Article by Disease – Critical Roles of EGFR Family Members in Breast Cancer and Breast Cancer Stem Cells – Current Pharmaceutical Design

ARTICLE BY DISEASE ON “BREAST CANCER

Abstract:

The roles of the epidermal growth factor receptor (EGFR) signaling pathway in various cancers including breast, bladder, brain, colorectal, esophageal, gastric, head and neck, hepatocellular, lung, neuroblastoma, ovarian, pancreatic, prostate, renal and other cancers have been keenly investigated since the 1980’s. While the receptors and many downstream signaling molecules have been identified and characterized, there is still much to learn about this pathway and how its deregulation can lead to cancer and how it may be differentially regulated in various cell types. Multiple inhibitors to EGFR family members have been developed and many are in clinical use. Current research often focuses on their roles and other associated pathways in cancer stem cells (CSCs), identifying sites where therapeutic resistance may develop and the mechanisms by which microRNAs (miRs) and other RNAs regulate this pathway. This review will focus on recent advances in these fields with a specific focus on breast cancer and breast CSCs. Relatively novel areas of investigation, such as treatments for other diseases (e.g., diabetes, metabolism, and intestinal parasites), have provided new information about therapeutic resistance and CSCs.

Read more: http://www.eurekaselect.com/node/140187/article

Article by Disease – Inhibition of the VEGF/VEGFR Pathway Improves Survival in Advanced Kidney Cancer – Current Drug Targets

ARTICLE BY DISEASE ON “KIDNEY CANCER

Abstract:

Despite the improvement in progression-free survival and response rates, none of the five anti- VEGF/VEGFR agents used for treatment of metastatic renal cell carcinoma (mRCC) reported a significant increase in patients’ survival. This analysis aims to investigate their effect on overall survival (OS), performing a meta-analysis of the available studies. MEDLINE/PubMed and the Cochrane Library were searched for randomised phase III trials that compared anti-VEGF/VEGFR agents with controls as upfront treatment for mRCC. The search was restricted to phase III trials, and data extraction was conducted according to the PRISMA statement. Five randomised phase III trials were included for a total of 3,469 patients; among these, 1,801 received anti-VEGF/VEGFR agents and 1,668 were treated with a placebo or interferon-α. In the overall population, the reduction in the risk of death was 13% (HR: 0.87; 95%CI, 0.80 – 0.95; p=0.002). When patients were divided based on use of VEGFR agents or an anti-VEGF monoclonal antibody, the reduction in the risk of death was 13% and 12%, respectively. If only treatmentnaïve patients are considered, we can confirm a significant reduction of 12% (HR=0.88; 95%CI, 0.79 – 0.97; p=0.010) in the risk of death. Our analysis reports a positive improvement of OS with the inhibition of the VEGF/VEGFR pathway in mRCC.

Read more: http://www.eurekaselect.com/node/126194/article

Article by Disease – Treatment of Patients with Advanced Thyroid Cancer – Current Biomarkers

Article by Disease on “THYROID CANCER

Abstract:

Background: Thyroid cancers are frequent in the endocrine system especially differentiated thyroid carcinoma and 95% of all thyroid cancer cases are differentiated neoplasmas. They have a favorable prognosis; however although, a small group present recurrence in 10-15% of patients following the standard treatment, surgery and radioiodine. Medullary thyroid carcinoma which is a neoplasm of the parafollicular C cells of the thyroid is responsible for a high number of thyroid cancer related deaths.

Objective: Nowadays, the therapeutic options for advanced differentiated neoplasms, metastatic disease or anaplastic carcinoma are scarce. Recently, multitargeted kinase inhibitors are considered as new treatments for differentiated thyroid neoplasms and have been introduced in their management. The American Thyroid Association recommendations stated in the guideline of 2015 that tyrosine kinase inhibitors should be used in the treatment of patients with refractory differentiated thyroid carcinoma and in those cases that present progression.

Methods: In this review, the purpose is to analyze the thyroid cancer tumorigeniesis and the action of the different targeted agents over these pathways of activation and the results in those cases of thyroid cancer without other possible treatments.

Results: Multikinase inhibitors, the most widely studied, are able in thyroid cancer to interfere in the proliferation, invasion, and neoangiogenesis of neoplastic cells in thyroid cancer. Recently, the US Food and Drug Administration and the European Medicine Agency approved sorafenib and lenvatinib, which in Europe received an orphan designation by European Medicine Agency for follicular thyroid cancer. Some other controlled trials with tyrosine kinase inhibitors, as vandetanib and carbozantinib, have been finished and are now the two approved drugs in advanced medullary thyroid cancers.

Conclusion: Thus, drug targeting represents a challenging approach with promising potential to circumvent some problems associated with many toxic effects of antineoplastic drugs.

Read more: http://www.eurekaselect.com/node/143979/article

Article by Disease – “Understanding Unmet Needs in the Older Acute Myeloid Leukemia (AML) Patient”

Article by Disease on “Oncology

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Abstract:

Introduction: Acute Myeloid Leukemia (AML) is a rare form of cancer characterized by the infiltration of abnormal white blood cells that accumulate in the bone marrow at a rapid rate. AML has an overall incidence of 4 per 100,000 persons and accounted for over 10,000 deaths within the United States in 2015 [1]. Indeed, AML also represents a disease typically associated with the elderly, as the median age of diagnosis for AML is around 72 years old [2].

Advances: Over the past decades we have seen major advances in terms of understanding AML’s biology and prognosis, but some questions still remain unanswered, particularly for the elderly population. This gap in our understanding of AML translates into unmet needs for this population.

Conclusion: The current paper seeks to describe these specific needs and their associated barriers related to treatment, prognostic factors and relapse, health-related quality of life, disease costs, and palliative care support. Acquiring a better understanding of AML for elderly patients can lead to improved therapy options and quality-of-life for this population.

Article by Disease – “Early Palliative Care in Advanced Oncologic and Non-Oncologic Chronic Diseases: A Systematic Review of Literature”

Article by Disease on “Oncology

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Abstract:

Background: To assess the role of early palliative care in patients with advanced oncologic and non-oncologic chronic diseases.

Methods: A qualitative systematic review of literature was performed. All the randomized phase III trials comparing early, simultaneous palliative care and standard care in patients with advanced oncologic and non-oncologic diseases were considered eligible and included into the analysis. The outcomes were classified into 6 classes: quality of life, symptoms control, overall survival, quality of care, patients’ and caregivers’ satisfaction, and costs of the assistance.

Results: Twelve papers reporting the data of 9 trials were considered eligible and included into the analysis. Two nonrandomized trials were also included into the selection because of the methods used by the authors. The early, simultaneous approach was reported to improve quality of life in two out of 7 papers, symptoms control in 1 out of 5 papers, overall survival in 2 out of 3 papers, quality of care in 5 out of 8 papers, patients’ or caregivers’ satisfaction in 3 out of 4 papers; and to reduce the costs of assistance in 2 out of 3 papers.

Conclusion: Early palliative care improves the main outcomes of the assistance in patients with advanced oncologic and non-oncologic chronic diseases. The available data are probably enough to consider early palliative cares a novel standard of care in these groups of patients.

Read more: http://www.eurekaselect.com/node/135802/article

Article by Disease – “Efficacy and Safety Assessment of Hypertension Management with Coveram (Perindopril/Amlodipine Fixed Combination) in Patients with Previous Angiotensin Receptor Blocker (ARB) Treatment: Arabian Gulf STRONG Study”

Article by Disease on “Cardiology

Abstract:

Objective: We evaluated the safety and efficacy of hypertension management with Coveram (perindopril/amlodipine combination) in patients with uncontrolled blood pressure (BP). All patients were on previous angiotensin receptor blocker (ARB) treatment.

Methods: This was a 3 country, multi-centre (7 cities), open-label, observational study in the Arabian Gulf. Patients (18 years) were recruited between October 2012 and November 2013 and followed-up for 3 months after enrolment. Outcomes included changes in BP from baseline and BP goal attainment rates as per Joint National Committee- 8 (<140/90 mmHg for diabetics and those <60 years of age and <150/90 mmHg for those 60 years of age without diabetes). Medication tolerance was also assessed from both patient and physician perspectives.

Results: Hypertensive patients (n=760; mean age: 51±10 years; 67% were males) were included. A total of 178 patients (23%) were lost to follow-up. The perindopril/amlodipine combination was associated with an overall reduction in systolic BP (SBP) (31 mmHg; p<0.001) and diastolic BP (DBP) (18 mmHg; p<0.001) from baseline. An overall BP control rate was achieved in 87% (n=507) of the participants. There were significant incremental BP reductions with dose up-titration, especially SBP (p<0.001). Those with high SBP (>180 mmHg) at baseline were associated with a mean reduction of 59 mmHg (p<0.001). The perindopril/amlodipine combination had excellent tolerance levels over the study period from both patient and physician perspectives (at 99% and 98%, respectively; p<0.001).

Conclusions: The perindopril/amlodipine combination is an effective and well tolerated anti-hypertensive option in patients on previous ARB treatment.

Read more: http://www.eurekaselect.com/node/144156/article

Article by Disease – “Current Perspectives on Novel Drug Delivery Systems and Approaches for Management of Cervical Cancer: A Comprehensive Review”

Article by Disease on “Oncology

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Abstract:

Cervical cancer is uterine cervix carcinoma, the second deadly cancer and has a high incidence and mortality rate. In the developing world conventional treatment strategies such as surgical intervention and chemoradiotherapy are less widely available. Currently cancer research focuses on improving treatment of cervical cancer using various therapies such as gene therapy, recombinant protein therapy, photodynamic therapy, photothermal therapy and delivery of chemotherapeutic agents using nanoparticles, hydrogel and liposomal based delivery systems and also localized delivery systems which exist in a variety of forms such as intravaginal rings, intravaginal patches, intravaginal films, etc. in order to improve the drug delivery in a controlled manner to the diseased site thereby reducing systemic side effects. The present review encloses existing diverse delivery systems and approaches intended for treatment of cervical cancer.

Read more: http://www.eurekaselect.com/node/130992/article

Article by Disease – “Vitiligo in Children: A Birds Eye View”

Article by Disease on “Endocrine Diseases

Abstract:

Vitiligo in children is a distinct subset of vitiligo and differs from adult vitiligo. Characteristic features include family history of autoimmune or endocrine disease, higher incidence of segmental vitiligo, development of early or premature graying, increased incidence of autoantibodies and poor response to topical PUVA. The exact prevalence of vitiligo in children varies between 0.1-4% of the world population and seems to be higher in India than in other countries and it occurs more frequently in females. Around 12% to 35% of pediatric vitiligo patients have family members with the disease. The most common type of vitiligo in pediatric patients is vitiligo vulgaris, representing 78% of cases. The most commonly associated autoimmune disease is thyroiditis. Phototherapy and topical corticosteroids are the most commonly used treatments for adult vitiligo but are less useful in the pediatric population.

Read more: http://www.eurekaselect.com/node/138295/article

Article by Disease – “Nanowired Drug Delivery Across the Blood-Brain Barrier in Central Nervous System Injury and Repair”

Article by Disease on “Neuroscience

Abstract:

The blood-brain barrier (BBB) is a physiological regulator of transport of essential items from blood to brain for the maintenance of homeostasis of the central nervous system (CNS) within narrow limits. The BBB is also responsible for export of harmful or metabolic products from brain to blood to keep the CNS fluid microenvironment healthy. However, noxious insults to the brain caused by trauma, ischemia or environmental/chemical toxins alter the BBB function to small as well as large molecules e.g., proteins. When proteins enter the CNS fluid microenvironment, development of brain edema occurs due to altered osmotic balance between blood and brain. On the other hand, almost all neurodegenerative diseases and traumatic insults to the CNS and subsequent BBB dysfunction lead to edema formation and cell injury. To treat these brain disorders suitable drug therapy reaching their brain targets is needed. However, due to edema formation or only a focal disruption of the BBB e.g., around brain tumors, many drugs are unable to reach their CNS targets in sufficient quantity. This results in poor therapeutic outcome. Thus, new technology such as nanodelivery is needed for drugs to reach their CNS targets and be effective. In this review, use of nanowires as a possible novel tool to enhance drug delivery into the CNS in various disease models is discussed based on our investigations. These data show that nanowired delivery of drugs may have superior neuroprotective ability to treat several CNS diseases effectively indicating their role in future therapeutic strategies.

Read more: http://www.eurekaselect.com/node/144937/article

Article by Disease – “Distribution of Podoplanin in Synovial Tissues in Rheumatoid Arthritis Patients Using Biologic or Conventional Disease-Modifying Anti-Rheumatic Drugs”

ARTICLE BY DISEASE ON “RHEUMATOLOGY”

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Abstract:

Objective: Podoplanin (PDPN) mediates tumor cell migration and invasion, which phenomena might also play a role in severe rheumatoid arthritis (RA). Therefore, the precise cellular distribution of PDPN and it’s relationships with inflammation was studied in RA treated with biologic disease-modifying anti-rheumatic drugs (DMARD) or conventional DMARDs (cDMARD).

Methods: PDPN+ cells were immunostained by NZ-1 mAb, and scored (3+; >50%/ area, 2+; 20%- 50%, 1+; 5%-20%, 0: <5%) in synovial tissues from RA treated with biologic DMARDs (BIO, n=20) or cDMARD (n=20) for comparison with osteoarthritis (OA, n=5), followed by cell grading of inflammation and cell-typing.

Results: Inflammatory synovitis score was 1.4 in both BIO and cDMARD, compared to only 0.2 in OA. PDPN+ cells were found in the lining layer (BIO 1.6, cDMARD 1.3, OA 0.2) and lymphoid aggregates (BIO 0.6, cDMRD 0.7, OA 0.2), and correlated with RA-inflammation in BIO- and cDMARD-groups in both area (r=0.7/0.9, r=0.6/0.7, respectively p<0.05). PDPN was expressed in CD68+ type A macrophage-like and 5B5+ type B fibroblast-like cells in the lining layer, and in IL- 17+ cells in lymphoid aggregates in RA.

Conclusion: PDPN was markedly increased in the immunologically inflamed RA synovitis, which was surgically treated due to BIO- and cDMARD-resistant RA. PDPN may have potential of a new marker of residual arthritis in local joints for inflammation-associated severe RA.

Read more: http://www.eurekaselect.com/node/140808/article