1,720,991 research outputs found
Drug therapy of advanced cutaneous squamous cell carcinoma: is there any evidence?
Full text linkThere are few randomized controlled studies to guide the treatment of advanced cutaneous squamous cell carcinoma. The existing treatments are mostly based on case reports and small case series. Here we review recently available insights concerning the treatment of locally advanced and metastatic squamous cell carcinoma, with a special emphasis on novel targeted therapy and immunotherapy
Cancer treatment-induced bone loss (CTIBL): Pathogenesis and clinical implications.
No full textOsteopenia and osteoporosis are often long-term complications of anti-neoplastic treatments, defined as ‘‘cancer treatment-induced bone loss” (CTIBL). This pathological condition in oncologic patients results in a higher fracture risk than in the general population, and so has a significant negative impact on their quality of life. Hormone treatment is the main actor in this scenario, but not the only one. In fact, chemotherapies, radiotherapy and tyrosine kinase inhibitors may contribute to deregulate bone remodeling via different mechanisms. Thus, the identification of cancer patients at risk for CTIBL is essential for early diagnosis and appropriate intervention, that includes both lifestyle modifications and pharmacological approaches to prevent bone metabolism failure during anti-tumor treatments
Molecular Aberrations Stratify Grade 2 Astrocytomas Into Several Rare Entities: Prognostic and Therapeutic Implications
Full text linkThe identification of specific molecular aberrations guides the prognostic stratification and management of grade 2 astrocytomas. Mutations in isocitrate dehydrogenase (IDH) 1 and 2, found in the majority of adult diffuse low-grade glioma (DLGG), seem to relate to a favorable prognosis compared to IDH wild-type (IDH-wt) counterparts. Moreover, the IDH-wt group can develop additional molecular alterations worsening the prognosis, such as epidermal growth factor receptor amplification (EGFR-amp) and mutation of the promoter of telomerase reverse transcriptase (pTERT-mut). This review analyzes the prognostic impact and therapeutic implications of genetic alterations in adult LGG
Abstract 2808: Characterization of the metastatic behavior and gene expression profile (RNAseq) of different melanoma cell lines: a comprehensive in vivo model
No full textResults
Conclusions
Metastasis is the major cause of death in malignant
melanoma. Several factors, including clinicalpathological
and tumor biological features may restrain
prognosis. Molecular mechanisms regulating melanoma
progression and metastasis have been partially
discovered, and thus we developed an in vivo model of
metastatic melanoma to investigate potential genes
implicated in these events.
To evaluate the in vivo metastatic activity of five
different melanoma cell lines (LCP, LCM, WM266, SKMel28
and A375), we completed intra-cardiac (ic)
injection of 1x106 luminescent cells or PBS as control in
three NOD-SCID mice per cell line. After 3 weeks, mice
were studies by in vivo bioluminescence imaging (IVIS
Lumina LT) to measure the mean radiance
(p/sec/cm2/sr), that we arbitrarily considered as a
surrogate of the total metastatic tumor burden (t-MTB).
Animals were euthanized at the humane endpoints
achievement and underwent X-ray evaluation for bone
metastasis detection. The Kaplan-Meyer curves
described the time to sacrifice from ic injection. Mouse
necropsy identified metastatic organs that were
explanted and processed for both histology and gene
expression analysis. Melanoma cell lines were profiled
for gene expression (RNAseq) of 118 genes notably
involved in cancer progression and metastasis.
Quantitative real time PCR (qRT-PCR) explored the
expression of a restrict number of genes on formalinfixed
paraffin-embedded (FFPE) metastatic samples
from euthanized animals.
All melanoma cell lines demonstrated a metastatic
behaviour following ic injection with a variable attitude
to produce bone and visceral metastasis (Figure 1).
Mice injected with LCP, LCM and WM266 showed a
lower t-MTB and increased survival (Figure 2) as
compared to A375 and SK-Mel28. Thus, we arbitrarily
defined LCP, LCM and WM-266 cells ‘poorly metastatic’
(group A), while A375 and SK-Mel28 ‘highly metastatic’
(group B).
The principal component analysis (Figure 3A) and the
unsupervised hierarchical clustering of 118 gene
transcriptome analysis (not shown) revealed similar
gene expression profiling among cell lines grouped for
the metastatic attitude. The gene expression analysis
performed on FFPE samples (Figure 3B) identified five
deregulated genes (WNT5A, COL6A3, PTHLH, SOX9 and
SERPINE1) between A and B.
We describe the metastatic capacity of five melanoma
cell lines. Gene expression profiling revealed the
activation of five genes as putatively responsible for the
high aggressiveness of A375 and SK-Mel28 cells. These
results suggest to investigate these genes in a clinical
setting and their possible application as druggable
target for future therapeutic strategies
Circulating tumor cells from melanoma patients show phenotypic plasticity and metastatic potential in xenograft NOD.CB17 mice
Full text linkBACKGROUND: Innovative therapies have improved the overall survival in melanoma, although a high number of patients still experience disease progression or recurrence. Ex-vivo culture of circulating tumour cells (CTCs) represents a valuable laboratory resource for in-depth characterization of rare cell populations responsible for disease progression. METHODS: CTCs from patients with metastatic melanoma were in-vitro established. Their stemness was demonstrated by both phenotypic and genotypic assays, as well as by functional studies. Xenograft experiments in NOD.CB17 mice injected with CTCs from a single patient were completed. Data were analysed by Student’s test and results expressed as mean ± SEM. RESULTS: CTCs share the mutational profile with primary cells, an intermediate epithelial-mesenchymal transition (EMT) phenotype and high expression of the immunosuppressive factors. A subclonal CTC population exhibited stem cell properties as high aldehyde dehydrogenase 1 activity, melanosphere-forming ability, and expression of major stemness transcription factors. Xenograft experiments confirmed the CTC ability to generate melanoma in-vivo and revealed enhanced metastatic propensity. CONCLUSIONS: CTCs play a relevant role in melanoma and may actively contribute to drive the disease progression and metastasis. Thus, they are a unique potential tool for pharmacogenomic studies to guide treatment strategies in advanced disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09829-1
Effect of vitaxin on hyperactive osteoclastogenesis in multiple myeloma: a preclinical study
No full textTe avbeta3/avbeta5 blockage by Cilengitide disables the osteoclast-like differentiation of malignant plasma cells in multiple myeloma
No full textCharacterization of the metastatic behavior and gene expression profile (RNAseq) of different melanoma cell lines: a comprehensive in vivo model.
No full textN
Exosomes in melanoma: A role in tumor progression, metastasis and impaired immune system activity
Full text linkExosomes (Exo) are small vesicles produced by melanoma cells and the accessory cells of the tumor microenvironment. They emerge via both classical and direct pathways and actively participate in tumor colonisation of distant tissues. The proteins, nucleic acids, cytokines and growth factors engulfed by Exo are transferred to recipient cells, where they drive numerous functions required for the tumor escape from immune system control and tumor progression. By positively or negatively modulating immune cell properties, Exo provoke immune suppression and, in turn, defective dendritic cell (DC) functions. Together, these effects limit the cytotoxicity of T-cells and expand both T-regulatory and myeloid-derived suppressor populations. They also hinder perforin and granzyme production by natural killer cells. Finally, Exo also control the organotropism of melanoma cells. The distinct phenotypic properties of Exo can be exploited both for diagnostic purposes and in the early identification of melanoma patients likely to respond to immunotherapy. The potential therapeutic application of Exo derived from DCs has been demonstrated in vaccination trials, which showed an increase in anti-melanoma activity with respect to circulating tumor cells. However, additional studies are required before Exo can be effectively used in diagnostic and therapeutic applications in melanoma
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