Inverted nucleation for photoinduced nonequilibrium melting.

Ultrafast photoinduced melting provides an essential platform for studying nonequilibrium phase transitions by linking the kinetics of electron dynamics to ionic motions. Knowledge of dynamic balance in their energetics is essential to understanding how the ionic reaction is influenced by femtosecond photoexcited electrons with notable time lag depending on reaction mechanisms. Here, by directly imaging fluctuating density distributions and evaluating the ionic pressure and Gibbs free energy from two-temperature molecular dynamics that verified experimental results, we uncovered that transient ionic pressure, triggered by photoexcited electrons, controls the overall melting kinetics. In particular, ultrafast nonequilibrium melting can be described by the reverse nucleation process with voids as nucleation seeds. The strongly driven solid-to-liquid transition of metallic gold is successfully explained by void nucleation facilitated by photoexcited electron-initiated ionic pressure, establishing a solid knowledge base for understanding ultrafast nonequilibrium kinetics.

Observational pilot study of multi-wavelength wearable light dosimetry for erythropoietic protoporphyria.

BACKGROUND: Erythropoietic protoporphyria (EPP) causes painful light sensitivity, limiting quality of life. Our objective was to develop and validate a wearable light exposure device and correlate measurements with light sensitivity in EPP to predict and prevent symptoms. METHODS: A wearable light dosimeter was developed to capture light doses of UVA, blue, and red wavelengths. A prospective observational pilot study was performed in which five EPP patients wore two light dosimeters for 3 weeks, one as a watch, and one as a shirt clip. RESULTS: Standard deviation (SD) increases from the mean in the daily blue light dose increased the odds ratio (OR) for symptom risk more than the self-reported outdoor time (OR 2.76 vs. 2.38) or other wavelengths, and a one SD increase from the mean in the daily blue light wristband device dose increased the OR for symptom risk more than the daily blue light shirt clip (OR 2.45 vs. 1.62). The area under the receiver operator curve for the blue light wristband dose was 0.78, suggesting 78% predictive accuracy. CONCLUSION: These data demonstrate that wearable blue light dosimetry worn as a wristband is a promising method for measuring light exposure and predicting and preventing symptoms in EPP.

Combination of oxaliplatin and ß-carotene suppresses colorectal cancer by regulating cell cycle, apoptosis, and cancer stemness in vitro.

BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide with a high recurrence rate. Oxaliplatin (OXA) resistance is one of the major reasons hindering CRC therapy. ß-Carotene (BC) is a provitamin A and is known to have antioxidant and anticancer effects. However, the combined effect of OXA and BC has not been investigated. Therefore, this study investigated the anticancer effects and mechanism of the combination of OXA and BC on CRC. MATERIALS/METHODS: In the present study, the effects of the combination of OXA and BC on cell viability, cell cycle arrest, and cancer stemness were investigated using HCT116, HT29, OXA-resistant cells, and human CRC organoids. RESULTS: The combination of OXA and BC enhanced apoptosis, G2/M phase cell cycle arrest, and inhibited cancer cell survival in human CRC resistant cells and CRC organoids without toxicity in normal organoids. Cancer stem cell marker expression and self-replicating capacity were suppressed by combined treatment with OXA and BC. Moreover, this combined treatment upregulated apoptosis and the stem cell-related JAK/STAT signaling pathway. CONCLUSIONS: Our results suggest a novel potential role of BC in reducing resistance to OXA, thereby enhances the anticancer effects of OXA. This enhancement is achieved through the regulation of cell cycle, apoptosis, and stemness in CRC.

Risk Factor Analysis of Lymph Node Metastasis for Rectal Neuroendocrine Tumors: Who Needs a Radical Resection in Rectal Neuroendocrine Tumors Sized 1-2 cm?

BACKGROUND: Rectal neuroendocrine tumors (NETs) have malignant potential, and lymph node (LN) or distant metastases can occur; however, treatment of NETs 1-2 cm in size is controversial. OBJECTIVE: This study aimed to identify predictive factors for LN metastasis and prognostic factors for recurrence of rectal NETs, especially tumors 1‒2 cm in size. METHODS: Between October 2004 and November 2020, 453 patients underwent endoscopic or surgical treatment for rectal NETs in Seoul National University Hospital. The data on these patients were prospectively collected in our database and reviewed retrospectively. In cases of local excision, we evaluated LN metastasis with radiologic imaging, including computed tomography or magnetic resonance imaging before treatment and during the follow-up periods. RESULTS: LN metastasis was observed in 40 patients (8.8%). A higher rate of LN metastasis was observed in larger-sized tumors, advanced T stage, lymphovascular invasion (LVI), perineural invasion (PNI), and high tumor grade. In multivariable analysis, the significant risk factors for LN metastasis were tumor size (1 ≤ size < 2 cm: hazard ratio [HR] 64.07; size ≥2 cm: HR 102.37, p < 0.001) and tumor grade (G2: HR 3.63, p = 0.034; G3: HR 5.09, p = 0.044). In multivariable analysis for tumors 1-2 cm in size, the risk factor for LN metastasis was tumor grade (G2: HR 6.34, p = 0.013). CONCLUSIONS: Tumor grade and size are important predictive factors for LN metastasis. In NETs 2 cm in size, tumor grade is also important for LN metastasis, and radical resection should be considered.

Clinical course of peripheral precocious puberty in girls due to autonomous ovarian cysts.

OBJECTIVE: Peripheral precocious puberty (PPP) is the precocious development of secondary sexual characteristics without pulsatile gonadotropin-releasing hormone (GnRH) secretion. In girls, PPP suggests a hyper-oestrogenic state, such as autonomous ovarian cysts and McCune-Albright syndrome (MAS). We aimed to investigate PPP in girls with ovarian cysts, with or without MAS. DESIGN: A retrospective study design was used. PATIENTS AND MEASUREMENTS: The study included 12 girls diagnosed with ovarian cysts with PPP between January 2003 and May 2022. Pelvic sonography was performed in cases of vaginal bleeding or areolar pigmentation in PPP. The clinical characteristics, clinical course and pelvic sonographic findings of girls with ovarian cysts were investigated. RESULTS: We found 18 episodes of ovarian cysts in the 12 girls. The median size of the ovarian cysts was 27.5 mm. Five of the girls were diagnosed with MAS. The median time to spontaneous regression was 6 months. Later, 4 out of 12 girls progressed to central precocious puberty (CPP), and three of them had a recurrence of ovarian cysts. Compared to the non-recurrent and recurrent groups, there was a difference in peak luteinizing hormone (LH) in the GnRH stimulation test and period to cyst regression. CONCLUSIONS: Most ovarian cysts in PPP spontaneously disappear. However, this could be one of the findings of MAS. Some girls progress from PPP to CPP. Therefore, follow-up is necessary for ovarian cysts in patients with PPP. The recurrence of ovarian cysts may occur when spontaneous regression is prolonged.

Navigating the nexus among thigh volume, myokine, and immunocytes in older adults with sarcopenia: A retrospective analysis in a male cohort.

BACKGROUND: This study investigated the association among thigh volume features, interleukin (IL)-6, and immunocytes in the context of the older people with sarcopenia. MATERIALS AND METHODS: This study comprised a cohort of 437 older males diagnosed with sarcopenia, and their average age of 70.41 ± 4.86 years. This study involved conducting correlation and multiple linear regression analyses to investigate the connections between thigh volume, IL-6, and immunocytes. RESULTS: Total thigh volume (TTV) showed positive connections with thigh muscle volume (TMV), natural killer (NK) cells, and CD8 + T cells. TMV had negative associations with thigh fat volume (TFV) and IL6 but displayed positive connections with other factors. IL-6 had adverse associations with all the other variables except for TFV. NK cells showed significant positive relations with all adaptive immune cells, though showing not TFV and IL-6. The CD3+ T cells, CD4+ T cells, CD8+ T cells, and CD19+ B cells exhibited positive correlations with each other including NK cells, though showing not TFV and IL-6. In the regression analysis, TMV exhibited significant positive effects on NK cells (ß = 0.304), CD3+ T cells (ß = 0.182), CD4+ T cells (ß = 0.109), CD8+ T cells (ß = 0.226), and CD19+ B cells (ß = 0.197). On the other hand, IL-6 had significant negative effects on NK cells (ß = -0.292), CD3+ T cells (ß = -0.352), CD4+ T cells (ß = -0.184), CD8+ T cells (ß = -0.387), and CD19+ B cells (ß = -0.366). CONCLUSIONS: This study found that there existed a direct association among thigh muscle with sarcopenia, myokine, and immunocytes. SIMPLE SUMMARY: The aging process involves the immune system playing a vital role in sarcopenia development, and it is thought that myokines released by skeletal myocytes. However, the exact relationship between TMV, myokines, and immunocytes in older male adults affected by sarcopenia remains unclear. This study found that myokines observed in sarcopenia showed a negative correlation with immunocytes, while muscle mass had a positive correlation with immunocytes. In the meantime, this research delved into the use of a regression model to examine how TMV and myokines individually contribute to explaining the presence of innate and adaptive immunocytes in older individuals with sarcopenia.

3D microprinting of inorganic porous materials by chemical linking-induced solidification of nanocrystals.

Three-dimensional (3D) microprinting is considered a next-generation manufacturing process for the production of microscale components; however, the narrow range of suitable materials, which include mainly polymers, is a critical issue that limits the application of this process to functional inorganic materials. Herein, we develop a generalised microscale 3D printing method for the production of purely inorganic nanocrystal-based porous materials. Our process is designed to solidify all-inorganic nanocrystals via immediate dispersibility control and surface linking-induced interconnection in the nonsolvent linker bath and thereby creates multibranched gel networks. The process works with various inorganic materials, including metals, semiconductors, magnets, oxides, and multi-materials, not requiring organic binders or stereolithographic equipment. Filaments with a diameter of sub-10 µm are printed into designed complex 3D microarchitectures, which exhibit full nanocrystal functionality and high specific surface areas as well as hierarchical porous structures. This approach provides the platform technology for designing functional inorganics-based porous materials.

Characteristics of Age Classification into Five-Year Intervals to Explain Sarcopenia and Immune Cells in Older Adults.

Background and Objectives: This study focused on investigating sarcopenic factors and immune cells in older adulthood. To achieve this, the variables related to sarcopenia and immune cells in people living in the same community were analyzed. Materials and Methods: A total of 433 elderly individuals aged 61 to 85 years were randomly categorized as follows in 5-year intervals: 68 in the youngest-old group (aged 61-65), 168 in the young-old group (aged 66-70), 127 in the middle-old group (aged 71-75), 46 in the old-old group (aged 76-80), and 19 in the oldest-old group (aged 81-85). Results: With the progression of age, calf circumference (-8.4 to -11.05%; p = 0.001) and grip strength (-9.32 to -21.01%; p = 0.001) exhibited a noticeable reduction with each successive 5-year age bracket. Conversely, the capability to complete the five-time chair stand demonstrated a clear incline (32.49 to 56.81%; p = 0.001), starting from the middle-aged group. As for appendicular skeletal muscle mass, there was an evident tendency for it to decrease (-7.08 to -26.62%; p = 0.001) with increasing age. A gradual decline in natural killer cells became apparent within the old-old and oldest-old groups (-9.28 to -26.27%; p = 0.001). The results of the post hoc test revealed that CD3 T cells showcased their peak levels in both the youngest-old and young-old groups. This was followed by the middle-old and old-old groups, with slightly lower levels. This pattern was similarly observed in CD4 T cells, CD8 T cells, and CD19 B cells. Conclusions: This study reaffirmed that sarcopenia and immune cell function decline with each successive 5-year increase in age. Considering these findings, the importance of implementing programs aimed at ensuring a high-quality extension of life for the elderly is strongly underscored.

Gorlin-Goltz Syndrome: A Case Report and Literature Review with PTCH1 Gene Sequencing.

Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is an autosomal dominant disease characterized by multisystemic developmental defects caused by pathogenic variants such as patched-1 ( PTCH1 ) gene variants and/or SUFU gene variants. The presence of either two main criteria or one major and two minor criteria are required for the diagnosis of Gorlin-Goltz syndrome. Recently, a major criterion for molecular confirmation has also been proposed. In this article, we report the case of an 80-year-old male who was admitted at our department for multiple brown-to-black papules and plaques on the entire body. He was diagnosed with Gorlin-Goltz syndrome with clinical, radiologic, and pathologic findings. While the diagnosis was made based on the clinical findings in general, confirmation of the genetic variants makes an ideal diagnosis and suggests a new treatment method for target therapy. We requested a genetic test of PTCH1 to ideally identify the molecular confirmation in the hedgehog signaling pathway. However, no pathogenic variants were found in the coding region of PTCH1, and no molecular confirmation was achieved.

Remote-access thyroidectomy with the da Vinci SP system: feasibility in a cadaveric model.

Background: This study aims to study the feasibility of a remote-access thyroidectomy through presternal and submental approaches with the da Vinci SP system. Methods: Bilateral thyroidectomies were performed in five cadaveric models. A single incision in the presternal area was used in two cadavers, and a submental facelift incision approach was used in three cadavers. Results: Performing remote-access thyroidectomy was completed with a presternal approach in one cadaver and with the submental approach in three cadavers. The required skin flap development was minimal, and the docking time for the SP system was quick for all procedures. Time to full exposure of the thyroid gland after skin incision was less than 30 min for the presternal approach and less than 27 min for the submental procedure. Completing total thyroidectomies took 83 min in the presternal approach and between 67 and 127 min in the submental access. No additional ports were required to expose the gland and complete the bilateral resection. Conclusions: Total thyroidectomy was feasible with the da Vinci SP system in single incision presternal and submental approaches comparing promisingly with other currently applied robotic methods. Further studies will be required to assess whether a presternal or submental thyroidectomy with the da Vinci SP system provides clinical benefits in real patients.

Effects of phytoncide on immune cells and psychological stress of gynecological cancer survivors: randomized controlled trials.

This study aimed to identify neuroendocrine substances and natural killer (NK) cells, including their subsets and receptors, to determine whether phytoncides scented in an urban hospital could help improve stress in cancer survivors. Fifty-five gynecological cancer survivors were assigned to either the control group (CG, n=28) or phytoncide group (PTG, n=27). The PTG meditated by lying down in a space scented with phytoncide for 1 hr a day, 5 days a week for 8 weeks. Stress levels in both groups were high prior to the experiment and decreased by 9.31%±45.98% (P=0.003) only in the PTG after the experiment. Although the parasympathetic nerve activity of the PTG increased, the epinephrine and cortisol levels were significantly (P<0.001) decreased by 5.29%±25.5% and by 24.94%±11.62%. Moreover, the PTG showed a significant increase in the levels of NK cell subsets after 8 weeks, whereas there was no improvement in the CG. In conclusion, phytoncide fragrance reduces stress, increases the number of NK cells and their family even in a nonforest environment, and improves innate immunocytes in gynecological cancer survivors; parasympathetic nerve activity and cortisol hormones play critical roles in this process. That is, a phytoncide essential oil helps to stimulate changes in immunocytes' mobility by affecting the human nervous and endocrine systems, thereby providing relief for psychological stress among cancer survivors who previously had cancer cells.

Ultrafast Energy Transfer Process in Confined Gold Nanospheres Revealed by Femtosecond X-ray Imaging and Diffraction.

Femtosecond laser pulses drive nonequilibrium phase transitions via reaction paths hidden in thermal equilibrium. This stimulates interest to understand photoinduced ultrafast melting processes, which remains incomplete due to challenges in resolving accompanied kinetics at the relevant space-time resolution. Here, by newly establishing a multiplexing femtosecond X-ray probe, we have successfully revealed ultrafast energy transfer processes in confined Au nanospheres. Real-time images of electron density distributions with the corresponding lattice structures elucidate that the energy transfer begins with subpicosecond melting at the specimen boundary earlier than the lattice thermalization, and proceeds by forming voids. Two temperature molecular dynamics simulations uncovered the presence of both heterogeneous melting with the melting front propagation from surface and grain boundaries and homogeneous melting with random melting seeds and nanoscale voids. Supported by experimental and theoretical results, we provide a comprehensive atomic-scale picture that accounts for the ultrafast laser-induced melting and evaporation kinetics.

In-situ ionic crosslinking of 3D bioprinted cell-hydrogel constructs for mechanical reinforcement and improved cell growth.

Hydrogels are commonly used in 3D bioprinting technology owing to their ability to encapsulate living cells. However, their inherent delicate properties limit their applicability in the fabrication of mechanically reliable tissue engineering constructs. Herein, we propose a novel reinvented layering integration method for the functional enhancement of 3D cell-hydrogel bioprinting. This was implemented by inserting electrospun microfiber sheets with a crosslinker between the 3D bioprinted layers. When surface-modified microfiber sheets were combined with Ca2+ ionic crosslinkers, the as-printed cell-hydrogel strand was immediately crosslinked when it contacted the sheet surface. The in-situ crosslinking in the bioprinting process not only improved the overall structural stability, but also reinforced the compressive strength and elastic modulus. The enhanced structural stability guaranteed the shape fidelity of the 3D architecture, which included the internal channel network, resulting in improved perfusion conditions for cell growth. The growth of NIH3T3 fibroblasts in 3D bioconstructs with in-situ crosslinking increased by up to five times compared to that of normally bioprinted constructs. The strengthened structural integrity was distinctly sustainable during the cell culture period owing to the sustained release of Ca2+ ions from the embedded microfiber sheets. The synergistic effect of the reinforced mechanical properties with enhanced cell growth is expected to extend the applicability of the proposed hydrogel-based bioprinting technique for soft tissue engineering.

Safety of early surgery after self-expandable metallic stenting for obstructive left-sided colorectal cancer.

BACKGROUND: Self-expanding metallic stenting (SEMS) is usual for the temporary resolution of obstructive left-sided colorectal cancer (CRC) as a bridge to elective surgery. However, there is no consensus regarding adequate time intervals from stenting to radical surgery. The aim of this study was to identify the optimal time interval that results in favorable short- and long-term outcomes. METHODS: Data on patients with obstructive left-sided CRC who underwent elective radical surgery after clinically successful SEMS deployment in five tertiary referral hospitals from 2004 to 2016 were analyzed, retrospectively. An inverse probability treatment-weighted propensity score analysis was used to minimize bias. Postoperative short- and long-term outcomes were compared between two groups: an early surgery (within 8 days) group and delayed surgery (after 8 days) group. RESULTS: Of 311 patients, 148 (47.6%) underwent early and 163 (52.4%) underwent delayed surgery. The median surgery interval was 9.0 days. After adjustment, the groups had similar patient and tumor characteristics. In terms of short-term outcomes, there was no difference in hospitalization length or postoperative complications. No deaths were observed. With a median follow-up of 71.0 months, no significant difference was observed between the groups in 5-year overall survival (early vs. delayed surgery: 79.6% vs. 71.3%, P = 0.370) and 5-year disease-free survival (early vs. delayed surgery: 59.1% vs. 60.4%, P = 0.970). CONCLUSIONS: In obstructive left-sided CRC, the time interval between SEMS and radical surgery did not significantly influence short- and long-term outcomes. Therefore, early surgery after SEMS could be suggested if there is no reason to postpone surgery for preoperative medical optimization.

ß-Carotene suppresses cancer cachexia by regulating the adipose tissue metabolism and gut microbiota dysregulation.

Cancer cachexia is a metabolic disease affecting multiple organs and characterized by loss adipose and muscle tissues. Metabolic dysregulated of adipose tissue has a crucial role in cancer cachexia. ß-Carotene (BC) is stored in adipose tissues and increases muscle mass and differentiation. However, its regulatory effects on adipose tissues in cancer cachexia have not been investigated yet. In this study, we found that BC supplementations could inhibit several cancer cachexia-related changes, including decreased carcass-tumor (carcass weight after tumor removal), adipose weights, and muscle weights in CT26-induced cancer cachexia mice. Moreover, BC supplementations suppressed cancer cachexia-induced lipolysis, fat browning, hepatic gluconeogenesis, and systemic inflammation. Altered diversity and composition of gut microbiota in cancer cachexia were restored by the BC supplementations. BC treatments could reverse the down-regulated adipogenesis and dysregulated mitochondrial respiration and glycolysis in adipocytes and colon cancer organoid co-culture systems. Taken together, these results suggest that BC can be a potential therapeutic strategy for cancer cachexia.

Prognostic roles of leptin-signaling proteins, PD-L1, and tumor-infiltrating lymphocytes in surgically-resected biliary tract cancers.

BACKGROUND: Biliary tract cancers are rare, with a poor patient prognosis. Leptin and programmed death-ligand 1 (PD-L1) influence CD8+ and forkhead box P3 (FOXP3)+ lymphocytes, and thus, cancer cell growth. We aimed to define the prognostic implications of these variables and the clinicopathological features of biliary tract cancers. METHODS: Immunohistochemistry for leptin signaling-related proteins (leptin, leptin receptor, pSTAT3, extracellular-regulated kinase, mammalian target of rapamycin), PD-L1, CD8, and FOXP3 and in situ hybridization for Epstein-Barr virus-encoded small RNAs were performed in 147 cases of surgically-resected biliary tract cancers. RESULTS: Immune cell PD-L1-positivity, tumor size < 3 cm, adjuvant chemotherapy, no recurrence, and early-stage tumors were correlated with better 5-year survival in the tumoral PD-L1(-) and leptin(-) subgroups, and extrahepatic cholangiocarcinoma through multivariate analysis (all p < 0.05). Immune cell PD-L1 and adjuvant chemotherapy lost its prognostic significance in the tumoral PD-L1+ and leptin+ subgroups. CONCLUSIONS: The prognostic implication of the variables may depend upon tumoral protein expression and the anatomical site. Immune cell PD-L1-positivity and the administration of adjuvant chemotherapy may indicate the favorable survival of patients with surgically-resected biliary tract cancers, specifically, in the tumoral PD-L1(-) or tumor leptin(-) subgroups and extrahepatic cholangiocarcinoma. PD-L1- or leptin-targeted therapy combined with conventional chemotherapy may benefit the tumoral PD-L1+ or leptin+ subgroups.

Generalised optical printing of photocurable metal chalcogenides.

Optical three-dimensional (3D) printing techniques have attracted tremendous attention owing to their applicability to mask-less additive manufacturing, which enables the cost-effective and straightforward creation of patterned architectures. However, despite their potential use as alternatives to traditional lithography, the printable materials obtained from these methods are strictly limited to photocurable resins, thereby restricting the functionality of the printed objects and their application areas. Herein, we report a generalised direct optical printing technique to obtain functional metal chalcogenides via digital light processing. We developed universally applicable photocurable chalcogenidometallate inks that could be directly used to create 2D patterns or micrometre-thick 2.5D architectures of various sizes and shapes. Our process is applicable to a diverse range of functional metal chalcogenides for compound semiconductors and 2D transition-metal dichalcogenides. We then demonstrated the feasibility of our technique by fabricating and evaluating a micro-scale thermoelectric generator bearing tens of patterned semiconductors. Our approach shows potential for simple and cost-effective architecturing of functional inorganic materials.

Investigation of the clinical features and recurrence patterns of acute right-sided colonic diverticulitis: A retrospective cohort study.

Background: Right-sided colonic diverticulitis (RCD) and left-sided colonic diverticulitis (LCD) are considered distinct diseases. However, separate guidelines for RCD do not exist. Since the establishment of RCD management would first require evaluation of disease characteristics and recurrence patterns, this study has aimed to investigate the differences in the clinical characteristics between RCD and LCD and the recurrence patterns of RCD. Methods: Patients admitted for colonic diverticulitis between January 2012 and August 2020 were retrospectively reviewed. Clinical characteristics and recurrence rates in RCD and LCD patients, and predictors for recurrence and the recurrence patterns of RCD were analyzed. Results: In total, 446 colonic diverticulitis patients (343 RCD, 103 LCD) were included in this study. RCD patients were more likely to be male, younger, taller, heavier, smoke, drink alcohol, have better physical performance scores, lower modified Hinchey stages and better initial laboratory findings. LCD patients were more likely to receive invasive treatments, have longer fasting and hospital days, higher mortality and cumulative recurrence rates (20.5% vs. 30.4%, P = 0.007). Recurrences in most RCD patients were of similar disease severity and received the same treatments for initial attacks, with rates of recurrence increasing after each recurrence. Predictors of the recurrence of RCD were complicated diverticulitis (hazard ratio[HR] 2.512, 95% confidence interval[CI] 0.127-5.599, p = 0.024) and percutaneous drainage (HR 6.549, 95% CI 1.535-27.930, p = 0.011). Conclusion: RCD is less severe and has a lower recurrence rate than LCD, suggesting that RCD should be treated conservatively. Patients with complicated diseases and those requiring percutaneous drainage are more likely to experience a disease recurrence, suggesting nonsurgical management may be insufficient.

Etoposide-induced MicroRNA-205-5p Suppresses Proliferation and Migration by Targeting ERBB4 in MCF-7 Cells.

BACKGROUND/AIM: Patients with breast cancer frequently encounter a dismal prognosis due to the lack of effective and curative therapies. MicroRNAs (miRNAs) are aberrantly regulated in many types of cancer and have been recognized to play crucial roles in cancer progression. We performed a preclinical investigation of the anti-cancer effect of etoposide and microRNA-205-5p (miRNA-205-5p) and their relationship in MCF-7 cells. MATERIALS AND METHODS: Two cell culture systems, namely monolayers and spheroids, were employed for evaluating the effect of etoposide and miRNA-205-5p on cell proliferation and migration. Real time quantitative polymerase chain reaction was used for the measurement of mRNA and miRNA levels. Luciferase and western blot assays were utilized for the validation of the target gene of miRNA-205-5p. RESULTS: Treatment with etoposide, suppressed both cell proliferation and migration in MCF-7 monolayers. Also, the growth of MCF-7 spheroids as demonstrated by size measurements was inhibited by etoposide treatment. Furthermore, etoposide was found to upregulate the level of miRNA-205-5p. Over-expression of miRNA-205-5p inhibits cell proliferation and migration by directly targeting Erb-B2 receptor tyrosine kinase 4 (ERBB4). CONCLUSION: miRNA-205-5p may act as an important mediator of the anti-cancer effect of etoposide and miRNA-205-5p-based therapy may expand the therapeutic opportunities for breast cancer.