Maltotriose-modified poly(propylene imine) Glycodendrimers as a potential novel platform in the treatment of chronic lymphocytic Leukemia. A proof-of-concept pilot study in the animal model of CLL.

Cancer nanotherapeutics have shown promise in resolving some of the limitations of conventional drug delivery systems such as nonspecific biodistribution and targeting, lack of water solubility, and low therapeutic indices, Among the various nanoparticles that are available, dendrimers, highly branched macromolecules with a specific size and shape, are one of the most promising ones. In this preliminary study, we tested the anti-tumor activity of maltotriose-modified fourth-generation poly(propylene imine) glycodendrimers (PPI-G4-M3) in vivo in the subcutaneous MEC-1 xenograft model of human chronic lymphocytic leukemia (CLL) in NOD scid gamma mice. Fludarabine was used for model validation and as a positive treatment control. The anti-tumor response was calculated as tumor volume, tumor control ratio, and tumor growth inhibition. The study showed that PPI-G4-M3 inhibited subcutaneous tumor growth more efficiently than fludarabine. The anti-tumor response was dose-dependent. Cationic PPI-G4-M3 showed the highest anti-tumor activity but also higher toxicity than the neutral dendrimers and fludarabine. These first promising results warrant further studies in the optimization of dendrimers charge, dose, route and schedule of administration to combat CLL.

Benign-looking primary fibrosarcoma of the uterus.

Fibrosarcomas are placed among the most infrequent malignant tumors of the uterus. We present a case of a 38 years-old woman, whose benign looking uterine mass was primary diagnosed as a sclerosing leiomyoma. However, the tumor relapsed in two years with multisite metastases in the abdomen. The complex differential diagnosis excluded the most common mesenchymal tumors of the gynecological tract. Finally, we diagnosed the tumor as an epithelioid sclerosing fibrosarcoma arising from the uterine.

A malignant astrocytoma with uncommon angiocentric features and dot-like EMA expression.

Angiocentric features are uncommon in high-grade World Health Organisation (WHO) brain tumours, whilst they are typical for WHO grade I tumours, e.g. angiocentric gliomas. We present an unusual glial tumour that occurred in a 59-year-old man. The tumour had equivocal radiologic and histopathologic features, especially a characteristic angiocentric pattern, low-to-moderate Ki67, and dot-like epithelial membrane antigen expression. The tumour did not show features characteristic for glioblastoma; however, it recurred as glioblastoma four months later. Based on this case, we show that high-grade WHO brain tumours may show an angiocentric pattern typical for low-grade WHO brain tumours, such as angiocentric gliomas.

Pure hepatocellular carcinoma originates from an ectopic liver nodule located in the pancreas.

Ectopic liver (EL) is a rare congenital abnormality, which is localised most commonly in the wall of the gallbladder. Histoarchitectural abnormalities, which lead to impaired transfer of blood and bile, as well as well demarcation, are characteristic features of ectopic liver nodules. Both features may explain the discrepancies between hepatocellular carcinoma (HCC) cases originating from ectopic liver in comparison to HCC cases originating from orthotopic liver: the strong propensity of ectopic liver to the development of HCC. The latter feature may be linked to the better treatment prognosis in patients with HCC originating from ectopic liver tissue in comparison to those with HCC within orthotopic liver. In this paper, we discuss these differences based on a unique case of pure HCC, which developed in a small ectopic liver nodule in the pancreas.

[Synchronous occurrence of four malignancies in a 55-year-old woman with uterine cervical cancer. Case report and review of literature]. / Synchroniczne wystepowanie czterech nowotworów u 55-letniej chorej z rakiem szyjki macicy. Opis przypadku i przeglad pismiennictwa.

Multiple primary malignancies are no longer rare in clinical practice. The incidence of multiple primary malignant neoplasms is the consequence of progress in oncological treatment and diagnostic methods, as well as the higher overall survival rate and life expectancy rate. We present a case of a patient who synchronously developed four malignancies: cervical cancer, breast cancer, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and an olfactory groove meningioma. This case proves that the diagnosis of the cervical cancer does not exclude the occurrence of other malignancies. It also emphasizes the fact that every case of uterine cervical cancer with atypical clinical presentation should be thoroughly analyzed to avoid diagnostic mistakes, which in turn may worsen the prognosis.

Intertumoral Heterogeneity of Primary Breast Tumors and Synchronous Axillary Lymph Node Metastases Reflected in IHC-Assessed Expression of Routine and Nonstandard Biomarkers.

Breast cancer (BC) remains a significant healthcare challenge. Routinely, the treatment strategy is determined by immunohistochemistry (IHC)-based assessment of the key proteins such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67. However, it is estimated that over 75% of deaths result from metastatic tumors, indicating a need to develop more accurate protocols for intertumoral heterogeneity assessment and their consequences on prognosis. Therefore, the aim of this preliminary study was the identification of the expression profiles of routinely used biomarkers (ER, PR, HER2, Ki-67) and additional relevant proteins [Bcl-2, cyclin D1, E-cadherin, Snail+Slug, gross cystic disease fluid protein 15 (GCDFP-15), programmed death receptor 1 (PD-L1), and phosphatase of regenerating liver 3 (PRL-3)] in breast primary tumors (PTs) and paired synchronous axillary lymph node (ALN) metastases. A total of 67 tissue samples met the inclusion criteria for the study. The expression status of biomarkers was assessed in PTs and ALN metastases using tissue microarrays followed by IHC. In 11 cases, the shift of intrinsic molecular BC subtype was noticed between PTs and paired ALN metastases. Moreover, a significant disproportion in E-cadherin presence (p = 0.0002) was noted in both foci, and the expression status of all proteins except for HER2 demonstrated considerable variance (k = 1, p < 0.0001). Importantly, in around 30% of cases, the ALN metastases demonstrated discordance, i.e., loss/gain of expression, compared to the PTs. Intertumoral synchronous heterogeneity in both foci (primary tumor and node metastasis) is an essential phenomenon affecting the clinical subtype and characteristics of BC. Furthermore, a greater understanding of this event could potentially improve therapeutic efficacy.

Anti-Tumour Activity of Glycodendrimer Nanoparticles in a Subcutaneous MEC-1 Xenograft Model of Human Chronic Lymphocytic Leukemia.

BACKGROUND: Chronic Lymphocytic Leukaemia (CLL) is an indolent disorder, which mainly affects older adults. Since the advent of chemoimmunotherapy, great progress has been made in its treatment. However, some patients develop a more aggressive form of the disease and are included in the group of high-risk CLL patients with a dismal prognosis and a need for new therapies. OBJECTIVE: Maltotriose-modified poly(propylene imine) dendrimers were presented as potential agents in targeted therapy for CLL in the murine xenograft model. METHODS: Tumour, brain and internal organs resected from NOD scid gamma mice were subjected to gross and histopathological evaluation. RESULTS: The results of ex vivo tissue examination indicated that open-shell glycodendrimers prevented/inhibited the spread of CLL into the brain and internal organs and its transformation into a more aggressive form. CONCLUSION: The results of the study have a potentially important impact on the design of future personalized therapies as well as clinical trials.

A large single-institution retrospective analysis of aggressive B-cell lymphomas according to the 2016/2017 WHO classification.

BACKGROUND: High-grade B-cell lymphomas (HGBLs) comprise a new entity in the revised 2016/2017 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. The diagnosis of HGBL encompasses histopathology and immunohistochemistry, with additional molecular examination of the BCL2/MYC or BCL6/MYC rearrangement status. OBJECTIVES: The aim of the study was to summarize our experience in the histopathological and immunohistochemical diagnosis of patients with aggressive B-cell lymphomas according to the revised 2016/2017 WHO classifications. MATERIAL AND METHODS: We reviewed our single-institution experience with accurate diagnoses of HGBL and diffuse large B-cell lymphoma (DLBCL) using the available histopathological and immunohistochemical tools. The timeframe was from January 1, 2017 to April 18, 2018. RESULTS: Out of 265 patients, 217 (81.9%) were diagnosed with DLBCL, 43 (16.2%) with HGBL/DLBCL and 5 (1.9%) with not otherwise specified HGBL (HGBL-NOS). Regarding concurrent expression of MYC and BCL2 and/or BCL6 (double expressors (DE) and triple expressors (TE)), more DE and TE cases were found in the HGBL/DLBCL group than in the DLBCL group (25.53% vs 8.47%, p < 0.001, for DE cases and 55.32% vs 6.21%, p < 0.001, for TE cases). All 48 (100.00%) of the HGBL-NOS and HGBL/DLBCL patients, and 26 (11.98%) of the DLBCL-DE/TE cases were recommended for molecular analysis. CONCLUSIONS: Our findings show that a comprehensive histopathological and immunohistochemical examination may identify potential HGBL cases. This study emphasizes the need to introduce a suitable molecular examination for patients with HGBL morphology and/or double/triple expression of BCL2/BCL6/MYC proteins.