BACKGROUND AND OBJECTIVE: Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is a rare variant of malignant pancreatic tumor. There is still no standardized treatment for this uncommon subtype, as surgical resection with lymphadenectomy is the only potentially curative treatment so far. In this paper, we describe the current knowledge of this very rare specific subtype of pancreatic cancer (PC) as a narrative review. METHODS: For this review, we did not specify the time range of studies referred to due to limited data availability. Our inclusion criteria comprised previous studies, which specifically focused on the rare UCOGC subtype of PC as a confirmed histopathology, either pure or present together with other subtypes. We disregarded the studies involving any other PC subtype but not UCOGC, including undifferentiated and anaplastic carcinomas without osteoclast-like giant cell components. KEY CONTENT AND FINDINGS: The limited available data precludes a definitive assessment of the efficacy of both neoadjuvant and adjuvant chemotherapy in the treatment of UCOGC. Monoclonal antibody pembrolizumab has been proven to be effective in metastatic cases. Multiple cases demonstrate a better overall survival rate for patients with UCOGC only versus those having UCOGC as a component with a pancreatic ductal adenocarcinoma (PDAC) histopathological subtype. The same conclusion can be also drawn comparing the survival rate of patients having pure UCOGC versus UCOGC with associated PDAC. Programmed cell death ligand-1 expression has been shown to be an important determinant, which shortens the survival period of patients diagnosed with UCOGC. CONCLUSIONS: The rarity of UCOGC limits data for clinical courses and treatment plans. We need more data to better understand the relationship between pathogenic mutations, histological subtypes, and prognosis in PC, including UCOGC. Understanding UCOGC's molecular, clinical, radiological, and pathological characteristics can lead to earlier, more accurate diagnoses and better management.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Patient-derived organoids (PDOs) and xenografts (PDXs) are powerful tools for personalized medicine in pancreatic cancer (PC) research. This study explores the complementary strengths of PDOs and PDXs in terms of practicality, genetic fidelity, cost, and labor considerations. Among other models like 2D cell cultures, spheroids, cancer-on-chip systems, cell line-derived xenografts (CDX), and genetically engineered mouse models (GEMMs), PDOs and PDXs uniquely balance genetic fidelity and personalized medicine potential, offering distinct advantages over the simplicity of 2D cultures and the advanced, but often resource-intensive, GEMMs and cancer-on-chip systems. PDOs excel in high-throughput drug screening due to their ease of use, lower cost, and shorter experimental timelines. However, they lack a complete tumor microenvironment. Conversely, PDXs offer a more complex microenvironment that closely reflects patient tumors, potentially leading to more clinically relevant results. Despite limitations in size, number of specimens, and engraftment success, PDXs demonstrate significant concordance with patient responses to treatment, highlighting their value in personalized medicine. Both models exhibit significant genetic fidelity, making them suitable for drug sensitivity testing. The choice between PDOs and PDXs depends on the research focus, resource availability, and desired level of microenvironment complexity. PDOs are advantageous for high-throughput screening of a diverse array of potential therapeutic agents due to their relative ease of culture and scalability. PDXs, on the other hand, offer a more physiologically relevant model, allowing for a comprehensive evaluation of drug efficacy and mechanisms of action.
- MeSH
- individualizovaná medicína * metody MeSH
- lidé MeSH
- myši MeSH
- nádorové mikroprostředí účinky léků MeSH
- nádory slinivky břišní * farmakoterapie patologie genetika MeSH
- organoidy * účinky léků patologie MeSH
- protinádorové látky farmakologie terapeutické užití MeSH
- screeningové testy protinádorových léčiv metody MeSH
- xenogenní modely - testy protinádorové aktivity * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Pancreatic cancer is a severe malignancy with increasing incidence and high mortality due to late diagnosis and low sensitivity to treatments. Search for the most appropriate drugs and therapeutic regimens is the most promising way to improve the treatment outcomes of the patients. This study aimed to compare (1) in vitro efficacy and (2) in vivo antitumor effects of conventional paclitaxel and the newly synthesized second (SB-T-1216) and third (SB-T-121605 and SB-T-121606) generation taxanes in KRAS wild type BxPC-3 and more aggressive KRAS G12V mutated Paca-44 pancreatic cancer cell line models. In vitro, paclitaxel efficacy was 27.6 ± 1.7 nM, while SB-Ts showed 1.7-7.4 times higher efficacy. Incorporation of SB-T-121605 and SB-T-121606 into in vivo therapeutic regimens containing paclitaxel was effective in suppressing tumor growth in Paca-44 tumor-bearing mice at small doses (≤3 mg/kg). SB-T-121605 and SB-T-121606 in combination with paclitaxel are promising candidates for the next phase of preclinical testing.
- Publikační typ
- časopisecké články MeSH
BACKGROUND/AIM: Inflammation-based prognostic scores have shown prognostic significance and have been associated with clinical outcomes in various types of cancer. Inflammation is known to promote tumor progression leading to reduced survival. In pancreatic cancer, systemic inflammation is common and contributes to its dismal prognosis. Although the prognosis of pancreatic cancer is improving with the introduction of new drugs, the prognostic indicators are still poorly understood. The present study aimed to evaluate inflammation-based prognostic scores in patients with metastatic pancreatic cancer receiving first-line chemotherapy. PATIENTS AND METHODS: A total of 43 patients with metastatic pancreatic cancer undergoing first-line chemotherapy (gemcitabine+nab-paclitaxel and mFOLFIRINOX) in our institution were analyzed. Baseline clinicopathological and pre-treatment laboratory data were collected. Survival was estimated using the Kaplan-Meier method and survival differences were evaluated using the log-rank test. RESULTS: In the whole cohort, we identified lymphocyte-to-monocyte ratio ≥3, systemic inflammatory response index <2.3, carcinoembryonic antigen <2.5, neutrophil-to-lymphocyte ratio <5, Memorial Sloane Kettering score <2, and prognostic index <2 as prognostic markers associated with improved overall survival in patients receiving first-line chemotherapy. CONCLUSION: The current analysis showed an association between inflammatory-based prognostic markers and overall survival in patients with metastatic pancreatic cancer treated in a real-world setting at a single institution.
- MeSH
- albuminy aplikace a dávkování MeSH
- deoxycytidin analogy a deriváty aplikace a dávkování terapeutické užití MeSH
- dospělí MeSH
- fluoruracil aplikace a dávkování terapeutické užití MeSH
- gemcitabin MeSH
- irinotekan aplikace a dávkování terapeutické užití MeSH
- Kaplanův-Meierův odhad MeSH
- leukovorin aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory slinivky břišní * farmakoterapie mortalita patologie MeSH
- neutrofily patologie MeSH
- oxaliplatin aplikace a dávkování terapeutické užití MeSH
- paclitaxel aplikace a dávkování MeSH
- paliativní péče * metody MeSH
- prognóza MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- zánět * patologie farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Taxanes are widely used in the treatment of ovarian carcinomas. One of the main problems with conventional taxanes is the risk of development of multidrug resistance. New-generation synthetic experimental taxoids (Stony Brook Taxanes; SB-T) have shown promising effects against various resistant tumor models. The aim of our study was to compare the in vitro efficacy, intracellular content, and in vivo antitumor effect of clinically used paclitaxel (PTX) and SB-Ts from the previously tested second (SB-T-1214, SB-T-1216) and the newly synthesized third (SB-T-121402, SB-T-121605, and SB-T-121606) generation in PTX resistant ovarian carcinoma cells NCI/ADR-RES. The efficacy of the new SB-Ts was up to 50-times higher compared to PTX in NCI/ADR-RES cells in vitro. SB-T-121605 and SB-T-121606 induced cell cycle arrest in the G2/M phase much more effectively and their intracellular content was 10-15-times higher, when compared to PTX. Incorporation of SB-T-121605 and SB-T-121606 into therapeutic regimens containing PTX were effective in suppressing tumor growth in vivo in NCI/ADR-RES based mice xenografts at small doses (≤3 mg/kg), where their adverse effects were eliminated. In conclusion, new SB-T-121605 and SB-T-121606 analogs are promising candidates for the next phase of preclinical testing of their combination therapy with conventional taxanes in resistant ovarian carcinomas.
- Publikační typ
- časopisecké články MeSH
Úvod: Karcinom pankreatu je závažné onkologické onemocnění se stále se zvyšující incidencí a vysokou mírou morbidity a mortality. Terapeutické možnosti jsou limitované a pětileté přežití je 7–20 %, v závislosti na možnosti chirurgické resekce a časnosti záchytu onemocnění. Většina nemocných s touto diagnózou umírá v důsledku rezistence nádorových buněk a mikroprostředí vůči používané léčbě. Metody: V naší práci jsme se zaměřili na zavedení dvou typů in vivo modelů, kterými jsou cell-line derived xenograft (CDX) a patient derived xenograft (PDX). Tyto dva modely se navzájem výrazně liší metodologicky, náročností technickou i finanční, ale i dosaženými výsledky. Výsledky: V pilotní studii se nám podařilo úspěšně zavést CDX model s velmi agresivní a rezistentní linií PaCa-44 karcinomu pankreatu o celkovém počtu 30 jedinců NU/NU myší. Dále jsme vytvořili tři PDX modely s různými subtypy karcinomu pankreatu, pacientů operovaných na Chirurgické klinice FNKV, s jejich následnou retransplantací do dalších generací o celkovém počtu 23 jedinců kmene NOD/SCID a 47 jedinců kmene NU/NU. Zavedené CDX i PDX modely pak slouží k porovnání jak konvenčních, tak experimentálních chemoterapeutických režimů. Závěr: Dalšími kroky bude vyhodnocení vlivu léčebných režimů pomocí zobrazovacích i molekulárně genetických metod a optimalizace celého procesu pro využití v rámci precizní personalizované léčby pacientů s karcinomem pankreatu. Nadcházejícím cílem je vytvořit knihovnu PDX modelů nejčastějšího duktálního adenokarcinomu pankreatu a dalších vzácných subtypů karcinomu pankreatu.
Introduction: Pancreatic cancer is a severe oncological disease with an ever-increasing incidence and a high rate of morbidity and mortality. Therapeutic options are limited and the five-year overall survival rate is 7–20%, depending on the possibility of surgical resection and the earliness of detection. Most patients with this diagnosis die due to the resistance of tumour cells and their microenvironment to the used treatment regimes. Methods: In our study, we focused on the implementation of two in vivo models, which are the cell-line derived xenograft (CDX) and the patient-derived xenograft (PDX). These two models differ significantly from each other methodologically, technically, financially, but also in their achieved results. Results: In a pilot study, we managed to successfully implement the CDX model with a very aggressive and resistant PaCa-44 line of pancreatic cancer in a total of 30 NU/NU strain mice. Furthermore, we created three PDX models with various subtypes of pancreatic cancer from patients operated at the University Hospital Kralovske Vinohrady, Department of General Surgery. These tumours were re-transplanted into subsequent generations of 23 individuals of NOD/SCID strain and 47 NU/NU strain mice. The established CDX and PDX models are then used to compare conventional and experimental chemotherapy regimens. Conclusion: The next steps will be to evaluate the effects of treatment regimens by using imaging and molecular genetic methods and to optimise the entire process for further use in precise personalised medicine for patients with pancreatic cancer. The upcoming goal is to create a library of PDX models of the most common pancreatic ductal adenocarcinoma and other rare subtypes of pancreatic cancer.
- MeSH
- modely nemocí na zvířatech MeSH
- myši nahé MeSH
- nádory slinivky břišní * chirurgie terapie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
