Role of Diet in Stem and Cancer Stem Cells.

Diet and lifestyle factors greatly affect health and susceptibility to diseases, including cancer. Stem cells' functions, including their ability to divide asymmetrically, set the rules for tissue homeostasis, contribute to health maintenance, and represent the entry point of cancer occurrence. Stem cell properties result from the complex integration of intrinsic, extrinsic, and systemic factors. In this context, diet-induced metabolic changes can have a profound impact on stem cell fate determination, lineage specification and differentiation. The purpose of this review is to provide a comprehensive description of the multiple "non-metabolic" effects of diet on stem cell functions, including little-known effects such as those on liquid-liquid phase separation and on non-random chromosome segregation (asymmetric division). A deep understanding of the specific dietetic requirements of normal and cancer stem cells may pave the way for the development of nutrition-based targeted therapeutic approaches to improve regenerative and anticancer therapies.

Pediatrics for Disability: A Comprehensive Approach to Children with Syndromic Psychomotor Delay.

Intellectual disability is the impairment of cognitive, linguistic, motor and social skills that occurs in the pediatric age and is also described by the term "mental retardation". Intellectual disability occurs in 3-28 % of the general population due to a genetic cause, including chromosome aberrations. Among people with intellectual disabilities, the cause of the disability was identified as a single gene disorder in up to 12 %, multifactorial disorders in up to 4 %, and genetic disorders in up to 8.5 %. Children affected by a malformation syndrome associated with mental retardation or intellectual disability represent a care challenge for the pediatrician. A multidisciplinary team is essential to manage the patient, thereby controlling the complications of the syndrome and promoting the correct psychophysical development. This requires continuous follow-up of these children by the pediatrician, which is essential for both the clinical management of the syndrome and facilitating the social integration of these children.

Molecular testing on bronchial washings for the diagnosis and predictive assessment of lung cancer.

Cytopathological analyses of bronchial washings (BWs) collected during fibre-optic bronchoscopy are often inconclusive for lung cancer diagnosis. To address this issue, we assessed the suitability of conducting molecular analyses on BWs, with the aim to improve the diagnosis and outcome prediction of lung cancer. The methylation status of RASSF1A, CDH1, DLC1 and PRPH was analysed in BW samples from 91 lung cancer patients and 31 controls, using a novel two-colour droplet digital methylation-specific PCR (ddMSP) technique. Mutations in ALK, BRAF, EGFR, ERBB2, KRAS, MAP2K1, MET, NRAS, PIK3CA, ROS1 and TP53 and gene fusions of ALK, RET and ROS1 were also investigated, using next-generation sequencing on 73 lung cancer patients and 14 tumour-free individuals. Our four-gene methylation panel had significant diagnostic power, with 97% sensitivity and 74% specificity (relative risk, 7.3; odds ratio, 6.1; 95% confidence interval, 12.7-127). In contrast, gene mutation analysis had a remarkable value for predictive, but not for diagnostic, purposes. Actionable mutations in EGFR, HER2 and ROS1 as well as in other cancer genes (KRAS, PIK3CA and TP53) were detected. Concordance with gene mutations uncovered in tumour biopsies was higher than 90%. In addition, bronchial-washing analyses permitted complete patient coverage and the detection of additional actionable mutations. In conclusion, BWs are a useful material on which to perform molecular tests based on gene panels: aberrant gene methylation and mutation analyses could be performed as approaches accompanying current diagnostic and predictive assays during the initial workup phase. This study establishes the grounds for further prospective investigation.

Neuroinflammatory Markers in the Serum of Prepubertal Children with Down Syndrome.

Down Syndrome (DS) is the most common chromosomal disorder. Although DS individuals are mostly perceived as characterized by some distinct physical features, cognitive disabilities, and cardiac defects, they also show important dysregulations of immune functions. While critical information is available for adults with DS, little literature is available on the neuroinflammation in prepubertal DS children. We aimed to evaluate in prepubertal DS children the serum levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), oxidative stress as free oxygen radicals defense (FORD), free oxygen radicals test (FORT), and cytokines playing key roles in neuroinflammation and oxidative processes as TNF-α, TGF-ß, MCP-1, IL-1α, IL-2, IL-6, IL-10, and IL-12. No differences were found in NGF between DS children and controls. However, BDNF was higher in DS subjects compared to controls. We also did not reveal changes in FORD and FORT. Quite interestingly, the serum of DS children disclosed a marked decrease in all analyzed cytokines with evident differences in serum cytokine presence between male and female DS children. In conclusion, the present study evidences in DS prepubertal children a disruption in the neurotrophins and immune system pathways.

Fetal alcohol spectrum disorders awareness in health professionals: implications for psychiatry.

Fetal Alcohol Spectrum Disorders (FASD) are a plethora of malformative conditions leading to mental retardation that affect newborns and children who have been exposed to alcohol during pregnancy or breastfeeding. FASD is a relevant topic for public health in Europe: European area is first in ranking for alcohol use during pregnancy with a prevalence of 25.2%. Italy ranked third among European countries with higher prevalence of FASD (45.0 per 1000 population). Furthermore, FASD could still be underestimated because of numerous undiagnosed and misdiagnosed cases. Aims of the study were to briefly summarize existing evidences about FASD and its psychiatric aspects to assess knowledge, attitudes and practice towards alcohol drinking during pregnancy in an Italian sample of health care professionals in order to provide information about FASD prevention. An anonymous online questionnaire containing the AUDIT-C, T-ACE model and the Drinking Motive Questionnaire was sent to 400 Italian healthcare professionals and students. The survey included socio-demographic information, questions about drinking habits and about knowledge, attitude and practice towards alcohol assumption during pregnancy. Among 320 respondents, 96.3% were women. AUDIT-C revealed that 52.4% were low risk drinkers but 27.6% were hazardous drinkers. The 90.6% of participants denied to ever attended a course about the fetus damage induced by alcohol consumption during pregnancy but 91.3% were willing to participate to professional update initiatives on the topic. Only 19.1% of participants talk regularly about the deleterious effects for the fetus of prenatal alcohol drinking to women and only 51.1% advise the 'zero alcohol' policy. Around 41% of participants tolerates the assumption of low-alcohol beverages. No differences were found between no drinkers and low and hazardous drinkers. In conclusion, data show that only specific and continuing updating for health care professionals about drinking habits may have impactful actions to prevent gestational alcohol intake in order to prevent the main cause of mental retardation in western countries.

Low prostate concentration of lycopene is associated with development of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia.

Prostate cancer (PC) is a frequent male malignancy and represents the second most diagnosed cancer in men. Since pre-cancerous lesions, i.e., the high-grade prostatic intraepithelial neoplasia (HGPIN), can be detected years before progression to PC, early diagnosis and chemoprevention are targeted strategies to reduce PC rates. Animal studies have shown that lycopene, a carotenoid contained in tomatoes, is a promising candidate for the chemoprevention of PC. However, its efficacy in humans remains controversial. The present study aimed to investigate the relevance of plasma and prostate concentration of lycopene after a lycopene-enriched diet in patients diagnosed with HGPIN. Thirty-two patients diagnosed with HGPIN were administered a lycopene-enriched diet (20-25 mg/day of lycopene; through 30 g/day of triple concentrated tomato paste) for 6 months. A 6-month follow-up prostate biopsy assessed progression to PC. Patients were classified into three groups according to the histopathological features of the 6-month follow-up biopsy results: prostatitis; HGPIN and PC. PSA and plasma lycopene levels were measured before and after the dietary lycopene supplementation. Prostatic lycopene concentration was only assessed after the supplementation diet. Only prostatic lycopene concentration showed significant differences between the three groups (p = 0.03). Prostatic lycopene concentration below a 1 ng/mg threshold was associated with PC at 6-month follow-up biopsy (p = 0.003). We observed no overall benefits from a 6-month lycopene supplementation, as the rate of HGPIN progression to PC in our population (9/32, 28%) was similar to rates reported in the literature. Baseline PSA levels also showed no significant changes after a lycopene-enriched diet. Our findings point to prostatic lycopene concentration as a promising biomarker of PC. Further prospective longitudinal studies are needed to assess the prognostic role of prostatic lycopene in PC.

Parenteral nutrition in advanced cancer patients.

Parenteral nutrition (PN) is a medical treatment aimed at providing intravenous nutrients in patients in whom gastrointestinal function is partially or totally impaired. An obvious indication of PN in advanced cancer patients is the prevention and/or treatment of malnutrition in hypo-aphagic patients with intestinal failure due to the disease itself or the consequences of antineoplastic treatments. However, PN may also improve compliance with palliative radio/chemotherapy, reduce its side effects, enhance quality of life and prolong survival. A careful evaluation of patients' clinical conditions and families' expectations is mandatory before the decision to initiate PN in ACPs is taken, in order to avoid administration of an inappropriate or even life-threatening medical treatment. Current available evidence indicates that patients expected to die earlier from the underlying tumour rather than from starvation gather no benefit from intravenous nutritional support. Although it is likely that intravenous nutrients provided to feed the patients are also utilized by cancer cells, at present there is no evidence that this translates into a clinically relevant harm to the patient. Fear of tumour growth stimulation must not be a reason for not considering parenteral nutrition in advanced cancer patients. The risk of septic, metabolic and mechanical complications has to be considered when PN support is prescribed, although a specialized and well trained medical and nursing staff may dramatically reduce complication rate. Decisions regarding treatment initiation and its possible withdrawal should be made based on the best available evidence and non on cultural and personal attitudes.

Nail disorders in a woman treated with ixabepilone for metastatic breast cancer.

Ixabepilone (Ix) (BMS-247550) is a potent member of a new class of microtubule-stabilizing cytotoxic agents known as epothilones. In pre-clinical studies, Ix has shown anticancer activity against several cancer types, including paclitaxel-resistant models, both in vitro and in vivo. The major toxicities associated with Ix are myelosuppression, sensory neuropathy and neutropenia. Other minor side-effects include asthenia/fatigue, stomatitis, anorexia, alopecia, skin reaction, hypersensitivity reactions and a fluid-retention syndrome. Although Ix is functionally correlated to taxanes, no previous evidence exists regarding Ix-related nail disorders. Here, we report a case of a 59-year-old woman treated with Ix at 40 mg/m2 day 1 q 21 days who, after 8 cycles of therapy, developed onycholysis and subungual hemorrhagic bullas in the fingernails.

New approaches to prevent intestinal toxicity of irinotecan-based regimens.

BACKGROUND: Irinotecan is a selective inhibitor of topoisomerase I, an enzyme part of the replication and transcription system of DNA. Irinotecan is employed, with different modalities, in the treatment of metastatic colorectal cancer, and recently it has been officially approved in association with fluorouracil (FU) and leucovorin (LV) as a first-line option in metastatic colorectal cancer. RESULTS: One of the problems linked to the administration of this drug is the high intestinal toxicity, which constitutes its dose limiting toxicity (DLT). In routine practice, loperamide is employed as symptomatic drug for the treatment of CPT-11-induced diarrhoea, but is not completely adequate to control the problem. The role of the intestinal bacterial microflora in the pathogenesis of CPT-11-induced intestinal toxicity has been recently discovered. The active metabolite of CPT-11, SN38, is generated from CPT-11 by sieric carboxylesterase, and subsequently conjugated to SN38-G by hepatic UDP-glucuronyltransferase. SN38-G is the inactive metabolite of CPT-11 and is excreted into the small intestine, from which it is eliminated in the faeces. Some studies have shown the ability of intestinal bacterial beta-glucoronidases to transform SN38-G into SN38, causing direct damage to the intestinal mucosa. Thus, alternative strategies such as intestinal alkalinization and anti-cyclooxygenase 2 (COX-2) therapy have been explored. CONCLUSIONS: In this review, we will illustrate the mechanisms which cause the CPT-11-induced diarrhoea and the potential measures available to prevent it.