Antitumor Therapy Research Articles

An innovative strategy harnessing self-activating CAR-NK cells to mitigate TGF-β1-driven immune suppression

The dysfunction of natural killer (NK) cells, mediated by transforming growth factor β1 (TGFβ1) within the tumor microenvironment, impedes antitumor therapy and contributes to poor clinical outcomes. Our study introduces self-activating chimeric antigen receptor (CAR)-NK cells that block TGFβ1 signaling by releasing a specifically designed peptide, P6, which targets mesothelin in pancreatic tumors. P6 originates from the interaction sites between TGFβ1 and TGFβ receptor 1 and effectively disrupts TGFβ1's inhibitory signaling in NK cells. Our analysis demonstrates that P6 treatment interrupts the SMAD2/3 pathway in NK cells, mitigating TGFβ1-mediated suppression of NK cell activity, thereby enhancing their metabolic function and cytotoxic response against pancreatic tumors. These CAR-NK cells exhibit potent antitumor capabilities, as evidenced in spheroid cultures with cancer-associated fibroblasts and in vivo mouse models. Our approach marks a substantial advancement in overcoming TGFβ1-mediated immune evasion, offering a promising avenue for revolutionizing cancer immunotherapy.

Readily constructed squaraine J-aggregates with an 86.0 % photothermal conversion efficiency for photothermal therapy

The development of photothermal agents with high photothermal conversion efficiency (PCE) and long absorption wavelengths is crucial for safe and effective anti-cancer treatment. However, achieving these advantages often requires precise molecular design and complex synthetic procedures. In this study, we present a simple, precise, and effective method for fabricating photothermal agents with high PCE using long wavelength excitation. This approach involves linking two electron-donating components, diphenylamine (DPA), and an electron-withdrawing squaraine (SQ), via a π-bridge thiophene (T). The resulting D-π-A-π-D structure leads to a red-shifted absorption band. Within the DTS structure, DPA functions as a molecular rotor, T serves as a coplanar backbone, and SQ promotes J aggregation. When DTS nanoparticles (NPs) are fabricated using an amphiphilic nano-carrier, the maximum absorption wavelength shifts from 701 to 803 nm. This shift is accompanied by reduced fluorescence and an exceptionally high PCE of 86.0 %. Both in vitro and in vivo assessments confirm that DTS NPs exhibit strong potential for photothermal antitumor therapy. Overall, this strategy offers a valuable framework for designing photothermal agents with clinical applications in mind, offering a simpler and more efficient approach to achieving high PCE and long absorption wavelengths.

Precision Photothermal Therapy at Mild Temperature: NIR-II Imaging-Guided, H2O2-Responsive Stealth Nanobomb.

The therapeutic efficacy of photothermal therapy (PTT) under mild temperatures (<45°C) is hindered as cancer cells can activate heat shock proteins (HSPs) to mend fever-type cellular damage swiftly. The previous attempt fabricated first-generation nanobombs (nanobomb1G) by self-assembly of polymeric NIR-II AIEgens and carbon monoxide (CO) carrier polymer mPEG(CO) to inhibit the expression of HSPs after intratumor injection. A new generation nanobomb (Stealth NanoBomb (SNB)) is developed by self-assembling small molecular NIR-II AIEgens with CO carrier polymer PLGA(CO) coated by PEG-lipid. This design allows for intravenous administration, enabling the SNB to circulate safely in the bloodstream and selectively target cancer cells. Upon accumulation in tumors, the SNB releases CO to effectively suppress HSP expression, enhancing the therapeutic efficacy of mild-temperature PTT. Compared to the previous generation, the SNB offers a safer, more stable, and more efficient CO gas/drug co-delivery system for cancer treatment. This work represents a significant advancement in PTT, providing a promising strategy for enhanced antitumor therapy with reduced systemic toxicity.

Systemic delivery of tannic acid-ferric-masked oncolytic adenovirus reprograms tumor microenvironment for improved therapeutic efficacy in glioblastoma.

Glioblastoma (GBM) represents the most aggressive primary brain tumor, and urgently requires effective treatments. Oncolytic adenovirus (OA) shows promise as a potential candidate for clinical antitumor therapy, including in the treatment of GBM. Nevertheless, the systemic delivery of OA continues to face challenges, leading to significantly compromised antitumor efficacy. In this study, we developed an innovative approach by encapsulating CXCL11-armed OA with tannic acid and Fe3+ (TA-Fe3+) to realize the systemic delivery of OA. The nanocarrier's ability to protect the OA from elimination by host immune response was evaluated in vitro and in vivo. We evaluated the antitumor effect and safety profile of OA@TA-Fe3+ in a GBM-bearing mice model. OA@TA-Fe3+ effectively safeguarded the virus from host immune clearance and extended its circulation in vivo. After targeting tumor sites, TA-Fe3+ could dissolve and release Fe3+ and OA. Fe3+-induced O2 production from H2O2 relieved the hypoxic state, and promoted OA replication, leading to a remarkable alteration of tumor immune microenvironment and enhancement in antitumor efficacy. Moreover, the systemic delivery of OA@TA-Fe3+ was safe without inflammation or organ damage. Our findings demonstrated the promising potential of systemically delivering the engineered OA for effective oncolytic virotherapy against GBM.

Polymorphic Supramolecular Therapeutic Platforms with Precise Dye/Drug Ratio to Perform Synergistic Chemo-Photo Anti-Tumor Therapy and Long-Term Immune Protection.

Malignant tumor has become one of the hellish killers threatening the health of people around the world, its diagnosis and treatment has become the concerns of public. However, the optimal therapeutic dose, undesired side-effect, and long-term immune activation werekey and bottleneck problems in tumor treatment. Herein, different batches of supramolecular therapeutic platforms, including vesicles, spherical nanoparticles, and cylindrical nanorods, with precise ratios of dye to drug (1:2) and multiple stimulus responsiveness wereconstructed by host-guest complexation between cyanine-camptothecin conjugates (IR780-CPT2) and β-cyclodextrin (β-CD) pendent hydrophilic copolymers. The reduction responsiveness, near-infrared photothermal conversion and singlet oxygen (1O2) generation performances endowed these platforms excellent cancer cells killing effect in both of in vitro cellular experiments and in vivo mice models. More importantly, without affecting the weight of mice, the maturation of dendritic cells, proliferation of T cells, up-regulation of high mobility group protein B1, and reduction of immunosuppressive regulatory T cells weredetected after employing a synergistic chemo-photo therapy, demonstrating the body's immune effect was successfully activated. Thus, during the treatment of primary tumor, the distal tumor was also inhibited. Webelieve this work could provide a distinctive way to fabricate supramolecular theranostic platforms with different morphologies and improve antitumor and antimetastasis capabilities.

Enhancing the Safety and Efficacy of Trastuzumab Emtansine (T-DM1) Through Nano-Delivery System in Breast Cancer Therapy.

Trastuzumab emtansine (T-DM1), an antibody-drug conjugate, revolutionizes breast cancer therapy by specifically delivering DM1 to human epidermal growth factor receptor 2 (HER2) overexpressing tumor cells, effectively inhibiting cell division and proliferation. While T-DM1 demonstrates superior efficacy and tolerability, T-DM1-induced thrombocytopenia remains a significant adverse event leading to treatment discontinuation. To address this issue, the study investigates the feasibility of using poly(lactic-co-glycolic acid) (PLGA)nanoparticles as a delivery vehicle to conjugate T-DM1, aiming to alleviate T-DM1-induced thrombocytopenia. The T-DM1-conjugated PLGA nanoparticles (NPs-T-DM1) reduce binding to megakaryocytes without compromising the targeting ability for HER2. Administration of NPs-T-DM1 not only significantly inhibits tumor growth but also reduces damage to megakaryocytes, inhibits T-DM1-induced thrombocytopenia, and remarkably improves the safety of antibody-conjugated drugs. This work presents a promising strategy to enhance the safety and efficacy of T-DM1 in antitumor therapy, offering significant potential for advancing clinical application in HER2-positive breast cancer patients.

Oncomatrix: Molecular Composition and Biomechanical Properties of the Extracellular Matrix in Human Tumors

The extracellular matrix is an organized three-dimensional network of protein-based molecules and other macromolecules that provide structural and biochemical support to tissues. Depending on its biochemical and structural properties, the extracellular matrix influences cell adhesion and signal transduction and, in general, can influence cell differentiation and proliferation through specific mechanisms of chemical and mechanical sensing. The development of body tissues during ontogenesis is accompanied by changes not only in cells but also in the composition and properties of the extracellular matrix. Similarly, tumor development in carcinogenesis is accompanied by a continuous change in the properties of the extracellular matrix of tumor cells, called ‘oncomatrix’, as the tumor matures, from the development of the primary focus to the stage of metastasis. In this paper, the characteristics of the composition and properties of the extracellular matrix of tumor tissues are considered, as well as changes to the composition and properties of the matrix during the evolution of the tumor and metastasis. The extracellular matrix patterns of tumor tissues can be used as biomarkers of oncological diseases as well as potential targets for promising anti-tumor therapies.

New options for treatment of chronic pain syndrome

According to the World Health Organization, 12.6 million new cases of cancer were identified in 2008. In 2022, this number reached 18.1 million cases, and it is projected to increase to 26 million in 2040. Chronic pain is defined by the International Association for the Study of Pain as pain that persists or recurs for 3 months. A similar definition is given in the International Classification of Diseases, 11th revision, which for the first time includes chronic pain as an independent category with a unique code MG30. The incidence of pain syndrome in advanced terminal or metastatic stages of cancer is 64 %, during antitumor therapy – 59 %, after successful treatment – 33 %. However, side effects from opioids significantly worsen the quality of life of patients.A new type of peptide drugs can reduce the toxic effects of drug pain therapy.

Problems and their solutions in accompanying therapy of oncological patients: regulatory and financial strategic approaches to solutions

Accompanying therapy (AT) is vital for oncological patients as it allows to alleviate complications associated with both cancer and antitumor therapy. These complications include anemia, febrile neutropenia, nausea, and chronic pain syndrome. The problem is that many patients do not receive sufficient AT because of the lack of clinical guidelines and regulations. Currently, clinical guidelines only for anemia are approved and none for the other complications. The main barriers are the absence of legislative funding of AT and impossibility to obtain medications on the outpatient basis. The system of clinical-statistical disease groups also causes difficulties with payment for medical treatment. Low cost ratios and impossibility to combine AT payment with payment for the main therapy also limit its availability.To solve these problems, separate clinical guidelines for AT should be developed, tariffs for the clinical-statistical disease groups should be revised, and coefficients of treatment complexity should be increased for wider medication coverage.

Differential chemoproteomic analysis of RRS-1 candidate molecule and molecules of several nonsteroidal anti-inflammatory drugs

Background. To plan effective and safe pharmacotherapy for inflammation and pain, it is important to evaluate the mechanisms and spectrum of action of nonsteroidal anti-inflammatory drugs (NSAIDs), including their effects on human proteome.Objective: to identify and evaluate the most significant specific differences of candidate molecule RRS-1 (N-{(Z)-2-(1-methyl-1H-indol-3-yl)-1-[(propylamino)carbonyl]vinyl}benzamide) from other NSAIDs through differential chemoreactome analysis.Materials and methods. Chemoproteomic modeling of pharmacological effects of RRS-1 molecule and a number of well-known NSAIDs (diclofenac, nimesulide, ketorolac) on human proteome was carried out on the basis of numerical prediction algorithms over the space of heterogeneous feature descriptions, developed in the topological approach to recognition by Yu.I. Zhuravlev and K.V. Rudakov scientific school.Results. Significant differences in the effects of the studied molecules were found for 1232 proteins of human proteome. The features of assessing interactions of the studied molecules with 47 target proteins, which most distinguished the effects of RRS-1 molecule from all others were identified. RRS-1 could activate adenosine and dopamine receptors, cannabinoid receptor 2 and GABAA receptor to a greater extent than other molecules. Activation of these receptors corresponded to anti-inflammatory, anti-nociceptive and neuroprotective effects. RRS-1 could preferably inhibit a number of pro-inflammatory proteins, receptor bradykinin 1, metabotropic glutamate receptor 5, matrix metalloproteinases 8, 9, 12, and blood coagulation factor X. Additionally, RRS-1 molecule showed preferable inhibition of a number of kinases targeted in antitumor and anti-inflammatory therapy. RRS-1, less than other studied molecules, interacted with the receptors of vitamin D3, thyroid hormone, acetylcholine, cannabinoids and opioids, orexin, and various metabolic enzymes, which is important in assessment of the safety of using drugs based on this molecule. RRS-1 characteristically exhibited a moderate profile of antivitamin action: the total score of vitamin and mineral loss (7.4±3.7) was significantly less in comparison to diclofenac (11.7±4.5) and was actually on the same level as nimesulide (6.9±3.7) and ketorolac (6.7±3.6).Conclusion. Chemoreactomic and chemoproteomic profiling of RRS-1 candidate molecule provided pre-experimental assessments of its efficacy and safety through modeling interactions with the human proteome.

The use of sodium-glucose cotransporter type 2 inhibitors for the treatment of chronic heart failure in cancer patients receiving cardiotoxic chemotherapy. Preliminary results.

Background. Chronic heart failure (CHF) is one of the most serious and late manifestations of cardiotoxicity during treatment with antitumor drugs in cancer patients. As of today, only 2 groups of drugs have proven significant cardioprotective effects in this category of patients: angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) and beta-blockers (BABs). Only recently has data emerged on the successful use of sodium-glucose cotransporter type 2 inhibitors (SGLT-2) in patients with CHF on anthracycline therapy.Aim. To evaluate the role of SGLT-2 inhibitors in the complex treatment of CHF in cancer patients receiving cardiotoxic chemotherapy.Methods. A prospective observational open study, including 60 patients with verified CHF who received cardiotoxic chemotherapy and dual cardioprotective therapy: ACEIs/ARBs + BABs (control group); and 56 patients who receive similar therapy with the addition of Dapagliflozin 10 mg 1 time in the morning (study group). The results were monitored after 6 months using laboratory and instrumental research methods, as well as additional control methods. Results. Troponin T, N-terminal prohormone of brain natriuretic peptide (NTproBNP) and left ventricular longitudinal strain (GLS) levels were compared in 47 patients who had completed all follow-up studies at 6 months. It was noted that the dynamics of troponin in both groups did not differ significantly (p0.753 and p0.260, respectively), and the level of NTproBNP significantly decreased in the study group by 7.8% compared to the control group (p0.006). Comparable data were obtained for GLS (a decrease in the study group by 6.5% in relative values) compared to the control group (p0.008)). 22 (46.8%) patients had CHF before the start of chemotherapy, and in 25 (53.2%) CHF arose during antitumor drug therapy. There were 17 (16%) deaths, but there were no deaths from heart failureinbothgroups.Conclusion. We believe that a decrease in the marker of heart failure and a less pronounced impairment of the longitudinal deformation of the left ventricle with the addition of SGLT-2 inhibitors to the basic therapy of CHF in cancer patients receiving cardiotoxic chemotherapy can slow down the progression of CHF.

Enzymatic TET-1 inhibition highlights different epigenetic behaviours of IL-1β and TNFα in tumour progression of OS cell lines

Osteosarcoma (OS) is the most frequent primary malignant bone tumour, whose heterogeneity represents a major challenge for common antitumour therapies. Inflammatory cytokines are known to be necessary for OS progression. Therefore, to optimise therapy, it is important to discover reliable biomarkers by identifying the mechanism generating OS and investigating the inflammatory pathways that support the undifferentiated state. In this work, we highlight the differences of epigenetic activities of IL-1β and TNFα, and the susceptibility of TET-1 enzymatic inhibition, in tumour progression of three different OS cell lines. Investigating DNA methylation of IL-6 promoter and determining its expression, we found that TET enzymatic inhibition influences proliferation induced by inflammatory cytokines in OS cell lines. Moreover, Bobcat 339 treatment blocks IL-1β epigenetic action on IL-6 promoter, while only partially those of TNFα as well as inhibits IL-1β-dependent epithelial–mesenchymal transition (EMT) process, but only partially those of TNFα. In conclusion, this work highlights that IL-1β and TNFα have different effects on DNA demethylation in OS cell lines, making DNA methylation a potential biomarker of disease. Specifically, in IL-1β treatment, TET-1 inhibition completely blocks tumour progression, while in TNFα actions, it is only partially effective. Given that these two inflammatory pathways can be therapeutic targets for treating these tumours, knowledge of their distinct epigenetic behaviours can be useful for developing precise and specific therapeutic strategies for this disease.

B-293 Enzyme linked immunosorbent assay development and full validation for the quantification of the antibody conjugated fraction of an antiFAP ADC in human serum

Abstract Background Cancer remains a global public health issue. Despite recent progress in early diagnosis and treatment strategies, development of anti-tumor therapies with reduced systemic toxicity remains a challenge. Antibody-drug conjugates (ADCs), a new, highly-potent drug class are synthesized by linking a small molecule cytotoxic drug to a tumor specific antibody, are an emerging treatment option for many cancers. Despite advances in ADCs, study of the pharmacokinetics (PK) is challenging. A complete PK profile requires at least three analytical methods to determine: conjugated antibody, total antibody, and free drug by Ligand Binding Assays (LBA) and liquid chromatography/tandem mass spectrometry (LC-MS/MS) respectively. Objective To develop and validate an ELISA method to quantify the conjugated antibody fraction of an anti-fibroblast activation protein (FAP) ADC against solid tumors in human serum. Methods Conjugated antibody assay: This indirect sandwich ELISA utilizes human FAP as capture antigen (Abcam) with a proprietary rabbit polyclonal anti-drug IgG as detection antibody. The signal is amplified by the use of a second antibody conjugated to Horse Radish Peroxidase (Abcam). Absorbance is measured at 450nm. Immunoassay method validation was done in compliance with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) M10 which establishes the limit for precision in CV% and accuracy in Relative Error (RE%) at ± 20% each (± 25% for LLOQ and ULOQ). Additionally, the total error (TE%) for accuracy and precision batches, should be ≤ 30% (≤ 40% at LLOQ and ULOQ). Results The weighted calibration curves were linear over a concentration range 0.5 to 100 µg/mL. A four-parameter regression model with a 1/Y2 weighting factor was adopted to best fit the OD450 values and concentrations. The intra- and inter-assay accuracy and precision for RE% and CV% was &amp;lt;12%, with a TE% &amp;lt; 23% for all concentrations tested. The quantification limit of 0.5 µg/mL complies with ICH criteria with a RE%, CV% and TE% of -10%, 8,5% and 15% respectively. Selectivity and specificity test fall within the criteria indicating that no individual matrix or co-medication affects the samples. The results from the dilution linearity obtained were an RE% of 11, -16 and -6 for 1:50, 1:100 and 1:200 respectively. Furthermore, not hook effect was observed as the dilution QC results gave above the quantification limit. Finally, the analyte was found to be stable at -20° and -80°for 148 days, at room temperature for 24hr and after 5 freeze/thaw cycles with a maximum RE and CV of 12 and 14% respectively in all the stability samples. Conclusions We have developed and optimized an ELISA method for measuring the antibody conjugated fraction of the ADC in serum. This method complies with the criteria of the ICH50 for selectivity, specificity, accuracy and precision, dilution linearity and hook effect in a concentration range between 0.5 - 100 µg/mL. Further, serum specimens are stable for 24h at room temperature, 5 freeze/thaw cycles and 148 days at -20 and -80 °C.

Echinacoside inhibits tumor immune evasion by downregulating inducible PD-L1 and reshaping tumor immune landscape in breast and colorectal cancer

BackgroundTargeting PD-L1 has become a crucial approach in tumor immunotherapy. Echinacoside (ECH) is a natural compound known for its extensive biological activities, its impact on antitumor immunity remains uncertain. PurposeThis work was designed to assess the effects of ECH on the PD-L1/PD-1-mediated tumor immune evasion and its underlying mechanisms. MethodsFlow cytometry and RT-qPCR were utilized to explore the influence of ECH on PD-L1 expression. Western blot was employed to examine the mechanism by which ECH might modulate PD-L1 expression. Flow cytometry was conducted to evaluate the influence of ECH therapy, or the synergistic effects of ECH combined with immune checkpoint blockade (ICB) on tumor immune microenvironment (TIME) in tumor-burden mice. Blood biochemistry tests were used to evaluate the safety of ECH treatment. ResultsECH downregulated both the protein and mRNA expression levels of IFN-γ-induced PD-L1 through JAK/STAT1/IRF1 signaling pathway. ECH treatment upregulated the infiltration of IFN-γ+ CD8+ T cells and Ki-67+ CD8+ T cells, lowered the frequency of of TIM-3+PD-1+ T cells, promoted the infiltration of effector CD4+ T cells and total CD8+ T cells while suppressed the percentage of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC). Moreover, the combination of ECH and anti-PD-1 or anti-CTLA-4 therapy exhibited synergistic anti-tumor effects, reshaping TIME. Blood biochemistry tests unveiled that ECH did not show additional toxicity. ConclusionECH upregulates the expression of inducible PD-L1 through the JAK/STAT1/IRF1 signaling pathway, enhances T cell function, and reshapes the tumor immune landscape into an anti-tumor phenotype. Importantly, ECH markedly enhances the efficacy of ICB treatment, indicating its potential application in anti-tumor therapy.

2′-Fluorinated nucleoside chemistry for new drug discovery: achievements and prospects

Abstract Fluorinated nucleosides are an important class of modified nucleosides that have demonstrated therapeutic potential for treating various human diseases, especially viral infections and cancer. Many fluorinated nucleosides have advanced into clinical trials or approved by the FDA for use in patients. Among these fluorinated nucleosides, the fluorinated nucleoside azvudine, developed by us, has been officially approved by the National Medical Products Administration (NMPA) for the treatment of coronavirus disease 2019 (COVID-19) and human immunodeficiency virus (HIV), indicating the therapeutic promise of fluorinated nucleosides. In view of the therapeutic promise of fluorinated nucleosides for antiviral and anticancer therapy, in this Review we will provide a comprehensive overview of well-established 2′-fluorinated nucleosides approved for use in the market or those in clinical stages for antiviral and antitumor therapies, highlighting the drug discovery strategies, structure-activity relationship (SAR) studies, mechanisms of actions, and preclinical/clinical studies and also discuss the challenges and future directions for nucleoside-based new drug discovery.

Redox Status and Protein Glutathionylation in Binase-Treated HPV16-Positive SiHa Carcinoma Cells

Human papillomavirus type 16 (HPV16) belongs to viruses of the high-risk type and is associated by overexpression of E6 and E7 oncoproteins, which determine the oncogenic properties of the virus, such as immortalization and malignant transformation of proliferating epithelial cells. The biogenesis of redox-sensitive proteins E6 and E7 at the early stages of viral infection leads to blocking of the cell antioxidant defense system and ubiquintin-dependent degradation of p53 and Rb tumor suppressors. Maintaining high rates of tumor cell proliferation contributes to an increase in the level of reactive oxygen species (ROS) and a shift in the redox balance towards oxidative processes. Reduced glutathione (GSH) provides antioxidant protection to tumor cells through S-glutathionylation of thiol groups of redox-sensitive proteins, which leads to the appearance of multidrug-resistant forms of cancer. In this regard, drugs restoring redox balance and increasing susceptibility to antitumor therapy are of particular importance. We have established that, Bacillus pumilus RNase (binase) modulates the redox-dependent regulatory mechanisms that ensure tumor cell resistance to apoptosis in HPV-16-positive SiHa cells of cervical squamous cell carcinoma,. Binase in nontoxic concentrations initiates a number of pre-apoptogenic changes, i.e., decreases ROS and reduced glutathione (GSH) levels, suppresses the expression of the E6 oncoprotein, activates the expression of the p53 tumor suppressor, and reduces the mitochondrial potential of tumor cells. Binase-induced disruption of the integrity of the mitochondrial membrane is a signal for activation of the mitochondrial apoptosis pathway.

Impact of Conventional Antitumoral Therapy on Estimated Glomerular Filtration Rate in Patients with Cancer Using Serum Creatinine and Cystatin C: A Prospective Cohort Study

Impact of Conventional Antitumoral Therapy on Estimated Glomerular Filtration Rate in Patients with Cancer Using Serum Creatinine and Cystatin C: A Prospective Cohort Study

When cancer patients encountered COVID-19: clinical characteristics and outcome in China.

Cancer patients were more likely to be affected by the coronavirus disease 2019 (COVID-19) pandemic. Therefore, we analyzed the clinical characteristics and outcomes in cancer patients who were infected with COVID-19 to determine if they were more vulnerable to COVID-19 than non-cancer patients. This retrospective study involved 150 cancer patients and 300 non-cancer patients with a laboratory-confirmed diagnosis of COVID-19 at the Cancer Hospital of the Chinese Academy of Medical Sciences, at the end of 2022. Multivariable analysis was carried out on the factors associated with COVID-19 severity in cancer patients. Compared to the non-cancer group, the cancer group saw a notably higher number of hospitalizations and fatalities. Multivariate analysis showed that COVID-19 severity was correlated with male gender (OR: 5.60, 95% CI, 1.89-16.57), and recovery duration was longer than 10 days (OR: 3.19, 95% CI, 1.09-9.32) in the cancer group. However, the severity of COVID-19 was not made worse by the administration of systemic anticancer treatments prior to the outbreak. During the COVID-19 Omicron epidemic, there seemed to be some association between various antitumor therapies, treatment intervals, and COVID-19 severity. The findings of this study can potentially help allay cancer patients` fears regarding COVID-19 infection and enable them to continue with crucial therapeutic processes for the treatment of cancer.

The Impact of Antitumor Treatment on Cancer Patients with COVID-19: A Systematic Review and Meta-Analysis

Background: Cancer is a chronic disease that can cause various complications, decrease the immune system, reduce quality of life, and even lead to death. In addition, the COVID-19 pandemic in various countries has had a significant adverse impact on patients. This study analyzed the impact of various antitumor treatments on cancer patients with COVID-19. Methods: This meta-analysis was conducted according to the PRISMA – P pathway. Source searches were conducted in PubMed, Cochrane Library, Research Gate, and Science Direct in cancer patients with COVID-19 receiving various types of antitumor treatment. Analysis was performed using RevMan V.5.3 software with the outcome of mortality rate and severe COVID-19. Results: Twenty-five observational studies met the inclusion criteria with a total of 21,940 patients. There was no significant difference in mortality rate (OR 1.08, 95% CI 0.99 – 1.18, p = 0.09), but there was a significant difference in severe COVID-19 (OR 1.19, 95% CI 1.02 – 1.39, p = 0.02). Immunotherapy provided the most significant worsening of both mortality rate (OR 1.39, 95% CI 1.17 – 1.64, p = 0.0001) and severe COVID-19 (OR 1.82, 95% CI 1.23 – 2.71, p = 0.003). There were no significant differences in other antitumor treatments. Conclusions: Antitumor treatment does not have a significant impact on mortality rate, but has a significant impact on worsening the degree of COVID-19. Among all the antitumor therapies that provide the highest potential for worsening is immunotherapy.

Assessment of Specific Biomarkers' Profile and Structural, Functional Parameters of the Left Ventricle in Patients With Lymphomas Undergoing Antitumor Therapy.

To evaluate the dynamics of specific biomarkers for cardiotoxicity, endothelial dysfunction, fibrosis, systemic inflammation, and morpho-functional alterations in the left ventricular (LV) myocardium in patients with newly diagnosed lymphomas during 6 courses of polychemotherapy (PCT). The study included 30 patients with newly diagnosed lymphomas. All patients were evaluated for laboratory markers of cardiotoxicity at baseline and after 6 courses of chemotherapy (6 months), including N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI), endothelin-1 (ET-1), circulating cardiac biomarker ST-2, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and LV structural and functional echocardiographic (EchoCG) parameters. The changes in NT-proBNP and hsTnI concentrations during 6 courses of PCT were not statistically significant. Comparison of the baseline values with those after 6 courses of PCT showed increases in the median concentrations of ET-1 (3.38 and 5.5 pg/ml, respectively; p=0.438) and ST-2 (12.21 and 26.75 ng/ml, respectively; p=0.687). Markers of systemic inflammation were significantly decreased after 6 courses of PCT: the median CRP decreased from 15.2 to 0.72 mg/ml (p=0.006), and the median IL-6 decreased from 12.2 to 5.1 pg/ml (p=0.034). EchoCG data revealed a statistically significant impairment of the LV diastolic function parameters (E/A; E/e' lateral; E/e' average; left atrial volume index; isovolumic relaxation time). A moderate direct correlation was found between the ET-1 concentration and the isovolumic relaxation time at baseline and after 6 courses of PCT, respectively (r1 = 0.387, p=0.047 and r2 = 0.391, p=0.035). No changes in the LV systolic function were observed. The study showed that patients with lymphoproliferative diseases had no signs of cardiotoxicity during PCT according to the accepted criteria. This study described and highlighted for the first time the interrelation of endothelial dysfunction, profibrotic status, and LV diastolic dysfunction as manifestations of cardiovascular toxicity in patients with lymphoproliferative diseases. It is advisable to supplement the integrated strategies for the prevention and monitoring of PCT cardiovascular toxicity with a thorough evaluation of instrumental parameters of diastolic dysfunction for timely initiation/correction of cardioprotective therapy.