Publications by authors named "Marco DE Velasco"

Gut microbiota plays a crucial role in the development and progression of prostate cancer, with previous studies indicating that certain bacterial taxa are more abundant in castration-resistant prostate cancer (CRPC) compared to hormone-sensitive prostate cancer (HSPC). Notably, the composition of gut microbiota can vary significantly by geographic region, and Japanese individuals have a distinct microbial profile. However, research exploring these differences within Japanese populations remains limited.

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Background: Genome DNA methylation profiling is a promising yet costly method for cancer classification, involving substantial data. We developed an ensemble learning model to identify cancer types using methylation profiles from a limited number of CpG sites.

Methods: Analyzing methylation data from 890 samples across 10 cancer types from the TCGA database, we utilized ANOVA and Gain Ratio to select the most significant CpG sites, then employed Gradient Boosting to reduce these to just 100 sites.

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Chronic systemic inflammation caused by diseases such as ulcerative colitis (UC) and Crohn's disease (CD) increases the risk of developing colorectal cancer (CRC). Recent evidence indicates that patients with UC are more susceptible to prostate cancer (PCa), and individuals with PCa may also be at a higher risk of developing CRC. However, these relationships are not well defined.

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Article Synopsis
  • Prostate cancer development is influenced by lifestyle factors and gut microbiome changes, with a specific link to gut dysbiosis, but the exact mechanisms are still unclear.
  • The study analyzed stool samples from tumor-bearing mice and humans to investigate the relationship between gut microbes and prostate cancer status, identifying key bacterial taxa associated with the disease.
  • Results indicate that both humans and mice show distinct gut microbiome profiles related to prostate cancer, highlighting potential bacterial metabolites that may promote the disease and suggesting a preclinical model for further research.
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  • Sarcomatoid hepatocellular carcinoma (SHCC) is a rare and aggressive form of liver cancer that has distinct biological markers.
  • The study analyzed gene expression in SHCC tissues and found a significant reduction of the PBRM1 gene, indicating its potential role in the disease.
  • Further analysis showed that many of the differentially expressed genes were related to DNA replication and histone methylation, supporting the idea that PBRM1 could serve as a useful biomarker for SHCC diagnosis and evaluation.
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Human prostate cancer is a heterogenous malignancy that responds poorly to immunotherapy targeting immune checkpoints. The immunosuppressive tumor microenvironment that is typical of human prostate cancer has been the main obstacle to these treatments. The effectiveness of these therapies is also hindered by acquired resistance, leading to slow progress in prostate cancer immunotherapy.

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Article Synopsis
  • - Obesity and high-fat diets increase the risk of prostate cancer and affect the gut microbiome, which is crucial in various diseases, including prostate cancer.
  • - Research shows that changes in the gut microbiome linked to prostate cancer involve gut dysbiosis, which contributes to cancer growth and influences androgen metabolism.
  • - Addressing lifestyle and modifying the gut microbiome through prebiotics or probiotics could help reduce prostate cancer risk, highlighting the significance of the "Gut-Prostate Axis" in treatment and screening.
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The human gut microbiota changes under the influence of environmental and genetic factors, affecting human health. Extensive studies have revealed that the gut microbiome is closely associated with many non-intestinal diseases. Among these, the influence of the gut microbiome on cancer biology and the efficacy of cancer therapy has attracted much attention.

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Background: The Biocartis Idylla platform is a fully automated, real-time PCR-based diagnostic system. The Idylla KRAS and NRAS-BRAF Mutation Tests have been developed for the qualitative detection of mutations in KRAS, NRAS and BRAF genes, facilitating the genomic profiling of patients with colorectal cancer. The aim of the present study was to evaluate clinical performances of these tests in Japan.

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The gut microbiome is linked to several diseases such as Alzheimer's disease, rheumatoid arthritis, and colon cancer. The gut microbiome is also associated with the modulation of immune function, resulting in a different response to immune checkpoint therapy. The gut microbiome differs according to lifestyle, diet, sex, race, genetic background, and country.

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Prostate cancer (PCa) is the most common malignancy in men worldwide, thus developing effective prevention strategies remain a critical challenge. Insulin-like growth factor 1 (IGF-1) is produced mainly in the liver by growth hormone signaling and is necessary for normal physical growth. However, several studies have shown an association between increased levels of circulating IGF-1 and the risk of developing solid malignancies, including PCa.

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Background/purpose Of The Study: Tumor heterogeneity based on copy number variations is associated with the evolution of cancer and its clinical grade. Clonal composition (CC) represents the number of clones based on the distribution of B-allele frequency (BAF) obtained from a genome-wide single nucleotide polymorphism (SNP) array. A higher CC number represents a high degree of heterogeneity.

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Immune checkpoint inhibitors (ICIs) have become the standard of care for several cancers. However, ICI therapy has also been associated with various immune-related adverse events (irAEs). Clinical manifestations of immune-related colitis resemble those of inflammatory bowel diseases such as ulcerative colitis (UC).

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Article Synopsis
  • * A 60-year-old man experienced Grade 3 disseminated intravascular coagulation (DIC) after being treated with pazopanib following nivolumab and ipilimumab, suggesting a potential interaction between the two treatments.
  • * The patient recovered after receiving thrombomodulin and platelet transfusion, and later resumed pazopanib without further DIC issues, highlighting the importance of closely monitoring patients transitioning from ICI therapies to molecular-targeted treatments.
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Significant improvements with apalutamide, a nonsteroidal antiandrogen used to treat patients suffering from advanced prostate cancer (PCa), have prompted evaluation for additional indications and therapeutic development with other agents; however, persistent androgen receptor (AR) signaling remains problematic. We used autochthonous mouse models of -deficient PCa to examine the context-specific antitumor activity of apalutamide and profile its molecular responses. Overall, apalutamide showed potent antitumor activity in both early-stage and late-stage models of castration-naïve prostate cancer (CNPC).

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Background: Inflammatory cytokines and immature myeloid derived suppressor cells (MDSCs), which increase during cancer progression, could lead to a neutrophil increase and lymphocyte reduction. Thus, the neutrophil-lymphocyte ratio (NLR) was used to predict survival of patients suffering from urological cancers including upper urinary tract carcinoma. We further determined whether the NLR during the first cycle of first-line chemotherapy could predict cancer specific survival.

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Colitis is a risk factor for colorectal cancer (CRC) and can change the dynamics of gut microbiota, leading to dysbiosis and contributing to carcinogenesis. The functional interactions between colitis-associated CRC and microbiota remain unknown. In this study, colitis and CRC were induced in BALB/c mice by the administration of dextran sodium sulfate (DSS) and/or azoxymethane (AOM).

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Immune checkpoint inhibitors (ICIs) are widely used to treat various malignancies. Although the gut microbiome is known to influence the efficacy of ICIs on epithelial tumors, the functional interactions between gut taxa and colonic mucosa remain poorly understood. Here we performed transcriptomic profiling and 16S rRNA sequencing to investigate the relationships between mucosal gene expression and microbial composition with ICI responses and gastrointestinal immune-related adverse events (GI irAEs).

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Given that sustained remission is the ultimate treatment goal in the management of patients with ulcerative colitis (UC), the decision to stop anti-tumor necrosis factor (anti-TNF) treatment in UC patients is difficult. The aim of this study was to evaluate mucosal microbiota and gene expression profiles associated with long-term remission after discontinuation of anti-TNF therapy. In nine UC patients who received anti-TNF therapy for 6 months, microbiota isolated from uninflamed mucosae and gene expression in inflamed and uninflamed mucosae were investigated at week 0 and at week 24.

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The present study investigated the antitumor activity and chemopreventive effects of a nanoparticle formulation of curcumin in preclinical models of mouse Pten-deficient prostate cancer. The antitumor activity of the nanoparticle curcumin was evaluated in mouse castration-naïve (7113-D3) and castration-resistant prostate cancer (2945-E10) derived cell lines in vitro. Cell viability was reduced in both cell lines in a dose and time-dependent manner.

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Article Synopsis
  • Traditional and next-generation antiandrogen therapies struggle in clinical settings due to resistance, leading to ongoing activity of the androgen receptor (AR).
  • Antisense oligonucleotides (ASOs) offer a promising alternative treatment for castration-resistant prostate cancer (CRPC) by blocking gene expression related to AR.
  • A combination treatment of a Generation-2.5 ASO targeting AR and an AKT inhibitor (AZD5363) showed improved efficacy and extended survival in advanced CRPC models, suggesting a viable therapeutic strategy.
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Background: HOX genes encode transcription factors that play key roles in modulating normal tissue morphogenesis, differentiation and homeostasis. Disruption of normal HOX gene expression occurs frequently in human cancers and is associated with both tumor promoting and suppressing activities. Among these is, HOXA10, a pleiotropic gene that is critical for normal prostate development.

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Phosphatase and tensin homolog (PTEN) deficiency is associated with development, progression, and metastasis of various cancers. However, changes in gene expression associated with PTEN deficiency have not been fully characterized. To explore genes with altered expression in PTEN‑deficient cells, the present study generated a PTEN‑knockout cell line (ΔPTEN) from a mouse prostate cancer‑derived cell line using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‑associated protein 9 (CRISPR/Cas9) gene editing system.

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Purpose Of Review: In this review, we present the progress and current landscape for prostate cancer immunotherapy and overview recent scientific findings that shed novel insights into immunoresistance and discuss potential therapeutic strategies.

Recent Findings: Prostate cancer immunogenicity is hampered by a highly immunosuppressive microenvironment and low mutation burden. Complex interactions between resident immunosuppressive cells such regulatory T cells, macrophages, myeloid-derived suppressor cells, and cancer cells cooperate to suppress antitumor immune responses and promote disease progression.

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Intratumoral heterogeneity of cancer cells remains largely unexplored. Here we investigated the composition of ovarian cancer and its biological relevance. A whole-genome single nucleotide polymorphism array was applied to detect the clonal composition of 24 formalin-fixed, paraffin-embedded samples of human ovarian cancer.

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