Alteration of HER2 Status During Breast Cancer Progression: A Clinicopathological Analysis Focusing on HER2-Low Status.

Recent studies have shown that novel antibody-drug conjugates (ADCs) can improve clinical outcomes in patients with HER2-low breast cancers. This study aimed to investigate alteration of HER2 status during breast cancer progression with an emphasis on HER2-low status. Using 386 paired samples of primary and recurrent breast cancers, HER2 discordance rate between primary and matched recurrent samples, the relationships between HER2 discordance and clinicopathological characteristics and clinical outcomes of the patients were analyzed. HER2 discordance rate between primary breast cancer and first recurrence was 25.9% (κ = 0.586) with mostly zero-to-low (10.6%) or low-to-zero (9.3%) conversion. There was no significant difference in the discordant rates according to type or location of the recurrence. Of 70 cases with a second recurrence, HER2 discordance rate between the primary tumor and the second recurrence was 27.1% (κ = 0.554). HER2 discordance was associated with lower HER2 level, lymphovascular invasion, and progesterone receptor positivity of the primary tumor. In further analyses, HER2-zero-to-low conversion was associated with lymph node metastasis and hormone receptor (HR) positivity, whereas HER2-low-to-zero conversion was associated with HR negativity and triple-negative subtype. In survival analyses, HER2 discordance was associated with decreased overall survival of patients in the HR-positive group but not in the HR-negative group. Furthermore, patients with HER2-low-to-zero converted tumors showed worse overall survival compared with those with HER2-low concordant tumors. In conclusion, HER2 status changes during breast cancer progression in significant proportions, mostly between zero and low status. As HER2 instability increases during progression and affects clinical outcome, HER2 status needs to be reevaluated in recurrent settings.

Alteration of PD-L1 (SP142) status after neoadjuvant chemotherapy and its clinical significance in triple-negative breast cancer.

PURPOSE: The tumor immune microenvironment can change after neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC). We aimed to investigate the effects of NAC on PD-L1 (SP142) status and its clinical significance in TNBC. METHODS: Paired samples of biopsy and resection specimens were collected from 182 patients with TNBC before and after NAC. PD-L1 (SP142) expression in immune cells in pre- and post-NAC breast cancer samples and the changes between them were analyzed, along with their relationships with the clinicopathological features and clinical outcomes of the patients. RESULTS: Of the 182 patients, 61 (33.5%) achieved pathologic complete response (pCR) after NAC. PD-L1 (SP142) positivity, defined as immune cell staining in ≥ 1% of tumor area, was a predictor for pCR. PD-L1-positive immune cells significantly increased after NAC (2.8% to 5.2% on average) in 109 patients with measurable residual disease. Alteration of PD-L1 status was observed in 24 (22.0%) of the 109 patients with measurable residual tumors after NAC, and all PD-L1 status-converted patients, except one, revealed negative-to-positive conversion. Regarding chemotherapeutic agents, the use of platinum agents was associated with a significant increase in PD-L1-positive immune cells after NAC. In survival analyses, a positive PD-L1 status after NAC and increase of PD-L1-positive immune cells after NAC were associated with better recurrence-free survival of the patients. CONCLUSION: PD-L1 (SP142) status changes after NAC, mostly as a positive conversion. As PD-L1 (SP142) status can convey prognostic and predictive information, it needs to be tested before and after NAC.

Osteoporotic Bone Regeneration via Plenished Biomimetic PLGA Scaffold with Sequential Release System.

Achieving satisfactory bone tissue regeneration in osteoporotic patients with ordinary biomaterials is challenging because of the decreased bone mineral density and aberrant bone microenvironment. In addressing this issue, a biomimetic scaffold (PMEH/SP), incorporating 4-hexylresorcinol (4HR), and substance P (SP) into the poly(lactic-go-glycolic acid) (PLGA) scaffold with magnesium hydroxide (M) and extracellular matrix (E) is introduced, enabling the consecutive release of bioactive agents. 4HR and SP induced the phosphorylation of p38 MAPK and ERK in human umbilical vein endothelial cells (HUVECs), thereby upregulating VEGF expression level. The migration and tube-forming ability of endothelial cells can be promoted by the scaffold, which accelerates the formation and maturation of the bone. Moreover, 4HR played a crucial role in the inhibition of osteoclastogenesis by interrupting the IκB/NF-κB signaling pathway and exhibiting SP, thereby enhancing the migration and angiogenesis of HUVECs. Based on such a synergistic effect, osteoporosis can be suppressed, and bone regeneration can be achieved by inhibiting the RANKL pathway in vitro and in vivo, which is a commonly known mechanism of bone physiology. Therefore, the study presents a promising approach for developing a multifunctional regenerative material for sophisticated osteoporotic bone regeneration.

Anithiactin D, a Phenylthiazole Natural Product from Mudflat-Derived Streptomyces sp., Suppresses Motility of Cancer Cells.

Anithiactin D (1), a 2-phenylthiazole class of natural products, was isolated from marine mudflat-derived actinomycetes Streptomyces sp. 10A085. The chemical structure of 1 was elucidated based on the interpretation of NMR and MS data. The absolute configuration of 1 was determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectral data. Anithiactin D (1) significantly decreased cancer cell migration and invasion activities at a concentration of 5 µM via downregulation of the epithelial-to-mesenchymal transition (EMT) markers in A549, AGS, and Caco-2 cell lines. Moreover, 1 inhibited the activity of Rho GTPases, including Rac1 and RhoA in the A549 cell line, suppressed RhoA in AGS and Caco-2 cell lines, and decreased the mRNA expression levels of some matrix metalloproteinases (MMPs) in AGS and Caco-2 cell lines. Thus 1, which is a new entity of the 2-phenylthiazole class of natural products with a unique aniline-indole fused moiety, is a potent inhibitor of the motility of cancer cells.

Novel differential scanning calorimetry (DSC) application to select polyhydroxyalkanoate (PHA) producers correlating 3-hydroxyhexanoate (3-HHx) monomer with melting enthalpy.

Polyhydroxyalkanoate (PHA) is an environmental alternative to petroleum-based plastics because of its biodegradability. The polymer properties of PHA have been improved by the incorporation of different monomers. Traditionally, the monomer composition of PHA has been analyzed using gas chromatography (GC) and nuclear magnetic resonance (NMR), providing accurate monomer composition. However, sequential analysis of the thermal properties of PHA using differential scanning calorimetry (DSC) remains necessary, providing crucial insights into its thermal characteristics. To shorten the monomer composition and thermal property analysis, we directly applied DSC to the analysis of the obtained PHA film and observed a high correlation (r2 = 0.98) between melting enthalpy and the 3-hydroxyhexanoate (3-HHx) mole fraction in the polymer. A higher 3-HHx fraction resulted in a lower melting enthalpy as 3-HHx provided the polymer with higher flexibility. Based on this, we selected the poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (P(3HB-co-3HHx)) producing strain from Cupriavidus strains that newly screened and transformed with vectors containing P(3HB-co-3HHx) biosynthetic genes, achieving an average error rate below 1.8% between GC and DSC results. Cupriavidus sp. BK2 showed a high 3-HHx mole fraction, up to 10.38 mol%, with Tm (℃) = 171.5 and ΔH of Tm (J/g) = 48.0, simultaneously detected via DSC. This study is an example of the expansion of DSC for PHA analysis from polymer science to microbial engineering.

Role of Adipose-Derived Mesenchymal Stem Cells in Bone Regeneration.

Bone regeneration involves multiple factors such as tissue interactions, an inflammatory response, and vessel formation. In the event of diseases, old age, lifestyle, or trauma, bone regeneration can be impaired which could result in a prolonged healing duration or requiring an external intervention for repair. Currently, bone grafts hold the golden standard for bone regeneration. However, several limitations hinder its clinical applications, e.g., donor site morbidity, an insufficient tissue volume, and uncertain post-operative outcomes. Bone tissue engineering, involving stem cells seeded onto scaffolds, has thus been a promising treatment alternative for bone regeneration. Adipose-derived mesenchymal stem cells (AD-MSCs) are known to hold therapeutic value for the treatment of various clinical conditions and have displayed feasibility and significant effectiveness due to their ease of isolation, non-invasive, abundance in quantity, and osteogenic capacity. Notably, in vitro studies showed AD-MSCs holding a high proliferation capacity, multi-differentiation potential through the release of a variety of factors, and extracellular vesicles, allowing them to repair damaged tissues. In vivo and clinical studies showed AD-MSCs favoring better vascularization and the integration of the scaffolds, while the presence of scaffolds has enhanced the osteogenesis potential of AD-MSCs, thus yielding optimal bone formation outcomes. Effective bone regeneration requires the interplay of both AD-MSCs and scaffolds (material, pore size) to improve the osteogenic and vasculogenic capacity. This review presents the advances and applications of AD-MSCs for bone regeneration and bone tissue engineering, focusing on the in vitro, in vivo, and clinical studies involving AD-MSCs for bone tissue engineering.

Predictive factors of substance misuse and abuse in South Korean adolescents: a secondary data analysis of the 2021 Youth Risk Behavior Web-based Survey.

PURPOSE: This study aimed to identify the general characteristics and health behaviors of students with non-therapeutic substance use. METHODS: This secondary data analysis used data from the 17th Korea Youth Risk Behavior Web-based Survey (2021). Analyses of the 54,848 adolescents used descriptive statistics, the Rao-Scott χ2 test, and logistic regression. RESULTS: The risk factors for substance use among students were anxiety, loneliness, living separately from family, suicidal ideation, e-cigarette use, and high stress. CONCLUSION: The findings help identify the risk factors for non-therapeutic drug use among adolescents. Since South Korea does not have a drug prevention program for its adolescent population, an educational plan based on these findings could help prevent adolescent substance abuse.

Association between allergic diseases, generalized anxiety disorder, and depressive symptoms in South Korean adolescents: a secondary data analysis of the 2022 Korea Youth Risk Behavior Survey.

PURPOSE: This study investigated the relationship between allergic diseases, general anxiety disorder, and depressive symptoms among Korean adolescents. METHODS: A secondary analysis was conducted on the findings of the 18th Korea Youth Risk Behavior Survey (2022). The study included 51,850 adolescents and analyzed the relationships among allergic diseases, general anxiety disorder, and depressive symptoms using complex samples logistic regression analysis. RESULTS: Among the Korean adolescents, 12.7% experienced general anxiety disorder, while 28.7% experienced depressive symptoms. The prevalence of allergic diseases was 5.7% for asthma, 36.3% for allergic rhinitis, and 22.2% for atopic dermatitis. General anxiety disorder was associated with asthma and allergic rhinitis but not atopic dermatitis. Depressive symptoms were associated asthma, allergic rhinitis, and atopic dermatitis. CONCLUSION: Examining the correlation among allergic diseases, general anxiety disorder, and depressive symptoms in adolescents underscores the need for implementing suitable strategies. Moreover, when addressing general anxiety disorder and depressive symptoms in adolescents, it becomes crucial to consider the presence of allergic diseases.

How are people coping with working from home during the COVID-19 pandemic?: Experiences from the Netherlands and South Korea.

COVID-19 has made working from home routine for many. People who have had to maintain their productivity, particularly in physically and/or socially unacceptable home-working situations, experienced one of the pandemic's disadvantages. The experience can vary substantially among individuals as well as by country. This study presents the results of a comparative study of the Netherlands and Korea. Working from home was not uncommon in the Netherlands before the pandemic; however, in Korea, employers adopted working from home from its start, and that increased rapidly. An online survey enabled us to compare the physical and social conditions of current home workspaces in both countries, to understand how well-equipped they were to support people who had to work from home. We studied the changes in productivity and physical/mental health before and during COVID-19, to learn how people coped with working from home in both countries. Contrary to expectations, Koreans showed better scores than people in the Netherlands, in terms of changes in health and productivity. This article discusses various aspects of that result, such as satisfaction with home workspace, housing type, job position and prior experience, compulsoriness, and frequency of working from home. Relieving stress and concentration appeared to be the most important dimensions of telecommuters' satisfaction with working from home environments in both countries. The results are the basis for suggesting the development of strategies for a desirable WFH environment, considering different background contexts, experiences and cultures.

Audience reconstructed: social media interaction by BTS fans during live stream concerts.

COVID-19-motivated social distancing made online concerts common practice in 2020 and 2021, with millions logging into streaming sites to see their favorite artists perform in realtime. For some fans, watching alone at home may have been enough, but concert-concurrent surges of social media activity suggest many virtual performance attendees are doing more. To understand why fans would turn their attention from these precious performance streams to social media, we explored Twitter engagement during four live streamed concerts performed by the Kpop group BTS in 2021. In public Tweets sampled by either concert hashtag or a predefined stream of users and keywords, we evaluated patterns in posting rates in relation to concert program events and investigated the content patterns in 1,200 Tweets sampled from four ranges of popularity (number of Retweets during the concert). Across concerts, short "Shout" Tweets surged at the start of songs, while the rate of retweets often fell during musical performances and shot up when BTS was off stage. Content analysis on the subsample found the materials most widely shared were informational or featured concert visuals, mimicking how fans use their phones at in-person concerts. Most original posts received few Retweets and were more personal and expressive of admiration for the performers. Comparison between the samples (concert hashtag vs. stream) also suggests users were strategic in using or omitting official concert hashtags with the strongest differences in the most widely disseminated content. Postings on Twitter during these performances seemed principally directed to fellow fans and audience members, by individuals choosing to share their own excitement and check in with others. By leveraging their existing social media networks, these concert attendees constructed a collective and interactive concert space, connecting with friends and strangers in the crowd and helping each other capture a richer experience than any broadcasting platform currently supports.

Gastric Organoid, a Promising Modeling for Gastric Stem Cell Homeostasis and Therapeutic Application.

The elucidation of the pathophysiology underlying various diseases necessitates the development of research platforms that faithfully mimic in vivo conditions. Traditional model systems such as two-dimensional cell cultures and animal models have proven inadequate in capturing the complexities of human disease modeling. However, recent strides in organoid culture systems have opened up new avenues for comprehending gastric stem cell homeostasis and associated diseases, notably gastric cancer. Given the significance of gastric cancer, a thorough understanding of its pathophysiology and molecular underpinnings is imperative. To this end, the utilization of patient-derived organoid libraries emerges as a remarkable platform, as it faithfully mirrors patient-specific characteristics, including mutation profiles and drug sensitivities. Furthermore, genetic manipulation of gastric organoids facilitates the exploration of molecular mechanisms underlying gastric cancer development. This review provides a comprehensive overview of recent advancements in various adult stem cell-derived gastric organoid models and their diverse applications.

Pipette-free field-deployable molecular diagnostic kit for bimodal visual detection of infectious RNA viruses.

Here, we developed a field-deployable molecular diagnostic kit for the detection of RNA viruses that operates in a pipette-free manner. The kit is composed of acrylic sticks, PCR tubes, and palm-sized three-dimensional(3D)-printed heaters operated by batteries. The kit performs RNA extraction, reverse transcriptase loop-mediated isothermal amplification (RT-LAMP), and visual detection in one kit. An acrylic stick was engraved with one shallow and one deep cylindrical chamber at each end for the insertion of an FTA card and ethidium homodimer-1 (EthD-1), respectively, to perform RNA extraction/purification and bimodal visual detection of the target amplicons. First, an intercalation of EthD-1 into the target DNA initially produces fluorescence upon UV illumination. Next, the addition of a strong oxidant, in this case sodium (meta) periodate (NaIO4 ), produces intense aggregates in the presence of EthD-1-intercalated DNA, realized by electrostatic interaction. In the absence of the target amplicon, no fluorescence or aggregates are observed. Using this kit, two major infectious viruses-severe fever with thrombocytopenia syndrome virus (SFTSV) and severe acute respiratory syndrome coronavirus (SARS-CoV-2)-were successfully detected in 1 h, and the limits of detection (LOD) were approximately 1 virus µL-1 for SFTSV and 103 copies µL-1 for SARS-CoV-2 RNA. The introduced kit is portable, end-user-friendly, and can be operated in a pipette-free manner, paving the way for simple and convenient virus detection in resource-limited settings.

Loganin Ameliorates Acute Kidney Injury and Restores Tofacitinib Metabolism in Rats: Implications for Renal Protection and Drug Interaction.

Tofacitinib, a Janus kinase (JAK) inhibitor used to treat rheumatoid arthritis, is metabolized through hepatic cytochrome P450 (CYP), specifically CYP3A1/2 and CYP2C11. Prolonged administration of rheumatoid arthritis medications is generally associated with an increased risk of renal toxicity. Loganin (LGN), an iridoid glycoside, has hepatorenal regenerative properties. This study investigates the potential of LGN to mitigate acute kidney injury (AKI) and its effects on the pharmacokinetics of tofacitinib in rats with cisplatin-induced AKI. Both intravenous and oral administration of tofacitinib to AKI rats significantly increased the area under the plasma concentration-time curve from time 0 to infinity (AUC) compared with control (CON) rats, an increase attributed to the decelerated non-renal clearance (CLNR) and renal clearance (CLR) of tofacitinib. Administration of LGN to AKI rats, however, protected kidneys from severe impairment, restoring the pharmacokinetic parameters (AUC, CLNR, and CLR) of tofacitinib to those observed in untreated CON rats, with partial recovery of kidney function, as evidenced by an increase in creatinine clearance (CLCR). Possible interactions between drugs and natural components should be considered, especially when co-administering both a drug and a natural extract containing LGN or iridoid glycosides to patients with kidney injury.

SleepMI: An AI-based screening algorithm for myocardial infarction using nocturnal electrocardiography.

Myocardial infarction (MI) is a common cardiovascular disease, the early diagnosis of which is essential for effective treatment and reduced mortality. Therefore, novel methods are required for automatic screening or early diagnosis of MI, and many studies have proposed diverse conventional methods for its detection. In this study, we aimed to develop a sleep-myocardial infarction (sleepMI) algorithm for automatic screening of MI based on nocturnal electrocardiography (ECG) findings from diagnostic polysomnography (PSG) data using artificial intelligence (AI) models. The proposed sleepMI algorithm was designed using representation and ensemble learning methods and optimized via dropout and batch normalization. In the sleepMI algorithm, a deep convolutional neural network and light gradient boost machine (LightGBM) models were mixed to obtain robust and stable performance for screening MI from nocturnal ECG findings. The nocturnal ECG signal was extracted from 2,691 participants (2,331 healthy individuals and 360 patients with MI) from the PSG data of the second follow-up stage of the Sleep Heart Health Study. The nocturnal ECG signal was extracted 3 h after sleep onset and segmented at 30-s intervals for each participant. All ECG datasets were divided into training, validation, and test sets consisting of 574,729, 143,683, and 718,412 segments, respectively. The proposed sleepMI model exhibited very high performance with precision, recall, and F1-score of 99.38%, 99.38%, and 99.38%, respectively. The total mean accuracy for automatic screening of MI using a nocturnal single-lead ECG was 99.387%. MI events can be detected using conventional 12-lead ECG signals and polysomnographic ECG recordings using our model.

Clonogenic assay and computational modeling using real cell images to study physical enhancement and cellular sensitization induced by metal nanoparticles under MV and kV X-ray irradiation.

This study was initiated due to the physically unexplainable tumor controls resulting from metal nanoparticle (MNP) experiments even under MV X-ray irradiation. A more accurate explanation of the mechanism of radiosensitization induced by MNP is warranted, considering both its physical dose enhancement and biological sensitization, as related research is lacking. Thus, we aimed to examine the intricate dynamics involved in MNP-induced radiosensitization. We conducted specifically designed clonogenic assays for the A549 lung cancer cell line with MNP irradiated by 6 MV and 300 kVp X-rays. Two types of MNP were employed: one based on iron oxide, promoting ferroptosis, and the other on gold nanoparticles known for inducing a significant dose enhancement, particularly at low-energy X-rays. We introduced the lethality enhancement factor (LEF) as the fraction in the cell killing attributed to biological sensitization. Subsequently, Monte Carlo simulations were conducted to evaluate the radial dose profiles for each MNP, corresponding to the physical enhancement. Finally, the local effect model was applied to the clonogenic assay results on real cell images. The LEF and the dose enhancement in the cytoplasm were incorporated to increase the accuracy in the average lethal events and, consequently, in the survival fraction. The results reveal an increased cell killing for both of the MNP under MV and kV X-ray irradiation. In both types of MNP, the LEF reveals a biological sensitization evident. The sensitizer enhancement ratio, derived from the calculations, exhibited only 3% and 1% relative differences compared to the conventional linear-quadratic model for gold and ferroptosis inducer nanoparticles, respectively. These findings indicate that MNPs sensitize cells via radiation through mechanisms akin to ferroptosis inducers, not exclusively relying on a physical dose enhancement. Their own contributions to survival fractions were successfully integrated into computational modeling.

Risk Factor Analysis of Complications and Mortality Following Coil Procedures in Patients with Intracranial Unruptured Aneurysms Using a Nationwide Health Insurance Database.

(1) Background: Unruptured intracranial aneurysm (UIA) occurs in 1-2% of the population and is being increasingly detected. Patients with UIA are treated with close observation, endovascular coiling or surgical clipping. The proportion of endovascular coiling has been rising. However, complications such as cerebral infarction (CI), intracranial hemorrhage (ICRH), and death remain crucial issues after coil treatment. (2) Methods: We analyzed the incidence and risk factors of complications after the use of coil in patients with UIA based on the patients' characteristics. We utilized the Health Insurance Review and Assessment (HIRA) database. Patients treated with coils for UIA between 1 January 2015 and 1 December 2021 were retrospectively analyzed. (3) Results: Of the total 35,140 patients, 1062 developed ICRH, of whom 87 died, with a mortality rate of 8.2%. Meanwhile, 749 patients developed CI, of whom 29 died, with a mortality rate of 3.9%. The overall mortality rate was 1.8%. In a univariate analysis of the risk factors, older age, males, a higher Charlson Comorbidity Index (CCI) score, and diabetes increase the risk of CI. Meanwhile, males with higher CCI scores and hemiplegia or paraplegia show increased ICRH risk. Older age, males and metastatic solid tumors relate to increased mortality risk. (4) Conclusions: This study is significant in that the complications based on the patient's underlying medical condition were analyzed.

PD-L1 (SP142) Expression in Primary and Recurrent/Metastatic Triple-Negative Breast Cancers and Its Clinicopathological Significance.

PURPOSE: The programmed death-ligand 1 (PD-L1) SP142 assay identifies patients with triple-negative breast cancer (TNBC) who are most likely to respond to the anti-PD-L1 agent atezolizumab. We aimed to compare PD-L1 (SP142) expression between primary and recurrent/metastatic TNBCs and elucidate the clinicopathological features associated with its expression. MATERIALS AND METHODS: Primary and recurrent/metastatic TNBCs tested with PD-L1 (SP142) were collected, and clinicopathological information of these cases was obtained through a review of slides and medical records. RESULTS: PD-L1 (SP142) positivity was observed in 50.9% (144/283) of primary tumors and 37.8% (31/82) of recurrent/metastatic TNBCs with a significant difference. Recurrent or metastatic sites were associated with PD-L1 positivity, with high PD-L1 positivity in the lung, breast, and soft tissues, and low positivity in the bone, skin, liver, and brain. When comparing PD-L1 expression between primary and matched recurrent/metastatic TNBCs using 55 paired samples, 20 cases (36.4%) showed discordance; 10 cases revealed positive conversion, and another 10 cases revealed negative conversion during metastatic progression. In primary TNBCs, PD-L1 expression was associated with a higher histologic grade, lower T category, pushing border, and higher tumor-infiltrating lymphocyte infiltration. In survival analyses, PD-L1 positivity, especially high positivity, was found to be associated with favorable prognosis of patients. CONCLUSION: PD-L1 (SP142) expression was lower in recurrent/metastatic TNBCs, and substantial cases showed discordance in its expression between primary and recurrent/metastatic sites, suggesting that multiple sites may need to be tested for PD-L1 (SP142) when considering atezolizumab therapy. PD-L1 (SP142)-positive TNBCs seems to be associated with favorable clinical outcomes.

Reprogramming anchorage dependency to develop cell lines for recombinant protein expression.

As the biopharmaceutical industry continues to mature in its cost-effectiveness and productivity, many companies have begun employing larger-scale biomanufacturing and bioprocessing protocols. While many of these protocols require cells with anchorage-independent growth, it remains challenging to induce the necessary suspension adaptations in many different cell types. In addition, although transfection efficiency is an important consideration for all cells, especially for therapeutic protein production, cells in suspension are generally more difficult to transfect than adherent cells. Thus, much of the biomanufacturing industry is focused on the development of new human cell lines with properties that can support more efficient biopharmaceutical production. With this in mind, we identified a set of "Adherent-to-Suspension Transition" (AST) factors, IKZF1, BTG2 and KLF1, the expression of which induces adherent cells to acquire anchorage-independent growth. Working from the HEK293A cell line, we established 293-AST cells and 293-AST-TetR cells for inducible and reversible reprogramming of anchorage dependency. Surprisingly, we found that the AST-TetR system induces the necessary suspension adaptations with an accompanying increase in transfection efficiency and protein expression rate. Our AST-TetR system therefore represents a novel technological platform for the development of cell lines used for generating therapeutic proteins.

Concordance of HER2 status between core needle biopsy and surgical resection specimens of breast cancer: an analysis focusing on the HER2-low status.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-low status has recently gained attention because of the potential therapeutic benefits of antibody-drug conjugates (ADCs) in breast cancer patients. We aimed to investigate the concordance of HER2 status between core needle biopsy (CNB) and subsequent surgical resection specimens focusing on the HER2-low status. METHODS: This retrospective study was conducted in 1,387 patients with invasive breast cancer whose HER2 status was evaluated in both CNB and surgical resection specimens. The discordance rates between CNB and surgical resection specimens and the clinicopathological features associated with HER2 status discordance were analyzed. RESULTS: The overall concordance rates of HER2 status between CNB and surgical resection specimens were 99.0% (κ = 0.925) for two-group classification (negative vs. positive) and 78.5% (κ = 0.587) for three-group classification (zero vs. low vs. positive). The largest discordance occurred in CNB-HER2-zero cases with 42.8% of them reclassified as HER2-low in surgical resection. HER2 discordance was associated with lower histologic grade, tumor multiplicity, and luminal A subtype. In multivariate analysis, tumor multiplicity and estrogen receptor (ER) positivity were independent predictive factors for HER2-zero to low conversion. CONCLUSIONS: Incorporation of HER2-low category in HER2 status interpretation reduces the concordance rate between CNB and surgical resection specimens. Tumor multiplicity and ER positivity are predictive factors for conversion from HER2-zero to HER2-low status. Therefore, HER2 status should be re-evaluated in resection specimens when considering ADCs in tumors exhibiting multiplicity and ER positivity.

Usnic Acid Targets 14-3-3 Proteins and Suppresses Cancer Progression by Blocking Substrate Interaction.

The anticancer therapeutic effects of usnic acid (UA), a lichen secondary metabolite, have been demonstrated in vitro and in vivo. However, the mechanism underlying the anticancer effect of UA remains to be clarified. In this study, the target protein of UA was identified using a UA-linker-Affi-Gel molecule, which showed that UA binds to the 14-3-3 protein. UA binds to 14-3-3, causing the degradation of proteasomal and autophagosomal proteins. The interaction of UA with 14-3-3 isoforms modulated cell invasion, cell cycle progression, aerobic glycolysis, mitochondrial biogenesis, and the Akt/mTOR, JNK, STAT3, NF-κB, and AP-1 signaling pathways in colorectal cancer. A peptide inhibitor of 14-3-3 blocked or regressed the activity of UA and inhibited its effects. The results suggest that UA binds to 14-3-3 isoforms and suppresses cancer progression by affecting 14-3-3 targets and phosphorylated proteins.