scholarly journals Selective Inhibition of Prostaglandin E2 Receptors EP2 and EP4 Induces Apoptosis of Human Endometriotic Cells through Suppression of ERK1/2, AKT, NFκB and β-CATENIN Pathways and Activation of Intrinsic Apoptotic Mechanisms

2009 ◽  
Vol 94 (7) ◽  
pp. 2673-2673
Author(s):  
Sakhila K. Banu ◽  
JeHoon Lee ◽  
V. O. Speights ◽  
Anna Starzinski-Powitz ◽  
Joe A. Arosh
Keyword(s):  
Prostaglandin E2 ◽  
Treatment Options ◽  
Uterine Cavity ◽  
Selective Inhibition ◽  
Current Treatment ◽  
Reproductive Age ◽  
Treatment Modalities ◽  
Migration And Invasion ◽  
Antiapoptotic Proteins ◽  
Apoptotic Pathways

Endometriosis is a benign chronic gynecological disease of reproductive age women characterized by the presence of functional endometrial tissues outside the uterine cavity. It is an estrogen-dependent disease. Current treatment modalities to inhibit biosynthesis and actions of estrogen compromise menstruation, pregnancy, reproductive health of women, and fail to prevent reoccurrence of disease. There is a critical need to identify new specific signaling modules for non-estrogen targeted therapies for endometriosis. In our previous study, we reported that selective inhibition of cyclooxygenase-2 prevented survival, migration and invasion of human endometriotic epithelial and stromal cells which was due to decreased PGE2 production. In this study, we determined mechanisms through which prostaglandin E2 (PGE2) promoted survival of human endometriotic cells. Results of the present study indicate that: (i) PGE2 promotes survival of human endometriotic cells through EP2 and EP4 receptors by activating ERK1/2, AKT, NFκB, and β-catenin signaling pathways; (ii) selective inhibition of EP2 and EP4 suppresses these cell survival pathways and augments interactions between proapoptotic proteins (Bax and Bad) and antiapoptotic proteins (Bcl-2/Bcl-XL), facilitates the release of cytochrome C and thus activates caspase-3/PARP-mediated intrinsic apoptotic pathways; and (iii) these PGE2 signaling components are more abundantly expressed in ectopic endometriosis tissues compared to eutopic endometrial tissues during the menstrual cycle in women. These novel findings may provide an important molecular framework for further evaluation of selective inhibition of EP2 and EP4 as potential therapy, including non-estrogen target, to expand the spectrum of currently available treatment options for endometriosis in women.

scholarly journals Targeting the Serine Pathway: A Promising Approach against Tuberculosis?

2019 ◽  
Vol 12 (2) ◽  
pp. 66 ◽  
Author(s):  
Marie Haufroid ◽  
Johan Wouters
Keyword(s):  
Treatment Options ◽  
Infectious Agent ◽  
Selective Inhibition ◽  
Current Treatment ◽  
New Drugs ◽  
Therapeutic Drug ◽  
Regulatory Domains ◽  
Starting Point ◽  
Drug Discovery Program ◽  
Serine Pathway

Tuberculosis is still the leading cause of death by a single infectious agent. Effective chemotherapy has been used and improved since the 1950s, but strains resistant to this therapy and most antibacterial drugs on the market are emerging. Only 10 new drugs are in clinical trials, and two of them have already demonstrated resistance. This paper gives an overview of current treatment options against tuberculosis and points out a promising approach of discovering new effective drugs. The serine production pathway is composed of three enzymes (SerA1, SerC and SerB2), which are considered essential for bacterial growth, and all of them are considered as a therapeutic drug target. Their crystal structure are described and essential regulatory domains pointed out. Sequence alignment with similar enzymes in other host would help to identify key residues to target in order to achieve selective inhibition. Currently, only inhibitors of SerB2 are described in the literature. However, inhibitors of human enzymes are discussed, and could be used as a good starting point for a drug discovery program. The aim of this paper is to give some guidance for the design of new hits for every enzyme in this pathway.

Current Treatment Recommendations for Leishmaniasis

1992 ◽  
Vol 26 (11) ◽  
pp. 1452-1455 ◽  
Author(s):  
Jeffrey T. Moss ◽  
James P. Wilson
Keyword(s):  
English Language ◽  
Clinical Presentation ◽  
Case Reports ◽  
Data Extraction ◽  
Treatment Options ◽  
Medical Personnel ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Management Options ◽  
Governmental Institutions

OBJECTIVE: To review the epidemiology, clinical presentation, risk factors for transmission, and pathogenesis of leishmaniasis, as well as current treatment options for this disease. DATA SOURCES/DATA SELECTION: We reviewed unclassified medical-threat briefing material, subject-matter reviews, and case reports from the world's infectious disease literature. We concentrated on literature pertaining to the pathogenesis and management of leishmaniasis indigenous to Southwest Asia. DATA EXTRACTION: Data from subject reviews published in the English language were evaluated. Case reports and clinical trials provided supplemental data on evolving theories and management options. DATA SYNTHESIS: The clinical presentation of leishmaniasis is highly variable. Management relies heavily upon the use of parenteral antimonial drugs. Although these agents are effective in most cases, toxicity and the emergence of resistance limit the usefulness of standard therapies. Alternative treatment modalities include heat, surgical curettage, ketoconazole, metronidazole, pentamidine, rifampin, amphotericin B, aminoglycosides, allopurinol, and immunotherapy. CONCLUSIONS: Although the number of reported cases of leishmaniasis in the US has generally been low, there is a possibility that more cases may be reported in the future because of the large number of military personnel returning to this country from endemic areas. Medical personnel, particularly those working in governmental institutions, should be familiar with the pathogenesis of this unusual infection as well as potential treatment options.

scholarly journals Recent trends in managing abnormal uterine bleeding

2021 ◽  
Vol 10 (4) ◽  
pp. 1742
Author(s):  
Shruthi Ananthula ◽  
Ushadevi Gopalan ◽  
Sivan Kumar Kumarapillai
Keyword(s):  
Surgical Treatment ◽  
Treatment Options ◽  
Abnormal Uterine Bleeding ◽  
Uterine Bleeding ◽  
Reproductive Age ◽  
Treatment Modalities ◽  
Major Surgery ◽  
High Morbidity ◽  
Management Options ◽  
Mesh Terms

Abnormal uterine bleeding is one of the most common problems among women of reproductive age. It is an important health care problem and may cause physiological as well as psycological stress impairing the quality of life. The aim of this review was to present various management options for women suffering from menorrhagia. An extensive electronic literature search was done using search engines like PubMed and Google scholar using the mesh terms/ key words like “abnormal uterine bleeding, menorrhagia, medical management, hysterectomy” to identify trials and reviews on management of abnormal uterine bleeding. Various pharmacological and surgical treatment options are available, among medical therapy Tranexamic acid being most effective. Second-generation endometrial ablation techniques are effective and safe alternatives compared to first-generation devices. Hysterectomy should be considered as a last resort in management of AUB as this major surgery is associated with high morbidity and mortality rates. Thus role of clinician is to counsel every women and provide full information regarding both medical as well as surgical treatment modalities available and facilitate them in making an appropriate choice.

scholarly journals Management of endometriosis-related infertility: Considerations and treatment options

2020 ◽  
Vol 47 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Dayong Lee ◽  
Seul Ki Kim ◽  
Jung Ryeol Lee ◽  
Byung Chul Jee
Keyword(s):  
Surgical Treatment ◽  
Ovarian Reserve ◽  
Intrauterine Insemination ◽  
Treatment Options ◽  
Oocyte Retrieval ◽  
Reproductive Age ◽  
Treatment Modalities ◽  
Inflammatory Reactions ◽  
Risk Of Cancer

Endometriosis is a common inflammatory disease in women of reproductive age and is one of the major causes of infertility. Endometriosis causes a sustained reduction of ovarian reserve through both physical mechanisms and inflammatory reactions, which result in the production of reactive oxygen species and tissue fibrosis. The severity of endometriosis is related to ovarian reserve. With regard to infertility treatment, medical therapy as a neoadjuvant or adjuvant to surgical therapy has no definite beneficial effect. Surgical treatment of endometriosis can lead to ovarian injury during the resection of endometriotic tissue, which leads to the deterioration of ovarian reserve. To overcome this disadvantage, a multistep technique has been proposed to minimize the reduction of ovarian reserve. When considering surgical treatment of endometriosis in patients experiencing infertility, it should be kept in mind that ovarian reserve can be reduced both due to endometriosis itself and by the process of removing endometriosis. In cases of mild- to moderate-stage endometriosis, intrauterine insemination with ovarian stimulation after surgical treatment may increase the likelihood of pregnancy. In cases of severe endometriosis, the characteristics of the patient should be considered in a multidisciplinary manner to determine the prioritization of treatment modalities, including surgical treatment and assisted reproduction methods such as <i>in vitro</i> fertilization. The risk of cancer, complications after pregnancy, and infection during oocyte retrieval should also be considered when making treatment decisions.

scholarly journals Anti-Migratory and Pro-Apoptotic Properties of Parvifloron D on Triple-Negative Breast Cancer Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 158 ◽  
Author(s):  
Nuno Saraiva ◽  
João G. Costa ◽  
Catarina Reis ◽  
Nuno Almeida ◽  
Patrícia Rijo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Treatment Options ◽  
Extraction Methods ◽  
Current Treatment ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Concentration Dependent Manner

Medicinal plants are important sources of new bioactive compounds with potential anticancer activity. Parvifloron D (ParvD) is an abietane diterpenoid, isolated in high amounts from Plectranthus ecklonii Benth. Previous reports have suggested potential therapeutic properties for ParvD. ParvD has shown pro-apoptotic and cytotoxic effects in leukemia and melanoma cell lines. However, to the best of our knowledge, there are no studies in triple-negative breast cancer (TNBC) models. TNBC is a breast cancer subtype characterized by an aggressive behavior with poor clinical outcomes and weak overall therapeutic responses to the current treatment options. This work aimed at evaluating the anticancer effect of ParvD in MDA-MB-231 cells, a model of human TNBC. To obtain sufficient amounts of purified ParvD the efficiency of several extraction methods was compared. ParvD (0.1–10 µM) decreased cell viability in a concentration-dependent manner. Treatment with ParvD (5 µM) significantly increased the percentage of apoptotic nuclei and exposure to 3 µM ParvD increased the sub-G1 population. Since altered cell adherence, migration, and invasion are determinant processes for the formation of metastases, the effect of ParvD on these cellular processes was tested. Although treatment with ParvD (1 µM) had no effect on cell-substrate attachment, ParvD (1 µM) significantly reduced cell chemotaxis and invasion. This is the first report describing the proapoptotic effect of ParvD in TNBC cells. Moreover, for the first time we have shown that ParvD reduces cell motility, unraveling potential anti-metastatic properties.

scholarly journals Niclosamide suppresses macrophage-induced inflammation in endometriosis†

2020 ◽  
Vol 102 (5) ◽  
pp. 1011-1019 ◽  
Author(s):  
Nikola Sekulovski ◽  
Allison E Whorton ◽  
Tomoki Tanaka ◽  
Yasushi Hirota ◽  
Mingxin Shi ◽  
...  
Keyword(s):  
Cell Viability ◽  
Stromal Cells ◽  
Human Peripheral Blood ◽  
Treatment Options ◽  
Current Treatment ◽  
Reproductive Age ◽  
Cytokines And Chemokines ◽  
Secreted Factors ◽  
Limited Efficacy ◽  
Gynecological Disease

Abstract Endometriosis is a common gynecological disease, which causes chronic pelvic pain and infertility in women of reproductive age. Due to limited efficacy of current treatment options, a critical need exists to develop new and effective treatments for endometriosis. Niclosamide is an efficacious and FDA-approved drug for the treatment of helminthosis in humans that has been used for decades. We have reported that niclosamide reduces growth and progression of endometriosis-like lesions via targeting STAT3 and NFĸB signaling in a mouse model of endometriosis. To examine the effects of niclosamide on macrophage-induced inflammation in endometriosis, a total of 29 stage III–IV endometrioma samples were used to isolate human endometriotic stromal cells (hESCs). M1 or M2 macrophages were isolated and differentiated from fresh human peripheral blood samples. Then, hESCs were cultured in conditioned media (CM) from macrophages with/without niclosamide. Niclosamide dose dependently reduced cell viability and the activity of STAT3 and NFκB signaling in hESCs. While macrophage CM stimulated cell viability in hESCs, niclosamide inhibited this stimulation. Macrophage CM stimulated the secretion of proinflammatory cytokines and chemokines from hESCs. Most of these secreted factors were inhibited by niclosamide. These results indicate that niclosamide is able to reduce macrophage-induced cell viability and cytokine/chemokine secretion in hESCs by inhibiting inflammatory mechanisms via STAT3 and/or NFκB signaling.

A Tutorial of the Current Treatment Modalities and Voice Management in Laryngeal Cancer

2019 ◽  
Vol 4 (5) ◽  
pp. 805-813
Author(s):  
Kathryn Regan ◽  
Ashwini Joshi
Keyword(s):  
Risk Factors ◽  
Laryngeal Cancer ◽  
Treatment Options ◽  
Current Treatment ◽  
Voice Therapy ◽  
Treatment Modalities ◽  
Cancer Risk Factors ◽  
Starting Point ◽  
Basic Understanding ◽  
The Voice

Purpose The purpose of this tutorial was to provide speech-language pathologists unfamiliar with the rehabilitation of laryngeal cancer a basic understanding of laryngeal cancer and the factors involved in the treatment of the voice. Conclusion This tutorial provides an overview of the types and subsites of laryngeal cancer, risk factors, stages and prognosis, and treatment options at these stages. The readers will gain the foundational knowledge necessary to work with this population and a starting point for further study. More research is needed regarding voice outcomes and the benefits of voice therapy in combination with the available laryngeal cancer treatment modalities so that we may better serve these patients.

The Utility of Anti-Inflammatory Agents in Cardiovascular Disease

2018 ◽  
Vol 23 (6) ◽  
pp. 483-493 ◽  
Author(s):  
Santhosh J. Kottoor ◽  
Rohit R. Arora
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
New England ◽  
Treatment Options ◽  
Current Treatment ◽  
Adverse Outcomes ◽  
Treatment Modalities ◽  
Clear Understanding ◽  
Acute Phase Reactants ◽  
Increased Risk

Approximately 40% of heart attack survivors remain at increased risk of recurrent cardiovascular events, despite the current treatment options showing that atherothrombosis is not exclusively a disorder of lipoprotein aggregation in the arterial wall. Clinical and experimental data suggest that inflammation plays an important role in atherothrombosis independent of the cholesterol level. Acute-phase reactants, such as C-reactive protein, increase in patients with coronary artery disease and are known to predict adverse outcomes in such patients. The recent CANTOS trial published in The New England Journal of Medicine provides evidence that interleukin-1β along with other cytokines play central roles in the inflammatory reaction that drives the interleukin-6 signaling pathway and have profound effects on cardiovascular outcomes. Several other ongoing studies are focused on multiple immune mediators involved in this process to support the inflammatory hypothesis of cardiovascular diseases. These new classes of drugs could represent the biggest breakthrough in cardiovascular medicine, which could have the greatest impact on cardiovascular mortality since the advent of statins. The drug canakinumab has shown promise in lowering atherosclerosis, and other drugs, such as colchicine and methotrexate, are gaining interest and are being investigated in multiple ongoing trials. A major concern is the affordability of these drugs, as most cardiovascular diseases are noted among people of lower socioeconomic statuses. The LoDoCo trial showed some benefits of colchicine, and whether this old drug can be marketed with a new label for cardiovascular disease remains in question. Therefore, a clear understanding of the different inflammatory pathways involved in atherosclerosis is needed to help develop more effective treatment modalities that will benefit humankind.

scholarly journals Assessment of the Antitumor Potential of Umbelliprenin, a Naturally Occurring Sesquiterpene Coumarin

Biomedicines ◽  
2020 ◽  
Vol 8 (5) ◽  
pp. 126 ◽  
Author(s):  
Iram Shahzadi ◽  
Zain Ali ◽  
Seung Ho Baek ◽  
Bushra Mirza ◽  
Kwang Seok Ahn
Keyword(s):  
Cell Lines ◽  
Treatment Options ◽  
Migration And Invasion ◽  
Artemisia Absinthium ◽  
Development Of Resistance ◽  
Naturally Occurring ◽  
Antitumor Potential ◽  
Antitumor Compounds ◽  
Causes Of Mortality ◽  
Apoptotic Pathways

Cancer is one of the greatest causes of mortality worldwide. The prevalence rates of different types of cancer is increasing around the world as well. Limitations in chemotherapy and radiotherapy, owing to multiple side effects including cytotoxic effects of antitumor compounds on normal cells as well as the development of resistance to these treatment options in patients, create a serious threat to successful treatment of cancer. The use of natural compounds to prevent and treat cancers has been found to be quite effective, with fewer adverse effects found in patients. Umbelliprenin (UMB) is a naturally occurring sesquiterpene compound found in Ferula species and recently in Artemisia absinthium. Many studies have highlighted the antitumor potential of UMB in different cancer cell lines as well as in animal models. UMB exerts its anticancer actions by regulating extrinsic and intrinsic apoptotic pathways; causing inhibition of the cell cycle at the G0/G1 phase; and attenuating migration and invasion by modulating the Wnt signaling, NF-ĸB, TGFβ, and Fox3 signaling pathways. UMB also affects the key hallmarks of tumor cells by attenuating tumor growth, angiogenesis, and metastasis. This review provides an insight into the role of UMB as a potential antitumor drug for different malignancies and highlights the signaling cascades affected by UMB treatment in diverse tumor cell lines and preclinical models.

Tolerability of toceranib phosphate (Palladia) when used in conjunction with other therapies in 35 cats with feline oral squamous cell carcinoma: 2009–2013

2016 ◽  
Vol 19 (6) ◽  
pp. 568-575 ◽  
Author(s):  
Gina A Olmsted ◽  
John Farrelly ◽  
Gerald S Post ◽  
Jaclyn Smith
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Treatment Options ◽  
Surgical Excision ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Low Grade ◽  
Treatment Delays ◽  
Gi Toxicity

Objectives Squamous cell carcinoma (SCC) is the most common oral tumor in cats and typically carries a poor prognosis with current treatment options. The objective of this study was to evaluate the toxicity of toceranib phosphate (Palladia; Pfizer) in cats with oral SCC in combination with other treatment modalities. Methods In this study, 35 cats were retrospectively evaluated to determine toxicity when treated with toceranib in combination with other treatment modalities. Cats received toceranib at a median dose of 2.75 mg/kg (range 1.9–4.17 mg/kg) 3 days a week. Cats also underwent additional therapies, including surgical excision, radiation therapy, chemotherapy and/or use of non-steroidal anti-inflammatory drugs. Results Toxicity was seen in six cats, with five cases of grade 1 or 2 gastrointestinal (GI) toxicity and one grade 4 metabolic toxicity. Toceranib was discontinued in one cat and two cats received dose reductions. None of the cats required treatment delays or hospitalization due to toxicity. Median toceranib treatment duration was 77 days (range 7–741 days). Conclusions and relevance This study revealed that toceranib was well tolerated by the majority of cats, with five cases of low-grade GI toxicity and one case of metabolic toxicity. Given the favorable toxicity profile, future studies further evaluating the safety and efficacy of toceranib for cats with oral SCC should be considered.

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