Promises and Dangers of Combination Therapy

2017 ◽  
Vol 35 (1-2) ◽  
pp. 56-60 ◽  
Author(s):  
Wolfgang Kruis ◽  
Phuong G. Nguyen ◽  
Julia Morgenstern
Keyword(s):  
Combination Therapy ◽  
Infectious Complications ◽  
Treatment Modalities ◽  
Therapeutic Effects ◽  
Aminosalicylic Acid ◽  
Number Of Patients ◽  
Tnf Α ◽  
Serious Infections ◽  
Current Therapies ◽  
New Treatment

The efficiency of the existing methods of treating inflammatory bowel disease (IBD) is limited. There are 2 ways to address this problem - either create new treatment modalities or optimize current therapies. Optimisation may be accomplished by using combinations of established therapeutic strategies. With regard to topically acting compounds such as 5-aminosalicylic acid, combining oral and rectal preparations is a commonly used method. Another commonly used combination is anti-tumor necrosis factor (TNF)-α antibody modalities together with immunosuppressants (thiopurines, methotrexate). Several aspects favour those combinations such as increased effectivity, prevention of immunogenicity and perhaps less adverse events. Currently, discussion on directly additive therapeutic effects is in progress, which have been demonstrated in some clinical trials. As on date, the combination of infliximab with azathioprine is most likely the most effective treatment of Crohn's disease. On the other hand, a combination therapy with both compounds affecting the immune system has, of course, risks. For sure, the frequency with which serious infectious complications are arising is increasing. Furthermore, the number of patients experiencing malignancies such as hepato-splenic lymphoma or melanoma is strongly suspected to be on the rise. In summary, combinations of current treatments for IBD are widely established. Various strategies have been studied and significant improvements of therapeutic effects have been demonstrated. Unfortunately, some of those proven combinations increase therapeutic risks, for example, increase the frequency of serious infections and also of some malignancies. Therefore, great caution has to be exercised when applying combination therapies.

scholarly journals Potent pro-apoptotic combination therapy is highly effective in a broad range of cancers

2021 ◽  
Author(s):  
Antonella Montinaro ◽  
Itziar Areso Zubiaur ◽  
Julia Saggau ◽  
Anna-Laura Kretz ◽  
Rute M. M. Ferreira ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Cancer Cells ◽  
Standard Of Care ◽  
Therapy Resistance ◽  
Treatment Modalities ◽  
Cancer Resistance ◽  
Therapeutic Approaches ◽  
Highly Effective ◽  
Drastic Increase ◽  
New Treatment

AbstractPrimary or acquired therapy resistance is a major obstacle to the effective treatment of cancer. Resistance to apoptosis has long been thought to contribute to therapy resistance. We show here that recombinant TRAIL and CDK9 inhibition cooperate in killing cells derived from a broad range of cancers, importantly without inducing detectable adverse events. Remarkably, the combination of TRAIL with CDK9 inhibition was also highly effective on cancers resistant to both, standard-of-care chemotherapy and various targeted therapeutic approaches. Dynamic BH3 profiling revealed that, mechanistically, combining TRAIL with CDK9 inhibition induced a drastic increase in the mitochondrial priming of cancer cells. Intriguingly, this increase occurred irrespective of whether the cancer cells were sensitive or resistant to chemo- or targeted therapy. We conclude that this pro-apoptotic combination therapy has the potential to serve as a highly effective new treatment option for a variety of different cancers. Notably, this includes cancers that are resistant to currently available treatment modalities.

Treatment Innovations of Opiate Dependence Treatment

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
W. van den Brink
Keyword(s):  
Partial Agonist ◽  
Treatment Strategies ◽  
Oral Morphine ◽  
Treatment Compliance ◽  
Psychosocial Interventions ◽  
Opiate Dependence ◽  
Treatment Modalities ◽  
List Type ◽  
Number Of Patients ◽  
New Treatment

Opiate dependence is a serious psychiatric disorder with substantial suffering for the patient, his environment and society as a whole. Currently available treatments include abstinence oriented treatment with naltrexone and substitutian treatments with methadone and buprenorphine. However, treatment compliance with naltrexone is very low resulting in low effectiveness. In addition, existing substituation treatments only show moderate effectiveness resulting in a large number of patients showing continued drug use and serious psychological, somatic and functional impairment.New treatment strategies involve:a.the development of long acting opiate antagonists (naltrexone) and partial agonist (buprenorphine) to improve treatment compliance and treatment retention,b.new substitution options such as slow release oral morphine (SROM), oral diacetylmorphine (heroin) and inhalable and injectable diacetyl morphine (heroin assisted treatment: HAT).Recently, a new approach using neurosurgical and neuromodulatory techniques has been advocated to help treatment refractory opiate dependent patients. Finally, certain combinations of farmacotherapy and psychosocial interventions have shown promise for future improvements.This presentation reviews the evidence of existing treatments for opiate dependence and explores the new treatment options for patients not fully responsive to the existing treatment modalities.

scholarly journals Modulation of miRNAs in Pulmonary Hypertension

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Sudhiranjan Gupta ◽  
Li Li
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Diseases ◽  
Treatment Modalities ◽  
Small Noncoding Rnas ◽  
New Class ◽  
Cell Remodeling ◽  
Arterial Endothelial Cell ◽  
Current Therapies ◽  
Pulmonary Arterial ◽  
New Treatment

MicroRNAs (miRNAs) have emerged as a new class of posttranscriptional regulators of many cardiac and vascular diseases. They are a class of small, noncoding RNAs that contributes crucial roles typically through binding of the 3′-untranslated region of mRNA. A single miRNA may influence several signaling pathways associated with cardiac remodeling by targeting multiple genes. Pulmonary hypertension (PH) is a rare disorder characterized by progressive obliteration of pulmonary (micro) vasculature that results in elevated vascular resistance, leading to right ventricular hypertrophy (RVH) and RV failure. The pathology of PH involves vascular cell remodeling including pulmonary arterial endothelial cell (PAEC) dysfunction and pulmonary arterial smooth muscle cell (PASMC) proliferation. There is no cure for this disease. Thus, novel intervention pathways that govern PH induced RVH may result in new treatment modalities. Current therapies are limited to reverse the vascular remodeling. Recent studies have demonstrated the roles of various miRNAs in the pathogenesis of PH and pulmonary disorders. This review provides an overview of recent discoveries on the role of miRNAs in the pathogenesis of PH and discusses the potential for miRNAs as therapeutic targets and biomarkers of PH at clinical setting.

scholarly journals Chemotherapeutic treatment modalities in the management of lung carcinoma: an observational study in a tertiary care teaching hospital in north India

2018 ◽  
Vol 5 (4) ◽  
pp. 1047
Author(s):  
Salma Koser Bhatt ◽  
Rohini Gupta ◽  
Swati Sharma
Keyword(s):  
Lung Cancer ◽  
Combination Therapy ◽  
Small Cell Lung Cancer ◽  
Performance Status ◽  
Stage Iv ◽  
Small Cell ◽  
Treatment Modalities ◽  
Small Cell Lung ◽  
Number Of Patients ◽  
Chemotherapeutic Treatment

Background: Lung cancer is one of the leading causes of cancer related mortality accounting for 1.61million new cases per year with 1.38 million deaths annually worldwide. In NSCLC, concurrent Chemoradiotherapy is usually employed in stage IIIA and IIIB when performance status of the patients is reasonable and chemotherapy alone in stage IV, if the performance status of the patients is adequate. In SCLC, combination chemotherapy is given in limited stage disease as well as in extensive stage if the performance status of the patients is adequate. The objective is to study the chemotherapeutic treatment modalities in the treatment of lung carcinoma.Methods: The present cross-sectional prospective study was conducted in the Postgraduate Department of Medicine and Department of Pharmacology in collaboration with the Department of Oncology, Government Medical College, Jammu for a period of one year from November 2012 to October 2013. A total of 80 patients having histopathological documentation of lung cancer, registered under regional cancer centre (RCC) and referred from various departments of the institute and from other hospitals of the region were included in the study. The treatment for each patient was then decided on the basis of performance status, stage and clinical condition. The treatment modalities used were in the form of radiation therapy, surgery and chemotherapy. In the chemotherapy, the details regarding the type of chemotherapeutic regimen employed in particular type of lung cancer variant, their doses, number of cycles given and the duration for which these chemotherapeutic drugs were administered was noted down.Results: Out of 80 patients in the present study, 68 (85%) were males and 12 (15%) were females. Majority of the patients fall in the age group of 46 to 75 years (81.25%). Staging of the patients with non-small cell lung cancer showed that majority of the patients were in stage IV (31; 45.59%) of the disease. Eighteen (26.46%) patients were in stage III and 10 (14.71%) in stage II and 9 (13.24%) patients in stage I. In patients with small cell lung cancer, 4 (33.33%) patients were in limited stage and 8 (66.67%) patients. Various treatment modalities were employed with maximum number of patients receiving combined treatment (48.75%), followed by chemotherapy alone (22.25%) and radiotherapy alone (11.25%). Among patients who received combination therapy, various combinations of surgery, radiotherapy and chemotherapy were used but maximum number of patients i.e. 37 out of 39 (94.87%) used combination of chemotherapy and radiotherapy.Conclusions: Most of the patients presented in an advanced stage III and IV (75.9%) and the main treatment modality used in this study was combination therapy of chemotherapy and radiotherapy in (48.75%) followed by chemotherapy alone (22.25%). In the chemotherapy, cisplatin-based combination regimens were most commonly used regimens. Thus, more of such studies need to be done so as to make patients as well as the health professionals more aware of the risk factors and the effective treatment modalities associated with the disease.

scholarly journals AB0209 SERIOUS INFECTIOUS COMPLICATIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH BIOLOGICS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1131.1-1131
Author(s):  
E. Aronova ◽  
G. Gridneva ◽  
A. Kudryavtseva ◽  
G. Lukina
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Reactions ◽  
Certolizumab Pegol ◽  
Significant Proportion ◽  
Infectious Complications ◽  
Tuberculosis Infection ◽  
Study Group ◽  
The Third ◽  
Tnf Α ◽  
Serious Infections

Objectives:To study infectious complications of therapy with biologics, analyze the frequency of withdrawal of bDMARDs due to infectious complications.Methods:The ambispective analysis included data on 505 cases of prescribing biologics with different mechanism of action in 188 patients with rheumatoid arthritis (160 women, 28 men).Results:Patients in the study group received from 2 to 5 bDMARDs, mediana (25% -75%) 2 (2-3). Biologics were discontinued 326 times, of which due to the development of serious adverse reactions - 70 times, of which due to the development of infectious complications - 16 times (5% of all cases of discontinuations, 29% of all serious adverse reactions). During treatment with the first bDMARD, infectious complications that required discontinuation of the drug developed in 5.3% of cases (N = 10), with the second bDMARD - in 5.2% of cases (N = 4), no statistical differences were found between these groups. On the background of treatment with the third bDMARD, infectious complications led to the withdrawal of treatment in 14.3% of cases (N = 1), in the fourth - 0%, and in the fifth - 33.4% of cases (N = 1). There was no correlation between the number of sequentially prescribed biologics and the incidence of infectious complications. Most often, serious infections developed during treatment with drugs of the TNF-α inhibitor group (infliximab, etanercept, adalimumab, golimumab, certolizumab pegol) and tofacitinib. Out of 16 cases of infectious complications, 5 were associated with tuberculosis infection.Conclusion:Infectious complications make up a significant proportion (29%) of all serious adverse reactions leading to the discontinuations of biologics in patients with rheumatoid arthritis. The frequency of discontinuation of bDMARDs due to infectious complications was about 5% and did not change during treatment with both the first and second biologics. It is necessary to remain alert about tuberculosis infection and examine patients before prescribing and during treatment with bDMARDs.Disclosure of Interests:None declared

scholarly journals A review on current therapies and its problems in smoking cessation

2020 ◽  
Vol 11 (3) ◽  
pp. 3946-3956
Author(s):  
Aravind S R ◽  
Jawahar N ◽  
Senthil V
Keyword(s):  
Smoking Cessation ◽  
Treatment Options ◽  
Premature Death ◽  
Pharmaceutical Formulations ◽  
Therapeutic Effects ◽  
Pharmacological Interventions ◽  
First Line ◽  
Quitting Smoking ◽  
Current Therapies ◽  
New Treatment

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.

Management of thoracic aortic lesions - the future is endovascular

VASA ◽  
2012 ◽  
Vol 41 (3) ◽  
pp. 163-176 ◽  
Author(s):  
Weidenhagen ◽  
Bombien ◽  
Meimarakis ◽  
Geisler ◽  
A. Koeppel
Keyword(s):  
Thoracic Aorta ◽  
Clinical Decision Making ◽  
Treatment Options ◽  
Clinical Decision ◽  
Clinical Results ◽  
Treatment Modalities ◽  
Traumatic Rupture ◽  
Descending Thoracic Aorta ◽  
New Treatment ◽  
Aneurysm Dissection

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.

New Trends and Developments in Patients with Severe Aortic Stenosis – Towards Optimal Treatment?

2009 ◽  
Vol 5 (2) ◽  
pp. 81 ◽  
Author(s):  
Martijn WA van Geldorp ◽  
Johanna JM Takkenberg ◽  
Ad JJC Bogers ◽  
A Pieter Kappetein ◽  
◽  
...  
Keyword(s):  
Aortic Stenosis ◽  
Severe Aortic Stenosis ◽  
Surgical Techniques ◽  
Treatment Strategies ◽  
Tissue Doppler ◽  
Doppler Imaging ◽  
Treatment Modalities ◽  
Diagnostic Tools ◽  
Number Of Patients ◽  
Transcatheter Valve

Over the next few decades the number of patients diagnosed with aortic stenosis is expected to rise as the population ages and the use of several diagnostic tools expands. This will result in a growing need for both medical and surgical treatment and stimulate the development of new diagnostic and surgical techniques. This article briefly describes the prevalence, pathogenesis and clinical presentation of patients with aortic stenosis and focuses on developments in diagnostic tools, treatment strategies and treatment modalities: the use of echocardiography, tissue Doppler imaging, stress testing and biomarkers is discussed, as well as timing of surgery and the role microsimulation can play in prosthesis selection. Furthermore, newly developed transcatheter valve implantation techniques and their possible role in treating ‘inoperable’ or ‘elderly’ patients are discussed.

Role of Resveratrol in Modulating microRNAs in Human Diseases: From Cancer to Inflammatory Disorder

2020 ◽  
Vol 28 (2) ◽  
pp. 360-376 ◽  
Author(s):  
Atefeh Amiri ◽  
Maryam Mahjoubin-Tehran ◽  
Zatollah Asemi ◽  
Alimohammad Shafiee ◽  
Sarah Hajighadimi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Antioxidant Activities ◽  
Natural Compounds ◽  
Therapeutic Effects ◽  
Inflammatory Disorder ◽  
Inflammatory Disorders ◽  
Therapeutic Modalities ◽  
Anti Cancer ◽  
Current Therapies ◽  
Anti Inflammatory

: Cancer and inflammatory disorders are two important public health issues worldwide with significant socio.economic impacts. Despite several efforts, the current therapeutic platforms are associated with severe limitations. Therefore, developing new therapeutic strategies for the treatment of these diseases is a top priority. Besides current therapies, the utilization of natural compounds has emerged as a new horizon for the treatment of cancer and inflammatory disorders as well. Such natural compounds could be used either alone or in combination with the standard cancer therapeutic modalities such as chemotherapy, radiotherapy, and immunotherapy. Resveratrol is a polyphenolic compound that is found in grapes as well as other foods. It has been found that this medicinal agent displays a wide pharmacological spectrum, including anti-cancer, anti-inflammatory, anti-microbial, and antioxidant activities. Recently, clinical and pre-clinical studies have highlighted the anti-cancer and anti-inflammatory effects of resveratrol. Increasing evidence revealed that resveratrol exerts its therapeutic effects by targeting various cellular and molecular mechanisms. Among cellular and molecular targets that are modulated by resveratrol, microRNAs (miRNAs) have appeared as key targets. MiRNAs are short non-coding RNAs that act as epigenetic regulators. These molecules are involved in many processes that are involved in the initiation and progression of cancer and inflammatory disorders. Herein, we summarized various miRNAs that are directly/indirectly influenced by resveratrol in cancer and inflammatory disorders.

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