GFP-fluorescence-guided UVC irradiation inhibits melanoma growth and angiogenesis in nude mice

Melanoma cell lines that stably express green fluorescent protein (GFP) and nude mice that ubiquitously express red fluorescent protein (RFP) have previously been developed to study tumor-host interaction by color-coded imaging. In the present study, the efficacy of fluorescence-guided ultraviolet C (UVC) irradiation on the growth of murine melanoma expressing GFP in the ear of RFP mice was determined using a non-invasive ear-tumor imaging model developed previously. The GFP-expressing melanoma and RFP-expressing blood vessels from the transgenic mice expressing RFP used as hosts were readily visible using non-invasive imaging. The melanoma was treated under fluorescence guidance with UVC at 650 J/m2/minute for 3 minutes. The ears of the mice were observed before and 24 hours after irradiation with UVC. UVC inhibited melanoma growth and also damaged blood vessels in the tumor. Thus, UVC irradiation has a direct effect on melanoma growth as well as an anti-angiogenesis effect. This color-coded tumor-host model is useful for evaluation of treatment efficacy on melanoma growth and angiogenesis, which are readily discernable with non-invasive color-coded fluorescent protein imaging. These results suggest that fluorescence-guided UVC irradiation is a promising therapeutic strategy for melanoma.     

Inhibition of bone and muscle metastases of lung cancer cells by a decrease in the number of monocytes/macrophages

Attention has recently focused on the critical role of inflammatory responses in the tumor stroma that provide favorable conditions for cancer-cell growth and invasion/metastasis. In particular, macrophages recruited into the tumor stroma and activated, known as tumor-associated macrophages, are suggested to promote tumorigenesis. In this study, we examined the effect of a decrease in the number of monocytes/macrophages in peripheral blood and the tumor stroma on the development of bone and muscle metastases by lung cancer cells. Treatment with clodronate encapsulated by liposomes (Cl₂MDP-LIP) has been developed for the depletion of monocytes/macrophages in an animal model. Subcutaneous administration of Cl₂MDP-LIP markedly reduced the number of monocytes in peripheral blood, resulting in efficient suppression of both bone metastasis and muscle metastasis when lung cancer HARA-B cells were injected into the left cardiac ventricle of mice. Treatment with Cl₂MDP-LIP significantly reduced the number of macrophages in tumors and the number of osteoclasts in bone marrow, as well as peripheral monocytes in mice harboring lung cancer cells. In contrast, treatment with an osteoclast-targeting antibiotic, reveromycin A, inhibited bone metastasis by lung cancer cells, but not muscle metastasis. The survival of human macrophages in culture was found to be specifically blocked by Cl₂MDP-LIP, but not by reveromycin A. Cl₂MDP-LIP thus exerted antimetastatic effects in both bone and muscle whereas reveromycin A did so only in bone. Liposome-encapsulated bisphosphonate may modulate metastasis through decreasing the number of monocytes/macrophages in both peripheral blood and the tumor stroma, suggesting that tumor-associated macrophages might be suitable targets for antimetastatic therapy. ( Cancer Sci 2008; 99: 1595–1602)     

Improvement in knee extension strength through training by means of combined electrical stimulation and voluntary muscle contraction

Weight training (WT) is the most common method of maintaining and increasing muscle strength. WT, however, is not always useful as it requires the external resistance and stabilization. We have developed a "hybrid training" (HYB) approach that avoids these problems by using electrically stimulated muscles to provide resistance to the motion of a muscle undergoing training. Here we report the efficacy of HYB compared with conventional WT for increasing the muscle strength around the knee at both slow and fast joint speeds (at 30 and 180 degrees /sec). Two matched groups, each of 8 healthy men aged 22 years, exercised 3 times/week for six weeks. Both groups showed significantly increased strength in concentric torque at 30 degrees /sec (HYB +28%, WT +33%) and at 180 degrees /sec (HYB +33%, WT +38%), and also in eccentric torque at 30 degrees /sec (HYB +25%, WT +24%) and at 180 degrees /sec (HYB +19%, WT +30%) (p < 0.001). HYB is comparable with WT exercising with the exception of high-speed contractions, while HYB has a clear advantage in not needing external resistance equipment or stabilization. HYB is therefore considered a useful approach for strengthening muscles when a person is restricted to bed rest or during space flight.     

Embryonic development of hair follicle pluripotent stem (hfPS) cells

Our laboratory discovered nestin-expressing hair follicle stem cells and demonstrated their pluripotency. We have shown that nestin-positive and K15-negative multipotent hair follicle stem cells are located above the hair follicle bulge, and we termed these cells hair follicle pluripotent stem (hfPS) cells. We have previously shown that hair follicle stem cells can regenerate peripheral nerve and spinal cord. In the present study, we describe the embryonic development of the hair follicle stem cell area (hfPSCA), which is located above the bulge and below the sebaceous glands in the adult mouse. At embryonic day 16.5 (E16.5) of nestindriven GFP (ND-GFP) transgenic mice, which express nestin in hfPS cells, the ND-GFP hair follicle stem cells are located in mesenchymal condensates. At postnatal day 0 (P0), the ND-GFP-expressing cells are migrating to the upper part of the hair follicle from the dermal papilla. At P3, keratin 15 (K15)-positive cells, derived from ND-GFP dermal papilla cells, are located in the outer-root sheath and basal layer of the epidermis. By P10, the ND-GFP have formed the K15-positive outer-root sheath as well as the ND-GFP hfPSA. These results suggest that ND-GFP hfPS cells in the dermal papilla form nestin-expressing hair follicle stem cells in the first hair cycle. These observations provide new insight into the origins of hfPS cells and the hfPSCA.     

Cyclosporine A as treatment of esophageal involvement in dermatomyositis

We report a case of a 70-year-old man with dermatomyositis complicated by esophageal involvement resistant to corticosteroid therapy. It had serious and potentially life-threatening implications, resulting in impossible oral feeding. This condition was successfully resolved by administration of cyclosporine A.     

Involvement of herbal medicine as a cause of mesenteric phlebosclerosis: results from a large-scale nationwide survey

Journal of Gastroenterology - Mesenteric phlebosclerosis (MP) is a rare disease characterized by venous calcification extending from the colonic wall to the mesentery, with chronic ischemic changes...     

Expression of Ku70 predicts results of radiotherapy in prostate cancer

Background and purpose

Therapeutic strategy for prostate cancer is decided according to T stage, Gleason score, and prostate-specific antigen (PSA) level. These clinical factors are not accurate enough to predict individual risk of local failure of prostate cancer after radiotherapy. Parameters involved with radiosensitivity are required to improve the predictive capability for local relapse.

Patients and methods

We analyzed 58 patients with localized adenocarcinoma of the prostate between August 2007 and October 2010 treated with 76 Gy of intensity-modulated radiotherapy (IMRT) as a discovery cohort and 42 patients between March 2001 and May 2007 treated with three-dimensional conformal radiotherapy (3D-CRT) as a validation cohort. Immunohistochemical examination for proteins involved in nonhomologous end-joining was performed using biopsy specimens.

Results

Ku70 expression was not correlated with various clinical parameters, such as the Gleason score and D’amico risk classification, indicating that Ku70 expression was an independent prognostic factor. The predictive value for PSA relapse was markedly improved after the combination of Gleason score and Ku70 expression, as compared with Gleason score alone. In patients treated with radiotherapy and androgen deprivation therapy (ADT), no relapses were observed in patients with Gleason score ≤7 or low Ku70 expression. In contrast, patients with Gleason score ≥8 and high Ku70 expression had high PSA relapse rates. In the validation cohort, similar results were obtained.

Conclusion

Treatment with 76 Gy and ADT can be effective for patients with Gleason score ≤7 or low Ku70 expression, but is not enough for patients with Gleason score ≥8 and high Ku70 expression and, thus, require other treatment approaches.

     

Increase in colonic diverticular hemorrhage and confounding factors

AIM: To classify changes over time in causes of lower gastrointestinal bleeding(LGIB) and to identify factors associated with changes in the incidence and characteristics of diverticular hemorrhage(DH).METHODS: A total of 1803 patients underwent colonoscopy for overt LGIB at our hospital from 1995 to 2013. Patients were divided into an early group(EG, 1995-2006, n = 828) and a late group(LG, 2007-2013, n = 975), and specific diseases were compared between groups. In addition, antithrombotic drug(ATD) use and nonsteroidal anti-inflammatory drug(NSAID) use were comparedbetween patients with and without DH. RESULTS: Older patients(≥ 70 years old) and those with colonic DH were more frequent in LG than in EG(P 0.01). Patients using ATDs as well as NSAIDs, male sex, obesity(body mass index ≥ 25 kg/m2), smoking, alcohol drinking, and arteriosclerotic diseases were more frequent in patients with DH than in those without. CONCLUSION: Incidence of colonic DH seems to increase with aging of the population, and factors involved include use of ATDs and NSAIDs, male sex, obesity, smoking, alcohol drinking, and arteriosclerotic disease. These factors are of value in handling DH patients.