Personalized Medicine Universe最新文献

A 40-year-old man was admitted to the hospital with multiple injuries, including head injury and his laboratory results were significant for sodium abnormalities. Initially, hypernatremia was from increased sodium intake. Subsequently, hyponatremia developed that was unresponsive to sodium supplementation. Syndrome of inappropriate antidiuretic hormone secretion or cerebral salt wasting syndrome was suspected. Additional tests suggested post-traumatic hypopituitarism was responsible for the hyponatremia. Corticosteroid were given which normalized the serum sodium level, but the urine volume increased. Masked diabetes insipidus was suspected and desmopressin was given, stabilizing the serum sodium level. Recognizing the factors that cause sodium abnormalities in trauma patients can help lead to the correct diagnosis.

Purpose

Non-muscle invasive bladder cancer (NMIBC) shows high rates of recurrence and frequently progresses to more advanced stages, such as muscle invasive bladder cancer (MIBC). Repetition of treatment and recurrence are serious burdens and cause severe reduction in the quality of life (QOL) of patients. Thus, a novel therapeutic strategy without high burdens on the patients is an urgent requirement. Consequently, we evaluated tumor growth inhibition in bladder cancer cell lines using a combination of cisplatin (CDDP), one of the prevailing anticancer drugs to treat bladder cancer, and lentiviral vector-mediated gene transfer, where the vector is known to have minimal cytotoxicity.

Methods

Lentiviral vector with tumor suppressor genes including p53, p16, and phosphatase and tensin homology (PTEN) were infected to human bladder cancer cell lines, UMUC3 and T24, followed by CDDP treatment.

Results

The transduction of the p53, p16, or PTEN gene was equivalent to the antitumor efficacy of CDDP against bladder cancer cells. Furthermore, lentiviral vector-mediated transduction of tumor suppressive genes in combination with CDDP showed superior antitumor effects relative to individual treatment strategies with the vector or CDDP alone.

Conclusion

Lentiviral vector-mediated gene transduction is a promising alternative to the existing therapy in treating bladder cancer. The current protocol of CDDP-based chemotherapy may be replaced in the future. Moreover, the combination of gene therapy and chemotherapy may be an effective treatment for bladder cancer.

Purpose

Viral vector-mediated gene therapies for cancers have been eagerly studied in recent years. However, lentiviral vectors are not widely used despite their practical characteristics such as low cytotoxicity and prolonged expression of the transgenes. Renal cell carcinoma (RCC) is highly refractory to known cancer treatment drugs, and surgical resection is used as the most common treatment of RCC. Therefore, we thought that lentiviral vector-mediated gene therapy would become a promising strategy of the treatment of RCC. In this study, we examine the lentiviral vector-mediated transfection of tumor suppressor genes against RCC cell lines.

Methods

Lentiviral vectors that contained the tumor suppressor genes, p53, p16, and PTEN, were transfected into human RCC cell lines, RCC4/VHL, 786-O and ACHN.

Results

Significant growth inhibition was observed in RCC cells on transfection with the tumor suppression genes. Especially, transfection of p16 showed remarkable effect on all experimental cell lines.

Conclusions

The results of this study demonstrate that lentivirus-mediated transfection of tumor suppressor genes exerts promising anti-tumor effects on RCC cell lines.

The global incidence and mortality rates of colorectal cancer is rising, and has surpassed lung cancer as the highest incidence of all types of cancers in Japan [1]. Standard treatments include surgery and chemotherapy, however immunotherapy using Dendritic Cell (DC) vaccines is also recognized as an effective treatment for many cancers including colorectal cancer. DCs are the most potent antigen presenting cells, which activate CD 4+/CD8+ T cells and induce cytotoxic T lymphocytes (CTLs) to attack cancer cells. Tumor antigens used in DC vaccines are typically defined tumor-derived peptides, however, using autologous tumor lysates produces significantly higher response rates [2]. It is not always feasible to obtain fresh whole tumor to use as lysate, and particularly in the case of colorectal cancer, it is difficult to collect an aseptic specimen for use. We therefore explored the possibility of producing lysate from circulating tumor cells (CTCs) that can be collected aseptically from peripheral blood. We created a model of capturing live CTCs from a colorectal cancer cell line, culturing and expanding these cells, and creating lysate from these cultured CTCs.

Introduction

Standardized treatments are intended to eliminate bias by each hospital and physician and provide unified and appropriate treatment. Personalized treatments clarify the pathological condition of each patient and provide treatment without any surplus or deficiency based on standardized treatments. In this study, we take the example of hemophilia, one of the rare diseases, and measure diffusion, practical use, and utility of medical devices at the clinical site, the drug cost and clinical outcome, demonstrate its usefulness, and present measures to introduce standardized and individualized treatment. myPKFiT® is a medical device that allows authorized users to simulate dosing regimens with Hemophilia patients' pharmacokinetic profiles of FVIII based on 2 blood samples.

Methods

We interviewed clinical psychologists, nurses, and physicians focusing on “improvement of awareness” and “removal of disability”, collecting clinical data, annualized bleeding rate (ABR), annualized joint bleeding rate (AJBR), and cost of FVIII consumption in Ogikubo Hospital, Hemophilia center.

Results

We specified the original method of Ogikubo Hospital from the results of interview on adopting medical devices. Clinical outcome analysis was performed on patients with medical devices who have transfusion records before and after an operation.

Conclusion

Though personalized treatment can be formalized to some extent, it is expected that medical treatment skills and management by tacit knowledge are affected in individualized treatment based on standardized treatment. Medical institutions and medical staff are the main body sharing and deploying measures to disseminate and utilize medical devices, cooperating with them can be an effective management of standardized and individualized treatment.

Purpose

Panax ginseng (P. ginseng) root is a complementary and alternative medicine (CAM) typically used in traditional Asian medicine. We have reported that oral consumption of the P. ginseng aqueous extract (PgE) by mice augments natural killer (NK) cell activity, which is critical for immune surveillance against tumors. In this study, we further examined the effect of oral consumption of PgE on human NK cell phenotypes and cytotoxicity.

Methods

Here we examined the effects of oral intake of PgE (1000 mg per day, as recommended by the manufacturer) for two weeks on NK cell activity in ten human volunteers in a cross-over trial.

Results

No adverse reactions were observed in any volunteers, although two dropped out due to personal reasons. Oral intake of 1000 mg of PgE for two weeks did not affect the size of the NK cell population or CD56 expression on NK cells. However, NK cell cytotoxicity was significantly augmented in five out of eight subjects. When the NK cell response was divided into two categories (significantly increased or stable/decreased), Fisher's exact test and the χ² test demonstrated a significant difference in NK cell cytotoxicity between the PgE-treated and placebo groups.

Conclusion

Oral intake of 1000 mg of PgE for two weeks significantly augmented NK cell cytotoxicity over that observed with the placebo.

Purpose

The cytochrome P450 (CYP) 3A family of enzymes metabolize the majority of clinically used drugs. CYP3A4 and CYP3A5 are the two major CYP3A isoforms, but exhinbit different substrate specificity. The aim of this study was to establish a simple screening method to determine the relative contributions of CYP3A4 and CYP3A5 to drug metabolism in vitro.

Methods

A screening method was developed based on competitive inhibition using luciferin-PPXE (L-PPXE), a luminogenic CYP3A substrate. CYP3cide, tacrolimus, and midazolam were selected as standard compounds metabolized by CYP3A4 or CYP3A5. Nine clinically-used drugs were evaluated for their abilities to inhibit luminescence resulting from L-PPXE metabolism. Appropriate reaction conditions for the screening method were determined using recombinant CYP3A4 and CYP3A5.

Results

A significant decrease in luminescence resulting from L-PPXE metabolism by CYP3A4 and CYP3A5 was observed only for drugs reported to be metabolized by CYP3As. The substrate specificities of CYP3A4 or CYP3A5 for the proposed CYP3A substrates using our screening method were consistent with those of previous reports or available drug information from pharmaceutical companies. The reaction volume for this method was 50 μL, and the time required for the entire procedure was 70 min. Furthermore, this screening can be performed using a single tube with minimal training.

Conclusions

Through the establishment of our screening method in the present study, we are sure it is useful to determine the relative contributions of CYP3A4 and CYP3A5 to drug metabolism in vitro.

Interleukin (IL)-6 is a myokine secreted from skeletal muscle fibers by the stimulation of muscle contraction. IL-6 then acts on skeletal muscle itself or on remote organs through the blood circulation, resulting in various health benefits.

The quantity of mobilized muscle, exercise intensity, and exercise time are deeply involved in the rise of blood IL-6 levels. In this study, we investigated whether high sensitivity C-reactive protein, IL-6, and the anti-inflammatory cytokine, IL-10, were produced in humans by muscle contraction due to electrical stimulation. Six healthy men underwent 20 min of belt electrode skeletal muscle electrical stimulation. No time-dependent changes in IL-6, IL-10, and high sensitivity C-reactive protein were observed. These results suggest that blood myokines do not increase in response to standard electrical stimulation.