Protein Therapeutics: An Updated Review

2021 ◽  
Vol 11 (3) ◽  
pp. 253-257
Author(s):  
Arindam Chakraborty ◽  
Dipak Kumar Singha ◽  
Manas Chakraborty ◽  
Payel Mukherjee
Keyword(s):  
Stability Problem ◽  
Clinical Success ◽  
Treatment Options ◽  
Therapeutic Proteins ◽  
Protein Therapeutics ◽  
Therapeutic Protein ◽  
Recent Advancement ◽  
Pharmaceutical Industries ◽  
Day By Day ◽  
Pharmaceutical Biotechnology

Therapeutic protein are one of the prime option of biologicals as per their clinical uses. In recent times, uses of therapeutic protein increases day by day. Protein therapeutics are used extensively to treat various diseases like cancer, AIDS etc. Due to recent advancement in pharmaceutical biotechnology the interest towards therapeutic proteins are augmenting nowadays. Various clinical research are going on in this field to treat different diseases and pharmaceutical industries are also make interest on therapeutic proteins. Among the various treatment options therapeutic protein will provide highest chance of clinical success. Some recent clinical trials demonstrate that therapeutic protein may provide the safe and potential option to treat various diseases, but there are some drawbacks also like some immunogenic issues, safety, stability problem of protein, degradation of protein in various conditions.

scholarly journals Oncogenic KRAS engages an RSK1/NF1 pathway to inhibit wild-type RAS signaling in pancreatic cancer

2021 ◽  
Vol 118 (21) ◽  
pp. e2016904118
Author(s):  
Derek K. Cheng ◽  
Tobiloba E. Oni ◽  
Jennifer S. Thalappillil ◽  
Youngkyu Park ◽  
Hsiu-Chi Ting ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Success ◽  
Treatment Options ◽  
Mass Spectrometry Analysis ◽  
Ductal Adenocarcinoma ◽  
Ras Signaling ◽  
Wild Type ◽  
Feedback Mechanisms ◽  
Spectrometry Analysis ◽  
Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with limited treatment options. Although activating mutations of the KRAS GTPase are the predominant dependency present in >90% of PDAC patients, targeting KRAS mutants directly has been challenging in PDAC. Similarly, strategies targeting known KRAS downstream effectors have had limited clinical success due to feedback mechanisms, alternate pathways, and dose-limiting toxicities in normal tissues. Therefore, identifying additional functionally relevant KRAS interactions in PDAC may allow for a better understanding of feedback mechanisms and unveil potential therapeutic targets. Here, we used proximity labeling to identify protein interactors of active KRAS in PDAC cells. We expressed fusions of wild-type (WT) (BirA-KRAS4B), mutant (BirA-KRAS4BG12D), and nontransforming cytosolic double mutant (BirA-KRAS4BG12D/C185S) KRAS with the BirA biotin ligase in murine PDAC cells. Mass spectrometry analysis revealed that RSK1 selectively interacts with membrane-bound KRASG12D, and we demonstrate that this interaction requires NF1 and SPRED2. We find that membrane RSK1 mediates negative feedback on WT RAS signaling and impedes the proliferation of pancreatic cancer cells upon the ablation of mutant KRAS. Our findings link NF1 to the membrane-localized functions of RSK1 and highlight a role for WT RAS signaling in promoting adaptive resistance to mutant KRAS-specific inhibitors in PDAC.

scholarly journals The NMR Spectral Measurement Database: A System for Organizing and Accessing NMR Spectra of Therapeutic Proteins

2021 ◽  
Vol 126 ◽  
Author(s):  
Niksa Blonder ◽  
Frank Delaglio
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Spectral Data ◽  
Data Storage ◽  
Nmr Spectra ◽  
Therapeutic Proteins ◽  
Data Access ◽  
Protein Therapeutics ◽  
Spectral Measurement ◽  
Storage And Retrieval

The Nuclear Magnetic Resonance Spectral Measurement Database (NMR-SMDB) was developed for the purpose of organizing and searching NMR spectral data of protein therapeutics, linking spectra to corresponding sample information and enabling quick access to full datasets and entire studies. In addition to supporting internal research at the National Institute of Standards and Technology (NIST), the system could facilitate data access to stakeholders outside of NIST, and future versions of the database software itself could be installed by others for their own data storage and retrieval.

scholarly journals Biomechanics of Disc Degeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
V. Palepu ◽  
M. Kodigudla ◽  
V. K. Goel
Keyword(s):  
Disc Degeneration ◽  
New Technologies ◽  
Clinical Success ◽  
Treatment Options ◽  
Surgical Methods ◽  
Spinal Arthroplasty ◽  
Orthopedic Literature ◽  
Posterior Dynamic Stabilization ◽  
Adjacent Level Degeneration

Disc degeneration and associated disorders are among the most debated topics in the orthopedic literature over the past few decades. These may be attributed to interrelated mechanical, biochemical, and environmental factors. The treatment options vary from conservative approaches to surgery, depending on the severity of degeneration and response to conservative therapies. Spinal fusion is considered to be the “gold standard” in surgical methods till date. However, the association of adjacent level degeneration has led to the evolution of motion preservation technologies like spinal arthroplasty and posterior dynamic stabilization systems. These new technologies are aimed to address pain and preserve motion while maintaining a proper load sharing among various spinal elements. This paper provides an elaborative biomechanical review of the technologies aimed to address the disc degeneration and reiterates the point that biomechanical efficacy followed by long-term clinical success will allow these nonfusion technologies as alternatives to fusion, at least in certain patient population.

scholarly journals Silicon Nitride (Si3N4) Implants: The Future of Dental Implantology?

2017 ◽  
Vol 43 (3) ◽  
pp. 240-244 ◽  
Author(s):  
Zahi Badran ◽  
Xavier Struillou ◽  
Francis J Hughes ◽  
Assem Soueidan ◽  
Alain Hoornaert ◽  
...  
Keyword(s):  
Silicon Nitride ◽  
Dental Implants ◽  
Dental Implant ◽  
Clinical Success ◽  
Treatment Options ◽  
Antibacterial Properties ◽  
Antimicrobial Properties ◽  
Future Research ◽  
Success Rates ◽  
Biological Performance

For decades titanium has been the preferred material for dental implant fabrication, with mechanical and biological performance resulting in high clinical success rates. These have been further enhanced by incremental development of surface modifications aimed at improving speed and degree of osseointegration and resulting in enhanced clinical treatment options and outcomes. However, increasing demand for metal-free dental restorations has also led to the development of ceramic-based dental implants, such as zirconia. In orthopedics, alternative biomaterials, such as polyetheretherketone or silicon nitride, have been used for implant applications. The latter is potentially of particular interest for oral use as it has been shown to have antibacterial properties. In this article we aim to shed light on this particular biomaterial as a future promising candidate for dental implantology applications, addressing basic specifications required for any dental implant material. In view of available preclinical data, silicon nitride seems to have the essential characteristics to be a candidate for dental implants material. This novel ceramic has a surface with potentially antimicrobial properties, and if this is confirmed in future research, it could be of great interest for oral use.

scholarly journals Evaluation of Nail Findings in Patients with COVID-19 History and Wood’s Lamp Examination

2021 ◽  
pp. 1-6
Author(s):  
Irem Yanatma ◽  
Hulya Cenk
Keyword(s):  
Titanium Dioxide ◽  
Ferric Oxide ◽  
Case Reports ◽  
Treatment Options ◽  
History Of ◽  
Day By Day ◽  
Shed Light

<b><i>Introduction:</i></b> Various skin findings due to coronavirus have been identified. There are a few case reports on nail findings after coronavirus (COVID-19) infection. We aimed to document the nail findings of the COVID-19 survivors and shed light on the interesting luminescence seen under the Wood’s light. <b><i>Methods:</i></b> One hundred and seventy-four patients diagnosed with COVID-19 infection in the last 100 days were grouped in terms of the agents used in the treatment. Fifty-seven volunteers without a history of infection were included. <b><i>Results:</i></b> Patients treated with favipiravir had a significantly higher positivity of luminescence (<i>p</i>: 0.0001). The most common nail findings in patients were splinter hemorrhage (13%), followed by leukonychia (12%) and longitudinal ridges (7.9%). <b><i>Discussion/Conclusions:</i></b> The luminescence may be seen due to the accumulation of favipiravir or its excipients (titanium dioxide and yellow ferric oxide) on the nails. Wood’s lamp examination of the plasma taken from a patient after favipiravir’s first dose revealed the same luminescence as we saw on the nails. Accordingly, this accumulation may be seen in the vital organs. Although our knowledge about the virus increases day by day, the potentially hazardous effects of the virus and long-term complications of the treatment options are still being investigated.

scholarly journals 1283. High Dose Minocycline for the Treatment of Acinetobacter Infections

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S730-S730
Author(s):  
Shelbye R Herbin ◽  
Amina Ammar ◽  
Ryan Gumbleton ◽  
Jing Zhao ◽  
Shannon Olson ◽  
...  
Keyword(s):  
Hospice Care ◽  
Clinical Success ◽  
Treatment Options ◽  
Signs And Symptoms ◽  
High Dose ◽  
Common Site ◽  
Duration Of Treatment ◽  
Susceptible Isolate ◽  
Source Use ◽  
Related Mortality

Abstract Background Acinetobacter (ACB) infections are difficult to treat due to increasing drug resistance. The aim of this study is to evaluate the effectiveness of high-dose (HD) minocycline (MIN) 200mg q12h for the treatment of ACB infections Methods This is a retrospective study of pts with ACB from 1/1/19 to 10/31/20. Exclusions included non-susceptibility to MIN, age &lt; 18 yrs, hospice care w/in 72 hrs of culture, or urine source. Use of HD MIN (IV or PO), was compared to alternative treatment (AT). Clinical and micro success at the end of therapy (EOT) was evaluated. Clinical success was elimination or improvement in signs and symptoms of infection. Micro success was eradication of ACB from the same site of infection at EOT. Length of stay (LOS), 30-day readmission (with or without ACB), isolation of a MIN non-susceptible ACB within 30 days of EOT, and adverse events related to MIN, were evaluated. Results A total of 320 pts were screened with the most common exclusion being MIN non-susceptible isolate. Of the 204 pts included, 38 received HD MIN and 166 received AT. The most common were cefepime (53/166) and meropenem (36/166). Median age (IQR) was 41 (30-50) yrs for HD MIN vs. 40 (27-48) yrs for AT. Both groups were mostly male (HD MIN: 63% vs. AT: 60%) and respiratory was the most common site (HD MIN: 61% vs. AT: 60%). HD MIN group had 74% of cultures that were polymicrobial vs. 86% in AT group. Lack of clinical response at the EOT occurred in 42% of pts on HD MIN and 37% on AT. Infection related mortality occurred in 24% on HD MIN vs. 15% on AT. In HD MIN group, 16 pts had a repeat culture from the same site after treatment with 25% still positive for ACB. In the AT group 61 pts had a repeat culture and 28% were positive for ACB. Duration of treatment (9 [6-11] days vs. 10 [2-18] days) and LOS (16 [18.25-26.75] vs. 29 [14-49]) were shorter in the HD MIN group. There was only one adverse event reported with the use of HD MIN Conclusion Pts in the HD MIN group had shorter treatment duration and a shorter LOS. Pts who received HD MIN had a lower rate of clinical cure and a higher mortality rate compared to pts in the AT group. Reasons for this difference will need to be investigated further. HD MIN should be reserved for pts who are unable to tolerate other treatment options or who have an ACB resistant to other treatment options. Disclosures All Authors: No reported disclosures

scholarly journals Recent Advances and Future Perspective of DC-Based Therapy in NSCLC

2021 ◽  
Vol 12 ◽  
Author(s):  
Iris A. E. van der Hoorn ◽  
Georgina Flórez-Grau ◽  
Michel M. van den Heuvel ◽  
I. Jolanda M. de Vries ◽  
Berber Piet
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Clinical Benefit ◽  
Clinical Success ◽  
Cytotoxic T Cells ◽  
Treatment Options ◽  
Treatment Modalities ◽  
Future Perspective ◽  
Dc Function ◽  
Anti Cancer

Current treatment for patients with non-small-cell lung cancer (NSCLC) is suboptimal since therapy is only effective in a minority of patients and does not always induce a long-lasting response. This highlights the importance of exploring new treatment options. The clinical success of immunotherapy relies on the ability of the immune system to mount an adequate anti-tumor response. The activation of cytotoxic T cells, the effector immune cells responsible for tumor cell killing, is of paramount importance for the immunotherapy success. These cytotoxic T cells are primarily instructed by dendritic cells (DCs). DCs are the most potent antigen-presenting cells (APCs) and are capable of orchestrating a strong anti-cancer immune response. DC function is often suppressed in NSCLC. Therefore, resurrection of DC function is an interesting approach to enhance anti-cancer immune response. Recent data from DC-based treatment studies has given rise to the impression that DC-based treatment cannot induce clinical benefit in NSCLC by itself. However, these are all early-phase studies that were mainly designed to study safety and were not powered to study clinical benefit. The fact that these studies do show that DC-based therapies were well-tolerated and could induce the desired immune responses, indicates that DC-based therapy is still a promising option. Especially combination with other treatment modalities might enhance immunological response and clinical outcome. In this review, we will identify the possibilities from current DC-based treatment trials that could open up new venues to improve future treatment.

scholarly journals Current Status and Perspectives of Oral Therapeutic Protein and Peptide Formulations: A Review

2021 ◽  
pp. 117-137
Author(s):  
G. Manu ◽  
Nagma Firdose ◽  
M. K. Jayanthi ◽  
Ranjith Raj ◽  
Shashank M. Patil ◽  
...  
Keyword(s):  
Delivery System ◽  
Oral Delivery ◽  
High Efficiency ◽  
Therapeutic Proteins ◽  
Therapeutic Protein ◽  
Current Status ◽  
Permeation Enhancers ◽  
Function Relationship ◽  
Particulate Delivery ◽  
Oral Therapeutic

Medicinal formulations have evolved from the use of small molecules that act by blocking various receptors. On the contrary, therapeutic proteins are a class of medicines that have gained increased popularity owing to its low toxicity, high stability and exquisite specificity. Oral delivery of protein drugs is a very interesting but a highly challenging area of medicine that requires advancements in terms of bioavailability of oral drugs. The main objective of the present review is to provide a systematic overview of the various physiological barriers of delivery of therapeutic proteins and novel approaches available in this field in order to counter these physiological barriers. Advances in terms of inhibitors of proteases, permeation enhancers, mucoadhesives, short peptide conjugates, particulate delivery system including nanoparticles. Oral therapeutic proteins face challenges with regard to oral bioavailability, stability of the protein and reproducibility. Among the various strategies, a co-administration of permeation enhancers with protease inhibitors have proven most effective, while particulate delivery system is still under clinical studies in order to be establishes as a method. Overall, a thorough and focused research with sufficient knowledge on the structure-function relationship, substrate specificity and physiological parameters can deliver a potent therapeutic protein with high efficiency.

scholarly journals Rational design of a nanoparticle platform for oral prophylactic immunotherapy to prevent immunogenicity of therapeutic proteins

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nhan H. Nguyen ◽  
Fiona Y. Glassman ◽  
Robert K. Dingman ◽  
Gautam N. Shenoy ◽  
Elizabeth A. Wohlfert ◽  
...  
Keyword(s):  
Immune Response ◽  
Rational Design ◽  
Therapeutic Proteins ◽  
Cost Effective ◽  
Therapeutic Protein ◽  
Safety And Efficacy ◽  
Life Saving ◽  
Pre Treatment ◽  
Design And Testing

AbstractThe safety and efficacy of several life-saving therapeutic proteins are compromised due to their immunogenicity. Once a sustained immune response against a protein-based therapy is established, clinical options that are safe and cost-effective become limited. Prevention of immunogenicity of therapeutic proteins prior to their initial use is critical as it is often difficult to reverse an established immune response. Here, we discuss a rational design and testing of a phosphatidylserine-containing nanoparticle platform for novel oral prophylactic reverse vaccination approach, i.e., pre-treatment of a therapeutic protein in the presence of nanoparticles to prevent immunogenicity of protein therapies.

scholarly journals KAIZEN AND LEAN IMPLEMENTATION IN PHARMACEUTICAL INDUSTRIES: A REVIEW

2018 ◽  
Vol 11 (7) ◽  
pp. 57
Author(s):  
Srinivasan G ◽  
Shah N
Keyword(s):  
Regulatory Compliance ◽  
Pharmaceutical Companies ◽  
Employee Morale ◽  
Lean Implementation ◽  
Management Philosophy ◽  
Production Values ◽  
The World ◽  
Pharmaceutical Industries ◽  
Day By Day ◽  
New Strategies

Kaizen is one of the most commonly used words in all kind of industries. It has been implemented in organizations around the world as a way to improve production values while also improving employee morale and safety. The kaizen process brings about improvements that are small and incremental, and significant results can be seen only after a certain period of time. Many organizations across the world have adopted kaizen management philosophy and have successfully increased the efficiency of their end-to-end supply chains. With a focus on quality and regulatory compliance that are getting stringent day by day, pharmaceutical companies have been adopting these new strategies. This review focuses on basic aspects of Kaizen and Lean implementation and highlights few examples from pharmaceutical industry.

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