Destruction Of Tumor Cells Research Articles

090. Effect of Turmeric Extract (Curcuma longa) on Granzyme Exoration and Tumour Mass Diameter Studi Pada Model Mencit Adenocarcinoma Mammae dengan Pemberian Kemoterapi Adriamycin Cyclophosphamide

Background: Breast cancer accounts for 11.6% of new cancer cases and 6.6% of cancer deaths. Treatment varies based on cancer type and stage, with Complementary Alternative Medicine (CAM) used as adjunct therapy. Turmeric (Curcuma longa) inhibits carcinogenesis, angiogenesis, and tumor growth. Granzyme, a protein involved in apoptosis, is a marker for immunity and tumor cell destruction. Methods: This in vivo experimental study used a Post Test Only Control Group Design. Twenty-five female Balb/c mice with DMBA-induced mammary adenocarcinoma were divided into five groups: positive control, negative control, and three treatment groups. Granzyme expression was measured through immunohistochemistry, and tumor diameters were assessed using calipers. Data were analyzed with SPSS. Results: The P3 group showed the highest granzyme expression (38.71 ± 18.20), while the K- group had the lowest (9.43 ± 3.25). The K- group had the largest tumor diameter (17.11 ± 3.28), and the P3 group had the smallest (10.55 ± 2.33). Granzyme expression significantly differed between groups (p = 0.022), with notable differences between the K- group and K+ (0.021), P1 (0.021), P2 (0.014), and P3 (0.021) groups. Significant differences were also found between the K+ group and the P1 (0.016), P2 (0.004), and P3 (0.014) groups. Conclusion: Granzyme expression was higher in the turmeric and chemotherapy treatment groups compared to the control groups, while tumor diameters were smaller, suggesting enhanced tumor suppression with turmeric extract.

Photothermal and enhanced chemodynamic reinforced anti-tumor therapy based on PDA@POM nanocomposites

Chemodynamic therapy (CDT) and photothermal therapy (PTT) have both demonstrated considerable efficacy in the tumor treatment individually, owing to their non-invasive nature and excellent selectivity. However, due to the propensity of tumors for metastasis and recurrence, a singular therapeutic approach falls short of achieving optimal treatment outcomes. Polydopamine (PDA) has excellent photothermal conversion ability and polyoxometalates (POMs) possess diverse enzymatic activities. Here, we synthesized PDA@POM nanospheres comprising polydopamine-coated Tungsten-based polyoxometalate (W-POM). These nanospheres leverage dual enzymatic activities that synergistically enhance both chemodynamic and photothermal therapies for tumor treatment. The PDA-mediated PTT effect enables precise tumor cell destruction, while the W-POM nanozymes catalyzes the generation of highly toxic reactive oxygen species (ROS) from hydrogen peroxide within tumor cells through a Fenton-like reaction, which mitigates tumor hypoxia and induces tumor cell death. This synergistic photothermal catalytic therapy shows enhanced efficacy in tumor suppression, providing a promising new approach for tumor treatment.

Photodynamic therapy with methylene blue and chlorin e6 photosensitizers: study on Ehrlich carcinoma mice model

Hypoxia negatively affcts the effctiveness of all types of anticancer therapy, in particular photodynamic therapy (PDT). In this regard, various approaches to overcome the limitations associated with hypoxia are widely discussed in the literature, one of them is the use of photosensitizers (PS) operating through the fist mechanism of the photodynamic reaction, such as methylene blue (MB). Previously, we have demonstrated that MB can have a positive effect on tumor oxygenation. In this work, we investigated the photodynamic activity of MB and a combination of MB with chlorin e6 on a tumor in vivo using a model of Ehrlich carcinoma. PDT was studied with the joint and separate administration of chlorin e6 and MB. The accumulation and localization of MB and its combination with chlorin e6 in vivo was assessed using video ˛uorescence and spectroscopic methods, and the effect of laser exposure on accumulation was analyzed. After the PDT with chlorin e6, MB and a combination of MB with chlorin e6, a good therapeutic effect and a decrease in the tumor growth rate were observed compared to the control, especially in groups with PDT with MB and with the simultaneous administration of chlorin e6 and MB. The level of tumor oxygenation on days 3 and 5 after PDT was higher for groups with irradiation, the highest oxygenation on the 5th day after PDT was observed in the group with PDT only with MB. Phasor diagrams of tumors after PDT show a deviation from the metabolic trajectory and a shift towards a longer lifetimes compared to the control tumor, which indicates the presence of lipid peroxidation products. Thus, tumor regression after PDT is associated with the direct destruction of tumor cells under the in˛uence of reactive oxygen species formed during PDT. Thus, the effectiveness of PDT with the combined use of MB and chlorin e6 has been demonstrated, and the main mechanisms of the antitumor effect of the combination of these PS have been studied.

Ultrasound-Activatable In Situ Vaccine for Enhanced Antigen Self- and Cross-Presentation to Overcome Cancer Immunotherapy Resistance.

Insufficient antigen self-presentation of tumor cells and ineffective antigen cross-presentation by dendritic cells (DCs) contribute to diminished immune recognition and activation, which cause resistance to immunotherapies. Herein, we present an ultrasound-activatable in situ vaccine by utilizing a hybrid nanovesicle composed of a thylakoid (TK)/platelet (PLT) membrane and a liposome encapsulating DNA methyltransferase inhibitor zebularine (Zeb) and sonosensitizer hematoporphyrin monomethyl ether (HMME). Upon local exposure to ultrasound, reactive oxygen species (ROS) are generated and induce the sequential release of the payloads. Zeb can efficiently inhibit tumor DNA hypermethylation, promoting major histocompatibility complex class I (MHC-I) molecules-mediated antigen self-presentation to improve immune recognition. Meanwhile, the catalase on the TK membrane can decompose the tumoral overexpressed H2O2 into O2, which boosts the generation of ROS and the destruction of tumor cells, resulting in the in situ antigen release and cross-presentation of tumor antigens by DCs. This in situ vaccine simultaneously promotes antigen self-presentation and cross-presentation, resulting in heightened antitumor immunity to overcome resistance.

Breaking the barrier: Nanoparticle-enhanced radiotherapy as the new vanguard in brain tumor treatment.

The pursuit of effective treatments for brain tumors has increasingly focused on the promising area of nanoparticle-enhanced radiotherapy (NERT). This review elucidates the context and significance of NERT, with a particular emphasis on its application in brain tumor therapy-a field where traditional treatments often encounter obstacles due to the blood-brain barrier (BBB) and tumor cells' inherent resistance. The aims of this review include synthesizing recent advancements, analyzing action mechanisms, and assessing the clinical potential and challenges associated with nanoparticle (NP) use in radiotherapy enhancement. Preliminary preclinical studies have established a foundation for NERT, demonstrating that nanoparticles (NPs) can serve as radiosensitizers, thereby intensifying radiotherapy's efficacy. Investigations into various NP types, such as metallic, magnetic, and polymeric, have each unveiled distinct interactions with ionizing radiation, leading to an augmented destruction of tumor cells. These interactions, encompassing physical dose enhancement and biological and chemical radio sensitization, are crucial to the NERT strategy. Although clinical studies are in their early phases, initial trials have shown promising results in terms of tumor response rates and survival, albeit with mindful consideration of toxicity profiles. This review examines pivotal studies affirming NERT's efficacy and safety. NPs have the potential to revolutionize radiotherapy by overcoming challenges in targeted delivery, reducing off-target effects, and harmonizing with other modalities. Future directions include refining NP formulations, personalizing therapies, and navigating regulatory pathways. NERT holds promise to transform brain tumor treatment and provide hope for patients.

Patient organ dose during multicycle radiation dosimetry in Lutetium −177 radionuclide therapy

Precise patient radiation dosimetry during theranostic procedures allows clinicians to tailor therapeutic procedures to each patient. Organ dose measurement aids in adjustment of the administered activity or number of treatment cycles to maximize tumor cell destruction while minimizing damage to healthy tissues. This study was aimed at quantifying patient organ doses during Lu-177 DOTATATE and Lu-177 PSMA theranostic procedures. Nine patients underwent Lu-177 radionuclide therapy, usually four cycles with 6–8 GBq administered activity per cycle. The typical dose is 7.5 GBq as a fixed activity. Using quantitative dosimetry, physicians can estimate the next dose cycle according to patient condition. The average dose per activity for critical organs were low, at 1.76, 1.96, 0.25, 0.5, and 2.43 mSv/MBq for the right kidney, left kidney, liver bladder, and spleen, respectively. The doses for the left and right kidneys, liver, urinary bladder, and spleen were lower than those in previously published studies. Wide variations were observed in patient organ doses for Lu-177 DOTATATE and Lu-177 PSMA procedures. Further studies are recommended to ensure organ safety during theransotic procedures, to minimize the radiogenic risks to healthy organs.

Newly synthesized acridone derivatives targeting lung cancer: A toxicity and xenograft model study.

AKT is one of the overexpressed targets in nonsmall cell lung cancer (NSCLC) and plays an important role in its progression and offers an attractive target for the therapy. The PI3K/AKT/mTOR pathway is upregulated in NSCLC. Acridone is an important heterocycle compound which treats cancer through various mechanisms including AKT as a target. In the present work, the study was designed to evaluate the safety profile of three acridone derivatives (AC-2, AC-7, and AC-26) by acute and repeated dose oral toxicity. In addition to this, we also checked the pAKT overexpression and its control by these derivatives in tumor xenograft model. The results from acute and repeated dose toxicity showed these compounds to be highly safe and free from any toxicity, mortality, or significant alteration in body weight, food, and water intake in the rats. In the repeated dose toxicity, compounds showed negligible variations in a few hematological parameters at 400 mg/kg. The histopathology, biochemical, and urine parameters remained unchanged. The xenograft model study demonstrated AC-2 to be inhibiting HOP-62 induced tumor via reduction in p-AKT1 (Ser473) expression significantly. In immunofluorescence staining AC-2 treated tissue section showed 2.5 fold reduction in the expression of p-AKT1 (Ser473). Histopathology studies showed the destruction of tumor cells with increased necrosis after treatment. The study concluded that AC-2 causes cell necrosis in tumor cells via blocking the p-AKT1 expression. The findings may provide a strong basis for further clinical applications of acridone derivatives in NSCLC.

Human lung cancer-derived mesenchymal stem cells promote tumor growth and immunosuppression

BackgroundThe presence of mesenchymal stem cells has been confirmed in some solid tumors where they serve as important components of the tumor microenvironment; however, their role in cancer has not been fully elucidated. The aim of this study was to investigate the functions of mesenchymal stem cells isolated from tumor tissues of patients with non-small cell lung cancer.ResultsHuman lung cancer-derived mesenchymal stem cells displayed the typical morphology and immunophenotype of mesenchymal stem cells; they were nontumorigenic and capable of undergoing multipotent differentiation. These isolated cells remarkably enhanced tumor growth when incorporated into systems alongside tumor cells in vivo. Importantly, in the presence of mesenchymal stem cells, the ability of peripheral blood mononuclear cell-derived natural killer and activated T cells to mediate tumor cell destruction was significantly compromised.ConclusionCollectively, these data support the notion that human lung cancer-derived mesenchymal stem cells protect tumor cells from immune-mediated destruction by inhibiting the antitumor activities of natural killer and T cells.

Phase II trial of vaccination with autologous, irradiated melanoma cells engineered by adenoviral mediated gene transfer to secrete granulocyte-macrophage colony stimulating factor in patients with stage III and IV melanoma.

In the era of immune checkpoint blockade, the role of cancer vaccines in immune priming has provided additional potential for therapeutic improvements. Prior studies have demonstrated delayed type hypersensitivity and anti-tumor immunity with vaccines engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF). The safety, efficacy and anti-tumor immunity of GM-CSF secreting vaccine in patients with previously treated stage III or IV melanoma needs further investigation. In this phase II trial, excised lymph node metastases were processed to single cells, transduced with an adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines were composed of 1x106, 4x106, or 1x107 tumor cells, and were injected intradermally and subcutaneously at weekly and biweekly intervals. The primary endpoints were feasibility of producing vaccine in stage III patients and determining the proportion of patients alive at two years in stage IV patients. GM-CSF vaccine was successfully developed and administered in all 61 patients. Toxicities were restricted to grade 1-2 local skin reactions. The median OS for stage III patients (n = 20) was 71.1 (95% CI, 43.7 to NR) months and 14.9 (95%CI, 12.1 to 39.7) months for stage IV patients. The median PFS in stage III patients was 50.7 (95%CI, 36.3 to NR) months and 4.1 (95% CI, 3.0-6.3) months in stage IV patients. In the overall population, the disease control rate was 39.3% (95%CI, 27.1 to 52.7%). In stage III patients, higher pre-treatment plasma cytokine levels of MMP-1, TRAIL, CXCL-11, CXCL-13 were associated with improved PFS (p<0.05 for all). An increase in post-vaccination levels of IL-15 and TRAIL for stage III patients was associated with improved PFS (p=0.03 for both). Similarly, an increase in post-vaccination IL-16 level for stage IV patients was associated with improved PFS (p=0.02) and clinical benefit. Vaccination with autologous melanoma cells secreting GM-CSF augments antitumor immunity in stage III and IV patients with melanoma, is safe, and demonstrates disease control. Luminex data suggests that changes in inflammatory cytokines and immune cell infiltration promote tumor antigen presentation and subsequent tumor cell destruction. Additional investigation to administer this vaccine in combination with immune checkpoint inhibitors is needed.

Heat shock factor 1 inhibition enhances the effects of modulated electro hyperthermia in a triple negative breast cancer mouse model

Female breast cancer is the most diagnosed cancer worldwide. Triple negative breast cancer (TNBC) is the most aggressive type and there is no existing endocrine or targeted therapy. Modulated electro-hyperthermia (mEHT) is a non-invasive complementary cancer therapy using an electromagnetic field generated by amplitude modulated 13.56 MHz frequency that induces tumor cell destruction. However, we have demonstrated a strong induction of the heat shock response (HSR) by mEHT, which can result in thermotolerance. We hypothesized that inhibition of the heat shock factor 1 (HSF1) can synergize with mEHT and enhance tumor cell-killing. Thus, we either knocked down the HSF1 gene with a CRISPR/Cas9 lentiviral construct or inhibited HSF1 with a specific small molecule inhibitor: KRIBB11 in vivo. Wild type or HSF1-knockdown 4T1 TNBC cells were inoculated into the mammary gland’s fat pad of BALB/c mice. Four mEHT treatments were performed every second day and the tumor growth was followed by ultrasound and caliper. KRIBB11 was administrated intraperitoneally at 50 mg/kg daily for 8 days. HSF1 and Hsp70 expression were assessed. HSF1 knockdown sensitized transduced cancer cells to mEHT and reduced tumor growth. HSF1 mRNA expression was significantly reduced in the KO group when compared to the empty vector group, and consequently mEHT-induced Hsp70 mRNA upregulation diminished in the KO group. Immunohistochemistry (IHC) confirmed the inhibition of Hsp70 upregulation in mEHT HSF1-KO group. Demonstrating the translational potential of HSF1 inhibition, combined therapy of mEHT with KRIBB11 significantly reduced tumor mass compared to either monotherapy. Inhibition of Hsp70 upregulation by mEHT was also supported by qPCR and IHC. In conclusion, we suggest that mEHT-therapy combined with HSF1 inhibition can be a possible new strategy of TNBC treatment with great translational potential.

Abstract 2679: Myeloid olfactory receptors in melanoma

Abstract Olfactory receptors are commonly found in the nasal cavity and function to detectodorants. However, very recent studies have determined that innate immune cells,including monocytes and macrophages, express olfactory receptors. OLFR2 (OR6A2 inhumans), was recently linked to atherosclerosis development through interaction with itsligand, octanal. Increased levels of octanal are considered as a risk factor foratherosclerosis. Conversely, octanal levels are associated with lower cancer incidence,suggesting that OLFR2 may play a protective role in cancer. Indeed, data from TheCancer Genome Atlas for liver and brain cancers show that OLFR2 expression isassociated with increased patient survival. Here, we utilized an orthotopic melanomamouse model using B16 cancer cells in C57/BL6 mice that had been transplanted witheither wild type or OLFR2 knockout bone marrow to directly test the role of OLFR2 onimmune cells in regulating tumor growth. We found that hematopoietic deletion of OLFR2exacerbated melanoma tumor growth in these mice; again, supporting the notion thatOLFR2 is anti-tumoral. The OLFR2+ cells present in the tumor were myeloid cells.Monocytes, non-classical monocytes specifically, function to detect cancer cells in tumorseeding sites, and recruit NK cells for tumor cell destruction. OLFR2-deficientmacrophages were found to migrate less to tumor cells in an in vitro assay, suggestingthat OLFR2 is involved in the sensing of newly seeding tumor cells, likely through sensingoctanal. Studies are ongoing to determine the exact functions of OLFR2+ monocytes andmacrophages in the tumor microenvironment. OLFR2 may be one of several olfactoryreceptors that is utilized by myeloid cells as a defense mechanism for detection of newlyseeding or metastatic tumor cells. As olfactory receptors are easily druggable targets,understanding their role in cancer prevention could lead to emerging newimmunotherapies for cancer. Citation Format: Elayne M. Benson, Klaus Ley, Marco Orecchioni, Catherine C. Hedrick. Myeloid olfactory receptors in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2679.

Toxicity Assessment of New Ag-ZnO/AgO Nanocomposites: An In Vitro and In Vivo Approach.

Zinc oxide nanoparticles (ZnO NPs) are metal oxide nanomaterials, which are important for several applications: antibacterial, anthelmintic, antiprotozoal and antitumoral, among others. These applications are mainly related to the ability to spontaneously produce and induce the production of reactive oxygen species that are important components for the destruction of pathogens and tumor cells. While trying to potentiate ZnO NPs, studies have associated these NPs with silver oxide (AgO) or silver (Ag) NPs. It has already been reported that this combination (Ag-ZnO/AgO NPs) is able to enhance the microbicidal potential. Although possessing much potential for several purposes, it is important to evaluate whether this association also poses the risk of toxicity to cells and experimental models. Therefore, this work aimed to evaluate the toxicity of various Ag-ZnO/AgO NP nanocomposites, in vitro and in vivo. Accordingly, ZnO nanocrystals and nanocomposites with various concentrations of AgO (ZnO:5Ag, ZnO:9Ag or ZnO:11Ag) were used in different cytotoxicity models: Galleria mellonella (G. mellonella), cell lines (VERO and RAW 264.7) and C57BL/6 mice. In the G. mellonella model, four concentrations were used in a single dose, with subsequent evaluation of mortality. In the case of cells, serial concentrations starting at 125 µg/mL were used, with subsequent cytotoxicity assessment. Based on the safe doses obtained in G. mellonella and cell models, the best doses were used in mice, with subsequent evaluations of weight, biochemistry as also renal and liver histopathology. It was observed that the toxicity, although low, of the nanocomposites was dependent upon the concentration of AgO used in association with ZnO NPs, both in vitro and in vivo.

Nanozymes in cancer immunotherapy: metabolic disruption and therapeutic synergy.

Over the past decade, there has been a growing emphasis on investigating the role of immunotherapy in cancer treatment. However, it faces challenges such as limited efficacy, a diminished response rate, and serious adverse effects. Nanozymes, a subset of nanomaterials, demonstrate boundless potential in cancer catalytic therapy for their tunable activity, enhanced stability, and cost-effectiveness. By selectively targeting the metabolic vulnerabilities of tumors, they can effectively intensify the destruction of tumor cells and promote the release of antigenic substances, thereby eliciting immune clearance responses and impeding tumor progression. Combined with other therapies, they synergistically enhance the efficacy of immunotherapy. Hence, a large number of metabolism-regulating nanozymes with synergistic immunotherapeutic effects have been developed. This review summarizes recent advancements in cancer immunotherapy facilitated by nanozymes, focusing on engineering nanozymes to potentiate antitumor immune responses by disturbing tumor metabolism and performing synergistic treatment. The challenges and prospects in this field are outlined. We aim to provide guidance for nanozyme-mediated immunotherapy and pave the way for achieving durable tumor eradication.

Aggregation-induced emission photosensitizer microneedles for enhanced melanoma photodynamic therapy.

The incidence and mortality rates of skin melanoma have been increasing annually. Photodynamic therapy (PDT) enables effective destruction of tumor cells while minimizing harm to normal cells. However, traditional photosensitizers (PSs) suffer from photobleaching, photodegradation and the aggregation-caused quenching (ACQ) effect, and it is challenging for light to reach the deep layers of the skin to maximize the efficacy of PSs. Herein, we developed dissolving microneedles (MNs) loaded with PSs of TPE-EPy@CB[7] through supramolecular assembly. The PSs effectively enhanced the type-I reactive oxygen species (ROS) generation capacity, with a concentration of 2 μM possessing nearly half of the tumor cell-killing ability under 10 min white light irradiation. The MNs were successfully pierced into the targeted site for precise drug delivery. Additionally, the conical structure of the MNs, as well as the lens-like structure after dissolution, facilitated the transmission of light in the subcutaneous tissue, achieving significant inhibition of tumor growth with a tumor suppression rate of 97.8% and no systemic toxicity or side effects in melanoma mice. The results demonstrated the potent melanoma inhibition and biosafety of this treatment approach, exhibiting a new and promising strategy to conquer malignant melanoma.

Stable pharmaceutical composition of cryo-protected non-pyrogenic isotonic chains of magnetosomes for efficient tumor cell destruction at 45 ± 1 °C under alternating magnetic field or ultrasound application.

We report a method to prepare biocompatible, stable, and highly pure iron oxide nano-minerals by following the steps consisting of: (i) amplifying magnetotactic bacteria in non-toxic minimal growth media; (ii) extracting magnetosomes from magnetotactic bacteria under alkaline lysis; (iii) heating magnetosomes above 400 °C to yield sterile magnetosome minerals, M-uncoated, devoid of active non-denatured bacterial organic material; (iv) coating M-uncoated with biocompatible carboxymethyl-dextran (CMD) compounds to yield stable M-CMD; (v) adding 5% sorbitol to M-CMD; and (vi) lyophilizing these mixtures, resulting in formulated nano-minerals in powder forms, designated as (M-CMD)F. The long-term stability of the final products is demonstrated by re-suspending (M-CMD)F in water after 12 months of storage, and by showing that these formulated magnetosomes have preserved their stability in suspension, chain arrangement, carbon content, surface charge, and surface composition. Furthermore, the formulation is optimized to yield an isotonic magnetosome suspension with an osmolality of between 275 and 290 mOsm kg-1 H2O upon reconstitution. On one hand, these formulated magnetosomes are fully biocompatible, i.e. sterile, non-pyrogenic, and non-cytotoxic towards 3T3, L929, and V79 healthy cells up to 1 mg mL-1 NP concentration iron. On the other hand, when they are brought into the presence of PC3-Luc prostate tumor cells and heated moderately at ∼41-46 °C for 20-30 minutes under low-intensity ultrasound or alternating magnetic field conditions, they efficiently destroy these tumor cells.

The Power of Nanovaccines in Immunotherapy of Melanoma, Lung, Breast, and Colon Cancers: A Comprehensive Review

Scientists are exploring new approaches to overcome cancer, and nanovaccines have emerged as one of the most promising tools in the fight against cancer. This review aimed to provide a thorough overview of nanovaccines as potential cancer immunotherapy agents by describing their mechanism of action and potential therapeutic implications. The growing incidence of cancer underscores the urgent need for comprehensive strategies focusing on prevention, early detection, and innovative treatment modalities to control and mitigate the impact of this widespread disease effectively. It is important to note that nanovaccines are a cutting-edge platform with a wide range of applications in immunotherapy for colon, breast, lung, melanoma, and ovarian cancers. Nanoscale formulations of tumor-specific antigens and adjuvants can initiate an efficient and targeted immune response. Research on nanovaccines involving melanoma has shown that they can trigger potent anti-tumor immune responses, which permit prolonged survival and tumor regression. Furthermore, nanovaccines have been effective in treating breast cancer since they can modulate the tumor microenvironment and stimulate the presence of cytotoxic T cells within the tumor. The nanovaccines strategy has enhanced the immune system’s recognition of tumor antigens, resulting in tumor cell destruction and effective immune recognition. There have also been studies that have utilized nanovaccines to modify the immune response of tumor cells to immune checkpoint inhibitors, thereby improving the synergistic outcomes of colon cancer treatment. Besides improving the immune response to malignancies, nanovaccines represent a transformative approach to cancer immunotherapy. The presence of compelling results across various cancer types suggests that nanovaccines are a powerful tool in cancer treatment despite further research required to optimize their design and validate their clinical applicability.

Modeling and Analysis of Cancer Electrothermic Therapy Technique Based on a Digital Arm

Background: Intramuscular hemangioma (IMH) is a diffuse growth hemangioma located in the striated muscle, which is often overlooked due to its rarity. background: Intramuscular hemangioma (IMH) is a diffuse growth hemangioma located in the striated muscle, which is often overlooked due to its rarity. Objective: This patent pertains to the integration of electroacupuncture with electrothermotherapy. By introducing electrical signals into the electroacupuncture system, electromagnetic heat is produced. This heat leads to the electrolysis and thermal destruction of tumor cells, enabling targeted and precise cancer treatment. Furthermore, the patent offers a theoretical foundation for exploring the distribution of electrical signals and the associated heat in arm muscles, ensuring accurate treatment. Material and Method: To enable subsequent experimental validation, this patent integrates human anatomy and histological structure theory. The arm's geometric structure was derived from segmentation, reconstruction, and substantiation based on a digital human image dataset. Using the COMSOL Multiphysics 5.5 software, a semi-detailed finite element model was developed for the numerical simulation of electrothermotherapy. Within a time domain setting, a carrier signal of 1 MHz and 22 V was introduced to assess the distribution of electrical signals and the associated heat in the arm muscle. Results: Electrical signals, electromagnetic heat, and tissue necrosis primarily concentrate in a spherical region within 10 mm of the exposed electroacupuncture tip, with the maximum coupling temperature reaching 250 °C at the tip. Time domain analysis revealed that the coupling temperature can rise within 1 min, sufficiently to cause complete tissue damage, with the tissue necrosis ratio reaching 100% in the same timeframe. While the coupling temperature continues to rise over time, the increment is modest. After 5 min, there is negligible temperature change, and once the tissue necrosis ratio reaches 100%, it remains consistent. Conclusion: In the precision tumor treatment system utilizing electrothermotherapy, factors, such as the magnitude of the injected electrical signal, placement of the electroacupuncture tip, and treatment duration play a crucial role in the treatment's accuracy. This model delves into the treatment of intramuscular hemangiomas using electroacupuncture electrothermotherapy from two perspectives: spatial and temporal domains. It provides a theoretical foundation for precise electrothermotherapy in cancer treatment. conclusion: In the precise tumor treatment system with electrothermotherapy, the size of the injected electrical signal, the position of the electroacupuncture tip and the treatment duration all have a significant impact on the precise treatment. This model is used to analyzes the treatment of intramuscular hemangiomas with electroacupuncture electrothermotherapy from two aspects: spatial and temporal domains, providing a theoretical basis for the precise electrothermotherapy for cancer. other: null

Intraepithelial CD8+ cytotoxic T-cells are the main component of the immune tumor microenvironment that drive prognosis in muscle-invasive bladder cancer

Abstract Introduction/Objective Quantity and the spatial relationship of individual immune cell (sub)types can provide prognostic information in muscle-invasive bladder cancer. Methods/Case Report To study the prognostic role of different immune cell subpopulations in muscle-invasive bladder cancer, we stained 521 muscle-invasive urothelial bladder carcinomas with 21 antibodies using BLEACH&amp;STAIN multiplex fluorescence immunohistochemistry (mfIHC) in a tissue microarray format. A framework of neuronal networks was trained and used for image analysis. Results (if a Case Study enter NA) The identification of more than 300 different immune cell subpopulations and the characterization of their spatial relationship resulted in numerous spatial interaction patterns. 40 immune parameters showed prognostic significance in univariate analyses of which 15 were independent from pT, pN, and histologic grade. The strongest association to clinical outcome was identified for intraepithelial CD8+cytotoxic T-cells (tAUC: 0.70) compared to all other 15 independent prognosis parameters (AUC: ≤0.68, p=0.039). Deeper spatial analysis revealed an increased expression levels of TIM3, CTLA-4 and PD-1 on CD8+ T cells that were located in the intraepithelial compartment. Furthermore, the cell-to-cell interaction profile of intraepithelial CD8+ T-cells was dominated by intraepithelial dendritic cells as well as intraepithelial M1-macrophages. Conclusion The intraepithelial CD8+T-cells that showed the highest expression level of TIM-3, PD-1 and CTLA-4 and were strongly interacting with M1-macrophages as well as dendritic cells and represented the strongest prognostic parameter in muscle-invasive bladder cancer. This can be explained by the fact that tumor cell destruction by CD8+ cytotoxic T-lymphocytes through direct cell-to-cell-contacts represents the “terminal-end-route” of anti-tumor immunity. The strongest prognostic immune-factor – intraepithelial CD8+T-cells – can be measured straightaway in routine pathology as the CD8-labelling index using conventional bright field immunohistochemistry.

Frailty Predicts Worse Outcomes in Tumor Lysis Syndrome

DISCUSSION Tumor lysis syndrome (TLS) is a potentially life-threatening complication that occurs in the setting of rapid tumor cell destruction. The Hospital Frailty Risk Score (HFRS) is a valuable tool to identify frailty in older individuals, signifying a decline in physiological reserves and coping ability due to age-related deterioration, and it has gained recognition as a crucial factor linked to adverse events, including mortality, hospitalization, and diminished functional outcomes. We aimed to assess the impact of HFRS on individuals admitted with a primary diagnosis of TLS. Using weighted data from the Nationwide Inpatient Sample (NIS) database from 2016 to 2020, we assessed the outcomes (mortality, hospital utilization, total healthcare charges, complications) of individuals admitted with a primary diagnosis of TLS stratified by the presence and absence of Frailty (determined by the combination of 109 ICD-10 codes each with a different score) (table 1). Baseline characteristics were analyzed using T-test and Chi-Square, and a multivariate regression analysis was used to estimate outcomes between races, adjusted for patient and hospital confounders. Data analysis was performed using STATA® Version 17.0/SE Software, with statistical significance set at p &amp;lt; 0.05. A total of 4,340 were admitted with a primary diagnosis of TLS from 2016 to 2020, among these, we selected 1,330 admissions aged 75 years or older; these admissions included 59% (N=785) with frailty, and 41% (N=545) without frailty. Frailty was associated with increased length of stay (adjusted mean difference (aMD) = 2.5 days, 95%CI: 1.2 - 3.8 days), and total healthcare expenditures (aMD = 22,541 U.S. dollars (USD), 95%CI: 2,175 - 42,908 USD). Pertaining to the outcomes, a 9- fold increase in the odds of mortality were noted among individuals with frailty, as opposed to those without frailty (adjusted Odds Ratio (aOR) = 8.93, 95%CI: 1.79 - 44.74). Our study depicts the significant impact of frailty on individuals hospitalized with TLS, revealing associations with elevated mortality rates, prolonged length of hospital stay, and increased healthcare costs. Considering a considerable portion of cancer patients fall within the elderly demographic and often present with multiple comorbidities, the Hospital Frailty Risk Score (HFRS) is a potential valuable tool for assessing the appropriateness of chemotherapy in conjunction with other scores like the Eastern Cooperative Oncology Group (ECOG). Moreover, the HFRS may aid in prognosticating disease outcomes, offering clinicians valuable insights to inform treatment decisions and improve patient care.

Racial Disparities in the Outcome of Tumor Lysis Sydrome (TLS) - a Five Year Population Based Analysis

DISCUSSION Tumor lysis syndrome (TLS) is a potentially life-threatening complication that occurs in the setting of rapid tumor cell destruction. While several studies have explored the risk factors and management strategies for TLS [1], the impact of racial disparities on the incidence, severity, and outcomes of this syndrome remains understudied. We aim to investigate the impact of race on the outcomes of TLS. Using weighted data from the Nationwide Inpatient Sample (NIS) database from 2016 to 2020, we assessed the outcomes (mortality, hospital utilization, total healthcare charges, complications) of individuals admitted with a primary diagnosis of TLS among races (non-Hispanic Whites, non-Hispanic Blacks, Hispanics, and Others including Native Americans, Asians, and other races/ethnicities). Baseline characteristics (table 1) were analyzed using T-test and Chi-Square, and a multivariate regression analysis was used to estimate outcomes between races, adjusted for patient and hospital confounders. Data analysis was performed using STATA® Version 17.0/SE Software, with statistical significance set at p &amp;lt; 0.05. A total of 4340 were admitted with a primary diagnosis of TLS from 2016 to 2020. Among these, Blacks were the most prevalent (46%), followed by others (34%), Hispanics and whites (33% each). There was no significant difference in comorbid conditions between races. Moreover, no significant differences in the total healthcare expenditures or length of hospital stays were found among races. Pertaining to TLS outcomes, When compared to Whites, Blacks had a statistically significant increase in mortality (OR 2.35, 95%CI: 1.14-4.87). Considering manifestations of TLS, Others (Native Americans, Asians, and other races/ethnicities) had an increased likelihood of cardiac arrest (OR 9.14, 95%CI: 1.11-75.6). No statistically significant difference between races was found for gastrointestinal (GI) bleeding, acute kidney injury (AKI) or sepsis. Our study highlights racial disparities in the outcomes of individuals hospitalized with TLS, including increased mortality in Blacks, and cardiac arrests in Others (Native Americans, Asians, and other races/ethnicities). Interestingly, there were no statistically significant differences in GI bleeding, or sepsis, which are commonly associated with increased mortality in TLS. Further investigations are warranted, particularly through prospective or retrospective studies, to elucidate the underlying factors contributing to these disparities.