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EXISTING AND NOVEL THERAPIES FOR PSORIASIS

EXISTING AND NOVEL THERAPIES FOR PSORIASIS

Psoriasis is persistent, familial, non-communicable skin disease, with no precise cure. A constellation of therapy is available which can control the disease of psoriasis among people. Along with existing therapies, the novel therapies such as anticytokines, small molecule inhibitor, NGF inhibitor, and corticosteroids [81] and other therapies became more prevalent in recent years for the treatment of psoriasis. Although various therapies and drugs are present in the market, still no drugs can permanently cure psoriasis and few of them elicit severe adverse effects. Biological drugs and novel immunological factors act as alternatives to conventional therapies which give a better understanding for functional and immunological pathways of treating psoriasis. These biological drugs show more efficacies with fewer side effects even in long-term usage. Despite their huge cost, it really offers a better alternate for improving the quality of life for patients. Novel drug delivery systems are also found to be effective for the treatment of psoriasis [82]. CONFLICTS OF INTEREST

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Malignant Pleural Mesothelioma: Treatment Options and Novel Therapies

Malignant Pleural Mesothelioma: Treatment Options and Novel Therapies

Malignant pleural mesothelioma is a rare primary tumor rising from the pleura and is associated with exposure to asbestos fibers. Mesothelioma is a locally aggressive disease that usually presents at an advanced stage and has a median overall survival of 1 year. Treatment options rarely result in cure of disease and range from trimodali- ty treatment, including chemotherapy, radiation, and surgery, to supportive care. In patients with limited local disease and good functional status, trimodality treatment with extra-pleural pneumonectomy, chemotherapy, and radiation is frequently employed. Best supportive care should be instituted for patients with metastatic dis- ease and poor functional status. Palliative therapy focuses on control of pleural effusions with drainage tech- niques and pain with radiation therapy. Novel therapies are showing promise, including photodynamic therapy, immunotherapy, and molecular targeted therapy.

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Novel therapies in genitourinary cancer: an update

Novel therapies in genitourinary cancer: an update

Vinflunine is a novel vinca alkaloid that inhibits tubulin and acts to inhibit assembly of microtubules. It has recently gained attention in the treatment of advanced bladder cancer after phase I studies confirmed anti-tumor activity. In a phase II study treating 51 patients who had failed first-line cisplatin containing regimens, vinflunine resulted in an ORR of 18%, a PFS of 3 months and a median OS of 6.6 months [89]. This study led to the initi- ation of a phase III trial of vinflunine plus best supportive care (BSC) versus BSC alone as second-line therapy after failure of a cisplatin-containing regimen in transitional cell carcinoma of the urothelium (TCCU) presented at ASCO 2008 [90]. Three hundred seventy patients were randomized in a 2:1 fashion to vinflunine plus BSC vs BSC, and the results showed that patients included in the vinflunine group achieved a median 2 month overall sur- vival advantage (6.9 months vs 4.6 months) but was not statistically significant (p = 0.29). However, the planned multivariate analysis adjusting for prognostic factors showed improved survival with vinflunine (HR = 0.77, p = 0.036). These results may support the role of vinflunine as a standard second line treatment for advanced TCCU. Traztuzumab

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Alternative pre approved and novel therapies for the treatment of anthrax

Alternative pre approved and novel therapies for the treatment of anthrax

Background: Bacillus anthracis, the causative agent of anthrax, is a spore forming and toxin producing rod-shaped bacterium that is classified as a category A bioterror agent. This pathogenic microbe can be transmitted to both animals and humans. Clinical presentation depends on the route of entry (direct contact, ingestion, injection or aerosolization) with symptoms ranging from isolated skin infections to more severe manifestations such as cardiac or pulmonary shock, meningitis, and death. To date, anthrax is treatable if antibiotics are administered promptly and continued for 60 days. However, if treatment is delayed or administered improperly, the patient ’ s chances of survival are decreased drastically. In addition, antibiotics are ineffective against the harmful anthrax toxins and spores. Therefore, alternative therapeutics are essential. In this review article, we explore and discuss advances that have been made in anthrax therapy with a primary focus on alternative pre-approved and novel antibiotics as well as anti-toxin therapies.

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Characterisation of novel therapies to mitigate inflammation in retinal degenerations

Characterisation of novel therapies to mitigate inflammation in retinal degenerations

The beneficial effects of light exposure in the red to near infrared (NIR) spectrum have been documented in a number of diseases/maladies over the past few decades [227, 321-325]. Recently, NIR therapies have been useful in treating a number of cardiovascular [326], musculoskeletal [218, 219] and central nervous system (CNS) conditions [220, 221], with studies in animal models showing positive effects in inflammation, neurodegeneration and soft tissue damage [225, 229, 237, 239, 327, 328]. It has been reported that red to NIR light is protective in retinal pathologies with several studies using animal models showing its ability to attenuate light induced retinal degeneration [96, 118, 234, 235], retinal lesion development in diabetic retinopathy [232], methanol toxicity [231] and degeneration during ageing [239]. Investigations using the light induced model of retinal degeneration have shown that 670nm light treatment significantly reduces photoreceptor damage, preserves retinal function, suppresses expression of inflammatory markers and ameliorates oxidative stress in light damaged retinas [118, 233, 234, 236]. However, none of these have looked at the early effects of 670nm light treatment on the retinal transcriptome, which might be key in understanding the molecular mechanisms underlying its anti-inflammatory properties. Although, the exact underlying mechanism of this protective effect is unknown, current evidence suggests the involvement of cytochrome c oxidase (the primary photo-acceptor of 670nm light wavelength) and its downstream effects on mitochondrial membrane potential, cellular ATP production, cell signaling, and transcription [224, 239, 329-333].

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Gout  Novel therapies for treatment of gout and hyperuricemia

Gout Novel therapies for treatment of gout and hyperuricemia

All uricase therapies have the potential to induce oxidative stress, since degradation of the high micromolar plasma concentrations of urate in gout patients by uricases has the capacity to generate substantial amounts of hydrogen peroxide [1,59,60]. Whether increased nitric oxide bioavaila- bility [61,62] and the profound, rapid decrement in the serum antioxidant activity normally exerted by serum urate [1] contri- bute to oxidative challenge by uricase therapy is not yet clear. Circulating oxidative stress triggered by hydrogen peroxide generation alone is subject to marked dampening by the normal abundance of catalase on erythrocytes [51,59,60] and potentially by other plasma antioxidant defenses. Yet methemoglobinemia and/or hemolysis have been unequivocal indicators of uricase-induced oxidative stress [1,59,60]. Importantly, with Rasburicase™ therapy, methemoglobinemia and hemolysis (fortunately <1% in incidence) were linked to glucose-6-phosphate dehydrogenase deficiency in some but not all affected subjects [59,60]; subsequently, this deficiency has become an exclusion criterion for any uricase therapy. It has been suggested that assessment for erythrocyte catalase activity should be done prior to uricase therapy [59,60]. In my opinion, monitoring for treatment-induced subclinical met- hemoglobinemia also could ultimately be informative.

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Molecular regulation of HDL metabolism and function: implications for novel therapies

Molecular regulation of HDL metabolism and function: implications for novel therapies

HDL metabolism represents a major target for the development of therapies intended to reduce the risk of atherosclerotic cardiovascular disease. HDL metabolism is complex and involves dissociation of HDL apolipoprotein and HDL cholesterol metabolism. Advances in our understanding of the molecular regulation of HDL metabolism, macrophage cholesterol efflux, and HDL function will lead to a variety of novel therapeutics.

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Schizophrenia: Neural Mechanisms for Novel Therapies

Schizophrenia: Neural Mechanisms for Novel Therapies

that is a partial agonist at the glycine site, is effective also. Subtle interactions between GABA- and glutamate-contain- ing neurons may clarify mechanisms of PCP psychosis and facili- tate antipsychotic drug development (Figure 1). GABA neurons, which contain NMDA receptors, synapse upon glutamate neurons, which possess on their nerve terminals Group II metabotropic glutamate receptors (mGluR2/3). When glutamate stimulates these mGluR sites, release of glutamate is inhibited. Firing of GABA neurons inhibits firing of glutamate neurons, consistent with GABA’s actions as an inhibitory transmitter. By blocking NMDA receptors on GABA neurons, PCP diminishes GABA release. The lessened inhibition of glutamate neurons leads to augmented glutamate release, which is well established in the prefrontal cerebral cortex following PCP treatment (16). Thus, PCP can stimulate glutamate release even though it blocks a sub- type of glutamate receptor. The GABA synthesizing enzyme, glutamate decarboxylase, is reportedly diminished in a schizo- phrenic’s prefrontal cortex (17,18). This lack presumably triggers a decrease in GABA release and an augmented glutamate release, similar to treatment of PCP. In the prefrontal cerebral cortex, mGluR2/3 agonist drugs inhibit the increased glutamate release provoked by PCP (19). They also block behavioral abnormalities induced by PCP in animals. Accordingly, mGluR2/3 agonists offer promise as a novel approach to schizophrenic therapy.

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Novel therapies for treating atrial fibrillation

Novel therapies for treating atrial fibrillation

While dronedarone is similar to amiodarone in its mode of action, there are other novel anti-arrhythmic agents that are amiodarone-derivatives, such as celivarone. Celi- varone, like dronedarone, is noniodinated and has multi- ple channel-blocking properties. Preliminary studies in canine models showed that celivarone has the ability to terminate vagal-induced AF [99]. A phase II dose-rang- ing study, MAIA (Maintenance of sinus rhythm in pa- tients with recent atrial fibrillation or flutter) trial took a closer look at the safety and efficacy of celivarone by enlisting 673 patients and randomizing them to 4 varying doses or placebo [100]. At 90 days, the lowest dose celi- varone had an incidence of 52.1% of AF recurrence, compared to placebo incidence of 67.1%. Another inves- tigation, a double-blind placebo trial, CORYFREE (Con- trolled Dose-Ranging study of the efficacy and safety of SSR149744c 300 or 600 mg for the conversion of atrial fibrillation/flutter), involved 150 patients with either AF or atrial flutter. They were randomly assigned to 300 mg celivarone, 600 mg celivarone, or placebo for a treatment period of 2 days and the study focused on the rate of conversion to sinus rhythm. Results of this trial have not yet been reported. Other amiodarone derivatives are also under development as attempts are being made to create modifications to amiodarone that could potentially allow for rapid hydrolization and thus, shorter half-life and more rapid action. One such derivative is ATI-2042, which was investigated by Arya et al. in a pilot study in

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Medical treatment of Cushing&#39;s disease: Overview and recent findings

Medical treatment of Cushing&#39;s disease: Overview and recent findings

Abstract: Cushing’s disease, due to pituitary adrenocorticotropic hormone (ACTH) hypersecretion, is the most common etiology of spontaneous excess cortisol production. The majority of pituitary tumors causing Cushing’s disease measure 1 cm and the excess morbidity associated with these tumors is mostly due to the effects of elevated, nonsuppressible, ACTH levels leading to adrenal steroid hypersecretion. Elevated circulating cortisol levels lead to abnormal fat deposition, hypertension, diabetes, coronary artery disease, osteoporosis, muscle weakness and psychological disturbances. At experienced centers, initial surgical remission rate via transnasal, transphenoidal resection approaches 80% for tumors less than 1 cm, but may be as low as 30% for larger lesions and long-term recurrence in all groups approaches 25%. Residual disease may be managed with more radical surgery, pituitary-directed radiation, bilateral adrenalectomy, or medical therapy. This paper addresses current and novel therapies in various stages of development for Cushing’s disease.

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Novel oncolytic viral therapies in patients with thoracic malignancies

Novel oncolytic viral therapies in patients with thoracic malignancies

Oncolytic virotherapies are under active investigation in lung cancer and mesothelioma both in vitro and in vivo. Replication-competent viruses show great promise for treatment in thoracic cancers in the coming decade. Criti- cal hurdles nonetheless remain, including eluding the host immune system. The final use of these novel therapies will become clearer in the very near future with the completion of ongoing clinical studies.

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Considerations for payers in managing hormone receptor-positive advanced breast cancer

Considerations for payers in managing hormone receptor-positive advanced breast cancer

Despite many advances in screening and treatment, BC is one of the most common causes of cancer-related death, and advanced disease has a particularly poor prognosis. The direct cost of $16.5 billion associated with BC care in 2010 was the highest among all cancers, and this is projected to increase every year. With recent approval of new treatments and combinations to overcome endo- crine resistance, the therapeutic tools available to combat HR + ABC in patients are expanding. Although guideline recommendations regarding endocrine and novel therapies exist, the optimal treatment sequence is unknown. Hence, it is critical that the providers, payers, and other stakeholders in the health care system have a clear understanding of the differences among therapeutic agents in terms of safety,

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Novel regulatory therapies for prevention of Graft-versus-host disease

Novel regulatory therapies for prevention of Graft-versus-host disease

Graft-versus-host disease is one of the major transplant-related complications in allogeneic hematopoietic stem cell transplantation. Continued efforts have been made to prevent the occurrence of severe graft-versus-host disease by eliminating or suppressing donor-derived effector T cells. Conventional immunosuppression does not adequately prevent graft-versus-host disease, especially in mismatched transplants. Unfortunately, elimination of donor-derived T cells impairs stem cell engraftment, and delays immunologic reconstitution, rendering the recipient susceptible to post-transplant infections and disease relapse, with potentially lethal consequences. In this review, we discuss the role of dynamic immune regulation in controlling graft- versus-host disease, and how cell-based therapies are being developed using regulatory T cells and other tolerogenic cells for the prevention and treatment of graft-versus-host disease. In addition, advances in the design of cytoreductive conditioning regimens to selectively target graft-versus-host disease-inducing donor-derived T cells that have improved the safety of allogeneic stem cell transplantation are reviewed. Finally, we discuss advances in our understanding of the tolerogenic facilitating cell population, a

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<p>Sorcin: a novel potential target in therapies of cancers</p>

<p>Sorcin: a novel potential target in therapies of cancers</p>

The fi ndings shed light on the relationship between sorcin and CSCs. 47 However, the issue of whether sorcin can directly or indirectly in fl uence the event remains resolved. Also, sorcin can regulate VEGF, which is a kind of cytokine that plays a huge role in the tumor vasculature. It may lead to downregulation of VEGF if the level of sorcin decreases, including a large amount of changes such as cell proliferation, migration, invasion, and survival in many solid cancers. 48,49 Therefore, the deple- tion of sorcin suppresses the growth and metastasis of breast cancer cells, impedes angiogenesis in vivo, reduces the CSC population, and sensitizes cancer cells to che- motherapeutics. All these serve as a novel way to develop the therapies in breast cancer.

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Current and novel drug therapies for idiopathic pulmonary fibrosis

Current and novel drug therapies for idiopathic pulmonary fibrosis

The rising incidence and poor prognosis of IPF has resulted in the discovery of new therapies becoming an increasing priority for the academic community and the pharmaceutical industry. The last decade has seen a huge rise in clinical trial activity in IPF. While these trials have produced a number of negative results, they have also led to the recent licensing in Europe and Asia of the first drug developed specifically for the treatment of IPF, pirfenidone (InterMune Inc, Brisbane, CA). This review will discuss the data underpinning the use of pirfenidone as a treatment for IPF and will assess the evidence supporting the growing number of compounds, all in varying phases of development, which may in the future revolutionize the treatment of this devastating condition.

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ZINC OXIDE NANOPARTICLES AS POTENTIAL NOVEL ANTICANCER THERAPIES

ZINC OXIDE NANOPARTICLES AS POTENTIAL NOVEL ANTICANCER THERAPIES

Subsequent exposure to shortwave radiofrequency energy, which is highly penetrant and non-ionizing, heats the NP sufficiently to kill the tumor cells without harm to surrounding tissues (Cherukuri and Curley, 2010). Quantum dots are being investigated for their potential to kill cancer cells via photodestruction. Because quantum dots exhibit quantum confinement, stimulation with light energy can cause liberation of valence band electrons into the conduction band, which, in oxygenated environments, leads to generation of reactive oxygen species. Organic photodynamic therapies (PDT) exist, but suffer from a need to be excited by light in either the visible or UV spectrum, which cannot readily penetrate into tissues. It is believed that the use of nanomaterial quantum dots that show absorption in the near-infrared region will help to overcome tissue penetrance limitation (Samia et al., 2003). Conjugation with targeting molecules is also expected to improve the selectivity of photodestruction to tumor sites (Bakalova et al., 2004).

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Proteomic and transcriptomic analysis of heart failure due to volume overload in a rat aorto-caval fistula model provides support for new potential therapeutic targets - monoamine oxidase A and transglutaminase 2

Proteomic and transcriptomic analysis of heart failure due to volume overload in a rat aorto-caval fistula model provides support for new potential therapeutic targets - monoamine oxidase A and transglutaminase 2

healing as well as during apoptosis [34,35]. Due to its G- protein properties, TGM2 participates in intracellular signaling via a1-adrenergic and thromboxane receptors [34], and has been recently shown to promote apoptosis of rat cardiomyocytes under oxidative stress [36]. Two independent groups have demonstrated that heart-speci- fic TGM2 over-expression results in detrimental hemo- dynamic changes, structural alterations, cardiomyocyte apoptosis, cardiac hypertrophy and fibrosis [37,38]. Our observation of up-regulated TGM2 in ACF hearts thus adds further evidence for the adverse effect of TGM2 up-regulation in cardiac hypertrophy and HF. Effective low molecular weight inhibitors such as cystamine and monodansylcadaverine are already known and their use inhibits TGM2-induced apoptosis in aortic smooth mus- cle cells [39] and partially repressed hypoxia-induced cardiac hypertrophy in rats [40]. This highlights the potential of TGM2 as a novel therapeutic target.

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Conventional and novel stem cell based therapies for androgenic alopecia

Conventional and novel stem cell based therapies for androgenic alopecia

Abstract: The prevalence of androgenic alopecia (AGA) increases with age and it affects both men and women. Patients diagnosed with AGA may experience decreased quality of life, depression, and feel self-conscious. There are a variety of therapeutic options ranging from prescription drugs to non-prescription medications. Currently, AGA involves an annual global market revenue of US$4 billion and a growth rate of 1.8%, indicating a growing consumer market. Although natural and synthetic ingredients can promote hair growth and, therefore, be useful to treat AGA, some of them have important adverse effects and unknown mechanisms of action that limit their use and benefits. Biologic factors that include signaling from stem cells, dermal papilla cells, and platelet-rich plasma are some of the current therapeutic agents being studied for hair restoration with milder side effects. However, most of the mechanisms exerted by these factors in hair restoration are still being researched. In this review, we analyze the therapeutic agents that have been used for AGA and emphasize the potential of new therapies based on advances in stem cell technologies and regenerative medicine.

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Platelets and platelet adhesion molecules: novel mechanisms of thrombosis and anti-thrombotic therapies

Platelets and platelet adhesion molecules: novel mechanisms of thrombosis and anti-thrombotic therapies

A direct anti-GPIbα drug, Anfibatide, is purified from the snake venom of Agkistrodon acutus [83, 84]. Notably, Anfibatide inhibits both VWF and α-thrombin binding to GPIbα, representing a more potent anti-thrombotic effect [85]. In experimental models, Anfibatide inhibited platelet adhesion, aggregation and thrombus formation, without increasing bleeding time [83]. The phase II human clinical trials have also shown the promise of Anfibatide being utilized as a novel antiplatelet agent in cardiovascular diseases without significantly affecting hemostasis in patients with non-ST segment elevation myocardial infarction (unpublished data) [85]. Addition- ally, anti-GPIbα antibody displayed a strong protective effect in the mouse stroke models without inducing sig- nificant intracranial bleeding [86–88]. Anfibatide has also been shown as a candidate to treat ischemic stroke in experimental models [89] (the same may hold true for anti-VWF therapy) and deserves further investigation. There are some other preclinical agents targeting GPIbα that are under investigation, such as h6B4-Fab [90], GPG-290 [91], and anti-GPIbα NIT family monoclonal antibodies [92]. The generation of these novel antago- nists is reaching the forefront of treatment against heart attack and stroke, although the efficacy and safety of these drugs remain to be further established or evaluated in human clinical trials. Notably, there are currently no clinically available direct GPIbα antagonists.

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Novel targeted therapies for mantle cell lymphoma

Novel targeted therapies for mantle cell lymphoma

Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy characterized by short median survival despite intensive therapies. The clinical behavior of MCL most likely relates to the complex pathophysiology of the disease which includes its genetic hallmark, the chromosomal translocation t(11;14) resulting in aberrant expression of cyclin D1, alteration in the DNA damage response, and constitutive activation of key antiapoptotic pathways such as phosphatidyl-inositol 3-kinase (PI3K)/Akt and nuclear factor-kB (NF-kB). Together, these changes result in cell cycle dysregulation and give rise to profound genetic instability. Given this complex pathophysiology, the limited number of options for patients with relapsed/refractory MCL, and the difficulty in achieving long-lasting remissions with conventional approaches, it is essential to explore new treatment options targeting the pathophysiology of MCL. We have recently reported that milatuzumab, a fully humanized anti-CD74 monoclonal antibody (mAb), in combination with anti-CD20 mAbs has significant preclinical and clinical activity in MCL. Here we discuss these results, provide additional insights into milatuzumab- mediated MCL cell death, and report preliminary data on the activity of other targeted biologic agents including PCI-32765, CAL-101 and mammalian target of rapamycin (mTOR) inhibitors currently undergoing evaluation at our institution and others.

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