scholarly journals An Overview on Molecular Characterization of Thymic Tumors: Old and New Targets for Clinical Advances

2021 ◽  
Vol 14 (4) ◽  
pp. 316
Author(s):  
Valentina Tateo ◽  
Lisa Manuzzi ◽  
Claudia Parisi ◽  
Andrea De Giglio ◽  
Davide Campana ◽  
...  

Thymic tumors are a group of rare mediastinal malignancies that include three different histological subtypes with completely different clinical behavior: the thymic carcinomas, the thymomas, and the rarest thymic neuroendocrine tumors. Nowadays, few therapeutic options are available for relapsed and refractory thymic tumors after a first-line platinum-based chemotherapy. In the last years, the deepening of knowledge on thymus’ biological characterization has opened possibilities for new treatment options. Several clinical trials have been conducted, the majority with disappointing results mainly due to inaccurate patient selection, but recently some encouraging results have been presented. In this review, we summarize the molecular alterations observed in thymic tumors, underlying the great biological differences among the different histology, and the promising targeted therapies for the future.

2011 ◽  
Vol 26 (S2) ◽  
pp. 698-698
Author(s):  
L. Timmerman

IntroductionNonrespons in first -line drug treatment of patients suffering from depression in psychiatric outpatient populations is a severe problem.The non respons rate is up tot 30% and the non remission rate more than 50% in the first line of treatment with antidepressants in this population.ObjectiveTo devellop more rapid and efficious drug treatment strategies in depression.AimsDuring the last few years several strategies to improve outcome in depression have been under investigation. A few have proven to be valuable.MethodsMedline search 2005–2010 into treatment resistent depression, combination therapy, augmentation therapy, drug therapy.ResultThere is growing evidence for the value of the combination of antidepressants and of combining antidepressants with antipsychotics.Treatment options as pindolol addition to antidepressants, substance P or folic acid addition do not seem of clinical significance yet.The same is true for treatment methods who directly influence the glucocorticoid system such as glucocorticoid receptor antagonists.NMDA antagonists look promising but more research into this option is needed.ConclusionsThere are two outstanding and much promising relatively new treatment options with: Combinations of antidepressants and with combinations of an antidepressant with an antipsychotic.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1088-1088 ◽  
Author(s):  
Sylvia Adams ◽  
Sherene Loi ◽  
Deborah Toppmeyer ◽  
David W. Cescon ◽  
Michele De Laurentiis ◽  
...  

1088 Background: Standard first-line treatment for mTNBC is chemotherapy. However, outcomes are poor, and new treatment options are needed. Cohort B of KEYNOTE-086 (NCT02447003) assessed the safety and antitumor activity of pembrolizumab as first-line therapy for patients (pts) with PD-L1–positive mTNBC. Methods: Men and women with centrally confirmed mTNBC, no prior systemic anticancer therapy for metastatic disease, ECOG PS 0-1, and a tumor PD-L1 combined positive score (CPS) ≥1% received pembrolizumab 200 mg Q3W for 24 mo or until disease progression, intolerable toxicity, or investigator or pt decision. Tumor imaging was performed Q9W for 12 mo and Q12W thereafter. Clinically stable pts with PD could remain on pembrolizumab until PD was confirmed on subsequent assessment. Primary end point was safety. Secondary end points included ORR, DOR, and PFS (RECIST v1.1, central review). Planned enrollment was 80 pts. This analysis included all pts who had ≥18 wk of follow-up as of Nov 10, 2016. Results: 79 of the first 137 pts with PD-L1–evaluable tumors (58%) had PD-L1 CPS ≥1%. Of the first 52 pts enrolled, 100% were women, median age was 53 y, 40% had elevated LDH, 69% had visceral metastases, and 87% received prior (neo)adjuvant therapy. After a median follow-up of 7.0 mo (range 4.4-12.5), 15 (29%) pts remained on pembrolizumab. Treatment-related AEs occurred in 37 (71%) pts, most commonly fatigue (31%), nausea (15%), and diarrhea (13%). 4 (8%) pts experienced 5 grade 3-4 treatment-related AEs: back pain, fatigue, hyponatremia, hypotension, and migraine (n = 1 each). No pts died or discontinued pembrolizumab due to an AE. ORR was 23% (95% CI 14%-36%). Best overall response was CR in 4%, PR in 19%, SD in 17%, PD in 58%, and not assessed in 2%. Median time to response was 8.7 wk (range 8.1-17.7). Median DOR was 8.4 mo (range, 2.1+ to 8.4), with 8 (67%) responses ongoing at cutoff. Median PFS was 2.1 mo (95% CI, 2.0-3.9); estimated 6-mo PFS rate was 29%. Conclusions: Data from the first 52 pts enrolled in KEYNOTE-086 cohort B suggest that pembrolizumab monotherapy has a manageable safety profile and promising antitumor activity as first-line therapy for PD-L1–positive mTNBC. Clinical trial information: NCT02447003.


Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2338
Author(s):  
Christopher M. Wright ◽  
Anuradha A. Shastri ◽  
Emily Bongiorno ◽  
Ajay Palagani ◽  
Ulrich Rodeck ◽  
...  

For the past 100 years, oncologists have relentlessly pursued the destruction of tumor cells by surgical, chemotherapeutic or radiation oncological means. Consistent with this focus, treatment plans are typically based on key characteristics of the tumor itself such as disease site, histology and staging based on local, regional and systemic dissemination. Precision medicine is similarly built on the premise that detailed knowledge of molecular alterations of tumor cells themselves enables better and more effective tumor cell destruction. Recently, host factors within the tumor microenvironment including the vasculature and immune systems have been recognized as modifiers of disease progression and are being targeted for therapeutic gain. In this review, we argue that—to optimize the impact of old and new treatment options—we need to take account of an epidemic that occurs independently of—but has major impact on—the development and treatment of malignant diseases. This is the rapidly increasing number of patients with excess weight and its’ attendant metabolic consequences, commonly described as metabolic syndrome. It is well established that patients with altered metabolism manifesting as obesity, metabolic syndrome and chronic inflammation have an increased incidence of cancer. Here, we focus on evidence that these patients also respond differently to cancer therapy including radiation and provide a perspective how exercise, diet or pharmacological agents may be harnessed to improve therapeutic responses in this patient population.


2019 ◽  
Vol 25 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Marjorie C. Argollo ◽  
Mariangela Allocca ◽  
Federica Furfaro ◽  
Laurent Peyrin-Biroulet ◽  
Silvio Danese

Over the past decades, the advent of anti-TNF agents has dramatically changed the treatment algorithms for IBD. However, primarily and more importantly, secondary loss of response to anti-TNF agents, is often observed. Thus, new treatment options have been actively explored and some have already been incorporated in the current clinical practice. Among the class of anti-cytokine agents, the anti-IL12/IL23 monoclonal antibodies (mAbs) have been first presented, in clinical practice, by the anti-p40 mAb ustekinumab in Crohn’s disease (CD). More selective anti-IL23 agents (anti-p19) have shown efficacy and are being further developed, in contrast to agents inhibiting IL-17 downstream, which have failed in IBD clinical trials despite their clear efficacy in psoriasis.


2020 ◽  
Author(s):  
Sander Lambo ◽  
Susanne Grübner ◽  
Tobias Rausch ◽  
Sebastian Waszak ◽  
Christin Schmidt ◽  
...  

2021 ◽  
pp. e1-e4
Author(s):  
Janice Mok ◽  
M.-J. Milloy ◽  
Cameron Grant ◽  
Stephanie Lake ◽  
Kora DeBeck ◽  
...  

Objectives. To characterize the prevalence and reasons for the use of cannabis as a strategy to reduce the harms arising from other substances. Methods. We drew data about recent cannabis use and intentions from 3 prospective cohort studies of marginalized people who use drugs based in Vancouver, Canada, from June 2016 to May 2018. The primary outcome was “use of cannabis for harm reduction,” defined as using cannabis for substitution for licit or illicit substances such as heroin or other opioids, cocaine, methamphetamine, or alcohol; treating withdrawal; or coming down off other drugs. Results. Approximately 1 in 4 participants reported using cannabis for harm reduction at least once during the study period. The most frequent reasons included substituting for stimulants (50%) and substituting for illicit opioids (31%). Conclusions. The use of cannabis for harm reduction is a common strategy among people who use drugs in our setting. Further research into the factors associated with this strategy is needed. Better characterization of the risks and benefits of substitution strategies, including for opioids and stimulants, may prompt new treatment options for PWUD. (Am J Public Health. Published online ahead of print March 18, 2021: e1–e4. https://doi.org/10.2105/AJPH.2021.306168 )


2020 ◽  
Vol 11 (3) ◽  
pp. 3946-3956
Author(s):  
Aravind S R ◽  
Jawahar N ◽  
Senthil V

Smoking is likely the most preventable reason for ailments and premature death in the world. In 2010 it was estimated that approximately there are 120 million smokers in India. Around 70% of tobacco smokers are willing to stop, yet just 2-3% prevail with regards to doing so for all time every year. The first line pharmacotherapies normally used for smoking cessation include Nicotine substitution products (gum, transdermal patch, nasal spray, inhaler, and lozenge), varenicline and bupropion. Non-pharmacological therapies such as patient education, Counselling when used by physicians along with pharmacotherapies are found to increase the cessation rates by two folds within a single year. Blend pharmacotherapies are expanding the smoking restraint rates and furthermore lessens the withdrawal manifestations and are demonstrated to be as powerful as monotherapies. Physicians assume a significant job in the smoking discontinuance process. Significant rates of quitting smoking are accomplished when non-pharmacologic help is joined with pharmacological interventions. New treatment options such as nicotine vaccines are found to have better therapeutic effects and abstinence rates on smokers compared to other pharmacotherapies available. This review article deals with the available therapies (pharmacological and non-pharmacological) for smoking cessation along with the limitations and adverse effects associated with different pharmaceutical formulations.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS587-TPS587
Author(s):  
Nabil Adra ◽  
Ralph J. Hauke ◽  
Hristos Z. Kaimakliotis ◽  
Shuchi Gulati ◽  
Neda Hashemi ◽  
...  

TPS587 Background: Patients (pts) with cisplatin ineligible metastatic urothelial carcinoma (mUC) who progress after first-line PD1/PDL1 inhibition have limited treatment options. The concept of maintenance therapy with targeted agents and adding onto it at time of progression is a proven effective strategy. Preclinical data indicate that carboplatin+gemcitabine have immunomodulatory effect to potentially augment immune response. We hypothesize that in pts with cisplatin ineligible mUC, the use of atezolizumab+chemotherapy after progression on single-agent PD1/PDL1 inhibitor will result in clinical benefit. Methods: Multi-center, single arm, open label phase 2 trial of atezolizumab+carboplatin+gemcitabine in pts with cisplatin ineligible mUC. Eligible pts are adults with mUC (mixed histology allowed) who progressed after first line PD1/PDL1 inhibitor. Pts should be cisplatin ineligible based on consensus criteria. Neoadjuvant/adjuvant chemotherapy completed ≥12 months prior to enrollment is allowed. Treatment with atezolizumab will continue until disease progression or unacceptable toxicity while carboplatin+gemcitabine can be stopped after 4-6 cycles. Primary objective is progression-free survival per RECIST and secondary objectives are overall response rate, clinical benefit rate, and overall survival (OS). Exploratory endpoints include to compare OS of atezolizumab+carboplatin+gemcitabine in this trial compared to a virtual control arm of carboplatin+gemcitabine in mUC after progression on first-line PD1/PDL1 inhibitors. Other exploratory endpoints include to compare PD-L1 status at time of diagnosis and at time of enrollment (after progression on PD1/PDL1 inhibitor). Using an alternate hypothesis that atezolizumab+carboplatin+gemcitabine will have a median PFS of 9 months compared to historical control of 5 months with a platinum regimen in 2nd line setting, we plan to enroll 33 patients. This study is currently enrolling pts. A protocol amendment is under way that will allow pts with prior platinum-based chemotherapy to enroll on this trial. Clinical trial information: NCT03737123.


VASA ◽  
2012 ◽  
Vol 41 (3) ◽  
pp. 163-176 ◽  
Author(s):  
Weidenhagen ◽  
Bombien ◽  
Meimarakis ◽  
Geisler ◽  
A. Koeppel

Open surgical repair of lesions of the descending thoracic aorta, such as aneurysm, dissection and traumatic rupture, has been the “state-of-the-art” treatment for many decades. However, in specialized cardiovascular centers, thoracic endovascular aortic repair and hybrid aortic procedures have been implemented as novel treatment options. The current clinical results show that these procedures can be performed with low morbidity and mortality rates. However, due to a lack of randomized trials, the level of reliability of these new treatment modalities remains a matter of discussion. Clinical decision-making is generally based on the experience of the vascular center as well as on individual factors, such as life expectancy, comorbidity, aneurysm aetiology, aortic diameter and morphology. This article will review and discuss recent publications of open surgical, hybrid thoracic aortic (in case of aortic arch involvement) and endovascular repair in complex pathologies of the descending thoracic aorta.


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