Castleman´s disease is an extremely rare heterogenous lymphoproliferative pathology with a mostly benign behavior. It is a localized or generalized lymph node enlargement of an unknown aetiology. ...Unicentric form is typically a slow-growing solitary mass occurring mostly in the mediastinum, abdominal cavity, retroperitoneum, pelvis and neck. Aetiology and pathogenesis of CD is probably diverse, varying in different types of this heterogeneous disease.
Authors present a review of this issue based on their extensive experience. The aim is to summarize the crucial factors in the management of diagnostics and a surgical treatment of the unicentric form of Castleman´s disease. One of the key issues in the unicentric form is precise preoperative diagnostics and thus choosing the right surgical treatment strategy. Authors highlight pitfalls of the diagnosis and surgical treatment.
All histological types such as a hyaline vascular type, plasmacytic type and a mixed type are presented as well as options of surgical and conservative treatment. Differential diagnosis and malignant potential is discussed.
Patients with Castleman´s disease should be treated in the high- volume centers, with a great experience in major surgical procedures as well as with preoperative imaging diagnostic techniques. Specialized pathologists and oncologists focusing on this issue are also absolutely necessary to avoid misdiagnosis. Only this complex approach can lead to excellent outcomes in patients with UCD.
RNA modifications are being recognized as an essential factor in gene expression regulation. They play essential roles in germ line development, differentiation and disease. In eukaryotic mRNAs, ...N6-adenosine methylation (m6A) is the most prevalent internal chemical modification identified to date. The m6A pathway involves factors called writers, readers and erasers. m6A thus offers an interesting concept of dynamic reversible modification with implications in fine-tuning the cellular metabolism. In mammals, FTO and ALKBH5 have been initially identified as m6A erasers. Recently, FTO m6A specificity has been debated as new reports identify FTO targeting N6,2′-O-dimethyladenosine (m6Am). The two adenosine demethylases have diverse roles in the metabolism of mRNAs and their activity is involved in key processes, such as embryogenesis, disease or infection. In this article, we review the current knowledge of their function and mechanisms and discuss the existing contradictions in the field. This article is part of a Special Issue entitled: mRNA modifications in gene expression control edited by Dr. Soller Matthias and Dr. Fray Rupert.
•mRNA adenosine methylation is chemical modification with an impact on broad spectrum of mRNA biology, development and disease•adenosine methylation marks in mRNAs can be reversed by FTO and ALKBH5 demethylases in mammalian cells•ALKBH5 targets m6A whereas FTO can demethylate two marks m6A and m6Am•the two enzymes display distinct phenotypes and expression pattern and have been linked to development and disease•the molecular mechanism of the in vivo function of these demethylases is still lacking behind the expanding field of m6A
Transfer RNAs acquire a large plethora of chemical modifications. Among those, modifications of the anticodon loop play important roles in translational fidelity and tRNA stability. Four human wobble ...U-containing tRNAs obtain 5-methoxycarbonylmethyluridine (mcm
U
) or 5-methoxycarbonylmethyl-2-thiouridine (mcm
s
U
), which play a role in decoding. This mark involves a cascade of enzymatic activities. The last step is mediated by alkylation repair homolog 8 (ALKBH8). In this study, we performed a transcriptome-wide analysis of the repertoire of ALKBH8 RNA targets. Using a combination of HITS-CLIP and RIP-seq analyses, we uncover ALKBH8-bound RNAs. We show that ALKBH8 targets fully processed and CCA modified tRNAs. Our analyses uncovered the previously known set of wobble U-containing tRNAs. In addition, both our approaches revealed ALKBH8 binding to several other types of noncoding RNAs, in particular C/D box snoRNAs.
•The evolution of parasitism on Kinetoplastid protists is presented.•Parasitism has repeatedly emerged within this group of flagellates.•We demonstrate rather unlike origin of dixenous life cycle in ...various groups.•Parasite (pre)adaptations for their co-existing with the hosts are discussed.•The biodiversity of monoxenous (one host) trypanosomatids is introduced.
Kinetoplastid protists offer a unique opportunity for studying the evolution of parasitism. While all their close relatives are either photo- or phagotrophic, a number of kinetoplastid species are facultative or obligatory parasites, supporting a hypothesis that parasitism has emerged within this group of flagellates. In this review we discuss origin and evolution of parasitism in bodonids and trypanosomatids and specific adaptations allowing these protozoa to co-exist with their hosts. We also explore the limits of biodiversity of monoxenous (one host) trypanosomatids and some features distinguishing them from their dixenous (two hosts) relatives.
Background: Portal vein ligation (PVL) could multiply the future liver remnant volume (FLRV). Interuleukin-6 (IL-6) is a pleiotropic
cytokine that is associated with an initial phase of liver ...regeneration. The aim of this study was to accelerate the regeneration
of liver parenchyma after PVL by intraportal cytokine application. Materials and Methods: After ligation of portal branches
of caudate and right lateral and right medial liver lobes, recombinant porcine IL-6 (IL-6 group) or physiological solution
(control group) were applied into non-occluded portal vein branches. The biochemical and immunoanalytical parameters were
assessed. The compensatory hypertrophy was evaluated by periodic ultrasonography. The histological examination of liver was
performed. Results: The acceleration of growth of hypertrophic liver lobes was maximal at the 7th postoperative day in comparison
with the control group (p<0.05), nevertheless, this stimulating effect was lost at the end of the experiment. Important differences
in biochemical or histological studied parametres were not proved. Conclusion: The presented study describes the use of IL-6
for stimulation of the first phase of liver regeneration. The achieved acceleration of growth of hypertrophic liver lobes
after application of IL-6 confirmed the key role of the studied cytokine in priming regenerating liver parenchyma after portal
vein ligation.
Patients with unresectable liver colorectal cancer metastases are treated with neoadjuvant chemotherapy often accompanied by biological therapy aimed at reducing the mass of metastases and thus ...increasing the chances of resectability. Bevacizumab comprises an anti-VEGF (vascular endothelial growth factor) humanized IgG monoclonal antibody that is used for biological therapy purposes. It acts to inhibit angiogenesis, thereby slowing down the growth of metastases. Due to its being administered systematically, bevacizumab also exerts an effect on the surrounding healthy liver parenchyma and potentially limits the process of neovascularization and thus regeneration of the liver. Since the remnant liver volume forms an important factor in postoperative morbidity and mortality following a major hepatectomy, we decided to study the effect of bevacizumab on vascular and biliary microarchitecture in healthy liver parenchyma and its ability to regenerate following major hepatectomy.
We performed an experiment employing a large animal model where a total of 16 piglets were divided into two groups (8 piglets in the control group and 8 piglets in the experimental group with bevacizumab). All the animals were subjected to major hepatectomy and the experimental group was given bevacizumab prior to hepatectomy. All the animals were sacrificed after 4 weeks. We performed biochemical analyses at regular time intervals during the follow-up period. Histological examination of the liver tissue was performed following sacrifice of the animals.
No statistical difference was shown between groups in terms of the biochemical and immunohistochemical parameters. The histological examination of the regenerating liver tissue revealed the higher length density of sinusoids in the experimental group.
Bevacizumab does not act to impair liver regeneration following hepatectomy.
Portal vein embolization (PVE) can be used prior to liver surgery to increase the volume of the remaining liver tissue after
an extensive resection. However, the application of PVE is limited and new ...strategies to augment liver regeneration by cellular
therapy are promising alternatives. Materials and Methods: The influence of syngeneic multipotent mesenchymal stromal cells
(MSC) on liver regeneration was analysed after the ligation of the right portal vein branches in a porcine model, closely
mimicking the situation of human surgery. Liver regeneration was monitored by ultrasonography, immunohistological analysis
and serum biochemistry. Results: The volume of the contra-lateral, non-ligated liver lobe increased in all piglets after portal
vein ligation. This hyperplasia occurred earlier and was more pronounced in those piglets receiving MSC infusions as compared
to non-treated controls. Biochemical liver function was stable in all pigs. Only solitary transplanted MSC were detected in
recipient livers two weeks after the infusion. Conclusion: The infusion of porcine MSC into the portal vein in a setting of
liver regeneration after surgical resection leads to accelerated and augmented hyperplasia. This effect is most likely due
to bystander effects of the transplanted MSC.
Summary
Background
The aim of this study was to evaluate the short- and long-term results and risk factors of liver surgery in patients over the age of 70 following liver resection for colorectal ...liver metastases.
Methods
A total of 650 patients with an average age of 63.8 ± 9.3 years were evaluated. We compared groups of patients younger and older than 70 years of age. Time of hospitalisation, 30-day postoperative morbidity and mortality, overall and recurrence-free survival, the number and largest diameter of metastases, small and large liver resections, and the interval between primary colorectal and liver surgery were evaluated according to the results of liver resections.
Results
Length of hospitalisation, 30-day postoperative morbidity and mortality, and long-term results did not differ between groups of patients. Pulmonary embolism and confusion had a higher incidence in patients ≥70 years old (
p
< 0.02 and 0.05, respectively). Diameter of the largest metastasis ≥50 mm was a negative prognostic factor for long-term results in patients ≥70 years old (
p
< 0.04, HR 1.7, 95% CI 1.0–2.9 and
p
< 0.03, HR 1.5, 95% CI 1.0–2.3, respectively). Large liver resections had worse long-term results in patients ≥70 years old (
p
< 0.01, HR 2.1, 95% CI 1.2–3.8 and
p
< 0.05, HR 1.5, 95% CI 0.9–2.3, respectively).
Conclusion
Our results confirm the safety of liver resections for colorectal liver metastases in elderly patients. Parenchymal sparing surgery should be the method of choice. Very early and intensive postoperative mobilisation and respiratory and mental rehabilitation is essential.
MicroRNAs have the potential to become valuable predictive markers for gastric cancer. Samples of biopsy tissue, routinely taken from gastric cancer patients undergoing palliative chemotherapy, ...constitute suitable material for microRNA profiling with the aim of predicting the effect of chemotherapy. Our study group consisted of 54 patients, all of whom underwent palliative chemotherapy based on 5-fluorouracil (5-FU) or 5-FU in combination with platinum derivatives between 2000 and 2013. The expression of 29 selected microRNAs and genes BRCA1, ERCC1, RRM1 and TS, in gastric cancer tissue macrodissected from FFPE tissue samples, was measured by quantitative RT-PCR. The relationship between gene expression levels and time to progression (TTP) and overall survival (OS) was analysed. From the set of the 29 microRNAs of interest, we found high expression of miR-150, miR-342-3p, miR-181b, miR-221, miR-224 and low levels of miR-520h relate to shorter TTP. High levels of miR-150, miR-192, miR-224, miR-375 and miR-342-3p related to shorter OS. In routinely available FFPE tissue samples, we found 6 miRNAs with a relation to TTP, which may serve as predictors of the effectiveness of palliative treatment in gastric cancer patients. These miRNAs could also help in deciding whether to indicate palliative chemotherapy.
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