|
Current
Drug Targets
ISSN: 1389-4501
Current Drug Targets
Volume 10, Number 1, January 2009
Contents
Biomarkers, Critical Disease Pathways, Drug Targets, and Alternative
Medicine in Male Breast Cancer Pp. 1-8
D. Barh
[Abstract] [Full
Text Article] [PMID:
19149530 PubMed - indexed for MEDLINE]
NPY Signalling Pathway in Bone Homeostasis: Y1 Receptor
as a Potential Drug Target Pp. 9-19
D.M. Sousa, H. Herzog and M. Lamghari
[Abstract] [Full
Text Article] [PMID:
19149531 PubMed - indexed for MEDLINE]
Role of ARBs in the Blood Hypertension Therapy and
Prevention of Cardiovascular Events Pp.
20-25
S. Novo, M. Lunetta, S. Evola and
G. Novo
[Abstract] [Full
Text Article] [PMID:
19149532 PubMed - indexed for MEDLINE]
Monoclonal Antibodies in the Treatment of Systemic
Lupus Erythematosus Pp. 26-37
E. Robak and T. Robak
[Abstract] [Full
Text Article] [PMID:
19149533 PubMed - indexed for MEDLINE]
PDGF-D Signaling: A Novel Target in Cancer Therapy
Pp. 38-41
Z. Wang, D. Kong, Y. Li and F.H.
Sarkar
[Abstract] [Full
Text Article] [PMID:
19149534 PubMed - indexed for MEDLINE]
Interactions Between Advanced Glycation End-Products
(AGE) and their Receptors in the Development and Progression
of Diabetic Nephropathy – are these Receptors Valid
Therapeutic Targets Pp. 42-50
K.C. Sourris and J.M. Forbes
[Abstract] [Full
Text Article] [PMID:
19149535 PubMed - indexed for MEDLINE]
HIV: A Raft-Targeting Approach for Prevention and
Therapy Using Plant-Derived Compounds (Review) Pp.
51-59
S.P. Verma
[Abstract] [Full
Text Article] [PMID:
19149536 PubMed - indexed for MEDLINE]
Pathophysiology of Sepsis in the Elderly: Clinical
Impact and Therapeutic Considerations Pp. 60-70
A.R. De Gaudio, S. Rinaldi, C. Chelazzi and
T. Borracci
[Abstract] [Full
Text Article] [PMID:
19149537 PubMed - indexed for MEDLINE]
Emerging Drug Candidates of Dipeptidyl Peptidase IV
(DPP IV) Inhibitor Class for the Treatment of Type 2 Diabetes
Pp. 71-87
R. Gupta, S.S. Walunj, R.K. Tokala, K.V.L.
Parsa, S.K. Singh and M. Pal
[Abstract] [Full
Text Article] [PMID:
19149538 PubMed - indexed for MEDLINE]
Abstracts
[Back to top] [PMID:
19149530 PubMed - indexed for MEDLINE]
Biomarkers, Critical Disease Pathways, Drug Targets,
and Alternative Medicine in Male Breast Cancer
D. Barh
[Full Text
Article]
While breast cancer (BC) is commonest malignancy among female
with highest death rate, male breast cancer (MBC) is very
rare but exhibits highest cancer specific death in men and
the incidences of MBCs are rising rapidly. Due to rarity of
the disease, no detail information about biomarkers and drug
targets available and because of late diagnosis and rarely
understood the pathogenesis at molecular level, the treatment
of MBC is also not yet standardized. Though the MBC biology,
pathogenesis, and the clinical outcomes resembles with female
breast cancer (FBC), they are quite unique in many aspects.
Therefore, the uses of FBC specific drugs for treatment of
MBC are not only dissatisfactory but also increases mortality
rate due to severe side effects of these conventional drugs.
To avoid side effects of usual therapeutic drugs, new drugs
and their targets should be identified and evaluated, where
the dietary phytochemicals may be the alternative of currently
used drugs. Similarly, an integrated strategy and pharmacogenomics
approach is now essential to fight against this malady. This
article will deal with different aspects of MBC including
biomarkers, pathways, drug targets, and common dietary phytochemicals
as effective alternatives of conventional chemotherapeutic
drugs for targeted therapy without any side effect.
[Back to top] [PMID:
19149531 PubMed - indexed for MEDLINE]
NPY Signalling Pathway in Bone Homeostasis: Y1 Receptor as
a Potential Drug Target
D.M. Sousa, H. Herzog and M. Lamghari
[Full Text
Article]
Neuropeptide (NPY) is a neurotransmitter widely distributed
in central and peripheral nervous system that has been implicated
in several physiological processes through activation of five
different Y receptors: Y1, Y2, Y4, Y5, and y6. NPY system
has been extensively studied for the last decades due to its
implications in a wide variety of physiological processes.
For this purpose a diversity of sophisticated animal models
and receptors agonists and antagonists has been developed
to better understand its actions throughout body homeostasis.
Consequently, NPY and its receptors have recently emerged
as a potential regulator of bone homeostasis. This is supported
by the demonstration of an increase of bone mass in mice lacking
Y1 or Y2 receptor genes. Recent findings revealed Y1 receptor
as a potential drug target candidate for prevention and treatment
of bone loss. Indeed, it has been demonstrated that osteoblasts
express Y1 receptor while no other Y receptor was detected
in these cells, implicating Y1 receptor signalling in the
local control of bone turnover. In this review, we have summarized
the findings obtained from studies on NPY system in skeletogenesis
focusing on Y1 receptor.
[Back to top] [PMID:
19149532 PubMed - indexed for MEDLINE]
Role of ARBs in the Blood Hypertension Therapy and Prevention
of Cardiovascular Events
S. Novo, M. Lunetta, S. Evola and
G. Novo
[Full Text
Article]
Hypertension has a worldwide high incidence in the general
population and undoubtedly it is the most important risk factor
for cardiovascular morbidity and mortality, in industrialized
countries. In this Review we investigated the role of angiotensin
II receptor antagonists (ARBs) therapy in the treatment of
essential hypertension. We selected in the PubMed and in a
list of selected sources the most significant clinical trials
and meta-analysis carried out from 1999 to now, to assess,
in adult patients populations, ARBs’ efficacy, safety
and tolerability profile, in comparison with the efficacy
of the other common antihypertensive drugs, with particular
regard to both the prevention of disabling consequences of
hypertension (like cerebrovascular events, coronary events
and heart failure) and the influence of an adequate anti-hypertensive
therapy on comorbidities which strongly influence the outcome
of hypertensive patients (like atherosclerosis, kidney damage,
type II diabetes mellitus and arrhythmias).
We also evaluated, in a detailed pharmacological and pharmaco-economic
analysis, the basilar differences between ACE-inhibitors and
ARBs in the control of the RAA system, and we assessed the
possible benefits of their associated use, according to the
new evidences concerning the treatment of arterial hypertension.
[Back to top] [PMID:
19149533 PubMed - indexed for MEDLINE]
Monoclonal Antibodies in the Treatment of Systemic Lupus Erythematosus
E. Robak and T. Robak
[Full Text
Article]
Systemic lupus erythematosus (SLE) is an autoimmune disease
characterized by B cell hyperactivity and defective T-cell
function, with production of high titer autoantibodies. In
the recent years, conceptual advances and the introduction
of new therapies are yielding improvements in the management
of this disease. In recent years, clinical studies have been
undertaken with selected monoclonal antibodies (mAbs) in the
treatment of SLE. The important role of B cells in the pathogenesis
of autoimmune disorders has provided a strong rationale to
target B cells in SLE. Selective therapeutic depletion of
B-cells became possible with the availability of the anti-CD20
antibody rituximab and anti-CD22 antibody epratuzumab. Several
clinical studies confirm high activity of rituximab in SLE
patients especially with lupus nephritis and neuropsychiatric
involvement. Recently, several new mAbs reacting with CD20
have been developed. New mAbs directed against CD20 include
fully human mAb ofatumumab (HuMax CD20), IMMU-106 (hA20) which
has a >90%
humanized framework and GA-101, a novel third–generation
fully humanized and optimized mAb. These agents are highly
cytotoxic against B-cell lymphoid cells. Proinflammatory cytokines
such as tumor necrosis factor-α
(TNF-α
) and iterleukin-6 (IL-6) play an important role in
propagating the inflammatory process responsible for tissue
damage. Blocking of these cytokines by mAbs can be also a
successful therapy for patients with SLE. Finally, mAb eculizumab
that specifically inhibits terminal complement activation
has been recently developed and investigated in the phase
I single dose study in SLE. In this review, new mAbs, potentially
useful in SLE are presented.
[Back to top] [PMID:
19149534 PubMed - indexed for MEDLINE]
PDGF-D Signaling: A Novel Target in Cancer Therapy
Z. Wang, D. Kong, Y. Li and F.H.
Sarkar
[Full Text
Article]
Platelet-derived growth factor-D (PDGF-D) is a newly recognized
growth factor that can regulate many cellular processes, including
cell proliferation, transformation, invasion, and angiogenesis
by specifically binding to and activating its cognate receptor
PDGFR-β.
The functions of PDGF-D in human cancer progression are largely
unknown. We discuss here the role of PDGF-D signaling pathway
in cancer and how its deregulation is involved in tumor development
and progression to metastatic disease.
[Back to top] [PMID:
19149535 PubMed - indexed for MEDLINE]
Interactions Between Advanced Glycation End-Products (AGE)
and their Receptors in the Development and Progression of
Diabetic Nephropathy – are these Receptors Valid Therapeutic
Targets
K.C. Sourris and J.M. Forbes
[Full Text
Article]
Diabetes, is a metabolic disorder characterised by chronic
hyperglycaemia, hypertension, dyslipidaemia, microalbuminuria
and inflammation. Moreover, there are a number of complications
associated with this condition including retinopathy, neuropathy
and nephropathy. Diabetic nephropathy, is the major cause
of end-stage renal disease in Western societies affecting
a substantial proportion (25-40%) of patients with diabetes.
Advanced glycation end products (AGEs) have been identified
as important modulators of the development and progression
of diabetic nephropathy, through both receptor dependant and
independent interactions. AGEs elicit their receptor mediated
effects via their engagement with numerous receptors
and binding proteins which are broadly thought to be either
inflammatory (RAGE and AGE-R2) or clearance receptors (AGE-R1,
AGE-R3, CD36, Scr-II, FEEL-1 and FEEL-2). Modulation of AGE
receptor expression is an important potential therapeutic
approach worth consideration as a treatment for diabetic nephropathy
and likely applicable to other vascular complications.
[Back to top] [PMID:
19149536 PubMed - indexed for MEDLINE]
HIV: A Raft-Targeting Approach for Prevention and Therapy
Using Plant-Derived Compounds (Review)
S.P. Verma
[Full Text
Article]
It has been widely accepted that HIV-1 enters into and buds
out from microdomains known as lipid rafts/caveolae of plasma
membranes of infected cells. Since lipid rafts are recognized
sites for budding and entry of HIV-1, and since lipids in
rafts (including composition/dynamic structure) play a crucial
role in modulating the functions of raft-associated signaling
proteins and receptors, it has been consistently shown that
modulating the composition/structure of lipid rafts have influenced
the life cycle of HIV-1 inhibiting its replication. Since
anti-retroviral multi-drugs treatment has severe side effects,
one of the strategies could be to block the HIV-1 entry and
its replication using natural compounds that can target lipid
rafts. Dietary and plant-derived compounds have advantage
over synthetic drugs exhibiting minimum side effects and are
available in cost effective manner. Studies exploring the
effects of dietary and plant-derived compounds targeting lipid
rafts could be an evolving strategy to control the progression
of AIDS. This article is intended to review: (i) composition/structure
and conditions for the formation of lipid rafts in plasma
membranes, (ii) interaction of HIV-1 with lipid rafts and
(iii) to introduce a novel concept that dietary and plant-derived
compounds, which can target lipid rafts, could have potential
preventive/therapeutic values against the progression of AIDS.
More emphasis has been given to the roles of omega-3 fatty
acids and plant-derived various triterpenes, especially euphane-types
of triterpenes extracted from Neem tree, targeting lipid rafts
and its major component cholesterol.
[Back to top] [PMID:
19149537 PubMed - indexed for MEDLINE]
Pathophysiology of Sepsis in the Elderly: Clinical Impact
and Therapeutic Considerations
A.R. De Gaudio, S. Rinaldi, C. Chelazzi and
T. Borracci
[Full Text
Article]
The aging world population will increase the incidence and
mortality of severe sepsis. The aim of the present article
is to review the pathophysiological differences in sepsis
and its clinical impact on the elderly. The impact of immunosenescence
on innate and acquired immunity is associated with relative
immunologic depression that may favor the spreading of inflammation.
Elderly patients also have enhanced apoptotic pathways that
may contribute to the incidence of mortality due to sepsis.
The inflammation-coagulation network is activated by age,
explaining the success of some specific therapies. The initial
clinical picture of sepsis in the elderly may be ambiguous
but the specific pathopysiological changes of aging increase
the risk of a sudden deterioration to severe sepsis with the
development of a serious cardiovascular dysfunction. The reduced
stress tolerance characteristic of aged tissues explains the
high incidence of multi-organ failure in such patients. The
specific pathophysiological and clinical picture of sepsis
underlies the increased mortality in such patients and prompts
research on therapeutic strategies with particular benefits
to elderly septic patients.
[Back to top] [PMID:
19149538 PubMed - indexed for MEDLINE]
Emerging Drug Candidates of Dipeptidyl Peptidase IV (DPP IV)
Inhibitor Class for the Treatment of Type 2 Diabetes
R. Gupta, S.S. Walunj, R.K. Tokala, K.V.L.
Parsa, S.K. Singh and M. Pal
[Full Text
Article]
Dipeptidyl peptidase IV (DPP IV) is a key regulator of insulin-stimulating
hormones, glucagon-like peptide (GLP-1) and glucose-dependent
insulinotropic polypeptide (GIP), thus it is a promising target
for the treatment of Type 2 Diabetes mellitus (T2DM). Inhibition
of plasma DPP IV enzyme leads to enhanced endogenous GLP-1
and GIP activity, which ultimately results in the potentiation
of insulin secretion by pancreatic β-cells
and subsequent lowering of blood glucose levels, HbA[1c],
glucagon secretion and liver glucose production. Various classes
of structurally different DPP IV inhibitors are currently
being explored and few of them such as Sitagliptin and Vildagliptin
were successfully launched. These drugs have been approved
as a once-daily oral monotherapy or as a combination therapy
with current anti-diabetic agents like pioglitazone, glibenclamide,
metformin etc. for the treatment of T2DM. Several
other novel DPP IV inhibitors are in pipeline. The present
review summarizes the latest preclinical and clinical trial
data of different DPP IV inhibitors with a special emphasis
on their DPP8/9 fold selectivity and therapeutic advantages
over GLP-1 based approach.
|
