Cationized liposomal keto-mycolic acids isolated from Mycobacterium bovis bacillus Calmette-Guérin induce antitumor immunity in a syngeneic murine bladder cancer model

Intravesical therapy using Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most established cancer immunotherapy for bladder cancer. However, its underlying mechanisms are unknown. Mycolic acid (MA), the most abundant lipid of the BCG cell wall, is suspected to be one of the essential active components of this immunogenicity. Here, we developed cationic liposomes incorporating three subclasses (α, keto, and methoxy) of MA purified separately from BCG, using the dendron-bearing lipid D22. The cationic liposomes using D22 were efficiently taken up by the murine bladder cancer cell line MB49 in vitro, but the non-cationic liposomes were not. Lip-kMA, a cationic liposome containing keto-MA, presented strong antitumor activity in two murine syngeneic graft models using the murine bladder cancer cell lines MB49 and MBT-2 in comparison to both Lip-aMA and Lip-mMA, which contained α-MA and methoxy-MA, respectively. Interestingly, Lip-kMA(D12), which was made of D12 instead of D22, did not exhibit antitumor activity in the murine syngeneic graft model using MB49 cells, although it was successfully taken up by MB49 cells in vitro. Histologically, compared to the number of infiltrating CD4 lymphocytes, the number of CD8 lymphocytes was higher in the tumors treated with Lip-kMA. Antitumor effects of Lip-kMA were not observed in nude mice, whereas weak but significant effects were observed in beige mice with natural killer activity deficiency. Thus, a cationized liposome containing keto-MA derived from BCG induced in vivo antitumor immunity. These findings will provide new insights into lipid immunogenicity and the underlying mechanisms of BCG immunotherapy

Easy Aligned Telescope for CubeSat

Recently there is high demand on earth observation with Cubesat. Usually the researcher only uses general COTS on board camera with Cubesat on its purpose. However, if the researcher needs more resolution or different wavelength, it needs custom designed telescope for it, but telescope needs high accurate optics components and its aligned accuracy. Creating a specially designed optical telescope not only costs enormously, but also takes time from design to manufacture. Furthermore, if the processing accuracy in optical processing and the accuracy in the degree of adjustment in the assembly adjustment stage are ensured, higher-precision design, processing, and assembly adjustment are required. When using Cubesat, considering how to shorten the time from kick-off to launch, and considering the short lifetime due to low orbit, it is important to build a system that can acquire fast, cheap, but high-definition images. In this study, we aimed to achieve higher resolution even with a limited optical element configuration by combining the optical design of the reflection system and the refraction system. Furthermore, by simplifying the assembling adjustment process as much as possible, a low cost and quick manufacturing was sought

Do TSH, FT3 and FT4 impact BAT visualization of clinical FDG-PET/CT images?

[Objectives] Several researchers have reported that type 2 idothyronine deiodinase (D2) is considered to be important for the synergism of thyroid hormone (TH) and to be required to generate the T3 from T4 in the BAT, which maintains the normal acute thermogenic function of BAT. However, to date, details about the relationship between visualization of BAT on FDG-PET/CT and the effect of TH remain unknown. In this study, we retrospectively analyze BAT visualization on FDG-PET/CT in patients with various conditions and TH levels. [Methods] In this retrospective investigation, we reviewed images from all patients who underwent clinical FDG-PET/CT studies from October 2010 to July 2015, and categorized patients in 5 groups: (i) Thyroid hormone withdrawal (THW) group; (ii) Recombinant human thyrotropin (rhTSH) group; (iii) Hypothyroidism group; (iv) hyperthyroidism group; and (v) BAT group. Total of sixty-two FDG-PET/CT imaging studies in fifty-nine patients were performed. A total of sixty-two FDG-PET/CT imaging studies in fifty-nine patients were performed. To compare each group; gender; age; body weight; serum TSH, FT3, FT4 levels; and outside temperature were evaluated. [Results] No significant visualization of BAT was noted in any of the images in the THW, rhTSH, hypothyroidism, and hyperthyroidism groups. Serum TSH level was significantly high in the rhTSH group and significantly low in the hyperthyroidism group. Elevated serum TSH was noted in the THW and hypothyroidism group. All patients in the BAT group were in a euthyroid state. When the BAT-negative and -positive patient groups were compared, it was noted that the minimum and maximum temperature on the day of the PET study and maximum temperature of the one day before of the PET study were significantly lower in BAT positive group than in all others those of other groups. [Conclusions] Elevated TSH condition before RIT, hyperthyroidism orhypothyroidism did not significantly impact BAT visualization of clinical FDG-PET/CT images

Induction of CD44 variant 9-expressing cancer stem cells might attenuate the efficacy of chemoradioselection and Worsens the prognosis of patients with advanced head and neck cancer.

At our institute, a chemoradioselection strategy has been used to select patients for organ preservation on the basis of response to an initial 30-40 Gy concurrent chemoradiotherapy (CCRT). Patients with a favorable response (i.e., chemoradioselected; CRS) have demonstrated better outcomes than those with an unfavorable response (i.e., nonchemoradioselected; N-CRS). Successful targeting of molecules that attenuate the efficacy of chmoradioselection may improve results. Thus, the aim of this study was to evaluate the association of a novel cancer stem cell (CSC) marker, CD44 variant 9 (CD44v9), with cellular refractoriness to chemoradioselection in advanced head and neck squamous cell carcinoma (HNSCC).Through a medical chart search, 102 patients with advanced HNSCC treated with chemoradioselection from 1997 to 2008 were enrolled. According to our algorithm, 30 patients were CRC following induction CCRT and 72 patients were N-CRS. Using the conventional immunohistochemical technique, biopsy specimens and surgically removed tumor specimens were immunostained with the anti-CD44v9 specific antibodies.The intrinsic expression levels of CD44v9 in the biopsy specimens did not correlate with the chemoradioselection and patient survival. However, in N-CRS patients, the CD44v9-positive group demonstrated significantly (P = 0.008) worse prognosis, than the CD44v9-negative group. Multivariate analyses demonstrated that among four candidate factors (T, N, response to CCRT, and CD44v9), CD44v9 positivity (HR: 3.145, 95% CI: 1.235-8.008, P = 0.0163) was significantly correlated with the poor prognosis, along with advanced N stage (HR: 3.525, 95% CI: 1.054-9.060, P = 0.0228). Furthermore, the survival rate of the CD44v9-induced group was significantly (P = 0.04) worse than the CD44v9-non-induced group.CCRT-induced CD44v9-expressing CSCs appear to be a major hurdle to chemoradioselection. CD44v9-targeting seems to be a promising strategy to enhance the efficacy of chemoradioselection and consequent organ preservation and survival

Do TSH, FT3, and FT4 Impact BAT Visualization of Clinical FDG-PET/CT Images?

Objective. We retrospectively analyzed activated BAT visualization on FDG-PET/CT in patients with various conditions and TH levels to clarify the relationships between visualization of BAT on FDG-PET/CT and the effect of TH. Methods. Patients who underwent clinical FDG-PET/CT were reviewed and we categorized patients into 5 groups: (i) thyroid hormone withdrawal (THW) group; (ii) recombinant human thyrotropin (rhTSH) group; (iii) hypothyroidism group; (iv) hyperthyroidism group; and (v) BAT group. A total of sixty-two FDG-PET/CT imaging studies in fifty-nine patients were performed. To compare each group, gender; age; body weight; serum TSH, FT3, and FT4 levels; and outside temperature were evaluated. Results. No significant visualization of BAT was noted in any of the images in the THW, rhTSH, hypothyroidism, and hyperthyroidism groups. All patients in the BAT group were in a euthyroid state. When the BAT-negative and BAT-positive patient groups were compared, it was noted that the minimum and maximum temperature on the day of the PET study and maximum temperature of the one day before the PET study were significantly lower in BAT-positive group than in all those of other groups. Conclusions. Elevated TSH condition before RIT, hyperthyroidism, or hypothyroidism did not significantly impact BAT visualization of clinical FDG-PET/CT images

The effect of an L/N-type calcium channel blocker on intradialytic blood pressure in intradialytic hypertensive patients

Background: Intradialytic hypertension (HTN), which is one of the poor prognostic markers in patients undergoing hemodialysis, may be associated with sympathetic overactivity. The L/N-type calcium channel blocker, cilnidipine, has been reported to suppress sympathetic nerves activity in vivo. Therefore, we hypothesized that cilnidipine could attenuate intradialytic systolic blood pressure (SBP) elevation. Methods: Fifty-one patients on chronic hemodialysis who had intradialytic-HTN (SBP elevation ≥10 mmHg during hemodialysis) and no fluid overload were prospectively randomized into two groups: control and cilnidipine groups. Cilnidipine group patients took cilnidipine (10 mg/day) for 12 weeks. The primary endpoint was the change in the intradialytic SBP elevation before and after the 12-week intervention. Results: Before the intervention, no differences were observed in age, sex or pre-dialytic SBP (148.5 ± 12.9 vs. 148.3 ± 19.3 mmHg) between the two groups. Intradialytic SBP elevation was unchanged in the control group. Cilnidipine significantly lowered the post-dialytic SBP with an attenuation of the intradialytic SBP elevation from 12.0 ± 15.4 mmHg to 4.8 ± 10.1 mmHg. However, the observed difference in the intradialytic SBP elevation by cilnidipine did not reach statistical significance (group×time interaction effect p = 0.25). Cathecolamine levels were unaffected by the intervention in both groups. Conclusion: Cilnidipine lowers both the pre- and post-dialytic SBP and might attenuate intradialytic SBP elevation. Therefore, cilnidipine may be effective in lowering SBP during HD in patients with intradialytic-HTN

(A) Disease specific survival curves of all patients (n = 102) according to the chemoradioselection.

<p>(B) Disease specific survival curves based on the CD44 v9 positivity of biopsy samples (n = 60) obtained from 30 chemoradioselected (CRS) patients and 30 non-chemoradioselected (N-CRS) patients. (C) Disease specific survival curves based on the CD44 v9 positivity of biopsy samples obtained from 30 N-CRS patients.</p

Representative pictures of anti-CD44v9-antibody immunostaining.

<p>The staining intensity obtained in the basal cells of normal epithelium was used as a control (A). Tumor samples demonstrated strong (B), moderate (C), and weak (D) intensities relative to the control (A). Respective positive (E) and negative <u>(F</u>) stainings. Bar indicates 200 um.</p

(A) Disease specific survival curves based on the CD44 v9 positivity of surgically removed samples obtained from 72 non-chemoradioselected (N-CRS) patients.

<p>(B) Diseasespecific survival curves of 30 N-CRS patients who had paired biopsy and surgically removed samples. The patients were divided into 2 groups according to their levels of CD44v9 expression before and after concurrent chemoradiotherapy.</p