Towards targeted colorectal cancer biopsy based on tissue morphology assessment by compression optical coherence elastography

Identifying the precise topography of cancer for targeted biopsy in colonoscopic examination is a challenge in current diagnostic practice. For the first time we demonstrate the use of compression optical coherence elastography (C-OCE) technology as a new functional OCT modality for differentiating between cancerous and non-cancerous tissues in colon and detecting their morphological features on the basis of measurement of tissue elastic properties. The method uses pre-determined stiffness values (Young’s modulus) to distinguish between different morphological structures of normal (mucosa and submucosa), benign tumor (adenoma) and malignant tumor tissue (including cancer cells, gland-like structures, cribriform gland-like structures, stromal fibers, extracellular mucin). After analyzing in excess of fifty tissue samples, a threshold stiffness value of 520 kPa was suggested above which areas of colorectal cancer were detected invariably. A high Pearson correlation (r =0.98; p <0.05), and a negligible bias (0.22) by good agreement of the segmentation results of C-OCE and histological (reference standard) images was demonstrated, indicating the efficiency of C-OCE to identify the precise localization of colorectal cancer and the possibility to perform targeted biopsy. Furthermore, we demonstrated the ability of C-OCE to differentiate morphological subtypes of colorectal cancer – low-grade and high-grade colorectal adenocarcinomas, mucinous adenocarcinoma, and cribriform patterns. The obtained ex vivo results highlight prospects of C-OCE for high-level colon malignancy detection. The future endoscopic use of C-OCE will allow targeted biopsy sampling and simultaneous rapid analysis of the heterogeneous morphology of colon tumors

The TESS Grand Unified Hot Jupiter Survey. II. Twenty New Giant Planets

NASA's Transiting Exoplanet Survey Satellite (TESS) mission promises to improve our understanding of hot Jupiters by providing an all-sky, magnitude-limited sample of transiting hot Jupiters suitable for population studies. Assembling such a sample requires confirming hundreds of planet candidates with additional follow-up observations. Here, we present twenty hot Jupiters that were detected using TESS data and confirmed to be planets through photometric, spectroscopic, and imaging observations coordinated by the TESS Follow-up Observing Program (TFOP). These twenty planets have orbital periods shorter than 7 days and orbit relatively bright FGK stars ($10.9 < G < 13.0$). Most of the planets are comparable in mass to Jupiter, although there are four planets with masses less than that of Saturn. TOI-3976 b, the longest period planet in our sample ($P = 6.6$ days), may be on a moderately eccentric orbit ($e = 0.18\pm0.06$), while observations of the other targets are consistent with them being on circular orbits. We measured the projected stellar obliquity of TOI-1937A b, a hot Jupiter on a 22.4 hour orbit with the Rossiter-McLaughlin effect, finding the planet's orbit to be well-aligned with the stellar spin axis ($|\lambda| = 4.0\pm3.5^\circ$). We also investigated the possibility that TOI-1937 is a member of the NGC 2516 open cluster, but ultimately found the evidence for cluster membership to be ambiguous. These objects are part of a larger effort to build a complete sample of hot Jupiters to be used for future demographic and detailed characterization work.Comment: 67 pages, 11 tables, 13 figures, 2 figure sets. Resubmitted to ApJS after revision

Pharmacokinetics of Chlorin e6-Cobalt Bis(Dicarbollide) Conjugate in Balb/c Mice with Engrafted Carcinoma

The necessary precondition for efficient boron neutron capture therapy (BNCT) is control over the content of isotope 10B in the tumor and normal tissues. In the case of boron-containing porphyrins, the fluorescent part of molecule can be used for quantitative assessment of the boron content. Study Objective: We performed a study of the biodistribution of the chlorin e6-Cobalt bis(dicarbollide) conjugate in carcinoma-bearing Balb/c mice using ex vivo fluorescence imaging, and developed a mathematical model describing boron accumulation and release based on the obtained experimental data. Materials and Methods: The study was performed on Balb/c tumor-bearing mice (CT-26 tumor model). A solution of the chlorin e6-Cobalt bis(dicarbollide) conjugate (CCDC) was injected into the blood at a dose of 10 mg/kg of the animal’s weight. Analysis of the fluorescence signal intensity was performed at several time points by spectrofluorimetry in blood and by laser scanning microscopy in muscle, liver, and tumor tissues. The boron content in the same samples was determined by mass spectroscopy with inductively coupled plasma. Results: Analysis of a linear approximation between the fluorescence intensity and boron content in the tissues demonstrated a satisfactory value of approximation reliability with a Spearman’s rank correlation coefficient of r = 0.938, p &lt; 0.01. The dynamics of the boron concentration change in various organs, calculated on the basis of the fluorescence intensity, enabled the development of a model describing the accumulation of the studied compound and its distribution in tissues. The obtained results reveal a high level of correspondence between the model and experimental data

Pericentromeric Non-Coding DNA Transcription Is Associated with Niche Impairment in Patients with Ineffective or Partially Effective Multiple Myeloma Treatment

Mesenchymal stromal cells (MSC) &lsquo;educated&rsquo; by tumor cells are an essential component of the multiple myeloma (MM) tumor microenvironment (TME) involved in tumor progression. Transcription of tandemly repeated (TR) non-coding DNA is often activated in many tumors and is required for tumor progression and cancer cells genome reorganization. The aim of the work was to study functional properties including the TR DNA transcription profile of MSC from the hematopoietic niche of treated MM patients. Healthy donors (HD) and patients after bortezomib-based treatment (with partial or complete response, PoCR, and non-responders, NR) were enrolled in the study. Their trephine biopsies were examined histologically to evaluate the hematopoietic niche. MSC cultures obtained from the biopsies were used for evaluation of the proliferation rate, osteogenic differentiation, presence of tumor MSC markers, resistance to bortezomib, and pericentromeric TR DNA transcription level. The MSC &lsquo;education&rsquo; by multiple myeloma cells was mimicked in co-culture experiments with or without bortezomib. The TR DNA transcription profile was accessed. The histological examination revealed the persistence of the tumor microenvironment (especially of the vasculature) in treated patients. In co-culture experiments, MSC of bortezomib-treated patients were more resistant to bortezomib and protected cancer MM cells of the RPMI8226 cell line more effectively than HD-MSC did. The MSC obtained from PoCR and NR samples differed in their functional properties (proliferation capacity, osteogenic potential, and cancer-associated fibroblasts markers). Transcriptome analysis revealed activation of the TR transcription in cells of non-hematopoietic origin from NR patients&rsquo; bone marrow. The pericentromeric TR DNA of HS2/HS3 families was among the most upregulated in stromal MSC but not in cancer cells. The highest level of transcription was observed in NR-MSC. Transcription of HS2/HS3 was not detected in healthy donors MSC unless they were co-cultured with MM cancer cells and acquired cancer-associated phenotype. Treatment with TNF&alpha; downregulated HS2/HS3 transcription in MSC and upregulated in MM cells. Our results suggest that the hematopoietic niche retains the cancer-associated phenotype after treatment. Pericentromeric non-coding DNA transcription is associated with the MSC cancer-associated phenotype in patients with ineffective or partially effective multiple myeloma treatment