The Complexity and Significance of Fibroblast Growth Factor (FGF) Signaling for FGF-Targeted Cancer Therapies.

Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers.

The Significance of Aldehyde Dehydrogenase 1 in Cancers.

The goal of this paper is to discuss the role of ALDH isozymes in different cancers, review advances in ALDH1-targeting cancer therapies, and explore a mechanism that explains how ALDH expression becomes elevated during cancer development. ALDH is often overexpressed in cancer, and each isoform has a unique expression pattern and a distinct role in different cancers. The abnormal expression of ALDHs in different cancer types (breast, colorectal, lung, gastric, cervical, melanoma, prostate, and renal) is presented and correlated with patient prognosis.

Cognitive ability, gender, and well-being in school contexts: longitudinal evidence from Sweden.

While well-being does generally constitute a moderate predictor of school achievement, research on the predictive validity of cognitive ability for well-being in school contexts remains scant. The current study analyzed longitudinal relations between cognitive ability measured at age 13 (Grade 6) and well-being measured at age 18 (Grade 12, valid  = 2,705) in a Swedish sample, using several multivariate model techniques. The results indicate that cognitive ability was not a statistically significant predictor when several predictors were entered in a multiple regression model.

The Gray Nine and Parallel Personality Patterns: Big Five, Dark Tetrad, and a "Well-Rounded Personality".

The vast literature on personality psychology generally focuses on neutral or socially beneficial personality traits such as the Five-Factor model (e.g., agreeableness, conscientiousness) or "dark" traits such as Machiavellianism, narcissism, psychopathy, and everyday sadism.

Links WNT and Retinoic Acid Signaling: A Target to Differentiate ALDH+ Stem Cells in -Mutant CRC.

mutation is the main driving mechanism of CRC development and leads to constitutively activated WNT signaling, overpopulation of ALDH+ stem cells (SCs), and incomplete differentiation. We previously reported that retinoic acid (RA) receptors are selectively expressed in ALDH+ SCs, which provides a way to target cancer SCs with retinoids to induce differentiation. : A functional link exists between the WNT and RA pathways, and mutation generates a WNT:RA imbalance that decreases retinoid-induced differentiation and increases ALDH+ SCs.

A Review of IsomiRs in Colorectal Cancer.

As advancements in sequencing technology rapidly continue to develop, a new classification of microRNAs has occurred with the discovery of isomiRs, which are relatively common microRNAs with sequence variations compared to their established template microRNAs. This review article seeks to compile all known information about isomiRs in colorectal cancer (CRC), which has not, to our knowledge, been gathered previously to any great extent. A brief overview is given of the history of microRNAs, their implications in colon cancer, the canonical pathway of biogenesis and isomiR classification.

The v8-10 variant isoform of CD44 is selectively expressed in the normal human colonic stem cell niche and frequently is overexpressed in colon carcinomas during tumor development.

CD44 protein and its variant isoforms are expressed in cancer stem cells (CSCs), and various CD44 isoforms can have different functional roles in cells. Our goal was to investigate how different CD44 isoforms contribute to the emergence of stem cell (SC) overpopulation that drives colorectal cancer (CRC) development. Specific CD44 variant isoforms are selectively expressed in normal colonic SCs and become overexpressed in CRCs during tumor development.

Beyond the Genetic Code:

The genetic code determines how the precise amino acid sequence of proteins is specified by genomic information in cells. But what specifies the precise histologic organization of cells in plant and animal tissues is unclear. We now hypothesize that another code, the , exists at an even higher level of complexity which determines how tissue organization is dynamically maintained.

Is the SES and academic achievement relationship mediated by cognitive ability? Evidence from PISA 2018 using data from 77 countries.

Introduction: Earlier research has suggested that that the international large-scale assessment, PISA (Programme for International Student Assessment), may be looked upon as a form of school test that is mostly explained by participating students' socioeconomic status, non-cognitive factors, and various school factors, whereas another strand of research focuses on the similarities between PISA and cognitive ability assessments such as IQ tests. The latter position does also highlight the strong relationships between PISA scores and IQ test scores, typically aggregated to the country level. The current article adds to this scholarly debate by examining the latest PISA survey from 2018.

Differential miRNA Expression Contributes to Emergence of Multiple Cancer Stem Cell Subpopulations in Human Colorectal Cancer.

One reason for lack of efficacy in cancer therapeutics is tumor heterogeneity. We hypothesize that tumor heterogeneity arises due to emergence of multiple cancer stem cell (CSC) subpopulations because miRNAs regulate expression of stem cell genes in CSCs. Our goal was to determine if: ) multiple CSC subpopulations exist in a human CRC cell population, and ) miRNAs are differentially expressed in the different CSC subpopulations.

A NEw MOdel of individualized and patient-centered follow-up for women with gynecological cancer (the NEMO study)-protocol and rationale of a randomized clinical trial.

Background: Follow-up programs for gynecological cancer patients are currently under revision. There is limited evidence that traditional follow-up and clinical examinations improve survival in an early-stage gynecological setting. Further, traditional follow-up programs fail to accommodate the patient's need for psychosocial and sexual supportive care and to actively involve patients and their relatives in the follow-up process.

Differential miRNA Expression Contributes to Emergence of Multiple Cancer Stem Cell Subpopulations in Human Colorectal Cancer.

One reason for lack of efficacy in cancer therapeutics is tumor heterogeneity. We hypothesize that tumor heterogeneity arises due to emergence of multiple Cancer Stem Cell (CSC) subpopulations because miRNAs regulate expression of stem cell genes in CSCs. Our goal was to determine if: i) multiple CSC subpopulations exist in a human CRC cell population, and ii) miRNAs are differentially expressed in the different CSC subpopulations.

HOXA9 Overexpression Contributes to Stem Cell Overpopulation That Drives Development and Growth of Colorectal Cancer.

HOX proteins are transcription factors that regulate stem cell (SC) function, but their role in the SC origin of cancer is under-studied. Aberrant expression of HOX genes occurs in many cancer types. Our goal is to ascertain how retinoic acid (RA) signaling and the regulation of expression might play a role in the SC origin of human colorectal cancer (CRC).

Retinoids as Chemo-Preventive and Molecular-Targeted Anti-Cancer Therapies.

Retinoic acid (RA) agents possess anti-tumor activity through their ability to induce cellular differentiation. However, retinoids have not yet been translated into effective systemic treatments for most solid tumors. RA signaling is mediated by the following two nuclear retinoic receptor subtypes: the retinoic acid receptor (RAR) and the retinoic X receptor (RXR), and their isoforms.

The Role of miRNAs, miRNA Clusters, and isomiRs in Development of Cancer Stem Cell Populations in Colorectal Cancer.

MicroRNAs (miRNAs or miRs) have a critical role in regulating stem cells (SCs) during development and altered expression can cause developmental defects and/or disease. Indeed, aberrant miRNA expression leads to wide-spread transcriptional dysregulation which has been linked to many cancers. Mounting evidence also indicates a role for miRNAs in the development of the cancer SC (CSC) phenotype.

Parallelization: the Fourth Leg of Cultural Globalization Theory.

Extending Pieterse's (1996) tripartite cultural globalization theory consisting of homogenization, hybridization and polarization, the current article outlines a set of exemplifications and justifications of a fourth theoretical underpinning labeled parallelization. The theory implies that at a global scale, crucial events that appear paradoxical or contradictory occur at the same time, such as carbon emissions due to growth-fixated global capitalism, while the causes of carbon emissions lead to greater resilience against the consequences of carbon emissions as wealth accumulates. Other examples discussed are large-scale migration flows which lead to increased segregation in host societies while integration of migrants occur as a parallel process; secularization visa-à-vis the resurgence of religions; clear indications of that the biological component of cognitive abilities decreases due to fertility patterns in many locations around the globe, while the IQ test scores have risen as a consequence of various environmental factors.

APC mutations in human colon lead to decreased neuroendocrine maturation of ALDH+ stem cells that alters GLP-2 and SST feedback signaling: Clue to a link between WNT and retinoic acid signalling in colon cancer development.

APC mutations drive human colorectal cancer (CRC) development. A major contributing factor is colonic stem cell (SC) overpopulation. But, the mechanism has not been fully identified.

MicroRNA Expression Profiling of Normal and Malignant Human Colonic Stem Cells Identifies as a Regulator of the Stem Cell Gene.

MicroRNAs (miRNAs) have a critical role in regulating stem cells (SCs) during development, and because aberrant expression of miRNAs occurs in various cancers, our goal was to determine if dysregulation of miRNAs is involved in the SC origin of colorectal cancer (CRC). We previously reported that aldehyde dehydrogenase (ALDH) is a marker for normal and malignant human colonic SCs and tracks SC overpopulation during colon tumorigenesis. MicroRNA expression was studied in ALDH-positive SCs from normal and malignant human colon tissues by Nanostring miRNA profiling.

Autocatalytic Tissue Polymerization Reaction Mechanism in Colorectal Cancer Development and Growth.

The goal of our study was to measure the kinetics of human colorectal cancer (CRC) development in order to identify aberrant mechanisms in tissue dynamics and processes that contribute to colon tumorigenesis. The kinetics of tumor development were investigated using age-at-tumor diagnosis (adenomas and CRCs) of familial adenomatous coli (FAP) patients and sporadic CRC patients. Plots of age-at-tumor diagnosis data as a function of age showed a distinct sigmoidal-shaped curve that is characteristic of an autocatalytic reaction.

Gene expression signatures for HOXA4, HOXA9, and HOXD10 reveal alterations in transcriptional regulatory networks in colon cancer.

We previously reported that HOXA4, HOXA9, and HOXD10 are selectively expressed in colonic stem cells (SCs) and their overexpression contributes to colorectal cancer (CRC). Our goals here were to determine how these HOX genes are transcriptionally regulated and whether transcriptional dysregulation of HOX genes occurs in CRC. Accordingly, we used correlation analysis to identify genes that are expression-correlated or anticorrelated with HOXA4, HOXA9, and HOXD10.

The anti-cancer effect of retinoic acid signaling in CRC occurs via decreased growth of ALDH+ colon cancer stem cells and increased differentiation of stem cells.

Background: Tumorigenesis is driven by stem cell (SC) overpopulation. Because ALDH is both a marker for SCs in many tissues and a key enzyme in retinoid acid (RA) signaling, we studied RA signaling in normal and malignant colonic SCs.

Hypothesis: RA signaling regulates growth and differentiation of ALDH+ colonic SCs; dysregulation of RA signaling contributes to SC overpopulation and colorectal cancer (CRC) development.

Role of HOX Genes in Stem Cell Differentiation and Cancer.

HOX genes encode an evolutionarily conserved set of transcription factors that control how the phenotype of an organism becomes organized during development based on its genetic makeup. For example, in bilaterian-type animals, HOX genes are organized in gene clusters that encode anatomic segment identity, that is, whether the embryo will form with bilateral symmetry with a head (anterior), tail (posterior), back (dorsal), and belly (ventral). Although HOX genes are known to regulate stem cell (SC) differentiation and HOX genes are dysregulated in cancer, the mechanisms by which dysregulation of HOX genes in SCs causes cancer development is not fully understood.

Multi-scale modeling of APC and [Formula: see text]-catenin regulation in the human colonic crypt.

Stem cell renewal and differentiation in the human colonic crypt are linked to the [Formula: see text]-catenin pathway. The spatial balance of Wnt factors in proliferative cells within the crypt maintain an appropriate level of cellular reproduction needed for normal crypt homeostasis. Mutational events at the gene level are responsible for deregulating the balance of Wnt factors along the crypt, causing an overpopulation of proliferative cells, a loss of structure of the crypt domain, and the initiation of colorectal carcinomas.

Increased Musashi-2 and Decreased NUMB Protein Levels Observed in Human Colorectal Cancer are reverted to Normal Levels by ATRA-Induced Cell Differentiation.

Background: Musashi stem cell (SC) proteins (MSI-1 & MSI-2) are known to become over expressed during colorectal tumorigenesis in humans and mice. MSI-1 overexpression induces tumorigenesis through Notch activation via inactivation of NUMB. Previous studies also show that MSI-2 overexpression in mice induces intestinal tumorigenesis but the mechanism is independent of NUMB.