant morbidity. In this study, we report on the development of a novel, long-acting formulation of human and mouse interferon-β (IFN-β). Pegylated IFN-β contains the site-specific conjugation of polyethylene glycol residue to IFN-β. We demonstrated that PEG-mIFN-β, but not PEG-hIFN-β, significantly suppressed the accumulation of ascites fluid in this model. These findings reveal a new facet of the long-acting PEG-hIFN-β and provide a therapeutic rationale for evaluating long-acting PEG-IFN-β in the treatment of malignant ascites.

Open Access

Programmed death-ligand 1 is prognostic factor in esophageal squamous cell carcinoma and is associated with epidermal growth factor receptor

  • Pages: 590-597
  • First Published: 13 February 2017
Programmed death-ligand 1 is prognostic factor in esophageal squamous cell carcinoma and is associated with epidermal growth factor receptor

Our study indicates that tumor-infiltrating immune cell PD-L1 expression is an independent prognostic factor for ESCC, and the association between EGFR and PD-L1 is vital to determining survival. It is important to consider radiotherapy-induced imbalance of pro-tumor and anti-tumor immune response. A combination of radiotherapy and PD-L1-targeted therapies could be a promising therapeutic strategy for ESCC patients.

Open Access

Immunological evaluation of peptide vaccination for cancer patients with the HLA -A11+ or -A33+ allele

  • Pages: 598-603
  • First Published: 08 February 2017
Immunological evaluation of peptide vaccination for cancer patients with the HLA -A11+ or -A33+ allele

IgG boosting were observed in HLA-A11+/A11+ patients and HLA-A33+/A33+ patients after personalized peptide vaccine(PPV). The patients with higher rate of changes of peptide-specific IgG titers after 2nd cycle of vaccination showed longer prognosis than those with lower rate.

CARCINOGENESIS

Open Access

Downregulation of delta-aminolevulinate dehydratase is associated with poor prognosis in patients with breast cancer

  • Pages: 604-611
  • First Published: 03 February 2017
Downregulation of delta-aminolevulinate dehydratase is associated with poor prognosis in patients with breast cancer

ALAD is down-regulated in breast cancer. ALAD inhibits breast cancer progression. ALAD regulates TGF-β-mediated EMT.

Open Access

Identification of FERM domain-containing protein 5 as a novel target of β-catenin/TCF7L2 complex

  • Pages: 612-619
  • First Published: 24 January 2017
Identification of FERM domain-containing protein 5 as a novel target of β-catenin/TCF7L2 complex

Deregulation of the canonical Wnt signaling pathway plays an important role in human tumorigenesis. In this study, we identified FRMD5 as a novel Wnt signaling target gene in colorectal cancer cells. Gene set enrichment analysis revealed that FRMD5 is associated with cell cycle and cell-extracellular interaction.

Open Access

MicroRNA-155-5p promotes hepatocellular carcinoma progression by suppressing PTEN through the PI3K/Akt pathway

  • Pages: 620-631
  • First Published: 28 January 2017
MicroRNA-155-5p promotes hepatocellular carcinoma progression by suppressing PTEN through the PI3K/Akt pathway

In this study, we verified PTEN as a novel miR-155-5p target and demonstrated that miR-155-5p promoted HCC progression by suppressing PTEN and activation of the PI3K/Akt pathway.

Open Access

Sox2-dependent inhibition of p21 is associated with poor prognosis of endometrial cancer

  • Pages: 632-640
  • First Published: 11 February 2017
Sox2-dependent inhibition of p21 is associated with poor prognosis of endometrial cancer

SOX2 is required for endometrial cancer cell growth. Expressions of SOX2 in endometrial cancer patients is significantly correlated with histological grade and poor prognosis. Low p21 together with high SOX2 expressions in advanced endometrial cancer patients are associated with the most unfavorable outcomes of patients.

Open Access

Hypoxia-inducible microRNA-210 regulates the DIMT1-IRF4 oncogenic axis in multiple myeloma

  • Pages: 641-652
  • First Published: 06 February 2017
Hypoxia-inducible microRNA-210 regulates the DIMT1-IRF4 oncogenic axis in multiple myeloma

By screening for targets of hypoxia-inducible microRNA-210, we identified a 18S rRNA base methyltransferase DIMT1 as a novel diagnostic marker and therapeutic target for all molecular subtypes of multiple myeloma.

Open Access

Long noncoding RNA SchLAH suppresses metastasis of hepatocellular carcinoma through interacting with fused in sarcoma

  • Pages: 653-662
  • First Published: 14 February 2017
Long noncoding RNA SchLAH suppresses metastasis of hepatocellular carcinoma through interacting with fused in sarcoma

Our results showed that SchLAH was down regulated in HCC. SchLAH may suppress the metastasis of HCC cells by interacting with FUS, which indicates potential of SchLAH for the prognosis and treatment of HCC.

CLINICAL RESEARCH

Open Access

Predictive and prognostic role of serum neopterin and tryptophan breakdown in prostate cancer

  • Pages: 663-670
  • First Published: 20 January 2017
Predictive and prognostic role of serum neopterin and tryptophan breakdown in prostate cancer

Accelerated neopterin and tryptophan breakdown seems to play an important role regarding prostate carcinogenesis, with the highest levels in patients with biochemical recurrence after radical prostatectomy. Neopterin was the only independent prognostic factor for cancer-specific survival after biochemical recurrence. These data may support the recommendation of neopterin measurement in making decision for further oncologic treatment strategies and in monitoring patients during therapy following biochemical recurrence.

Open Access

HER2 somatic mutations are associated with poor survival in HER2-negative breast cancers

  • Pages: 671-677
  • First Published: 06 February 2017
HER2 somatic mutations are associated with poor survival in HER2-negative breast cancers

We identified HER2 somatic mutations in tumors from 1348 unselected breast cancer patients by sequencing the entire HER2 coding region. Here, we are first to report that HER2-negative breast cancer patients with HER2 somatic mutation have an unfavorable survival. Therefore, HER2-negative patients with HER2 somatic mutation are potentially good candidates for HER2-targeted therapy or for recruitment into ongoing clinical trials.

CELL, MOLECULAR, AND STEM CELL BIOLOGY

Open Access

Cluster microRNAs miR-194 and miR-215 suppress the tumorigenicity of intestinal tumor organoids

  • Pages: 678-684
  • First Published: 16 January 2017
Cluster microRNAs miR-194 and miR-215 suppress the tumorigenicity of intestinal tumor organoids

Here we established organoids derived from intestinal tumors of Min mice. Expression of the cluster miRNAs, miR-194 and miR-215, was markedly suppressed in intestinal tumor organoids in comparison with organoids derived from normal intestinal epithelia. Enforced expression of miR-194 and miR-215 suppresses intestinal tumor organoids.

Open Access

MicroRNA-9 plays a role in interleukin-10-mediated expression of E-cadherin in acute myelogenous leukemia cells

  • Pages: 685-695
  • First Published: 20 January 2017
MicroRNA-9 plays a role in interleukin-10-mediated expression of E-cadherin in acute myelogenous leukemia cells

The present study explored the novel biological function of IL-10 in regulation of expression of adhesion molecules in AML cells and found that exposing AML cells to IL-10 induced expression of E-cadherin. IL-10/E-cadherin axis may be a promising therapeutic target for treating AML.

Open Access

Podoplanin promotes progression of malignant pleural mesothelioma by regulating motility and focus formation

  • Pages: 696-703
  • First Published: 09 February 2017
Podoplanin promotes progression of malignant pleural mesothelioma by regulating motility and focus formation

Podoplanin (PDPN) is an established diagnostic marker for malignant pleural mesothelioma (MPM), but the function of PDPN in MPM is not fully understood. In the present study, we demonstrated that PDPN plays a major role in the progression of MPM by stimulating cell motility via RhoA/ROCK pathway activation and by blocking contact inhibition associated with decreased E-cadherin expression and YAP1 activation.Collectively, our findings indicate that PDPN is an ideal target for treatment of patients with MPM.

Open Access

Radiosensitivity of quiescent and proliferating cells grown as multicellular tumor spheroids

  • Pages: 704-712
  • First Published: 30 January 2017
Radiosensitivity of quiescent and proliferating cells grown as multicellular tumor spheroids

The Fucci system enabled us to separately determine radiosensitivity of quiescent and proliferating cells grown as multicellular spheroids, and made it possible to comprehensively characterize the radiosensitivity of spheroids for the first time.

Open Access

Protein-arginine deiminase 2 suppresses proliferation of colon cancer cells through protein citrullination

  • Pages: 713-718
  • First Published: 03 February 2017
Protein-arginine deiminase 2 suppresses proliferation of colon cancer cells through protein citrullination

PADI2 isoform 1 was expressed in normal colon epithelial cells but downregulated during colon carcinogenesis. Overexpression of PADI2 suppressed cell proliferation concomitant with increased protein citrullination.

Open Access

SOX2 is required to maintain cancer stem cells in ovarian cancer

  • Pages: 719-731
  • First Published: 06 February 2017
SOX2 is required to maintain cancer stem cells in ovarian cancer

we demonstrate that SOX2 is overexpressed in ovarian cancer spheroids, and prove that SOX2 plays a key role in maintaining ovarian cancer stem cell properties, including self-renewal, chemotherapy resistance and tumorigenicity.

Open Access

Identification of proteasomal catalytic subunit PSMA6 as a therapeutic target for lung cancer

  • Pages: 732-743
  • First Published: 06 February 2017
Identification of proteasomal catalytic subunit PSMA6 as a therapeutic target for lung cancer

By doing an integrative analysis we have identified PSMA6, a subunit of the proteasome complex, as one of the most promising targets for lung cancer. We showed that PSMA6 knockdown suppressed the viability of cancer cells through the induction of apoptosis or cell cycle arrest at G2/M, with only a minimal effect on normal lung epithelial cells. Our data suggested that targeting PSMA6 for lung cancer may be an attractive novel therapeutic strategy.

Open Access

Amino-terminal enhancer of split gene AES encodes a tumor and metastasis suppressor of prostate cancer

  • Pages: 744-752
  • First Published: 08 February 2017
Amino-terminal enhancer of split gene AES encodes a tumor and metastasis suppressor of prostate cancer

Aes suppresses metastatic spread of human prostate cancer cell grafts to the bone in mice. In vivo bioluminescence images of mice injected with luciferase-expressing PC3 cels into the left cardiac ventricle.

Open Access

Effect of a hypoxic microenvironment after radiofrequency ablation on residual hepatocellular cell migration and invasion

  • Pages: 753-762
  • First Published: 09 February 2017
Effect of a hypoxic microenvironment after radiofrequency ablation on residual hepatocellular cell migration and invasion

A sustained hypoxic microenvironment after RFA may exert a negative impact on the prognosis of HCC patients, and minimizing exposure to a hypoxic microenvironment and targeting HIF-1α signaling might be effective strategies for patients who experience insufficient RFA therapy.

DRUG DISCOVERY AND DELIVERY

Open Access

Targeting of tumor growth and angiogenesis underlies the enhanced antitumor activity of lenvatinib in combination with everolimus

  • Pages: 763-771
  • First Published: 20 January 2017
Targeting of tumor growth and angiogenesis underlies the enhanced antitumor activity of lenvatinib in combination with everolimus

Lenvatinib is a multiple receptor tyrosine kinase (RTK) inhibitor that selectively inhibits VEGFR, FGFR, and other proangiogenic and oncogenic pathway-related RTKs. Here we show that simultaneous targeting of tumor cell growth and angiogenesis by lenvatinib plus everolimus, and enhanced inhibition of VEGF- and FGF-driven angiogenesis through greater inhibition of the mTOR–S6K–S6 signaling pathway underlie the antitumor activity conferred by the combination of lenvatinib plus everolimus in preclinical RCC models.

Open Access

Mitochondrial uncoupler exerts a synthetic lethal effect against β-catenin mutant tumor cells

  • Pages: 772-784
  • First Published: 20 January 2017
Mitochondrial uncoupler exerts a synthetic lethal effect against β-catenin mutant tumor cells

We screened an in-house natural product library for compounds that exhibited synthetic lethality towards beta-catenin mutations and isolated nonactin, an antibiotic mitochondrial uncoupler, as a hit compound. Nonactin, as well as other mitochondrial uncouplers, induced apoptosis selectively in beta-catenin mutated tumor cells in vitro and in vivo. Furthermore, we found that expression of an active mutant form of beta-catenin induced a decrease in the glycolysis rate.

Open Access

Protein kinase A inhibition facilitates the antitumor activity of xanthohumol, a valosin-containing protein inhibitor

  • Pages: 785-794
  • First Published: 25 January 2017
Protein kinase A inhibition facilitates the antitumor activity of xanthohumol, a valosin-containing protein inhibitor

The inhibition of protein kinase A (PKA), a downstream kinase of adenylate cyclase (AC) pathway, enhanced the apoptosis-inducing activity of xanthohumol (XN). It indicated that the AC/PKA pathway could contribute to preventing apoptosis induced by XN and that the activity of AC/PKA pathway in tumor cells could determine sensitivity to XN.

Open Access

Immune-complex level of cofilin-1 in sera is associated with cancer progression and poor prognosis in pancreatic cancer

  • Pages: 795-803
  • First Published: 04 February 2017
Immune-complex level of cofilin-1 in sera is associated with cancer progression and poor prognosis in pancreatic cancer

High cofilin-1 expression is associated with hematogenous dissemination in recurrence forms of pancreatic cancer (PDAC) patients. The immune-complex (IC) levels of cofilin-1 in sera of PDAC patients were higher than those in sera of healthy volunteers and patients with pancreatitis. The IC levels of cofilin-1 showed a stepwise increase during PDAC progression, and high IC levels of cofilin-1 indicated poor prognosis of patients after surgery.