Limitations Of Monotherapy Research Articles

Effect of injectable calcium alginate-amelogenin hydrogel on macrophage polarization and promotion of jawbone osteogenesis.

Due to persistent inflammation and limited osteogenesis, jawbone defects present a considerable challenge in regenerative medicine. Amelogenin, a major protein constituent of the developing enamel matrix, demonstrates promising capabilities in inducing regeneration of periodontal supporting tissues and exerting immunomodulatory effects. These properties render it a potential therapeutic agent for enhancing jawbone osteogenesis. Nevertheless, its clinical application is hindered by the limitations of monotherapy and its rapid release characteristics, which compromise its efficacy and delivery efficiency. In this context, calcium alginate hydrogel, recognized for its superior physicochemical properties and biocompatibility, emerges as a candidate for developing a synergistic bioengineered drug delivery system. This study describes the synthesis of an injectable calcium amelogenin/calcium alginate hydrogel using calcium alginate loaded with amelogenin. We comprehensively investigated its physical properties, its role in modulating the immunological environment conducive to bone healing, and its osteogenic efficacy in areas of jawbone defects. Our experimental findings indicate that this synthesized composite hydrogel possesses desirable mechanical properties such as injectability, biocompatibility, and biodegradability. Furthermore, it facilitates jawbone formation by regulating the bone-healing microenvironment and directly inducing osteogenesis. This research provides novel insights into the development of bone-tissue regeneration materials, potentially advancing their clinical application.

Oncolytic virotherapy in cancer treatment: challenges and optimization prospects.

Oncolytic viruses (OVs) are emerging cancer therapeutics that offer a multifaceted therapeutic platform for the benefits of replicating and lysing tumor cells, being engineered to express transgenes, modulating the tumor microenvironment (TME), and having a tolerable safety profile that does not overlap with other cancer therapeutics. The mechanism of OVs combined with other antitumor agents is based on immune-mediated attack resistance and might benefit patients who fail to achieve durable responses after immune checkpoint inhibitor (ICI) treatment. In this Review, we summarize data on the OV mechanism and limitations of monotherapy, which are currently in the process of combination partner development, especially with ICIs. We discuss some of the hurdles that have limited the preclinical and clinical development ofOVs. We also describe the available data and provide guidance for optimizing OVs in clinical practice, as well as a summary of approved and promising novel OVs with clinical indications.

Narrative review on the role of immunotherapy in early triple negative breast cancer: unveiling opportunities and overcoming challenges.

Triple negative breast cancer (TNBC) represents a highly aggressive breast cancer subtype, historically managed with chemotherapy regimens predominantly involving anthracyclines and taxanes, yielding unfavorable prognoses. This review endeavors to offer a thorough examination of the present state of treatment strategies for early stage triple negative breast cancer (eTNBC), with a particular emphasis on immunotherapy modalities, combination therapies, predictive biomarkers, and ongoing clinical trials. The principal aim of this review is to meticulously assess the available literature, ascertain significant discoveries, and engage in discussions regarding their potential implications for future research endeavors, clinical applications, and policy formulation. This review was conducted using PubMed and Google Scholar databases, with the latest update performed in March 2023. The search strategy was designed to ensure a comprehensive analysis of the literature, with a focus on recent advancements. We critically assess the current eTNBC treatment landscape, covering efficacy and limitations of monotherapy, combination therapies, and predictive biomarkers. We highlight promising results from recent trials, address controversies surrounding chemotherapy, and explore optimal approaches for adjuvant and neoadjuvant therapy (NAT). Insights into personalized treatment strategies, ongoing trials, and future perspectives are provided, advancing our understanding of therapeutic options for eTNBC. Through a comprehensive analysis of the literature, this review highlights the potential of immunotherapy, particularly in combination with chemotherapy, as a promising approach for treating eTNBC. However, further research is warranted to optimize treatment strategies, refine patient selection criteria, and identify reliable biomarkers for predicting response to immune checkpoint inhibitors (ICIs). The findings of this review hold significant implications for future research, clinical practice, and policy-making, offering valuable insights into the current challenges and advancements in eTNBC treatment. Ultimately, this knowledge can contribute to improved patient outcomes, enhanced quality of life, and the development of more effective therapeutic approaches for eTNBC.

A comparison between mesoporous and nonporous polydopamine as nanoplatforms for synergistic chemo-photothermal therapy

Photothermal therapy (PTT) combined with chemotherapy can break through the limitations of monotherapy and enhance the therapeutic efficacy. Polydopamine (PDA), an organic material with excellent photothermal conversion property and degradability, has broad application prospects in PTT. In this paper, PDA nanoparticles and mesoporous polydopamine (MPDA) nanoparticles were prepared with similar and uniform particle size to compare the photothermal performance, degradability, drug loading efficiency and release behavior. Polyethylene glycol (PEG) was coated on the surfaces of PDA and MPDA to boost their dispersion stability and biocompatibility. In vitro experimental results revealed that the two vehicles had satisfactory photothermal effect, drug storage capacity, and multi-responsive release properties of near-infrared (NIR) light /pH/H2O2/glutathione (GSH) for doxorubicin (DOX), while MPDA-PEG had superior photothermal performance, drug loading efficiency and longer-lasting release due to the mesoporous structure and higher surface area. Degradation experiments showed that MPDA degraded more quickly than PDA. The degradation behaviors of MPDA under different conditions were observed, and the possible degradation process was illustrated. Furthermore, the cell viability tests verified that DOX/MPDA-PEG had more eminent synergistic therapeutic effects in thermo-chemotherapy with a lower combination index (CI) of 0.313 compared with DOX/PDA-PEG (0.497). Therefore, MPDA has a broader application prospect for thermo-chemotherapy.

Nonopioid drug combinations for cancer pain: a systematic review.

Pain is highly prevalent in patients with cancer-nearly 40% report moderate-severe pain, which is commonly treated with opioids. Increasing cancer survivorship, opioid epidemics in some regions of the world, and limited opioid access in other regions have focused attention on nonopioid treatments. Given the limitations of monotherapy, combining nonopioids-such as antiepileptics and antidepressants-have shown promise in noncancer pain. This review seeks to evaluate efficacy of nonopioid combinations for cancer-related pain. Systematic searches of PubMed, EMBASE, and Cochrane CENTRAL were conducted for double-blind, randomized, controlled trials comparing a nonopioid combination with at least one of its components and/or placebo. This search yielded 4 randomized controlled trials, published between 1998 and 2019 involving studies of (1) imipramine + diclofenac; (2) mitoxantrone + prednisone + clodronate; (3) pentoxifylline + tocopherol + clodronate; and (4) duloxetine + pregabalin + opioid. In the first 3 of these trials, trends favouring combination efficacy failed to reach statistical significance. However, in the fourth trial, duloxetine + pregabalin + opioid was superior to pregabalin + opioid. This review illustrates recognition for the need to evaluate nonopioid drug combinations in cancer pain, although few trials have been published to date. Given the growing practice of prescribing more than 1 nonopioid for cancer pain and the need to expand the evidence base for rational combination therapy, more high-quality trials in this area are needed.

Mitochondria-specific nanocatalysts for chemotherapy-augmented sequential chemoreactive tumor therapy.

Endogenic tumor chemodynamic therapy (CDT) is emerging as a tumor-therapeutic strategy featuring in situ treatments with high efficiency and specificity based on the Fenton reaction principle. Considering the limitation of monotherapy and relatively insufficient intracellular level of endogenous hydrogen peroxide (H2O2) in tumor tissues, a mitochondria-specific nanocatalyst composed of cisplatin prodrug and gallic acid-ferrous (GA-Fe(II)) nanocomposites is successfully fabricated to fulfill chemotherapy-augmented sequential chemoreactive tumor therapy. The bioactive cisplatin elevates the level of endogenous H2O2 through the activation of nicotinamide adenine dinucleotide phosphate oxidase (NOX)-related cascaded reactions, and the GA-Fe(II) nanocomposites possessing sustainable Fenton catalytic activity subsequently catalyzes H2O2 into highly reactive and toxic hydroxyl radicals to substantially inhibit tumor progression. Especially, this mitochondria-specific nanocatalyst amplifies oxidative stress, stimulates mitochondrial dysfunction, downregulates AKT/mTOR signaling and finally induces cell autophagic death. Both in vitro and in vivo measurements verify that the chemotherapy-augmented sequential chemoreactive nanotherapy based on the mitochondria-specific nanocatalyst implements excellent anticancer efficiency and avoids undesired side effects. This work reveals the enormous potential of chemotherapy-augmented CDT for combating tumors.

Oncolytic Virotherapy Treatment of Breast Cancer: Barriers and Recent Advances.

Oncolytic virotherapy (OV) is an emerging class of immunotherapeutic drugs. Their mechanism of action is two-fold: direct cell lysis and unmasking of the cancer through immunogenic cell death, which allows the immune system to recognize and eradicate tumours. Breast cancer is the most common cancer in women and is challenging to treat with immunotherapy modalities because it is classically an immunogenically “cold” tumour type. This provides an attractive niche for OV, given viruses have been shown to turn “cold” tumours “hot,” thereby opening a plethora of treatment opportunities. There has been a number of pre-clinical attempts to explore the use of OV in breast cancer; however, these have not led to any meaningful clinical trials. This review considers both the potential and the barriers to OV in breast cancer, namely, the limitations of monotherapy and the scope for combination therapy, improving viral delivery and challenges specific to the breast cancer population (e.g., tumour subtype, menopausal status, age).

Intravenous ibuprofen as an adjunct in acute postoperative pain: A review

Background: Postoperative pain can have a significant effect on patient recovery. Studies suggest that 82% patients experience some pain following surgery, of those 47% complaining of moderate pain, 39% experiencing severe to very severe pain. The failure to adequately treat postoperative pain is due to limitations of monotherapy with opioid analgesics. Intravenous ibuprofen is a nonsteroidal antiinflammatory drug with anti-inflammatory, antipyretic, and analgesic properties that may be related to prostaglandin synthetase inhibition and have been shown to reduce opioid requirements with better postoperative pain management. This paper reviews analgesic outcomes of intravenous ibuprofen as an adjunct to opioid for acute postoperative pain in adults.Methods: Relevant studies were searched using cochrane database of systematic reviews, embase and pubmed databases using key words about intravenous ibuprofen and postoperative pain that were appropriate to each database.Results: Tools to assess pain intensity such as visual analog scale, verbal response scale and self-report of pain scores at rest and with movement have been studied. Multimodal approach with preemptive use of nonsteroidal anti-inflammatory drugs for treatment of postoperative pain is considered.Conclusion: Randomized controlled trials and other studies concluded that postoperative pain control protocols can now consider inclusion of intravenous ibuprofen as an adjunct in multimodal approach to offer patients a significant analgesic benefit while reducing the risks associated with opioid administration.Journal of Society of Anesthesiologists of Nepal 2015; 2(1): 21-24

Combination Chemotherapy for Influenza

The emergence of pandemic H1N1 influenza viruses in April 2009 and the continuous evolution of highly pathogenic H5N1 influenza viruses underscore the urgency of novel approaches to chemotherapy for human influenza infection. Anti-influenza drugs are currently limited to the neuraminidase inhibitors (oseltamivir and zanamivir) and to M2 ion channel blockers (amantadine and rimantadine), although resistance to the latter class develops rapidly. Potential targets for the development of new anti-influenza agents include the viral polymerase (and endonuclease), the hemagglutinin, and the non-structural protein NS1. The limitations of monotherapy and the emergence of drug-resistant variants make combination chemotherapy the logical therapeutic option. Here we review the experimental data on combination chemotherapy with currently available agents and the development of new agents and therapy targets.

Current Use of Nucleoside Analogues in the Treatment of HIV Infection

Nucleoside analogues continue to play a central role in the treatment of HIV infection. The recently published Concorde I.rial has been misinterpreted as demonstrating a Jack of efficacy of zidovudine in the treatment of HIV disease. This is clearly not the case because zidovudine was prescribed to patients in both arms of the study. The Concorde study did confirm, however, the limitations of monotherapy in the treatment of this disease. Increased availability of other nucleoside analogues has allowed the development of newer therapeutic strategies. In this context, sequential use of zidovudine, followed by didanosine, has proved to be safe and effective in patients in varying stages of HIV disease. Preliminary results suggest that this strategy could be improved upon by using simultaneous combinations of zidovudine with didanosine or zalcitabine in full closes. The relative efficacy of these combinations remains to be established by phase III clinical trials, currently underway, Several new agents, including d4T, 3TC, nevirapine, other non‐nucleoside reverse transcriptase inhibitors and the more recent protein inhibitors. are being tested either a lone or in combination therapy regimens. It is anticipated that one or more of these agents will be clinically available soon. At present. the British Columbia Centre for Excellence in HIV/AIDS continues to recommend initiation of antiretroviral therapy with zidovudine in doses of 500 mg/day for all HIV‐infected individuals who are symptomatic (ie. who have AIDS or AIDS‐related complex) and for those who are asymptomatic with a CD4 count consistently below 500/mm3. If the CD4 count is lower than 350/mm3, it is recommended that combination antiretroviral therapy be considered. namely zidovudine plus didanosine or zalcitabine in full doses. Obviously, the available evidence should be thoroughly discussed with eligible individuals to ensure that they have a full understanding of the potential benefits, adverse effects and limitations of currently available therapy.