Structural Elucidation and Anti-Tumor Activity of a Polysaccharide (CP2-S) from Cordyceps militaris Fruit Bodies.

A polysaccharide (CP2-S), consisting of glucose with a weight average molecular weight of 5.9 × 106, was purified from the fruit bodies of Cordyceps militaris. In this work, the corresponding structure and anti-tumor activity in vivo were investigated. Methylation and NMR analysis revealed that CP2-S was composed of a →4)-α-D-Glcp-(1→ backbone with partial substitution occurring at O-6 by T-linked α-D-Glcp in every ten residues, which has not been reported in previous reports. In vivo anti-tumor experiments showed that CP2-S could inhibit the growth of Lewis lung carcinoma in mice. Tumor inhibition rates were 17.8%, 24.5%, and 29.5% at dosages of 12.5, 50, and 100 mg/kg/d, respectively. Compared with the cisplatin group, mice treated with CP2-S exhibited a significant increase in spleen index (increased 22.7-42.4%) and thymus index (increased 47.7-36.8%). Additionally, serum levels of IgM and IgG in tumor-bearing mice increased by approximately 6.11~10.75-folds and 1.31~1.38-folds, respectively. These findings prove that CP2-S significantly inhibited the growth of Lewis lung carcinoma through immune-enhancing activity in mice.

An Overview of Nanoparticle-Based Delivery Platforms for mRNA Vaccines for Treating Cancer.

With its unique properties and potential applications, nanoparticle-based delivery platforms for messenger RNA (mRNA) vaccines have gained significant attention in recent years. Nanoparticles have the advantages of enhancing immunogenicity, targeting delivery, and improving stability, providing a new solution for drug and vaccine delivery. In some clinical studies, a variety of nanoparticle delivery platforms have been gradually applied to a wide range of vaccine applications. Current research priorities are exploring various types of nanoparticles as vaccine delivery systems to enhance vaccine stability and immunogenicity. Lipid nanoparticles (LNPs) have shown promising potential in preclinical and clinical studies on the efficient delivery of antigens to immune cells. Moreover, lipid nanoparticles and other nanoparticles for nucleic acids, especially for mRNA delivery systems, have shown vast potential for vaccine development. In this review, we present various vaccine platforms with an emphasis on nanoparticles as mRNA vaccine delivery vehicles. We describe several novel nanoparticle delivery platforms for mRNA vaccines, such as lipid-, polymer-, and protein-based nanoparticles. In addition, we provide an overview of the anti-tumor immunity of nanovaccines against different tumors in cancer immunotherapy. Finally, we outline future perspectives and remaining challenges for this promising technology of nanoparticle-based delivery platforms for vaccines.

Research Progress on Flavonoids in Traditional Chinese Medicine to Counteract Cardiotoxicity Associated with Anti-Tumor Drugs.

The development of anti-tumor drugs has notably enhanced the survival rates and quality of life for patients with malignant tumors. However, the side effects of these drugs, especially cardiotoxicity, significantly limit their clinical application. The cardiotoxicity associated with anti-tumor drugs has been a subject of extensive attention and research. Traditional to mitigate these side effects have included reducing drug dosages, shortening treatment duration, modifying administration methods, and opting for drugs with lower toxicity. However, either approach may potentially compromise the anti-tumor efficacy of the medications. Therefore, exploring other effective methods for anti-cardiotoxicity will be the focus of future research. The potential of traditional Chinese medicine (TCM) in managing cardiovascular diseases and cancer treatment has gained widespread recognition. TCM is valued for its minimal side effects, affordability, and accessibility, offering promising avenues in the prevention and treatment of cardiotoxicity caused by anti-tumor drugs. Among its constituents, flavonoids, which are present in many TCMs, are particularly notable. These monomeric compounds with distinct structural components have been shown to possess both cardiovascular protective properties and anti-tumor capabilities. In this discussion, we will delve into the classification of anti-tumor drugs and explore the underlying mechanisms of their associated cardiotoxicity. Additionally, we will examine flavonoids found in TCM and investigate their mechanisms of cardiovascular protection. This will include an analysis of how these natural compounds can mitigate the cardiac side effects of anti-tumor therapies while potentially enhancing overall patient health and treatment outcomes.

Establishment and Application of Novel Hypoxia-driven Dual-reporter Model to Investigate Hypoxic Impact on Radiation Sensitivity in Human Nasopharyngeal Carcinoma Xenografts.

Background: Tumor hypoxia has been frequently detected in nasopharyngeal carcinoma (NPC) and is intently associated with therapeutic resistance. The aim of the study is to establish a clonogenically stable hypoxia-inducible dual reporter model and apply it to investigate the effect of tumor hypoxia on DNA double strand break (DSB) and synergistic effect of irradiation in combination with chemotherapy or targeted therapy. Methods: The plasmid vector consisting of hypoxia response elements to regulate HSV1-TK and GFP genes, was constructed and stably transfected into human NPC cells. The expected clone was identified and validated by in vivo and in vitro assay. DSB repair was measured by γH2AX foci formation. Tumor growth delay assay and spatial biodistribution of various biomarkers was designed to investigate the anti-tumor effect. Results: The system has the propensity of high expression of reporter genes under hypoxia and low to no expression under normoxia. Intratumoral biodistributions of GFP and classic hypoxic biomarkers were identical in poor-perfused region. Upon equilibration with 10% O2, the xenografts showed higher expression of hypoxic biomarkers. Cisplatin radiosensitized SUNE-1/HRE cells under hypoxia by suppressing DSB repair while the addition of PI3K/mTOR inhibitor further enhanced the anti-tumoral therapeutic efficacy. Combination of IR, DDP and NVP-BEZ235 exhibited most effective anti-tumor response in vivo. These observations underline the importance of dual reporter model for imaging tumor hypoxia in therapeutic study. Conclusions: Our preclinical model enables the investigation of heterogeneous tumor hypoxic regions in xenograft tissues and explores the treatment efficacy of combinations of various therapeutic approaches to overcome hypoxia.

Impact of high-salt diet in health and diseases and its role in pursuit of cancer immunotherapy by modulating gut microbiome.

Cancer chemotherapy remains an area of concern, as many of the therapies are uncomfortable involving side effects and unpleasant experiences. These factors could further reduce patient's quality of life, and even endanger their life. Many therapeutic strategies have been tried to reduce the unpleasant side effects and increase the treatment effectiveness; however, none have shown to have promising effects. One of the main hindrances to cancer therapy is the escape strategies by tumor cells to the immune attack. Promoting inflammation in the tumor microenvironment is the cornerstone and key therapeutic target in cancer chemotherapy. High-salt diet (HSD) intake, though it has deleterious effects on human health by promoting chronic inflammation, is found to be advantageous in the tumor microenvironment. Studies identified HSD favors an increased abundance of Bifidobacterium species in the tumor environment due to gut barrier alteration, which, in turn, promotes inflammation and favors improved response to cancer chemotherapy. A review of the literature was carried out to find out the effects of an HSD on health and diseases, with special mention of its effect on cancer chemotherapy. Studies emphasized HSD would block the myeloid-derived suppressor cells which will enhance the tumor immunity. Exploration of the precise mechanism of simple HSD regime/ingestion of specific bacterial species as probiotics will be effective and essential to formulate the game-changing cancer chemotherapy. With the modern era of healthcare moving toward precision medicine where the physician can choose the treatment option suitable for the individual, HSD regime/ingestion of specific bacterial species can be considered.

[Clinical efficacy and safety of blinatumomab bridging CAR-T cell therapy in the treatment of patients with adult acute B-cell lymphoblastic leukemia].

Objective: Exploring the efficacy and safety of bridging blinatumomab (BiTE) in combination with chimeric antigen receptor T (CAR-T) cell therapy for the treatment of adult patients with acute B-cell lymphoblastic leukemia (B-ALL) . Methods: Clinical data from 36 adult B-ALL patients treated at the First Affiliated Hospital of Suzhou University from August 2018 to May 2023 were retrospectively analyzed. A total of 36 cases were included: 18 men and 18 women. The median age was 43.5 years (21-72 years). Moreover, 21 cases of Philadelphia chromosome-positive acute lymphoblastic leukemia were reported, and 16 of these cases were relapsed or refractory. Eighteen patients underwent blinatumomab bridging followed by CAR-T cell therapy, and 18 patients received CAR-T cell therapy. This study analyzed the efficacy and safety of treatment in two groups of patients. Results: In the BiTE bridge-to-CAR-T group, 16 patients achieved complete remission (CR) after BiTE immunotherapy, with a CR rate of 88.9%. One month after bridging CAR-T therapy, bone marrow examination showed a CR rate of 100.0%, and the minimal residual disease (MRD) negativity rate was higher than the nonbridging therapy group (94.4% vs. 61.1%, Fisher, P=0.041). The incidence of cytokine release syndrome and other adverse reactions in the BiTE bridge-to-CAR-T group was lower than that in the nonbridging therapy group (11.1% vs. 50.0%, Fisher, P=0.027). The follow-up reveals that 13 patients continued to maintain MRD negativity, and five patients experienced relapse 8.40 months (2.57-10.20 months) after treatment. Two of five patients with relapse achieved CR after receiving the second CAR-T cell therapy. In the nonbridging therapy group, 10 patients maintained continuous MRD negativity, 7 experienced relapse, and 6 died. The 1 year overall survival rate in the BiTE bridge-to-CAR-T group was higher than that in the nonbridging therapy group, with a statistically significant difference at the 0.1 level (88.9%±10.5% vs. 66.7%±10.9%, P=0.091) . Conclusion: BiTE bridging CAR-T cell therapy demonstrates excellent efficacy in adult B-ALL treatment, with a low recent recurrence rate and ongoing assessment of long-term efficacy during follow-up.

The advancements and prospective developments in anti-tumor targeted therapy.

Cancer poses a major threat to human health worldwide. The development of anti-tumor materials provides new modalities for cancer diagnosis and treatment. In this review, we comprehensively summarize the research progress and clinical applications of anti-tumor materials. First, we introduce the etiology and pathogenesis of cancer, and the significance and challenges of anti-tumor materials research. Then, we classify anti-tumor materials and discuss their mechanisms of action. After that, we elaborate the research advances and clinical applications of anti-tumor materials, including those targeting tumor cells and therapeutic instruments. Finally, we discuss the future perspectives and challenges in the field of anti-tumor materials. This review aims to provide an overview of the current status of anti-tumor materials research and application, and to offer insights into future directions in this rapidly evolving field, which holds promise for more precise, efficient and customized treatment of cancer.

Beyond surgery: Overcoming postoperative depression in cancer patients.

Depression is a common occurrence among cancer patients, and it significantly impacts their clinical outcomes and quality of life, with a high incidence during anti-tumor treatment or after surgery. The association between surgery and depression is the result of the interaction of various factors, including physiological, psychological, and social factors, all of which are intertwined and make patients susceptible to depression after surgical treatment. Postoperative depression has a significant negative impact on many aspects of cancer patients, and it requires timely identification and intervention to improve the overall outcome.

A multifaceted role of bisphosphonates from palliative care to anti-cancer therapy in solid tumors.

INTRODUCTION: Bisphosphonates (P-C-Ps) also called diphosphonates are the structural analogs of naturally occurring pyrophosphates. Bisphosphonates are traditionally used and shown to provide long-term success in the treatment and prevention of osteoporosis and other bone loss pathologies. Furthermore, bisphosphonates are gaining popularity in the present era of cancer therapeutics and prevention. The usage of bisphosphonates as adjuvant or neoadjuvant therapy, either as a single agent or combined with other chemotherapy, has been studied in different solid tumors. This review aims to present the various roles of bisphosphonates in solid tumors. DATA SOURCES: Articles in MEDLINE/PubMed and the National Institutes of Health Clinical Trials Registry (http://www. Clinicaltrials.gov) between 1 January 2011 and 1 February 2022 were extracted using MeSH terms "bisphosphonates/diphosphosphonates and mechanism," "bisphosphonates and breast cancer," "bisphosphonates and prostate cancer," "bisphosphonates and lung cancer," "bisphosphonates and cancer risk," and "bisphosphonates and adverse events." Manual searches of some major oncology journals were also conducted. DISCUSSION: This review article focuses on the antitumor activity of bisphosphonates, safety profile, and the role of bisphosphonates as preventive, neoadjuvant, and adjuvant chemotherapy. A significant improvement in overall survival and cancer-specific survival and recurrence-free survival with the usage of bisphosphonates is noted in breast cancer patients, particularly in post-menopausal women. Though great progress has been achieved in over 20 years, further research is needed to identify the subgroup of patients that are most likely to benefit from adjuvant bisphosphonate therapy and to determine regimens with greater efficacy and better safety profile.

Discovering novel derivatives of STAT3 and HDAC inhibitors with anti-tumor activity.

In modern cancer therapy, blockage of more than one target is a standard approach, and there are already many dual-target drugs that can achieve multiple inhibition through a single molecule. Herein, we designed and synthesized a series of novel derivatives with signal transducer and activator of transcription 3 (STAT3) and histone deacetylase (HDAC) inhibitory activity through strategy of combining pharmacophore based on the STAT3 inhibitor E28 and HDAC inhibitor MS-275. Among them, compound 24 (IC50 = 8.22 ± 0.27 µM) showed better anti-tumor activity than the clinical Class I HDAC inhibitor MS-275 (IC50 = 14.65 ± 0.24 µM) in MCF-7 breast cancer cells. Furthermore, the dual inhibition to HDAC and STAT3 of compound 24 was validated by western blot analysis. The study provides new tool compounds for further exploration of STAT3-HDAC pathway inhibitor achieved with a single molecule.

Pomegranate seeds: a comprehensive review of traditional uses, chemical composition, and pharmacological properties.

Pomegranate seeds (PS) are the dried seeds derived from pomegranate fruit, accounting for approximately 20% of the fruit's total weight, and are a by-product of pomegranate juice extraction. These seeds hold significance in traditional medicine among Uyghurs and Tibetan cultures, featuring diverse clinical applications within traditional Chinese medicine. These applications include management of gastric coldness and acidity, abdominal distension, liver and gallbladder fever, and pediatric enteritis. PS demonstrates properties such as stomach tonicity, qi regulation, analgesia, and anti-inflammatory effects. Extensive research underscores the richness of PS in various phytochemical compounds and metabolites, notably unsaturated fatty acids (particularly linolenic acid and linoleic acid), phenolic compounds tocopherols, proteins, and volatile oils. Notably, among these bioactive compounds, punicic acid (PA), found within PS, demonstrates potential in the prevention and treatment of cancers, diabetes, obesity, and other ailments. Despite extensive literature on pomegranate as a botanical entity, a comprehensive review focusing specifically on the chemical composition and pharmacological effects of PS remains elusive. Therefore, this review aimed to consolidate knowledge regarding the medicinal properties of PS, summarizing its chemical composition, traditional uses, and pharmacological effects in treating various diseases, thereby laying a foundation for the advancement and application of PS in the field of pharmacology.

Differential tumor immune microenvironment coupled with tumor progression or tumor eradication in HPV-antigen expressing squamous cell carcinoma (SCC) models.

Human papilloma virus (HPV) is an etiological factor of head and neck squamous cell carcinoma (HNSCC). To investigate the role of HPV antigen in anti-tumor immunity, we established mouse models by expressing HPV16 E6 and E7 in a SCC tumor cell line. We obtained two HPV antigen-expressing clones (C-225 and C-100) transplantable into C57BL/6 recipients. We found that C-225 elicited complete eradication in C57BL/6 mice (eradicated), whereas C-100 grew progressively (growing). We examined immune tumor microenvironment (TME) using flow cytometry and found that eradicated or growing tumors exhibited differential immune profiles that may influence the outcome of anti-tumor immunity. Surprisingly, the percentage of CD8 and CD4 tumor-infiltrating lymphocytes (TILs) was much higher in growing (C-100) than eradicated (C-225) tumor. However, the TILs upregulated PD-1 and LAG-3 more potently and exhibited impaired effector functions in growing tumor compared to their counterparts in eradicated tumor. C-225 TME is highly enriched with myeloid cells, especially polymorphonuclear (PMN) myeloid-derived suppressor cells (MDSC), whereas the percentage of M-MDSC and tumor-associated macrophages (TAMs) was much higher in C-100 TME, especially M2-TAMs (CD206+). The complete eradication of C-225 depended on CD8 T cells and elicited anti-tumor memory responses upon secondary tumor challenge. We employed DNA sequencing to identify differences in the T cell receptor of peripheral blood lymphocytes pre- and post-secondary tumor challenge. Lastly, C-225 and C-100 tumor lines harbored different somatic mutations. Overall, we uncovered differential immune TME that may underlie the divergent outcomes of anti-tumor immunity by establishing two SCC tumor lines, both of which express HPV16 E6 and E7 antigens. Our experimental models may provide a platform for pinpointing tumor-intrinsic versus host-intrinsic differences in orchestrating an immunosuppressive TME in HNSCCs and for identifying new targets that render tumor cells vulnerable to immune attack.

Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor.

The gut microbiome significantly influences immune responses and the efficacy of immune checkpoint inhibitors. We conducted a clinical trial (NCT04264975) combining an anti-programmed death-1 (PD-1) inhibitor with fecal microbiota transplantation (FMT) from anti-PD-1 responder in 13 patients with anti-PD-1-refractory advanced solid cancers. FMT induced sustained microbiota changes and clinical benefits in 6 of 13 patients, with 1 partial response and 5 stable diseases, achieving an objective response rate of 7.7% and a disease control rate of 46.2%. The clinical response correlates with increased cytotoxic T cells and immune cytokines in blood and tumors. We isolated Prevotella merdae Immunoactis from a responder to FMT, which stimulates T cell activity and suppresses tumor growth in mice by enhancing cytotoxic T cell infiltration. Additionally, we found Lactobacillus salivarius and Bacteroides plebeius may inhibit anti-tumor immunity. Our findings suggest that FMT with beneficial microbiota can overcome resistance to anti-PD-1 inhibitors in advanced solid cancers, especially gastrointestinal cancers.

A Comparative Analysis of the Anti-Tumor Activity of Sixteen Polysaccharide Fractions from Three Large Brown Seaweed, Sargassum horneri, Scytosiphon lomentaria, and Undaria pinnatifida.

Searching for natural products with anti-tumor activity is an important aspect of cancer research. Seaweed polysaccharides from brown seaweed have shown promising anti-tumor activity; however, their structure, composition, and biological activity vary considerably, depending on many factors. In this study, 16 polysaccharide fractions were extracted and purified from three large brown seaweed species (Sargassum horneri, Scytosiphon lomentaria, and Undaria pinnatifida). The chemical composition analysis revealed that the polysaccharide fractions have varying molecular weights ranging from 8.889 to 729.67 kDa, and sulfate contents ranging from 0.50% to 10.77%. Additionally, they exhibit different monosaccharide compositions and secondary structures. Subsequently, their anti-tumor activity was compared against five tumor cell lines (A549, B16, HeLa, HepG2, and SH-SY5Y). The results showed that different fractions exhibited distinct anti-tumor properties against tumor cells. Flow cytometry and cytoplasmic fluorescence staining (Hoechst/AO staining) further confirmed that these effective fractions significantly induce tumor cell apoptosis without cytotoxicity. qRT-RCR results demonstrated that the polysaccharide fractions up-regulated the expression of Caspase-3, Caspase-8, Caspase-9, and Bax while down-regulating the expression of Bcl-2 and CDK-2. This study comprehensively compared the anti-tumor activity of polysaccharide fractions from large brown seaweed, providing valuable insights into the potent combinations of brown seaweed polysaccharides as anti-tumor agents.

Diagnostic and prognostic value of independent and combined detection of computed tomography, ultrasound, and positron emission tomography - computed tomography in lymphoma.

Lymphoma is a malignant tumor originating from the lymphopoietic system, which can affect all tissues and organs of the body. Lymphoma is highly heterogeneous and the therapeutic effect varies greatly. Different pathological types and stages of lymphoma differ greatly in terms of treatment intensity and prognosis. Early diagnosis of lymphoma is very important to improve the prognosis of patients. Therefore, this work explored the diagnostic value of independent and combined detection of computed tomography (CT), ultrasound, and positron emission tomography - computed tomography (PET-CT) for lymphoma. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in the PET-CT and combination groups were greatly higher than those in the CT and ultrasound groups, showing obvious differences (P < 0.05). The area under curve (AUC) values in the CT group, ultrasound group, PET-CT group, and combination group were 0.632 (P = 0.032), 0.614 (P = 0.025), 0.793 (P = 0.002), and 0.859 (P = 0.001), respectively, exhibiting observable differences (P < 0.05). the sensitivity and specificity of PET/CT for lymphoma were higher than those of CT and ultrasound, which can clearly show the early mild results of lymphatic lymphoma. Therefore, the combined diagnosis of lymphatic lymphoma with PET/CT was of high clinical value.

Molecular mechanism of co-stimulatory domains in promoting CAR-T cell anti-tumor efficacy.

Chimeric antigen receptor (CAR)-engineered T cells have been defined as 'living drug'. Adding a co-stimulatory domain (CSD) has enhanced the anti-hematological effects of CAR-T cells, thereby elevating their viability for medicinal applications. Various CSDs have helped prepare CAR-T cells to study anti-tumor efficacy. Previous studies have described and summarized the anti-tumor efficacy of CAR-T cells obtained from different CSDs. However, the underlying molecular mechanisms by which different CSDs affect CAR-T function have been rarely reported. The role of CSDs in T cells has been significantly studied, but whether they can play a unique role as a part of the CAR structure remains undetermined. Here, we summarized the effects of CSDs on CAR-T signaling pathways based on the limited references and speculated the possible mechanism depending on the specific characteristics of CAR-T cells. This review will help understand the molecular mechanism of CSDs in CAR-T cells that exert different anti-tumor effects while providing potential guidance for further interventions to enhance anti-tumor efficacy in immunotherapy.

Anti-tumor withanolides as signal transducers and activators of transcription 3 (STAT3)-inhibition from Withania obtusifolia.

The Solanaceae family and the Withania genus specifically are rich sources of medicinal plants. Liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS/MS) revealed a predominance of withanolides from an organic extract of Withania obtusifolia. A constructed molecular network uncovered the presence of potentially novel withanolides. A series of withanolides were then isolated and structurally characterized from the extract including two new withanolides (withafolia A and withafolia B) and seven previously reported metabolites. Of the isolated compounds, cytotoxicity of withanolide J, physaperuvin G, and a commercial STAT3 inhibitor (S3I-201) were assessed against a human leukemia HL-60 cell line resulting in IC50 values of 26, 29, and 120 µM, respectively. In silico molecular docking simulations indicate that withanolide J and physaperuvin G can bind as an inhibitor in the active site of STAT3 with docking scores comparable to the selective STAT3 inhibitor, S3I-201.

Hainanenin-1, an oncolytic peptide, triggers immunogenic cell death via STING activation in triple-negative breast cancer.

BACKGROUND: In triple-negative breast cancer (TNBC) therapy, insufficient tumor infiltration by lymphocytes significantly hinders the efficacy of immune checkpoint inhibitors. We have previously demonstrated that Hainanenin-1 (HN-1), a host defense peptide (HDP) identified from Hainan frog skin, induces breast cancer apoptosis and boots anti-tumor immunity via unknown mechanism. METHODS: We used in vitro experiments to observe immunogenic cell death (ICD) indicators in HN-1-treated TNBC cell lines, a mouse tumor model to verify HN-1 promotion of mice anti-tumor immune response, and an in vitro drug sensitivity test of patient-derived breast cancer cells to verify the inhibitory effect of HN-1. RESULTS: HN-1 induced ICD in TNBC in a process during which damage-associated molecular patterns (DAMPs) were released that could further increase the anti-tumor immune response. The secretion level of interleukin 2 (IL-2), IL-12, and interferon γ in the co-culture supernatant was increased, and dendritic cells (DCs) were activated via a co-culture with HN-1-pretreated TNBC cells. As a result, HN-1 increased the infiltration of anti-tumor immune cells (DCs and T lymphocytes) in the mouse model bearing both 4T1 and EMT6 tumors. Meanwhile, regulatory T cells and myeloid-derived suppressor cells were suppressed. In addition, HN-1 induced DNA damage, and double-strand DNA release in the cytosol was significantly enhanced, indicating that HN-1 might stimulate ICD via activation of STING pathway. The knockdown of STING inhibited HN-1-induced ICD. Of note, HN-1 exhibited inhibitory effects on patient-derived breast cancer cells under three-dimensional culture conditions. CONCLUSIONS: Collectively, our study demonstrated that HN-1 could be utilized as a potential compound that might augment immunotherapy effects in patients with TNBC.

Efficacy and safety of a combination anti-tumor against breast cancer in the central and south of Iraq.

OBJECTIVE: Aim: To explore efficacy and safety of combined anti-tumor treatments against breast cancer to help health professionals and decision-makers take strategies to slow the spread of breast cancer and improve women's health. PATIENTS AND METHODS: Material and Methods: A cross-sectional study was used by various Iraqi governments. The survey was conducted between July 1, 2022 and April 30, 2023. The study depended on describing studying of 100 patients in detail and with long-term follow-up who go to hospitals and take anti-cancer medications from different provinces of central and south Iraq. The questionnaire form contains 17 fields divided into three sections. The diagnosis tumor before and after treatment parameters: histopathology, CT-scan, tumor marker (Nuclear protein Ki67, Cancer antigen 153 (CA 153), human epidermal growth factor receptor 2, and carcinoembryonic antigen), renal function tests, liver function tests, and Complete Blood Count. RESULTS: Results: The use of anti-tumor medications was coupled with markedly decreased tumor cell proliferation via reduced biomarker levels of cancer (CA-15-3), HER-2, and Ki-67 levels, and decreased the mammary ductal epithelium's thickness. CONCLUSION: Conclusions: The study showed efficiency of combination medications to prevent breast cancer cell development by preventing cell growth.

Lrp10 suppresses IL7R limiting CD8 T cell homeostatic expansion and anti-tumor immunity.

Signals emanating from the T-cell receptor (TCR), co-stimulatory receptors, and cytokine receptors each influence CD8 T-cell fate. Understanding how these signals respond to homeostatic and microenvironmental cues can reveal new ways to therapeutically direct T-cell function. Through forward genetic screening in mice, we discover that loss-of-function mutations in LDL receptor-related protein 10 (Lrp10) cause naive and central memory CD8 T cells to accumulate in peripheral lymphoid organs. Lrp10 encodes a conserved cell surface protein of unknown immunological function. T-cell activation induces Lrp10 expression, which post-translationally suppresses IL7 receptor (IL7R) levels. Accordingly, Lrp10 deletion enhances T-cell homeostatic expansion through IL7R signaling. Lrp10-deficient mice are also intrinsically resistant to syngeneic tumors. This phenotype depends on dense tumor infiltration of CD8 T cells, which display increased memory cell characteristics, reduced terminal exhaustion, and augmented responses to immune checkpoint inhibition. Here, we present Lrp10 as a new negative regulator of CD8 T-cell homeostasis and a host factor that controls tumor resistance with implications for immunotherapy.