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Indian Journal of Ophthalmology Jul 2024
Topics: Humans; Angiogenesis Inhibitors; Vascular Endothelial Growth Factor A; Visual Acuity; Intravitreal Injections; Diabetic Retinopathy; Macular Edema; Bevacizumab; Ranibizumab; Treatment Outcome; Tomography, Optical Coherence
PubMed: 38953138
DOI: 10.4103/IJO.IJO_40_24 -
Indian Journal of Ophthalmology Jul 2024
Topics: Humans; Intravitreal Injections; Administration, Oral; Central Serous Chorioretinopathy; Rifampin; Vascular Endothelial Growth Factor A; Propranolol; Angiogenesis Inhibitors; Adrenergic beta-Antagonists
PubMed: 38953136
DOI: 10.4103/IJO.IJO_3022_23 -
Frontiers in Immunology 2024Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of...
BACKGROUND
Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of solid tumors, particularly heterogeneity, metabolic aggressiveness, and fewer immune cells in tumor microenvironment (TME), the practical utility of CAR-T cells for solid tumors remains as a challenging issue. Meanwhile, although anti-PD-1 monoclonal antibody (mAb) has shown clinical efficacy, most mAbs also show limited clinical benefits for solid tumors due mainly to the issues associated with the lack of immune cells in TME. Thus, the infiltration of targeted immunological active cells into TME could generate synergistic efficacy for mAbs.
METHODS
We present a combinational strategy for solid tumor treatment, which combines armored-T cells to express Fc-gamma receptor I (FcγRI) fragment on the surfaces for targeting various tumors with therapeutically useful mAbs. Choosing CD20 and HER-2 as the targets, we characterized the and efficacy and latent mechanism of the combination drug by using flow cytometry, ELISA and other methods.
RESULTS
The combination and preprocessing of armored T-cells with corresponding antibody of Rituximab and Pertuzumab exerted profound anti-tumor effects, which is demonstrated to be mediated by synergistically produced antibody-dependent cellular cytotoxicity (ADCC) effects. Meanwhile, mAb was able to carry armored-T cell by preprocessing for the infiltration to TME in cell derived xenograft (CDX) model.
CONCLUSIONS
This combination strategy showed a significant increase of safety profiles from the reduction of antibody doses. More importantly, the present strategy could be a versatile tool for a broad spectrum of cancer treatment, with a simple pairing of engineered T cells and a conventional antibody.
Topics: Receptors, IgG; Humans; Animals; Mice; Neoplasms; T-Lymphocytes; Tumor Microenvironment; Antibodies, Monoclonal; Cell Line, Tumor; Xenograft Model Antitumor Assays; Immunotherapy, Adoptive; Receptor, ErbB-2; Antineoplastic Agents, Immunological; Receptors, Chimeric Antigen; Female; Antigens, CD20
PubMed: 38953027
DOI: 10.3389/fimmu.2024.1400177 -
Research (Washington, D.C.) 2024Hyperthermia therapy is considered an effective anticancer strategy. However, high temperature can trigger an excessive inflammatory response, leading to tumor...
Hyperthermia therapy is considered an effective anticancer strategy. However, high temperature can trigger an excessive inflammatory response, leading to tumor self-protection, immunosuppression, metastasis, and recurrence. To address this issue, we reported a multifunctional photothermal nanoplatform to achieve mild hyperthermia photothermal therapy (mild PTT) based on cisplatin (DDP) and a ferrocene metal-organic framework (MOF-Fc) nanocomposite, which can specifically enhance ferroptosis-triggered oxidative stress levels and synchronously amplify mild hyperthermia PTT-mediated anticancer responses. Both in vitro and in vivo antineoplastic results verify the superiority of mild PTT with DDP/MOF-Fc@HA. The combination of DDP and MOF-Fc exhibits Fenton catalytic activity and glutathione depletion capacity, magnifying mild hyperthermia effects via the radical oxygen species (ROS)-adenosine triphosphate (ATP)-HSP silencing pathway, with important implications for clinical hyperthermia therapy.
PubMed: 38952997
DOI: 10.34133/research.0397 -
The Canadian Veterinary Journal = La... Jul 2024A 5-year-old spayed female mixed-breed dog was referred to the Atlantic Veterinary College (Charlottetown, Prince Edward Island) because of a 7-month history of...
A 5-year-old spayed female mixed-breed dog was referred to the Atlantic Veterinary College (Charlottetown, Prince Edward Island) because of a 7-month history of intermittent pink, mucoid, vulvar discharge. The dog was imported from the Bahamas at 3.5 y of age and had a history of transmissible venereal tumor (TVT) of the vulva that was successfully treated with a course of vincristine chemotherapy. Complete remission was achieved with a disease-free interval of 6 mo before clinical signs recurred. Abdominal ultrasound and CT scan identified a large caudal abdominal mass thought to arise from the uterine stump. An exploratory laparotomy was performed and the mass grossly excised. Histopathology was consistent with a poorly differentiated round cell tumor, and immunohistochemical analysis confirmed TVT as the most likely diagnosis. No further treatment was carried out. Repeat abdominal ultrasound at 4 mo after surgery showed no evidence of mass recurrence. At 8 mo after surgery, the dog was reported to be doing well clinically. Key clinical message: Transmissible venereal tumor should be considered as a differential diagnosis for masses arising from the deep genital tissues of dogs in cases where there is a history of previous TVT. Transmissible venereal tumor should be considered even in dogs that have had complete resolution of a primary mass after chemotherapy.
Topics: Animals; Dogs; Female; Dog Diseases; Venereal Tumors, Veterinary; Vincristine; Vulvar Neoplasms; Antineoplastic Agents, Phytogenic
PubMed: 38952767
DOI: No ID Found -
The Canadian Veterinary Journal = La... Jul 2024An 11-year-old neutered male large crossbreed dog was presented for investigation because of a 10-day history of progressive lethargy, hyporexia, and pyrexia. Physical...
An 11-year-old neutered male large crossbreed dog was presented for investigation because of a 10-day history of progressive lethargy, hyporexia, and pyrexia. Physical and dermatological examinations were unremarkable. Blood biochemical analysis identified a marked total and ionized hypercalcemia and increased C-reactive protein concentration. Bicavitary computed tomography screening for causes of the dog's clinical and biochemical abnormalities identified a diffuse panniculitis. Histopathological examination of full-thickness skin biopsies was consistent with pyogranulomatous inflammation. Extensive histochemical staining revealed no infectious etiology. Complete clinical and biochemical remissions were observed after starting immunosuppressive, followed by tapering, doses of prednisolone, supporting an immune-mediated etiology. Key clinical message: Sterile, immune-mediated pyogranulomatous inflammation should remain a differential diagnosis for hypercalcemia in dogs. Significant dermatological disease may occur without visible abnormalities.
Topics: Animals; Dogs; Dog Diseases; Male; Panniculitis; Hypercalcemia; Prednisolone; Immunosuppressive Agents
PubMed: 38952756
DOI: No ID Found -
Oncoimmunology 2024The role of CD161CD127CD8 T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and...
The role of CD161CD127CD8 T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function of CD8 T cell subsets in NSCLC with diabetes. We recruited NSCLC patients ( = 436) treated with anti-PD-1 immunotherapy as first-line treatment. The progression-free survival (PFS), overall survival (OS), T cells infiltration, and peripheral blood immunological characteristics were analyzed in NSCLC patients with or without diabetes. NSCLC patients with diabetes exhibited shorter PFS and OS ( = 0.0069 and = 0.012, respectively) and significantly lower CD8 T cells infiltration. Mass cytometry by time-of-flight (CyTOF) showed a higher percentage of CD161CD127CD8 T cells among CD8T cells in NSCLC with diabetes before anti-PD-1 treatment ( = 0.0071) than that in NSCLC without diabetes and this trend continued after anti-PD-1 treatment ( = 0.0393). Flow cytometry and multiple-immunofluorescence confirmed that NSCLC with diabetes had significantly higher CD161CD127CD8 T cells to CD8T cells ratios than NSCLC patients without diabetes. The RNA-sequencing analysis revealed immune-cytotoxic genes were reduced in the CD161CD127CD8 T cell subset compared to CD161CD127CD8 T cells in NSCLC with diabetes. CD161CD127CD8 T cells exhibited more T cell-exhausted phenotypes in NSCLC with diabetes. NSCLC patients with diabetes with ≥ 6.3% CD161CD127CD8 T cells to CD8T cells ratios showed worse PFS. These findings indicate that diabetes is a risk factor for NSCLC patients who undergo anti-PD-1 immunotherapy.CD161CD127CD8 T cells could be a key indicator of a poor prognosis in NSCLC with diabetes. Our findings would help in advancing anti-PD-1 therapy in NSCLC patients with diabetes.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Male; Female; CD8-Positive T-Lymphocytes; Middle Aged; Aged; Immunotherapy; Programmed Cell Death 1 Receptor; Immune Checkpoint Inhibitors; Interleukin-7 Receptor alpha Subunit; Diabetes Mellitus; T-Lymphocyte Subsets; Prognosis; Adult
PubMed: 38952673
DOI: 10.1080/2162402X.2024.2371575 -
Oncoimmunology 2024The randomized METIMMOX trial (NCT03388190) examined if patients with previously untreated, unresectable abdominal metastases from microsatellite-stable (MSS) colorectal... (Randomized Controlled Trial)
Randomized Controlled Trial
The randomized METIMMOX trial (NCT03388190) examined if patients with previously untreated, unresectable abdominal metastases from microsatellite-stable (MSS) colorectal cancer (CRC) might benefit from potentially immunogenic, short-course oxaliplatin-based chemotherapy alternating with immune checkpoint blockade (ICB). Three of 38 patients assigned to this experimental treatment had metastases from -mutant MSS-CRC, in general a poor-prognostic subgroup explored here. The ≥70-year-old females presented with ascending colon adenocarcinomas with intermediate tumor mutational burden (6.2-11.8 mutations per megabase). All experienced early disappearance of the primary tumor followed by complete response of all overt metastatic disease, resulting in progression-free survival as long as 20-35 months. However, they encountered recurrence at previously unaffected sites and ultimately sanctuary organs, or as intrahepatic tumor evolution reflected in the terminal loss of initially induced T-cell clonality in liver metastases. Yet, the remarkable first-line responses to short-course oxaliplatin-based chemotherapy alternating with ICB may offer a novel therapeutic option to a particularly hard-to-treat MSS-CRC subgroup.
Topics: Humans; Oxaliplatin; Female; Proto-Oncogene Proteins B-raf; Colorectal Neoplasms; Immune Checkpoint Inhibitors; Aged; Antineoplastic Combined Chemotherapy Protocols; Mutation; Microsatellite Instability; Treatment Outcome; Aged, 80 and over
PubMed: 38952672
DOI: 10.1080/2162402X.2024.2372886 -
Molecular Imaging 2024Labeled antibodies are excellent imaging agents in oncology to non-invasively visualize cancer-related antigens expression levels. However, tumor tracer uptake (TTU) of... (Comparative Study)
Comparative Study
BACKGROUND
Labeled antibodies are excellent imaging agents in oncology to non-invasively visualize cancer-related antigens expression levels. However, tumor tracer uptake (TTU) of specific antibodies in-vivo may be inferior to non-specific IgG in some cases.
OBJECTIVES
To explore factors affecting labeled antibody visualization by PD-L1 specific and non-specific imaging of nude mouse tumors.
METHODS
TTU was observed in RKO model on Cerenkov luminescence (CL) and near-infrared fluorescence (NIRF) imaging of radionuclide I or NIRF dyes labeled Atezolizumab and IgG. A mixture of NIRF dyes labeled Atezolizumab and I-labeled IgG was injected, and TTU was observed in the RKO and HCT8 model by NIRF/CL dual-modality in-situ imaging. TTU were observed by I-labeled Atezolizumab and IgG in-vitro distribution.
RESULTS
Labeled IgG concentrated more in tumors than Atezolizumab. NIRF/CL imaging in 24 to 168 h showed that TTU gradually decreased over time, which decreased more slowly on CL imaging compared to NIRF imaging. The distribution data in-vitro showed that TTU of I-labeled IgG was higher than that of I-labeled Atezolizumab at any time point.
CONCLUSION
Non-specific IgG may not be suitable as a control for Atezolizumab in comparing tumor PD-L1 expression in nude mice via labeled antibody optical imaging under certain circumstances.
Topics: Animals; B7-H1 Antigen; Mice, Nude; Humans; Mice; Cell Line, Tumor; Antibodies, Monoclonal, Humanized; Optical Imaging; Iodine Radioisotopes; Neoplasms; Immunoglobulin G; Female; Luminescence
PubMed: 38952401
DOI: 10.1177/15353508241261473 -
Drug Delivery Dec 2024In this study, chitosan low molecular weight (LCH) and chitosan medium molecular weight (MCH) were employed to encapsulate a yarrow extract rich in chlorogenic acid and...
In this study, chitosan low molecular weight (LCH) and chitosan medium molecular weight (MCH) were employed to encapsulate a yarrow extract rich in chlorogenic acid and dicaffeoylquinic acids (DCQAs) that showed antiproliferative activity against colon adenocarcinoma cells. The design of CH micro/nanoparticles to increase the extract colon delivery was carried out by using two different techniques: ionic gelation and spray drying. Ionic gelation nanoparticles obtained were smaller and presented higher yields values than spray-drying microparticles, but spray-drying microparticles showed the best performance in terms of encapsulation efficiency (EE) (> 94%), also allowing the inclusion of a higher quantity of extract. Spray-drying microparticles designed using LCH with an LCH:extract ratio of 6:1 (1.25 mg/mL) showed a mean diameter of 1.31 ± 0.21 µm and EE values > 93%, for all phenolic compounds studied. The release profile of phenolic compounds included in this formulation, at gastrointestinal pHs (2 and 7.4), showed for most of them a small initial release, followed by an increase at 1 h, with a constant release up to 3 h. Chlorogenic acid presented the higher release values at 3 h (56.91% at pH 2; 44.45% at pH 7.4). DCQAs release at 3 h ranged between 9.01- 40.73%, being higher for 1,5- and 3,4-DCQAs. After gastrointestinal digestion, 67.65% of chlorogenic and most DCQAs remained encapsulated. Therefore, spray-drying microparticles can be proposed as a promising vehicle to increase the colon delivery of yarrow phenolics compounds (mainly chlorogenic acid and DCQAs) previously described as potential agents against colorectal cancer.
Topics: Chitosan; Humans; Plant Extracts; Achillea; Chlorogenic Acid; Nanoparticles; Cell Proliferation; Colorectal Neoplasms; Particle Size; Cell Line, Tumor; Quinic Acid; Drug Liberation; Drug Delivery Systems; Antineoplastic Agents, Phytogenic; Colon; Drug Carriers; Molecular Weight
PubMed: 38952133
DOI: 10.1080/10717544.2024.2372285