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Crosstalk between gut microbiota and pineal hormones and its impact on CRC pathobiology is addressed from a race-specific perspective. Lastly, the status of melatonin-focused CRC treatments, the need to better understand the perturbed melatonin signaling, and the potential of pineal hormone-directed therapeutic interventions to reduce CRC-associated disparity are discussed.A novel peptide that interferes with the PD-1/PD-L1 immune checkpoint pathway, termed PD-L1 inhibitory peptide 3 (PD-L1ip3), was computationally designed, experimentally validated for its specific binding to PD-L1, and evaluated for its antitumor effects in cell culture and in a mouse colon carcinoma syngeneic murine model. In several cell culture studies, direct treatment with PD-L1ip3, but not a similar peptide with a scrambled sequence, substantially increased death of CT26 colon carcinoma cells when co-cultured with murine CD8+ T cells primed by CT26 cell antigens. In a syngeneic mouse tumor model, the growth of CT26 tumor cells transduced with the PD-L1ip3 gene by an adenovirus vector was significantly slower than that of un-transduced CT26 cells in immunocompetent mice. This tumor growth attenuation was further enhanced by the coadministration of the peptide form of PD-L1ip3 (10 mg/kg/day). The current study suggests that this peptide can stimulate host antitumor immunity via blockade of the PD-1/PD-L1 pathway, thereby increasing CD8+ T cell-induced death of colon carcinoma cells. The tumor site-specific inhibition of PD-L1 by an adenovirus carrying the PD-L1ip3 gene, together with direct peptide treatment, may be used as a local immune checkpoint blockade therapy to inhibit colon carcinoma growth.
The prevalence of depression in oncological patients is 3, 4-fold compared to the general population. However, the specific risk factors for these prevalence rates are not fully understood.
A systematic literature review was conducted in nine electronic databases between 2005 and 2020. The quality of the eligible studies was appraised by two persons using the adapted 11-items Downs and Black checklist.
Among 2010 potentially relevant articles, 40 studies were eligible, with 27 studies of high quality and 13 studies of moderate quality. A total of 156 factors associated with depression were identified which were clustered into somatic, psychological, social and sociodemographic factors. Pre-existing depression and personality factors were the most consistent associated factors with depression in cancer patients, while for most somatic and treatment-related factors only modest associations were found.
Grouped as bio-psycho-social associated factors, somatic factors showed a modest influence, whereas social relationship (support) and previous depression are unequivocally significantly associated with depression.
Grouped as bio-psycho-social associated factors, somatic factors showed a modest influence, whereas social relationship (support) and previous depression are unequivocally significantly associated with depression.Photoelectron emission microscopy (PEEM) and low energy electron microscopy (LEEM) can easily distinguish between organic molecules adsorbed in crystallites or in the wetting layers as well as the bare metal substrate due to their different electronic properties. Already before (and during) the condensation of such solid phases (2D islands or 3D crystallites), there is a dilute 2D gas phase. Such a 2D gas phase consists of molecules, which are highly mobile and diffuse across the surface. The individual molecules are too small to be resolved in PEEM/LEEM images. Here, we discuss, how image features below and above the resolution limit of a PEEM/LEEM affect the mean electron yield and its (normalized) standard deviation. We support our findings with two experimental examples the deposition of cobalt phthalocyanine (CoPc) on Ag(100) and of perfluoro-pentacene on Ag(110). Our results demonstrate, how a spatial and temporal analysis of image series can be used to obtain information about molecular phases, which cannot be directly resolved in microscopy images.Radiation therapy (RT) is regarded as the primary treatment for cancer in the clinic, aiming to deliver an accurate dose to the planning target volume (PTV) while protecting the surrounding organs at risk (OARs). To improve the effectiveness of the treatment planning, deep learning methods are widely adopted to predict dose distribution maps for clinical treatment planning. In this paper, we present a novel multi-constraint dose prediction model based on generative adversarial network, named Mc-GAN, to automatically predict the dose distribution map from the computer tomography (CT) images and the masks of PTV and OARs. Specifically, the generator is an embedded UNet-like structure with dilated convolution to capture both the global and local information. During the feature extraction, a dual attention module (DAM) is embedded to force the generator to take more heed of internal semantic relevance. To improve the prediction accuracy, two additional losses, i.e., the locality-constrained loss (LCL) and the self-supervised perceptual loss (SPL), are introduced besides the conventional global pixel-level loss and adversarial loss. Concretely, the LCL tries to focus on the predictions of locally important areas while the SPL aims to prevent the predicted dose maps from the possible distortion at the feature level. Evaluated on two in-house datasets, our proposed Mc-GAN has been demonstrated to outperform other state-of-the-art methods in almost all PTV and OARs criteria.Early-stage gastric cancer (GC) is asymptomatic. How to diagnose the early-stage GC is challenging. The sensitivity and specificity of diagnosing signatures for early-stage patients are still poor. Elastic-net-based analysis was used to identify potential diagnostic signatures of early-stage GC. The expression level of candidate gene was evaluated by immunohistochemistry staining. The potential function of candidate gene was verified by overexpressing in vitro. Consensus genes (including GAMT) were identified using the different strengths of the penalty. Surprisingly, GAMT was still identified even if some multicollinear variables were deleted directly. IHC staining showed that there are no GAMT-positive signals in the cell nuclei of all tumor tissues, while GAMT does express in nuclei of adjacent normal tissue. There are 16.33% positive cell nuclei in paracancerous tissues. In addition, the number of larger-area colonies of overexpression-GAMT group, empty-vector group, and AGS group is 70±29.21, 151.33±15.95, and 111.67±22.03, respectively. Number of larger colonies in group with overexpression of GAMT is significantly less than control groups. Elastic-net-penalty-based workflow is a effective tool to identify diagnostic biomarker for early-stage solid tumor. GAMT has strong potential to be the diagnostic biomarker for the early-stage GC.Inhalation of the fungus Alternaria alternata is associated with an increased risk of allergic asthma development and exacerbations. Recent work in acute exposure animal models suggests that A. alternata-induced asthma symptoms, which include inflammation, mucus overproduction and airway hyperresponsiveness, are due to A. alternata proteases that act via protease-activated receptor-2 (PAR2). However, because other active components present in A. alternata may be contributing to asthma pathophysiology through alternative signaling, the specific role PAR2 plays in asthma initiation and maintenance remains undefined. Airway epithelial cells provide the first encounter with A. alternata and are thought to play an important role in initiating the physiologic response. To better understand the role for PAR2 airway epithelial signaling we created a PAR2-deficient human bronchial epithelial cell line (16HBEPAR-/-) from a model bronchial parental line (16HBE14o-). Comparison of in vitro physiologic responses in these cell lines demonstrated a complete loss of PAR2 agonist (2at-LIGRL-NH2) response and significantly attenuated protease (trypsin and elastase) and A. alternata responses in the 16HBEPAR-/- line. Apical application of A. alternata to 16HBE14o- and 16HBEPAR2-/- grown at air-liquid interface demonstrated rapid, PAR2-dependent and independent, inflammatory cytokine, chemokine and growth factor basolateral release. In conclusion, the novel human PAR2-deficient cell line allows for direct in vitro examination of the role(s) for PAR2 in allergen challenge with polarized human airway epithelial cells.After a diagnosis of breast cancer women with increased genetic risk often have a risk reducing contralateral mastectomy, and may opt for a nipple or skin sparing mastectomy with immediate reconstruction. A variable amount of residual breast tissue remains which may substantially increase in volume during pregnancy. Whether this increases later risk of breast cancer is unknown. We describe the clinical details of 3 patients with a history of unilateral breast cancer, including 2 with a BRCA mutation, who developed hyperplasia of residual breast tissue in the 3rd trimester of a later pregnancy. They all had a delayed contralateral risk reducing skin sparing mastectomy and immediate reconstruction. Pregnancy occurred some years later. We summarise their management, review the literature and raise questions for discussion. All developed prominent hyperplasia of breast tissue in the 3rd trimester that was clinically obvious asymmetrical breast swelling in the reconstructed contralateral breast. MRI demonstrated substantial breast tissue. The risk of breast cancer, particularly in those at high genetic risk developing in the residual breast tissue is unknown but in view of the volume, breast tissue was excised postpartum. This phenomenon of pregnancy induced hyperplasia of breast tissue after risk reducing mastectomy is not well described .There is residual breast tissue following a risk reducing subcutaneous mastectomy. The risk factors include age and skin flap thickness. MRI can demonstrate the residual breast tissue. Pregnancy induced hyperplasia of residual breast tissue may occur after risk reducing mastectomy with a hypothetical increased risk of subsequent breast cancer.Immune checkpoint inhibitors and their associated immune-related cutaneous adverse events are continuing to become a mainstay of cancer treatment regimens. While most rashes are mild and easily manageable, severe or persistent rashes like lichenoid dermatoses can significantly impact the quality of life and may require ICI cessation. Lichenoid dermatoses currently have no management guidelines beyond the use of topical or oral steroids. Our study is a single-institution retrospective chart review to characterize ICI-induced lichenoid eruptions, their treatments, and associated tumor response. We utilized natural language processing and our institutional medical record to identify patients with lichenoid eruptions on ICI therapy. One-hundred nineteen patients were identified, of which 108 rashes were characterized as lichenoid dermatitis and fifteen as lichenoid mucositis. Most patients presented with a diffuse distribution (86%, 101/117), with pruritus in lichenoid dermatoses (82%, 89/108) and pain in lichenoid mucositis (80%, 12/15).
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