Microbial and Metabolic Gut Profiling across Seven Malignancies Identifies Fecal Faecalibacillus intestinalis and Formic Acid as Commonly Altered in Cancer Patients.

The key association between gut dysbiosis and cancer is already known. Here, we used whole-genome shotgun sequencing (WGS) and gas chromatography/mass spectrometry (GC/MS) to conduct metagenomic and metabolomic analyses to identify common and distinct taxonomic configurations among 40, 45, 71, 34, 50, 60, and 40 patients with colorectal cancer, stomach cancer, breast cancer, lung cancer, melanoma, lymphoid neoplasms and acute myeloid leukemia (AML), respectively, and compared the data with those from sex- and age-matched healthy controls (HC). α-diversity differed only between the lymphoid neoplasm and AML groups and their respective HC, while ß-diversity differed between all groups and their HC. Of 203 unique species, 179 and 24 were under- and over-represented, respectively, in the case groups compared with HC. Of these, Faecalibacillus intestinalis was under-represented in each of the seven groups studied, Anaerostipes hadrus was under-represented in all but the stomach cancer group, and 22 species were under-represented in the remaining five case groups. There was a marked reduction in the gut microbiome cancer index in all case groups except the AML group. Of the short-chain fatty acids and amino acids tested, the relative concentration of formic acid was significantly higher in each of the case groups than in HC, and the abundance of seven species of Faecalibacterium correlated negatively with most amino acids and formic acid, and positively with the levels of acetic, propanoic, and butanoic acid. We found more differences than similarities between the studied malignancy groups, with large variations in diversity, taxonomic/metabolomic profiles, and functional assignments. While the results obtained may demonstrate trends rather than objective differences that correlate with different types of malignancy, the newly developed gut microbiota cancer index did distinguish most of the cancer cases from HC. We believe that these data are a promising step forward in the search for new diagnostic and predictive tests to assess intestinal dysbiosis among cancer patients.

µ-Opioid receptor gene (OPRM1) polymorphism in patients with breast cancer.

Structure-dependent µ-opioid receptor (MOR) activity is an important element in cancer opioid analgesic effectiveness. It is widely accepted that guanine (G) substitution for adenine (A) at OPRM1 gene sequence position 118 changes receptor glycosylation pattern. This is associated with decreased binding ability in both exogenous and endogenous opioids, resulting in increased human pain resistance. The endogenous opioid system's function in body homeostasis maintenance is considered mainly regulatory, so its participation in breast tumor formation and progression is identified herein. We examine the association of the most frequent MOR (A118G) gene polymorphism on breast cancer risk in a Northeastern Polish population by PCR-RFLP comparison of A and G allele frequency at OPRM1 gene A118G polymorphic site in breast cancer-diagnosed patients with healthy control group frequencies. Our results highlight a strong association between G allele presence at µ-opioid receptor A118G and increased breast cancer incidence (OR = 3.3, 95 % CI 2.2-5.0, p < 0.0001) and female gender (OR = 2.0, 95 % CI 1.4-2.9, p = 0.0004). Consequently, OPRM1 G allele presence at that site is a highly significant risk factor in breast cancer development.

[Helicobacter pylori morphological forms and their potential role in the transmission of infection]. / Formy morfologiczne Helicobacter pylori i ich przypuszczalna rola w transmisji zakazen

More than 50% of the world's population is infected with Helicobacter pylori (H. pylori) - a Gram negative bacterium, which persists in the human stomach and duodenum, causing gastric or duodenal ulcers and gastric cancer. The majority of H. pylori cells demonstrate rod-shape morphology occurring in two subtypes: spiral and S-shaped. Both are isolated from mucus layer biopsy specimens of the stomach or from short-term cultures. However, results obtained from electron microscopy revealed that H. pylori long-term cultures not only consist of classic, spiral shaped bacteria, but also contain alternative forms of coccoid cells. Further investigations showed that coccoid forms of H. pylori may be divided into two types: viable but non-culturable coccus (VBnC) and a degenerative form, coccoid stage which is probably the effect of bacterial cell death. Transformation from spiral to coccoid form is induced under stress conditions, such as the presence of antibiotics. But still there is no evidence for reversion from the coccoid state to the viable and infectious spiral form. Besides the planktonic form, H. pylori also forms homo-, and heterogenic biofilms, which may constitute a potential environmental reservoir of this bacterium. The antigenic repertoire and the immunomodulatory and infectious properties of different H. pylori forms differ greatly. The variation in those properties suggests that morphological forms of H. pylori are potentially involved in the transmission of the infection. This review presents recent findings on the variability, antigenicity and infectious properties of H. pylori morphological forms and their potential role in the transmission of the infection.

Breast cancer but not the menopausal status is associated with small changes of the gut microbiota.

Background: Possible relationships between gut dysbiosis and breast cancer (BC) development and progression have been previously reported. However, the results of these metagenomics studies are inconsistent. Our study involved 88 patients diagnosed with breast cancer and 86 cancer-free control women. Participants were divided into groups based on their menopausal status. Fecal samples were collected from 47 and 41 pre- and postmenopausal newly diagnosed breast cancer patients and 51 and 35 pre- and postmenopausal controls, respectively. In this study, we performed shotgun metagenomic analyses to compare the gut microbial community between pre- and postmenopausal BC patients and the corresponding controls. Results: Firstly, we identified 12, 64, 158, and 455 bacterial taxa on the taxonomy level of phyla, families, genera, and species, respectively. Insignificant differences of the Shannon index and ß-diversity were found at the genus and species levels between pre- and postmenopausal controls; the differences concerned only the Chao index at the species level. No differences in α-diversity indexes were found between pre- and postmenopausal BC patients, although ß-diversity differed these subgroups at the genus and species levels. Consistently, only the abundance of single taxa differed between pre- and postmenopausal controls and cases, while the abundances of 14 and 23 taxa differed or tended to differ between premenopausal cases and controls, and between postmenopausal cases and controls, respectively. There were similar differences in the distribution of enterotypes. Of 460 bacterial MetaCyc pathways discovered, no pathways differentiated pre- and postmenopausal controls or BC patients, while two and one pathways differentiated cases from controls in the pre- and postmenopausal subgroups, respectively. Conclusion: While our findings did not reveal an association of changes in the overall microbiota composition and selected taxa with the menopausal status in cases and controls, they confirmed differences of the gut microbiota between pre- and postmenopausal BC patients and the corresponding controls. However, these differences were less extensive than those described previously.

Left-sided renal colic as a symptom of advanced stomach cancer - a case report.

The typical symptoms of advanced cancer of the stomach are well known in clinical practice. The presented case concerns a patient with symptoms of left-sided renal colic, caused by a malignant tumour involving the ureter, which was diagnosed with a CT scan. The multifocal process, involving the stomach, two parts of the colon, the left ovary and the side of the pelvis, was confirmed only during surgery. The resection or partial resection of the above-mentioned organs involved by the malignant process and reconstruction of the alimentary tract as well as the ureter were performed at time of this operation. The patient's recovery was without any complications. The histopathological findings support the diagnosis of this malignant process as disseminated stomach cancer. In the available literature only two cases of stomach cancer metastasis to the ureter have been described. In both cited examples resection of the ureter with nephrectomy was performed. The review of the literature supports the value of stomach palliative resection in prolonging life and improving quality of life.

The Value of Somatostatin Receptor Scintigraphy (SRS) in Patients with NETG1/G2 Pancreatic Neuroendocrine Neoplasms (p-NENs).

BACKGROUND: Neuroendocrine neoplasms of the pancreas (p-NEN) are common gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs). The aim of this retrospective study was to review the of value of Somatostatin Receptor Scintigraphy (SRS) in initial detection of p-NEN, evaluation of tumour extent and as imaging follow-up after radical surgery in patients with confirmed well (NETG1) or moderate (NETG2) differentiated p-NEN based on pathological WHO 2017 classification. MATERIAL AND METHODS: Overall 281 patients with confirmed p-NEN were enrolled. The SRS was performed to evaluation of primary p-NEN, also to assess clinical stage of disease, based on current World Health Organization (WHO) classification and during clinical follow-up. A total of 829 examinations were performed over time in these 281 patients using 99mTc HYNICTOC. Images were acquired between 1 - 3 h after i.v. injection of radiotracer. Initially whole body WB-SPECT and then WB-SPECT/CT, with standard iterative reconstruction were used. RESULTS: There were 159 patients with NETG1 (57%) and 122 subjects with NETG2 (43%). The female to male ratio was 1.1:1. In 68 patients (22%) with NETG1/G2 eight-seven SRS (10%) were performed to confirm initial diagnosis. SRS results were as follow: true positive (TP) = 84 (97%), false negative (FN) = 3 (3%), no true negative (TN) or false positive (FP) results of SRS examination (sensitivity of SRS per patient was 96%). In 198 subjects (66%) SRS was used in evaluation and re-evaluation of the clinical stage, A total of 661 (80%) examinations were carried out in these patients. There were TP=514 (77%), TN=136 (21%), FN=7 (1%) and FP=4 (1%) results. The sensitivity and specificity per patient were: 96% and 95%. The sensitivity and specificity per study: 98% and 97%. In 35 patients (12%) SRS was used as imaging follow-up after radical surgery, there were overall 81 examination (10%) which were performed. There were 76 (91%) TN results of examinations of SRS and in 4 patients we identified recurrence (TP). In total, which consists of initial diagnosis/staging and follow-up patients, the sensitivity of SRS was 96% and specificity 97% per patient and per study sensitivity and specificity was 98%. CONCLUSIONS: SRS using 99mTc HYNICTOC acquired in WB-SPECT or WB-SPECT/CT techniques is an excellent imaging modality in detection of primary NETG1/G2 p-NEN. Our study confirms that SRS has high sensitivity and specificity, as a result has tremendous value as an examination method to assess clinical stage of disease and as an imaging follow-up after radical treatment.

Multimodal ultrasound computer-assisted tomography: An approach to the recognition of breast lesions.

The research here presented aims at developing a new, promising method for the imaging diagnostics of breast lesions - ultrasound tomography (UST). A currently implemented device enables the reconstruction three complementary images for each coronal breast section. Based on in vivo breast examination, the authors developed an approach to breast diagnostics which employs ultrasound transmission and reflection tomography imaging. The obtained transmission images of ultrasound speed distribution show good correlation of glandular tissue areas with their visualization on MRI images. The results also allow a prediction that the implemented UST device offering fusion of reconstructed images may contribute to achieving a new standard for breast cancer diagnostics through non-invasive, fast and cheap screening tests.

[Potential prognostic value of angiogenesis, cell proliferation and metastasing in patients with surgically treated gastric cancer--current knowledge]. / Badania nad znaczeniem prognostycznym wybranych markerów angiogenezy, proliferacji komórkowej i przerzutowania u chorych operowanych z powodu raka zoladka--aktualny stan wiedzy.

Gastric cancer is nowadays one of the most severe human malignant tumours. Surgeons and oncologists often encounter in their clinical practice the course of disease that cannot be fully accounted for by commonly used classical histo-clinical prognostic parameters. Gastric tumours of similar size, similar progression stage and similarly treated may develop along significantly different courses, the phenomenon that seems to depend on as yet not fully recognized biological factors. Preliminary observations from different centers concerning the role of new molecular parameters having potential influence on prognosis in gastric cancer are often contradictory. This study based on bibliography and own observations presents current data connected with potential prognostic value of angiogenesis, proliferation and metastasing in patients with surgically treated gastric cancer. It is very possible that in the future the evaluation of these molecular parameters will find its place in clinical practice for determination of more precise prognosis and improving distant results of combined treatment in gastric cancer patients.

PLAGL1 protein is differentially expressed in the nephron segments and collecting ducts in human kidney.

INTRODUCTION: PLAGL1 (pleiomorphic adenoma gene-like 1) is a C2H2-type zinc finger transcription factor associated with the regulation of cell growth and development. Although PLAGL1 expression in kidney was assessed by biochemical methods, the exact localization of the PLAGL1 protein in human kidney has not yet been described. MATERIAL AND METHODS: Macroscopically unchanged specimens of kidney tissue were collected from 39 patients undergoing nephrectomy due to renal cell carcinoma. H & E staining of paraffin sections was used to assess histology of the kidney whereas immunohistochemistry was used to localize PLAGL1 protein in kidney compartments. In addition, database sequences search for putative PLAGL1 binding sites among the kidney-related genes was performed. RESULTS: PLAGL1 staining intensity differed depending on the kidney compartment. Strong PLAGL1 immunoreactivity was found in thick ascending limbs of Henle's loop, distal tubules and collecting ducts, whereas PLAGL1 expression in proximal tubules and renal corpuscles (including podocytes) was moderate and weak, respectively. By the in sillico screening of promoter sequences for PLAGL1 specific DNA-binding sites GGG-GCCCC we designated 43 candidate genes for PLAGL1-regulated genes. Analysis of their functional annotations identified three significantly over-represented gene sets: inositol phosphate metabolic processes (GO), endocrine and other factor-regulated calcium reabsorption (KEGG) and calcium signaling pathways (KEGG). CONCLUSION: Differences in the renal expression of PLAGL1 suggest that this protein may be involved in the regulation of several cellular pathways both as transcriptional factor and coactivator/corepressor of other tran-scription factors reflecting its role in the cell type-specific control of gene expression.

Mesh repair of umbilical hernia without a visible abdominal scar.

UNLABELLED: Experience in the use of Single Incision Laparoscopic Surgery procedures and the persistent urge to improve the cosmetic effect have contributed to the introduction of mesh repair of an umbilical hernia by means of a small incision in the natural position of the umbilicus. The aim of the study was to present the surgical technique and assess its postoperative results. MATERIAL AND METHODS: During the period between 24.08.2011 and 01.01.2013, twenty-three umbilical hernia repair operations with the use of a polypropylene mesh by means of a small incision in the natural position of the umbilicus were performed. The synthetic material was placed in the preperitoneal space. The wound was closed and the umbilicus was reconstructed simultaneously, in order to make the scar invisible. Cutaneous stitches were not used. RESULTS: The average duration of the operation was 49 minutes. In one case of an obese patient with coexisting linea alba dehiscence, hernia recurrence was observed. All wounds healed without complications. The cosmetic effect was very good. CONCLUSIONS: Based on the presented experience mesh repair of the umbilical hernia by means of a small incision in the natural position of the umbilicus contributes essential benefits, such as a very good cosmetic effect without consecutive increasing costs, as compared to standard treatment by means of an infraumbilical incision.

Immunophenotype of peripheral blood natural killer cells and IL-10 serum levels in relation to Helicobacter pylori status.

Recent findings suggest that NK (Natural Killer) cells may directly modulate the antimicrobial immune responses. In this study, we performed immunophenotypic analysis of peripheral blood NK cells with regard to CD56, CD16, Nkp46, and CD25 markers, as well as IL-10 levels quantification in the sera samples of asymptomatic, H. pylori (Hp)-infected or uninfected individuals, and combined these results with our previous findings on lymphocyte cytotoxic activity. Twenty healthy volunteers [10 Hp(-);10 Hp(+)] were included in the study. The percentages of classic lymphocytes (CD3(+) ) and NK cells (CD3(-) CD56(+) , CD3(-) Nkp46(+) , CD3(-) CD16(+) ) with or without CD25 receptor were evaluated by fluorochrome-conjugated monoclonal antibody staining and flow cytometry analysis. IL-10 quantification was performed by enzyme-linked immunosorbent assay-ELISA. Our study showed elevated levels of IL-10 and higher NK cell numbers of both CD3(-) CD56(+) CD25(+) and CD3(-) Nkp46(+) CD25(+) phenotypes, as well as CD3(+) CD25(+) classic lymphocytes in Hp(+) compared with Hp(-) individuals. No differences between Hp(-) and Hp(+) individuals were found either in total number of classic lymphocytes or NK cell subtypes. Our data suggest that in Hp(+) donors, there is a domination of lymphocytes and NK cells co-expressing CD25 marker, which might be influenced by the regulatory IL-10. This phenomenon may be a result of H. pylori adaptation to a changing environment in vivo leading to a chronic infection and lack of severe gastric pathologies.