Universal scaling laws rule explosive growth in human cancers.

Most physical and other natural systems are complex entities composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws relating an observable quantity with a measure of the size of the system. Here we describe the discovery of universal superlinear metabolic scaling laws in human cancers. This dependence underpins increasing tumour aggressiveness, due to evolutionary dynamics, which leads to an explosive growth as the disease progresses. We validated this dynamic using longitudinal volumetric data of different histologies from large cohorts of cancer patients. To explain our observations we put forward increasingly-complex biologically-inspired mathematical models that captured the key processes governing tumor growth. Our models predicted that the emergence of superlinear allometric scaling laws is an inherently three-dimensional phenomenon. Moreover, the scaling laws thereby identified allowed us to define a set of metabolic metrics with prognostic value, thus providing added clinical utility to the base findings.

Assessment of adherence to preventive treatment of plaque-induced oral diseases using sugar-free gums: a controlled clinical trial / Evaluación de la adhesión al tratamiento preventivo de enfermedades bucales inducidas por placa bacteriana mediante el uso de gomas de mascar sin azúcar: ensayo clínico controlado

Abstract Introduction: the aim of this study was to assess the adherence to a preventive treatment of plaque-induced oral diseases using two sugar-free gums, establishing their effect on cariogenic bacteria counts as a biological marker of treatment response. Methods: a double-blind, randomized, parallel-group, controlled intervention study was conducted in 96 young adult university students in an experimental period of 30 days. Participants were distributed into two groups and given a chewing gum with either pentitol or hexitol + CPP-ACP complex to be taken three times a day for 20 minutes after conventional oral hygiene. Saliva samples were collected at baseline to evaluate counts of Streptococcus mutans (SM) and Lactobacillus spp. A survey was conducted at the end of the experimental period to assess the levels of adherence to treatment, remeasuring bacterial counts. Results: SM counts showed statistically significant differences between the study groups at the end of the experimental period, with a decreasing tendency in both groups. Intragroup difference was observed in patients who took pentitol gum with a marked reduction in SM counts. Conclusion: the final estimate of adherence to treatment showed that the type of chewing gum patients were given had no influence and therefore such gums can be used, considering the therapeutic agents that most contribute to patient's particular case and preferences.

Resumen Introducción: el objetivo consistió en evaluar la adherencia a un tratamiento preventivo de enfermedades bucales inducidas por placa bacteriana, utilizando dos gomas de mascar sin azúcar y establecer su efecto sobre recuentos de bacterias cariogénicas como indicador biológico de los efectos del tratamiento. Métodos: se realizó un estudio de intervención, doble ciego, de grupos paralelos, aleatorizado controlado, en 96 adultos jóvenes universitarios, en un período experimental de 30 días. Los participantes fueron distribuidos en dos grupos con asignación de una goma de mascar con pentitol o con hexitol + complejo CPP-ACP que debían ser consumidas 20 minutos/tres veces al día después de la higiene oral convencional. Al inicio del studio fueron recolectadas muestras de saliva para evaluar recuentos de Estreptococos del grupo mutans (SM) y Lactobacillus spp. Al finalizar el período experimental, se realizó una encuesta para evaluar los niveles deadherencia al tratamiento y los recuentos bacterianos fueron medidos nuevamente. Resultados: Los recuentos de SM mostraron diferencias estadísticamente significativas entre los grupos de estudio al final del período experimental, con tendencia hacia la disminución en ambos grupos. Se observó diferencia intragrupo en los pacientes que consumieron la goma de mascar con pentitol, con marcada reducción de los recuentos de SM. Conclusión: la estimación final de la adherencia al tratamiento mostró que el tipo de goma de mascar asignada al paciente no tuvo influencia y, por lo tanto, estas pueden ser utilizadas teniendo en cuenta los agentes terapéuticos que más aporten al caso particular del paciente y las preferencias del mismo.

Association analysis between rs6184 and rs6180 polymorphisms of growth hormone receptor gene regarding skeletal-facial profile in a Colombian population.

Background/Objective: There is strong evidence that genetic factors may affect the craniofacial morphology. This study aimed to examine the association between the rs6184 and rs6180 polymorphic variants of the growth hormone receptor (GHR) gene and skeletal-facial profile in a Colombian population. Subjects/Methods: Saliva samples from 306 individuals ranging in age from 15 to 53 (mean 24.33) years were collected. Cephalometric parameters were used to categorize the participants as Class I, Class II, or Class III skeletal-facial profile. The polymerase chain reaction-restriction fragment length polymorphism method was used to identify genotypes of the rs6184 and rs6180 single nucleotide polymorphisms (SNPs). The association of polymorphisms with the skeletal-facial profile was assessed separately and adjusted for confounding using a multivariate binary logistic regression model, alongside with analysis of linkage disequilibrium and haplotype associations. Results: Although individuals carrying the CA genotype of the rs6184 SNP showed both significantly decreased values for ANB angle and increased measures concerning mandibular body length and mandibular length, no significant differences amongst genotype groups of rs6180 SNP were observed. Moreover, chi-square test and logistic regression analysis revealed that the CA genotype of rs6184 SNP and the A-A haplotype were highly associated with Class III skeletal-facial profile. Conclusions: Although these results do not support that rs6180 SNP could be identified as a predictor for skeletal-facial profile, they suggest that the allele A of rs6184 SNP alone or in combination with other SNPs in the GHR gene yields significant horizontal and longitudinal variations of the mandibular morphology and might be a strong/independent prognostic indicator for Class III skeletal-facial profile in the present population.

Correlation of DNA Repair Gene Polymorphisms With Clinical Outcome in Patients With Locally Advanced Non-Small-Cell Lung Cancer Receiving Induction Chemotherapy Followed by Surgery.

OBJECTIVE: The aim of this study was to evaluate whether xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) polymorphisms influenced clinical outcome in patients with stage IIIA-B non-small-cell lung cancer (NSCLC) treated with neoadjuvant gemcitabine/cisplatin/docetaxel followed by surgery. MATERIALS AND METHODS: A total of 109 patients with stage IIIA and IIIB NSCLC were prospectively genotyped to examine a potential association between XPD 312 (aspartic acid [Asp]/asparagine [Asn]), XPD 751 (lysine [Lys]/glutamine [Gln]), and RRM1 (-37 C/A) polymorphisms with response and survival. RESULTS: The median survival was 32.14 months for carriers of XPD 312 Asp/Asp and 12.04 months for those with the variant Asn allele (P = .05). In addition, event-free survival was longer for patients with the XPD 312 Asp/Asp genotype compared with patients with Asp/Asn or Asn/Asn (P = .03). A similar but nonsignificant trend was observed for the XPD 751 genotype. In a multivariate analysis, complete resection and age emerged as prognostic factors for overall survival; in patients with incomplete resection or exploratory thoracotomy, XPD 312 was the most significant prognostic factor (P = .03). CONCLUSION: The XPD 312 single nucleotide polymorphism is a prognostic factor for survival in patients with locally advanced NSCLC receiving induction chemotherapy followed by surgery. The Asn allele is associated with unfavorable outcome and could be used for better stratification of patients.

A sensitive method for detecting EGFR mutations in non-small cell lung cancer samples with few tumor cells.

BACKGROUND: Detection of epidermal growth factor receptor (EGFR) mutations in advanced non-small cell lung cancer (NSCLC) patients has relied on DNA purification from biopsies, amplification, and sequencing. However, the number of tumor cells in a sample is often insufficient for EGFR assessment. METHODS: We prospectively screened 1380 NSCLC patients for EGFR mutations but found that 268 were not evaluable because of insufficient tumor tissue. We therefore developed and validated a method of detecting EGFR mutations in these samples. Tumor cells were microdissected into polymerase chain reaction buffer and amplified. EGFR mutations were detected by length analysis of fluorescently labeled polymerase chain reaction products and TaqMan assay. RESULTS: We determined EGFR status in 217 (81%) of the 268 primary NSCLC samples not evaluable in our original study-fresh and paraffin-embedded with less than 150 cells. Exon 19 deletions were detected in 11.5% of patients and exon 21 L858R mutations in 5.5%. In addition, the exon 20 T790M mutation was detected in 6 of 15 (40%) patients at the time of progression to erlotinib. The primary, sensitive mutation was present in all tumor cells, whereas the T790M mutation was absent in some groups. CONCLUSIONS: The method presented here eliminates the need for DNA purification and allows for detection of EGFR mutations in samples containing as few as eight cancer cells.