Cancer stem cell biomarkers predictive of radiotherapy response in rectal cancer: A systematic review

Background: Rectal cancer (RC) is one of the most commonly diagnosed and particularly challenging tumours to treat due to its location in the pelvis and close proximity to critical genitouri-nary organs. Radiotherapy (RT) is recognised as a key component of therapeutic strategy to treat RC, promoting the downsizing and downstaging of large RCs in neoadjuvant settings, although its therapeutic effect is limited due to radioresistance. Evidence from experimental and clinical studies indicates that the likelihood of achieving local tumour control by RT depends on the complete eradica-tion of cancer stem cells (CSC), a minority subset of tumour cells with stemness properties. Methods: A systematic literature review was conducted by querying two scientific databases (Pubmed and Scopus). The search was restricted to papers published from 2009 to 2021. Results: After assessing the quality and the risk of bias, a total of 11 studies were selected as they mainly focused on biomarkers predictive of RT-response in CSCs isolated from patients affected by RC. Specifically these studies showed that elevated levels of CD133, CD44, ALDH1, Lgr5 and G9a are associated with RT-resistance and poor prognosis. Conclusions: This review aimed to provide an overview of the current scenario of in vitro and in vivo studies evaluating the biomarkers predictive of RT-response in CSCs derived from RC patients

Anterior cruciate ligament recostruction with bone-patellar tendon-bone autograft in Tanner 3 stage patients with open physes

Ten skeletally immature patients were treated with an arthroscopic-assisted anterior cruciate ligament reconstruction with bone-patellar tendon bone autograft (compass, 50\u2013558; holes, 7\u20139 mm). Radiological assessments (standard radiograph), Orthopa\ua8 dische Arbeitsgruppe Knie (OAK) score and KT 1000, were conducted on all patients, 1 year after surgery. Skeletal maturity had been reached by all patients and no complications were observed. All patients returned to their preinjury sport level. Drilling more vertical tunnels when bone-tendon-bone autograft was chosen to avoid partial epiphysiodesis and offers good functional and isometric results

Characterization of Nonlinear Finger Pad Mechanics for Tactile Rendering

The computation of skin forces and deformations for tactile rendering requires an accurate model of the extremely nonlinear behavior of the skin. In this work, we investigate the characterization of finger mechanics with the goal of designing accurate nonlinear models for tactile rendering. First, we describe a measurement setup that enables the acquisition of contact force and contact area in the context of controlled finger indentation experiments. Second, we describe an optimization procedure that estimates the parameters of strain-limiting deformation models that match best the acquired data. We show that the acquisition setup allows the measurement of force and area information with high repeatability, and the estimation method reaches nonlinear models that match the measured data with high accuracy

Hyperthermic intraperitoneal chemotherapy and colorectal cancer: From physiology to surgery

The pursuit of this paper is to collect principal reviews and systematic reviews about hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) used in colorectal cancer (CRC). We focus on principal biological aspects of CRC, hyperthermia effects, and surgical procedures. We searched PubMed/MEDLINE for the principal reviews and systematic reviews published from 2010 to 2021 regarding the bimodal treatment (CRS + HIPEC) against local and advanced CRC. In the literature, from several studies, it seems that the efficacy of bimodal treatment with an accurate CRS can extend overall survival. Despite these studies, there are not still any straight guidelines more detailed and scheduled about the use of combined treatment in patients with CRC. Even if the concept is still not very clear and shared, after a careful evaluation of the published data, and after some technical and pathophysiological descriptions, we concluded that it is possible to improve the overall survival and quality of life and to reduce the tumor relapse in patients affected by locally advanced (pT4) CRC with peritoneal metastases

Lactate dehydrogenase in hepatocellular carcinoma: something old, something new

Hepatocellular carcinoma (HCC) is the most common primary liver tumour (80-90%) and represents more than 5.7% of all cancers. Although in recent years the therapeutic options for these patients have increased, clinical results are yet unsatisfactory and the prognosis remains dismal. Clinical or molecular criteria allowing a more accurate selection of patients are in fact largely lacking. Lactic dehydrogenase (LDH) is a glycolytic key enzyme in the conversion of pyruvate to lactate under anaerobic conditions. In preclinical models, upregulation of LDH has been suggested to ensure both an efficient anaerobic/glycolytic metabolism and a reduced dependence on oxygen under hypoxic conditions in tumour cells. Data from several analyses on different tumour types seem to suggest that LDH levels may be a significant prognostic factor. The role of LDH in HCC has been investigated by different authors in heterogeneous populations of patients. It has been tested as a potential biomarker in retrospective, small, and nonfocused studies in patients undergoing surgery, transarterial chemoembolization (TACE), and systemic therapy. In the major part of these studies, high LDH serum levels seem to predict a poorer outcome. We have reviewed literature in this setting trying to resume basis for future studies validating the role of LDH in this diseas

dynamic investigation test rig on haptics dita

Research on tactile sensitivity has been conducted since the last century and many devices have been proposed to study in detail this sense through experimental tests. The sense of touch is essential in every-day life of human beings, but it can also play a fundamental role for the assessment of some neurological disabilities and pathologies. In fact, the level of tactile perception can provide information on the health state of the nervous system. In this paper, authors propose the design and development of a novel test apparatus, named DITA (Dynamic Investigation Test-rig on hAptics), aiming to provide the measurement of the tactile sensitivity trough the determination of the Just Noticeable Difference (JND) curve of a subject. The paper reports the solution adopted for the system design and the results obtained on the set of experiments carried out on volunteers

Stard3: A prospective target for cancer therapy

Cancer is one of the major causes of death in developed countries and current therapies are based on surgery, chemotherapeutic agents, and radiation. To overcome side effects induced by chemo-and radiotherapy, in recent decades, targeted therapies have been proposed in second and even first lines. Targeted drugs act on the essential pathways involved in tumor induction, progression, and metastasis, basically all the hallmark of cancers. Among emerging pathways, the cholesterol metabolic pathway is a strong candidate for this purpose. Cancer cells have an accelerated metabolic rate and require a continuous supply of cholesterol for cell division and membrane renewal. Steroidogenic acute regulatory related lipid transfer (START) proteins are a family of proteins involved in the transfer of lipids and some of them are important in non-vesicular cholesterol transportation within the cell. The alteration of their expression levels is implicated in several diseases, including cancers. In this review, we report the latest discoveries on StAR-related lipid transfer protein domain 3 (STARD3), a member of the START family, which has a potential role in cancer, focusing on the structural and biochemical characteristics and mechanisms that regulate its activity. The role of the STARD3 protein as a molecular target for the development of cancer therapies is also discussed. As STARD3 is a key protein in the cholesterol movement in cancer cells, it is of interest to identify inhibitors able to block its activity

Chromophobe renal cell carcinoma with prolonged response to targeted therapy: a case report

Abstract Introduction Chromophobe renal cell carcinoma is universally accepted as a distinct subtype of renal cell carcinoma. There are conflicting reports on prognosis, and few data on response to treatment exist. Currently, we do not have any effective treatment for the metastatic disease apart from surgical procedures. Current strategies are based on results obtained in the context of clear cell-type renal cell carcinoma. Separate trials for rare histologies seem unfeasible and are unlikely to be performed. For these cases, clinical observations are an important part for advancing therapeutic insight. In recent years, novel tyrosine kinase inhibitors have been shown to have significant clinical benefit in advanced renal cell carcinoma. Case presentation We present the case of a 43-year-old Caucasian man with advanced chromophobe renal cell carcinoma treated with the tyrosine kinase inhibitor sunitinib and subsequently with sorafenib and the mammalian target of the rapamycin inhibitor everolimus, achieving a prolonged response and significant clinical benefit. We report an unexpectedly high efficacy of everolimus as a third-line treatment in a patient with metastatic chromophobe renal cell carcinoma. Conclusions Up to now, no published data from randomized clinical studies have addressed the question of efficacy of everolimus as a third-line treatment after failure of tyrosine kinase inhibitors. To the best of our knowledge, this case is the first report of chromophobe renal cell carcinoma treated successfully with sequential tyrosine kinase and mammalian target of rapamycin inhibitor therapy. Notably, the time on treatment with sunitinib exceeded four years. The case presented here implies that everolimus could be a viable option for patients with metastatic chromophobe renal cell carcinoma.</p

The VIMOS VLT Deep Survey :Evolution of the major merger rate since z~1 from spectroscopicaly confirmed galaxy pairs

From the VIMOS VLT Deep Survey we use a sample of 6447 galaxies with I_{AB} < 24 to identify 251 pairs of galaxies, each member with a secure spectroscopic redshift, which are close in both projected separation and in velocity. We find that at z ~ 0.9, 10.9 +/- 3.2 % of galaxies with M_B(z) < -18-Qz are in pairs with separations dr < 20 kpc/h, dv < 500 km/s, and with dM_B < 1.5, significantly larger than 3.76 +/- 1.71 % at z ~ 0.5; we find that the pair fraction evolves as (1+z)^m with m = 2.49 +/- 0.56. For brighter galaxies with M_B(z=0) < -18.77, the pair fraction is higher and its evolution with redshift is somewhat flatter with m=1.88 \pm 0.40, a property also observed for galaxies with increasing stellar masses. Early type, dry mergers, pairs increase their relative fraction from 3 % at z ~ 0.9 to 12 % at z ~ 0.5. We find that the merger rate evolves as N_{mg}=(9.05 +/- 3.76) * 10^{-4}) * (1+z)^{2.43 +/- 0.76}. We find that the merger rate of galaxies with M_B(z) < -18-Qz has significantly evolved since z ~ 1. The merger rate is increasing more rapidly with redshift for galaxies with decreasing luminosities, indicating that the flat evolution found for bright samples is not universal. The merger rate is also strongly dependent on the spectral type of galaxies involved, late type mergers being more frequent in the past, while early type mergers are more frequent today, contributing to the rise in the local density of early type galaxies. About 20 % of the stellar mass in present day galaxies with log(M/M_{sun}) > 9.5 has been accreted through major merging events since z ~ 1, indicating that major mergers have contributed significantly to the growth in stellar mass density of bright galaxies over the last half of the life of the Universe.Comment: 22 pages, 19 figures, accepted in A&

The zCOSMOS 10k-sample: the role of galaxy stellar mass in the colour-density relation up to z=1

[Abridged] With the first 10000 spectra of the flux limited zCOSMOS sample (I<=22.5) we study the evolution of environmental effects on galaxy properties since z=1.0, and disentangle the dependence among galaxy colour, stellar mass and local density (3D local density contrast `delta', computed with the 5th nearest neighbour approach). We confirm that within a luminosity-limited sample (M_B=1) galaxies 'f_red' depends on delta at least up to z=1, with red galaxies residing mainly in high densities. This trend weakens for increasing z, and it is mirrored by the behaviour of the fraction of galaxies with D4000A break >=1.4. We also find that up to z=1 the fraction of galaxies with log(EW[OII]) >=1.15 is higher for lower delta, and also this dependence weakens for increasing z. Given the triple dependence among galaxy colours, stellar mass and delta, the colour-delta relation found in the luminosity-selected sample can be due to the broad range of stellar masses. Thus, we fix the stellar mass and we find that in this case the colour-delta relation is flat up to z=1 for galaxies with log(M/M_sun)>=10.7. This means that for these masses the colour-delta relation found in a luminosity-selected sample is the result of the combined colour-mass and mass-delta relations. In contrast, we find that for 0.1<=z<=0.5 and log(M/M_sun)<=10.7 'f_red' depends on delta even at fixed mass. In these mass and z ranges, environment affects directly also galaxy colours. We suggest a scenario in which the colour depends primarily on stellar mass, but for relatively low mass galaxies the local density modulates this dependence. These galaxies formed more recently, in an epoch when evolved structures were already in place, and their longer SFH allowed environment-driven physical processes to operate during longer periods of time.Comment: 19 pages, 12 figures, submitted to A&A, revised version after referee comment