Emerging immunologic approaches as cancer anti-angiogenic therapies.

Targeting tumor angiogenesis, the formation of new blood vessels supporting cancer growth and spread, has been an intense focus for therapy development. However, benefits from anti-angiogenic drugs like bevacizumab have been limited by resistance stemming from activation of compensatory pathways. Recent immunotherapy advances have sparked interest in novel immunologic approaches that can induce more durable vascular pruning and overcome limitations of existing angiogenesis inhibitors. This review comprehensively examines these emerging strategies, including modulating tumor-associated macrophages, therapeutic cancer vaccines, engineered nanobodies and T cells, anti-angiogenic cytokines/chemokines, and immunomodulatory drugs like thalidomide analogs. For each approach, the molecular mechanisms, preclinical/clinical data, and potential advantages over conventional drugs are discussed. Innovative therapeutic platforms like nanoparticle delivery systems are explored. Moreover, the importance of combining agents with distinct mechanisms to prevent resistance is evaluated. As tumors hijack angiogenesis for growth, harnessing the immune system's specificity to disrupt this process represents a promising anti-cancer strategy covered by this review.

Spatial effects of infiltrating T cells on neighbouring cancer cells and prognosis in stage III CRC patients.

Colorectal cancer (CRC) is one of the most frequently occurring cancers, but prognostic biomarkers identifying patients at risk of recurrence are still lacking. In this study, we aimed to investigate in more detail the spatial relationship between intratumoural T cells, cancer cells, and cancer cell hallmarks as prognostic biomarkers in stage III colorectal cancer patients. We conducted multiplexed imaging of 56 protein markers at single-cell resolution on resected fixed tissue from stage III CRC patients who received adjuvant 5-fluorouracil (5FU)-based chemotherapy. Images underwent segmentation for tumour, stroma, and immune cells, and cancer cell 'state' protein marker expression was quantified at a cellular level. We developed a Python package for estimation of spatial proximity, nearest neighbour analysis focusing on cancer cell-T-cell interactions at single-cell level. In our discovery cohort (Memorial Sloan Kettering samples), we processed 462 core samples (total number of cells: 1,669,228) from 221 adjuvant 5FU-treated stage III patients. The validation cohort (Huntsville Clearview Cancer Center samples) consisted of 272 samples (total number of cells: 853,398) from 98 stage III CRC patients. While there were trends for an association between the percentage of cytotoxic T cells (across the whole cancer core), it did not reach significance (discovery cohort: p = 0.07; validation cohort: p = 0.19). We next utilised our region-based nearest neighbour approach to determine the spatial relationships between cytotoxic T cells, helper T cells, and cancer cell clusters. In both cohorts, we found that shorter distance between cytotoxic T cells, T helper cells, and cancer cells was significantly associated with increased disease-free survival. An unsupervised trained model that clustered patients based on the median distance between immune cells and cancer cells, as well as protein expression profiles, successfully classified patients into low-risk and high-risk groups (discovery cohort: p = 0.01; validation cohort: p = 0.003). © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Emergent method for management of splenic artery aneurysms rupture: A case report.

INTRODUCTION AND IMPORTANCE: Although endovascular therapy is becoming more used for the treatment of splenic artery aneurysms (SAAs) instead of open surgery, there is limited information available on the emergent hybrid approach, selectively. We present our experience of hybrid therapy using an emergent endovascular balloon for inflow control and open resection. CASE PRESENTATION: A 34-year-old woman was brought to the emergency room after it was reported that she had a pseudoaneurysm in her splenic artery at a different medical facility. The patient was hemodynamically stable. Then we underwent a combination of endovascular and open procedures, using balloon proximal control and open aneurysm resection. She was discharged from hospital on the fifth postoperative day after the operation. CLINICAL DISCUSSION: There is no agreement on how to treat SAA patients. Endovascular procedures such as endovascular intervention are also being used, minimizing the risks of surgery and shortening the patient's hospital stay, but complications remain. We propose to try SAA's emergency hybrid strategy operation with a good prognosis and fewer complications. CONCLUSION: It seems that, compared to open surgery alone when endovascular procedures were impossible, elective hybrid procedures are more secure and efficient in stable patients and could make the operation easier without more dissection for proximal control of splenic artery.

Spatial Effects of Infiltrating T cells on Neighbouring Cancer Cells and Prognosis in Stage III CRC patients.

Colorectal cancer (CRC) is one of the most frequently occurring cancers, but prognostic biomarkers identifying patients at risk of recurrence are still lacking. In this study, we aimed to investigate in more detail the spatial relationship between intratumoural T cells, cancer cells, and cancer cell hallmarks, as prognostic biomarkers in stage III colorectal cancer patients. We conducted multiplexed imaging of 56 protein markers at single cell resolution on resected fixed tissue from stage III CRC patients who received adjuvant 5-fluorouracil-based chemotherapy. Images underwent segmentation for tumour, stroma and immune cells, and cancer cell 'state' protein marker expression was quantified at a cellular level. We developed a Python package for estimation of spatial proximity, nearest neighbour analysis focusing on cancer cell - T cell interactions at single-cell level. In our discovery cohort (MSK), we processed 462 core samples (total number of cells: 1,669,228) from 221 adjuvant 5FU-treated stage III patients. The validation cohort (HV) consisted of 272 samples (total number of cells: 853,398) from 98 stage III CRC patients. While there were trends for an association between percentage of cytotoxic T cells (across the whole cancer core), it did not reach significance (Discovery cohort: p = 0.07, Validation cohort: p = 0.19). We next utilized our region-based nearest neighbourhood approach to determine the spatial relationships between cytotoxic T cells, helper T cells and cancer cell clusters. In the both cohorts, we found that lower distance between cytotoxic T cells, T helper cells and cancer cells was significantly associated with increased disease-free survival. An unsupervised trained model that clustered patients based on the median distance between immune cells and cancer cells, as well as protein expression profiles, successfully classified patients into low-risk and high-risk groups (Discovery cohort: p = 0.01, Validation cohort: p = 0.003).

Superparamagnetic Iron Oxide Nanoparticles Induce Apoptosis in HT-29 Cells by Stimulating Oxidative Stress and Damaging DNA.

Nanoparticles have garnered considerable scientific attention in recent years due to their diagnostic and therapeutic applications in cancer. The purpose of this study was to determine the effect of superparamagnetic iron oxide nanoparticles (Fe3O4 MNPs) on the induction of apoptosis in human colorectal adenocarcinoma cell line (HT-29) cells. The purpose of this study was to elucidate the mechanisms of apoptosis induced by Fe3O4 MNPs following MTT assay and to determine the optimal dose of 2.5 g/mL for inducing apoptosis in HT-29 cells. In HT-29 cells, Fe3O4 MNPs increased reactive oxygen species (ROS), calcium ion (Ca2+), and DNA damage. Additionally, the Fe3O4 MNPs significantly increased caspase 3 and 9 expression and decreased Bcl-2 expression at the protein and mRNA levels when compared to the control group (P = 0.0001). Fe3O4 MNPs also induced apoptosis in cancer cells by increasing the level of (ROS) and intracellular Ca2+, followed by an increase in caspase 3 and 9 expression and a decrease in Bcl-2 expression and direct DNA damage. Fe3O4 MNPs are an appropriate choice for colon cancer treatment based on their cell toxicity and induction of apoptosis in HT29 cells.

A Comparison of the Characteristics of Cytokine Storm between Lichen Planus and Oral Squamous Cell Carcinoma.

INTRODUCTION: Lichen planus (LP) is a relatively common chronic mucocutaneous disease that affects the skin and mucous membranes, including oral mucosa. The etiology of the disease is unknown. Some evidence suggests that the immune system and inflammation may play a role in the formation and progression of lichen planus. Some authorities believe that LP is a precancerous condition. The purpose of this study was to investigate the serum levels of the inflammatory cytokines CRP, IL-1, IL-6, and TNF- in patients with oral lichen planus and oral squamous cell carcinoma (OSCC), as well as to assess the relationship between these cytokine levels and clinical symptoms. METHODS: A total of 75 subjects, with 25 in each group of oral lichen planus, healthy control, and oral squamous cell carcinoma, participated in this cross-sectional study. Serum levels of IL-1α, TNF-α, IL-6, and CRP were determined and compared. In comparison to the healthy control group, the lichen planus and oral squamous cell carcinoma groups had higher levels of CRP, IL-1α, IL-6, and TNF-α. RESULTS: We discovered that the mean mRNA and protein levels of CRP, IL-1α, IL-6, and TNF-α were significantly higher in the blood and tissue of lichen planus and OSCC patients than in normal controls. CONCLUSION: Higher levels of CRP, IL-1α, IL-6, and TNF-α may be linked to OLP and oral carcinogenesis. More research with larger groups is required.

The Effect of Thymus vulgaris on Hepatic Enzymes Activity and Apoptosis-Related Gene Expression in Streptozotocin-Induced Diabetic Rats.

Many diseases, including diabetes, are involved in the development of liver disorders through changes in the expression of genes such as apoptosis-related genes. In the present study, the effect of Thymus vulgaris (T. vulgaris) on hepatic enzyme activity and apoptosis-related gene expression in streptozotocin (STZ)-induced diabetic rats was examined. In this study, 50 adult male Wistar rats weighing approximately 200-220 g were divided into five groups. Diabetes was induced by an intraperitoneal injection of STZ (60 mg/kg). Following 18 days, all the animals in different groups were weighed and blood samples were taken from their cardiac veins. Gas chromatography-mass spectrometry (GC-MS) analysis revealed 45 different compounds in the T. vulgaris, including thymol (39.1%), p-cymene (20.63%), and γ-terpinene (14.85%). The results showed a significant increase in liver enzymes (aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)) in diabetic or STZ mice compared to the control group (healthy mice) (P < 0.0001). The levels of AST, ALT, and ALP in rats treated with 200 mg/kg and 400 mg/kg of T. vulgaris extract showed a significant decrease in these enzymes in comparison with diabetic rats (P < 0.0001). The expression of caspase 3 and 9 genes in the groups treated with thyme significantly decreased compared to diabetic mice (P < 0.0001), and the expression of B-cell lymphoma-2 (Bcl-2) in the group receiving 400 mg/kg of thyme significantly increased compared to diabetic mice (P < 0.0001). Due to its antioxidant compounds, thyme improves the liver tissue cells in STZ-induced diabetic mice by reducing caspases 3 and 9 as well as increasing Bcl-2.

Apoptosis Induced by Ziziphora tenuior Essential Oil in Human Colorectal Cancer Cells.

Ziziphora (Cacotti in Persian) belongs to the Lamiaceae family (mint group) and is vastly found in Iran and Asia. This traditional medicinal plant is normally used as analgesic and for treatment of particular gastrointestinal diseases. Since colorectal cancer is one of the most common causes of death in the world and the second leading cause of cancer death among adults, there is a pressing need to inhibit this malignancy by using methods with minimal side effects. One of these methods is the use of natural resources such as medical plants. This study is aimed at investigating the expression of apoptosis-related genes in the adjacent culture of colorectal cancer epithelial cells (HT-29) with Ziziphora essential oil (ZEO). The essential oil was extracted from Ziziphora leaves, and its compounds were determined and then added to the HT-29 culture medium at different concentrations. After 24 hours, the HT-29 cells were harvested from the medium and cytotoxicity was analyzed by MTT assay. After MTT assay and determination of the percentage of apoptosis by flow cytometry, RNA extraction was performed and the expression levels of Bax, Bcl-2, caspase 3 (C3), and caspase 9 (C9) were analyzed using newly designed primers by reverse transcription (RT) qPCR method and GeniX6 software. Also, specific antibodies were used for western blot analyses of those molecules. GC analysis revealed 42 different compounds in the ZEO, including pulegone (26.65%), menthone (5.74%), thymol (5.51%), and menthol (1.02%). MTT assay showed that the concentration of 200 µg/ml of ZEO had the highest HT-29 cell death during 24 hours. After incubation with the concentration of 50 µg/ml of ZEO for 24 and 48 hours, caspase 3 and 9 gene expressions in the treated group increased compared to those in the control group (P < 0.001), while the Bcl-2 expression decreased. The results showed that having anticancer compounds, ZEO can increase C3 and C9 and decrease Bcl-2 expressions, causing apoptosis in HT-29 cells in vitro. This can lead to the use of ZEO as a factor for colorectal cancer treatment.

Age dependency of the diabetes effects on the iris recognition systems performance evaluation results.

In this paper, we attempt to answer the questions whether iris recognition task under the influence of diabetes would be more difficult and whether the effects of diabetes and individuals' age are uncorrelated. We hypothesized that the health condition of volunteers plays an important role in the performance of the iris recognition system. To confirm the obtained results, we reported the distribution of usable area in each subgroup to have a more comprehensive analysis of diabetes effects. There is no conducted study to investigate for which age group (young or old) the diabetes effect is more acute on the biometric results. For this purpose, we created a new database containing 1,906 samples from 509 eyes. We applied the weighted adaptive Hough ellipsopolar transform technique and contrast-adjusted Hough transform for segmentation of iris texture, along with three different encoding algorithms. To test the hypothesis related to physiological aging effect, Welches's t-test and Kolmogorov-Smirnov test have been used to study the age-dependency of diabetes mellitus influence on the reliability of our chosen iris recognition system. Our results give some general hints related to age effect on performance of biometric systems for people with diabetes.

Iris recognition under the influence of diabetes.

In this study, iris recognition under the influence of diabetes was investigated. A new database containing 1318 pictures from 343 irides - 546 images from 162 healthy irides (62% female users, 38% male users, 21% <20 years old, 61% (20) < 40 years old, 12% (40) <60 years old and 6% more than 60 years old) and 772 iris images from 181 diabetic eyes but with a clearly visible iris pattern (80% female users, 20% male users, 1% <20 years old, 17.5% (20) <40 years old, 46.5% (40) <60 years old and 35% more than 60 years old) - were collected. All of the diabetes-affected eyes had clearly visible iris patterns without any visible impairments and only type II diabetic patients with at least 2 years of being diabetic were considered for the investigation. Three different open source iris recognition codes and one commercial software development kit were used for achieving the iris recognition system's performance evaluation results under the influence of diabetes. For statistical analysis, the t-test and the Kolmogorov-Simonov test were used.

Investigating Brain MRI Findings in Children with Headache.

OBJECTIVE: Migraine is a common headache associated with structural changes in brain. The purpose of this study was to evaluate brain MRI findings in children with migraine. MATERIALS & METHODS: This cross-sectional study was conducted at Booali Hospital, Mazandaran University of Medical Sciences, Sari, Iran. Participants with headache and age between 5 and 15 yr were evaluated with MRI and their headache type was diagnosed by the standard criteria. The findings of the MRI were interpreted by a radiologist blinded to the diagnoses. RESULTS: Overall, 81 individuals with symptom of headache and the mean age of 9.56±3.25 yr were enrolled. Twenty patients with the mean age of 9.65±2.75 yr were diagnosed with migraine without aura. Among the 54 male patients, 8 patients (14.8%) were diagnosed with migraine; and among the 27 female patients, 12 patients (44.4%) were diagnosed with migraine (RR: 1.5, 95%CI: 1.07-2.18, P=0.004). Ten migraine patients had abnormal MRI findings (50%), including 8 cases with high signal white matter lesion, and 2 cases with empty sella. The occurrence of the high signal white matter lesions was significantly greater in the migraine patients (RR: 3.91, 95% CI: 2.10-7.25, P=0.001). CONCLUSION: The possibility of occurrence of the high signal white matter lesions in the brain MRI of children with migraine was significantly higher compared with other headache types.