Ipilimumab plus nivolumab in patients with symptomatic melanoma brain metastasis requiring corticosteroids.

Study Aim: To investigate the efficacy of PD-1-directed antibody-based therapy in patients with symptomatic melanoma brain metastases (MBM) and concurrent treatment with corticosteroids.

Methods: This retrospective cohort study included patients with cutaneous melanoma with symptomatic MBM and concurrent treatment with corticosteroids who received PD-1-directed antibody-based treatment at the Royal Marsden Hospital London between 2016 and 2021. The primary outcome was overall survival (OS), secondary outcomes were intracranial response rate (ORR) and duration of response (DOR).

Amphiphilic Dendritic Hydrogels with Carbosilane Nanodomains: Preparation and Characterization as Drug Delivery Systems.

Carbosilane dendrimers are hyperbranched lipophilic scaffolds widely explored in biomedical applications. This work exploits, for the first time, the ability of these scaffolds to generate functional hydrogels with amphiphilic properties. The monodispersity and multivalency enable a precise synthetic control of the network, while the lipophilicity improves the compatibility with poorly soluble cargo.

Temporal trends in the use and outcomes of temporary mechanical circulatory support as a bridge to cardiac transplantation in Spain. Final report of the ASIS-TC study.

Background: We aimed to describe recent trends in the use and outcomes of temporary mechanical circulatory support (MCS) as a bridge to heart transplantation (HTx) in Spain.

Methods: Retrospective case-by-case analysis of 1,036 patients listed for emergency HTx while on temporary MCS in 16 Spanish institutions from January 1st, 2010 to December 31st, 2020. Patients were classified in 3 eras according to changes in donor allocation criteria (Era 1: January 2010/May 2014; Era 2: June 2014/May 2017; Era 3: June 2017/December 2020).

Tumorigenic transformation of human prostatic epithelial cell line RWPE-1 by growth hormone-releasing hormone (GHRH).

Background: Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in the progression of various tumors. In this study, we analyzed the carcinogenetic potential of exposure to GHRH of a nontumor human prostate epithelial cell line (RWPE-1) as well as its transforming effect in a xenograft model.

Methods: We performed cell viability, cell proliferation, adhesion and migration assays.

Organ Donation: With Great Power Comes Great Responsibility.

Spain is a world leader in donation and transplantation. This model has been exported to other countries with favorable results. The objective of this study was to compare the actual donation intention rate with the effective donation figures, and analyze the main reasons why families decline organ donation.

Heterofunctional ruthenium(II) carbosilane dendrons, a new class of dendritic molecules to fight against prostate cancer.

A family of heterofunctional Schiff base carbosilane metallodendrons with [Ru(η-CH)(PTA)Cl] (PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.

Stimulation of neuroendocrine differentiation in prostate cancer cells by GHRH and its blockade by GHRH antagonists.

Prostate cancer is the second leading cause of cancer-related deaths among men in developed countries. Neuroendocrine prostate cancer, in particular, is associated with an aggressive phenotype and a poor prognosis. Neuroendocrine cells produce and secrete peptide hormones and growth factors in a paracrine/autocrine manner which promote the progression of the disease.

Anticancer Activity of Dendriplexes against Advanced Prostate Cancer from Protumoral Peptides and Cationic Carbosilane Dendrimers.

The interaction of neuropeptides, vasoactive intestinal peptide (VIP), or growth hormone-releasing hormone (GHRH), with a cationic carbosilane dendrimer forms dendriplexes with antitumoral behavior in advanced prostate cancer cells PC3. At the concentrations used for dendriplexes formation, the free peptides were protumoral and prometastatic in advanced prostate cancer, while dendrimer only showed low cytotoxicity, but did not avoid the metastatic behavior of PC3 cells. However, these nanoplexes favored also cell adhesion and avoided cell migration.

Systematic Analysis of Compounds Specifically Targeting Telomeres and Telomerase for Clinical Implications in Cancer Therapy.

The targeting of telomerase and telomere maintenance mechanisms represents a promising therapeutic approach for various types of cancer. In this work, we designed a new protocol to screen for and rank the efficacy of compounds specifically targeting telomeres and telomerase. This approach used two isogenic cell lines containing a circular human artificial chromosome (HAC, lacking telomeres) and a linear HAC (containing telomeres) marked with the transgene; compounds that target telomerase or telomeres should preferentially induce loss of the linear HAC but not the circular HAC.

Publisher Correction: A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage.

The original PDF version of this Article listed the authors as "Marcus J.G.W.

Growth hormone-releasing hormone receptor antagonists modify molecular machinery in the progression of prostate cancer.

Background: Therapeutic strategies should be designed to transform aggressive prostate cancer phenotypes to a chronic situation. To evaluate the effects of the new growth hormone-releasing hormone receptor (GHRH-R) antagonists: MIA-602, MIA-606, and MIA-690 on processes associated with cancer progression as cell proliferation, adhesion, migration, and angiogenesis.

Methods: We used three human prostate cell lines (RWPE-1, LNCaP, and PC3).

A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage.

The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH).

Growth hormone-releasing hormone (GHRH) promotes metastatic phenotypes through EGFR/HER2 transactivation in prostate cancer cells.

The involvement of growth hormone-releasing hormone (GHRH) in several relevant processes that contribute to prostate cancer progression was analyzed. Firstly, we evaluated GHRH effects on cell proliferation and adhesion in human cancer prostate cell lines, LNCaP and PC3, by using specific assays (BrdU incorporation and collagen adhesion). The expression levels of the main marker molecules of these processes were measured by RT-PCR, Western blotting and zymography assays.

Growth hormone-releasing hormone induced transactivation of epidermal growth factor receptor in human triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is a subset of breast cancers which is negative for expression of estrogen and progesterone receptors and human epidermal growth factor receptor-2 (HER2). Chemotherapy is currently the only form of treatment for women with TNBC. Growth hormone-releasing hormone (GHRH) and epidermal growth factor (EGF) are autocrine/paracrine growth factors in breast cancer and a substantial proportion of TNBC expresses receptors for GHRH and EGF.

Anti-proliferative and pro-apoptotic effects of GHRH antagonists in prostate cancer.

Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in the progression of various tumors. In vitro and in vivo studies have demonstrated that GHRH antagonists inhibit the growth of several cancers. GHRH antagonists, JMR-132 and JV-1-38 inhibit the growth of androgen-independent prostate tumors.

The Dawn of Aurora Kinase Research: From Fly Genetics to the Clinic.

Aurora kinases comprise a family of highly conserved serine-threonine protein kinases that play a pivotal role in the regulation of cell cycle. Aurora kinases are not only involved in the control of multiple processes during cell division but also coordinate chromosomal and cytoskeletal events, contributing to the regulation of checkpoints and ensuring the smooth progression of the cell cycle. Because of their fundamental contribution to cell cycle regulation, Aurora kinases were originally identified in independent genetic screens designed to find genes involved in the regulation of cell division.

VIP induces NF-κB1-nuclear localisation through different signalling pathways in human tumour and non-tumour prostate cells.

The nuclear factor κB (NF-κB) is a powerful activator of angiogenesis, invasion and metastasis. Transactivation and nuclear localisation of NF-κB is an index of recurrence in prostate cancer. Vasoactive intestinal peptide (VIP) exerts similar effects in prostate cancer models involving increased expression of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) which are related to NF-κB transactivation.

Polo kinase regulates the localization and activity of the chromosomal passenger complex in meiosis and mitosis in Drosophila melanogaster.

Cell cycle progression is regulated by members of the cyclin-dependent kinase (CDK), Polo and Aurora families of protein kinases. The levels of expression and localization of the key regulatory kinases are themselves subject to very tight control. There is increasing evidence that crosstalk between the mitotic kinases provides for an additional level of regulation.

Growth hormone-releasing hormone antagonists abolish the transactivation of human epidermal growth factor receptors in advanced prostate cancer models.

Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in a variety of cellular phenotypes related with tumorigenesis process. Human epidermal growth factor receptor family members (HER) such as EGFR and HER2 are involved in mitogenic signaling pathways implicated in the progression of prostate cancer. We analyzed the cross-talk between GHRH and EGF receptors in prostate cancer.

Signalling pathways involved in antitumoral effects of VIP in human renal cell carcinoma A498 cells: VIP induction of p53 expression.

Vasoactive intestinal peptide (VIP) decreases cell proliferation through PI3K signalling and prevents tumour progression in clear renal cell carcinoma (RCC). Here we analyzed the signalling pathways that mediate such VIP effects by using human RCC A498 cells. The effects of treatment with 1 μM VIP and/or specific protein kinase inhibitors such as H89, Wortmannin and PD98059 were studied by cell adhesion assay, ELISA of VEGF165 and ROS production assays.