p38 Molecular Targeting for Next-Generation Multiple Myeloma Therapy.

Resistance to therapy and disease progression are the main causes of mortality in most cancers. In particular, the development of resistance is an important limitation affecting the efficacy of therapeutic alternatives for cancer, including chemotherapy, radiotherapy, and immunotherapy. Signaling pathways are largely responsible for the mechanisms of resistance to cancer treatment and progression, and multiple myeloma is no exception.

Parameterizable Design on Convolutional Neural Networks Using Chisel Hardware Construction Language.

This paper presents a parameterizable design generator on convolutional neural networks (CNNs) using the Chisel hardware construction language (HCL). By parameterizing structural designs such as the streaming width, pooling layer type, and floating point precision, multiple register-transfer level (RTL) implementations can be created to meet various accuracy and hardware cost requirements. The evaluation is based on generated RTL designs including 16-bit, 32-bit, 64-bit, and 128-bit implementations on field-programmable gate arrays (FPGAs).

Strength versus aerobic program: effects on body composition and health-related physical fitness levels of youths with Down syndrome.

To determine the effect of a 16-week fitness program (strength vs. aerobic) on different indicators of body composition and components of health-related physical fitness in youths with Down syndrome. Fifty adolescents (19 girls and 31 boys; average age, 18.

Role of MicroRNA-7 (MiR-7) in Cancer Physiopathology.

miRNAs are non-coding RNA sequences of approximately 22 nucleotides that interact with genes by inhibiting their translation through binding to their 3' or 5' UTR regions. Following their discovery, the role they play in the development of various pathologies, particularly cancer, has been studied. In this context, miR-7 is described as an important factor in the development of cancer because of its role as a tumor suppressor, regulating a large number of genes involved in the development and progression of cancer.

Turnover of the mTOR inhibitor, DEPTOR, and downstream AKT phosphorylation in multiple myeloma cells, is dependent on ERK1-mediated phosphorylation.

DEPTOR is a 48 kDa protein upregulated in multiple myeloma (MM) cells. DEPTOR inhibits mTOR and, by repressing a negative feedback loop, promotes AKT activation. We previously identified a compound that binds to DEPTOR in MM cells and induces its proteasomal degradation.

Roles and Regulation of BCL-xL in Hematological Malignancies.

Members of the Bcl-2 family are proteins that play an essential role in the regulation of apoptosis, a crucial process in development and normal physiology in multicellular organisms. The essential mechanism of this family of proteins is given by the role of pro-survival proteins, which inhibit apoptosis by their direct binding with their counterpart, the effector proteins of apoptosis. This family of proteins was named after the typical member Bcl-2, which was named for its discovery and abnormal expression in B-cell lymphomas.

Function of Deptor and its roles in hematological malignancies.

Deptor is a protein that interacts with mTOR and that belongs to the mTORC1 and mTORC2 complexes. Deptor is capable of inhibiting the kinase activity of mTOR. It is well known that the mTOR pathway is involved in various signaling pathways that are involved with various biological processes such as cell growth, apoptosis, autophagy, and the ER stress response.

KLF4 inhibition by Kenpaullone induces cytotoxicity and chemo sensitization in B-NHL cell lines via YY1 independent.

Krüppel-like factor 4 (KLF4) is a member of the KLF transcription factor family containing zinc-fingers, and is involved in the regulation of apoptosis, proliferation and differentiation of B cells and B-cell malignancies. KLF4 can act like an oncogene, we shown that KLF4 overexpression correlated with poor prognostic and chemoresistance in B-NHL. In addition, we shown that KLF4 is regulated by YY1.

[Pharmacogenomics of vitamin K antagonists].

There is an important interindividual variability in dose requirement for coumarinic anticoagulants, which could be explained by genetic and non-genetic factors. Among hereditary factors, there are gene polymorphisms that code the therapeutic target and the main enzyme responsible for their metabolism. However, there are other candidate genes that could modulate dose requirements.

MicroRNA-7 Regulates Migration and Chemoresistance in Non-Hodgkin Lymphoma Cells Through Regulation of KLF4 and YY1.

The discovery and description of the role of microRNAs has become very important, specifically due to their participation in the regulation of proteins and transcription factors involved in the development of cancer. microRNA-7 (miR-7) has been described as a negative regulator of several proteins involved in cancer, such as YY1 and KLF4. We have recently reported that YY1 and KLF4 play a role in non-Hodgkin lymphoma (NHL) and that the expression of KLF4 is regulated by YY1.

Building Oncofertility Core Competency in Developing Countries: Experience From Egypt, Tunisia, Brazil, Peru, and Panama.

Purpose: Little is known about oncofertility practice in developing countries that usually suffer from a shortage of health services, especially those related to cancer care.

Materials And Methods: To learn more about oncofertility practice in developing countries, we generated a survey to explore the barriers and opportunities associated with oncofertility practice in five developing countries from Africa and Latin America within our Oncofertility Consortium Global Partners Network. Responses from Egypt, Tunisia, Brazil, Peru, and Panama were collected, reviewed, and discussed.

Survey of Fertility Preservation Options Available to Patients With Cancer Around the Globe.

Purpose: Oncofertility focuses on providing fertility and endocrine-sparing options to patients who undergo life-preserving but gonadotoxic cancer treatment. The resources needed to meet patient demand often are fragmented along disciplinary lines. We quantify assets and gaps in oncofertility care on a global scale.

Survey of Third-Party Parenting Options Associated With Fertility Preservation Available to Patients With Cancer Around the Globe.

Purpose: In the accompanying article, "Survey of Fertility Preservation Options Available to Patients With Cancer Around the Globe," we showed that specific fertility preservation services may not be offered at various sites around the world because of cultural and legal barriers. We assessed global and regional experiences as well as the legal status of third-party reproduction and adoption to serve as a comprehensive international data set and resource for groups that wish to begin oncofertility interventions.

Methods: We provide data on the legalities of third-party assisted reproductive technologies and other family-building options in the 28 oncofertility-practicing countries surveyed.

Building Oncofertility Core Competency in Developing Countries: Experience From Egypt, Tunisia, Brazil, Peru, and Panama.

Purpose: Little is known about oncofertility practice in developing countries that usually suffer from a shortage of health services, especially those related to cancer care.

Materials And Methods: To learn more about oncofertility practice in developing countries, we generated a survey to explore the barriers and opportunities associated with oncofertility practice in five developing countries from Africa and Latin America within our Oncofertility Consortium Global Partners Network. Responses from Egypt, Tunisia, Brazil, Peru, and Panama were collected, reviewed, and discussed.

Dissociation of Pubertal Development Abnormality and Gonadal Dysfunction in Childhood Cancer Survivors.

To determine the relationship between pubertal development and postpubertal gonadal function in childhood cancer survivors. Childhood cancer survivors (≥10 years of age) who received follow-up care in a pediatric oncology group in an academic medical center during the period from January 1, 1985, to July 1, 2010 were included in this case series. Their pubertal development and gonadal function were evaluated.

A Novel Therapeutic Induces DEPTOR Degradation in Multiple Myeloma Cells with Resulting Tumor Cytotoxicity.

Prior work indicates DEPTOR expression in multiple myeloma cells could be a therapeutic target. DEPTOR binds to mTOR via its PDZ domain and inhibits mTOR kinase activity. We previously identified a drug, which prevented mTOR-DEPTOR binding (NSC126405) and induced multiple myeloma cytotoxicity.

Regulation of Krüppel-Like Factor 4 (KLF4) expression through the transcription factor Yin-Yang 1 (YY1) in non-Hodgkin B-cell lymphoma.

Krüppel-Like Factor 4 (KLF4) is a member of the KLF transcription factor family, and evidence suggests that KLF4 is either an oncogene or a tumor suppressor. The regulatory mechanism underlying KLF4 expression in cancer, and specifically in lymphoma, is still not understood. Bioinformatics analysis revealed two YY1 putative binding sites in the KLF4 promoter region (-950 bp and -105 bp).

Direct toxicity of insulin on the human placenta and protection by metformin.

Objective: To study the effects of insulin and metformin on primary trophoblasts from early pregnancies.

Design: Experimental in vitro study.

Setting: Academic research institute.

The impact of using donor sperm in assisted reproductive technology cycles on perinatal outcomes.

Objective: To assess the impact of using donor sperm in assisted reproductive technology (ART) cycles on perinatal outcomes.

Design: Historical cohort study.

Setting: US national database from the Society of Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 2012 to 2013.

Cytotoxic effect caspase activation dependent of a genetically engineered fusion protein with a CD154 peptide mimetic (OmpC-CD154) on B-NHL cell lines is mediated by the inhibition of bcl-6 and YY1 through MAPK p38 activation.

The interaction between CD40, and its ligand, CD154, is essential for the development of humoral and cellular immune responses. The selective inhibition or activation of this pathway forms the basis for the development of new therapeutics against immunologically based diseases and malignancies. We are developing a gene fusion of Salmonella typhi OmpC protein expressing the CD154 Tyr140-Ser-149 amino acid strand.

Comparison of perinatal outcomes following frozen embryo transfer cycles using autologous versus donor oocytes in women 40 to 43 years old: analysis of SART CORS data.

Objective: To study the differences in perinatal outcomes after frozen embryo transfer cycles using autologous or donor oocytes in women of advanced maternal age.

Design: Historical cohort study.

Setting: US national database from the Society of Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 2009 to 2013.

Dual role of hypoxia-inducible factor 1 α in experimental pulmonary tuberculosis: its implication as a new therapeutic target.

Aim: Investigate the role of hypoxia-inducible factor-1α (HIF-1α) in pulmonary tuberculosis (TB).

Methods & Results: A model of progressive pulmonary TB in BALB/c mice, immunohistochemistry and digital pathology were used. High HIF-1α expression was observed during early TB in activated macrophages.

Role of Yin Yang-1 (YY1) in the transcription regulation of the multi-drug resistance () gene.

Resistance to chemotherapy hinders the successful treatment of acute lymphoblastic leukemia (ALL). The multi-drug resistance-1 (/ABCB1) gene encodes P-glycoprotein (P-gp), which plays an important role in chemoresistance; however, its transcriptional regulation remains unclear. We investigated the role of YY1 in the regulation of and its relation to ALL outcomes.

Not all twins are monozygotic after elective single embryo transfer: analysis of 32,600 elective single embryo transfer cycles as reported to the Society for Assisted Reproductive Technology.

Objective: To study the incidence and risk factors of multiple pregnancies after elective single ET.

Design: Historic cohort.

Setting: Not applicable.

Structure-activity relationship study of small molecule inhibitors of the DEPTOR-mTOR interaction.

DEPTOR is a 48kDa protein that binds to mTOR and inhibits this kinase within mTORC1 and mTORC2 complexes. Over-expression of DEPTOR specifically occurs in the multiple myeloma (MM) tumor model and DEPTOR knockdown is cytotoxic to MM cells, suggesting it is a potential therapeutic target. Since mTORC1 paralysis protects MM cells against DEPTOR knockdown, it indicates that the protein-protein interaction between DEPTOR and mTOR is key to MM viability vs death.