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Activation of the Ras pathway is a common finding in pediatric hematologic neoplasms. Implementation of precision medicine with a goal of improving outcomes for these patients will require testing of Ras pathway inhibitors in combination with other drugs in the context of current and future clinical trials.
Activation of the Ras pathway is a common finding in pediatric hematologic neoplasms. Saracatinib Implementation of precision medicine with a goal of improving outcomes for these patients will require testing of Ras pathway inhibitors in combination with other drugs in the context of current and future clinical trials.
The treatment of Wilms tumor is one of the great achievements in the field of oncology. One of the key success factors has been improved risk stratification, enabling augmentation or reduction of therapy depending on a patient's risk of relapse. This article highlights the evolution of clinical and biological prognostic markers that have been applied in the treatment of Wilms tumor.
Historically, tumor stage and histology were the sole determinants of Wilms tumor treatment. Recent clinical trials conducted by the Children's Oncology Group (COG) and the International Society of Pediatric Oncology (SIOP) Renal Tumor Study Group have expanded the menu of prognostic factors to include histologic and volumetric response to therapy and tumor-specific loss of heterozygosity (LOH) at chromosomes 1p and 16q. Augmentation of therapy has been able to overcome the adverse risk factors. An emerging prognostic marker is chromosome 1q gain, will be incorporated into future clinical trials.
The application of new clinical and biological prognostic factors has created unprecedented ability to tailor therapy for Wilms tumor, accompanied with improved outcomes. Current and future trials will continue to enhance precision medicine for Wilms tumor.
The application of new clinical and biological prognostic factors has created unprecedented ability to tailor therapy for Wilms tumor, accompanied with improved outcomes. link= Saracatinib Current and future trials will continue to enhance precision medicine for Wilms tumor.
To give an overview of recent advances in therapeutic approaches of radiation-induced salivary gland cancers (ri-SGCs).
Reirradiation with protons and carbon ions demonstrated to be feasible, safe and to offer good local control rates, with the possibility of overcoming radioresistance and dosimetric issues in previously irradiated cancer patients. Chromosomal rearrangements, gene fusions and expression profiles are important to identify specific cancer subtypes and can guide tailored systemic therapy.
Ri-SGCs are rare and heterogeneous. Patients are often heavily pretreated and at risk of toxicities, and their management remain challenging. A multidisciplinary approach in referral centers is mandatory. Knowledge about SGCs cellular and molecular mechanisms is constantly evolving. Saracatinib In the last years, novel advances in therapeutic approaches, such as carbon ion radiotherapy, are emerging as safe and effective options in active treatment, but further efforts are needed to offer tailored personalized treatments and to improve survival.
Ri-SGCs are rare and heterogeneous. Patients are often heavily pretreated and at risk of toxicities, and their management remain challenging. A multidisciplinary approach in referral centers is mandatory. Knowledge about SGCs cellular and molecular mechanisms is constantly evolving. In the last years, novel advances in therapeutic approaches, such as carbon ion radiotherapy, are emerging as safe and effective options in active treatment, but further efforts are needed to offer tailored personalized treatments and to improve survival.
The purpose of this review is to define the issues regarding oral potentially malignant disorders (OPMDs) and provide an overview of currently available treatments and ongoing clinical trials for future opportunities.
Nowadays, the treatment of choice of OPMD is surgery, whose role in preventing malignant transformation is however limited because of the high rate of recurrence and field cancerization. There have been several attempts of combining systemic therapies with surgery to reduce risk of malignant transformation. The identification of biomarkers that could predict malignant transformation is crucial in better tailoring the risk profile and possible therapeutic approaches.
Loss of heterozygosity remains the most predictive marker of malignant transformation; however, role of specific microRNA and OPMD immune infiltration are emerging as potential biomarkers. Given the failure of previous trials with various chemopreventive strategies, new strategies should be defined to address the issue of systemic prevention of malignant transformation. Recent updates about immune infiltration and the immune-equilibrium concept for OPMD could shed light into new preventive approaches.
Loss of heterozygosity remains the most predictive marker of malignant transformation; however, role of specific microRNA and OPMD immune infiltration are emerging as potential biomarkers. Given the failure of previous trials with various chemopreventive strategies, new strategies should be defined to address the issue of systemic prevention of malignant transformation. Recent updates about immune infiltration and the immune-equilibrium concept for OPMD could shed light into new preventive approaches.
Image guided navigation has had significant impact in head and neck surgery, and has been most prolific in endonasal surgeries. Although conventional image guidance involves static computed tomography (CT) images attained in the preoperative setting, the continual evolution of surgical navigation technologies is fast expanding to incorporate both real-time data and bioinformation that allows for improved precision in surgical guidance. With the rapid advances in technologies, this article allows for a timely review of the current and developing techniques in surgical navigation for head and neck surgery.
Current advances for cross-sectional-based image-guided surgery include fusion of CT with other imaging modalities (e.g., magnetic resonance imaging and positron emission tomography) as well as the uptake in intraoperative real-time 'on the table' imaging (e.g., cone-beam CT). These advances, together with the integration of virtual/augmented reality, enable potential enhancements in surgical navigation. In addition to the advances in radiological imaging, the development of optical modalities such as fluorescence and spectroscopy techniques further allows the assimilation of biological data to improve navigation particularly for head and neck surgery.
The steady development of radiological and optical imaging techniques shows great promise in changing the paradigm of head and neck surgery.
The steady development of radiological and optical imaging techniques shows great promise in changing the paradigm of head and neck surgery.
In a conventional IVF cycle, final oocyte maturation and ovulation is triggered with a bolus of hCG, followed by progesterone-based luteal support that spans several weeks if pregnancy is achieved. This article summarizes several approaches of the exogenous progesterone-free luteal support in IVF.
Triggering ovulation with GnRH agonist may serve as an alternative to hCG, with well established advantages. link2 In addition, the luteal phase can be individualized in order to achieve a more physiologic hormonal milieu, and a more patient friendly treatment, alleviating the burden of a lengthy exogenous progesterone therapy.
GnRH agonist trigger followed by a 'freeze all' policy is undoubtedly the best approach towards the 'OHSS-free clinic'. If fresh embryo transfer is considered well tolerated after GnRH agonist trigger, rescue of the corpora lutea by LH activity supplementation is mandatory. Herein we discuss the different approaches of corpus luteum rescue.
GnRH agonist trigger followed by a 'freeze all' policy is undoubtedly the best approach towards the 'OHSS-free clinic'. If fresh embryo transfer is considered well tolerated after GnRH agonist trigger, rescue of the corpora lutea by LH activity supplementation is mandatory. Herein we discuss the different approaches of corpus luteum rescue.
Rapidly emerging evidence implicates an important role of gut-brain-bone marrow (BM) axis involving gut microbiota (GM), gut epithelial wall permeability, increased production of pro-inflammatory BM cells and neuroinflammation in hypertension (HTN). However, the precise sequence of events involving these organs remains to be established. link2 Furthermore, whether an impaired gut-brain-BM axis is a cause or consequence of HTN is actively under investigation. This will be extremely important for translation of this fundamental knowledge to novel, innovative approaches for the control and management of HTN. Therefore, our objectives are to summarize the latest hypothesis, provide evidence for and against the impaired gut, BM and brain interactions in HTN and discuss perspectives and future directions.
Hypertensive stimuli activate autonomic neural pathways resulting in increased sympathetic and decreased parasympathetic cardiovascular modulation. This directly affects the functions of cardiovascular-relevant organs to increase blood pressure. link3 Increases in sympathetic drive to the gut and BM also trigger sequences of signaling events that ultimately contribute to altered GM, increased gut permeability, enhanced gut- and brain-targeted pro-inflammatory cells from the BM in perpetuation and establishment of HTN.
In this review, we present the mechanisms involving the brain, gut, and BM, whose dysfunctional interactions may be critical in persistent neuroinflammation and key in the development and establishment of HTN.
In this review, we present the mechanisms involving the brain, gut, and BM, whose dysfunctional interactions may be critical in persistent neuroinflammation and key in the development and establishment of HTN.
Hypertension has been demonstrated to be a chief contributor to morbidity and mortality throughout the world. Although the cause of hypertension is multifactorial, emerging evidence, obtained in experimental studies, as well as observational studies in humans, points to the role of inflammation and immunity. Many aspects of immune function have now been implicated in hypertension and end-organ injury; this review will focus upon the recently-described role of Th17 cells in this pathophysiological response.
Studies in animal models and human genetic studies point to a role in the adaptive immune system as playing a contributory role in hypertension and renal tissue damage. Th17 cells, which produce the cytokine IL17, are strongly pro-inflammatory cells, which may contribute to tissue damage if expressed in chronic disease conditions. The activity of these cells may be enhanced by physiological factors associated with hypertension such as dietary salt or Ang II. This activity may culminate in the increased sodium retaining activity and exacerbation of inflammation and renal fibrosis via multiple cellular mechanisms.
Th17 cells are a distinct component of the adaptive immune system that may strongly enhance pathways leading to increased sodium reabsorption, elevated vascular tone and end-organ damage. link3 Moreover, this pathway may lend itself towards specific targeting for treatment of kidney disease and hypertension.
Th17 cells are a distinct component of the adaptive immune system that may strongly enhance pathways leading to increased sodium reabsorption, elevated vascular tone and end-organ damage. Moreover, this pathway may lend itself towards specific targeting for treatment of kidney disease and hypertension.
