Overview and Comparison of Chinese and Western Medical Treatments for Osteoporosis.

Objective: Traditional Chinese medicine (TCM) can achieve similar effects to Western medicine in increasing bone mineral density, improving the destruction of bone micro-structure, inhibiting bone resorption, etc. However, there exist great differences between TCM and Western medicine in terms of theoretical basis and treatment methods. Therefore, to gain insights into their differences in treating osteoporosis (OP), we compared the disease name, etiology, pathogenesis, and clinical effectiveness to explore the potential benefits of combining the two approaches. Methods Overview: The method of literature review is used in the study. We firstly use academic databases such as PubMed and CNKI to search relevant literature on the understanding of OP in TCM and Western medicine in the past 10 years, then exclude the literature that is not relevant to the study topic or does not meet the study purpose, and finally compare and summarize the findings, views and conclusions of the literature. Key Findings or Insights: In the study, we find that the integrated approach of TCM and Western medicine can provide a gentler and more individualized treatment for patients with OP. By combining the conditioning means of Chinese herbs, compound prescription, acupuncture, moxibustion and Tuina can make up for the adverse reactions and side effects of Western medicine. Besides, TCM can make use of the clinical trials and animal experiments of Western medicine to prove the effectiveness of TCM theories and promote the clinical application. Practical Implications: By exploring the differences between TCM and Western medicine and the potential benefits of their combination, this study can provide a theoretical basis for the individualized treatment of OP. Especially for the patients with postmenopausal OP, senile OP, long-term hormone use, hyperthyroidism and other secondary OP, this study can provide a more comprehensive rehabilitation guidance, prevent the recurrence of these diseases, and improve the quality of patients' life. Recommendations or Future Directions: It is suggested that further clinical trials should be conducted to evaluate the effectiveness of the integrated treatment.

Progression of radiographic fibrosis in rheumatoid arthritis-associated interstitial lung disease.

Background and objectives: Preclinical interstitial lung disease (pILD) may represent the early stages of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, the characteristics, clinical outcomes, and risk factors associated with fibrosis progression in RA-ILD, including pILD and ILD, remain poorly understood. Methods: Baseline data were compared between patients with RA-ILD and those with RA alone. Multivariate logistic regression and Cox regression analyses were performed to identify risk factors associated with the prevalence and imaging progression of RA-ILD, respectively. Results: Among the 371 enrolled RA patients, 32.3% had RA-ILD. Multiple logistic regression analyses identified age over 60.0 years (OR 2.22), smoking (OR 2.09), diabetes mellitus (DM) (OR 3.09), mixed connective tissue disease (MCTD) (OR 2.98), serum lactate dehydrogenase (LDH) levels exceeding 250.0 U/L (OR 6.73), and positive anti-cyclic citrullinated peptide (anti-CCP) antibody (OR 2.06) as independent risk factors for RA-ILD (p< 0.05 or 0.01). Among the 98 RA-ILD patients who underwent follow-up for a median duration of 19.1 months, 51.0% demonstrated fibrotic progression on high-resolution computed tomography (HRCT). Multiple Cox regression analysis identified DM (HR 2.03), Disease Activity Score in 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR) greater than 5.1 (HR 2.21), and baseline HRCT scores exceeding 5.0 (HR 2.30) as independent risk factors for fibrosis progression in RA-ILD (p< 0.05 or 0.01). Conclusion: Nearly one-third of RA patients in this cohort had prevalent pILD or ILD, and half of them demonstrated imaging progression during follow-up. DM, higher DAS28-ESR, and advanced HRCT scores were identified as independent risk factors for progressive fibrosis in RA-ILD.

Combined exposure to benzo(a)pyrene and dibutyl phthalate aggravates pro-inflammatory macrophage polarization in spleen via pyroptosis involving cathepsin B.

Humans are often simultaneously exposed to benzo(a)pyrene (BaP) and dibutyl phthalate (DBP) through consumption of food and water. Yet, direct evidence of the link between BaP and DBP co-exposure and the risk of splenic injury is lacking. In the present study, we established the rats and primary splenic macrophages models to evaluate the effects of BaP or/and DBP exposure on spleen and underlying mechanisms. Compared to the single exposure or control groups, the co-exposure group showed more severe spleen damage and higher production of pro-inflammatory cytokines. Co-exposure to BaP and DBP resulted in a 1.79-fold, 2.11-fold and 1.9-fold increase in the M1 macrophage markers iNOS, NLRP3 (pyroptosis marker protein) and cathepsin B (CTSB), respectively, and a 0.8-fold decrease in the M2 macrophage marker Arg1 in vivo. The more prominent effects in perturbation of imbalance in M1/M2 polarization (iNOS, 2.25-fold; Arg1, 0.55-fold), pyroptosis (NLRP3, 1.43-fold), and excess CTSB (1.07-fold) in macrophages caused by BaP and DBP co-exposure in vitro were also found. Notably, MCC950 (the NLRP3-specific inhibitor) treatment attenuated the pro-inflammatory macrophage polarization and following pro-inflammatory cytokine production triggered by BaP and DBP co-exposure. Furthermore, CA-074Me (the CTSB-specific inhibitor) suppressed the macrophages pyroptosis, pro-inflammatory macrophage polarization, and secretion of pro-inflammatory cytokine induced by BaP and DBP co-exposure. In conclusion, this study indicates co-exposure to BaP and DBP poses a higher risk of spleen injury. Pro-inflammatory macrophage polarization regulated by pyroptosis involving CTSB underlies the spleen injury caused by BaP and DBP co-exposure.

Integration of nanomaterial sensing layers on printable organic field effect transistors for highly sensitive and stable biochemical signal conversion.

Organic field effect transistor (OFET) devices are one of the most popular candidates for the development of biochemical sensors due to their merits of being flexible and highly customizable for low-cost large-area manufacturing. This review describes the key points in constructing an extended-gate type OFET (EGOFET) biochemical sensor with high sensitivity and stability. The structure and working mechanism of OFET biochemical sensors are described firstly, emphasizing the importance of critical material and device engineering to higher biochemical sensing capabilities. Next, printable materials used to construct sensing electrodes (SEs) with high sensitivity and stability are presented with a focus on novel nanomaterials. Then, methods of obtaining printable OFET devices with steep subthreshold swing (SS) for high transconductance efficiency are introduced. Finally, approaches for the integration of OFETs and SEs to form portable biochemical sensor chips are introduced, followed by several demonstrations of sensory systems. This review will provide guidelines for optimizing the design and manufacturing of OFET biochemical sensors and accelerating the movement of OFET biochemical sensors from the laboratory to the marketplace.

DBP and BaP co-exposure induces kidney injury via promoting pyroptosis of renal tubular epithelial cells in rats.

Dibutyl phthalate (DBP) and benzo(a)pyrene (BaP) are widespread environmental and foodborne contaminants that have detrimental effects on human health. Although people are often simultaneously exposed to DBP and BaP via the intake of polluted food and water, the combined effects on the kidney and potential mechanisms remain unclear. Hence, we treated rats with DBP and BaP for 90 days to investigate their effects on kidney histopathology and function. We also investigated the levels of paramount proteins and genes involved in pyroptosis and TLR4/NF-κB p65 signaling in the kidney. Our research showed that combined exposure to DBP and BaP triggered more severe histopathological and renal function abnormalities than in those exposed to DBP or BaP alone. Simultaneously, combined exposure to DBP and BaP enhanced the excretion of IL-1ß and IL-18, along with the release of LDH in rat renal tubular epithelial cells (RTECs). Moreover, combined exposure to DBP and BaP increased the expression of pyroptosis marker molecules, including NLRP3, ASC, cleaved-Caspase-1, and GSDMD. Meanwhile, the combination of DBP and BaP activated TLR4/NF-κB signaling in the kidney. Taken together, the combined exposure to DBP and BaP causes more severe kidney injury than that caused by DBP or BaP exposure separately. In addition, pyroptosis of RTECs regulated by TLR4/NF-κB signaling may add to the kidney damage triggered by combined exposure to DBP and BaP.

[Effect of heat-reinforcing needling on expression of serum inflammatory factors and autophagy of knee joint synovial tissue in rheumatoid arthritis rabbits with cold syndrome].

OBJECTIVE: To observe the effect of heat-reinforcing needling on the expression of serum inflammatory factors and autophagy of knee synovial tissue in rheumatoid arthritis (RA) rabbits with cold syndrome, so as to explore its mechanism of anti-inflammatory in the treatment of RA. METHODS: Fifty rabbits were randomly divided into normal, model, heat-reinforcing needling, inhibitor and agonist groups (n=10 rabbits in each group). The model of RA with cold syndrome was established by Freund's adjuvant and ovalbumin mixed solution injection combined with freezing and wind-cold dampness method. Heat-reinforcing needling was applied at "Zusanli" (ST36) for 30 min, once a day for 14 days. Rabbits of the inhibitor and agonist groups were given intraperitoneally injected with autophagy inhibitor 3-methyladenine (3-MA) or autophagy agonist rapamycin, once every 2 days for 7 days. The knee circumference and skin temperature of the rabbits in each group were measured. Color doppler ultrasonography was applied to examine the synovial membrane, joint effusion and blood flow signals in the knee joints of the rabbits in each group. Serum tumor necrosis factor (TNF) -α, interleukin (IL)-1ß, IL-6 and C-creactive protein (CRP) were detected by ELISA. Transmission electron microscopy was applied to observe the ultrastructure and autophagosomes of synovial cells. The protein expressions of autophagy-related protein Atg5, serine/threonine protein kinase-dysregulated 51-like kinase 1 (ULK1), microtubule-associated protein light chain 3B (LC3B), and Beclin-1 were detected by Western blot. Fluorescence quantitative PCR was used to detect the mRNA expressions of NOD-like receptor 3 (NLRP3) and nuclear factor-κB (NF-κB). RESULTS: Compared with the normal group, the circumference of the knee joint was increased (P<0.01), the skin temperature was decreased (P<0.01), the knee joint synovium was thickened and the blood flow signal was abundant, the contents of serum TNF-α, IL-1ß, IL-6, and CRP were increased (P<0.01), the protein expressions of Atg5, ULK1, Beclin-1 and LC3BⅡ/LC3BⅠof synovial tissue were significantly decreased (P<0.01), the mRNA expressions of NLRP3 and NF-κB were increased (P<0.01) in the model group. In comparison with the model and inhibitor groups, the circumference of the knee joint was decreased (P<0.01), whlie the skin temperature was increased (P<0.01), the synovial membrane became thinner and the blood flow signal was wea-kened, the contents of TNF-α, IL-1ß, IL-6 and CRP were decreased (P<0.01), the protein expressions of Atg5, ULK1, Beclin-1 and LC3B Ⅱ/LC3B Ⅰ were increased (P<0.01), and the mRNA expressions of NLRP3 and NF-κB were decreased (P<0.01) in the heat-reinforcing needling and agonist groups. CONCLUSION: Heat-reinforcing needling can alleviate the inflammatory response of the knee joint synovium in RA rabbits with cold syndrome, which may be related to its function in enhancing the autophagy activity of synovial cells and inhibiting the synthesis and release of inflammatory factors TNF-α, IL-1ß, IL-6 and CRP.

Sporoderm-broken spores of Ganoderma lucidum alleviates liver injury induced by DBP and BaP co-exposure in rat.

Dibutyl phthalate (DBP) and Benzo(a)pyrene (BaP) are ubiquitous contaminants in environment and foodstuffs, which increase the chance of their combined exposure to humans in daily life. However, the combined effects of DBP and BaP on liver and the underlying mechanisms are still unclear. In this study, we explored the combined effects of DBP and BaP on liver and the potential mechanisms in a rat model. We found that DBP and BaP co-exposure activated the MyD88/NF-κB pathway through increasing TLR4 acetylation (TLR4ac) level, leading to the imbalance of pro-inflammatory factors (CXCL-13, IL-6 and TNF-α) and anti-inflammatory factors (IL-10), ultimately resulting in liver tissue damage and functional changes. Sporoderm-broken spores of Ganoderma lucidum (SSGL) had strong alleviating effects on liver injury induced by DBP and BaP co-exposure. Our study found that SSGL suppressed TLR4ac-regulated MyD88/NF-κB signaling to reduce the release of pro-inflammatory factors, and promote the secretion of IL-10, thus alleviating liver injury caused by DBP and BaP co-exposure. In conclusion, SSGL contributed to liver protection against DBP and BaP-induced liver injury in rats via suppressing the TLR4ac-regulated MyD88/NF-κB signaling.

Long-term co-exposure DBP and BaP causes imbalance in liver macrophages polarization via activation of Notch signaling regulated by miR-34a-5p in rats.

Humans are often exposed to complex mixtures of environmental pollutants over long periods of time. It is reported that Dibutyl phthalate (DBP) and benzo[a]pyrene (BaP) are typical environmental pollutants, which are associated with liver injury. Nevertheless, little is known about the effects of DBP and BaP combined exposure on liver. In the current study, rats were exposed to DBP alone (50, or 250 mg/kg), BaP alone (1, or 5 mg/kg), or DBP and BaP (50 + 1, or 250 + 5 mg/kg) for ninety days. More serious liver damage, including abnormal liver function, infiltration of inflammatory cells and disturbed secretion of inflammatory factors, were observed in long-term co-exposure to DBP and BaP group relative to those in single exposure group. Our data showed that long-term co-exposure to DBP and BaP induces macrophages to polarize toward M1 and inhibits polarization of M2 macrophages. Long-term co-exposure to DBP and BaP downregulated miR-34a-5p level and upregulated Notch signaling. These results indicated that imbalance in macrophages M1/M2 polarization mediated by activation of Notch signaling due to reduced miR-34a-5p level may contribute to additive effects on disorder of inflammatory factors secretion and subsequent liver injury following long-term DBP and BaP co-exposure.

Perpendicular magnetization anisotropy induced dynamical coherence reduction in stripe domain film.

We investigated the magnetization dynamics of the 350 nm permalloy film with in plane domain (IPD), stripe domain (SD), and labyrinth domain (LD) patterns. Experimental and micromagnetic simulation results showed that the change in magnetic domain structure from IPD to LD was due to the increasing perpendicular magnetic anisotropy (PMA) of the film. The magnetization dynamics indicated that the resonant modes of the film strongly depended on the magnetic domain structure. IPD films presented a uniform precession mode. The film with well-regular SD exhibited clear acoustic and optical resonance modes, and the formation of LD suppressed both resonance modes. Finally, the dynamics of magnetization dependent on the domain structure in these films were discussed by using the phenomenological resonance models.

The relationship between pesticide exposure during critical neurodevelopment and autism spectrum disorder: A narrative review.

Agricultural pesticides have been one of the most extensively used compounds throughout the world. The main sources of contamination for humans are dietary intake and occupational exposure. The impairments caused by agricultural pesticide exposure have been a significant global public health problem. Recent studies have shown that low-level agricultural pesticide exposure during the critical period of neurodevelopment (pregnancy and lactation) is closely related to autism spectrum disorder (ASD). Inhibition of acetylcholinesterase, gut microbiota, neural dendrite morphology, synaptic function, and glial cells are targets for the effects of pesticides during nervous system development. In the present review, we summarize the associations between several highly used and frequently studied pesticides (e.g., glyphosate, chlorpyrifos, pyrethroids, and avermectins) and ASD. We also discusse future epidemiological and toxicological research directions on the relationship between pesticides and ASD.

The Notch signaling pathway regulates macrophage polarization in liver diseases.

The liver is not only the main metabolic site of exogenous compounds and drugs, but also an important immune organ in the human body. When a large number of nonself substances (such as drugs, alcohol, pathogens, microorganisms and their metabolites) enter the liver, they will cause serious liver diseases, including liver fibrosis, liver cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Macrophages are the first line of defense against the invasion of exogenous pathogens and significant cellular components of the innate immune system. Macrophages have strong heterogeneity and plasticity. When different pathogens invade the body, they cause different types of polarization of macrophages through different molecular mechanisms. Notch signaling is considered to be the key regulator of the biological function of macrophages. Activating Notch signaling can regulate the differentiation of macrophages into M1 and play a role in promoting inflammation and antitumor activity, while blocking Notch signaling can polarize macrophages to M2, suppressing inflammation and promoting tumor growth. However, there are few studies on regulation of macrophage polarization by the Notch signaling pathway in liver diseases. Therefore, in this review, we will introduce the role of the Notch signaling pathway in regulating macrophage polarization in liver diseases.

Research progress on FASN and MGLL in the regulation of abnormal lipid metabolism and the relationship between tumor invasion and metastasis.

Tumorigenesis involves metabolic reprogramming and abnormal lipid metabolism, which is manifested by increased endogenous fat mobilization, hypertriglyceridemia, and increased fatty acid synthesis. Fatty acid synthase (FASN) is a key enzyme for the de novo synthesis of fatty acids, and monoacylglycerol esterase (MGLL) is an important metabolic enzyme that converts triglycerides into free fatty acids. Both enzymes play an important role in lipid metabolism and are associated with tumor-related signaling pathways, the most common of which is the PI3K-AKT signaling pathway. They can also regulate the immune microenvironment, participate in epithelial-mesenchymal transition, and then regulate tumor invasion and metastasis. Current literature have shown that these two genes are abnormally expressed in many types of tumors and are highly correlated with tumor migration and invasion. This article introduces the structures and functions of FASN and MGLL, their relationship with abnormal lipid metabolism, and the mechanism of the regulation of tumor invasion and metastasis and reviews the research progress of the relationship of FASN and MGLL with tumor invasion and metastasis.

sLex expression in invasive micropapillary breast carcinoma is associated with poor prognosis and can be combined with MUC1/EMA as a supplementary diagnostic indicator.

OBJECTIVE: Mucin 1 (MUC1/EMA) and sialyl Lewis X (sLex) indicate polarity reversal in invasive micropapillary carcinoma (IMPC). The purpose of this study was to evaluate the expression of MUC1/EMA and sLex and to assess their diagnostic and prognostic value in patients with IMPC. METHODS: The expression of sLex and MUC1/EMA in 100 patients with IMPC and a control group of 89 patients with invasive ductal carcinoma not otherwise specified (IDC-NOS) were analyzed with IHC. Fresh tumor tissues were collected from patients with IMPC or IDC-NOS for primary culture and immunofluorescence analysis. RESULTS: The rate of nodal metastasis was higher in patients with IMPC than those with IDC-NOS, and IMPC cells tended to express more sLex and MUC1/EMA in the cytomembranes (the stroma-facing surfaces of the micropapillary clusters) than IDC-NOS cells. In IMPC, high cytomembrane expression of sLex, but not MUC1/EMA, indicated poor prognosis. In addition, among the 100 patients with IMPC, 10 patients had sLex+/EMA- expression patterns, and 8 patients had sLex-/EMA+ expression patterns. The primary IMPC cells were suspended, non-adherent tumor cell clusters, whereas the primary IDC cells were adherent tumor cells. Immunofluorescence analysis showed that MUC1/EMA and sLex were co-expressed on the cytomembranes in IMPC cell clusters and in the cytoplasm in IDC-NOS cells. CONCLUSIONS: sLex can be used as a prognostic indicator and can be combined with MUC1/EMA as a complementary diagnostic indicator to avoid missed IMPC diagnosis.

In vitro and in vivo activity analysis of poplar CLE dodecapeptides that are most divergent from Arabidopsis counterparts.

Intercellular communication mediated by the plant-specific CLAVATA3/ENDOSPERM SURROUNDING REGION (ESR)-related (CLE) family members is one of the fundamental mechanisms coordinating the development of complex bodies of plants. In this work, we chose 8 out of 38 putative CLE dodecapeptides encoded in the genome of P. trichocarpa based on their lowest sequence similarity with Arabidopsis CLE peptides, and investigated how such sequence variations affect their functional characteristics. In group 1, PtCLE16p faithfully retained the AtCLE1-7p activity, while PtCLE49p reversed the root-enhancing effect to an inhibitory one with two extra amino acid substitutions, which might have disrupted the capacity of PtCLE49p to recognize the corresponding receptors. In group 2, PtCLE9p conferred Arabidopsis with retarded root growth and suppressed phloem differentiation in a negative dominant manner just like AtCLE25G6T did. PtCLE9p enhanced the vegetative growth in both basal and aerial rosettes by regulating the expression of AERIAL ROSETTE 1 (ART1) and FRIGIDA (FRI) as well as the downstream FLOWERING LOCUS C (FLC) genes. In group 3, PtCLE34p and PtCLE5p slightly promoted primary root growth, while PtCLE40p revealed CLV3p-like and TDIF activity in root and hypocotyls, respectively. The remaining PtCLE18p in group 4 dramatically disturbed the expression of WOX5 and promoted the development of root hairs by repressing the expression of GLABRA2 (GL2) gene, which encoded a negative regulator of epidermal cells differentiation towards root hairs. In summary, our data indicated that with significant functional conservation and common signaling machinery existing for CLE families of land plants, unique and diverse activities of CLE peptides have evolved to perform specific functions in different plant species.

Trichothecin inhibits invasion and metastasis of colon carcinoma associating with SCD-1-mediated metabolite alteration.

Lipid metabolic abnormalities have received intensified concerns and increased de novo synthesis of lipids is recognized as a common feature of many human cancers. Nevertheless, the role of lipid metabolism that confers aggressive properties on human cancers still remains to be revealed. Natural compounds represent an abundant pool of agents for the discovery of novel lead compounds. Trichothecin (TCN) is a sesquiterpenoid originating from an endophytic fungus of the herbal plant Maytenus hookeri Loes. Here, we assess the association of stearoyl-CoA desaturase 1 (SCD-1) over-expression with malignant progression of colorectal cancer (CRC). Based on this association, the effect of TCN on migration and invasion of colon carcinoma cells closely related to the inhibition of SCD-1 is evaluated. We further demonstrate that reduced production of unsaturated fatty acids (FAs) by blocking SCD-1 activity is beneficial for the anti-invasion effect of TCN. The aim of this study was to clarify the mechanistic connection between metabolite alterations induced by metabolic rewiring and the aggressive tumor phenotype and further develop novel pharmacological tools for the intervention of tumor invasion associated with SCD-1-mediated metabolite alterations.

Overexpression of ß1 integrin contributes to polarity reversal and a poor prognosis of breast invasive micropapillary carcinoma.

Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive breast cancer. Polarity reversal exemplified by cluster growth is hypothesized to contribute to the invasiveness and metastasis of IMPC. In this study, we demonstrate that levels of ß1 integrin and Rac1 expression were greater in breast IMPC than in invasive breast carcinoma of no specific type and paraneoplastic benign breast tissue. We show that silencing ß1 integrin expression using the ß1 integrin inhibitor AIIB2 partially restored polarity in IMPC primary cell clusters and downregulated Rac1. Thus, overexpression of ß1 integrin upregulates Rac1. Univariate analysis showed that overexpression of ß1 integrin and Rac1 was associated with breast cancer cell polarity reversal, lymph node metastasis, and poor disease-free survival in IMPC patients. Multivariate analysis revealed that polarity reversal was an independent predictor of poor disease-free survival. These findings indicate that overexpression of ß1 integrin and the resultant upregulation of Rac1 contribute to polarity reversal and metastasis of breast IMPC, and that ß1 integrin and Rac1 could be potential prognostic biomarkers and targets for treatment of breast IMPC.

Spontaneous vesicle formation and vesicle-to-micelle transition of sodium 2-ketooctanate in water.

Single-tailed short-chain alkyl keto-acids/salts, a class of fatty acid/salt derivatives, such as sodium 2-ketooctanate (KOCOONa), are a kind of weakly acid/salt type amphiphiles and plausible prebiotic molecules, and the current understanding of their aggregation behavior in aqueous solutions is still limited. Herein, the aggregation behavior of KOCOONa in aqueous solution was studied by changing its concentration (C), using equilibrium surface tension, conductivity, and fluorescence measurements. The aggregates formed were characterized using freeze-fracture and cryogenic transmission electron microscopy, dynamic light scattering, atomic force microscopy, and confocal laser scanning microscopy. A concentration-driven stepwise aggregation was identified in the KOCOONa solution. Vesicles can spontaneously form from the single-component aqueous solution, with a critical vesicle concentration (CVC) of ∼15mM, which is obviously lower than that of octanoic acid/salt (120-200mM). With increasing C, a vesicle-to-micelle transition can occur, showing a critical micelle concentration (CMC) of ∼80mM. In addition, the membrane permeability of the KOCOONa vesicles was examined using small-size Calcein and large-size FITC-BSA as fluorescence probes, showing a size-selective permeability, similar to short-chain (C8-C11) fatty acid vesicles. For the first time, the aggregation behavior of single-tailed keto-acid salt surfactant is reported.

Amplification and overexpression of PSCA at 8q24 in invasive micropapillary carcinoma of breast.

PURPOSE: Invasive micropapillary carcinoma (IMPC) of the breast has distinct histological features and molecular genetic profiles. Gains/amplifications of 8q24 are found associated with IMPC. Although the prostate stem cell antigen (PSCA) gene is located at chromosome 8q24, and found over-expressed in prior studies, its prognostic values and biological significance in IMPC have not been well studied. METHODS: Fluorescence in situ hybridization (FISH) was used to assess the frequencies of PSCA copy number gains in IMPC, invasive ductal carcinoma of no special type (IDC-NST), and invasive lobular carcinoma (ILC) samples. The protein expression levels of PSCA were examined in 56 IMPC, 72 IDC-NST, and 56 ILC samples using immunohistochemical analysis. RESULTS: PSCA gene amplification was detected in 45.2% (14/31) of the IMPC, 28.1% (9/32) of the IDC-NST, and none (0/25) of the ILC. PSCA protein expression was observed in 58.9% (33/56), 40.3% (29/72), and 3.6% (2/56) of IMPC, IDC-NST, and ILC samples, respectively. The concordant rate of the immunohistochemistry and FISH data was 85.2%. PSCA gene amplification highly correlated with its protein overexpression (rs = 0.687, P < 0.001), suggesting that gene amplification is an important mechanism involved in PSCA overexpression. Our univariate analysis showed that the patients with PSCA-positive IMPC had a decreased disease-free survival (DFS) compared to PSCA-negative IMPC patients (P = 0.003). Our multivariate analysis confirmed the worse DFS in PSCA-positive IMPC patients (P = 0.022). CONCLUSIONS: Our results indicate that PSCA may be an attractive target in the 8q24 amplicon and that it may serve as a molecular marker of metastasis and recurrence in IMPC. The differential expression of PSCA may be associated with cell adhesion. Detection of PSCA protein and gene amplification may help manage and predict the prognosis of IMPC patients.