Histotripsy - Hype or Hope? Review of Innovation and Future Implications.

BACKGROUND: Histotripsy is a novel, ultrasound-based ablative technique recently FDA-approved for hepatic targets. It has several promising additional theoretical applications that continue to be investigated. Its basis as a non-thermal cavitational technology presents a unique advantage over existing thermal ablation techniques in maximizing local effects while minimizing adjacent tissue destruction. This review discusses the technical basis and current preclinical and clinical data surrounding histotripsy. METHODS: We comprehensively reviewed the literature surrounding histotripsy and the clinical landscape of existing ablative techniques utilizing the PubMed database. We described a technical summary of histotripsy's physics and cellular impact. We also discussed data from recent clinical trials, including Hope4Liver, and future implications regarding its application in various benign and malignant conditions. RESULTS: Preclinical data demonstrated the efficacy of histotripsy ablation in a wide range of organ systems with minimal tissue destruction when examined on the histological level. The first prospective clinical trial involving histotripsy in hepatocellular carcinoma and liver metastases, Hope4Liver, demonstrated a primary efficacy of 95.5% with minimal complications (6.8%). This efficacy was replicated in similar trials involving the treatment of benign prostatic hypertrophy. DISCUSSION: In addition to the non-invasive ability to ablate lesions in the liver, histotripsy offers additional therapeutic potential. Early data suggests a potential complementary therapeutic effect when combining histotripsy with existing immunological therapies owing to the technology's theoretical ability to sensitize tumors to adaptive immunity. As with most novel therapies, the impact of histotripsy on the oncologic therapeutic landscape remains uncertain.

Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

N-tert-butoxycarbonyl-methylenedioxymethamphetamine, an methylenedioxymethamphetamine derivative, exhibits rewarding and reinforcing effects by increasing dopamine levels.

An N-protected methylenedioxymethamphetamine (MDMA), N-tert-butoxycarbonyl-3,4-methylenedioxymethamphetamine (t-BOC-3,4-MDMA), contains tert-butoxycarbonyl and can remain undetected in the illicit drug market. It is a new type of precursor substance that is not a chemical intermediate and can be converted into a controlled substance, MDMA, by deprotection of the N-tert-butoxycarbonyl group. Categorization of this chemical into a precursor or psychotropic substance is an issue because it is an unprecedented precursor that could have misuse potential. Although MDMA causes rewarding and reinforcing effect through dopaminergic transmission, the misuse potential of t-BOC-3,4-MDMA has not yet been characterized. Here, we aim to evaluate the misuse potential of t-BOC-3,4-MDMA. The response to the drug at a dose of 5 mg/kg was determined by a climbing test, and its rewarding and reinforcing properties were assessed through conditioned place preference and self-administration tests. In the conditioned place preference test, intraperitoneal administration of t-BOC-3,4-MDMA (5 mg/kg) significantly altered place preference in mice. In the self-administration models, t-BOC-3,4-MDMA induced drug-taking behavior at the dose of 0.5 mg/kg/infusion (intravenous) during 2 hr sessions under fixed-ratio schedules in mice. In addition, microdialysis experiments verified that t-BOC-3,4-MDMA impacted the dopamine levels of the brain (striatum) of rats. These experimental results indicate that t-BOC-3,4-MDMA has a potential for misuse. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation.

Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that are crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in the treatment of PNETs at an advanced stage. Epigenetic alterations profoundly impact the activity of signaling pathways in cancer development, offering potential opportunities for drug development. There is currently a lack of extensive research on epigenetic regulation in PNETs. To fill this gap, we first summarize major signaling events that are involved in PNET development. Then, we discuss the epigenetic regulation of these signaling pathways in the context of both PNETs and commonly occurring-and therefore more extensively studied-malignancies. Finally, we will offer a perspective on the future research direction of the PNET epigenome and its potential applications in patient care.

Disparities in Pancreatic Cancer Outcomes in the Disaggregated Asian American Population.

BACKGROUND: The Asian American, Native Hawaiian, and Pacific Islander (AANHPI) population is among the fastest-growing population in the USA. However, this is not reflected in scientific research, in which ethnic groups are often combined. We identified trends in treatment and outcomes for pancreatic cancer in a disaggregated AANHPI population. We hypothesize that patients from different AANHPI groups have differences in survival. PATIENTS AND METHODS: A retrospective analysis of the National Cancer Database between 2010 and 2019 identified patients treated for pancreatic cancer. We identified demographic factors for patients of Caucasian, African American, and disaggregated Asian subpopulations. Survival curves were generated and multivariate analysis was performed to help determine which factors impacted overall survival. RESULTS: A total of 296,448 patients met the inclusion criteria. Of those, 8568 (3%) patients were Asian. Median survival of AANHPI patients was 11.3 months, as compared with Caucasians (8.9 months) and African Americans (8.1 months) (p < 0.0001). Asian Indians had the highest median survival (14.3 months), whereas the Japanese subpopulation had the lowest (7.6 months) (p < 0.0001). There were significant differences in median survival between the different AANHPI subpopulations irrespective of stage. Multivariate analysis demonstrated that belonging to an AANHPI racial/ethnic group, excluding Japanese and Filipino, was associated with decreased risk of overall mortality. DISCUSSION: Significant differences were identified in the overall median survival for patients with pancreatic cancer between AANHPI subpopulations. Disparities in socioeconomic factors may have played a role in overall survival. This study highlights the need to include disaggregated data in future studies to subdue disparities in cancer care for patients.

Development of a Temperature-Responsive Hydrogel Incorporating PVA into NIPAAm for Controllable Drug Release in Skin Regeneration.

Melanoma, a highly malignant and aggressive form of skin cancer, poses a significant global health threat, with limited treatment options and potential side effects. In this study, we developed a temperature-responsive hydrogel for skin regeneration with a controllable drug release. The hydrogel was fabricated using an interpenetrating polymer network (IPN) of N-isopropylacrylamide (NIPAAm) and poly(vinyl alcohol) (PVA). PVA was chosen for its adhesive properties, biocompatibility, and ability to address hydrophobicity issues associated with NIPAAm. The hydrogel was loaded with doxorubicin (DOX), an anticancer drug, for the treatment of melanoma. The NIPAAm-PVA (N-P) hydrogel demonstrated temperature-responsive behavior with a lower critical solution temperature (LCST) around 34 °C. The addition of PVA led to increased porosity and faster drug release. In vitro biocompatibility tests showed nontoxicity and supported cell proliferation. The N-P hydrogel exhibited effective anticancer effects on melanoma cells due to its rapid drug release behavior. This N-P hydrogel system shows great promise for controlled drug delivery and potential applications in skin regeneration and cancer treatment. Further research, including in vivo studies, will be essential to advance this hydrogel system toward clinical translation and impactful advancements in regenerative medicine and cancer therapeutics.

Enhanced Photoluminescence of Crystalline Alq3 Micro-Rods Hybridized with Silver Nanowires.

An enhancement of the local electric field at the metal/dielectric interface of hybrid materials due to the localized surface plasmon resonance (LSPR) phenomenon plays a particularly important role in versatile research fields resulting in a distinct modification of the electrical, as well as optical, properties of the hybrid material. In this paper, we succeeded in visually confirming the LSPR phenomenon in the crystalline tris(8-hydroxyquinoline) aluminum (Alq3) micro-rod (MR) hybridized with silver (Ag) nanowire (NW) in the form of photoluminescence (PL) characteristics. Crystalline Alq3 MRs were prepared by a self-assembly method under the mixed solution of protic and aprotic polar solvents, which could be easily applied to fabricate hybrid Alq3/Ag structures. The hybridization between the crystalline Alq3 MRs and Ag NWs was confirmed by the component analysis of the selected area electronic diffraction attached to high-resolution transmission electron microscope. Nanoscale and solid state PL experiments on the hybrid Alq3/Ag structures using a lab-made laser confocal microscope exhibited a distinct enhancement of the PL intensity (approximately 26-fold), which also supported the LSPR effects between crystalline Alq3 MRs and Ag NWs.

Novel treatment strategy of targeting epigenetic dysregulation in pancreatic neuroendocrine tumors.

BACKGROUND: Epigenetic dysregulation is an integral step in the progression of pancreatic neuroendocrine tumors. We hypothesized that tumor suppressor repression by DNA methyltransferase 1 in pancreatic neuroendocrine tumors could be targeted with epigenetic treatment. METHODS: Resected pancreatic neuroendocrine tumors from 32 patients were stained for DNA methyltransferase 1 and scored. Human (BON1) and murine (STC) pancreatic neuroendocrine tumor cells were treated with DNA methyltransferase 1 inhibitor 5-azacytidine and chemotherapeutic agents 5-fluorouracil and temozolomide. Cell proliferation assay and tumor suppressor gene analysis were performed with qRT-PCR and Clarion S microarray. Tumor measurements were compared in a murine treatment model. RESULTS: High DNA methyltransferase scores were associated with high Ki-67 (6.7% vs 70.6% P < .01), mitotic rate (0.0% vs 31.3%), and grade (20.0% vs 80.4%, P < .01). Treatment with 5-azacytidine and chemotherapy resulted in a reduction of cell proliferation compared to chemotherapy alone in BON1 (77.3% vs 53.1%, P < .001) and STC (73.4% vs 34.2%, P < .001). Treatment with 5-azacytidine and chemotherapy resulted in upregulation of tumor suppressors CDKN1A (7.6 rel. fold, P < .001), BRCA2 (4.3 rel. fold, P < .001), and CDH1 (6.0 rel. fold, P = .026) in BON1 and CDKN1a (14.5 rel. fold, P < .001) and CDH (17.5 rel. fold, P < .001) in STC. In microarray, 5-azacytidine drove global genetic changes in combination treatment. In vivo tumors treated with chemotherapy measured 88.6 ± 19.54 mm3 vs 52.89 ± 10.51 mm3 in those treated with combination therapy (P = .009). CONCLUSION: Epigenetic dysregulation with DNA methyltransferase 1 is associated with pancreatic neuroendocrine tumors and is a potential targetable strategy. 5-azacytidine and chemotherapy in combination can reduce cell proliferation, upregulate silenced tumor suppressor genes, and decrease in vivo tumors in pancreatic neuroendocrine tumors.

Rewarding and Reinforcing Effects of 25H-NBOMe in Rodents.

The drug 25H-NBOMe is a new psychoactive substance (NPS). The use of these substances is likely to pose a threat to public health because they elicit effects similar to those of known psychoactive substances with similar chemical structures. However, data regarding the abuse potential of 25H-NBOMe are lacking. Here, we evaluated the abuse liability of 25H-NBOMe in rodents. The rewarding and reinforcing effects were evaluated through conditioned place preference (CPP) and self-administration (SA) tests after administration of 25H-NBOMe. To investigate the effects of 25H-NBOMe on the central nervous system, we determined the changes in dopamine levels by in vivo microdialysis. In the locomotor activity test, 25H-NBOme significantly increased locomotor activity in mice. In the place conditioning test, the 25H-NBOMe (0.1 and 0.5 mg/kg) groups showed a significantly increase in CPP in mice. In the SA test, the 25H-NBOMe (0.01 mg/kg) administered group showed a significant increased number of infusions and active lever presses. In microdialysis, the 25H-NBOMe (10 mg/kg) administered group was significantly increased in rats.

The Early Impact of the COVID-19 Pandemic on Lung, Colorectal, and Breast Cancer Screening and Treatment at a Tertiary Cancer Center.

OBJECTIVES: During the coronavirus-19 pandemic, experts recommended delaying routine cancer screening and modifying treatment strategies. We sought to understand the sequalae of these recommendations. MATERIALS AND METHODS: We performed a retrospective single-center analysis of screening, diagnosis, and treatment of lung, colorectal, and breast cancer. Data was collected from our institutional cancer registry. Prepandemic (2016-2019) was compared with pandemic (2020) data. RESULTS: Three thousand three sixty one screening chest computed tomography scans (CTs), 35,917 colonoscopies, and 48,093 screening mammograms were performed. There was no difference in CTs [81.0 (SEM10.0) vs. 65.6 (SEM3.29), P =0.067] or mammograms [1017.0 (SEM171.8) vs. 809.4 (SEM56.41), P =0.177] in 2020 versus prepandemic. There were fewer colonoscopies in 2020 [651.4 (SEM103.5) vs. 758.91 (SEM11.79), P =0.043]. There was a decrease in cancer diagnoses per month in 2020 of lung [22.70 (SEM1.469) vs. 28.75 (SEM0.8216), P =0.003] and breast [38.56 (SEM6.133) vs. 51.82 (SEM1.257), P =0.001], but not colorectal [13.11 (SEM1.467) vs. 15.88 (SEM0.585), P =0.074] cancer. There was no change in stage at presentation for lung ( P =0.717), breast ( P =0.115), or colorectal cancer ( P =0.180). Lung had a shorter time-to-treatment in 2020 [38.92 days (SEM 2.48) vs. 66 (SEM1.46), P =0.002]. CONCLUSIONS: In 2020, there was no difference in screening studies for lung and breast cancer but there was a decrease in new diagnoses. Although there were fewer colonoscopies performed in 2020, there was no change in new colorectal cancer diagnoses. Despite changes in guidelines during the pandemic, the time-to-treatment for lung cancer was shorter and was unchanged for colorectal and breast cancer. These findings highlight the importance of continuing care for a vulnerable patient population despite a pandemic.

Current State of Cell Therapies for Gastrointestinal Cancers.

ABSTRACT: Adoptive cell therapies include multiple cell-based therapies to harness the immune system's power to mount a robust anticancer effect. Early successes in solid tumors with checkpoint inhibition have increased the research and development of immunotherapy. The utilization of cell-based therapy for gastrointestinal malignancies is still in its infancy because of challenges of antigen specificity and access to the tumor microenvironment. In this review, we discuss the current state of adoptive cell therapies in terms of challenges and early successes in preclinical and clinical studies.

Potential of Snapshot-Type Hyperspectral Imagery Using Support Vector Classifier for the Classification of Tomatoes Maturity.

It is necessary to convert to automation in a tomato hydroponic greenhouse because of the aging of farmers, the reduction in agricultural workers as a proportion of the population, COVID-19, and so on. In particular, agricultural robots are attractive as one of the ways for automation conversion in a hydroponic greenhouse. However, to develop agricultural robots, crop monitoring techniques will be necessary. In this study, therefore, we aimed to develop a maturity classification model for tomatoes using both support vector classifier (SVC) and snapshot-type hyperspectral imaging (VIS: 460-600 nm (16 bands) and Red-NIR: 600-860 nm (15 bands)). The spectral data, a total of 258 tomatoes harvested in January and February 2022, was obtained from the tomatoes' surfaces. Spectral data that has a relationship with the maturity stages of tomatoes was selected by correlation analysis. In addition, the four different spectral data were prepared, such as VIS data (16 bands), Red-NIR data (15 bands), combination data of VIS and Red-NIR (31 bands), and selected spectral data (6 bands). These data were trained by SVC, respectively, and we evaluated the performance of trained classification models. As a result, the SVC based on VIS data achieved a classification accuracy of 79% and an F1-score of 88% to classify the tomato maturity into six stages (Green, Breaker, Turning, Pink, Light-red, and Red). In addition, the developed model was tested in a hydroponic greenhouse and was able to classify the maturity stages with a classification accuracy of 75% and an F1-score of 86%.

Direct Visualization of UV-Light on Polymer Composite Films Consisting of Light Emitting Organic Micro Rods and Polydimethylsiloxane.

We experimentally demonstrate the direct visualization of ultraviolet (UV) light using flexible polymer composite films consisting of crystalline organic tris-(8-hydroxyquinoline) aluminum (Alq3) micro-rods and polydimethylsiloxane (PDMS). The representative organic mono-molecule Alq3, which is a core material of organic light-emitting diodes, was used to detect light in the invisible UV region and visualize photoluminescence (PL). Alq3 shows absorption in the UV region and light-emitting characteristics in the green region, making it an optimal material for UV visualization because of its large Stokes transition. Crystalline Alq3 micro-rods were fabricated in a deionized water solution through a sequential process of reprecipitation and self-assembly. Highly bright photoluminescence was observed on the highly crystalline Alq3 micro-rods under UV light excitation, indicating that the crystalline structures of Alq3 molecules affect the visible emission decay of excitons. The Alq3 micro-rods were manufactured as flexible polymer composite films using a PDMS solution to observe UV photodetector characteristics according to UV intensity, and it was confirmed that the intensity of the fine UV light reaching the earth's surface can be visualized by making use of this UV photodetector.

Clinicopathologic characteristics of early-onset colorectal cancer.

PURPOSE: The aim of this study was to analysis of the clinicopathological characteristics and prognosis of colorectal cancer (CRC) under the age of 50 years. METHODS: Between January 2009 and December 2018, 1,126 primary CRC patients were included from National Health Insurance Service Ilsan Hospital. The patients were divided into group 1 (n=111, ≤50 years) and group 2 (n=1,015, >50 years). The clinicopathologic features and prognostic outcomes were compared. In addition, to analyze whether there were any differences of those characteristics in 3 groups, patients aged under 50 years were divided into their 20s, 30s, and 40s. RESULTS: Group 1 had a slightly higher distribution in the left colon and rectum, lower T stage I and higher T stage IV rate, and a significantly higher distribution in stage N2 than group 2 (30.6%:16.3%, P<0.001). Poor histological differentiation of tumors was significantly high in group 1 (P=0.003). The 5-year survival rate for those in their 30s (69.2%) and 40s (91.6%) was higher than those in their 20s who died immediately after surgery (P<0.001). The 5-year disease-free survival rate was also confirmed to be meaningful for each age group, with 0% in their 20s, 53.8% in their 30s, 79.2% in their 40s (P<0.001). CONCLUSION: Although the age was not an independent prognostic factor for overall survival in this study, the early onset group of CRCs is more advanced at the time of diagnosis and has a more aggressive histologic type.

The abuse potential of prolintane in rodents: Behavioral pharmacology approaches.

Prolintane (1-Phenyl-2-pyrrolidinylpentane), a synthetic central nervous system (CNS) stimulant, is structurally similar to amphetamine but pharmacologically acts as a dopamine reuptake inhibitor like cocaine. While several case studies reported adverse effects and recreational use of prolintane, the abuse potential of the drug has not been systemically examined yet. In the present study, we evaluated the behavioral effects of prolintane regarding its abuse liability in rodents using locomotor activity, conditioned place preference (CPP), self-administration (SA), and drug discrimination paradigms, as well as in-vivo microdialysis experiment. First, acute prolintane (10 and 20 mg/kg, intraperitoneal injection) increased locomotor activity (distance traveled, cm) in mice but to a lesser degree than methamphetamine (as a positive control). We also found that a single and solitary injection of prolintane (20 mg/kg, IP) significantly increased extracellular dopamine in the striatum. The following result suggests that its stimulatory effects might be associated with the mesolimbic dopaminergic pathway. Further, prolintane produced a significant drug-paired place preference at doses of both 10 and 20 mg/kg. In the SA experiment, the mice that self-administered prolintane intravenously (4 mg/kg/inf) showed a higher infusion and active lever responses but not inactive lever responses. Additionally, cumulative doses of prolintane partially elicited cocaine-appropriate lever responses (38.57% at doses up to 10 mg/kg) in rats. These results implied that prolintane has not only rewarding and reinforcing effects but also interoceptive stimulus properties, which are similar to cocaine at a moderate level. Taken together, this study was the first to show, to our knowledge, that prolintane has a certain level of abuse potential and should be considered carefully as a valuable basis for legal restrictions on use.