Treatment Toxicity Research Articles

Chemical composition, cytotoxic potential and antioxidant properties of Punica granatum peel extract

Purpose: To evaluate the antioxidant activity of pomegranate peel extract and its effects on the survival of colorectal cancer cells (Caco-2) and kidney cells (HEK293). Methods: An ethanol extract was prepared from the outer layer of pomegranate peels. The chemical composition of the extract was examined using high-performance liquid chromatography with diodearray detection (HPLC-DAD) and liquid chromatography with tandem mass spectrometry (LC-MS-MS). Antioxidant activity was determined using DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'- azinobis(3-ethylbenzothiazoline-6-sulfonic acid)) assays. Cytotoxicity was tested against Caco-2 colorectal cancer cells and HEK293 normal kidney cells using MTT assay. Results: The pomegranate peel extract was rich in phenolic compounds and demonstrated significant antioxidant activity, with IC50 values comparable to Trolox in DPPH and ABTS assays. The extract exhibited selective and concentration-dependent cytotoxicity against Caco-2 cells, with an EC50 of 121.05 ± 13.12 µg/mL, while showing minimal toxicity towards HEK293 cells. Conclusion: Pomegranate peel extract's high phenolic content and potent antioxidant properties highlight its potential as a therapeutic agent against colorectal cancer. The findings suggest that this extract could serve as a viable, natural alternative with reduced toxicity for colorectal cancer treatment.

Contribution of Shankar Nighantu w.r.t. Vishahara Dravyas: A Review

Toxicity, which may be intentional, unintentional or accidental, is a grave problem throughout the world from ages. Advancements in the literature of Ayurveda address this problem by including the various treatments of toxicities, where Shankar Nighantu is one of them. Shankar Nighantu is a modern lexicon in Ayurvedic Materia Medica, originating in the 20th century and written by Shankar datta Gauda in the Hindi language. This lexicon based on Ayurvedic and Unani references, constructed in Hindi alphabetical order, is in three parts and contains vast information about the botanical characteristics, medicinal properties, and therapeutic indications of numerous plants, animals, and their products, as well as metals and minerals, aiding in the effective practice of this ancient healing tradition in contemporary times. Various Vishahara dravyas (Antivenom or Anti-toxic properties or Anti-poisonous drugs) are also listed highlighting the significance of toxicity treatment. Vishahara dravyas are elements that can prevent and eliminate toxins or poisons from the body. These elements play a crucial role in Ayurveda, which emphasises the importance of detoxification for maintaining health and treating diseases. Unani dravyas that are referred from ‘Makhjan’, are also mentioned as a unique entity as Vishahara property in this Nighantu. This Nighantu also includes various drugs used as folklore medicine. The author indicates various single drug as well as compound formulations to be used as antitoxic. Chuk, Hatthajodi, Chumbak patthar (Magnetic stone) are a few controversial and unexplored drugs that need further research for its antitoxic properties. This literary review aims to focus on the data found in Shankar Nighantu regarding various antitoxic drugs that is Vishahara dravyas. It will assist researchers and medical practitioners in gaining better insight about principle of treatment of toxicity.

8035 Severe Hyperglycemia Induced By Enfortumab Vedotin (EV) Treatment For Urothelial Carcinoma

Abstract Disclosure: N. Semreen: None. M.D. Goldberg: None. Introduction: Immunotherapy has revolutionized cancer treatment, but it has a wide range of adverse events including endocrinopathies. Here we present a case of severe hyperglycemia induced by enfortumab vedotin (EV) treatment for advanced urothelial carcinoma. Clinical Case: A 56-year-old male was admitted to our hospital with a painful rash in sun-exposed areas. He had metastatic urothelial carcinoma, with progression of disease after platinum-based chemotherapy, radiation therapy, and pembrolizumab, and had begun treatment with EV six weeks prior to presentation. He also had type 2 diabetes mellitus, with a recent A1c of 6.1% on metformin monotherapy, and obesity (BMI, 31 kg/m2). His blood glucose on admission was 600 mg/dL, and insulin therapy was initiated. There was no evidence for DKA or HHS. Over the course of his 9-day admission he required approximately 200 units of insulin per day to control his glucose. A fasting C-peptide level was 6.89 ng/mL (0.81-3.89 ng/mL) concurrent with a glucose of 181 mg/dL. Skin biopsy revealed erythema multiforme, which represented a grade 4 toxicity of EV treatment, and the EV was discontinued. Symptoms improved with oral glucocorticoids. The patient was discharged on multiple daily injections of insulin in addition to metformin. His insulin requirements fell rapidly, and one month later he was able to discontinue insulin completely. He was started on sacituzumab for his cancer treatment. Discussion: EV is a first-in-class antibody-drug conjugate directed against Nectin-4, which was approved in 2019 for previously treated locally advanced or metastatic urothelial carcinoma. Hyperglycemia was reported in 6.4% of patients receiving EV in the initial phase III study; BMI ≥ 30 kg/m2 and pretreatment A1c ≥ 6.5% were identified as risk factors. In a 24-month follow-up analysis, the incidence of grade ≥ 3 hyperglycemia was 4.4%, and the median time to onset of hyperglycemia was 19 days. There have been postmarketing reports of EV-induced DKA, as well as cases of refractory hyperglycemia requiring more than 1,000 units of insulin daily. The mechanism explaining the hyperglycemia is not yet defined, but in the prior case reports, as well as the current case, C-peptide levels have been elevated. It is assumed, therefore, that the mechanism involves insulin resistance as opposed to insulin deficiency. The marked hyperglycemia appears to be reversible once EV therapy is discontinued. In 2023, EV was approved in combination with pembrolizumab for first-line therapy of locally advanced or metastatic urothelial cancer, as an alternative to platinum-based chemotherapy. With this expanded indication, providers should be aware of the risk of hyperglycemia, which in some cases may be severe. Presentation: 6/3/2024

B-221 Combined RT-PCR and Whole Exome Sequencing Pharmacogenetic Testing in Polypharmacy Patient: A Case Report

Abstract Background Pharmacogenetics has become one of the main branches of Precision Medicine owing to its usefulness for patients’s optimal therapeutic management. Notwithstanding, pharmacogenetic testing results must be taken carefully, specially in multimorbidity patients with a variety of drugs prescribed. The aim of the present work is to introduce a combined RT-PCR and Whole Exome Sequencing Approach for pharmacogenetic testing in a patient with multiple drug-related adverse events. Case Background A 67 years old female was derived to our Clinical Chemistry Unit for pharmacogenetic testing due to multiple drug-related adverse events: nifedipine-voriconazole interaction, voriconazole-related neurological toxicity and moxifloxacin-related dizziness. Aditionally, she had been receiving morphine, corticoid for her reumatoid arthritis and antituberculous therapy (r isoniazid / pyrazinamide / rifampin and ethambutol). Methods Patient’s DNA was extracted from a blood sample and undergone by pharmacogenetic testing in two parallel ways: -A first genotyping assay was carried out using Taqman® OpenArray™ PGx Express 120 panel (ThermoFisher™), according to manufacturer’s instructions. -Simultaneusly, in order to cover possible copy number variants and SNPs not covered by our RT-PCR array, a whole exome sequencing run was performed on IlluminaTM NextSeq 1000. Sample library was prepared applying a custom GRCh38 pipeline. Results Relevant variants related to patient’s therapy found by RT-PCR are shown in table 1. SNPs genotyped by RT-PCR were confirmed by NGS. Moreover, whole exome sequencing revealed a deletion in exon 5 of SLCO1B1 gene, which corresponds to SLCO1B1*49 (loss of function); and some variants in NAT2 that may cause toxicity in antituberculous treatment (diplotype NAT2*6C/*7C). Conclusions In those challenging cases that involve multimorbidity and polypharmacy patients, pharmacogenetic testing must be approached taking into account variants that are not covered by the analytical method routinely used and the possibility of complement it with alternative proccedures.

Mesoporous Silica Administration as a New Strategy in the Management of Warfarin Toxicity; In Vitro and In Vivo Study

Purpose: Warfarin is one of the most widely used anticoagulants that function by inhibiting vitamin K epoxide reductase. Warfarin overdose, whether intentional or unintentional, can cause life-threatening bleeding. Here, we present a novel warfarin adsorbent based on mesoporous silica that can act as an antidote to warfarin toxicity. Method: Amino-functionalized mesoporous silica (MS-NH2) was synthesized based on co-condensation method through a soft template technique followed by template removal. The prepared structure and functional group were studied by FT-IR, XRD. The morphology was checked by SEM and TEM. The capacity of MS-NH2 in the adsorption of warfarin was evaluated in vitro, at pH=7.4 and pH=1.2. In vivo evaluation was performed in control and warfarin-overdosed animal models. Overdosed animals were treated with MS-NH2 by oral gavage. Biomarkers of organ injury were assessed in animal serum. Results: The MS-NH2 were relatively uniform, spherical with defined diameters (400 nm) and homogeneous structure. synthesized particles had a large surface area (1015 m2 g-1) and mean pore diameter 2.4 nm which leaded considerable adsorption capacity for warfarin 1666 mg/g. In vivo studies revealed that oral administration of MS-NH2 in mice poisoned with warfarin caused a significant difference (p < 0.05) on International Normalized Ratio (INR) and prothrombin time (PT). Moreover, the warfarin with MS-NH2 group demonstrated a notable decrease in biomarkers associated with tissue damage, such as bilirubin, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Conclusion: The results confirm that MS-NH2 administration can be an effective treatment for warfarin toxicity and could potentially mitigate the adverse effects of warfarin poisoning.

Use of Metallic Nanoparticles Against Eimeria-the Coccidiosis-Causing Agents: A Comprehensive Review.

Coccidiosis is a protozoan disease caused by Eimeria species and is a major threat to the poultry industry. Different anti-coccidial drugs (diclazuril, amprolium, halofuginone, ionophores, sulphaquinoxaline, clopidol, and ethopabate) and vaccines have been used for their control. Still, due to the development of resistance, their efficacy has been limited. It is continuously damaging the economy of the poultry industry because under its control, almost $14 billion is spent, globally. Recent research has been introducing better and more effective control of coccidiosis by using metallic and metallic oxide nanoparticles. Zinc, zinc oxide, copper, copper oxide, silver, iron, and iron oxide are commonly used because of their drug delivery mechanism. These nanoparticles combined with other drugs enhance the effect of these drugs and give their better results. Moreover, by using nanotechnology, the resistance issue is also solved because by using several mechanisms at a time, protozoa cannot evolve and thus resistance cannot develop. Green nanotechnology has been giving better results due to its less toxic effects. Utilization of metallic and metallic oxide nanoparticles may present a new, profitable, and economical method of controlling chicken coccidiosis, thus by changing established treatment approaches and improving the health and production of chickens. Thus, the objective of this review is to discuss about economic burden of avian coccidiosis, zinc, zinc oxide, iron, iron oxide, copper, copper oxide, silver nanoparticles use in the treatment of coccidiosis, their benefits, and toxicity.

Dendrobium Officinale Kimura & Migo Attenuates High Cholesterol Diet-Induced Atherosclerosis

Objectives: This study aimed to investigate the potential of Dendrobium officinale Kimura & Migo (DOKM) in ameliorating high cholesterol-induced atherosclerosis (AS) in zebrafish, focusing on the development of safe and effective drugs with low toxicity for AS treatment. Methods: A zebrafish AS model was established by feeding zebrafish a high cholesterol diet (HCD). Treatment was administered using 1 mg/L and 10 mg/L DOKM water extract. Fluorescence microscopy was utilised to observe the effects of DOKM on HCD-induced cholesterol accumulation, neutrophil accumulation, and macrophage infiltration in the vasculature. The impact of DOKM on HCD-induced disorders of lipid metabolism was assessed using Nile red staining. Total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL-C) levels in zebrafish were measured using kits. The expression of pcsk9, srebf2, and hmgcr genes in zebrafish was determined using RT-PCR. HE staining and Elvitegravir (EVG) staining were employed to assess the effect of DOKM on plaque formation in the blood vessels of AS zebrafish. Results: A total of 145 compounds were collected from Dendrobium officinale, along with 680 corresponding targets. Additionally, 1583 atherosclerosis-related targets were identified, with 202 representing interaction targets between Dendrobium officinale and atherosclerosis-related targets. Key compounds identified included Gigantol, Chrysotobibenzyl, Naringenin Chalcone, Hesperetin, and Tangeretin. The core targets of Dendrobium officinale for atherosclerosis treatment were STAT3, PTPN11, JAK2, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor alpha (PDGFRA), proto-oncogene tyrosine-protein kinase Src (SRC), STAT1, TP53, ESR1, and AKT1. GO functional enrichment analysis revealed a total of 2090 GO biological functional entries. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed 200 AS signalling pathways associated with DOKM treatment for atherosclerosis. DOKM significantly attenuated cholesterol accumulation, neutrophil aggregation, and macrophage infiltration in the blood vessels of AS zebrafish, ultimately leading to reduced plaque formation. AS zebrafish exhibited lipid metabolism disorders, characterised by significant increases in TC, TG, and LDL-C levels, as well as mRNA expression of pcsk9, srebf2, and hmgcr genes. Treatment with DOKM significantly improved these lipid metabolism disorders. Conclusion: DOKM effectively attenuates HCD-induced AS, and this therapeutic effect on AS may be related to its role in improving lipid metabolism dysfunction.

Comparing robust proton versus online adaptive photon radiotherapy for short-course treatment of rectal cancer

Background and purposeImage-guided proton beam therapy (IG-PBT) and cone-beam CT (CBCT)-based online adaptive photon radiotherapy (oART) have potentials to restrict radiation toxicity. They are both hypothesised to reduce therapy limiting bowel toxicity in the multimodality treatment of locally advanced rectal cancer (LARC). This study aimed to quantify the difference in relevant dose-volume metrics for these modalities. Material and MethodsSix-degrees-of-freedom IG-PBT and oART short-course radiotherapy (SCRT) were simulated for 18 LARC patients. Relative biological effectiveness (RBE) was 1.1 for IG-PBT. Delivered dose was evaluated using post-CBCTs. Target coverage was considered robust if average dose to 99 % of the clinical target volume was ≥ 95 % of the prescription. Organ at risk (OAR) doses were compared using dose-volume histograms and severe bowel toxicity estimated using dose–response modelling. ResultsTarget coverage was robust in all patients for oART and all but one patient for IG-PBT. For the main OARs, IG-PBT increased the volume exposed to ≥ 15 Gy (RBE), but reduced volumes exposed to lower doses. Both low- and high-dose exposure to bowel loops were significantly different between the modalities (median (interquartile range) IG-PBT-V8.9Gy(RBE) = 92 cm3 (51–156), oART-V8.9Gy(RBE) = 166 cm3 (107–234), p < 0.001; IG-PBT-V23Gy(RBE) = 62 cm3 (25–106), oART-V23Gy(RBE) = 38 cm3 (18–75), p < 0.001), translating into similar total grade ≥ 3 bowel toxicity risk. ConclusionIG-PBT and oART delivered comparable and satisfying target coverage in SCRT for LARC with similar estimated risk of severe bowel toxicity. Volumes of OAR exposed to 15 Gy (RBE) or more were reduced by oART, while IG-PBT reduced the volumes receiving doses below this level.

Long-term cause-specific mortality in adolescent and young adult Hodgkin lymphoma patients treated with contemporary regimens-A nationwide Danish cohort study.

The documented treatment-induced excess mortality in Hodgkin lymphoma (HL) has spurred important treatment changes over recent decades. This study aimed to examine mortality among young HL patients treated with contemporary strategies, including historical data comparison. This nationwide study included 1348 HL patients, diagnosed in 1995-2015 and aged 15-40 at diagnosis. Among the patients, 66.5% had Ann Arbor stage I-II and 33.5% had stage III-IV disease. With a median follow-up of 14.76 years, 139 deaths occurred, yielding a 5-year overall survival of 94.6%. Older age, advanced disease, earlier treatment periods and extensive regimens were associated with higher overall mortality risk. The cumulative risk of HL-related death showed an initial sharp rise, with a plateau at 5.3% 10-year post-diagnosis. Deaths due to cardiovascular or pulmonary diseases and second cancers initially had minimal risk, gradually reaching 1.2% and 2.0% at the 20-year mark respectively. HL cases had a 7.5-fold higher mortality hazard than the background population. This study suggests that contemporary HL treatment still poses excess mortality risk, but recent changes have notably reduced overall and cause-specific mortality compared to earlier eras. Balancing treatment efficacy and toxicity remains crucial, but our findings highlight improved outcomes with modern treatment approaches.

Impact of Sarcopenia on Treatment Outcomes and Toxicity in Locally Advanced Rectal Cancer

Background and Objectives: Sarcopenia, a condition characterized by muscle mass loss, is prevalent in up to 68% of rectal cancer patients and has been described as a negative prognostic factor, impacting overall survival and tumor response. While there are extensive data on rectal cancer globally, only a handful of studies have evaluated the role of sarcopenia in locally advanced rectal cancer (LARC). Our study aimed to investigate the relationship between sarcopenia, overall response rate, and toxicity in patients who underwent total neoadjuvant treatment (TNT) for LARC. Materials and Methods: We performed a retrospective study of patients with rectal cancer treated with TNT and surgery with curative intent between 2021 and 2023 at Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj-Napoca. Sarcopenia was assessed on MRI images by measuring the psoas muscle area (PMA) at the level of the L4 vertebra before and after neoadjuvant therapy. The primary endpoints were the overall complete response rate (oCR) and acute toxicity. Results: This study included 50 patients with LARC. The oCR rate was 18% and was significantly associated with post-treatment sarcopenia (OR 0.08, p = 0.043). Patients who did not achieve a clinical or pathologic complete response had, on average, an 8% muscle loss during neoadjuvant therapy (p = 0.022). Cystitis and thrombocytopenia were significantly associated with post-treatment sarcopenia (p = 0.05 and p = 0.049). Conclusions: Sarcopenia and loss of psoas muscle during neoadjuvant therapy were negatively associated with tumor response in locally advanced rectal cancer. Thrombocytopenia and cystitis are more frequent in sarcopenic than non-sarcopenic patients undergoing neoadjuvant chemoradiation for rectal cancer.

Healthcare utilization disparities among children with high-risk neuroblastoma treated on Children's Oncology Group clinical trials.

Disparities in relapse and survival from high-risk neuroblastoma (HRNBL) persist among children from historically marginalized groups even in highly standardized clinical trial settings. Research in other cancers has identified differential treatment toxicity as one potential underlying mechanism. Whether racial and ethnic disparities in treatment-associated toxicity exist in HRNBL is poorly understood. This is a retrospective study utilizing a previously assembled merged cohort of children with HRNBL on Children's Oncology Group (COG) post-consolidation immunotherapy trials ANBL0032 and ANBL0931 at Pediatric Health Information System (PHIS) centers from 2005 to 2014. Race and ethnicity were categorized to reflect historically marginalized populations as Hispanic, non-Hispanic Black (NHB), non-Hispanic other (NHO), and non-Hispanic White (NHW). Associations between race-ethnicity and intensive care unit (ICU)-level care utilization as a proxy for treatment-associated toxicity were examined with log binomial regression and summarized as risk ratio (RR) and corresponding 95% confidence interval (CI). The analytic cohort included 370 children. Overall, 88 (23.8%) patients required ICU-level care for a median of 3.0days (interquartile range [IQR]: 1.0-6.5days). Hispanic children had nearly three times the risk of ICU-level care (RR 3.1, 95% CI: 2.1-4.5; fully adjusted RR [aRR] 2.5, 95% CI: 1.6-3.7) compared to NHW children and the highest percentage of children requiring cardiovascular-driven ICU-level care. Children of Hispanic ethnicity with HRNBL receiving clinical trial-delivered therapy were more likely to experience ICU-level care compared to NHW children. These data suggest that further investigation of treatment-related toxicity as a modifiable mechanism underlying outcome disparities is warranted.

Docetaxel Versus Androgen-Receptor Signaling Inhibitors (ARSI) as Second-Line Therapy After Failure of First-Line Alternative ARSI for the Elderly ≥ 75 Years Old With Metastatic Castration-Resistant Prostate Cancer (mCRPC): A SPARTACUSS—Meet-URO 26 Real-World Study

BackgroundAndrogen receptor signalling inhibitors (ARSIs) abiraterone acetate (AA) enzalutamide (Enza), are currently the standard first-line (L1) treatments for metastatic castration-resistant prostate cancer (mCRPC), and docetaxel (D) is reserved as second-line (L2) after ARSI failure. Nonetheless, D use in men ≥ 75 years old is restricted owing to treatment toxicities and patient comorbidities, and a L2 alternative ARSI is frequently used. We aimed to evaluate real-life survival and toxicity outcomes of these elderly patients after failure of L1 ARSI treatment. Material and MethodsWe retrospectively evaluated efficacy and safety in a real-world international cohort of consecutive patients ≥ 75 years old when starting L1 ARSI for mCRPC according to the choice of L2 treatment (D versus alternative ARSI). ResultsOf the 122 identified patients, 57 (46.7%) had received L2 ARSI and 65 (53.3%) L2 D. No difference was found in the L1 overall survival (OS) for the ARSI and D groups (32.8 vs. 30.0 months, respectively; Hazard ratio [HR] = 1.22; 95% CI, 0.77-1.95; P = .40) or in the L2 OS (18.5 vs. 17.8 months, respectively; HR = 1.09; 95% CI, 0.69-1.74; P = .71). No difference was observed for rPFS from L2 (P = .12), although a trend was observed for a numerically improved rPFS on D. ConclusionWithin the limitations of a retrospective design and small population, our study suggests that D or ARSI after failure of L1 alternative ARSI are clinically comparable L2 options for elderly patients with mCRPC.

Doxorubicin, Paclitaxel, and Cisplatin (ATP) for Relapsed/Refractory Germ Cell Tumors

Patients with relapsed/refractory germ cell tumors (GCT) have limited treatment options and poor survival outcomes. We describe our institutional experience with doxorubicin, paclitaxel, and cisplatin (ATP) as an outpatient regimen for 35 patients with relapsed/refractory GCT between 2017 and 2022. Twenty-four patients received non-palliative intent ATP, with a median of 2 lines of prior therapy, 23 (96%) having received at least one cisplatin-based regimen and one (4%) with a prior stem cell transplant. The objective response rate for the non-palliative intent cohort was 37.5% (one complete response and eight partial responses). Post-ATP, 12 patients underwent stem cell transplant, 7 patients had surgical resections, and 4 patients received radiation. The median PFS was 4.3 months (95% CI: 3.8, 32.7) and median OS of 13.1 months (95% CI: 10.7, NA) for the non-palliative intent cohort. Eleven patients received palliative intent ATP, with a median of 4 lines of prior therapy, all having received at least one cisplatin-based regimen, and 7 (64%) having received prior stem cell transplants. Within the palliative intent cohort, the objective response rate was 9% (one partial response). Patients who received palliative intent ATP had a median PFS of 0.92 months (95% CI 0.46, NA) and median OS of 5.2 months (95% CI 3.3, NA). Treatment toxicities occurred in five (14%) patients who required dose reductions and five (14%) patients who were admitted for treatment related toxicities, most commonly for myelosuppression. Our results support the use of ATP in a primarily anthracycline naïve patient population and show the safety of continued cisplatin use in patients who have previously received cisplatin-based regimens. Therefore, ATP is a feasible and well tolerated chemotherapy regimen in the salvage setting and can serve as a bridge to other treatments for patients with relapsed/refractory GCT. Micro-abstractWe report our institutional experience with doxorubicin, paclitaxel, and cisplatin (ATP) in patients with relapsed/refractory germ cell tumors (GCT). A total of 35 patients received ATP. In the non-palliative intent cohort (24 patients), the objective response rate was 37.5%, with a median progression free survival (PFS) of 4.3 months and a median overall survival (OS) of 13.1 months. For the palliative intent cohort (11 patients), the objective response rate was 9%, with a median PFS of 0.92 months and a median OS of 5.2 months. Treatment-related toxicities were observed in 14% of patients, with five requiring dose reductions and five requiring hospital admission, primarily due to myelosuppression. Overall, ATP is a feasible and well-tolerated outpatient chemotherapy regimen that may serve as a bridge to other therapies.

Eugenol-loaded nanoemulsions: Antiproliferative activity against breast cancer cells and hemocompatibility

Breast cancer poses a substantial global health challenge, lacking specific and less toxic treatment options. Eugenol, a phenolic compound, has demonstrated potential in vitro, but its susceptibility to degradation, volatility, and limited water solubility hampers its practical application. This study aimed to enhance eugenol's efficacy and stability by formulating nanoemulsions, offering a novel therapeutic strategy for breast cancer. Eugenol-loaded nanoemulsions were developed using high-energy (NE-Et) and low-energy (NE-Er) methods. Eugenol-nanoemulsions exhibited favorable nanometric characteristics, with sizes ranging from 110 to 120 nm, polydispersity index below 0.3, negative zeta potential, and an acidic pH. The eugenol content approached theoretical values, reaching approximately 100 % for NE-Et and 50 % for NE-Er. Moreover, these nanoformulations exhibited excellent physicochemical stability throughout a 90-day period. With a high antioxidant potential (190 μMol TE/μL), concentrations of 50–150 μg/mL free and nanoemulsified eugenol were considered non-toxic to blood cells. Finally, demonstrated a significant antitumor effect of eugenol-loaded nanoemulsions (150, 300, and 600 μg/mL) against breast cancer cells (MCF-7), with a notable enhancement of this activity attributed to the process of nanoemulsification. This research underscores nanotechnology's promise in advancing bioactive compound formulations for cancer therapy and clinical translation.

Circulating Tumor DNA Sequencing for Biologic Classification and Individualized Risk Stratification in Patients With Hodgkin Lymphoma.

Current clinical challenges in Hodgkin lymphoma (HL) include difficult-to-treat relapsed/refractory disease and considerable long-term toxicities of treatment. Since clinical risk factors lack discriminatory power, intensity of therapy is mainly based on tumor burden. Exploring HL genetics and tumor microenvironment (TME) might provide valuable insights for improved risk stratification. In this study, we applied circulating tumor DNA sequencing to 243 patients obtained from pivotal German Hodgkin Study Group trials to identify subtypes of HL. Independent validation of the subtypes was performed in 96 patients treated in the EuroNet-PHL-C2 study. Outcome differences of subtypes were assessed in an event-enriched clinical validation cohort comprising 72 patients from the HD21 trial, using a refined, validated, and clinically feasible assay. We propose a biologic classification of HL consisting of three distinct subtypes: inflammatory immune escape HL is characterized by frequent copy-number variations including immune escape variants such as high-level amplifications of the PD-L1 locus and an inflammatory TME. Virally-driven HL is associated with Epstein-Barr virus and/or human herpesvirus 6 and an inflammatory TME with neutrophils and macrophages, while the tumor mutational burden (TMB) is low. Oncogene-driven HL is defined by a high TMB, recurrent mutations in oncogenic drivers such as TNFAIP3, ITPKB, and SOCS1, and a cold TME. A refined and validated assay version aiming at clinically feasible risk stratification showed significant progression-free survival differences between subtypes. In addition, assessment of minimal residual disease (MRD) allowed for the detection of patients at very high risk of relapse within the subtypes. We propose a clinically feasible, noninvasive method for individualized risk stratification and MRD monitoring in patients with HL on the basis of circulating tumor DNA sequencing.

Characteristics of Chemotherapy Treatments for Breast Cancer Patients at Bhayangkara Tk.1 Pudsdokkes Polri Hospital, Jakarta

Background: Breast cancer is a malignant breast tumor that develops in the ductal or lobular epithelium and usually attacks women. Chemotherapy is a cornerstone of breast cancer treatment, particularly for patients with advanced disease or those who are not candidates for surgery or radiation therapy. This research aims to observe the use of chemotherapy drugs for breast cancer patients in terms of chemotherapy regimens and cycles at Bhayangkara Tk.1 Pudsdokkes Polri Hospital. Methods: This study employs descriptive quantitative approaches. Data were gathered retrospectively from medical records of breast cancer patients receiving chemotherapy at Bhayangkara Tk.1 Pudsdokkes Polri Hospital Jakarta from July to December 2021. Results: From 110 patients, 86 (78.18%) patients used the CAF regimen, 18 (16.36%) patients used the AC regimen, and 3 (2.73%) patients used the TAC regimen, while the regimen that did not comply with the guidelines was 2 (1.82%) patients using the combination of paclitaxel and epirubicin, 1 patient utilizing the combination of paclitaxel and doxorubicin. Forty-six (41.82%) patients with the CAF regimen had completed six cycles of chemotherapy with intervals of 3 weeks or 21 days, while only 5 patients (3.63%) completed four cycles of the AC regimen at 3-week or 21-day intervals. At the time of data collection, 11 patients, and 1 patient utilizing the AC regimen. This was because 59 patients had not yet finished the chemotherapy cycle, specifically in the advanced stage. Conclusions: The CAF regimen was the most commonly used chemotherapy regimen, followed by the AC and TAC regimens. This finding aligns with current clinical guidelines for breast cancer treatment. A significant number of patients had not yet completed their chemotherapy cycles, particularly those with advanced-stage breast cancer. This highlights the challenges associated with treating advanced disease and the need for more effective and less toxic treatment options.

Neoadjuvant Capecitabine in Operable HPV-Negative Head and Neck Cancer: Fortuitous Findings in a Resource Constrained Setting.

Limited progress has occurred in treating operable human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). Accessing timely care remains challenging in public health care systems, potentially resulting in disease progression before treatment initiation. A prospective cohort of patients receiving neoadjuvant capecitabine (NC) was compared to stage-matched patients undergoing standard of care (SC). This study was performed at 2 academic centers in Montreal, Canada. To ascertain the effect of 2 cycles of NC in operable HPV-negative HNSCC patients on clinical-to-pathologic stage migration. Comparison to an SC group was performed to site and TNM stage matched patients. Pathologic treatment response was measured using the modified Ryan score. We compared 16 NC patients (11 oral cavity, 3 skin, 2 larynx) with 32 SC patients. Ten NC patients exhibited a pathologic response (1 complete, 3 major, 6 minor). Clinical-to-pathologic stage migration differed significantly between NC and SC groups: downstage (6 vs 1), upstage (3 vs 14), no change (7 vs 17, P = .0047). There was no severe treatment toxicity related to capecitabine. All patients in the NC group underwent surgery. NC followed by surgery demonstrates measurable pathologic response in HPV-negative HNSCC, suggesting potential utility in resource-limited health care settings.

Treatment Outcomes and Prognostic Factors of Chemotherapy Combined With Radiation Therapy for Patients With Early-Stage Extranodal Natural Killer/T-Cell Lymphoma

BackgroundThis study aimed to assess the treatment outcomes, toxicity, and potential prognostic factors in patients with early stage extranodal natural killer/T-cell lymphoma treated with radiotherapy combined with chemotherapy. MethodsOne hundred and eighteen patients with Stage I/II extranodal natural killer/T-cell lymphoma who were treated with radiotherapy combined with chemotherapy were retrospectively analyzed between July 2003 and January 2019. The median dose was 50 Gy (range, 45–61.2 Gy). The Kaplan–Meier method was used to calculate progression-free survival and overall survival. The patients were scored according to their prognostic indices. ResultsThe overall and complete response rates were 93.2% and 82.2%, respectively. At a median follow-up of 43 months, the 5-year overall survival and progression-free survival rates were 73.9% and 68.4%, respectively. Adverse events of grade 3 or higher was observed in 20 patients (16.9%). Patients with primary disease in the Waldeyer's ring had poorer survival (P=0.015). Compared with anthracycline-based regimens, non-anthracycline-based regimens significantly improved the 5-year overall survival (76.6% vs. 54.8%, P=0.027) and progression-free survival (72.4% vs. 53.1%, P=0.013). After treatment, the 5-year overall survival rate was 78.6% in complete response patients versus 44.9% in non-complete response patients (P=0.003). For patients with low-and intermediate-low-risk according to the nomogram-revised risk index model, the complete response rate was 100%. When primary lesion data were added to the nomogram-revised risk index as the basis for another prognostic index (modified nomogram-revised risk index), the low-risk (zero to two risk factors) and high-risk (three or more risk factors) categories were noted (84.2% vs 62.2%, P=0.036). ConclusionPatients with early stage extranodal natural killer/T-cell lymphoma had high response rates and favorable survival rates with radiotherapy and non-anthracycline-based chemotherapy regimens. Patients who achieved complete response had better survival than those who did not. The extranodal natural killer/T-cell lymphoma-specific prognostic models may require further optimization.

Landscape of exosomes to modified exosomes: a state of the art in cancer therapy.

Exosomes are a subpopulation of extracellular vesicles (EVs) that naturally originate from endosomes. They play a significant role in cellular communication. Tumor-secreted exosomes play a crucial role in cancer development and significantly contribute to tumorigenesis, angiogenesis, and metastasis by intracellular communication. Tumor-derived exosomes (TEXs) are a promising biomarker source of cancer detection in the early stages. On the other hand, they offer revolutionary cutting-edge approaches to cancer therapeutics. Exosomes offer a cell-free approach to cancer therapeutics, which overcomes immune cell and stem cell therapeutics-based limitations (complication, toxicity, and cost of treatment). There are multiple sources of therapeutic exosomes present (stem cells, immune cells, plant cells, and synthetic and modified exosomes). This article explores the dynamic source of exosomes (plants, mesenchymal stem cells, and immune cells) and their modification (chimeric, hybrid exosomes, exosome-based CRISPR, and drug delivery) based on cancer therapeutic development. This review also highlights exosomes based clinical trials and the challenges and future orientation of exosome research. We hope that this article will inspire researchers to further explore exosome-based cancer therapeutic platforms for precision oncology.

Reduction of Cr(VI) by Bacillus toyonensis LBA36 and its effect on radish seedlings under Cr(VI) stress.

Chromium, being among the most toxic heavy metals, continues to demand immediate attention in the remediation of Cr-contaminated environments. In this study, a strain of LBA36 (Bacillus toyonensis) was isolated from heavy metal contaminated soil in Luanchuan County, Luoyang City, China. The reduction and adsorption rates of LBA36 in 30 mg·L-1 Cr-containing medium were 97.95% and 8.8%, respectively. The reduction mechanism was confirmed by Fourier-transform infrared spectroscopy, and X-ray photoelectron spectroscopy (XPS). Cr(VI) reduction by this strain predominantly occurred outside the cell, with hydroxyl, amide, carboxyl, C-N group, carbonyl, and sulfur carbonyl as the main reaction sites. XPS analysis revealed the presence of Cr2p1/2 and Cr2p3/2. Furthermore, the hydroponic experiment showed that the fresh weight and plant height of radish seedlings increased by 87.87% and 37.07%, respectively, after inoculation with LBA36 strain under 7 mg·L-1 Cr(VI) stress. The levels of chlorophyll, total protein, malondialdehyde, superoxide dismutase and catalase were also affected to different degrees. In conclusion, this study demonstrated the potential of microbial and phytoremediation in the treatment of heavy metal toxicity, and laid the foundation for the development of effective bioremediation methods for Cr(VI) pollution.