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Toll-like receptor 4 signaling pathway mediates proinflammatory immune response to cobalt-alloy particles.

Metal orthopedic implant debris-induced osteolysis of hip bone is a major problem in patients with prosthetic-hips. Although macrophages are the principal targets for implant-wear debris, the receptor(s) and mechanisms underlying these responses are not fully elucidated. We examined whether the TLR4 pathway mediates immune response to metal-on-metal (MoM) implant-generated wear particles. Human monocytes (THP-1) were exposed to Co-alloy particles at increasing particle:cell ratio for 24 h. Challenge with particles caused up-regulation of IL-1β, TNF-α and IL-8, and mediated degradation of cytos

[Effects of sodium tanshinone II A sulfonate on proliferation of fibroblasts in scar and the mRNA and protein expressions of transforming growth factor beta 1 and alpha smooth muscle actin].

OBJECTIVE: To study the effects of sodium tanshinone II A sulfonate (STS) on proliferation of fibroblasts (Fbs) in human hypertrophic scar (HS), the mRNA and protein expressions of transforming growth factor beta 1 (TGF-β1) and alpha smooth muscle actin (α-SMA), and to investigate the scar inhibition mechanism of STS. METHODS: Fbs were isolated from HS tissues that were removed from eight patients after burn injury, and they were cultured in vitro. Cells from the 3rd to the 6th passages were used in the experiment. Fbs were divided into control group and experimental group according to the ra

Expression of multidrug resistance genes MVP, MDR1, and MRP1 determined sequentially before, during, and after hyperthermic isolated limb perfusion of soft tissue sarcoma and melanoma patients.

PURPOSE: Isolated, hyperthermic limb perfusion (ILP) with recombinant human tumor necrosis factor alpha and melphalan is a highly effective treatment for advanced soft tissue sarcoma (STS) and locoregional metastatic malignant melanoma. Multidrug resistance (MDR)-associated genes are known to be inducible by heat and drugs; expression levels of the major vault protein (MVP), MDR1, and MDR-associated protein 1 (MRP1) were determined sequentially before, during, and after ILP of patients. PATIENTS AND METHODS: Twenty-one STS or malignant melanoma patients were treated by ILP. Tumor tissue tempe

Green Synthesized Zinc Oxide Nanoparticles as a Promising Adjuvant to Albendazole in the Management of Hydatid Cyst Disease: Molecular and Biochemical Insights.

BACKGROUND: This research focused on the green production and characterization of zinc oxide nanoparticles (ZNOP), as well as assessing their potential to manage hydatidosis infection in mice through affecting hydatid cysts, inflammatory factors, oxidative stress markers, apoptosis-related genes, as well as its hepatoprotective effects. METHODS: ZNOP was green synthesized using Ferula macrecolea extract. To induce experimental hydatidosis, mice were intraperitoneally inoculated with 1,500 viable Echinococcus granulosus protoscoleces. The experimental framework comprised eight distinct treatmen

Development of CD46 targeted alpha theranostics in prostate cancer using 134Ce/225Ac-Macropa-PEG4-YS5.

Rationale: 225Ac, a long-lived α-emitter with a half-life of 9.92 days, has garnered significant attention as a therapeutic radionuclide when coupled with monoclonal antibodies and other targeting vectors. Nevertheless, its clinical utility has been hampered by potential off-target toxicity, a lack of optimized chelators for 225Ac, and limitations in radiolabeling methods. In a prior study evaluating the effectiveness of CD46-targeted radioimmunotherapy, we found great therapeutic efficacy but also significant toxicity at higher doses. To address these challenges, we have developed a radioimmu

Exploratory study of microparticle transcatheter arterial chemoembolization combined with resection for huge hepatocellular carcinoma.

OBJECTIVE: To investigate the safety and clinical efficacy of microparticle transcatheter arterial chemoembolization (mTACE) combined with surgical resection for the treatment of huge hepatocellular carcinoma (hHCC; ≥ 10 ​cm). METHODS: A retrospective descriptive study was conducted to gather the clinical data of nine patients with hHCCs treated with mTACE combined with resection in Beijing Tsinghua Changgung Hospital from December 2016 to July 2020. The outcome were as follows: (1) the excellent effect and adverse reactions of mTACE and (2) the efficacy and safety of perioperative resection.

Influence of post-etching cleaning and connecting porcelain on the microtensile bond strength of composite resin to feldspathic porcelain.

STATEMENT OF PROBLEM: There are different methods to fabricate layered feldspathic porcelain restorations, including the refractory die technique and the hot-press technique. Standard adhesive protocol for such restorations requires etching and silanating the fitting surface of the porcelain. Variations in bond strength between porcelain and composite resin might result from the different fabrication methods for porcelain restorations. PURPOSE: The purpose of this study was to determine differences in microtensile bond strength between composite resin (used as a luting agent) and feldspathic

Preclinical efficacy of hK2 targeted [177Lu]hu11B6 for prostate cancer theranostics.

Androgen ablating drugs increase life expectancy in men with metastatic prostate cancer, but resistance inevitably develops. In a majority of these recurrent tumors, the androgen axis is reactivated in the form of increased androgen receptor (AR) expression. Targeting proteins that are expressed as a down-stream effect of AR activity is a promising rationale for management of this disease. The humanized IgG1 antibody hu11B6 internalizes into prostate and prostate cancer (PCa) cells by binding to the catalytic cleft of human kallikrein 2 (hK2), a prostate specific enzyme governed by the AR-path

Phloretin-nanospanlastics for targeting the Akt/PI3K signaling pathways in dimethylhydrazine-induced colon cancer in mice.

OBJECTIVES: Colorectal cancer is the third most common cancer worldwide, accounting for approximately 10 % of all cancer cases. It is also the second leading cause of cancer-related deaths globally. Phloretin is a natural compound found in apples and other fruits. It has been studied for its potential health benefits, including antioxidant and anti-inflammatory properties. However, more research is needed to fully understand its impact on cancer prevention or treatment. This article aimed to prepare phloretin-nanospanlastics (Ph-NSLs) to evaluate their effects on dimethylhydrazine (DMH)-induce

Full-length recombinant antibodies from Escherichia coli: production, characterization, effector function (Fc) engineering, and clinical evaluation.

Although several antibody fragments and antibody fragment-fusion proteins produced in Escherichia coli (E. coli) are approved as therapeutics for various human diseases, a full-length monoclonal or a bispecific antibody produced in E. coli has not yet been approved. The past decade witnessed substantial progress in expression of full-length antibodies in the E. coli cytoplasm and periplasm, as well as in cell-free expression systems. The equivalency of E. coli-produced aglycosylated antibodies and their mammalian cell-produced counterparts, with respect to biochemical and biophysical propertie

Induction of cytochrome P450 (CYP)1A1, CYP1A2, and CYP3A4 but not of CYP2C9, CYP2C19, multidrug resistance (MDR-1) and multidrug resistance associated protein (MRP-1) by prototypical inducers in human hepatocytes.

Human hepatocytes cultured serum-free for up to 6 weeks were used to study expression and induction of enzymes and membrane transport proteins involved in drug metabolism. Phase I drug metabolizing enzymes cytochrome P450 (CYP)1A1, CYP1A2, CYP2C9, CYP2C19, CYP2E1, and CYP3A4 were detected by Western blot analyses and, when appropriate, by enzymatic assays for ethoxyresorufin-O-deethylase(EROD)-activity and testosterone-6beta-hydroxylase(T6H)-activity. Expression of the membrane transporter multi-drug resistance protein (P-glycoprotein, MDR-1), multidrug resistance-associated protein (MRP-1), a

Current landscape and future directions of targeted-alpha-therapy for glioblastoma treatment.

Glioblastoma (GB) is the most aggressive malignancy of the central nervous system. Despite two decades of intensive research since the establishment of the standard of care, emerging strategies have yet to produce consistent satisfactory outcomes. Because of its specific localisation and intricate characteristics, GB is a uniquely regulated solid tumour with a strong resistance to therapy. Advances in targeted radionuclide therapy (TRT), particularly with the introduction of a-emitting radionuclides, have unveiled potential avenues for the management of GB. Recent preclinical and clinical stud

Dual targeting with 224Ra/212Pb-conjugates for targeted alpha therapy of disseminated cancers: A conceptual approach.

Metastases are the primary cause of death among cancer patients and efficacious new treatments are sorely needed. Targeted alpha-emitting radiopharmaceuticals that are highly cytotoxic may fulfill this critical need. The focus of this paper is to describe and explore a novel technology that may improve the therapeutic effect of targeted alpha therapy by combining two radionuclides from the same decay chain in the same solution. We hypothesize that the dual targeting solution containing bone-seeking 224Ra and cell-directed complexes of progeny 212Pb is a promising approach to treat metastatic c

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… The diffusion of 220 Rn up to a few hundred micrometers can extend the effective range of the shorter-range alpha particles from 224 Ra itself and may cause a “dose-smoothening” effect in the metastases. … Targeted alpha-particle therapy with 227Th-labeled antibodies. Curr Radiopharm. ( 2008 ) 1 : 209 – 14 . 10.1097/MNM.0b013e328354df7c 22643311 38. Henriksen G Bruland O Larsen R . Thorium and actinium polyphosphonate compounds as bone-seeking alpha particle-emitting agents. …

The Mode-of-Action of Targeted Alpha Therapy Radium-223 as an Enabler for Novel Combinations to Treat Patients with Bone Metastasis.

Bone metastasis is a common clinical complication in several cancer types, and it causes a severe reduction in quality of life as well as lowering survival time. Bone metastases proceed through a vicious self-reinforcing cycle that can be osteolytic or osteoblastic in nature. The vicious cycle is characterized by cancer cells residing in bone releasing signal molecules that promote the differentiation of osteoclasts and osteoblasts either directly or indirectly. The increased activity of osteoclasts and osteoblasts then increases bone turnover, which releases growth factors that benefit metast

The current status of prostate cancer treatment and PSMA theranostics.

In the treatment of cancer, understanding the disease status, or accurate staging, is extremely important, and various imaging techniques are used. Computed tomography (CT), magnetic resonance imaging, and scintigrams are commonly used for solid tumors, and advances in these technologies have improved the accuracy of diagnosis. In the clinical practice of prostate cancer, CT and bone scans have been considered especially important for detecting metastases. Nowadays, CT and bone scans are called conventional methods because positron emission tomography (PET), especially prostate-specific membra

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… Beta particles have a lower mass and charge compared to alpha particles and can travel farther in tissue. This allows them to penetrate deeper into the body and target tumors located at a greater distance from the radiation source. … In contrast, alpha particles have a higher mass and charge, and a shorter range in tissue. This makes them less suitable for treating tumors located deep within the body, but highly effective for treating small, localized tumors. …

Radiometals in Imaging and Therapy: Highlighting Two Decades of Research.

The present article highlights the important progress made in the last two decades in the fields of molecular imaging and radionuclide therapy. Advancements in radiometal-based positron emission tomography, single photon emission computerized tomography, and radionuclide therapy are illustrated in terms of their production routes and ease of radiolabeling. Applications in clinical diagnostic and radionuclide therapy are considered, including human studies under clinical trials; their current stages of clinical translations and findings are summarized. Because the metalloid astatine is used for

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… Alpha-Particle-Emitting Radiopharmaceuticals Alpha radiations are better suited for the treatment of small metastasis due to their short tissue penetration range and high LET per micrometer of tissue compared to β − -emitting radionuclide via double strand DNA breaks in cancerous cells, while sparing … Several research studies are ongoing to investigate its dosimetry approach [ 322 , 323 , 324 ]. 224 Ra is a pure α-emitter that decays via a series of six daughter nuclides ( 220 Rn, 216 Po, 212 Pb, 212 Bi, 212 Po, 208 Tl) and emit overall four alpha particles and two beta particles before stabilizing …

Clinical Experience with Targeted Alpha-Emitter Peptide Receptor Radionuclide Therapy (α-PRRT) for Somatostatin Receptor-Positive Neuroendocrine Tumors.

Background: α-emitting Peptide Receptor Radionuclide Therapy (α-PRRT) is emerging as a promising new generation of PRRT for neuroendocrine tumors (NETs), providing enhanced tumor cell cytotoxicity and reduced irradiation of adjacent healthy tissues due to its high linear energy transfer (LET) and short particle range. This review summarizes available clinical evidence on α-PRRT using different α-emitting isotopes, including actinium-225, lead-212, and bismuth-213, in somatostatin receptor (SSTR)-positive NETs. Methods: A comprehensive literature search was conducted across PubMed, Embase, Coch

Evolving role of biomaterials in diagnostic and therapeutic radiation oncology.

Radiation therapy to treat cancer has evolved significantly since the discovery of x-rays. Yet, radiation therapy still has room for improvement in reducing side effects and improving control of cancer. Safer and more effective delivery of radiation has led us to novel techniques and use of biomaterials. Biomaterials in combination with radiation and chemotherapy have started to appear in pre-clinical explorations and clinical applications, with many more on the horizon. Biomaterials have revolutionized the field of diagnostic imaging, and now are being cultivated into the field of theranostic

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… Alpha particles comparatively, are made of neutrons and protons, which make it difficult for them to penetrate tissue. Alpha particles are the least ionizing in terms of radiation in an environmental sense. … The two main disadvantages of alpha particles are their delivery and limited availability [ 20 ]. Even with the limited range of alpha particles, excessive radiation exposure has the potential for severe unwanted effects. …

Targeting Bone Metastases in Metastatic Castration-Resistant Prostate Cancer.

Skeletal involvement in metastatic castrate-resistant prostate cancer (mCRPC) is common and results in significant morbidity and mortality. The interaction of prostate cancer with the bone microenvironment contributes to progression of cancer in the bone leading to skeletal-related events (SREs). Studies aimed at targeting the bone have been carried out over the recent years. Bisphosphonates are synthetic pyrophosphate analogs first investigated for their role in SRE prevention with zoledronic acid as the main bisphosphonate that is approved by the US Food and Drug Administration for retardati

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… particles and two-beta particles, with alpha particles emitting 95.3% of the energy and beta particles emitting 3.6%. … Only 1.1% of the energy emitted is gamma rays. 56 – 58 The released alpha particles are directly cytotoxic to cells by inducing double-stranded DNA breaks. …

Радиум - с момента открытия и до настоящего времени - обзор событий.

После его открытия радий первоначально пропагандировался в качестве терапевтического агента для широкого круга заболеваний, включая расстройства кожи, аллергию, проблемы зрения, боль в суставах и общее средство для укрепления здоровья. Однако последующие исследования продемонстрировали ее значительную радиологическую токсичность и вредное воздействие на здоровье человека. Несмотря на эти риски, более чем через сто лет после его открытия, некоторые радиевые изотопы по-прежнему имеют ограниченное применение в медицинских целях, особенно при лечении конкретных раковых заболеваний. После поглощени

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… The alpha particles produced involve high linear energy transfer (LET) radiation with dense ionizing tracks, causing complex DNA damage. Unfortunately, alpha particles also induce cytotoxicity in non-irradiated neighboring cells through specific radiation-induced side effects. … Understanding the effects of 223 RaCl 2 and other alpha-particle emitters has significant therapeutic potential due to the short range of the emitted alpha particles. The decay of 223 Ra affects the production of daughter radionuclides by emitting alpha particles, beta particles, and gamma rays. …