Inhibition of Multifunctional Protein p32/C1QBP Promotes Cytostatic Effects in Colon Cancer Cells by Altering Mitogenic Signaling Pathways and Promoting Mitochondrial Damage.

The protein p32 (C1QBP) is a multifunctional and multicompartmental homotrimer that is overexpressed in many cancer types, including colon cancer. High expression levels of C1QBP are negatively correlated with the survival of patients. Previously, we demonstrated that C1QBP is an essential promoter of migration, chemoresistance, clonogenic, and tumorigenic capacity in colon cancer cells. However, the mechanisms underlying these functions and the effects of specific C1QBP protein inhibitors remain unexplored. Here, we show that the specific pharmacological inhibition of C1QBP with the small molecule M36 significantly decreased the viability rate, clonogenic capacity, and proliferation rate of different colon cancer cell lines in a dose-dependent manner. The effects of the inhibitor of C1QBP were cytostatic and non-cytotoxic, inducing a decreased activation rate of critical pro-malignant and mitogenic cellular pathways such as Akt-mTOR and MAPK in RKO colon cancer cells. Additionally, treatment with M36 significantly affected the mitochondrial integrity and dynamics of malignant cells, indicating that p32/C1QBP plays an essential role in maintaining mitochondrial homeostasis. Altogether, our results reinforce that C1QBP is an important oncogene target and that M36 may be a promising therapeutic drug for the treatment of colon cancer.

Role of Incretins in Muscle Functionality, Metabolism, and Body Composition in Breast Cancer: A Metabolic Approach to Understanding This Pathology.

A poorly studied issue in women with breast cancer is the role of incretins (GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1)) in the quantity and quality of muscle mass in lean and obese individuals. The current report aims to analyze the patterns of association and the role of incretin in muscle functionality and body composition in women with cancer compared with healthy women (mammography BI-RADS I or II) to elucidate whether GIP and GLP-1 can be used to estimate the risk, in conjunction with overweight or obesity, for breast cancer. We designed a case-control study in women with a breast cancer diagnosis confirmed by biopsy in different clinical stages (CS; n = 87) and healthy women with a mastography BI-RADS I or II within the last year (n = 69). The women were grouped according to body mass index (BMI): lean (<25 kg/m2BS), overweight (≥25-<30 kg/m2BS), and obese (≥30 kg/m2BS). We found that GLP-1 and GIP levels over 18 pg/mL were associated with a risk of breast cancer (GIP OR = 36.5 and GLP-1 OR = 4.16, for the entire sample), particularly in obese women (GIP OR = 8.8 and GLP-1 OR = 6.5), and coincidentally with low muscle quality indexes, showed an association between obesity, cancer, incretin defects, and loss of muscle functionality.

WNT Signaling in Stem Cells: A Look into the Non-Canonical Pathway.

Tissue homeostasis is crucial for multicellular organisms, wherein the loss of cells is compensated by generating new cells with the capacity for proliferation and differentiation. At the origin of these populations are the stem cells, which have the potential to give rise to cells with both capabilities, and persevere for a long time through the self-renewal and quiescence. Since the discovery of stem cells, an enormous effort has been focused on learning about their functions and the molecular regulation behind them. Wnt signaling is widely recognized as essential for normal and cancer stem cell. Moreover, ß-catenin-dependent Wnt pathway, referred to as canonical, has gained attention, while ß-catenin-independent Wnt pathways, known as non-canonical, have remained conspicuously less explored. However, recent evidence about non-canonical Wnt pathways in stem cells begins to lay the foundations of a conceivably vast field, and on which we aim to explain this in the present review. In this regard, we addressed the different aspects in which non-canonical Wnt pathways impact the properties of stem cells, both under normal conditions and also under disease, specifically in cancer.

Functional Roles of CD133: More than Stemness Associated Factor Regulated by the Microenvironment.

CD133 protein has been one of the most used surface markers to select and identify cancer cells with stem-like features. However, its expression is not restricted to tumoral cells; it is also expressed in differentiated cells and stem/progenitor cells in various normal tissues. CD133 participates in several cellular processes, in part orchestrating signal transduction of essential pathways that frequently are dysregulated in cancer, such as PI3K/Akt signaling and the Wnt/ß-catenin pathway. CD133 expression correlates with enhanced cell self-renewal, migration, invasion, and survival under stress conditions in cancer. Aside from the intrinsic cell mechanisms that regulate CD133 expression in each cellular type, extrinsic factors from the surrounding niche can also impact CD33 levels. The enhanced CD133 expression in cells can confer adaptive advantages by amplifying the activation of a specific signaling pathway in a context-dependent manner. In this review, we do not only describe the CD133 physiological functions known so far, but importantly, we analyze how the microenvironment changes impact the regulation of CD133 functions emphasizing its value as a marker of cell adaptability beyond a cancer-stem cell marker.

Mutant p53 gain-of-function stimulates canonical Wnt signaling via PI3K/AKT pathway in colon cancer.

Aberrant canonical Wnt signaling is a hallmark of colon cancer. The TP53 tumor suppressor gene is altered in many solid tumors, including colorectal cancer, resulting in mutant versions of p53 (mut-p53) that lose their tumor suppressor capacities and acquire new-oncogenic functions (GOFs) critical for disease progression. Although the mechanisms related to mut-p53 GOF have been explored extensively, the relevance of mut-p53 in the canonical Wnt pathway is not well defined. This work investigated the influence of mut-p53 compared to wt-p53 in ß-catenin-dependent Wnt signaling. Using the TCGA public data from Pan-Cancer and the GEPIA2 platform, an in silico analysis of wt-p53 versus mut-p53 genotyped colorectal cancer patients showed that TP53 (p53) and CTNNB1 (ß-catenin) are significantly overexpressed in colorectal cancer, compared with normal tissue. Using p53 overexpression or p53 knockdown assays of wt-p53 or mut-p53, we found that while wt-p53 antagonizes canonical Wnt signaling, mut-p53 induces the opposite effect, improving the ß-catenin-dependent transcriptional activity and colony formation ability of colon cancer cells, which were both decreased by mut-p53 knockdown expression. The mechanism involved in mut-p53-induced activation of canonical Wnt appears to be via AKT-mediated phosphorylation of Ser 552 of ß-catenin, which is known to stabilize and enhance its transcriptional activity. We also found that while wt-p53 expression contributes to 5-FU sensitivity in colon cancer cells, the RITA p53 reactivating molecule counteracted the resistance against 5-FU in cells expressing mut-p53. Our results indicate that mut-p53 GOF acts as a positive regulator of canonical Wnt signaling and participates in the induction of resistance to 5-FU in colon cancer cells.

Experimental infection of Artibeus lituratus bats and no detection of Zika virus in neotropical bats from French Guiana, Peru, and Costa Rica suggests a limited role of bats in Zika transmission.

Bats are important natural reservoir hosts of a diverse range of viruses that can be transmitted to humans and have been suggested to play an important role in the Zika virus (ZIKV) transmission cycle. However, the exact role of these animals as reservoirs for flaviviruses is still controversial. To further expand our understanding of the role of bats in the ZIKV transmission cycle in Latin America, we carried out an experimental infection in wild-caught Artibeus lituratus bats and sampled several free-living neotropical bats across three countries of the region. Experimental ZIKV infection was performed in wild-caught adult bats (4 females and 5 males). The most relevant findings were hemorrhages in the bladder, stomach and patagium. Significant histological findings included inflammatory infiltrate consisting of a predominance of neutrophils and lymphocytes, in addition to degeneration in the reproductive tract of males and females. This suggests that bat reproduction might be at some level affected by ZIKV. Leukopenia was also observed in some inoculated animals. Hemorrhages, genital alterations, and leukopenia are suggested to be caused by ZIKV; however, since these were wild-caught bats, we cannot exclude other agents. Detection of ZIKV by qPCR was observed at low concentrations in only two urine samples in two inoculated animals. All other animals and tissues tested were negative. Finally, no virus-neutralizing antibodies were found in any animal. To determine ZIKV infection in nature, the blood of a total of 2056 bats was sampled for ZIKV detection by qPCR. Most of the sampled individuals belonged to the genus Pteronotus sp. (23%), followed by the species Carollia sp. (17%), Anoura sp. (14%), and Molossus sp. (13.7%). No sample of any tested species was positive for ZIKV by qPCR. These results together suggest that bats are not efficient amplifiers or reservoirs of ZIKV and may not have an important role in ZIKV transmission dynamics.

Phase Angle in Head and Neck Cancer: A Sex-Differential Analysis from Biological and Clinical Behavior to Health-Related Quality of Life.

Head and neck cancer (H&NC) is a diverse category of tumors related to malignancies in the common aerodigestive pathway, with high metabolic rate, poor nutritional and treatment outcomes, and elevated mortality despite the best standard treatment. Herein, we focus on determining how the phase angle (PA) differs across sex as a predictor of poor prognosis, low quality-of-life (QoL) scores, and mortality in patients with head and neck cancer. This follow-up study presents a sex-differential analysis in a prospective cohort of 139 head and neck cancer patients categorized by sex as male (n = 107) and female (n = 32). Patients were compared in terms of nutritional, biochemical, and quality-of-life indicators between low and normal PA in women (<3.9° (n = 14, 43.75%) and ≥3.9°) and men (<4.5° (n = 62, 57.9%) and ≥4.5°). Our results show that most patients were in locally advanced clinical stages (women: n = 21 (65.7%); men: n = 67 (62.6%)) and that patients with low PA had a lower punctuation in parameters such as handgrip strength, four-meter walking speed, albumin, C-reactive protein (CRP), and CRP/albumin ratio (CAR), as well as the worst QoL scores in functional and symptomatic scales in both the male and female groups. A comparison between sexes revealed significant disparities; malnourishment and tumor cachexia related to an inflammatory state was more evident in the women's group.

Canonical Wnt Pathway Is Involved in Chemoresistance and Cell Cycle Arrest Induction in Colon Cancer Cell Line Spheroids.

The presence of cancer stem cells (CSCs) has been associated with the induction of drug resistance and disease recurrence after therapy. 5-Fluorouracil (5FU) is widely used as the first-line treatment of colorectal cancer (CRC). However, its effectiveness may be limited by the induction of drug resistance in tumor cells. The Wnt pathway plays a key role in the development and CRC progression, but it is not clearly established how it is involved in CSCs resistance to treatment. This work aimed to investigate the role played by the canonical Wnt/ß-catenin pathway in CSCs resistance to 5FU treatment. Using tumor spheroids as a model of CSCs enrichment of CRC cell lines with different Wnt/ß-catenin contexts, we found that 5FU induces in all CRC spheroids tested cell death, DNA damage, and quiescence, but in different proportions for each one: RKO spheroids were very sensitive to 5FU, while SW480 were less susceptible, and the SW620 spheroids, the metastatic derivative of SW480 cells, displayed the highest resistance to death, high clonogenic capacity, and the highest ability for regrowth after 5FU treatment. Activating the canonical Wnt pathway with Wnt3a in RKO spheroids decreased the 5FU-induced cell death. But the Wnt/ß-catenin pathway inhibition with Adavivint alone or in combination with 5FU in spheroids with aberrant activation of this pathway produced a severe cytostatic effect compromising their clonogenic capacity and diminishing the stem cell markers expression. Remarkably, this combined treatment also induced the survival of a small cell subpopulation that could exit the arrest, recover SOX2 levels, and re-grow after treatment.

Non-canonical Wnt/Ca2+ signaling is essential to promote self-renewal and proliferation in colon cancer stem cells.

Introduction: Cancer Stem Cells (CSC) are responsible for maintaining tumor growth, chemoresistance, and metastasis. Therefore, understanding their characteristics is critical to progress in cancer therapy. While the contribution of the canonical Wnt/b-catenin signaling in both normal and CSCs had been well established, the function of non-canonical Wnt signaling cascades in stem cells is unclear. Recently, we reported that Wnt ligands trigger complex signaling in which the canonical and non-canonical responses can be simultaneously activated by one ligand in colon cancer cells, suggesting, therefore, that noncanonical Wnt pathways may also be important in CSCs. Methods: The present work aimed to know the role of the Wnt/Ca2+ pathway in colon CSCs. We used tumorspheres as a model of CSCs enrichment of CRC cell lines with different Wnt/b-catenin contexts. Results: Using Wnt3a and Wnt5a as prototype ligands to activate the canonical or the non-canonical pathways, respectively, we found that both Wnt3a and Wnt5a promote sphere-formation capacity and proliferation without stimulating b-catenin-dependent transcription. Upregulation of sphere formation by Wnt5a or Wnt3a requires the downstream activation of Phospholipase C and transcriptional factor NFAT. Moreover, the single specific inhibition of PLC or NFAT, using U73122 and 11R-VIVIT, respectively, leads to impaired sphere formation. Discussion: Our results indicate that both types of ligands activate the Wnt/Ca2+ signaling axis to induce/maintain the self-renewal efficiency of CSCs, demonstrating to be essential for the functions of CSC in colon cancer.

Hypoxia-inducible factors, mTOR, and astrin constitute an integrative regulatory network in colon cancer cells.

Astrin/SPAG5 is a mitotic spindle protein found to be overexpressed in several human cancers, functioning as an oncogene. The expression of Astrin has not been reported so far in colon cancer, nor has it been related to HIFs expression or action. Since mTOR, Astrin, and hypoxia-inducible factors (HIFs) are involved in promoting the growth and survival of cancer cells, we investigated the possible interaction between them in cultured colon cancer cells. Both Astrin and HIF-1α and HIF-2α protein levels were found only expressed in colon cancer cells compared with nonmalignant cells. Our data indicate that mTOR stimulates both Astrin and HIFs expression, but notably, mTORC activity seems to be independent of Astrin expression levels. However, while HIF-1α or HIF-2α stable knockdown increased Astrin expression, mTOR activity was affected in an opposite way by HIF-1α or HIF-2α silencing, indicating that HIF-1α inhibits mTOR while HIF-2α stimulates its activity. These data suggest that mTOR, Astrin, and HIFs compose an integrative network interacting to activate positive or negative regulatory loops probably to coordinate cancer cell growth, metabolism, and survival under oncogenic stress.

Association of water intake and hydration status with risk of kidney stone formation based on NHANES 2009-2012 cycles.

OBJECTIVE: Evaluating the association of water intake and hydration status with nephrolithiasis risk at the population level. DESIGN: It is a cross-sectional study in which daily total plain water intake and total fluid intake were estimated together with blood osmolality, urine creatinine, urine osmolality, urine flow rate (UFR), free water clearance (FWC) and urine/blood osmolality ratio (Uosm:Bosm). The associations of fluid intake and hydration markers with nephrolithiasis were evaluated using multivariable logistic regression. SETTING: General US population. PARTICIPANTS: A total of 8195 adults aged 20 years or older from the National Health and Nutritional Examination Survey 2009-2012 cycles. RESULTS: The population medians (interquartile ranges, IQR) for daily total plain water intake and total fluid intake were 807 (336-1481) and 2761 (2107-3577) ml/d, respectively. The adjusted OR (95 % CI) of nephrolithiasis for each IQR increase in total plain water intake and total fluid intake were 0·92 (95 % CI 0·79, 1·06) and 0·84 (95 % CI 0·72, 0·97), respectively. The corresponding OR of nephrolithiasis for UFR, blood osmolality, Uosm:Bosm and urine creatinine were 0·87 (95 % CI 0·76, 0·99), 1·18 (95 % CI 1·06, 1·32), 1·38 (95 % CI 1·17, 1·63) and 1·27 (95 % CI 1·11, 1·45), respectively. A linear protective relationship of fluid intake, UFR and FWC with nephrolithiasis risk was observed. Similarly, positive dose-response associations of nephrolithiasis risk with markers of insufficient hydration were identified. Encouraging a daily water intake of >2500 ml/d and maintaining a urine output of 2 l/d was associated with a lower prevalence of nephrolithiasis. CONCLUSION: This study verified the beneficial role of general water intake recommendations in nephrolithiasis prevention in the general US population.

An approach to p32/gC1qR/HABP1: a multifunctional protein with an essential role in cancer.

P32/gC1qR/HABP1 is a doughnut-shaped acidic protein, highly conserved in eukaryote evolution and ubiquitous in the organism. Although its canonical subcellular localization is the mitochondria, p32 can also be found in the cytosol, nucleus, cytoplasmic membrane, and it can be secreted. Therefore, it is considered a multicompartmental protein. P32 can interact with many physiologically divergent ligands in each subcellular location and modulate their functions. The main ligands are C1q, hyaluronic acid, calreticulin, CD44, integrins, PKC, splicing factor ASF/SF2, and several microbial proteins. Among the functions in which p32 participates are mitochondrial metabolism and dynamics, apoptosis, splicing, immune response, inflammation, and modulates several cell signaling pathways. Notably, p32 is overexpressed in a significant number of epithelial tumors, where its expression level negatively correlates with patient survival. Several studies of gain and/or loss of function in cancer cells have demonstrated that p32 is a promoter of malignant hallmarks such as proliferation, cell survival, chemoresistance, angiogenesis, immunoregulation, migration, invasion, and metastasis. All of this strongly suggests that p32 is a potential diagnostic molecule and therapeutic target in cancer. Indeed, preclinical advances have been made in developing therapeutic strategies using p32 as a target. They include tumor homing peptides, monoclonal antibodies, an intracellular inhibitor, a p32 peptide vaccine, and p32 CAR T cells. These advances are promising and will allow soon to include p32 as part of targeted cancer therapies.

Morphological and genetic characterization of the broad mite Polyphagotarsonemus latus Banks (Acari: Tarsonemidae) from two Mexican populations.

Polyphagotarsonemus latus Banks is considered a polyphagous pest of diverse agricultural and ornamental crops of global economic significance. Its distribution, host range, variety of symptoms, morphological differences, chaetotaxy and several ontogeny reports have advanced the idea of P. latus as a species complex. Correct pest identification leads to suitable control treatment. Therefore, the objective of this study was the identification of mites collected in two different geographic regions in Mexico (Chiapas and Guanajuato) that had been tentatively designated as Polyphagotarsonemus sp. Biometric differences on the morphology of adults as well the genetic variability were determined by taxonomical and molecular (mitochondrial COI gene) characterization techniques. The identity of the mites from both populations was confirmed as P. latus based on taxonomic characters. Biometric parameter variations were found between both populations (70.58% and 53.84% for females and males, respectively). The average sequenced fragment size was 447 bp (both populations). A homology search against six P. latus sequences available in the GenBank database revealed that sequence KM580507.1 (from India) shows 83.0-86.41% and 99.26-99.52% similarity with the sequences from Guanajuato and Chiapas, respectively. Molecular data indicated a significant divergence between the populations. The genetic distance demonstrates the population from Chiapas has a higher genetic correspondence (0.010) to the sequence from India (KM580507.1) whereas the population from Guanajuato is more distant (0.191). The genetic distance between the populations of this study and other GenBank sequences is even larger. We consider our results strengthen the hypothesis of P. latus consisting of a species-complex. However, it is essential to extend the study to other regions including its country of origin (Sri Lanka), and to include ultrastructural features.

Increased O-GlcNAcylation promotes IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells.

O-linked ß-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. O-GlcNAcylation level is regulated by OGT (O-GlcNAc transferase), which adds GlcNAc on proteins, and OGA (O-GlcNAcase), which removes it. Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. In the present study, we have evaluated the effect of increasing protein O-GlcNAcylation on cervical cancer-derived CaSki cells. We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. Moreover, we showed that increased O-GlcNAcylation promotes IGF-1 receptor (IGF1R) autophosphorylation, possibly through inhibition of protein tyrosine-phosphatase 1B activity. This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation.

The gut microbiota of chickens in a commercial farm treated with a Salmonella phage cocktail.

The microbiota in broiler chicken intestines affects the animals' health, metabolism, and immunity both positively and negatively. Accordingly, it has a significant impact on animal productivity. Phages, host-specific parasites of bacterial cells, are a promising antimicrobial alternative that selectively target pathogens without disturbing the microbiota. The purpose of this study is to further characterize the commensal microbial community at production scale in broiler chickens treated with a Salmonella phage treatment. We evaluated the cecal microbiota of broilers reared in a commercial farming system where a phage cocktail against Salmonella, SalmoFree was supplied to animals. To do so, two field trials were conducted, incorporating three doses of phages in the broilers' drinking water. Our results showed that the core microbiome (taxa that were present in more than 50% of samples) contained species that are key to microbiota adaptation in the last stage of the production cycle. Among these, there are some important degraders of complex polysaccharides and producers of short chain fatty acids (SCFA) such as Eisenbergiella and Lachnoclostridium. The phage cocktail did not affect the normal development of the microbiota's structure. The addition of the phage cocktail resulted in a significant reduction in Campylobacter and an increase in Butyricimonas, Helicobacter and Rikenellaceae, which are common inhabitants in chicken gut with known negative and positive effects on their health and metabolism. Altogether, we consider that these results contribute valuable information to the implementation of large-scale phage therapy technologies.

Socioeconomic inequalities in low birth weight risk before and during the COVID-19 pandemic in Argentina: A cross-sectional study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic may have exacerbated existing socioeconomic inequalities in health. In Argentina, public hospitals serve the poorest uninsured segment of the population, while private hospitals serve patients with health insurance. This study aimed to assess whether socioeconomic inequalities in low birth weight (LBW) risk changed during the first wave of the COVID-19 pandemic. METHODS: This multicenter cross-sectional study included 15929 infants. A difference-in-difference (DID) analysis of socioeconomic inequalities between public and private hospitals in LBW risk in a pandemic cohort (March 20 to July 19, 2020) was compared with a prepandemic cohort (March 20 to July 19, 2019) by using medical records obtained from ten hospitals. Infants were categorized by weight as LBW < 2500 g, very low birth weight (VLBW) < 1500 g and extremely low birth weight (ELBW) < 1000 g. Log binomial regression was performed to estimate risk differences with an interaction term representing the DID estimator. Covariate-adjusted models included potential perinatal confounders. FINDINGS: Of the 8437 infants in the prepandemic cohort, 4887 (57•9%) were born in public hospitals. The pandemic cohort comprised 7492 infants, 4402 (58•7%) of whom were born in public hospitals. The DID estimators indicated no differences between public versus private hospitals for LBW risk (-1•8% [95% CI -3•6, 0•0]) and for ELBW risk (-0•1% [95% CI -0•6, 0•3]). Significant differences were found between public versus private hospitals in the DID estimators (-1•2% [95% CI, -2•1, -0•3]) for VLBW risk. The results were comparable in covariate-adjusted models. INTERPRETATION: In this study, we found evidence of decreased disparities between public and private hospitals in VLBW risk. Our findings suggest that measures that prioritize social spending to protect the most vulnerable pregnant women during the pandemic contributed to better birth outcomes. FUNDING: No funding was secured for this study.

Overexpression of Multifunctional Protein p32 Promotes a Malignant Phenotype in Colorectal Cancer Cells.

p32 is a multifunctional and multicompartmental protein that has been found upregulated in numerous adenocarcinomas, including colorectal malignancy. High levels of p32 expression have been correlated with poor prognosis in colorectal cancer. However, the functions performed by p32 in colorectal cancer have not been characterized. Here we show that p32 is overexpressed in colorectal cancer cell lines compared to non-malignant colon cells. Colon cancer cells also display higher nuclear levels of p32 than nuclear levels found in non-malignant cells. Moreover, we demonstrate that p32 regulates the expression levels of genes tightly related to malignant phenotypes such as HAS-2 and PDCD4. Remarkably, we demonstrate that knockdown of p32 negatively affects Akt/mTOR signaling activation, inhibits the migration ability of colon malignant cells, and sensitizes them to cell death induced by oxidative stress and chemotherapeutic agents, but not to cell death induced by nutritional stress. In addition, knockdown of p32 significantly decreased clonogenic capacity and in vivo tumorigenesis in a xenograft mice model. Altogether, our results demonstrate that p32 is an important promoter of malignant phenotype in colorectal cancer cells, suggesting that it could be used as a therapeutic target in colorectal cancer treatment.

Signaling Pathways Involved in Nutrient Sensing Control in Cancer Stem Cells: An Overview.

Cancer cells characteristically have a high proliferation rate. Because tumor growth depends on energy-consuming anabolic processes, including biosynthesis of protein, lipid, and nucleotides, many tumor-associated conditions, including intermittent oxygen deficiency due to insufficient vascularization, oxidative stress, and nutrient deprivation, results from fast growth. To cope with these environmental stressors, cancer cells, including cancer stem cells, must adapt their metabolism to maintain cellular homeostasis. It is well- known that cancer stem cells (CSC) reprogram their metabolism to adapt to live in hypoxic niches. They usually change from oxidative phosphorylation to increased aerobic glycolysis even in the presence of oxygen. However, as opposed to most differentiated cancer cells relying on glycolysis, CSCs can be highly glycolytic or oxidative phosphorylation-dependent, displaying high metabolic plasticity. Although the influence of the metabolic and nutrient-sensing pathways on the maintenance of stemness has been recognized, the molecular mechanisms that link these pathways to stemness are not well known. Here in this review, we describe the most relevant signaling pathways involved in nutrient sensing and cancer cell survival. Among them, Adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway, mTOR pathway, and Hexosamine Biosynthetic Pathway (HBP) are critical sensors of cellular energy and nutrient status in cancer cells and interact in complex and dynamic ways.

ROP Screening Tool Assessment and Validation in a Third-Level Hospital in Argentina: A Pilot Study.

PURPOSE: To evaluate whether a mathematical tool that predicts severe retinopathy of prematurity (ROP) using clinical parameters at 6 weeks of life (ROPScore calculator smartphone application; PABEX Corporation) can be useful to predict severe ROP in a population of premature infants in Argentina. METHODS: In this retrospective study, data from the clinical records of all premature infants examined between 2012 and 2018 in the ophthalmology department of a public third-level hospital in Córdoba, Argentina, were obtained. ROPScore screening was applied using a Microsoft Excel spreadsheet (Microsoft Corporation). The sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values of the algorithm were analyzed. RESULTS: Between 2012 and 2018, a total of 2,894 pre-term infants were examined and 411 met the inclusion criteria, of whom 34% (n = 139) presented some form of ROP and 6% (n = 25) developed severe forms that required treatment. The sensitivity of the algorithm for any ROP and severe ROP was 100%. The PPV and NPV were 35.64% and 100%, respectively, for any ROP and 9.88% and 100% for severe ROP. CONCLUSIONS: One-time only calculation of the ROPScore algorithm could identify severe cases after validation, reducing the number of screened infants by 38% in infants with a birth weight of 1,500 g or less or a gestational age of 32 weeks or younger. [J Pediatr Ophthalmol Strabismus. 2021;58(1):55-61.].