Tumor growth suppression by the combination of nanobubbles and ultrasound

We previously developed novel liposomal nanobubbles (Bubble liposomes [BL]) that oscillate and collapse in an ultrasound field, generating heat and shock waves. We aimed to investigate the feasibility of cancer therapy using the combination of BL and ultrasound. In addition, we investigated the anti‐tumor mechanism of this cancer therapy. Colon‐26 cells were inoculated into the flank of BALB/c mice to induce tumors. After 8 days, BL or saline was intratumorally injected, followed by transdermal ultrasound exposure of tumor tissue (1 MHz, 0–4 W/cm², 2 min). The anti‐tumor effects were evaluated by histology (necrosis) and tumor growth. In vivo cell depletion assays were performed to identify the immune cells responsible for anti‐tumor effects. Tumor temperatures were significantly higher when treated with BL + ultrasound than ultrasound alone. Intratumoral BL caused extensive tissue necrosis at 3–4 W/cm² of ultrasound exposure. In addition, BL + ultrasound significantly suppressed tumor growth at 2–4 W/cm². In vivo depletion of CD8⁺ T cells (not NK or CD4⁺ T cells) completely blocked the effect of BL + ultrasound on tumor growth. These data suggest that CD8⁺ T cells play a critical role in tumor growth suppression. Finally, we concluded that BL + ultrasound, which can prime the anti‐tumor cellular immune system, may be an effective hyperthermia strategy for cancer treatment.     

Potential role of vitamin K2 as a chemopreventive agent against hepatocellular carcinoma

Vitamin K, a cofactor necessary for the production of several antihemorrhagic factors, can inhibit the growth of various types of cells derived from neoplasms. In hepatoma cells, vitamin K₂ causes cell-cycle arrest and apoptosis. Vitamin K₂ is widely used in Japan to treat osteoporosis. The safety, relatively low cost and ease of use of vitamin K₂ have led to good compliance with treatment. The result of preliminary clinical trials in patients with chronic liver diseases are intriguing and suggest that vitamin K₂ might reduce the risk of hepatocellular carcinoma (HCC) in patients with liver cirrhosis as well as prevent disease recurrence after curative therapy in patients with HCC. This article reviews the potential role of vitamin K₂ as a chemopreventive agent against HCC and discusses future directions for clinical trials.     

Preferential gene expression and epigenetic memory of induced pluripotent stem cells derived from mouse pancreas

Induced pluripotent stem cells (iPSCs) have been established from various somatic cell types. Accumulating evidence suggests that iPSCs from different cell sources have distinct molecular and functional properties. Here, we establish iPSC derived from mouse pancreas (Panc‐iPSC) and compared their properties with those of iPSC derived from tail‐tip fibroblast (TTF‐iPSC). The metabolic profile differs between Panc‐iPSC and TTF‐iPSC, indicating distinct cell properties in these iPSCs. Expression of Pdx1, a marker of pancreas differentiation, is increased through formation of embryoid body (EB) in Panc‐iPSC, but the level is similar to that in TTF‐iPSC. In contrast, EBs derived from Panc‐iPSC express liver‐specific albumin (Alb) and alpha‐fetoprotein (Afp) genes much more strongly than those from TTF‐iPSC. Epigenetic analysis shows a different histone modification pattern between Panc‐iPSC and TTF‐iPSC. Promoter regions of Alb and Afp genes in Panc‐iPSC are suggested to have a more open chromatin structure than those in TTF‐iPSC, which also is seen in primary cultured pancreatic cells. Our data suggest that Panc‐iPSC possesses distinct differentiation capacity from that of TTF‐PSC, which may be influenced by epigenetic memory.     

Children with flat feet have weaker toe grip strength than those having a normal arch

[Purpose] This study investigated the relationship between toe grip strength and foot posture in children. [Subjects and Methods] A total of 619 children participated in this study. The foot posture of the participants was measured using a foot printer and toe grip strength was measured using a toe grip dynamometer. Children were classified into 3 groups; flatfoot, normal, and high arch, according to Staheli’s arch index. The differences in demographic data and toe grip strength among each foot posture group were analyzed by analysis of variance. Additionally, toe grip strength differences were analyzed by analysis of covariance, adjusted to body mass index, age, and gender. [Results] The number of participants classified as flatfoot, normal, and high arch were 110 (17.8%), 468 (75.6%), and 41 (6.6%), respectively. The toe grip strength of flatfoot children was significantly lower than in normal children, as shown by both analysis of variance and analysis of covariance. [Conclusion] A significant difference was detected in toe grip strength between the low arch and normal foot groups. Therefore, it is suggested that training to increase toe grip strength during childhood may prevent the formation of flat feet or help in the development of arch.Key words: Flatfoot, Toe grip strength, Children     

Four cases of fusiform posterior inferior cerebellar artery aneurysms successfully treated by trapping and occipital artery-PICA bypass

Aneurysms located on the proximal portion of the posterior inferior cerebellar artery (PICA) are rare, and even rarer are fusiform aneurysms in this location. Therefore the principles of surgical management are poorly understood and still subject to debate. The management plan for these lesions is based on the proper understanding of the PICA anatomy, and particularly the origin of important perforating arteries. As many anatomic variations of PICA can be observed and the perforator's origin is sometimes in complex anatomical relations with the aneurysm, the management has to be individualized in each case. The objective of management is to exclude of the aneurysm from the circulation while preserving the perforator and distal flow. We report four cases of PICA fusiform aneurysms of the anterior or lateral medullary segments which were treated successfully with trapping of the abnormal arterial segment and distal revascularization of PICA. Trapping was adjusted to the specific anatomical circumstances in each case, preserving perforators to the maximum and revascularizing (OA-distal PICA) distal territory.     

Lymph node metastasis from colon carcinoma at 11 years after the initial operation managed by lymph node resection and chemoradiation: A case report and a review of the literature

INTRODUCTIONLymph node metastasis from colorectal cancer after a disease-free interval (DFI) of >5 years is extremely rare, and occurs in <0.6% cases.PRESENTATION OF CASEA 60-year-old man underwent low anterior resection for sigmoid colon cancer. The lesion was an adenocarcinoma with no lymph node metastasis of Stage II. At 9 years after the colectomy, he was diagnosed with prostate cancer and was treated with radiation and hormonal therapies; at 11 years, he exhibited suddenly elevated carcinoembryonic antigen levels. Computed tomography (CT) and positron emission tomography-CT revealed a 2.0-cm para-aortic lymph nodes swelling invading the small intestine. These lymph nodes and the affected segment of the small intestine were resected, and histopathology of the resected specimen confirmed a metastatic tumor. The patient was administered radiation therapy after 22 cycles of 5-fluorouracil, oxaliplatin and leucovorin. He however presented with a residual lesion in the para-aortic lymph node, but currently, he has been symptom free for 4 years.DISCUSSIONA review of the literature indicates that the median survival of all previously reported patients is 12 months, and that colon cancer with a long DFI might be a slow growing. One of these patients and our patient both had received radiation and/or hormonal therapy for another cancer, which probably impaired their immune systems, thus resulting in metastatic tumors.CONCLUSIONWe report a case of lymph node metastasis after a DFI of >5 years and review relevant literature to assess the significance and possible reasons for delayed colorectal cancer metastases.     

Association of disorganization of retinal inner layers with optical coherence tomography angiography features in branch retinal vein occlusion

Graefe's Archive for Clinical and Experimental Ophthalmology - To examine the associations between the disorganization of the retinal inner layers (DRIL) and optical coherence tomography...     

Immunochromatography and chemiluminescent enzyme immunoassay for COVID-19 diagnosis

IntroductionThe rapid and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required to prevent the spread of COVID-19. This study evaluated the utility of two SARS-CoV-2 antigen detection methods.MethodsWe evaluated two types of antigen detection methods using immunochromatography (Espline) and quantitative chemiluminescent enzyme immunoassay (Lumipulse). RT-PCR was performed as a standard procedure for COVID-19 diagnosis. Lumipulse and RT-PCR were performed for all 486 nasopharyngeal swabs and 136 saliva samples, and the Espline test was performed for 271 nasopharyngeal swabs and 93 saliva samples.ResultsThe sensitivity and specificity of the Espline test were 10/11 and 260/260 (100%), respectively for the nasopharyngeal swabs and 3/9 and 84/84 (100%), respectively for the saliva samples. High sensitivities for both saliva (8/9) and nasopharyngeal swabs (22/24) were observed in the Lumipulse test. The specificities of the Lumipulse test for nasopharyngeal swabs and saliva samples were 460/462 (99.6%) and 123/127 (96.9%), respectively.ConclusionThe Espline test is not effective for saliva samples but is useful for simple and rapid COVID-19 tests using nasopharyngeal swabs because it does not require special devices. The Lumipulse test is a powerful high-throughput tool for COVID-19 diagnosis because it has high detection performance for nasopharyngeal swabs and saliva samples.     

Activation of adenylate cyclase‐cyclic AMP‐protein kinase A signaling by corticotropin‐releasing factor within the dorsolateral bed nucleus of the stria terminalis is involved in pain‐induced aversion

Pain is a complex experience involving sensory and affective components. Although the neuronal mechanisms underlying the sensory component of pain have been extensively studied, those underlying its affective component have yet to be elucidated. Recently, we reported that corticotrophin‐releasing factor (CRF)‐induced depolarization in type II neurons within the dorsolateral bed nucleus of the stria terminalis (dlBNST) is critical for pain‐induced aversive responses in rats. However, the intracellular signaling underlying the excitatory effects of CRF and the contribution of such signaling to the induction of pain‐induced aversion remain unclear. In the present study, we addressed these issues by conducting whole‐cell patch‐clamp recordings in rat brain slices and by undertaking behavioral pharmacological analyses. Intracellular perfusion of protein kinase A (PKA) inhibitor Rp‐cyclic adenosine monophosphorothioate (Rp‐cAMPS) or KT5720 suppressed the excitatory effects of CRF in type II dlBNST neurons, and bath application of Rp‐cAMPS also suppressed it. In addition, bath application of forskolin, an adenylate cyclase (AC) activator, mimicked the effects of CRF, and pretreatment with forskolin diminished the excitatory effects of CRF. Furthermore, a conditioned place aversion (CPA) test showed that co‐administration of Rp‐cAMPS with CRF into the dlBNST suppressed CRF‐induced CPA. Intra‐dlBNST injection of Rp‐cAMPS also suppressed pain‐induced CPA. These results suggest that CRF increases excitability of type II dlBNST neurons through activation of the AC‐cAMP‐PKA pathway, thereby causing pain‐induced aversive responses. The present findings shed light on the neuronal mechanisms underlying the negative affective component of pain and may provide therapeutic targets for treating intractable pain accompanied by psychological factors.