Background: Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by ...its invasiveness and high cost. Therefore, non-invasive, cost-effective, and accurate alternatives are urgently needed. Objective and design: This retrospective multi-center plasma proteomics study was performed to identify potential blood-based biomarkers in 36 CRC patients and 26 healthy volunteers by high-resolution mass spectrometry proteomics followed by the validation in an independent CRC cohort (60 CRC patients and 44 healthy subjects) of identified selected biomarkers. Results: Among the 322 identified plasma proteins, 37 were changed between CRC patients and healthy volunteers and were associated with the complement cascade, cholesterol metabolism, and SERPIN family members. Increased levels in CRC patients of the complement proteins C1QB, C4B, and C5 as well as pro-inflammatory proteins, lipopolysaccharide-binding protein (LBP) and serum amyloid A4, constitutive (SAA4) were revealed for first time. Importantly, increased level of C5 was verified in an independent validation CRC cohort. Increased C4B and C8A levels were correlated with cancer-associated inflammation and CRC progression, while cancer-associated inflammation was linked to the acute-phase reactant leucine-rich alpha-2-glycoprotein 1 (LRG1) and ceruloplasmin. Moreover, a 4-protein signature including C4B, C8A, apolipoprotein C2 (APO) C2, and immunoglobulin heavy constant gamma 2 was changed between early and late CRC stages. Conclusion: Our results suggest that C5 could be a potential biomarker for CRC diagnosis. Further validation studies will aid the application of these new potential biomarkers to improve CRC diagnosis and patient care.
It is assumed that lymphatic vessels are responsible for breast cancer dissemination.
In 32 male breast carcinomas we evaluated the correlation between: (i) lymphatic vessel density (LVD), ...distribution of podoplanin-immunostained vessels (DPV), blood vessel density (BVD), infiltration of immune cells and (ii) known clinicopathological parameters.
Lymphatic and blood vessels were found in 77.8% and 100% of breast carcinomas, respectively. Double-negative estrogen and progesterone receptor tumors (ER-/PR-) presented significantly higher LVD than ER/PR positive cases, while high-grade tumors exhibited significantly higher DPV than low-grade carcinomas. We detected significantly higher frequency of vascular invasion in high-grade and double-negative carcinomas than in low-grade and ER/PR-positive ones, respectively.
The relationship between high number of lymphatic vessels and high tumor grade or steroid receptor negativity might confirm the hypothesis regarding the influence of lymphangiogenesis on the formation of a more aggressive phenotype in male breast cancer.
Bladder urothelial carcinoma (BLCA) is the 10th most common cancer with a low survival rate and strong male bias. We studied the field cancerization in BLCA using multi-sample- and ...multi-tissue-per-patient protocol for sensitive detection of autosomal post-zygotic chromosomal alterations and loss of chromosome Y (LOY). We analysed 277 samples of histologically normal urothelium, 145 tumors and 63 blood samples from 52 males and 15 females, using the in-house adapted Mosaic Chromosomal Alterations (MoChA) pipeline. This approach allows identification of the early aberrations in urothelium from BLCA patients. Overall, 45% of patients exhibited at least one alteration in at least one normal urothelium sample. Recurrence analysis resulted in 16 hotspots composed of either gains and copy number neutral loss of heterozygosity (CN-LOH) or deletions and CN-LOH, encompassing well-known and new BLCA cancer driver genes. Conservative assessment of LOY showed 29%, 27% and 18% of LOY-cells in tumors, blood and normal urothelium, respectively. We provide a proof of principle that our approach can characterize the earliest alterations preconditioning normal urothelium to BLCA development. Frequent LOY in blood and urothelium-derived tissues suggest its involvement in BLCA.
Electrospinning is an increasingly popular technique for obtaining scaffolds for skin regeneration. However, electrospun scaffolds may also have some disadvantages, as the densely packed fibers in ...the scaffold structure can limit the penetration of skin cells into the inner part of the material. Such a dense arrangement of fibers can cause the cells to treat the 3D material as 2D one, and thus cause them to accumulate only on the upper surface. In this study, bi-polymer scaffolds made of polylactide (PLA) and polyvinyl alcohol (PVA) electrospun in a sequential or a concurrent system were investigated in a different PLA:PVA ratio (2:1 and 1:1). The properties of six types of model materials were investigated and compared i.e.; the initial materials electrospun by the sequential (PLA/PVA, 2PLA/PVA) and the concurrent system (PLA||PVA) and the same materials with removed PVA fibers (PLA/rPVA, 2PLA/rPVA, PLA||rPVA). The fiber models were intended to increase the porosity and coherent structure parameters of the scaffolds. The applied treatment involving the removal of PVA nanofibers increased the size of interfibrous pores formed between the PLA fibers. Ultimately, the porosity of the PLA/PVA scaffolds increased from 78 % to 99 %, and the time of water absorption decreased from 516 to 2 s. The change in wettability was induced by a synergistic effect of decrease in roughness after washing out and the presence of residual PVA fibers. The chemical analysis carried out confirmed the presence of PVA residues on the PLA fibers (FTIR-ATR study). In vitro studies were performed on human keratinocytes (HaKaT) and macrophages (RAW264.7), for which penetration into the inner part of the PLAIIPVA scaffold was observed. The new proposed approach, which allows the removal of PVA fibers from the bicomponent material, allows to obtain a scaffold with increased porosity, and thus better permeability for cells and nutrients.
Melanoma comprises <5% of cutaneous malignancies, yet it causes a significant proportion of skin cancer-related deaths worldwide. While new therapies for melanoma have been developed, not all ...patients respond well. Thus, further research is required to better predict patient outcomes. Using long-range nanopore sequencing, RT-qPCR, and RNA sequencing analyses, we examined the transcription of
splice isoforms in melanoma cell lines and patient tissue samples. Seventy-six
mRNA variants were identified in total, with several previously characterised isoforms (γ, φ, δ, ε, and η) contributing to a large proportion of the expressed transcripts. In addition, we identified four novel splice events, namely, Δ(E3_E9), ▼(i8), IVS10+131▼46, and IVS10▼176, occurring in various combinations in multiple transcripts. We found that short-read RNA-Seq analyses were limited in their ability to predict isoforms containing multiple non-contiguous splicing events, as compared to long-range nanopore sequencing. These studies suggest that further investigations into the functional significance of the identified
splice variants in melanoma are warranted.
Contrast-enhanced spectral mammography (CESM) is one of the new diagnostic modalities implemented in clinical practice. In the case of these techniques, there are two major issues to be addressed: ...(1) their diagnostic usefulness, and (2) the relation between parameters assessed using these techniques and well-known diagnostic/prognostic/predictive markers (histological, clinical, and molecular). Therefore, we studied the relationship between the tumour margin assessed on CESM and (1) tumour borders defined on the basis of macroscopic and microscopic examination, (2) pT, (3) pN, and (4) tumour grade in a group of 82 breast cancer patients. Based on CESM, the tumour border was defined as sharp, indistinct or spiculated, whereas in the case of lesions showing weak or medium enhancement on CESM the borders were classified as unspecified. We found a statistically significant relationship between tumour margin on CESM and (1) macroscopic border (a spiculated margin on CESM was found only in carcinomas with an invasive border on histological examination; p = 0.004), (2) pT (p = 0.016), and (3) pN (nodal involvement was observed most frequently in carcinomas with a spiculated or indistinct margin on CESM; p = 0.045). Moreover, in cases with an undefined margin on CESM (cases showing weak or medium enhancement on CESM), both invasive and pushing borders were found on histological examination. The results of our preliminary study suggest that it is possible to assess macroscopic borders of examined lesions on the basis of CESM imaging. This might be useful in planning the extent of surgical excision. On the other hand, the assessment of the tumour margin on CESM might not be precise in cases showing weak enhancement.
The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are ...explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available "-omics" approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups.
Objectives
In healthy people, the vibrotactile perception threshold (VPT) at fingertips depends on a given measurement method and on individual characteristics such as age, gender and finger skin ...temperature. The aim of the study was to compare the VPT values in 2 groups of healthy subjects with different finger skin temperature.
Materials and Methods
The study group comprised 56 males and 76 females, who formed pairs matched with respect to age, gender and body mass index (BMI) but differing in terms of finger skin temperature at pre-launch testing. The finger skin temperature of less than 29°C indicated the subjects with “cold hands” and that of more than 29°C, the subjects with “warm hands”. The measuring system made use of P8 pallesthesiometer (EMSON-MAT, Poland) and the measurement procedure was in compliance with the ISO 13091-1:2001 standard. VPT measurements were performed for the index, middle and ring fingers of both hands at the frequencies of 4 Hz, 25 Hz, 31.5 Hz, 63 Hz, 125 Hz and 250 Hz.
Results
The findings of the study revealed that the mean VPTs among the subjects with “cold hands” were significantly higher than the corresponding values among the subjects with “warm hands”.
Conclusions
The type of individual peripheral thermoregulation should be considered when assessing the VPT and determining its reference values.
The Dermaptera is a small insect order, traditionally divided into three separate taxa: the Hemimerina, Arixeniina and Forficulina. The first two suborders are highly modified and adapted for epizoic ...(ectoparasitic) life conditions. Recent morphological and molecular analyses have suggested that the Hemimerina and Arixeniina should be placed among the most derived subgroup of the Forficulina, the Eudermaptera.
Here we present the results of the histological and EM analyses of oogenesis and ovariole structure/ultrastructure in a representative of Arixeniina, Arixenia esau. We show that the studied species shares several important “ovariolar” characters with derived earwigs (Forficulidae). We believe that this finding reinforces the inclusion of the Arixeniina to the Eudermaptera. Our studies indicate additionally that the vitellogenic and postvitellogenic oocytes of A. esau show interesting features that can be interpreted as the adaptations to viviparity, and consequently epizoic life conditions. Thus, the oogenesis of A. esau exemplifies unique mixture of the characters shared with derived earwigs (Forficulidae) and adaptations to the viviparity.
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