Hematological Effects Research Articles

Cardiopulmonary function, anesthetic effects, quality of arousal, hematology, and blood biochemistry during continuous intravenous infusion of a combination solution of xylazine, butorphanol, and propofol in calves.

General anesthesia in calves is easier to perform under field conditions, total intravenous anesthesia (TIVA) than using inhalation anesthesia. In the present study, cardiopulmonary function, anesthetic effects, quality of arousal, hematology, and blood biochemistry were assessed during continuous infusion of a combination solution of 0.01% xylazine, 0.001% butorphanol, and 0.2% propofol (XBP) at doses of 6 (G6; 10μg/kg/min xylazine, 1μg/kg/min butorphanol, 200μg/kg/min propofol) and 9mL/kg/h (G9; 15μg/kg/min xylazine, 1.5μg/kg/min butorphanol 300μg/kg/min propofol). For both groups, five castrated Holstein calves received intravenous injections of xylazine (0.2mg/kg) and propofol (2mg/kg), followed by a continuous infusion of XBP for 60min to maintain anesthesia. Respiratory management consisted of tracheal intubation followed by spontaneous inhalation of pure oxygen. Cardiopulmonary, anesthesia, hematology, and blood biochemistry variables were assessed at rest (baseline) and every 5 or 15min after the start of the XBP infusion. Quality of arousal was assessed based on the swallowing reflex recovery time from the stop of XBP infusion, and the sternal position time and standing time after atipamezole administration. XBP produced adequate sedation, analgesia, and muscle relaxation in all calves and maintained stable anesthesia for 60min. As XBP infusion time passed, rectal temperature and heart rate became lower, and mean arterial blood pressure increased. In both groups, hematologic and blood biochemical effects were mild. The quality of arousal was not different, and all calves were standing. The results of the present study suggested that XBP is useful for TIVA in calves.

Haematological, Renal and Gastric Effects of Ethanol Leaf Extract of Bauhinia variegate Linn

Haematological, Renal and Gastric Effects of Ethanol Leaf Extract of Bauhinia variegate Linn

Abstract PO5-20-10: Treatment with CDK4/6 Inhibitor in a Patient with Metastatic Breast Cancer Causing Myelophthisis

Abstract Background: Symptomatic bone marrow metastasis causing myelophthisis is a rare manifestation of metastatic breast cancer, indicating a poor prognosis due to significant cytopenias. CDK4/6 inhibitors are first-line therapies for metastatic hormone-positive breast cancer but remain an unclear choice in breast cancer patients with significant cytopenias due to associated hematological adverse effects. We present a case of biopsy-proven hormone-positive breast cancer with bone marrow infiltration causing profound pancytopenia. CDK4/6 inhibitors were safely administered despite their cytopenic effects. Case Presentation: A 59-year-old female presented after an abnormal annual mammogram and biopsy showed calcifications stromal fibrosis, cyst formation, and usual ductal hyperplasia in the right upper outer quadrant. One month later, she presented to an outside hospital with gingival bleeding, epistaxis, progressive dyspnea on exertion, and generalized weakness. Labs showed severe anemia with a hemoglobin of 4.8 g/dL (baseline 12.1 g/dL), thrombocytopenia with platelets of 5 K/mm (baseline 215 K/mm), LDH of 879, reticulocyte count of 5%, and negative direct Coombs test. Peripheral smear showed no schistocytes, but showed nucleated RBCs, severely reduced platelets, and occasional giant platelets. The patient was treated for presumed ITP, and the presence of nucleated RBCs prompted bone marrow biopsy which confirmed metastatic invasive lobular carcinoma breast cancer (ER 90-95%, PR 90-95%, HER2 1+). She was discharged on letrozole 2.5 mg daily with close outpatient oncologic follow-up. One week later, she presented to our institution with persistent symptomatic anemia and thrombocytopenia. Inpatient systemic therapy was begun using dose-reduced Palbociclib (75mg) and letrozole with close CBC monitoring while also receiving packed red blood cells (goal >6.5) and platelet transfusions (goal >10). Repeat bone marrow biopsy showed extensive marrow fibrosis, but no significant hematopoietic elements. ADAMTS13 was 134%, ruling out TTP, and she was treated again for presumed ITP with dexamethasone and IVIG, Throughout the 4-week admission, her right breast mass decreased in size and she was discharged after completing 3 weeks of Palbociclib with biweekly outpatient transfusions. During follow-up, the patient’s hemoglobin and platelets slowly started to respond allowing her to become transfusion-independent and allowing dose escalation. Restaging scans 2 months after hospitalization showed an overall improvement of disease burden. The patient continued to do well for almost 18 months, however, later redeveloped visceral crisis and is responding to chemotherapy. Discussion: There is limited data on the management of breast cancer with bone marrow infiltration at presentation. A wide range of survival data in different case reports exists, ranging from 5 to 44 months. However, chemotherapy was used in these studies rather than CDK4/6 inhibitors. By far, cytopenias are the most concerning grade 3 and 4 side effect of Palbociclib. Data from the PALOMA-1 trial suggest that hematologic toxicities, specifically neutropenia, were different from those associated with cytotoxic chemotherapies and are more transient and reversible in nature. Studies have examined the in vitro mechanism of bone marrow suppression in Palbociclib versus cytotoxic chemotherapy, and its cytostatic effect on neutrophil precursors allows for hematological toxicities to be transient. With strong supportive care measures, patients in bone marrow visceral crisis can be safely treated with cytopenic CDK4/6 inhibitors. Citation Format: Nikita Dahake, Jordan Senchak, Jalil Nasibli, Jason Incorvati. Treatment with CDK4/6 Inhibitor in a Patient with Metastatic Breast Cancer Causing Myelophthisis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-20-10.

Clinicopathologic Profile and Treatment Outcomes of Colorectal Cancer in Young Adults: A Multicenter Study From India.

Colorectal cancer (CRC) in young adults is a rising concern in developing countries such as India. This study investigates clinicopathologic profiles, treatment patterns, and outcomes of CRC in young adults, focusing on adolescent and young adult (AYA) CRC in a low- and middle-income country (LMIC). A retrospective registry study from January 2018 to December 2020 involved 126 young adults (age 40 years and younger) with CRC. Patient demographics, clinical features, tumor characteristics, treatment modalities, and survival outcomes were analyzed after obtaining institutional ethics committees' approval. Among 126 AYA patients, 62.70% had colon cancer and 37.30% had rectal cancer. Most patients (67%) were age 30-39 years, with no significant gender predisposition. Females had higher metastatic burden. Abdominal pain with obstruction features was common. Adenocarcinoma (65%) with signet ring differentiation (26%) suggested aggressive behavior. Limited access to molecular testing hindered mutation identification. Capecitabine-based chemotherapy was favored because of logistical constraints. Adjuvant therapy showed comparable recurrence-free survival in young adults and older patients. For localized colon cancer, the 2-year median progression-free survival was 74%, and for localized rectal cancer, it was 18 months. Palliative therapy resulted in a median overall survival of 33 months (95% CI, 18 to 47). Limited access to targeted agents affected treatment options, with only 27.5% of patients with metastatic disease receiving them. Chemotherapy was generally well tolerated, with hematologic side effect being most common. This collaborative study in an LMIC offers crucial insights into CRC in AYA patients in India. Differences in disease characteristics, treatment patterns, and limited access to targeted agents highlight the need for further research and resource allocation to improve outcomes in this population.

Hematological effects for rabbits immunized by Corynebacterium pseudotuberculosis sonicated antigen

Background: Analyzing Hematological parameters is usually in use to monitor various circumstances such as infection, inflammation and anemia. For that we studied blood parameters which are in touch with immunized laboratory animals (rabbits) after immunizing these animals with Corynebacterium pseudotuberculosis then used an adjuvant of Pseudomonas aeruginosa to stimulate the immune response cells after 2 to 3 weeks of immunization. Different concentrations were used to examine the effect on the animals’ blood parameters changing.Methods: Corynebacterium pseudotuberculosis bacterium was used at current study for evaluating the effect of immunizing laboratory rabbits with two different immune stimulators working together as adjuvant on the blood picture with the aid of 12 breed rabbits from different genders, dividing them at the base of inoculation with pre-killed and sonicated cells of bacteria (antigens) onto 4 categories as following: the group-1 members of rabbits were injected with the antigen, group-2 and group-3 included rabbits injected with the two inoculations at various concentrations; final group, group-4 was the control group.Results: Thus, white blood cells known to be our main line of defenses act firstly in our body towards different infecting microorganisms, their count always was increased through the immunization correlated with other measured parameters. From the results we can see that the lymphocytes percentage had no alteration between the infected and the immunized compared to control group, while the percentage of MID that refers to the monocytes was at the same range in both infected and the immunized control rabbit’s groups. Granulocyte cells percentage, which is including heterophilic, basophilic and eosinophilic cells, was significantly decreased (P>0.05) compared with control at all groups.Conclusion: We conclude that C. pseudotuberculosis might function as a potent immunogen to notice the complete blood picture variations.Keywords: Corynebacterium pseudotuberculosis; Pseudomonas aeruginosa; Sonicated antigen; Blood parameters; Blood picture; Adjuvant

Postoperative Hypofractionated Intensity-Modulated Radiotherapy With Concurrent Chemotherapy in Cervical Cancer

Prospective data assessing the safety of hypofractionated (40 Gy in 16 fractions) radiotherapy (RT) among patients who receive postoperative concurrent chemoradiotherapy for cervical cancer are lacking. To evaluate the acute toxic effects of hypofractionated pelvic intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy among women with cervical cancer who underwent radical hysterectomy. The POHIM-CCRT (Postoperative Hypofractionated Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy in Cervical Cancer) study was designed as a multicenter, phase 2 nonrandomized controlled trial that accrued and followed up patients from June 1, 2017, to February 28, 2023. In total, 84 patients were enrolled from 5 institutions affiliated with the Korean Radiation Oncology Group. Eligible patients experienced lymph node metastasis, parametrial invasion, or positive resection margins after radical hysterectomy for treatment of confirmed cervical cancer. Postoperative pelvic radiation using hypofractionated IMRT with 40 Gy in 16 fractions to the whole pelvis combined with concurrent chemotherapy. The primary end point was incidence of acute grade 3 or higher gastrointestinal tract, genitourinary, and hematologic toxic effects (based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) in the evaluable population during RT or within 3 months after RT completion. Of 84 patients enrolled, 5 dropped out prior to RT, and data from 79 patients were analyzed. The patients' median (IQR) age was 48 (42-58) years, and the median (IQR) tumor size was 3.7 (2.7-4.5) cm. Of these patients, 31 (39.7%) had lymph node metastasis, 4 (5.1%) had positive resection margins, and 43 (54.4%) had parametrial invasion. Grade 3 or higher acute toxic effects occurred in 2 patients (2.5% [90% CI, 0%-4.8%]). After a median (IQR) follow-up of 43.0 (21.1-59.0) months, the 3-year disease-free survival rate was 79.3%, and the overall survival rate was 98.0%. Findings from this nonrandomized control trial indicated that postoperative pelvic irradiation combined with concurrent chemotherapy using hypofractionated IMRT with 40 Gy in 16 fractions was safe and well-tolerated in women with cervical cancer. Studies assessing long-term toxic effects and oncological outcomes with longer follow-up periods are needed. ClinicalTrials.gov Identifier: NCT03239613.

Essential Oil of Piper marginatum (Piperaceae) Against Monogeneans, and Its Hematological and Histopathological Effects on Colossoma macropomum.

This study investigated the anthelmintic efficacy of therapeutic baths with the essential oil of Piper marginatum Jacq against the monogeneans Anacanthorus spathulatus Kritsky, Thatcher & Kayton, 1979, Notozothecium janauachensis Belmont-Jégu, Domingues & Laterça 2004, Mymarothecium boegeri Cohen & Kohn, 2005 and Linguadactyloides brinkmanni Thatcher & Krytsky, 1983 in Colossoma macropomum Cuvier, 1818, and its hematological and histopathological effects on this fish. Short six therapeutic baths with 100mg/L of the essential oil of P. marginatum and two control groups (water from the cultivation tank and water from the cultivation tank + 70% alcohol) were used for 20min every two days. The therapeutic baths with 100mg/L of the essential oil of P. marginatum had efficacy of 42.8% against monogeneans of C. macropomum gills. Toxicity was low for C. macropomum, because there were few physiological and histopathological changes that did not compromise the functioning of the gills of this fish. Short therapeutic baths with 100mg/L of the essential oil of P. marginatum had low efficacy for controlling monogeneans in C. macropomum and thus cannot be recommended.

Altered Haematological Parameters in Gasoline Station Workers Due to Benzene Exposure

Benzene is harmful to human health and early detection of haematological alterations is important in preventing adverse health effects. This study aimed to investigate the biomarkers of benzene exposure and its effects due to haematological alterations. Gasoline station workers with potential risks according to the biomatrix concerning benzene exposure underwent blood and urine evaluation for the biological monitoring of urinary trans, trans-muconic acid (tt-MA), and haematological and biochemical parameter evaluation. The results were analysed for correlations between biological and haematological effects. The tt-MA biomarker was detected in some workers and approximately 50% of workers had a blood profile that showed abnormal parameters with respect to the haemoglobin (Hb), haematocrit (Hct) and white blood cell parameters, which were outside the normal range. A significant correlation was observed between the tt-MA biomarker’s level and the levels of the haematological and biochemical parameters, which were Hb, Hct, eosinophil, neutrophil, SGOT and blood creatinine. The level of urinary tt-MA as a marker of benzene exposure correlated with haematological and biochemical changes in the blood, suggesting that the gasoline station workers were affected by benzene exposure. Moreover, the current study suggests that early detection of haematological abnormalities may be possible by analysing biomarkers of their effects through regular health surveillance of workers.

Evaluation of Hematological and Biochemical Effects of Kabuuti Herbal Cough Syrup: A Sub-acute Study in Wistar Rats

Herbal medicines, including Kabuuti cough syrup, have gained popularity in treating various ailments, yet their safety and efficacy require scientific scrutiny. This study aimed to evaluate the hematological and biochemical effects of Kabuuti herbal cough syrup after 28 days of oral administration in Wistar rats. The herbal extracts, containing secondary metabolites like terpenes, alkaloids, steroids, and phenols, were administered at different doses to rats, with distilled water as a control. Hematological and biochemical parameters were assessed, showing no statistically significant changes in most parameters. However, there were decreases in mean corpuscular volume (MCV) levels and lymphocyte percentage and increases in hemoglobin (HB) levels and gamma glutamyl transferase (GGT) levels observed in certain dosage groups. Despite these variations, the overall findings suggest that Kabuuti herbal cough syrup is safe for liver and kidney function in the short term, with no significant adverse effects observed. Keywords: Kabuuti Cough Herbal Preparation; Haematological Effects; Biochemical Effects; Oral Administration; Wistar Rats.

Abstract LB268: Discovery of a potent, selective and brain penetrating PARP1 inhibitor, XZP-7797

Abstract First-generation PARP1/2 inhibitors are approved for the treatment of cancers, such as ovarian, prostate, pancreas, and breast cancers, with maximal activity against tumors harboring BRCA1/2 mutation or homologous recombination deficiency (HRD). However, PARP1/2 inhibitors in clinical use have severe hematological toxicities due to the inhibition of PARP2, which has been shown to play an important role in the survival of hematopoietic progenitor cells. Furthermore, the current data indicate that synthetic lethality with BRCA mutations is primarily caused by PARP1 inhibition and trapping, whereas PARP2 inhibition and trapping are not critical for anticancer activity. Therefore, the development of selective PARP1 inhibitors is expected to reduce the hematological adverse effects associated with PARP2 inhibition while maintaining the required efficacy. XZP-7797 is a potent, selective, and brain-penetrating PARP1 inhibitor with trapping ability. In biochemical assays, XZP-7797 is more than 1000-fold selective for PARP1 over PARP2 and other members of the PARP family, including PARP3, PARP5a, PARP5b, and PARP6. XZP-7797 can significantly inhibit MDA-MB-436 cell proliferation in vitro (IC50=2.4nM). In MDA-MB-436 tumor cells, XZP-7797 inhibits PARylation and increases γH2AX level in a concentration-dependent manner. XZP-7797 demonstrates rapid tumor regression in a dose-dependent manner in the BRCA1 mutant MDA-MB-436 breast cancer xenograft model. In a pancreatic cancer xenograft model, XZP-7797 can also significantly inhibit tumor growth. To evaluate the ability of XZP-7797 to cross the blood-brain barrier, an intracranial xenograft model of breast cancer is used. The results show that XZP-7797 can significantly inhibit the growth of intracranial tumors in mice at a dose of 10 mg/kg, demonstrating the brain-penetrating ability of XZP-7797. Additionally, XZP-7797 has great PK profiles in preclinical species after oral dosing and good ADME properties. In a 14-day toxicology study of XZP-7797 in SD Rats, XZP-7797 has no hematological adverse effects at the exposure that is 10 times higher than the exposure required to achieve superior efficacy. Citation Format: Yeqing Gao, Yuqian Lu, Bo Chen, Benke Jiang, Feng Wang, Genyan Zhang, Xifeng Ma, Dapeng Zhou, Chunmin Shi, Yunling Wang, Zhipeng Liu, Jun Sun, Huimin Zhou, Mei Xu, Jiakui Li, Bin Liu. Discovery of a potent, selective and brain penetrating PARP1 inhibitor, XZP-7797 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB268.

A nationwide phase II study of delayed local treatment for children with high-risk neuroblastoma: The Japan Children's Cancer Group Neuroblastoma Committee Trial JN-H-11.

Survival rates of patients with high-risk neuroblastoma are unacceptable. A time-intensified treatment strategy with delayed local treatment to control systemic diseases has been developed in Japan. We conducted a nationwide, prospective, single-arm clinical trial with delayed local treatment. This study evaluated the safety and efficacy of delayed surgery to increase treatment intensity. Seventy-five patients with high-risk neuroblastoma were enrolled in this study between May 2011 and September 2015. Delayed local treatment consisted of five courses of induction chemotherapy (cisplatin, pirarubicin, vincristine, and cyclophosphamide) and myeloablative high-dose chemotherapy (melphalan, etoposide, and carboplatin), followed by local tumor extirpation with surgery and irradiation. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), response rate, adverse events, and surgical complications. Seventy-five patients were enrolled, and 64 were evaluable (stage 3, n=8; stage 4, n=56). The estimated 3-year PFS and OS rates (95% confidence interval [CI]) were 44.4% [31.8%-56.3%] and 80.7% [68.5%-88.5%], resspectively. The response rate of INRC after completion of the treatment protocol was 66% (42/64; 95% CI: 53%-77%; 23 CR [complete response], 10 VGPR [very good partial response], and nine PR [partial response]). None of the patients died during the protocol treatment or within 30days of completion. Grade 4 adverse effects, excluding hematological adverse effects, occurred in 48% of patients [31/64; 95% CI: 36%-61%]. Major Surgical complications were observed in 25% of patients [13/51; 95% CI: 14%-40%]. This study indicates that delayed local treatment is feasible and shows promising efficacy, suggesting that this treatment should be considered further in a comparative study of high-risk neuroblastoma.

Hematological impact of COVID-19 mRNA vaccination in patients treated with Clozapine

IntroductionClozapine is an atypical antipsychotic that is primarily prescribed for treatment-resistant schizophrenia. Despite its proven efficacy, the prescription of clozapine is sometimes limited by its hematologic side effects, including agranulocytosis. During the SARS-CoV-2 pandemic, schizophrenia is recognized as a risk factor for developing severe forms of the infection. Early and complete vaccination of patients has been recommended. However, there is limited data on the effect of the vaccine on the risk of hematologic abnormalities in patients treated with clozapine.ObjectivesTo study the hematologic effect of the mRNA vaccine against COVID-19 in a population of patients with treatment-resistant schizophrenia treated with clozapine.MethodsTwenty-five patients hospitalized for schizophrenia at the forensic psychiatry department of Razi Hospital in Manouba, Tunisia, were included. Eighteen patients were treated with clozapine, and seven patients were treated with other antipsychotics. Consent from patients and/or their relatives was obtained before vaccination. The results of complete blood counts performed as part of the therapeutic protocol were compared between the two groups before and after administration of the vaccine.ResultsNo patient experienced agranulocytosis induced by clozapine after vaccination against COVID-19.Blood cells counts,red blood cells counts,and platelets were within the normal ranges.However,a decrease in the number of WBCs,neutrophils,and lymphocytes was observed in patients treated with clozapine without significant difference compared to the patients treated with other neuroleptics, but there was no severe neutropenia or need to stop treatment.ConclusionsThe prescription of clozapine, the introduction protocol, and treatment administration have been greatly influenced by the COVID-19 pandemic due to the hepatotoxic risk of the drug. Vaccination is essential to prevent severe forms of the infection, especially in at-risk populations such as patients treated for schizophrenia.The potentiation of hematologic side effects induced by clozapine by the vaccine is not documented.The COVID-19 mRNA vaccine is safe even with clozapineDisclosure of InterestNone Declared

Specific CpG sites methylation is associated with hematotoxicity in low-dose benzene-exposed workers

Benzene is a broadly used industrial chemicals which causes various hematologic abnormalities in human. Altered DNA methylation has been proposed as epigenetic biomarkers in health risk evaluation of benzene exposure, yet the role of methylation at specific CpG sites in predicting hematological effects remains unclear. In this study, we recruited 120 low-level benzene-exposed and 101 control male workers from a petrochemical factory in Maoming City, Guangdong Province, China. Urinary S-phenylmercapturic acid (SPMA) in benzene-exposed workers was 3.40-fold higher than that in control workers (P < 0.001). Benzene-induced hematotoxicity was characterized by reduced white blood cells counts and nuclear division index (NDI), along with an increased DNA damage and urinary 8-hydroxy-2′-deoxyguanosine (all P < 0.05). Methylation levels of TRIM36, MGMT and RASSF1a genes in peripheral blood lymphocytes (PBLCs) were quantified by pyrosequencing. CpG site 6 of TRIM36, CpG site 2, 4, 6 of RASSF1a and CpG site 1, 3 of MGMT methylation were recognized as hot CpG sites due to a strong correlation with both internal exposure and hematological effects. Notably, integrating hot CpG sites methylation of multiple genes reveal a higher efficiency in prediction of integrative damage compared to individual genes at hot CpG sites. The negative dose–response relationship between the combined methylation of hot CpG sites in three genes and integrative damage enabled the classification of benzene-exposed individuals into high-risk or low-risk groups using the median cut-off value of the integrative index. Subsequently, a prediction model for integrative damage in benzene-exposed populations was built based on the methylation status of the identified hot CpG sites in the three genes. Taken together, these findings provide a novel insight into application prospect of specific CpG site methylation as epi-biomarkers for health risk assessment of environmental pollutants.

Clozapine and the Risk of Severe COVID-19: A Retrospective Cohort Study

IntroductionClozapine is the standard treatment for managing treatment-resistant schizophrenia (TRS). However, concerns arise due to potential hematologic side effects, such as agranulocytosis, especially during the COVID-19 pandemic.ObjectivesThis study aims to investigate the association between clozapine treatment and an increased risk of severe COVID-19 infection in patients with TRS.MethodsA retrospective study reviewed clinical records of forensic patients with TRS from 2020 to 2022 at Razi Hospital’s forensic psychiatry department in Tunisia. Twenty-five patients, including 18 on clozapine treatment, were included.Results All patients were male, with an average age of 39.7 years. Twenty-three patients received at least one vaccine dose. Twenty-two patients contracted COVID-19. Among those treated with clozapine, two required intensive care unit admission and oxygen therapy without intubation. Clozapine treatment remained uninterrupted, with no dose escalation during infection episodes. Lymphopenia was the most commonly reported hematologic abnormality.ConclusionsWhile there may be an association between clozapine use and an increased risk of COVID-19 infection, no clear correlation with infection severity and antipsychotic treatment was established in this study. Further research is needed to explore this potential association comprehensively.Disclosure of InterestNone Declared

In Vivo Toxicology of Metabolizable Atomically Precise Au25 Clusters at Ultrahigh Doses.

Ultrasmall Au25(MPA)18 clusters show great potential in biocatalysts and bioimaging due to their well-defined, tunable structure and properties. Hence, in vivo pharmacokinetics and toxicity of Au nanoclusters (Au NCs) are very important for clinical translation, especially at high dosages. Herein, the in vivo hematological, tissue, and neurological effects following exposure to Au NCs (300 and 500 mg kg-1) were investigated, in which the concentration is 10 times higher than in therapeutic use. The biochemical and hematological parameters of the injected Au NCs were within normal limits, even at the ultrahigh level of 500 mg kg-1. Meanwhile, no histopathological changes were observed in the Au NC group, and immunofluorescence staining showed no obvious lesions in the major organs. Furthermore, real-time near-infrared-II (NIR-II) imaging showed that most of the Au25(MPA)18 and Au24Zn1(MPA)18 can be metabolized via the kidney. The results demonstrated that Au NCs exhibit good biosafety by evaluating the manifestation of toxic effects on major organs at ultrahigh doses, providing reliable data for their application in biomedicine.

Analysis of the Role of Age Factors on Hemoglobin, Leukocyte and Platelet Levels in Breast Cancer Patients Post Chemotherapy 3 Cycles at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia

Introduction: Breast cancer is one of the most common cancers in women. Chemotherapy is one of the main modalities in the treatment of breast cancer, but it can cause hematological side effects such as anemia, leukopenia, and thrombocytopenia. Age is one factor that is thought to influence these side effects.&#x0D; Methods: This study used an analytical observational design with data collected from medical records of breast cancer patients who had undergone 3 cycles of chemotherapy at Dr. Mohammad Hoesin General Hospital Palembang. Data on hemoglobin, leukocyte, and platelet levels before and after chemotherapy were analyzed using the t-test and ANOVA.&#x0D; Results: A significant decrease in hemoglobin levels was observed in patients aged &gt; 60 years after chemotherapy (p &lt; 0.05). Leukocyte levels showed fluctuations, especially in patients aged &lt;40 years, while platelet levels fluctuated more in patients aged &lt;40 years and decreased in the age group 40-60 years after chemotherapy.&#x0D; Conclusion: Age does not significantly influence the decrease in hemoglobin, leukocyte, and platelet levels in breast cancer patients after chemotherapy.

Cardioprotective and Hematological Effects of Wonderful Kola (Buchholzia coriacea) in Wistar Rats Exposed to Aluminum Chloride-Induced Toxicity

Aluminium pervades ecosystems, posing a nuanced risk of intoxication for both animal and human cohorts. In this paper, cardioprotective and haematological effects of wonderful kola (Buchholzia coriacea) in Wistar rats exposed to aluminum chloride-induced toxicity was investigated by different methods including haematological analysis revealed significant decreases in PCV, HB, RBC, and PLT, with increased WBC in the aluminum chloride-induced group, indicating hematological toxicity (p &lt; 0.05). Vitamin C partially restored parameters, while both low and high doses of Wonderful Kola extract showed positive effects, suggesting potential protection against aluminum chloride-induced toxicity (p &lt; 0.05). Histological assessment demonstrated severe inflammation in the aluminum chloride-induced group, partial protection with vitamin C, and potential protective effects with Wonderful Kola, especially at higher doses. Wonderful Kola extract exhibited protective effects on cardiac tissue histology in aluminum chloride-induced toxicity, highlighting its potential as a therapeutic agent. These results contribute to the understanding of the potential therapeutic benefits of natural products in mitigating cardiovascular diseases. Further research on natural remedies for cardiovascular diseases is warranted, and caution should be exercised when considering treatments that may have detrimental effects on cardiac structure.

(O-21) MAJOR ADVERSE EFFECTS OF ANABOLIC STEROID USE IN TRANSGENDER MEN DURING GENDER-REAFFIRMING HORMONE THERAPY: A SYSTEMATIC REVIEW OF THE LITERATURE

Abstract Objective Gender-affirming hormone therapy for female-to-male transsexuals is based on testosterone administration. Testosterone therapy (TT) is associated with side effects such as arteriosclerosis and insulin resistance, among others. This review aims to synthesize the main findings in the literature regarding these adverse effects and identify gaps in knowledge that will guide future studies Methodology A systematic review of the literature was carried out with search strategies based on Mesh terms. The bibliographic databases PubMed, Embase, and SCOPUS were selected, and the following search algorithm was applied. We included clinical trials, meta-analyses, systematic reviews, and cohort studies. The articles were evaluated by three investigators, who initially reviewed the title and abstract and determined whether the article met the inclusion criteria. We followed the recommendations of the PRISMA statement for this process. Results The search provided a total of 93 articles (PubMed n = 61, Embase n = 2, Scopus n = 30). Four duplicates were eliminated. Finally, 22 articles met the inclusion criteria. Two studies found hematologic side effects of TT; 4 studies evidenced an increase of metabolic profile without any clinically significant side effects, 1 cohort showed an incidence of hepatic failure of 0.6% in the first year. 2 studies showed that TT was associated with endothelial disfunction and a proinflammatory state. 1 study showed an increase in body weight and lean mass and reduction in body fat. 3 studies showed that TT has no association with an increased risk of breast cancer. 1 study reported a high prevalence of acne with a highest value at 6 months post initiation of therapy. Conclusions The use of TT showed side effects on metabolic profile bases without clinically significant repercussions. Additionally, even after showing endothelial damage, no cardiovascular events were reported. Further studies are required about this topic. Figure 1. Flowchart Selection of items according to PRISMA 2020. Financing No conflict.

Abstract 5087: ILB-3101, a novel B7H3-targeting ADC with Eribulin as payload, demonstrates strong tumor killing activities and favorable PK/TOX profile in preclinical evaluation

Abstract B7H3, a B7 family member of immune checkpoint proteins, is overexpressed in a broad spectrum of malignant tumors. It has become an attractive target for cancer therapies in recent years. ILB-3101, a potential best-in-class ADC, was constructed by conjugating a potent mitotic inhibitor Eribulin to a proprietary anti-B7H3 mAb through a proprietary linker. This ADC molecule has been developed and preclinically evaluated as both the 1st line ADC treatment with B7H3 expressed patients in Eribulin sensitive cancer types and the later line treatment for patients whose cancer are B7H3 positive but TopoI inhibitor resistant. The humanized antibody of ILB-3101 is IgG1 type and shows high affinity to both human and monkey B7H3 proteins. It also shows better internalization than benchmark antibodies such as that of DS-7300 analog. The DAR value of ILB-3101 is 3.5. ILB-3101 has potent and dose-dependent cytotoxicity to B7H3-positive tumor cells and shows better activities than DS-7300 analog as positive control. In vivo studies based on xenograft tumor models reveal that ILB-3101 has potent anti-tumor activities in various tumor types including TNBC, sarcoma, ovarian cancer and AML etc., which are superior or comparable to DS-7300 analog. Furthermore, ILB-3101 shows strong anti-tumor activity on Dxd based ADC resistant tumors in xenograft tumor models. The PK study of ILB-3101 in cynomolgus monkeys shows dose-dependent exposure and desirable PK profile. ILB-3101 was well tolerated in cynomolgus monkeys with HNSTD at 6 mg/kg. No serious adverse events were observed, and the main safety findings were limited and reversible hematological and immunological effects, which are consistent with the safety profile of Eribulin as an approved chemotherapy. The in vitro and in vivo preclinical results above demonstrate that ILB-3101 has good efficacy and safety profile and it is a promising and potentially best-in-class B7H3 targeting ADC drug candidate. ILB-3101 is worthy of further translational research and clinical trials. Its IND application has been submitted in China, followed by US FDA filing soon. Citation Format: Yushuan Shang, Junzhuan Qiu, Yanfei Xin, Min Zhao, Qiang Liu, Zhengsheng Wang, Xiaojing Gong, Yan Xu, Yan Li, Mingde Xia, Rulei Chen. ILB-3101, a novel B7H3-targeting ADC with Eribulin as payload, demonstrates strong tumor killing activities and favorable PK/TOX profile in preclinical evaluation [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 5087.

Abstract 3327: L-pampo™, a TLR2/3 agonist, enhances anti-tumor immune responses and synergistically improves the anti-tumor efficacy of immune checkpoint inhibitors in cold tumors

Abstract Introduction: Immunotherapy is a promising therapeutic approach for a wide range of cancers. However, some tumors called "cold tumors" lack infiltrating T-cells and are not responsive to immune checkpoint inhibitors (ICIs), leading to worse clinical outcomes. This study demonstrates that L-pampo, a novel TLR2/3 agonist, promotes an anti-tumor immune response in cold tumors. Also, combining L-pampo with ICIs can improve the anti-tumor efficacy more safely than standard-of-care (SoC) chemotherapies. Method: We utilized syngeneic tumor models using CT26 colon cancer and 4T1 triple-negative breast cancer (TNBC). L-pampo was administered alone or in combination with ICIs such as anti-PD-1 (aPD-1) and anti-CTLA-4 (aCTLA-4) antibodies to tumor-bearing mice (n=8/group). Tumor size was measured every three days, and the survival rate was monitored until day 60. On day 21 or 27 after transplantation, we analyzed the tumor weight and tumor-infiltrating immune cells. Furthermore, we assessed the respective anti-tumor efficacies and safety of L-pampo and SoC chemotherapies (FOLFOX and paclitaxel). Result: In the CT26 colon cancer model, L-pampo effectively reduced the tumor size compared to the vehicle group (83.7%). The combination of L-pampo and ICI reduced tumor size by 86.1% (with aCTLA4) and 90.5% (with aPD-1), while the ICI alone did not effectively inhibit tumor growth (aPD-1; 17.3%, aCTLA-4; 23.6%). Notably, the triple concurrent treatment with L-pampo, aPD-1 and aCTLA-4 reduced tumor size by 96.6% and induced completed tumor regression in 1 out of 8. In the 4T1 TNBC model, L-pampo reduced tumor size by 64.2% compared to the vehicle treatment, and combined treatment with L-pampo and a-PD-1 suppressed tumor growth compared to aPD-1 alone (9.6% vs. 61.5%). Additionally, L-pampo improved median overall survival in each tumor model (CT26; 25.5 vs. 35.5, 4T1; 29.5 vs. 53.5 days). To compare the anti-tumor efficacy of L-pampo and conventional cytotoxic chemotherapy, we treated tumor-bearing mice with FOLFOX or paclitaxel as SoC regimen, respectively. Compared with each chemotherapy, L-pampo revealed comparable antitumor efficacies (Tumor growth inhibition CT26; 75.6% vs. 70.6%, 4T1; 65.5% vs. 58.8%). Interestingly, L-pampo inhibited tumor growth without significant adverse effects. In contrast, conventional chemotherapies induced acute hematological side effects such as leukopenia/neutropenia/thrombocytopenia and rapid weight loss. Furthermore, L-pampo increased the active cytotoxic T-cells infiltration through antigen-presenting cells stimulation within the tumors. Conclusion: This study suggests that L-pampo, a novel TLR2/3 agonist, can be a potent anti-tumor agent, improving the anti-tumor efficacy of ICIs in cold tumors with enhanced anti-tumor immunity and minimal toxicities than conventional chemotherapies. Citation Format: Guentae Kim, Yoonki Heo, Hye Jung Kim, Sejung Park, Byung Cheol Ahn, Won Suk Lee, Chan Kim, Hong Jae Chon, Eunyoung Chun, Jung Sun Yum. L-pampo™, a TLR2/3 agonist, enhances anti-tumor immune responses and synergistically improves the anti-tumor efficacy of immune checkpoint inhibitors in cold tumors [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 3327.