scholarly journals Genomic and Transcriptomic Underpinnings of Melanoma Genesis, Progression, and Metastasis

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 123
Author(s):  
Olga S. Cherepakhin ◽  
Zsolt B. Argenyi ◽  
Ata S. Moshiri
Keyword(s):  
Prognostic Markers ◽  
Treatment Resistance ◽  
Immune Checkpoint Blockade ◽  
World Health ◽  
Significant Advance ◽  
Molecular Pathways ◽  
Metastatic Progression ◽  
Acquired Drug Resistance ◽  
Melanoma Subtypes ◽  
Health Organization

Melanoma is a deadly skin cancer with rapidly increasing incidence worldwide. The discovery of the genetic drivers of melanomagenesis in the last decade has led the World Health Organization to reclassify melanoma subtypes by their molecular pathways rather than traditional clinical and histopathologic features. Despite this significant advance, the genomic and transcriptomic drivers of metastatic progression are less well characterized. This review describes the known molecular pathways of cutaneous and uveal melanoma progression, highlights recently identified pathways and mediators of metastasis, and touches on the influence of the tumor microenvironment on metastatic progression and treatment resistance. While targeted therapies and immune checkpoint blockade have significantly aided in the treatment of advanced disease, acquired drug resistance remains an unfortunately common problem, and there is still a great need to identify potential prognostic markers and novel therapeutic targets to aid in such cases.

scholarly journals Retinoic Acids in the Treatment of Most Lethal Solid Cancers

2020 ◽  
Vol 9 (2) ◽  
pp. 360 ◽  
Author(s):  
Lara Costantini ◽  
Romina Molinari ◽  
Barbara Farinon ◽  
Nicolò Merendino
Keyword(s):  
Retinoic Acid ◽  
World Health ◽  
Solid Cancer ◽  
Molecular Pathways ◽  
Acid Therapy ◽  
Retinoic Acids ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Cancer Types ◽  
Health Organization

Although the use of oral administration of pharmacological all-trans retinoic acid (ATRA) concentration in acute promyelocytic leukaemia (APL) patients was approved for over 20 years and used as standard therapy still to date, the same use in solid cancers is still controversial. In the present review the literature about the top five lethal solid cancers (lung, stomach, liver, breast, and colon cancer), as defined by The Global Cancer Observatory of World Health Organization, and retinoic acids (ATRA, 9-cis retinoic acid, and 13-cis retinoic acid, RA) was compared. The action of retinoic acids in inhibiting the cell proliferation was found in several cell pathways and compartments: from membrane and cytoplasmic signaling, to metabolic enzymes, to gene expression. However, in parallel in the most aggressive phenotypes several escape routes have evolved conferring retinoic acids-resistance. The comparison between different solid cancer types pointed out that for some cancer types several information are still lacking. Moreover, even though some pathways and escape routes are the same between the cancer types, sometimes they can differently respond to retinoic acid therapy, so that generalization cannot be made. Further studies on molecular pathways are needed to perform combinatorial trials that allow overcoming retinoic acids resistance.

scholarly journals Updated Review on Pathology of Endocervical Adenocarcinoma with Emphasis on Clinically Relevant Findings

2021 ◽  
Vol 50 (1) ◽  
pp. 126
Author(s):  
Adela Cimic ◽  
Xiaolin Liu-Jarin
Keyword(s):  
Treatment Options ◽  
World Health ◽  
Molecular Pathways ◽  
Stromal Invasion ◽  
Data Set ◽  
Endocervical Adenocarcinoma ◽  
Health Organization ◽  
Pattern Of Invasion ◽  
Invasion Patterns

<p>In the present review, we summarize and critically appraise recent advances in the pathology of endocervical adenocarcinoma. In recent years, the diagnosis of endocervical adenocarcinoma has shifted from morphologic criteria classification in 2014 World Health Organization (WHO) to etiology- based classification of International endocervical adenocarcinoma criteria and classification (IECC). IECC recommends classifying endocervical adenocarcinoma into Human Papillomavirus (HPV)- associated and non-HPV-associated. Ultimately, this approach may lead to different treatment options based on molecular pathways rather than purely based on the tumor’s grade and stage. Recently, the College of American Pathologists (CAP) has incorporated stromal invasion patterns as an optional data set in the synoptic report. The pattern of invasion classification is a valuable prognostic tool in excision specimens. Conclusion: IECC is a simple classification system that recognizes and classifies endocervical tumors based on pathogenesis and association to HPV. The pathologists should also be familiar with the pattern-based classification of endocervical adenocarcinoma.</p>

scholarly journals Mapping Dietary Sodium Reduction Policies and Initiatives in the Region of the Americas

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1714-1714
Author(s):  
Nadia Flexner ◽  
Mary L'Abbé ◽  
Barbara Legowski ◽  
Ruben Grajeda Toledo
Keyword(s):  
Sodium Intake ◽  
Cost Effective ◽  
Dietary Sodium ◽  
World Health ◽  
Significant Advance ◽  
Relative Reduction ◽  
Sodium Reduction ◽  
Pan American ◽  
Reduce Sodium Intake ◽  
Health Organization

Abstract Objectives To map existing country policies addressing population dietary sodium reduction in the Americas; to identify policy gaps in the region following what is outlined in the World Health Organization (WHO) “Best Buys” most cost-effective recommendations for the prevention and control of diet-related noncommunicable diseases (NCDs); and to discuss priorities for future work in the Region. Methods This study used mixed methods to analyze data from 34 countries. Data were collected through a structured review, of mostly national official sources, to identify current policies in place to reduce population sodium intake. Also, responses from the last Pan American Health Organization (PAHO) online Survey on National Initiatives for Sodium Reduction in the Americas were included. Finally, country profiles were prepared and sent to each country's Public Health Agency for validation and comments. Results Almost all countries (n = 23/34) had a recommendation to reduce salt intake included in policies related to NCDs. Only six countries had specific and comprehensive policies to reduce sodium intake, and only one of them was a National Law. Adoption of the WHO “Best Buys” in national policies included: reformulation of food products with voluntary (n = 9/34) and mandatory targets (n = 2/34); establishment of a supportive environment in public institutions (n = 14/34); and implementation of front-of-pack labelling (n = 5/34). Some countries have implemented regulations restricting marketing of foods high in sodium to children (n = 5/34); nutritional labelling that includes sodium content, either voluntary (n = 9/34) or mandatory (n = 10/34); and no country has yet implemented taxes on high sodium foods. Conclusions In recent years, there has been a significant advance in policies to reduce sodium intake in the Region of the Americas. However, this review identified that the level of implementation in practice is complex to assess and quite heterogeneous. Reducing sodium consumption is a cost-effective intervention that can save many lives, by preventing and reducing the burden of diet related NCD's. Therefore, a further call to action is needed for governments to accelerate efforts in order to meet the 2025 global target of a 30% relative reduction in mean population intake of sodium. Funding Sources Pan American Health Organization (PAHO/WHO).

Review of meningioma histopathology

2007 ◽  
Vol 23 (4) ◽  
pp. E3 ◽  
Author(s):  
Deborah L. Commins ◽  
Roscoe D. Atkinson ◽  
Margaret E. Burnett
Keyword(s):  
Healthcare Professionals ◽  
Prognostic Markers ◽  
Molecular Techniques ◽  
World Health ◽  
Ki 67 ◽  
Genetic Changes ◽  
Histological Characteristics ◽  
Health Organization ◽  
And Behavior ◽  
The Relationship

✓The histological appearance of a meningioma is an important predictor of tumor behavior and is frequently a factor in decisions concerning therapy. The relationship between histological features and prognosis is formalized in grading schemes such as those published by the World Health Organization (WHO), most recently in 2007. Although the latest edition is an improvement over previous grading schemes, the WHO scheme still fails to fully address a variety of important issues regarding the relationship between meningioma histological characteristics and behavior. In particular, routine histological examination fails to identify the subset of Grade I tumors that behave aggressively. Because of this, many additional prognostic markers that require immunohistochemical, cytogenetic, or molecular techniques to evaluate are under investigation. Only one, immunohistochemistry for the proliferation marker, Ki 67 (MIB-1), is used routinely and it has only limited utility. It is hoped that an understanding of the genetic changes that underlie tumor progression will improve healthcare professionals' ability to predict the behavior of meningiomas.

Clinical Management of Major Depressive Disorder

CNS Spectrums ◽  
2009 ◽  
Vol 14 (S10) ◽  
pp. 3-6 ◽  
Author(s):  
Laurence Mignon ◽  
Stephen M. Stahl
Keyword(s):  
Antidepressant Treatment ◽  
Treatment Resistance ◽  
World Health ◽  
Treatment Resistant ◽  
Major Depressive ◽  
Residual Symptoms ◽  
Number Of Patients ◽  
One Year ◽  
Health Organization ◽  
Treatment Alternatives

The World Health Organization estimates that depression is the fourth leading cause of disability worldwide with a lifetime prevalence of ∼15% to 20%. While the antidepressants currently on the market will be effective in most patients, a significant number of patients will experience residual symptoms, treatment-resistance, and relapse. The recent Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study has shed some light on the reality of antidepressant treatment. At first, only one-third of patients on citalopram monotherapy remitted. The other two-thirds who failed to remit saw their likelihood of remission decrease with each successive trial of another antidepressant monotherapy. Thus, after four successive monotherapies were tried over the course of one year, (ie, after four treatments each lasting 12 weeks), only two-thirds of patients achieved remission (Figure 1). Besides this poor prognosis, the patients who required more treatment cycles to get better also had a higher likelihood of relapsing. Once patients reach that point, they are considered treatment-resistant.

scholarly journals Aggressive and malignant pituitary tumours: state-of-the-art

2018 ◽  
Vol 25 (11) ◽  
pp. R559-R575 ◽  
Author(s):  
Dorota Dworakowska ◽  
Ashley B Grossman
Keyword(s):  
Who Classification ◽  
Prognostic Markers ◽  
State Of The Art ◽  
Therapeutic Strategies ◽  
Malignant Potential ◽  
World Health ◽  
Histological Classification ◽  
Pituitary Tumours ◽  
The World ◽  
Health Organization

Pituitary adenomas are unique in multiple ways. They are rarely malignant in terms of metastases; yet, they may be aggressive. Their cancerous potential is defined in a classic oncological way by the ability to metastasise, and therefore, it has been crucial to differentiate this process from aggressive behaviour, characterised as a particularly invasive and/or recurrent behaviour and resistance to common modalities of therapy. Recently, however, important changes have been introduced to the diagnosis and management of aggressive and malignant pituitary tumours including the 4th edition of the World Health Organization (WHO) classification for endocrine tumours (2017) as well as ESE Clinical Guidelines (2018), although an attempt to establish predictive and/or prognostic markers of clinical aggressiveness remains difficult. In this review, we focus on a group of pituitary tumours causing significant problems in clinical practice and requiring multidisciplinary input. We summarise updates in definitions of tumour invasiveness, aggressiveness and malignant transformation, as well as histological classification, and emphasise the new considerations regarding aggressive and malignant potential and its relationship to therapeutic strategies.

Obstacles to Claiming Permanence and Injury-Relatedness for “Posttraumatic” Headache

2009 ◽  
Vol 14 (3) ◽  
pp. 3-6
Author(s):  
Robert J. Barth
Keyword(s):  
Complete Recovery ◽  
World Health ◽  
Related Factors ◽  
Posttraumatic Headache ◽  
Sixth Edition ◽  
Causative Relationship ◽  
Short Period ◽  
The One ◽  
Health Organization ◽  
Subjective Reports

Abstract “Posttraumatic” headaches claims are controversial because they are subjective reports often provided in the complex of litigation, and the underlying pathogenesis is not defined. This article reviews principles and scientific considerations in the AMAGuides to the Evaluation of Permanent Impairment (AMA Guides) that should be noted by evaluators who examine such cases. Some examples in the AMA Guides, Sixth Edition, may seem to imply that mild head trauma can cause permanent impairment due to headache. The author examines scientific findings that present obstacles to claiming that concussion or mild traumatic brain injury is a cause of permanent headache. The World Health Organization, for example, found a favorable prognosis for posttraumatic headache, and complete recovery over a short period of time was the norm. Other studies have highlighted the lack of a dose-response correlation between trauma and prolonged headache complaints, both in terms of the frequency and the severity of trauma. On the one hand, scientific studies have failed to support the hypothesis of a causative relationship between trauma and permanent or prolonged headaches; on the other hand, non–trauma-related factors are strongly associated with complaints of prolonged headache.

Sixth Edition: the New Standard

2008 ◽  
Vol 13 (1) ◽  
pp. 1-12
Author(s):  
Christopher R. Brigham ◽  
Robert D. Rondinelli ◽  
Elizabeth Genovese ◽  
Craig Uejo ◽  
Marjorie Eskay-Auerbach
Keyword(s):  
Review Process ◽  
Peer Review Process ◽  
World Health ◽  
International Classification Of Functioning ◽  
Revision Process ◽  
Sixth Edition ◽  
Impairment Ratings ◽  
Health Organization ◽  
Impairment Severity

Abstract The AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Sixth Edition, was published in December 2007 and is the result of efforts to enhance the relevance of impairment ratings, improve internal consistency, promote precision, and simplify the rating process. The revision process was designed to address shortcomings and issues in previous editions and featured an open, well-defined, and tiered peer review process. The principles underlying the AMA Guides have not changed, but the sixth edition uses a modified conceptual framework based on the International Classification of Functioning, Disability, and Health (ICF), a comprehensive model of disablement developed by the World Health Organization. The ICF classifies domains that describe body functions and structures, activities, and participation; because an individual's functioning and disability occur in a context, the ICF includes a list of environmental factors to consider. The ICF classification uses five impairment classes that, in the sixth edition, were developed into diagnosis-based grids for each organ system. The grids use commonly accepted consensus-based criteria to classify most diagnoses into five classes of impairment severity (normal to very severe). A figure presents the structure of a typical diagnosis-based grid, which includes ranges of impairment ratings and greater clarity about choosing a discreet numerical value that reflects the impairment.

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