Experimental oncology最新文献

Cholangiocarcinoma during pregnancy is a very rare condition. We present the case of a 35-year-old pregnant woman with intrahepatic cholangiocarcinoma. To our knowledge, this is the first case of cholangiocarcinoma in a patient with twin pregnancy. At 25 weeks of gestation, surgical intervention was performed: right-sided hemihepatectomy, lymphadenectomy D3, and diaphragmatic peritoneumectomy on the right side. At 33 weeks of pregnancy, a cesarean section was performed. Currently, the patient is receiving chemotherapy. A multidisciplinary approach should be a standard workup in making decisions regarding the treatment strategy for a pregnant patient with a cancer diagnosis.

Obstructive jaundice (OJ) is a common diagnosis in everyday clinical practice, which requires a thorough understanding of pathophysiological changes occurring in the liver to plan ongoing treatment and predict its effectiveness in the postoperative period. The study aimed to determine the dynamics of changes in the levels of apoptosis markers (caspase-3 and BCL-2) at the time of preoperative biliary decompression (PBD) and major surgery depending on the severity of the hepatic failure (HF) and to evaluate their correlation with the severity grade of HF in patients with malignant obstructive jaundice (MOJ).

Materials and methods: The study included 104 patients with MOJ who underwent PBD. All patients were diagnosed with HF of moderate severity (n = 65) or severe HF (n = 39). During PBD and main surgical intervention, the levels of caspase-3 and BCL-2 were determined in blood serum and bile by the Sandwich-ELISA method.

Results: The values of apoptosis markers in patients with moderate and severe HF were significantly different at the time of PBD and major surgery (p < 0.001). PBD significantly reduced the levels of caspase-3 and increased the levels of BCL-2 in sera of patients with MOJ and HF, which was confirmed by further intraoperative values of the indicators, p < 0.001. Imbalance of serum caspase-3 (R2 Nagelkerke = 0.553, p = 0.013) and BCL-2 (R2 Nagelkerke = 0.327, p = 0.003) levels was associated with severe HF.

Conclusions: The indicators of apoptosis after PBD can serve as additional markers of the effectiveness of a patient's treatment in the preoperative period and can be included in the diagnostic and therapeutic algorithm for patients with MOJ.

Atypical BRAF Mutations in Hairy Cell Leukemia: Diagnostic and Therapeutic Considerations.

Background: Immune checkpoint blockade (ICB) therapy targeting the PD-1/PD-L1 axis results in poor outcomes in prostate cancer (PCa). PD-L1, the most commonly used predictive marker for the efficacy of PD-1/PD-L1-targeted immunotherapy, appears to be rarely or at low levels expressed in primary androgen-responsive PCa tumors, with higher levels in advanced PCa. PD-L1 expression has not yet been studied regarding the androgen receptor (AR) status.

Materials and methods: We investigated the effect of hormone stimulation by dihydrotestosterone (DHT) and AR inhibition by enzalutamide on PD-L1 expression in LNCaP and LNCaP-AR+ cells, the latter overexpressing AR. Cells were grown for 24 h under hormone-free conditions and then for 24 h in the presence of DHT (10 nM) and/or enzalutamide (10 μM). Cell viability was assessed by Annexin V and propidium iodi de staining. PD-L1 expression was determined semiquantitatively at the mRNA level. ANOVA and independent t-tests were used to compare experimental results between different treatment modalities.

Results: DHT treatment induced some degree of apoptosis in AR-overexpressing LNCaP-AR + cells, but not in parental LNCaP cells. We found low basal expression of PD-L1 in both cell lines, with 2.7-fold higher levels in LNCaP-AR+ cells. DHT treatment increased PD-L1 expression by approximately three-fold in LNCaP cells, while in enzalutamide-treated cells, the expression was lower than the basal level. In LNCaP cells treated concomitantly with DHT and enzalutamide, AR inhibition reduced DHT-induced PD-L1, suggesting an androgen-dependent expression of PD-L1. Unlike in LNCaP cells, androgen stimulation did not increase PD-L1 expression in LNCaP-AR+ cells, and enzalutamide did not affect PD-L1 expression either.

Conclusion: Our data reveal that PD-L1 is expressed in an AR-dependent manner in PCa cells, and its expression in AR-overexpressing cells is not modulated by receptor inhibition.

Background: Colorectal cancer (CRC) is one of the most common cancer types diagnosed globally with high rates of morbidity and mortality. Several biomarkers are associated with cancer stem cells present in various solid tumors, including CRC.

Aim: This study aimed to investigate the expression of CD44 and OCT3/4 cancer stem cell markers in samples of CRC biopsies and benign colon tumors of Iraqi patients using the immunohistochemical (IHC) technique.

Materials and methods: The IHC analysis was used to determine CD44 and OCT3/4 expression levels in tissue samples of 42 CRC cases and 18 benign neoplasms.

Results: The findings revealed a significant increase in high expression levels of CD44 in CRC cases (81%) vs 23% in benign tumor tissue samples. Similarly, a significant rise in OCT3/4 expression was observed in CRC cases (66%) compared to benign tumors (29%). The expression levels of CD44 and OCT3/4 were significantly associated with the CRC stages.

Conclusion: Our data indicated that CD44 and OCT3/4 may play a role in CRC progression.

Background: World statistics demonstrates that about 15% of liver resections are performed laparoscopically. Nevertheless, in Ukrainian specialized centers, this figure is about 5% or even less. The aim of the forthcoming trial is to determine whether laparoscopic liver resections (LLR) performed in the state Ukrainian specialized centers have better surgical and long-term oncological outcomes compared to an open approach (OLR) with the parallel examination of the surgically induced systemic stress response.

Methods: This trial is a national (Ukrainian) multicenter randomized controlled trial, with patients and ward personnel blinded to the treatment approach. Patients will be randomized in a 1:1 ratio to LLR or OLR with REDCap® software. The primary end-point is to compare the time to discharge in the cohorts under study. The goal is to reduce the length of hospital stay in the LLR group at least by 28%. To obtain a power of 80% and an alpha level of 0.05 for a two-sided p-value, a minimum of 126 patients (63 in each group) are to be included.

Discussion: Conducting a randomized trial in Ukraine comparing laparoscopic and open minor liver surgery techniques can leverage the country's diverse patient demographics and healthcare infrastructure. This study will be able to provide crucial insights into the effectiveness, safety, and feasibility of both surgical approaches in a population that may have different disease presentations and healthcare access compared to Western countries. Trial registration and status. The trial was registered in Researchregistry.com (UIN10336) on May 26, 2024, and currently has recruited 38 patients.

A rare case of hairy cell leukemia with CD10+CD23+ expression and leukocytosis is described. The key point marker for hairy cell leukemia is the presence of the BRAF V600E mutation regardless of the leukocyte count and atypical aberrant CD10+ or CD23+ expression. The presented clinical case report is important for understanding the biology of hairy cell leukemia and emphasizes the role of molecular genetic testing in atypical morpho-phenotyping disease presentation.

Background: Colorectal cancer, ranking second place in global cancer mortality, arises from diverse causes. There is growing recognition of the substantial involvement of the epigenetic modifications of histones at the DNA level in the occurrence of CRC.

Aim: To assess the expression of p53, HDAC1, and HDAC3 proteins in a cohort of CRC patients and to analyze potential relationship between their expression and the stages of CRC progression.

Materials and methods: The retrospective investigation was carried out on 95 paraffin-embedded CRC tissue samples. The expression of p53, HDAC1, and HDAC3 was assessed immunohistochemically.

Results: Notably, the expression of the p53 protein in CRC tissue samples exhibited a prominent correlation with the protein expression of both HDAC1 (p < 0.001, rho = 0.522) and HDAC3 (p < 0.001, rho = 0.411), as well as the advanced TNM staging of CRC (p = 0.002, rho = 0.313). Downregulation of p53 was correlated with underexpressed HDAC1 and HDAC3. Nevertheless, the observed expression of p53 exhibited a significant negative correlation with the age of the patients.

Conclusion: The data on HDACs-p53 co-expression suggest a possible mechanism of interaction between the expression of these proteins.

Background: Exosomes have become a potential field of nanotechnology for the treatment and identification of many disorders. However, the generation of exosomes is a difficult, time-consuming, and low-yielding procedure. At the same time, exosome mimetics (EM) resemble exosomes in their characteristics but have higher production yields. The aim of this study was to produce natural killer (NK) cell-derived EM (NKEM) loaded with sorafenib and test their killing ability against thyroid cancer cell lines.

Materials and methods: Sorafenib was loaded into NKEM by mixing sorafenib with NK cells during NKEM production (NKEM-S). Then, these two types of nanoparticles were characterized with nanoparticle tracking analysis (NTA) to measure their sizes. In addition, the cellular uptake and in vitro killing effect of NKEM-S on thyroid cancer cell lines were investigated using confocal laser microscopy and bioluminescence imaging (BLI) techniques.

Results: The uptake of NKEM and NKEM-S by the thyroid cancer cells was observed. Moreover, BLI confirmed the killing and anti-proliferation effect of NKEM-S on two thyroid cancer cell lines. Especially important, the NKEM-S demonstrated a desirable killing effect even for anaplastic thyroid cancer (ATC) cells.

Conclusion: Sorafenib-loaded NKEM showed the ability to kill thyroid cancer cells in vitro, even against ATC. This provides a new opportunity for drug delivery systems and thyroid cancer treatment.

Using the Ukrainian version of the Medical Outcomes Study Short Form, MOS SF-36 questionnaire for assessment of quality of life (QoL), a prospective analysis of the QoL of patients with bladder cancer who underwent radical surgery in the scope of radical cystectomy (group 1, 15 patients) and organ-preserving surgeries (bladder resection or transurethral resection, group 2, 40 patients) was conducted in the period from 2020 to 2022 at the Center for Urology and Urologic Oncology of the Feofania Clinical Hospital. The survey was conducted 1 week before radical surgery and 6 months after surgery. None of the studied patients had signs of recurrence or progression of bladder cancer during the postoperative survey. With identical QoL indicators before surgery, patients who underwent organ-preserving surgeries demonstrated significantly higher QoL indicators, such as physical, role, social, emotional functioning, and psychological health.