http://web.stanford.edu/group/brunet/Cell1999

Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor

Convergence of Probability Measures. By P. Billingsley. Chichester, Sussex, Wiley, 1968. xii, 253 p. 9 1/4“. 117s.

Convergence of Probability Measures

Mitogen-activated protein kinases (MAPKs) are important signal transducing enzymes, unique to eukaryotes, that are involved in many facets of cellular regulation. Initial research concentrated on defining the components and organization of MAPK signalling cascades, but recent studies have begun to shed light on the physiological functions of these cascades in the control of gene expression, cell proliferation and programmed cell death.

/pdf/mammalian-map-kinase-signalling-cascades-2wtn4qrixr.pdf

Mammalian MAP kinase signalling cascades

Cells undergo a variety of biological responses when placed in hypoxic conditions, including activation of signalling pathways that regulate proliferation, angiogenesis and death. Cancer cells have adapted these pathways, allowing tumours to survive and even grow under hypoxic conditions, and tumour hypoxia is associated with poor prognosis and resistance to radiation therapy. Many elements of the hypoxia-response pathway are therefore good candidates for therapeutic targeting.

Hypoxia — a key regulatory factor in tumour growth

Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation

Mesothelin is a membrane-associated protein overexpressed in pancreatic ductal adenocarcinoma (PDAC). Some mesothelin-targeted therapies are in clinical development but the identification of patients eligible for such therapies is still challenging. The objective of this study was to perform the imaging of mesothelin in mice models of PDAC with a technetium-labeled anti-mesothelin single-domain antibody (99mTc-A1). Methods: The Cancer Genomic Atlas (TCGA) database was used to determine the prognostic role of mesothelin in PDAC. 99mTc-A1 was evaluated both in vitro in PDAC cells (SW1990 and AsPC-1) and in vivo in an experimental model of mesothelin-expressing PDAC (AsPC-1) in mice. Results: TCGA analysis showed that PDAC patients with high mesothelin expression had a shorter overall survival (P = 0.00066). The binding of 99mTc-A1 was 2.1-fold greater in high-mesothelin-expressing AsPC-1 cells when compared to moderate-mesothelin-expressing SW1990 cells (p < 0.05). In vivo, the 99mTc-A1 uptake was 3.5-fold higher in AsPC-1-derived tumors as compared to a technetium-labeled irrelevant antibody (99mTc-Ctl) (p < 0.01). Conclusions: 99mTc-A1 accurately allows imaging of mesothelin-expressing experimental PDAC tumors. Our experiments paved the way for the development of a companion test for mesothelin-targeted therapies.

https://www.mdpi.com/2072-6694/11/10/1531/pdf

99mTc-A1 as a Novel Imaging Agent Targeting Mesothelin-Expressing Pancreatic Ductal Adenocarcinoma

The invention provides an isolated antibody or a fragment thereof, which is directed to the human chemokines CXCL1, CXCL7 and CXCL8, said antibody or fragment being capable of binding to the human chemokine CXCL1 with an equilibrium dissociation constant (K D ) of at most 16 nM, to the human chemokine CXCL7 with an equilibrium dissociation constant (K D ) of at most 5 nM and to the human chemokine CXCL8 with an equilibrium dissociation constant (K D ) of at most 45 nM, as determined by surface plasmon resonance. The invention also provides some applications of said isolated antibody.

Anti-cxcl1, cxcl7 and cxcl8 antibodies and their applications

https://hal.archives-ouvertes.fr/hal-01026116/document

Greedy vector quantization

In this paper, we present an overview of the recent developments of functional quantization of stochastic processes, with an emphasis on the quadratic case. Functional quantization is a way to approximate a process, viewed as a Hilbert-valued random variable, using a nearest neighbour projection on a finite codebook. A special emphasis is made on the computational aspects and the numerical applications, in particular the pricing of some path-dependent European options.

Quadratic optimal functional quantization of stochastic processes and numerical applications

Breast cancer is the most common malignancy in women throughout the world. Metastatic dissemination to vital organs is the leading cause of breast cancer-related deaths. The treatment of metastases is mainly based on the primary tumor characteristics. However, breast cancer metastases exhibit high heterogeneity leading to different prognosis and therapeutic responses. Getting access to phenotype of metastases would allow better management of patients. The advent of theranostics in nuclear medicine has opened new opportunities for the diagnosis and treatment of cancer patients. The aim of this review is to provide an overview of current knowledge and future directions in nuclear medicine for therapeutic management of metastatic breast cancer patients.

Gilles Pagès

Papers

99mTc-A1 as a Novel Imaging Agent Targeting Mesothelin-Expressing Pancreatic Ductal Adenocarcinoma

Anti-cxcl1, cxcl7 and cxcl8 antibodies and their applications

Greedy vector quantization

Quadratic optimal functional quantization of stochastic processes and numerical applications

Metastatic Heterogeneity of Breast Cancer: Companion and Theranostic Approach in Nuclear Medicine.