A5005672422- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Cancer Research and Treatments
- Nanoplatforms for cancer theranostics
- Radiopharmaceutical Chemistry and Applications
- CAR-T cell therapy research
- vaccines and immunoinformatics approaches
- Virus-based gene therapy research
- Medical Imaging Techniques and Applications
- Essential Oils and Antimicrobial Activity
- Brain Metastases and Treatment
- Phytochemistry and Biological Activities
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Apelin-related biomedical research
- Cancer, Hypoxia, and Metabolism
- Cancer, Stress, Anesthesia, and Immune Response
- Toxin Mechanisms and Immunotoxins
- Cancer-related molecular mechanisms research
- Paraoxonase enzyme and polymorphisms
- Chemotherapy-induced cardiotoxicity and mitigation
- Lung Cancer Research Studies
- Heat shock proteins research
- Cancer Genomics and Diagnostics
- Advances in Cucurbitaceae Research
University of Wisconsin–Madison
2017-2024
Hospital Universiti Sains Malaysia
2010
Universiti Sains Malaysia
2009
Neoantigens induced by random mutations and specific to an individual's cancer are the most important tumor antigens recognized T cells. Among immunologically "cold" tumors, limited recognition of neoantigens results in absence a de novo antitumor immune response. These tumors present clinical challenge as they poorly responsive immunotherapies, including checkpoint inhibitors (ICIs). Radiation therapy (RT) can enhance resulting more diversified T-cell response, yet RT alone rarely systemic...
Low-dose targeted radionuclide therapy combined with immune checkpoint inhibition enhances complete response rates in preclinical tumor models.
Abstract Radiation therapy (RT) activates an in situ vaccine effect when combined with immune checkpoint blockade (ICB), yet this may be limited because RT does not fully optimize tumor antigen presentation or overcome suppressive mechanisms the tumor-immune microenvironment. To this, we develop a multifunctional nanoparticle composed of polylysine, iron oxide, and CpG (PIC) to increase presentation, ratio M1:M2 tumor-associated macrophages, enhance stimulation type I interferon response...
Abstract In situ vaccination is an emerging cancer treatment strategy that uses local therapies to stimulate a systemic antitumor immune response. We previously reported in effect when combining radiation (RT) with intratumor (IT) injection of tumor-specific immunocytokine (IC), fusion antibody and IL2 cytokine. mice bearing two tumors, we initially hypothesized delivering RT plus IT-IC the “primary” tumor would induce response causing regression “secondary” tumor. To test this, one or...
Clinical interest in combining targeted radionuclide therapies (TRT) with immunotherapies is growing. External beam radiation therapy (EBRT) activates a type 1 interferon (IFN1) response mediated via stimulator of genes (STING), and this critical to its therapeutic interaction immune checkpoint blockade. However, little known about the time course IFN1 activation after EBRT or whether may be induced by decay TRT source.
The in situ vaccine effect of radiation therapy (RT) has been shown to be limited both preclinical and clinical settings, possibly due the inadequacy RT alone stimulate vaccination immunologically "cold" tumor microenvironments (TMEs) mixed effects promoting infiltration effector suppressor immune cells. To address these limitations, we combined intratumoral injection radiated site with IL2 a multifunctional nanoparticle (PIC). local agents produced cooperative that favorably immunomodulated...
Abstract Background Most patients with estrogen receptor positive (ER+) breast cancer do not respond to immune checkpoint inhibition (ICI); the tumor microenvironment (TME) of these cancers is generally immunosuppressive and contains few tumor-infiltrating lymphocytes. Radiation therapy (RT) can increase inflammation infiltration by lymphocytes but does improve responses ICIs in patients. This may result, part, from additional effects RT that suppress anti-tumor immunity, including increased...
In head and neck squamous cell carcinoma (HNSCC) tumors that over-expresses huEGFR, the anti-EGFR antibody, cetuximab, antagonizes tumor viability sensitizes to radiation therapy. However, immunologic interactions between cetuximab therapy are not well understood. We transduced two syngeneic murine HNSCC lines express human EGFR (MOC1- MOC2-huEGFR) in order facilitate evaluation of cetuximab. Cetuximab was capable inducing antibody-dependent cellular cytotoxicity (ADCC) MOC1- MOC2-huEGFR...
Background Radiation therapy (RT) has been demonstrated to generate an in situ vaccination (ISV) effect murine models and patients with cancer; however, this not routinely translated into enhanced clinical response immune checkpoint inhibition (ICI). We investigated whether the commonly used vaccine adjuvant, monophosphoryl lipid A (MPL) could augment ISV regimen consisting of combination RT ICI. Materials/methods syngeneic melanoma (B78) prostate cancer (Myc-CaP). Tumor-bearing mice...
The current study evaluated the cardioprotective activity of genistein in cases doxorubicin-(Dox) induced cardiac toxicity and a probable mechanism underlying this protection, such as an antioxidant pathway tissues. Animals used were categorized into four groups. first group was treated with sodium carboxymethylcellulose (0.3%; CMC-Na) solution. second received Dox (3.0 mg/kg, i.p.) on days 6, 12, 18, 24. third fourth groups (3 24 protective doses (100 [group 3] 200 4] mg/kg/day, p.o.) for...
The aim of the investigation was to prepare nimesulide emulsion for incorporation in Aloe vera gel base formulate 'nimesulide - transemulgel' (NAE) and carryout in-vitro assessment in-vivo anti-inflammatory studies product. Although use is banned oral administration, due its potential inducing hepatotoxicity thrombocytopenia, topical delivery prominent treatment many inflammatory conditions including rheumatoid arthritis. drug loading capacity transdermal gels low hydrophobic drugs such as...
In a syngeneic murine melanoma (MEL) model, we recently reported an in situ vaccination response to combined radiation (RT) and intra-tumoral (IT) injection of anti-GD2 hu14.18-IL2 immunocytokine (IC). This treatment resulted 71% complete durable regression 5-week tumors, tumor-specific memory T cell response, augmented systemic anti-CTLA-4 antibody checkpoint blockade. While the ability diversify anti-tumor has been reported, hypothesize that mice rendered disease-free (DF) by RT-based ISV...
We investigated the vascular responses and blood pressure reducing effects of different fractions obtained from methanol extract Loranthus ferrugineus Roxb. (F. Loranthaceae). By means solvent-solvent extraction, L. (LFME) was successively fractionated with chloroform, ethyl acetate n-butanol. The ability these LFME to relax smooth muscle against phenylephrine (PE)- KCl-induced contractions in isolated rat aortic rings determined. In another set experiments, were tested for lowering activity...
Abstract Radiopharmaceutical therapies (RPT) activate a type I interferon (IFN1) response in tumor cells. We hypothesized that the timing and amplitude of this varies by isotope. compared equal doses delivered 90 Y, 177 Lu, 225 Ac vitro as unbound radionuclides vivo when chelated to NM600, tumor-selective alkylphosphocholine. Response murine MOC2 head neck carcinoma B78 melanoma was evaluated qPCR flow cytometry. Therapeutic Ac-NM600+anti-CTLA4+anti-PD-L1 immune checkpoint inhibition (ICI)...
Brain metastases develop in over 60% of advanced melanoma patients and negatively impact quality life prognosis. In a murine model, we previously showed that an situ vaccination (ISV) regimen, combining radiation treatment intratumoral (IT) injection immunocytokine (IC: anti-GD2 antibody fused to IL2), along with the immune checkpoint inhibitor anti-CTLA-4, robustly eliminates peripheral flank tumors but only has modest effects on co-occurring intracranial tumors. this study, investigated...
In the present study, L. ferrugineus methanol extract (LFME) was evaluated for its blood pressure lowering effect in anesthetized normotensive Sprague Dawley (SD) rats and spasmogenic isolated guinea pig ileum. The possible mechanism(s) of action were also investigated. LFME obtained by Soxhlet extraction. fasted overnight with sodium pentobarbitone (60 mg/kg i.p.). administered i.v. boluses concentrations 25, 50, 100 200 respectively, concomitant monitoring mean arterial (MAP). It found...
Background Immune checkpoint inhibition (ICI) alone is not efficacious for a large number of patients with melanoma brain metastases. We previously established an in situ vaccination (ISV) regimen combining radiation and immunocytokine to enhance response ICIs. Here, we tested whether ISV inhibits the development metastases murine model. Methods B78 (GD2 + ) ‘primary’ tumors were engrafted on right flank C57BL/6 mice. After 3–4 weeks, primary treated (radiation (12 Gy, day 1), α-GD2...
This study aimed to elucidate the mechanism(s) of spasmogenic action Loranthus ferrugineus in isolated guinea pig ileum. Thus contractile responses ileum graded additions either L. methanol extract or its n-butanol fraction were tested presence and absence various pharmacological interventions. The data showed that produced a concentration-dependent effect segments. These effects significantly inhibited 1 μM atropine. In contrast, response lowest concentrations (0.25, 0.5 mg/mL) (0.125, 0.25...