APNet: Adaptive projection network for medical image denoising.

BACKGROUND: In clinical medicine, low-dose radiographic image noise reduces the quality of the detected image features and may have a negative impact on disease diagnosis. OBJECTIVE: In this study, Adaptive Projection Network (APNet) is proposed to reduce noise from low-dose medical images. METHODS: APNet is developed based on an architecture of the U-shaped network to capture multi-scale data and achieve end-to-end image denoising. To adaptively calibrate important features during information transmission, a residual block of the dual attention method throughout the encoding and decoding phases is integrated. A non-local attention module to separate the noise and texture of the image details by using image adaptive projection during the feature fusion. RESULTS: To verify the effectiveness of APNet, experiments on lung CT images with synthetic noise are performed, and the results demonstrate that the proposed approach outperforms recent methods in both quantitative index and visual quality. In addition, the denoising experiment on the dental CT image is also carried out and it verifies that the network has a certain generalization. CONCLUSIONS: The proposed APNet is an effective method that can reduce image noise and preserve the required image details in low-dose radiographic images.

Unveiling the Enhancement of Spontaneous Emission at Exceptional Points.

Exceptional points (EPs), singularities of non-Hermitian physics where complex spectral resonances degenerate, are one of the most exotic features of nonequilibrium open systems with unique properties. For instance, the emission rate of quantum emitters placed near resonators with EPs is enhanced (compared to the free-space emission rate) by a factor that scales quadratically with the resonance quality factor. Here, we verify the theory of spontaneous emission at EPs by measuring photoluminescence from photonic-crystal slabs that are embedded with a high-quantum-yield active material. While our experimental results verify the theoretically predicted enhancement, they also highlight the practical limitations on the enhancement due to material loss. Our designed structures can be used in applications that require enhanced and controlled emission, such as quantum sensing and imaging.

A blind medical image denoising method with noise generation network.

BACKGROUND: In the process of medical images acquisition, the unknown mixed noise will affect image quality. However, the existing denoising methods usually focus on the known noise distribution. OBJECTIVE: In order to remove the unknown real noise in low-dose CT images (LDCT), a two-step deep learning framework is proposed in this study, which is called Noisy Generation-Removal Network (NGRNet). METHODS: Firstly, the output results of L0 Gradient Minimization are used as the labels of a dental CT image dataset to form a pseudo-image pair with the real dental CT images, which are used to train the noise generation network to estimate real noise distribution. Then, for the lung CT images of the LIDC/IDRI database, we migrate the real noise to the noise-free lung CT images, to construct a new almost-real noisy images dataset. Since dental images and lung images are all CT images, this migration can be achieved. The denoising network is trained to realize the denoising of real LDCT for dental images by using this dataset but can extend for any low-dose CT images. RESULTS: To prove the effectiveness of our NGRNet, we conduct experiments on lung CT images with synthetic noise and tooth CT images with real noise. For synthetic noise image datasets, experimental results show that NGRNet is superior to existing denoising methods in terms of visual effect and exceeds 0.13dB in the peak signal-to-noise ratio (PSNR). For real noisy image datasets, the proposed method can achieve the best visual denoising effect. CONCLUSIONS: The proposed method can retain more details and achieve impressive denoising performance.

Melanoma Skin Cancer Detection Method Based on Adaptive Principal Curvature, Colour Normalisation and Feature Extraction with the ABCD Rule.

According to statistics of the American Cancer Society, in 2015, there are about 91,270 American adults diagnosed with melanoma of the skin. For the European Union, there are over 90,000 new cases of melanoma annually. Although melanoma only accounts for about 1% of all skin cancers, it causes most of the skin cancer deaths. Melanoma is considered one of the fastest-growing forms of skin cancer, and hence the early detection is crucial, as early detection is helpful and can provide strong recommendations for specific and suitable treatment regimens. In this work, we propose a method to detect melanoma skin cancer with automatic image processing techniques. Our method includes three stages: pre-process images of skin lesions by adaptive principal curvature, segment skin lesions by the colour normalisation and extract features by the ABCD rule. We provide experimental results of the proposed method on the publicly available International Skin Imaging Collaboration (ISIC) skin lesions dataset. The acquired results on melanoma skin cancer detection indicates that the proposed method has high accuracy, and overall, a good performance: for the segmentation stage, the accuracy, Dice, Jaccard scores are 96.6%, 93.9% and 88.7%, respectively; and for the melanoma detection stage, the accuracy is up to 100% for a selected subset of the ISIC dataset.

Regulation of somatostatin receptor 4-mediated cytostatic effects by CD26 in malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm arising from mesothelial lining of pleura. CD26 molecules preferentially expressed on epithelioid type of MPM. This study investigates the molecular mechanisms of CD26 regulating MPM cells in vitro and in vivo. METHODS: Biochemical and cell biological approaches were used for identifying a novel molecular target of MPM. Its contribution to tumour expansion has been also assessed using animal models. The clinical samples of MPM were also assessed for its expression. RESULTS: We identify that cytostatic effects in MPM are mediated by somatostatin (SST) receptor 4 (SSTR4), being inhibited by the interaction of CD26 molecules. We also indicates that SSTR4-mediated cytostatic effects are regulated by SHP-2 PTP, and that this inhibitory effect by SST agonist is enhanced via lipid raft clustering of associated molecules following crosslinking of anti-CD26 antibody. Finally, using an in vivo xenograft model, we demonstrate that the anti-tumour effect of anti-CD26 mAb is enhanced when combined with SSTR4 agonist treatment, and that SSTR4 is highly coexpressed with CD26 on epithelioid or biphasic types of MPM tissues obtained from patients' surgical specimens. CONCLUSIONS: Combination therapy with humanised anti-CD26 mAb and SSTR4 agonist may therefore potentiate anti-tumour effect on MPM.

Double enhanced residual network for biological image denoising.

With the achievements of deep learning, applications of deep convolutional neural networks for the image denoising problem have been widely studied. However, these methods are typically limited by GPU in terms of network layers and other aspects. This paper proposes a multi-level network that can efficiently utilize GPU memory, named Double Enhanced Residual Network (DERNet), for biological-image denoising. The network consists of two sub-networks, and U-Net inspires the basic structure. For each sub-network, the encoder-decoder hierarchical structure is used for down-scaling and up-scaling feature maps so that GPU can yield large receptive fields. In the encoder process, the convolution layers are used for down-sampling to obtain image information, and residual blocks are superimposed for preliminary feature extraction. In the operation of the decoder, transposed convolution layers have the capability to up-sampling and combine with the Residual Dense Instance Normalization (RDIN) block that we propose, extract deep features and restore image details. Finally, both qualitative experiments and visual effects demonstrate the effectiveness of our proposed algorithm.

Diagnosis of breast cancer based on modern mammography using hybrid transfer learning.

Breast cancer is a common cancer in women. Early detection of breast cancer in particular and cancer, in general, can considerably increase the survival rate of women, and it can be much more effective. This paper mainly focuses on the transfer learning process to detect breast cancer. Modified VGG (MVGG) is proposed and implemented on datasets of 2D and 3D images of mammograms. Experimental results showed that the proposed hybrid transfer learning model (a fusion of MVGG and ImageNet) provides an accuracy of 94.3%. On the other hand, only the proposed MVGG architecture provides an accuracy of 89.8%. So, it is precisely stated that the proposed hybrid pre-trained network outperforms other compared Convolutional Neural Networks. The proposed architecture can be considered as an effective tool for radiologists to decrease the false negative and false positive rates. Therefore, the efficiency of mammography analysis will be improved.

Human CD4 helper T cell activation: functional involvement of two distinct collagen receptors, 1F7 and VLA integrin family.

In the present study, we showed that activation of human CD4 T cells can be induced by anti-CD3 and collagen in a serum-free system. This activation was inhibited by the addition of peptides containing the RGD or Gly-Pro-X sequences. Significantly, we demonstrated that both the 1F7 (CD26) structure and the VLA integrin family, particularly the VLA-3 complex, contribute to the functional interaction between collagen and CD4 cells since anti-1F7 and anti-VLA-3 specifically inhibited this collagen-induced CD4 cell activation. Biochemical studies showed that the 1F7 structure is not a member of the VLA integrin family. These results thus indicated that two different families of antigens serve as functional collagen receptors for CD4 T cell activation.

CD26 expression on T cell lines increases SDF-1-alpha-mediated invasion.

BACKGROUND: CD26 is a multifunctional membrane-bound glycoprotein that regulates tumour growth in addition to its other activities. Because disease aggressiveness is correlated with CD26 expression in several T-cell malignancies, we decided to investigate the invasiveness of cells expressing different levels of CD26. METHODS: To assess CD26 involvement in cell invasion, we performed in vitro invasion assays with human T cell lines expressing different levels of CD26. These included the parental CD26-positive T-lymphoblast cell line HSB-2 and clones infected with a retrovirus expressing siRNA vectors that either targeted CD26 or encoded a missense siRNA, and the parental CD26-negative T-leukaemia cell line Jurkat and clones expressing CD26. CD26 expression in these cell lines was evaluated by flow cytometry and western immunoblotting. CXCR4 expression, phosphorylation of signalling kinases, and MMP-9 secretion were also evaluated by western immunoblotting, whereas MMP-9 activity and the effect of kinase and CD45 inhibitors on activity were measured by zymography of conditioned media. RESULTS: The presence of CD26 enhanced stromal-cell-derived factor-1-alpha (SDF-1-alpha)-mediated invasion of T cell lines. This process was regulated in part by the PI-3K and MEK1 pathways, as indicated by increased phosphorylation of p44/42 MAP kinase and Akt in the presence of SDF-1-alpha and the effect of their respective inhibitors on MMP-9 secretion and in vitro invasion. In addition, CD26-associated enhancement of SDF-1-alpha-induced invasion was decreased when CD45 was inhibited. CONCLUSIONS: Our results indicate that the expression of CD26 in T cell lines leads to increased SDF-1-alpha-mediated invasion in an in vitro system and that this is controlled in part by the PI-3K and MEK1 pathways. The data also suggest that CD26 enhancement of invasion may be mediated by CD45, however, more studies are required to confirm this involvement.

Hepatosplenic gamma-delta T-cell lymphoma: clinicopathological features and treatment.

BACKGROUND: Hepatosplenic T-cell lymphoma (HSTCL) is a rare peripheral T-cell lymphoma; treatment with standard anthracycline-containing chemotherapy regimens has been disappointing, and an optimal treatment strategy for this patient population has not yet been determined. METHODS: We identified 15 cases of pathologically confirmed HSTCL in the institution's database. Clinical characteristics and treatment results were reviewed. RESULTS: Complete responses (CRs) were achieved in 7 of 14 patients who received chemotherapy. Achievement of CR was followed by hematopoietic stem-cell transplantation in three patients. Median duration of CR was 8 months (range 2 to 32+ months) with four patients currently alive and in CR at 5, 8, 12, and 32 months, respectively. Median overall survival (OS) was 11 months (range 2 to 36+ months). Patients who achieved a CR had a median OS of 13 months, compared with 7.5 months in patients who did not achieve a CR. Risk factors associated with worse outcome included male gender, failure to achieve a CR, history of immunocompromise, and absence of a T-cell receptor gene rearrangement in the gamma chain. CONCLUSION: A better understanding of the pathophysiology of HSTCL and new therapeutic strategies are needed.

Histamine H1-receptor antagonists with immunomodulating activities: potential use for modulating T helper type 1 (Th1)/Th2 cytokine imbalance and inflammatory responses in allergic diseases.

Being a first-line treatment for hypersensitivity allergic disease, histamine H1-receptor antagonists possess anti-inflammatory activity in addition to being H1-receptor antagonists. While it is not purely a histamine-related condition, hypersensitivity allergic disease is associated with an increase in the number of T helper type 2 (Th2) cells and Th2 cytokines, and a decrease in the number of Th1 cells and Th1 cytokines. Suppression of Th2-type cytokine production in addition to H1-receptor blockade may therefore represent a successful therapeutic strategy for the treatment of hypersensitivity allergic diseases. H1-receptor antagonists have been reported to modulate immune cascade at various points by acting on T cell-related inflammatory molecules, including adhesion molecules, chemokines and inflammatory cytokines. These effects of H1-receptor antagonists may be optimized for the treatment of allergic diseases. Besides their ability to regulate inflammatory molecules, some H1-receptor antagonists have been reported to down-regulate Th2 cytokine production. In particular, it has been shown that several H1-receptor antagonists specifically inhibit the production of Th2, but not Th1, cytokines. Accumulating evidence indicates a crucial role for Th1/Th2 cytokine imbalance on the development of allergic diseases. Accordingly, the use of H1-receptor antagonist with Th2 cytokine inhibitory activity to modulate Th1/Th2 cytokine imbalance might be a favourable strategy for the treatment of hypersensitivity allergic diseases. Furthermore, the identification of H1-receptor antagonists which possess immunoregulatory activities in addition to their anti-histamine activity will provide an important insight into the development of novel immunoregulatory drugs.

Crk-associated substrate lymphocyte type regulates transforming growth factor-beta signaling by inhibiting Smad6 and Smad7.

Crk-associated substrate lymphocyte type (Cas-L) is a 105 kDa docking protein with diverse functional properties, including regulation of cell division, proliferation, migration and adhesion. Cas-L is also involved in beta1 integrin- or antigen receptor-mediated signaling in B and T cells. In the present study, we demonstrate that Cas-L potentiates transforming growth factor-beta (TGF-beta) signaling pathway by interacting with Smad6 and Smad7. Immunoprecipitation experiments reveal that single domain deletion of full-length Cas-L completely abolishes its docking function with Smad6 and Smad7, suggesting that the natural structure of Cas-L is necessary for its association with Smad6 and Smad7. On the other hand, both N-terminal and C-terminal deletion mutants of Smad6 and Smad7 still retain their docking ability to Cas-L, suggesting that Smad6 and Smad7 possess several binding motifs to Cas-L. Moreover, Cas-L interaction with Mad-homology (MH)2 domain, but not with MH1 domain of Smad6 or Smad7, ameliorates TGF-beta-induced signaling pathway. Finally, depletion of Cas-L by small-interfering RNA oligo attenuates TGF-beta-induced growth inhibition of Huh-7 cells, with a concomitant reduction in phosphorylation of Smad2 and Smad3. These results strongly suggest that Cas-L is a potential regulator of TGF-beta signaling pathway.

Expression of CD26 and its associated dipeptidyl peptidase IV enzyme activity enhances sensitivity to doxorubicin-induced cell cycle arrest at the G(2)/M checkpoint.

CD26, a M(r) 110,000 surface-bound ectopeptidase with dipeptidyl peptidase IV (DPPIV) activity, has an array of diverse functional properties, with a role in T-cell physiology and the development of certain human cancers. In this study, we report that surface expression of CD26, through its associated DPPIV enzyme activity, enhanced sensitivity of Jurkat T-cell transfectants to G(2)-M arrest induced by the chemotherapeutic drug, doxorubicin. This was associated with disruption of cell cycle-related events, including hyperphosphorylation and inhibition of p34(cdc2) kinase activity, phosphorylation of cdc25C, and alteration in cyclin B1 expression. In addition, we demonstrate that the addition of exogenous soluble DPPIV enhanced sensitivity of lymphoid tumor cell lines to doxorubicin, suggesting a potentially useful clinical role for CD26/DPPIV in the treatment of selected human hematological malignancies.

Glioma invasion mediated by the p75 neurotrophin receptor (p75(NTR)/CD271) requires regulated interaction with PDLIM1.

The invasive nature of glioblastoma renders them incurable by current therapeutic interventions. Using a novel invasive human glioma model, we previously identified the neurotrophin receptor p75(NTR) (aka CD271) as a mediator of glioma invasion. Herein, we provide evidence that preventing phosphorylation of p75(NTR) on S303 by pharmacological inhibition of PKA, or by a mutational strategy (S303G), cripples p75(NTR)-mediated glioma invasion resulting in serine phosphorylation within the C-terminal PDZ-binding motif (SPV) of p75(NTR). Consistent with this, deletion (ΔSPV) or mutation (SPM) of the PDZ motif results in abrogation of p75(NTR)-mediated invasion. Using a peptide-based strategy, we identified PDLIM1 as a novel signaling adaptor for p75(NTR) and provide the first evidence for a regulated interaction via S425 phosphorylation. Importantly, PDLIM1 was shown to interact with p75(NTR) in highly invasive patient-derived glioma stem cells/tumor-initiating cells and shRNA knockdown of PDLIM1 in vitro and in vivo results in complete ablation of p75(NTR)-mediated invasion. Collectively, these data demonstrate a requirement for a regulated interaction of p75(NTR) with PDLIM1 and suggest that targeting either the PDZ domain interactions and/or the phosphorylation of p75(NTR) by PKA could provide therapeutic strategies for patients with glioblastoma.

In vitro and in vivo antitumor effect of the anti-CD26 monoclonal antibody 1F7 on human CD30+ anaplastic large cell T-cell lymphoma Karpas 299.

CD26 is a M(r) 110,000 surface glycoprotein with diverse functional properties, including having a potentially significant role in tumor development, and antibodies to CD26 mediate pleomorphic cellular functions. In this report, we show that binding of soluble anti-CD26 monoclonal Ab 1F7 inhibits the growth of the human CD30+ anaplastic large cell T-cell lymphoma cell line Karpas 299 in both in vitro and in vivo experiments. In vitro experiments show that 1F7 induces cell cycle arrest at the G1-S checkpoint, associated with enhanced p21 expression that is dependent on de novo protein synthesis. Furthermore, experiments with a severe combined immunodeficient mouse tumor model demonstrate that 1F7 treatment significantly enhances survival of tumor-bearing mice by inhibiting tumor formation. Our data therefore suggest that anti-CD26 treatment may have potential clinical use for CD26+ hematological malignancies.

Biochemical characterization of CD26 (dipeptidyl peptidase IV): functional comparison of distinct epitopes recognized by various anti-CD26 monoclonal antibodies.

In this paper, we performed further biochemical characterization of the CD26 antigen, as defined by the mAbs in anti-1F7 and anti-Ta1, in order to clarify the observed functional differences among these mAbs. For this purpose, we developed a mAb, anti-5F8, which recognizes yet another epitope on the CD26 antigen different from that recognized by anti-1F7 and anti-Ta1 and compared their respective effect on T cell activation as well as the structures recognized by these mAbs. Functionally, anti-5F8 did not exhibit a comitogenic effect on T cell activation via the CD3 and CD2 pathways. Peptide mapping studies suggested that the 110 kDa molecules precipitated by these mAbs are identical. We showed that the 110 kDa CD26 structure on human T cells is composed of a family of heterogeneous molecules, as determined by isoelectric focusing studies. In addition, we demonstrated that the CD26 antigen has a DPPIV enzyme activity and this enzyme activity is found only on the principal basic structure of CD26 but not on the additional acidic structures. Biochemical studies also revealed that these mAbs recognized distinct epitopes on the CD26 antigen. Pulse-chase studies showed the the 1F7 epitope was found on both the immature (100 kDa) and mature (110 kDa) forms of the CD26 antigen. On the other hand, the Ta1 and 5F8 epitopes were expressed mainly on the mature form of the CD26 antigen. Moreover, anti-IF7 consistently precipitated an additional 43 kDa molecule in association with the principal 110 kDa molecule. Taken together, these data suggested that the additional 43 kDa structure or the distinct epitope recognized by anti-IF7 may play a role in human T cell activation via the CD3 and CD2 pathways.

Safety of fludarabine, mitoxantrone, and dexamethasone combined with rituximab in the treatment of stage IV indolent lymphoma.

Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA) is an effective agent for the treatment of CD20-positive B-cell lymphomas. Because its toxicities are minimal and do not overlap with the toxicities of standard chemotherapy, it is an appealing agent to use in combination with chemotherapy. Moreover, there is evidence for synergy between rituximab and some chemotherapeutic agents. The combination of fludarabine/ mitoxantrone/dexamethasone (FND) has been a well-tolerated and effective regimen for the treatment of indolent lymphomas. When given together with prophylaxis for Pneumocystis carinii, infectious complications with FND have been modest. We report on preliminary safety data using FND in conjunction with rituximab, along with maintenance alpha interferon. Toxicity has been modest. The concurrent use of rituximab with FND modestly increases neutropenia, but has not resulted in any change in the pattern of infectious or other toxicity that occurs with FND alone.

Absence of CD26 expression is a useful marker for diagnosis of T-cell lymphoma in peripheral blood.

We report flow cytometric characterization of surface CD26 expression in 271 peripheral blood samples from 154 patients evaluated for the presence of a T-cell lymphoproliferative disorder, primarily mycosis fungoides/Sézary syndrome (MF/SS). The presence of morphologically identifiable tumor cells on peripheral blood smears was the criterion for lymphomatous involvement. In 66 of 69 samples from 28 patients, we identified an abnormal CD26-/dim T-cell population that was distinct from the variable CD26 expression seen in normal peripheral blood T cells. This population was CD26- in 23 patients and weakly CD26+ in 5 patients. CD7 was more variably expressed in MF/SS tumor cells, allowing recognition of a distinct, quantifiable abnormal T-cell population in only 34 of 69 involved samples. An increased CD4/CD8 ratio and lower surface expression of CD4 in tumor cells also helped separate the CD26-/dim atypical population for quantification. In 35 blood samples from other types of T-cell tumors, tumor cells in 10 of 11 morphologically involved cases showed absent/dim CD26. Although capable of detecting abnormalities in most cases of MF/SS, CD7 expression does not provide as clear a separation of the neoplastic population and can be replaced by CD26 staining in routine peripheral blood flow cytometric screening of MF/SS patients.

CD26/dipeptidyl peptidase IV and its role in cancer.

CD26/Dipeptidyl Peptidase IV (DPPIV) is a 110-kDa glycoprotein that is expressed on numerous cell types and has multiple biological functions. A key facet of CD26/DPPIV biology is its enzymatic activity and its physical and functional interaction with other molecules. The substrates of CD26/DPPIV are proline-containing peptides and include growth factors, chemokines, neuropeptides, and vasoactive peptides. DPPIV plays an important role in immune regulation, signal transduction, and apoptosis. Furthermore, CD26 appears to play an important role in tumor progression. In the present review, we summarize key aspects of CD26/DPPIV involvement in tumor biology and its potential role in cancer development and behavior.

CD26: an expanding role in immune regulation and cancer.

In this review, we highlight major aspects of the biology of CD26, a dipeptidyl peptidase IV (DPPIV)-containing surface glycoprotein with multiple functions. In particular, we discuss findings demonstrating that CD26/DPPIV has an essential role in immune regulation as a T cell activation molecule and a regulator of chemokine function. We also review recent studies that identify key cellular molecules that physically associate with CD26 and the potential consequences of their interaction, including those with clinically-related implications. Furthermore, we present work suggesting a role for CD26 in the pathogenesis and behavior of selected human cancers, both solid tumors and hematological malignancies. We present recent studies that investigate the potential role of CD26 as a molecular target for novel treatment modalities for T cell lymphoid malignancies and possibly other hematological malignancies, with work involving the use of anti-CD26 monoclonal antibody, CD26-transfected cells as well as soluble CD26 molecules.