Safety and effectiveness of lenalidomide in Japanese patients with relapsed/refractory ATLL: post-marketing surveillance.

Lenalidomide is an oral immunomodulatory agent approved for the treatment of relapsed/refractory adult T-cell leukemia/lymphoma (ATLL) in Japan. Post-marketing surveillance (PMS) was conducted to confirm its safety and effectiveness. From April 2017 until April 2020, safety data were obtained for 77 patients and effectiveness data for 65 patients (31.

Effect of Functional Inhibition of BACE1 on Sensitization to γ-Irradiation in Cancer Cells.

Developing strategies for the radiosensitization of cancer cells by the inhibition of genes, which harbor low toxicity to normal cells, will be useful for improving cancer radiotherapy. Here, we focused on a β-site of amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1; β-secretase, memapsin-2). By functional inhibition of this peptidase by siRNA, it has also recently been shown that the DNA strand break marker, γH2AX foci, increased, suggesting its involvement in DNA damage response.

Radiosensitization to γ-Ray by Functional Inhibition of APOBEC3G.

The radiosensitization of tumor cells is one of the promising approaches for enhancing radiation damage to cancer cells and limiting radiation effects on normal tissue. In this study, we performed a comprehensive screening of radiosensitization targets in human lung cancer cell line A549 using an shRNA library and identified () as a candidate target. is an innate restriction factor that inhibits HIV-1 infection as a cytidine deaminase.

A newly established monoclonal antibody against ERCC1 detects major isoforms of ERCC1 in gastric cancer.

Identifying patients resistant to cisplatin treatment is expected to improve cisplatin-based chemotherapy for various types of cancers. Excision repair cross-complementing group 1 (ERCC1) is involved in several repair processes of cisplatin-induced DNA crosslinks. ERCC1 overexpression is reported as a candidate prognostic factor and considered to cause cisplatin resistance in major solid cancers.

Dysfunction of Poly (ADP-Ribose) Glycohydrolase Induces a Synthetic Lethal Effect in Dual Specificity Phosphatase 22-Deficient Lung Cancer Cells.

Poly (ADP-ribose) glycohydrolase (PARG) is the main enzyme responsible for catabolism of poly (ADP-ribose) (PAR), synthesized by PARP. PARG dysfunction sensitizes certain cancer cells to alkylating agents and cisplatin by perturbing the DNA damage response. The gene mutations that sensitize cancer cells to PARG dysfunction-induced death remain to be identified.

Concomitant administration of radiation with eribulin improves the survival of mice harboring intracerebral glioblastoma.

Glioblastoma is the most common and devastating type of malignant brain tumor. We recently found that eribulin suppresses glioma growth in vitro and in vivo and that eribulin is efficiently transferred into mouse brain tumors at a high concentration. Eribulin is a non-taxane microtubule inhibitor approved for breast cancer and liposarcoma.

PARG Inhibitors and Functional PARG Inhibition Models.

Poly(ADP-ribose) polymerases (PARPs) family proteins catalyze poly(ADP-ribosylation) (PARylation) by conjugating ADP-ribose residues repeatedly on amino acid residues using nicotinamide adenine dinucleotide as a substrate. The inhibitors of PARP widely block DNA repair processes and are currently examined in clinical trials of cancer therapy. Poly(ADP-ribose) glycohydrolase (PARG) is the main nuclear enzyme, which digests poly(ADP-ribose) into ADP-ribose.

Radiosensitization by PARP inhibition to proton beam irradiation in cancer cells.

The poly(ADP-ribose) polymerase (PARP)-1 regulates DNA damage responses and promotes base excision repair. PARP inhibitors have been shown to enhance the cytotoxicity of ionizing radiation in various cancer cells and animal models. We have demonstrated that the PARP inhibitor (PARPi) AZD2281 is also an effective radiosensitizer for carbon-ion radiation; thus, we speculated that the PARPi could be applied to a wide therapeutic range of linear energy transfer (LET) radiation as a radiosensitizer.

Synergetic Effects of PARP Inhibitor AZD2281 and Cisplatin in Oral Squamous Cell Carcinoma in Vitro and in Vivo.

Cisplatin is a commonly used chemotherapeutic drug for treatment of oral carcinoma, and combinatorial effects are expected to exert greater therapeutic efficacy compared with monotherapy. Poly(ADP-ribosyl)ation is reported to be involved in a variety of cellular processes, such as DNA repair, cell death, telomere regulation, and genomic stability. Based on these properties, poly(ADP-ribose) polymerase (PARP) inhibitors are used for treatment of cancers, such as BRCA1/2 mutated breast and ovarian cancers, or certain solid cancers in combination with anti-cancer drugs.

Loss of CtIP disturbs homologous recombination repair and sensitizes breast cancer cells to PARP inhibitors.

Breast cancer is one of the leading causes of death worldwide, and therefore, new and improved approaches for the treatment of breast cancer are desperately needed. CtIP (RBBP8) is a multifunctional protein that is involved in various cellular functions, including transcription, DNA replication, DNA repair and the G1 and G2 cell cycle checkpoints. CtIP plays an important role in homologous recombination repair by interacting with tumor suppressor protein BRCA1.

A comprehensive analysis of radiosensitization targets; functional inhibition of DNA methyltransferase 3B radiosensitizes by disrupting DNA damage regulation.

A comprehensive genome-wide screen of radiosensitization targets in HeLa cells was performed using a shRNA-library/functional cluster analysis and DNMT3B was identified as a candidate target. DNMT3B RNAi increased the sensitivity of HeLa, A549 and HCT116 cells to both γ-irradiation and carbon-ion beam irradiation. DNMT3B RNAi reduced the activation of DNA damage responses induced by γ-irradiation, including HP1β-, γH2AX- and Rad51-foci formation.

Proteomic analysis of cellular response induced by boron neutron capture reaction in human squamous cell carcinoma SAS cells.

To understand the mechanism of cell death induced by boron neutron capture reaction (BNCR), we performed proteome analyses of human squamous tumor SAS cells after BNCR. Cells were irradiated with thermal neutron beam at KUR after incubation under boronophenylalanine (BPA)(+) and BPA(-) conditions. BNCR mainly induced typical apoptosis in SAS cells 24h post-irradiation.

Parp-1 deficiency in ES cells promotes invasive and metastatic lesions accompanying induction of trophoblast giant cells during tumorigenesis in uterine environment.

Embryonic stem (ES) cells deficient in poly(ADP-ribose) polymerase-1 (Parp-1) develop into teratocarcinomas with the appearance of trophoblast giant cells (TGCs) when injected subcutaneously into nude mice. Because the uterus is one of the original organs in which germ cell tumors develop with induction of trophoblast lineage, here we investigated whether Parp-1 deficiency in ES cells affects teratocarcinoma formation processes by grafting ES cells into the horns of uteri. Teratocarcinomas developed from both wild-type (Parp-1(+/+) ) and Parp-1(-/-) ES cells.

The H19 induction triggers trophoblast lineage commitment in mouse ES cells.

Trophoblast lineage differentiation is properly regulated to support embryogenesis. Besides normal developmental process, during germ cell tumor formation or development of other reproductive system diseases, unregulated trophoblast differentiation is also observed and affects the pathogenesis of the diseases. During normal embryogenesis, cell fate of late-stage blastcyst is regulated by a reciprocal repression of the key transcriptional factors; Oct3/4 dominancy inhibits Cdx2 expression in inner cell mass (ICM) and leads them to epiblast/primitive ectoderm but Cdx2 dominancy in trophectoderm (TE) leads them to trophoblast lineage.

Poly(ADP-ribosyl)ation in carcinogenesis.

Cancer develops through diverse genetic, epigenetic and other changes, so-called 'multi-step carcinogenesis', and each cancer harbors different alterations and properties. Here in this article we review how poly(ADP-ribosyl)ation is involved in multi-step and diverse pathways of carcinogenesis. Involvement of poly- and mono-ADP-ribosylation in carcinogenesis has been studied at molecular and cellular levels, and further by animal models and human genetic approaches.

Parg deficiency confers radio-sensitization through enhanced cell death in mouse ES cells exposed to various forms of ionizing radiation.

Poly(ADP-ribose) glycohydrolase (Parg) is the main enzyme involved in poly(ADP-ribose) degradation. Here, the effects of Parg deficiency on sensitivity to low and high linear-energy-transfer (LET) radiation were investigated in mouse embryonic stem (ES) cells. Mouse Parg(-/-) and poly(ADP-ribose) polymerase-1 deficient (Parp-1(-/-)) ES cells were used and responses to low and high LET radiation were assessed by clonogenic survival and biochemical and biological analysis methods.

The Arf/p53 protein module, which induces apoptosis, down-regulates histone H2AX to allow normal cells to survive in the presence of anti-cancer drugs.

Background: It is unclear how DNA-damaging agents target cancer cells over normal somatic cells.

Results: Arf/p53-dependent down-regulation of H2AX enables normal cells to survive after DNA damage.

Conclusion: Transformed cells, which harbor mutations in either Arf or p53, are more sensitive to DNA-damaging agents.

Rapid degradation of poly(ADP-ribose) after injection into the mouse bloodstream.

Extensive DNA damage leads to the activation of poly(ADP-ribose) polymerase and subsequently to the formation of poly(ADP-ribose). When the damage is severe or leads to cell death, poly(ADP-ribose) may leak into the blood circulation. The metabolism of poly(ADP-ribose) in the bloodstream is not well understood.

Induction of cancerous stem cells during embryonic stem cell differentiation.

Stem cell maintenance depends on their surrounding microenvironment, and aberrancies in the environment have been associated with tumorigenesis. However, it remains to be elucidated whether an environmental aberrancy can act as a carcinogenic stress for cellular transformation of differentiating stem cells into cancer stem cells. Here, utilizing mouse embryonic stem cells as a model, it was illustrated that environmental aberrancy during differentiation leads to the emergence of pluripotent cells showing cancerous characteristics.

Radiosensitization effect of poly(ADP-ribose) polymerase inhibition in cells exposed to low and high liner energy transfer radiation.

Poly(ADP-ribose) polymerase (PARP)-1 promotes base excision repair and DNA strand break repair. Inhibitors of PARP enhance the cytotoxic effects of γ-irradiation and X-irradiation. We investigated the impact of PARP inhibition on the responses to γ-irradiation (low liner energy transfer [LET] radiation) and carbon-ion irradiation (high LET radiation) in the human pancreatic cancer cell line MIA PaCa-2.

Onset of quiescence following p53 mediated down-regulation of H2AX in normal cells.

Normal cells, both in vivo and in vitro, become quiescent after serial cell proliferation. During this process, cells can develop immortality with genomic instability, although the mechanisms by which this is regulated are unclear. Here, we show that a growth-arrested cellular status is produced by the down-regulation of histone H2AX in normal cells.

Inhibitory effects of phytoncide solution on melanin biosynthesis.

To determine the component-activity relationships of phytoncide solutions on inhibitory activity in melanin biosynthesis, four types of phytoncide solution (A-type, AB-type, D-type, and G-type) were evaluated for inhibition of mushroom tyrosinase activity and melanin synthesis on murine B-16 melanoma cells and a human reconstituted skin model. The A-type, AB-type, D-type, and G-type of phytoncide solution treatment resulted in significant inhibition of tyrosinase activity. The amount of melanin was increased by treatment with phytoncide solutions in a concentration-dependent manner on murine B-16 melanoma cells without affecting cell growth.

DNA lesions induced by replication stress trigger mitotic aberration and tetraploidy development.

During tumorigenesis, cells acquire immortality in association with the development of genomic instability. However, it is still elusive how genomic instability spontaneously generates during the process of tumorigenesis. Here, we show that precancerous DNA lesions induced by oncogene acceleration, which induce situations identical to the initial stages of cancer development, trigger tetraploidy/aneuploidy generation in association with mitotic aberration.

Stability of the DMF-protected Au nanoclusters: photochemical, dispersion, and thermal properties.

We have reported the synthesis of dimethylformamide (DMF)-protected gold nanoclusters using a surfactant-free DMF reduction method. DMF-protected gold nanoclusters (Au NCs) are obtained without the formation of gold nanoparticles and bulk metals as byproducts using a hot injection process for the homogeneous reduction. The as-prepared DMF-protected Au NCs were a mixture of various-sized Au NCs with a cluster number of less than 20 including at least Au(8) and Au(13).

Protecting effect of phytoncide solution, on normal human dermal fibroblasts against reactive oxygen species.

Four types of phytoncide solutions (A-Type, AB-Type, D-Type and G-Type) was evaluated for reduction of cell damage induced by oxidative stress, ultraviolet A (UVA), ultraviolet B (UVB), hydroxyperoxide (H2O2) and t-butyl-hydroperoxide (t-BHP); stimulation of collagen synthesis against UVA irradiation; and inhibition of matrix metalloproteinase-1 (MMP-1) activity induced by UVA in human normal dermal fibroblasts and human reconstituted skin model. The A-Type, AB-Type, D-Type and G-Type of phytoncide solutions pretreatment resulted in significant protection against cell damage induced by UVB, UVA, H2O2 and t-BHP. The amount of type I collagen following UVA irradiation was increased by treatment with phytoncide solutions in a concentration-dependent manner.