evaluation of percutaneous carbon dioxide treatment for improving intratumoral hypoxia using F-fluoromisonidazole PET-CT.

Carbon dioxide (CO) treatment is reported to have an antitumor effect owing to the improvement in intratumoral hypoxia. Previous studies were based on histological analysis alone. In the present study, the improvement in intratumoral hypoxia by percutaneous CO treatment was determined using F-fluoromisonidazole positron emission tomography-computed tomography (F-FMISO PET-CT) images.

Transcutaneous carbon dioxide application inhibits muscle atrophy after fracture in rats.

Background: Muscle atrophy causes difficulty in resuming daily activities after a fracture. Because transcutaneous carbon dioxide (CO) application has previously upregulated oxygen pressure in the local tissue, thereby demonstrating its potential in preventing muscle atrophy, here we investigated effects of CO application on muscle atrophy after femoral shaft fracture.

Methods: Thirty fracture model rats were produced and randomly divided into a no treatment (control group) and treatment (CO group) groups.

Induced Pluripotent Stem Cell-related Genes Correlate With Poor Prognoses of Oral Squamous Cell Carcinoma.

Background/aim: We recently investigated the contribution of the iPS-related genes SOX2, OCT4, and Nanog to de-differentiation by assaying for their mRNA levels. Given that mRNA expression does not always correlate with the protein levels, the aim of this study was to retrospectively determine the expression of these four iPS-related factors in human OSCC specimens by immunohistochemistry and examine their association with patient prognosis.

Materials And Methods: iPS cell-related gene expression in 89 OSCC patients by tissue microarray, and its correlation with clinicopathological factors, differentiation, metastasis, and poor prognoses were investigated.

Transcutaneous carbon dioxide application suppresses bone destruction caused by breast cancer metastasis.

Hypoxia plays a significant role in cancer progression, including metastatic bone tumors. We previously reported that transcutaneous carbon dioxide (CO2) application could decrease tumor progression through the improvement of intratumor hypoxia. Therefore, we hypothesized that decreased hypoxia using transcutaneous CO2 could suppress progressive bone destruction in cancer metastasis.

Effect of local application of transcutaneous carbon dioxide on survival of random-pattern skin flaps.

Introduction: Skin flap procedures are widely used to reconstruct skin and soft tissue defects. Skin flap necrosis is a serious postoperative complication. Many researchers have introduced pharmacological agents to improve flap ischemia in experimental studies.

Transcutaneous carbon dioxide enhances the antitumor effect of radiotherapy on oral squamous cell carcinoma.

Radiotherapy (RT) is one of the main treatment modalities for oral squamous cell carcinoma (OSCC), however, radioresistance is a major impediment to its clinical success and poses as a concern that needs to be addressed. Tumor hypoxia is known to be significantly associated with radioresistance in various malignancies, hence, resolving the hypoxic state of a tumor may improve the antitumor effect of RT on OSCC. We have previously revealed that transcutaneous CO2 induced mitochondrial apoptosis and suppressed tumor growth in OSCC by resolving hypoxia.

Methotrexate upregulates circadian transcriptional factors PAR bZIP to induce apoptosis on rheumatoid arthritis synovial fibroblasts.

Background: Effects of methotrexate (MTX) on the proliferation of rheumatoid arthritis (RA) synovial fibroblasts are incompletely understood. We explored actions of MTX in view of circadian transcriptions of synovial fibroblasts.

Methods: Under treatment with MTX, expression of core circadian clock genes, circadian transcriptional factor proline and acidic amino acid-rich basic leucine zipper (PAR bZIP), and proapoptotic molecule Bcl-2 interacting killer (Bik) was examined by real-time polymerase chain reaction.

The Influence of Ruptured Scar Pattern on the Healing Potential of Anterior Cruciate Ligament Remnant Cells.

Background: Vascular CD34+ cells in anterior cruciate ligament (ACL) tissues have a potential for high proliferation and multilineage differentiation, which can accelerate tendon-bone healing after ACL reconstruction. To predict outcomes of ACL reconstruction with remnant preservation or ruptured tissue incorporation, patient characteristics should be considered. However, the influence of ACL remnant morphologic pattern on healing potential remains unknown.

Transcutaneous carbon dioxide application with hydrogel prevents muscle atrophy in a rat sciatic nerve crush model.

Unlabelled: The acceleration of nerve regeneration remains a clinical challenge. We previously demonstrated that transcutaneous CO application using a novel hydrogel increases the oxygen concentration in local tissue via an "artificial Bohr effect" with the potential to prevent muscle atrophy. In this study, we investigated the effect of transcutaneous CO administration on limb function after peripheral nerve injury in a rat sciatic nerve injury model.

Synergistic Effects of a Smac Mimetic with Doxorubicin Against Human Osteosarcoma.

Background/aim: Second mitochondria-derived activator of caspase (Smac) is a proapoptogenic mitochondrial protein that antagonizes inhibitors of apoptosis proteins (IAPs), resulting in induction of apoptosis. In the present study we investigated the effects of a Smac mimetic in combination with doxorubicin against osteosarcoma.

Materials And Methods: In vitro effects of the combination of a Smac mimetic AT-406 and doxorubicin on cell proliferation and apoptosis in osteosarcoma cell lines were examined using cell proliferation assays, flow cytometry, and immunoblot analyses.

Intra-arterially infused carbon dioxide-saturated solution for sensitizing the anticancer effect of cisplatin in a rabbit VX2 liver tumor model.

The present study aimed to evaluate the efficacy of an intra-arterially infused carbon dioxide (CO2)-saturated solution in sensitizing the anticancer effect of cisplatin in a rabbit VX2 liver tumor model. Forty VX2 liver tumor-bearing Japanese white rabbits were randomly divided into four groups and infused via the proper hepatic artery with a saline solution (control group), CO2-saturated solution (CO2 group), cisplatin solution (cisplatin group), or CO2-saturated solution and cisplatin solution (combined group). The tumor volume (TV) and the relative tumor volume (RTV), RTV = (TV on day 3 or 7)/(TV on day 0) x 100, were calculated using contrast-enhanced computed tomography.

Increase in carbon dioxide accelerates the performance of endurance exercise in rats.

Endurance exercise generates CO via aerobic metabolism; however, its role remains unclear. Exogenous CO by transcutaneous delivery promotes muscle fibre-type switching to increase endurance power in skeletal muscles. Here we determined the performance of rats running in activity wheels with/without transcutaneous CO exposure to clarify its effect on endurance exercise and recovery from muscle fatigue.

Optimization of antitumor treatment conditions for transcutaneous CO2 application: An in vivo study.

Carbon dioxide (CO2) therapy can be applied to treat a variety of disorders. We previously found that transcutaneous application of CO2 with a hydrogel decreased the tumor volume of several types of tumors and induced apoptosis via the mitochondrial pathway. However, only one condition of treatment intensity has been tested.

Induced Pluripotent-stem-cell Related Genes Contribute to De-differentiation in Oral Squamous Cell Carcinoma.

Background/aim: Cancer stem cells are suspected to contribute to malignancy in tumors. Hypoxia affects cell differentiation and induces stem-cell-like characteristics in malignancies. Induced pluripotency was demonstrated in mouse fibroblasts by reprogramming with four transcriptional factors: Oct3/4, Sox2, c-Myc, and Klf4.

Transcutaneous carbon dioxide application accelerates muscle injury repair in rat models.

Purpose: Skeletal muscle injuries are commonly observed in sports and traumatology medicine. Previously, we demonstrated that transcutaneous application of carbon dioxide (CO) to lower limbs increased the number of muscle mitochondria and promoted muscle endurance. Therefore, we aimed to investigate whether transcutaneous CO application could enhance recovery from muscle injury.

AICAR induces mitochondrial apoptosis in human osteosarcoma cells through an AMPK-dependent pathway.

The AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) modulates cellular energy metabolism, and promotes mitochondrial proliferation and apoptosis. Previous studies have shown that AICAR has anticancer effects in various cancers, however the roles of AMPK and/or the effects of AICAR on osteosarcoma have not been reported. In the present study, we evaluated the effects of AICAR on tumor growth and mitochondrial apoptosis in human osteosarcoma both in vitro and in vivo.

Decreased mitochondrial copy numbers in oral squamous cell carcinoma.

Background: Mitochondrial dysfunction and altered respiration have long been suspected to affect the development and progression of cancer. Although quantitative changes in mitochondrial DNA (mtDNA) have been reported in head and neck squamous cell carcinoma (SCC), differences in mtDNA copy numbers between normal and cancerous tissues from same patients have not been assessed.

Methods: We compared mtDNA copy numbers and expressions of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and mitochondrial transcription factor A (TFAM) between normal mucous membrane and cancerous tissues resected from 35 patients with oral SCC, using TaqMan quantitative real-time polymerase chain reaction (PCR) and immunohistochemical staining.

Transcutaneous carbon dioxide suppresses epithelial-mesenchymal transition in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common form of oral cancers. Recent studies have shown that the malignant transformation of various carcinomas, including OSCC, is associated with epithelial-mesenchymal transition (EMT), and that expression of the EMT factors are significantly associated with tumor invasion, tumor metastasis, and survival rates in OSCC patients. Hence, there is a possibility that EMT suppression may improve the prognosis of OSCC patients.

Recombinant human SIRT1 protects against nutrient deprivation-induced mitochondrial apoptosis through autophagy induction in human intervertebral disc nucleus pulposus cells.

Introduction: Nutrient deprivation is a likely contributor to intervertebral disc (IVD) degeneration. Silent mating type information regulator 2 homolog 1 (SIRT1) protects cells against limited nutrition by modulation of apoptosis and autophagy. However, little evidence exists regarding the extent to which SIRT1 affects IVD cells.

Antitumor effect of YM155, a novel small-molecule survivin suppressant, via mitochondrial apoptosis in human MFH/UPS.

Survivin is a member of the inhibitor of apoptosis family, which is known to inhibit mitochondrial apoptosis. Survivin is highly expressed in cancers and plays an important role in cancer cell survival, and increased survivin expression is an unfavorable prognostic marker in cancer patients. YM155, a novel small-molecule survivin suppressant, selectively suppresses survivin expression, resulting in the induction of apoptosis in various malignancies.

P21 deficiency delays regeneration of skeletal muscular tissue.

The potential relationship between cell cycle checkpoint control and tissue regeneration has been indicated. Despite considerable research being focused on the relationship between p21 and myogenesis, p21 function in skeletal muscle regeneration remains unclear. To clarify this, muscle injury model was recreated by intramuscular injection of bupivacaine hydrochloride in the soleus of p21 knockout (KO) mice and wild type (WT) mice.

Topical cutaneous CO2 application by means of a novel hydrogel accelerates fracture repair in rats.

Background: We previously demonstrated that topical cutaneous application of CO2, by means of a hydrogel in which the CO2 readily dissolves, increases blood flow and oxygen dissociation from hemoglobin in the soft tissues surrounding bone. In the present study, we utilized a rat fracture model to test the hypothesis that application of this treatment to fractured limbs would accelerate fracture repair.

Methods: A closed femoral shaft fracture was created in each rat.

Oxidative stress-induced apoptosis and matrix loss of chondrocytes is inhibited by eicosapentaenoic acid.

Eicosapentaenoic acid (EPA) is an antioxidant and n-3 polyunsaturated fatty acid that reduces the production of inflammatory cytokines. We evaluated the role of EPA in chondrocyte apoptosis and degeneration. Normal human chondrocytes were treated with EPA and sodium nitroprusside (SNP).

Comparative analysis of rat mesenchymal stem cells derived from slow and fast skeletal muscle in vitro.

Purpose: Skeletal muscle comprises different kinds of muscle fibres that can be classified as slow and fast fibres. The purpose of this study was to compare the yield, proliferation, and multi-potentiality of rat mesenchymal stem cells (MSCs) from the tibialis anterior (TA; fast muscle) and soleus (SO; slow muscle) in vitro.

Methods: The TA and SO muscles were harvested, and isolated cells were plated.