Tyrosine Kinase Receptors in Oncology Esteban-Villarrubia, Jorge; Soto-Castillo, Juan José; Pozas, Javier ...
International journal of molecular sciences,
11/2020, Letnik:
21, Številka:
22
Journal Article
Recenzirano
Odprti dostop
Tyrosine kinase receptors (TKR) comprise more than 60 molecules that play an essential role in the molecular pathways, leading to cell survival and differentiation. Consequently, genetic alterations ...of TKRs may lead to tumorigenesis and, therefore, cancer development. The discovery and improvement of tyrosine kinase inhibitors (TKI) against TKRs have entailed an important step in the knowledge-expansion of tumor physiopathology as well as an improvement in the cancer treatment based on molecular alterations over many tumor types. The purpose of this review is to provide a comprehensive review of the different families of TKRs and their role in the expansion of tumor cells and how TKIs can stop these pathways to tumorigenesis, in combination or not with other therapies. The increasing growth of this landscape is driving us to strengthen the development of precision oncology with clinical trials based on molecular-based therapy over a histology-based one, with promising preliminary results.
Aortitis is a rare entity that may cause fever of unknown origin. This entity has a wide various etiologies, which main cause is rheumatologic, but not only. Iatrogenia has also been described, ...including chemotherapy and supporting treatment (like granulocyte-colony stimulating factor in oncological patients. The evidence in favour of this pharmacological link is growing. The differential diagnosis of fever, in febrile neutropenia setting, can be difficult to itemize.
Oral cancer is the 11th most common type of cancer in the world, with established major risk factors as tobacco and alcohol, and recently included high-risk human papillomavirus types 16 and 18. HPV ...types 16 and 18 are the etiologic agents of cervical cancers and a proportion of oropharyngeal cancers. However, the picture of HPV and the clinical implications of oral cancers are not clear with most reports combining oral cancer data with head and neck cancers. It has been confirmed as a favorable prognostic factor in oropharyngeal cancer. However, the prognostic value of HPV in oral squamous cell carcinoma is still unclear.
The main objective of this article is to present the evidence encountered following a bibliographical review of recent publications specifically related to oral cancer and its differences from oropharyngeal cancer. The secondary goals are to present the findings of a five-year retrospective observational study of the prevalence of HPV infection in oral cancer patients treated by the Oral and Maxillofacial Surgery Department at La Paz University Hospital (Madrid, Spain), and finally, we to evaluate and compare our country's HPV prevention program in comparison to other European countries.
According to the review of the literature, HPV positive oral squamous cell carcinoma is associated with significantly decreased overall survival and distant control. Bibliographic review suggest HPV infection can be used as a negative prognostic factor in oral squamous cell carcinoma.
As regards diagnostic testing for HPV, it should be extended to as many cases of oral cavity squamous cell carcinoma as possible, especially in those with risk factors. The current vaccination program in Spain does not have adequate coverage and is significantly under the level of other European Union countries; it should be expanded and catch-up strategies should be included.
HPV, OSSC, Papillomavirus, oral carcinoma, prevention.
The SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex is one of the most remarkably altered epigenetic regulators in cancer. Pathogenic mutations in genes encoding SWI/SNF-related ...proteins have been recently described in many solid tumors, including rare and aggressive malignancies with rhabdoid features with no standard therapies in advanced or metastatic settings. In recent years, clinical trials with targeted drugs aimed at restoring its function have shown discouraging results. However, preclinical data have found an association between these epigenetic alterations and response to immune therapy. Thus, the rationale for immunotherapy strategies in SWI/SNF complex alteration-related tumors is strong. Here, we review the SWI/SNF complex and how its dysfunction drives the oncogenesis of rhabdoid tumors and the proposed strategies to revert this alteration and promising novel therapeutic approaches, including immune checkpoint inhibition and adoptive cell therapy.
El estudio denominado El estado de la seguridad alimentaria y la nutrición en el mundo: Protegerse frente a la desaceleración es una producción de la Organización de las Naciones Unidad para la ...Alimentación y la Agricultura del año 2019, la cual presenta una brillante exposición sobre las condiciones que guarda la alimentación en el mundo. En el libro se muestra la estructura capitular que permite observar su conformación general. A lo largo de este texto se desarrollan las temáticas más relevantes.
Early clinical trials investigating antiPD(L)-1 agents rarely reached a maximum tolerated dose (MTD), and efficacy signals were observed even at the lowest dose levels. Most extended treatment ...intervals investigated indicated that these drugs do not follow a direct dose-toxicity or dose-efficacy relationship. Within this context and considering the high cost of antiPD(L)-1 agents, there is a significant debate on whether lower doses or the administration of such agents at an extended interval should be prospectively evaluated in already-approved agents, or at least be considered in novel combination trials involving antiPD(L)-1 drugs. Herein, we review the dosing, overall response rates, and incidence of treatment-related adverse events of antiPD(L)-1 agents in early dose-escalation trials and discuss the appropriateness of recommended Phase 2 dose selection as well as the final regulatory approved doses of such agents. Efficacy and safety data from randomized dose-range Phase 2 trials and real-world data (RWD) on the usage of lower doses and/or non-standard extended treatment intervals are also examined. As the accumulating evidence suggests lower doses or extended dosing intervals of antiPD(L)-1 may achieve a similar clinical benefit in comparison to the currently approved doses, we address the clinical and financial toxicity implications of using potentially higher doses than necessary. Last, we discuss ways to resolve the current dosing conundrum of antiPD-(L)1 agents such as performing near-equivalence studies and propose a framework for future development of immunotherapeutics to find the lowest efficacious dose instead of MTD.
Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at ...disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤ 30 years (early onset), age between 31 and 59 years (standard onset), and age ≥ 60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients.
•The absorptance of a cryogenic radiometer is reported to several wavelengths.•The absorptance value uncertainty is optimized at 632.8nm.•The developed method use cap of Teflon coatings allows high ...reproducibility.•The method provided the versatility to mount cavities with different geometry.
This paper presents the results of absorptance measurements of the cavity used in the cryogenic radiometer of the National Metrology Center of Mexico (CENAM) as absorptance device. The cavity absorptance was determined for several reference wavelengths in the visible range (VIS) using a He–Ne laser source and a tunable Ar–Kr laser at 476nm, 488nm, 520nm, 568nm and 676nm. The absorptance value of 0.999 816±1.9×10−6 (k=2) at 632.8nm obtained, matches with the reference value reported by the manufacturer of the cavity, L-1 Standards and Technology Inc., which is 0.999 823±8.0×10−6 (k=2). The variations found in the absorptance values goes from −4.4×10−6 to −5.1×10−7 for the wavelengths listed above.
Objectives The aim was to evaluate the relaxant effect of extracts from Valeriana edulis and determine the possible mechanism of action of the hexanic extract as vasorelaxant agent.
Methods ...Extracts from rhizomes obtained by maceration (hexanic (HEVe), dichloromethanic (DEVe), methanolic (MEVe) and hydroalcoholic (HAEVe) (3.03–500 µg/ml)) were evaluated on aortic rat rings with and without endothelium.
Key findings Extracts induced a significant concentration‐dependent and endothelium‐independent relaxation on isolated rat aorta pre‐contracted with noradrenaline (0.1 µm). HEVe, the most potent extract (0.15–50 µg/ml), induced relaxation in aortic rings pre‐contracted with KCl (80 mm), with an IC50 value of 34.61 ± 1.41 µg/ml and Emax value of 85.0 ± 4.38%. Pretreatment with HEVe (30 µg/ml) also inhibited contractile responses to noradrenaline and CaCl2. HEVe (9.98 ± 2.0 µg/ml) reduced noradrenaline‐induced transient contraction in Ca2+‐free solution, and inhibited contraction induced by KCl (80 mm). In endothelium‐denuded rings, the vasorelaxant effect of HEVe was not modified by 1‐H‐1,2,4‐oxadiazolo‐4,3a‐quinoxalin‐1‐one (1 µm), tetraethylammonium (5 mm), glibenclamide (10 µm) or 2‐aminopyridine (100 µm).
Conclusions Our results suggest that HEVe induces relaxation through an endothelium‐independent pathway, involving blockade of Ca2+ channels, and this effect could be related to the presence of valepotriates.
To assess the clinical manifestations and prognosis of Spanish patients with systemic sclerosis (SSc) according to their immunological profile.
From the Spanish Scleroderma Study Group or RESCLE ...(Registro de ESCLErodermia as Spanish nomenclature) Registry we selected those patients in which anti-centromere (ACA), anti-topoisomerase I (ATA), and anti-RNA polymerase III (ARA) antibodies had been determined, and a single positivity for each SSc specific antibody was detected. Demographic, clinical, laboratory, and survival data were compared according to the serologic status of these antibodies.
Overall, 209 SSc patients were included. In 128 (61%) patients ACA was the only positive antibody, 46 (22%) were only positive for ATA, and 35 (17%) for ARA. Of note, the three groups were mutually exclusive. In univariate analysis, patients with ACA presented more frequently limited cutaneous SSc (lcSSc) (p<0.001), whereas diffuse cutaneous SSc (dcSSc) was the most frequent subtype in patients with ATA (54%) and ARA (62%) (both p<0.001). Positive patients for ARA showed the highest prevalence of joint involvement (p<0.001) and those from ATA group had a higher prevalence of interstitial lung disease (ILD) (p<0.001). Scleroderma renal crisis was more frequent in the ARA group (p<0.001). In multivariate analysis, ACA were associated with female gender and were protective for dcSSc and ILD. ATA were found to be protective for lcSSc and they were independently associated with interstitial reticular pattern. ARA positivity was independently associated with dcSSc. We did not find differences in mortality between the three groups.
In Spanish SSc patients, the presence of SSc specific antibodies conferred a distinctive clinical profile.
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