Echocardiography-based machine learning algorithm for distinguishing ischemic cardiomyopathy from dilated cardiomyopathy.

BACKGROUND: Machine learning (ML) can identify and integrate connections among data and has the potential to predict events. Heart failure is primarily caused by cardiomyopathy, and different etiologies require different treatments. The present study examined the diagnostic value of a ML algorithm that combines echocardiographic data to automatically differentiate ischemic cardiomyopathy (ICM) from dilated cardiomyopathy (DCM). METHODS: We retrospectively collected the echocardiographic data of 200 DCM patients and 199 ICM patients treated in the First Affiliated Hospital of Guangxi Medical University between July 2016 and March 2022. All patients underwent invasive coronary angiography for diagnosis of ICM or DCM. The data were randomly divided into a training set and a test set via 10-fold cross-validation. Four ML algorithms (random forest, logistic regression, neural network, and XGBoost [ML algorithm under gradient boosting framework]) were used to generate a training model for the optimal subset, and the parameters were optimized. Finally, model performance was independently evaluated on the test set, and external validation was performed on 79 patients from another center. RESULTS: Compared with the logistic regression model (area under the curve [AUC] = 0.925), neural network model (AUC = 0.893), and random forest model (AUC = 0.900), the XGBoost model had the best identification rate, with an average sensitivity of 72% and average specificity of 78%. The average accuracy was 75%, and the AUC of the optimal subset was 0.934. External validation produced an AUC of 0.804, accuracy of 78%, sensitivity of 64% and specificity of 93%. CONCLUSIONS: We demonstrate that utilizing advanced ML algorithms can help to differentiate ICM from DCM and provide appreciable precision for etiological diagnosis and individualized treatment of heart failure patients.

MIF/SCL3A2 depletion inhibits the proliferation and metastasis of colorectal cancer cells via the AKT/GSK-3ß pathway and cell iron death.

This study investigated the mechanisms of migration inhibitory factor (MIF) and solute carrier family 3 member 2 (SLC3A2) in colorectal cancer progression. The levels of MIF and SLC3A2 expression in cells were measured by RT-qPCR. SW480 and SW620 cells were transfected with sh-MIF and sh-SLC3A2, respectively. MIF, SLC3A2, GPX4, E-cadherin and N-cadherin expression were detected by immunofluorescence (IF). CCK8 and Transwell assays were performed to detect cell proliferation and migration. Co-immunoprecipitation (CoIP) was used to measure the binding activity of MIF and SLC3A2. Finally, a nude mouse tumorigenicity assay was used to confirm the functions of MIF and SLC3A2 in colorectal cancer. Results showed that the levels of MIF and SLC3A2 expression were up-regulated in colorectal cancer cells. Inhibition of MIF or SLC3A2 expression prevented cell proliferation, migration, epithelial-mesenchymal transition (EMT) and invasion. In addition, knockdown of MIF and SLC3A2 promoted iron death in SW480 and SW620 cells. CoIP results showed that MIF and SLC3A2 directly interact with each other. Knockdown of both MIF and SLC3A2 inhibited tumour growth and metastasis via the AKT/GSK-3ß pathway in vivo. The Akt/GSK-3ß pathway was found to participate in regulating MIF and SLC3A2 both in vivo and in vitro. MIF and SLC3A2 might be potential biomarkers for monitoring the treatment of colorectal cancer.

Deciphering the d-/l-lactate-producing microbiota and manipulating their accumulation during solid-state fermentation of cereal vinegar.

Symphony orchestra of multi-microorganisms characterizes the solid-state acetic acid fermentation process of Chinese cereal vinegars. Lactate is the predominant non-volatile acid and plays indispensable roles in flavor formation. This study investigated the microbial consortia driving the metabolism of D-/l-lactate during fermentation. Sequencing analysis based on D-/l-lactate dehydrogenase genes demonstrated that Lactobacillus (relative abundance: > 95%) dominated the production of both d-lactate and l-lactate, showing species-specific features between the two types. Lactobacillus helveticus (>65%) and L. reuteri (~80%) respectively dominated l- and d-lactate-producing communities. D-/l-lactate production and utilization capabilities of eight predominant Lactobacillus strains were determined by culture-dependent approach. Subsequently, D-/l-lactate producer L. plantarum M10-1 (d:l ≈ 1:1), l-lactate producer L. casei 21M3-1 (D:L ≈ 0.2:9.8) and D-/l-lactate utilizer Acetobacter pasteurianus G3-2 were selected to modulate the metabolic flux of D-/l-lactate of microbial consortia. The production ratio of D-/l-lactate was correspondingly shifted coupling with microbial consortia changes. Bioaugmentation with L.casei 21M3-1 merely enhanced l-lactate production, displaying ~4-fold elevation at the end of fermentation. Addition of L.plantarum M10-1 twice increased both D- and l-lactate production, while A. pasteurianus G3-2 decreased the content of D-/l-isomer. Our results provided an alternative strategy to specifically manipulate the metabolic flux within microbial consortia of certain ecological niches.

Disentangled Cross-Modal Transformer for RGB-D Salient Object Detection and Beyond.

Previous multi-modal transformers for RGB-D salient object detection (SOD) generally directly connect all patches from two modalities to model cross-modal correlation and perform multi-modal combination without differentiation, which can lead to confusing and inefficient fusion. Instead, we disentangle the cross-modal complementarity from two views to reduce cross-modal fusion ambiguity: 1) Context disentanglement. We argue that modeling long-range dependencies across modalities as done before is uninformative due to the severe modality gap. Differently, we propose to disentangle the cross-modal complementary contexts to intra-modal self-attention to explore global complementary understanding, and spatial-aligned inter-modal attention to capture local cross-modal correlations, respectively. 2) Representation disentanglement. Unlike previous undifferentiated combination of cross-modal representations, we find that cross-modal cues complement each other by enhancing common discriminative regions and mutually supplement modal-specific highlights. On top of this, we divide the tokens into consistent and private ones in the channel dimension to disentangle the multi-modal integration path and explicitly boost two complementary ways. By progressively propagate this strategy across layers, the proposed Disentangled Feature Pyramid module (DFP) enables informative cross-modal cross-level integration and better fusion adaptivity. Comprehensive experiments on a large variety of public datasets verify the efficacy of our context and representation disentanglement and the consistent improvement over state-of-the-art models. Additionally, our cross-modal attention hierarchy can be plug-and-play for different backbone architectures (both transformer and CNN) and downstream tasks, and experiments on a CNN-based model and RGB-D semantic segmentation verify this generalization ability.

Interferon-γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells.

The bioactivity of interferon-γ (IFN-γ) in cancer cells in the tumor microenvironment (TME) is not well understood in the current immunotherapy era. We found that IFN-γ has an immunosuppressive effect on colorectal cancer (CRC) cells. The tumor volume in immunocompetent mice was significantly increased after subcutaneous implantation of murine CRC cells followed by IFN-γ stimulation, and RNA sequencing showed high expression of B7 homologous protein 4 (B7H4) in these tumors. B7H4 promotes CRC cell growth by inhibiting the release of granzyme B (GzmB) from CD8+ T cells and accelerating apoptosis in CD8+ T cells. Furthermore, interferon regulatory factor 1 (IRF1), which binds to the B7H4 promoter, is positively associated with IFN-γ stimulation-induced expression of B7H4. The clinical outcome of patients with CRC was negatively related to the high expression of B7H4 in cancer cells or low expression of CD8 in the microenvironment. Therefore, B7H4 is a biomarker of poor prognosis in CRC patients, and interference with the IFN-γ/IRF1/B7H4 axis might be a novel immunotherapeutic method to restore the cytotoxic killing of CRC cells.

A modified method for isolation of bladder cancer stem cells from a MB49 murine cell line.

BACKGROUND: The vaccine was efficiently effective against bladder cancer in earlier studies. However, a part of the mouse bladder tumour regrew due to regression after a period of time as the cancer stem cells could not be eliminated. In this study, we showed a modified method for the isolation of MB49 bladder cancer stem cells (MCSCs). METHODS: Through a comparison of different serum-free culture mediums (SFM), MCSCs were isolated by a combination of the limited dilution method and the optimal SFM method. The characterizations of MCSCs were verified by the fluorescence activated cell sorting, the quantitative polymerase chain reaction, the western blotting, the cell proliferation assay, the soft agar assay, the transwell assay, the resistance to chemotherapy assay and the tumor xenograft formation assay. RESULTS: The optimal SFM contained a RPMI1640+ epidermal growth factor (20 ng/ml), a basic fibroblast growth factor (20 ng/ml), a leukemia inhibitory factor (20 ng/ml), a B-27 serum-free supplement (20 µl/ml), and a bovine serum albumin (4 µg/ml). MCSCs possessed the high expression of cancer stem cell markers (CD133, CD44, OCT4, NANOG, and ABCG2) and the ability of differentiation. In functional comparisons, MCSCs had higher proliferative abilities, lower susceptibility to chemotherapy, greater migration in vitro, and stronger tumorigenic abilities in vivo. CONCLUSION: MCSCs displayed specific cancer stem cells properties. Our study showed MCSCs were isolated successfully with a modified method using a combination of limited dilution and SFM methods.

Perfusion heterogeneity in breast tumors for assessment of angiogenesis.

OBJECTIVES: The purpose of this study was to investigate the perfusion heterogeneity of malignant and benign breast tumors and assay their vascular architecture changes and molecular expression, thereby evaluating the relevance between imaging and histologic characteristics of angiogenesis. METHODS: Real-time grayscale contrast-enhanced sonography was performed in 310 women with 317 breast tumors. The enhancement patterns and perfusion parameters for malignant and benign tumors were analyzed by contrast-enhanced sonography with microvascular imaging and quantitative time-intensity curve analysis. Structural characteristics were observed by light and electron microscopy. The microvessel density, vascular endothelial growth factor (VEGF) expression, and human kinase insert domain-containing receptor (KDR) expression for all tumors were assessed by immunohistochemical staining of CD31, KDR, and VEGF. RESULTS: Surgical pathologic analysis showed 163 malignant and 154 benign tumors. Significant morphologic differences, including perfusion defects, vessel distortion, vessel dilatation, and heterogeneous enhancement, were observed between the malignant and benign groups (P < .05). The mean perfusion parameters (peak intensity, ascending slope, area under the curve, and wash-out time) were greater in the malignant tumors (P < .05). There were significant differences in the peak intensity, ascending slope, area under the curve, and wash-out time between peripheral and central regions of the malignant tumors (P < .05) but none in the benign tumors. Vessels had various morphologic and distributional characteristics in the peripheral and central regions of the malignant tumors. The microvessel density and VEGF and KDR expression were significantly higher in the malignant group (P < .05), especially in the peripheral regions. CONCLUSIONS: Perfusion heterogeneity was closely associated with the tumor microvascular architecture and molecular expression. Perfusion features, especially regional morphologic and hemodynamic features, can provide valuable information for differentiating malignant from benign breast tumors.

Orientation Cues-Aware Facial Relationship Representation for Head Pose Estimation via Transformer.

Head pose estimation (HPE) is an indispensable upstream task in the fields of human-machine interaction, self-driving, and attention detection. However, practical head pose applications suffer from several challenges, such as severe occlusion, low illumination, and extreme orientations. To address these challenges, we identify three cues from head images, namely, critical minority relationships, neighborhood orientation relationships, and significant facial changes. On the basis of the three cues, two key insights on head poses are revealed: 1) intra-orientation relationship and 2) cross-orientation relationship. To leverage two key insights above, a novel relationship-driven method is proposed based on the Transformer architecture, in which facial and orientation relationships can be learned. Specifically, we design several orientation tokens to explicitly encode basic orientation regions. Besides, a novel token guide multi-loss function is accordingly designed to guide the orientation tokens as they learn the desired regional similarities and relationships. Experimental results on three challenging benchmark HPE datasets show that our proposed TokenHPE achieves state-of-the-art performance. Moreover, qualitative visualizations are provided to verify the effectiveness of the token-learning methodology.

FMNL2 is a positive regulator of cell motility and metastasis in colorectal carcinoma.

FMNL2 is a member of diaphanous-related formins which act as effectors of Rho family GTPases and control the actin-dependent processes such as cell motility or invasion. We previously found that FMNL2 overexpression in metastatic cell lines and tissues of colorectal carcinoma is associated with more aggressive tumour behaviour. Here we used gain-of-function and loss-of-function approaches to investigate the effects of FMNL2 on colorectal carcinoma in vitro and in vivo. Forced expression of FMNL2 caused a significant increase in tumour cell proliferation, motility, invasion in vitro, and metastasis in vivo, whereas FMNL2 depletion showed opposite effects. We examined gene expression profiles following knockdown of FMNL2 in SW480/M5 cells. Expression of 323 genes was up-regulated by more than two-fold, whereas 222 genes were down-regulated by more than two-fold in FMNL2-depleting SW480/M5 cells. Gene ontology analysis showed that most of genes belong to functional categories such as cell cycle, cytoskeleton, transcription factor, and G-protein modulator. Pathway analysis revealed that cytoskeletal regulation by the Rho GTPase pathway, the Wnt pathway, the G-protein pathway, and the P53 pathway were affected by FMNL2. Many of these genes are in functional networks associated with cell proliferation, metastasis, Wnt or the Rho signalling pathway involved in the regulation of FMNL2. The expression of five differentially expressed genes including CXXC4, CD200, VAV1, CSF1, and EPHA2 was validated by real-time PCR and western blot analysis. Thus, FMNL2 is a positive regulator of cell motility, invasion, and metastasis of colorectal carcinoma.

[Infantile DiGeorge syndrome: autopsy diagnosis and clinicopathologic analysis in 5 cases].

OBJECTIVE: To investigate clinicopathological features of DiGeorge syndrome (DGS). METHOD: The clinical features, histological and immunohistochemical findings were analyzed in 5 cases of DGS by autopsy. RESULTS: Five cases of DGS in male infants aged 4 days, 1 month, 7 months, 10 months, and 13 months respectively. Gross and microscopic observations revealed that thymic cortex was depleted of lymphocytes or showed few, dispersed lymphocytes. The thymic medulla showed predominantly epithelial cells with calcified Hassall bodies as well as lymphocyte depletion. T lymphocytes were also scarce in the tonsils, lymph nodes, spleen, and mucosa-associated lymphatic tissue of ileum. In addition, 3 of the 5 patients also showed parathyroid aplasia or dysplasia, and congenital hypertrophy of the ventricular septum. CONCLUSIONS: The pathological changes indicate that clinicians should be aware of defects of immune system if the infants suffer from severe infections. Pathologists should recognize the importance of abnormalities of lymphohematopoietic tissues in the diagnosis of primary immunodeficiency diseases such as DGS.

Thymic hypoplasia induced by copy number variations contributed to explaining sudden infant death based on forensic autopsies.

Thymic hypoplasia is a primary cellular immunodeficiency that causes susceptibility to serious infections leading to sudden death in infants. Some genetic disorders in humans could result in the evident permanent hypoplasia or occasional aplasia of the thymus at birth. However, determining the genetic etiology of thymic hypoplasia is challenging for the sudden infant death due to primary cellular immunodeficiency. In this study, in order to find the fundamental reasons for sudden death of infants with thymic hypoplasia, 5 infants with suspected thymic hypoplasia and 10 control infants were assessed, and the immunohistochemistry and DNA analysis were used to investigate whether the infants with thymic hypoplasia had DiGeorge syndrome (DGS) with copy number variations (CNVs) in 22q11.2 and other chromosomes. The results showed that the weight of the thymus was significantly lower than the normal except the case 4, and that all the infants had hypocalcemia and a significant decrease or even absence of the markers CD1a, CD2, CD3, CD4 and CD8, which are related to T-cell maturation. In addition, multiplex ligation-dependent probe amplification (MLPA) analysis showed that these infants carried CNVs in 22q11.2 and other associated chromosomes with deletion and duplication of 25 genes. The results of thymus weight, histopathology, molecular pathology and MLPA analysis suggested that DGS predominantly with thymic hypoplasia induced by CNVs caused the sudden death of these infants under various infections or other unexplained reasons, which may provide new insights into the diagnosis of sudden infant death and could help the parents of deceased infants to attach more importance of genetic screening and thymus ultrasound to reduce the postnatal mortality of the infant, and demonstrates the value of genetic diagnosis in the forensic pathology.

Promotion of colorectal cancer growth and metastasis by the LIM and SH3 domain protein 1.

BACKGROUND: LIM and SH3 protein 1 (LASP-1), initially identified from a cDNA library of metastatic axillary lymph nodes of breast cancer patients, is a specific focal adhesion protein involved in numerous biological and pathological processes. The overexpression of LASP-1 has been described in several types of cancers, but the role of LASP-1 in colorectal cancer (CRC) is unknown. In a previous study, comparative proteomic analysis was performed and LASP-1 was identified as a CRC-associated protein in those patients with CRC. METHODS: Using immunohistochemistry, we analysed LASP-1 protein expression in 126 clinicopathologically characterised CRC cases. Using gene transfection and RNA interference, we investigated the effects of LASP-1 overexpression and depletion on tumor cellular behavior in vitro and in vivo. Using 2-D DIGE, we analysed the effect of the presence and absence of LASP-1 gene on protein expression profiles of CRC cells. RESULTS: Overexpression of LASP-1 was found in metastatic CRC tissues (p=0.002), and its expression level was closely correlated with overall survival of patients with CRC (p=0.002). RNA interference-mediated silencing of the LASP-1 gene in SW620 CRC cells inhibited cell proliferation and migration significantly. However, gene transfection-mediated overexpression of LASP-1 in SW480 CRC cells resulted in aggressive phenotypes of cancer cells and promoted cancer growth and metastasis. Furthermore, both overexpression and silencing of the LASP-1 gene caused a very similar protein expression pattern in different CRC cell lines. The identified LASP-1-modulated proteins, including some key cellular molecules, were involved in various biological processes. CONCLUSIONS: The results show that LASP-1 might be a promising target in the treatment of patients with CRC with growth and metastasis of CRC.

Learning From Images: A Distillation Learning Framework for Event Cameras.

Event cameras have recently drawn massive attention in the computer vision community because of their low power consumption and high response speed. These cameras produce sparse and non-uniform spatiotemporal representations of a scene. These characteristics of representations make it difficult for event-based models to extract discriminative cues (such as textures and geometric relationships). Consequently, event-based methods usually perform poorly compared to their conventional image counterparts. Considering that traditional images and event signals share considerable visual information, this paper aims to improve the feature extraction ability of event-based models by using knowledge distilled from the image domain to additionally provide explicit feature-level supervision for the learning of event data. Specifically, we propose a simple yet effective distillation learning framework, including multi-level customized knowledge distillation constraints. Our framework can significantly boost the feature extraction process for event data and is applicable to various downstream tasks. We evaluate our framework on high-level and low-level tasks, i.e., object classification and optical flow prediction. Experimental results show that our framework can effectively improve the performance of event-based models on both tasks by a large margin. Furthermore, we present a 10K dataset (CEP-DVS) for event-based object classification. This dataset consists of samples recorded under random motion trajectories that can better evaluate the motion robustness of the event-based model and is compatible with multi-modality vision tasks.

RGBD Salient Object Detection via Disentangled Cross-modal Fusion.

Depth is beneficial for salient object detection (SOD) for its additional saliency cues. Existing RGBD SOD methods focus on tailoring complicated cross-modal fusion topologies, which although achieve encouraging performance, are with a high risk of over-fitting and ambiguous in studying cross-modal complementarity. Different from these conventional approaches combining cross-modal features entirely without differentiating, we concentrate our attention on decoupling the diverse cross-modal complements to simplify the fusion process and enhance the fusion sufficiency. We argue that if cross-modal heterogeneous representations can be disentangled explicitly, the cross-modal fusion process can hold less uncertainty, while enjoying better adaptability. To this end, we design a disentangled cross-modal fusion network to expose structural and content representations from both modalities by cross-modal reconstruction. For different scenes, the disentangled representations allow the fusion module to easily identify, and incorporate desired complements for informative multi-modal fusion. Extensive experiments show the effectiveness of our designs and a large outperformance over state-of-the-art methods.

Regulatory T-cell expansion in oral and maxillofacial Langerhans cell histiocytosis.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare myeloid-origin neoplasm characterized by the expansion and dissemination of CD1 a+/CD207+ dendritic cells (LCH cells), but the rarity of its occurrence has long impeded progress in understanding its pathology. We focus on the potentially important role that regulatory T cells (T-reg) play in the oral and maxillofacial LCH tumor microenvironment (TME). STUDY DESIGN: Nine cases of oral and maxillofacial LCH, diagnosed from 2009 to 2019, were collected retrospectively from the affiliated hospitals of Southern Medical University. Immunohistochemistry was conducted characterizing T cells and T-reg phenotype. Data were evaluated by 1-sample Wilcoxon's test. RESULTS: Significantly increased frequency and abnormal distributions of T-reg were identified in all the LCH lesion sections. Proliferating T-reg account for a mean average of 11.5% of the total T-cell subsets, with significant difference (Wilcoxon's test; P < .05). CONCLUSIONS: T-reg expansion in the localized inflammatory TME leads to a failure of immune regulation by suppressing antitumor response, which can be a latent and significant factor contributing to LCH progression. However, T-reg may also acquire the capability for aiding in initiating T-cell responses under the "cytokine storm" at the beginning of LCH onset. T-reg might contribute to the augmentation of tissue repair by transforming growth factor-ß (TGF-ß), explaining the self-limiting character of LCH.

Modulating microbiota metabolism via bioaugmentation with Lactobacillus casei and Acetobacter pasteurianus to enhance acetoin accumulation during cereal vinegar fermentation.

Acetoin, giving a creamy yogurt aroma and buttery taste, exists in cereal vinegar as an important flavor substance and is mainly produced by the metabolism of Lactobacillus and Acetobacter during multispecies solid-state acetic acid fermentation. However, the impacts of Lactobacillus-Acetobacter interactions on acetoin accumulation and the microbial metabolism during acetic acid fermentation are not completely clear. Here, six strains isolated from vinegar fermentation culture and associated with acetoin metabolism, namely, Lactobacillus reuteri L-0, L. buchneri F2-6, L. brevis 4-20, L. fermentum M10-7, L. casei M1-6 and Acetobacter pasteurianus G3-2, were selected for microbial growth and metabolism analysis in monoculture and coculture fermentations. Lactobacillus sp. and A. pasteurianus G3-2 respectively utilized glucose and ethanol preferentially. In monocultures, L. casei M1-6 (183.7 mg/L) and A. pasteurianus G3-2 (121.0 mg/L) showed better acetoin-producing capacity than the others. In the bicultures with Lactobacillus sp. and A. pasteurianus G3-2, biomass analysis in the stationary phase demonstrated that significant growth depressions of Lactobacillus sp. occurred compared with monocultures, possibly due to intolerance to acetic acid produced by A. pasteurianus G3-2. Synergistic effect between Lactobacillus sp. and A. pasteurianus G3-2 on enhanced acetoin accumulation was identified, however, cocultures of two Lactobacillus strains could not apparently facilitate acetoin accumulation. Coculture of L. casei M1-6 and A. pasteurianus G3-2 showed the best performance in acetoin production amongst all mono-, bi- and triculture combinations, and the yield of acetoin increased from 1827.7 to 7529.8 mg/L following optimization of culture conditions. Moreover, the interactions of L. casei M1-6 and A. pasteurianus G3-2 regulated the global metabolism of vinegar microbiota during fermentation through performing in situ bioaugmentation, which could accelerate the production of acetic acid, lactic acid, acetoin, ethyl acetate, ethyl lactate, ligustrazine and other important flavoring substances. This work provides a promising strategy for the production of acetoin-rich vinegar through Lactobacillus sp.-A. pasteurianus joint bioaugmentation.

Cdc42 subcellular relocation in response to VEGF/NRP1 engagement is associated with the poor prognosis of colorectal cancer.

Microscopic indications of malignancy and hallmark molecules of cancer are pivotal to determining cancer patient prognosis and subsequent medical intervention. Here, we found that compared to apical expression of Cdc42, which indicated that basal expression of Cdc42 occurred at the migrating cell front, glandular basal expression of Cdc42 (cell division cycle 42) in tissues indicated poorer prognoses for colorectal cancer (CRC) patients. The current study shows that activated Cdc42 was rapidly recruited to the migrating CRC cell front after VEGF stimulation through engagement of membrane-anchored neuropilin-1 (NRP1). When VEGF signalling was blocked with NRP1 knockdown or ATWLPPR (A7R, antagonist of VEGF/NRP1 interaction), Cdc42 activation and relocation to the cell front was attenuated, and filopodia and invadopodia formation was inhibited. The VEGF/NRP1 axis regulates directional migration, invasion, and metastasis through Cdc42 activation and relocation resulting from actin filament polymerisation of the extensions of membrane protrusions. Collectively, the immuno-micromorphological pattern of subcellular Cdc42 at the cell front indicated aggressive behaviours and predicted poor prognosis in CRC patients. Disruption of the intra- and extracellular interactions of the VEGF/NRP1 axis or Cdc42 relocation could be performed in clinical practice because it might inhibit cancer cell motility and metastasis.

Transgelin as a suppressor is associated with poor prognosis in colorectal carcinoma patients.

We performed comparative proteomic analysis of colorectal cancer to investigate potential target proteins correlated with carcinogenesis and prognosis. Among them, transgelin, a 22 kDa protein also called SM22, was identified as a novel tumor suppressor protein, but little is known about this protein in tumors so far. A remarkable reduced expression of transgelin was found in colorectal cancer samples compared with normal colorectal mucosa. The effect of 5-aza-2'-deoxycytidine as a demethylation agent would obviously restore the original expression level of transgelin, implicating DNA hypermethylation of transgelin is important in the regulation of transgelin transcription in colorectal cancer. As a control, the investigation at cell line level confirms that transgelin protein comes from epithelium but not mesenchymal cells. Further, immunohistochemical staining for transgelin was performed on paraffin sections of 62 and 126 cases of normal colorectal mucosa and colorectal cancer specimens, respectively. As compared to normal colorectal tissue, we observed a significantly lower transgelin expression in colorectal cancer samples (P<0.001). Survival analysis demonstrated that patients without transgelin expression had shorter overall survival, whereas patients with transgelin expression had better survival (P=0.006). Multivariate analysis showed that negative transgelin expression was an independent prognostic indicator for patient's survival. Our results suggest that transgelin as a suppressor may serve as important biomarker of malignancy. Loss of transgelin involves gene promoter hypermethylation and is closely associated with poor overall survival in colorectal cancer patients.

Treatment of perianal Paget's disease using photodynamic therapy with assistance of fluorescence examination: case report.

Our aim was to determine the usefulness of fluorescence examination and photodynamic therapy (PDT) for the management of perianal extramammary Paget's disease. A 75-year-old woman underwent two courses of PDT. The first treatment was carried out with topically applied 5-aminolevulinic acid (ALA) to the affected area (2.5 x 2.5 cm(2)) 3 h before light treatment. We used ALA/protoporphyrin IX (PpIX)-mediated fluorescence to visualize the lesion and its margins. The lesion was treated with a 630 nm laser at 120 J/cm(2). Forty days later, the residual lesion was given a second treatment at the same light dose after topical application of ALA and intravenous injection of HiPorfin. ALA/PpIX-mediated fluorescence served as a useful tool to visualize the lesion's location. Complete cure was achieved after the second course of PDT. During 7 months of follow up, no recurrence, scarring or functional loss was noticed. We concluded that ALA-assisted fluorescence examination can be a useful tool to determine the lesion and its margins. ALA-PDT is effective for superficial lesions, but, for thicker and deeper lesions, the systemic administration of photosensitizer is needed.

[Evaluation of angiogenesis in the tumorigenesis and progression of breast cancer].

OBJECTIVES: To investigate the expression of CD34, vascular endothelial growth factor (VEGF) and its receptor Flk-1/KDR in precancerous lesion, atypical hyperplasia (AH) and infiltrating carcinoma of breast cancer and to explore the correlation between angiogenesis abnormality and the tumor progression. METHODS: One hundred and sixty cases of resected tissues from breast cancer patients were enrolled in the study and were divided into 5 groups: 30 cases as normal controls, 30 cases with simple hyperplasia, 30 cases with AH, 20 cases with intraductal carcinoma in situ and 50 cases with infiltrating ductal carcinoma. The expression of CD34, VEGF and its receptor, Flk-1/KDR in those tissues were determined with immunohistochemical techniques. The micro vascular density (MVD) in those tissues was determined with the expression of CD34. RESULTS: The expression level of CD34, VEGF and Flk-1/KDR were different among the groups, with the highest expression in the infiltrating ductal carcinoma group. With the progression of breast cancer, the major indexes showed no significant changes in the early stage of progression, but the expression of VEGF and Flk-1/KDR increased significantly from AH stage. Meanwhile, the MVD increased in the same way. There was significant difference between AH and intraductal carcinoma group in the expression of VEGF and Flk-1/KDR (P<0.05), but not in the MVD (P>0.05). CONCLUSIONS: Abnormality in angiogenesis may be an early event in the tumorigenesis of breast cancer. Abnormal expression of VEGF and Flk-1/KDR may be the initiating factor of angiogenesis in the process of breast hyperplasia-AH-breast cancer, it could be the molecular target of early diagnosis and treatment.