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1.
Curr Oncol ; 31(7): 3682-3689, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-39057143

ABSTRACT

Small-cell lung cancer (SCLC) remains a disease with poor prognosis, particularly in extensive-stage SCLC (ES-SCLC). Current standard-of-care treatment includes chemotherapy with platinum agents and etoposide plus immunotherapy with atezolizumab or durvalumab, which has achieved a mean overall survival of 12-13 months in clinical trials. However, long-term survival in ES-SCLC, even with the addition of immunotherapy, continues to be rare. We present the case of a middle-aged male patient diagnosed with ES-SCLC who was treated with four cycles of induction chemotherapy (carboplatin and etoposide) and atezolizumab, starting maintenance atezolizumab every 21 days thereafter, and thoracic radiotherapy. After 9 months, he experienced mild disease progression and was rechallenged with six cycles of carboplatin and etoposide with continued atezolizumab. Subsequent imaging showed near-complete disease resolution which has been sustained since. He has continued on maintenance atezolizumab since diagnosis and has achieved 60 months overall survival and 44 months progression-free survival. Throughout treatment, he has maintained a high functional capacity and only experienced one immune-related adverse event. Our patient is representative of a small subset who are capable of achieving durable responses to immunotherapy and his case highlights the need for further research to elucidate the clinical and biological factors driving this response.


Subject(s)
Antibodies, Monoclonal, Humanized , Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Small Cell Lung Carcinoma/drug therapy , Male , Antibodies, Monoclonal, Humanized/therapeutic use , Lung Neoplasms/drug therapy , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Treatment Outcome , Etoposide/therapeutic use
2.
Clin J Oncol Nurs ; 28(4): 380-388, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39041693

ABSTRACT

BACKGROUND: Surface contamination with antineoplastic drugs (ADs) is persistent. The use of personal protective equipment (PPE) is recommended to reduce exposure to ADs. OBJECTIVES: This study explored the impact of the COVID-19 pandemic on nurses' PPE use and surface contamination with ADs. METHODS: Demographic characteristics, PPE use, and associated factors were assessed on two inpatient oncology units where etoposide and cyclophosphamide were administered before (N = 26) and during the COVID-19 pandemic (N = 31). FINDINGS: PPE use when handling contaminated excreta was significantly higher during the pandemic. Perceived risk of chemotherapy exposure was significantly associated with greater PPE use when handling AD-contaminated excreta, and conflict of interest was related to less PPE use during AD administration and handling of AD-contaminated excreta. During the pandemic, surface contamination with etoposide increased in shared areas and decreased in patient rooms.


Subject(s)
Antineoplastic Agents , COVID-19 , Personal Protective Equipment , Humans , COVID-19/prevention & control , Female , Male , Antineoplastic Agents/therapeutic use , Adult , Middle Aged , Pandemics , SARS-CoV-2 , Occupational Exposure/prevention & control , Oncology Nursing/standards , Etoposide/therapeutic use , Cyclophosphamide/therapeutic use , Nursing Staff, Hospital
3.
Front Immunol ; 15: 1415597, 2024.
Article in English | MEDLINE | ID: mdl-39040100

ABSTRACT

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by hyperinflammation and organ failure, with a high mortality rate. Current first-line treatments for adult patients have limited efficacy and significant toxicity. The novel selective histone deacetylase inhibitor (HDACi), chidamide, has shown promise in preclinical studies for the potential treatment of HLH. Methods: An open-label, single-center study was conducted to evaluate the efficacy and safety of chidamide in combination with etoposide and glucocorticoids for the treatment of HLH in adult patients. Seventeen patients who fulfilled at least five of the eight HLH-2004 criteria were enrolled and treated with the combination therapy. The primary outcome was overall response rate (ORR), and secondary outcomes included survival, safety and tolerability, and changes in laboratory indicators. Results: A total of 17 HLH patients who met the inclusion criteria were enrolled in this study, with a male to female ratio of 1.8:1. The age range at enrollment was 31 to 71 years old, with a median age of 52 years old. The ORR was 76.5% (13/17 patients), with a complete response (CR) rate of 17.6% (3/17 patients) and a partial response (PR) rate of 58.8% (10/17 patients). The median overall survival (OS) was not achieved, with OS at 6 months and 12 months being 81% and 65%, respectively. The median progression free survival (PFS) was not achieved, with PFS at 6 months and 12 months being 68% and 55%, respectively. Hematologic toxicities is the most common. Safety profile was favorable, with very few cases of grade 3/4 toxicities observed. The results showed that the levels of sCD25, platelets, aspartate aminotransferase, lactate dehydrogenase, and albumin in these patients were significantly improved 3 weeks after treatment. Conclusion: The addition of chidamide to etoposide and glucocorticoids may be a promising new treatment option for patients with HLH, with a high ORR, manageable safety profile, and significant improvement in laboratory indicators. Further research is needed to confirm these findings and determine the optimal dosing and duration of therapy.


Subject(s)
Aminopyridines , Benzamides , Etoposide , Glucocorticoids , Lymphohistiocytosis, Hemophagocytic , Humans , Etoposide/administration & dosage , Etoposide/adverse effects , Etoposide/therapeutic use , Male , Female , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/mortality , Adult , Middle Aged , Benzamides/administration & dosage , Benzamides/adverse effects , Benzamides/therapeutic use , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Glucocorticoids/adverse effects , Aminopyridines/administration & dosage , Aminopyridines/adverse effects , Aminopyridines/therapeutic use , Treatment Outcome , Aged , Drug Therapy, Combination , Histone Deacetylase Inhibitors/therapeutic use , Histone Deacetylase Inhibitors/adverse effects , Histone Deacetylase Inhibitors/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects
4.
Zhonghua Nan Ke Xue ; 30(1): 40-43, 2024 Jan.
Article in Chinese | MEDLINE | ID: mdl-39046412

ABSTRACT

OBJECTIVE: To explore the clinical manifestations, diagnosis, pathological features and treatment of small-cell carcinoma of the prostate (SCCP). METHODS: We conducted a retrospective analysis of the clinical and pathological data of 2 cases of confirmed SCCP treated from November 2017 to March 2018, and reviewed relevant literature. RESULTS: Both the patients had the symptoms of frequent, urgent and difficult urination, with an elevated level of PSA and gradesⅡ-Ⅲ enlargement of the prostate at palpation. One underwent prostate puncture biopsy and the other received transurethral 1470 laser vaporization resection of the tumor. Postoperative pathology indicated prostate adenocarcinoma accompanied by SCCP in both of the cases. One of them was treated by etoposide-platinum (EP) chemotherapy and died of systemic multiple organ failure 20 months after diagnosis, while the other underwent endocrine therapy and has lived with tumor up to the present day. CONCLUSION: The incidence rate of SCCP is low, its malignancy is high, and its prognosis is poor. The average survival of the patient is about 7 to 10 months after diagnosis. Currently there is no effective management of the dissease, except by relying on the experience of the treatment of small-cell lung cancer, with chemotherapy as the main option.


Subject(s)
Carcinoma, Small Cell , Prostatic Neoplasms , Humans , Male , Carcinoma, Small Cell/diagnosis , Carcinoma, Small Cell/therapy , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/therapy , Prostatic Neoplasms/pathology , Retrospective Studies , Etoposide/therapeutic use , Etoposide/administration & dosage , Aged , Middle Aged , Prostate/pathology , Prognosis , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Prostate-Specific Antigen/blood
5.
J Med Case Rep ; 18(1): 323, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39004746

ABSTRACT

BACKGROUND: Diagnosing non-gestational uterine choriocarcinoma in children is challenging because of its rarity and nonspecific imaging findings. Herein, we report a case of non-gestational uterine choriocarcinoma in a child, which was unexpectedly found during exploratory laparotomy and confirmed by histopathological findings. However, the tumor did not respond to chemotherapy. CASE PRESENTATION: A 4-year-old Indonesian female patient was brought into the emergency unit with chief complaint of vaginal bleeding. She had suffered from vaginal spotting 4 months before being admitted to the hospital. Physical examination revealed a distended abdomen in the left lumbar region and a palpable fixed mass with a smooth surface. Abdominal computed tomography scans revealed a large mass (10 × 6 × 12 cm) with fluid density and calcification. Thus, we suspected left ovarian teratoma. The patient's luteinizing hormone, follicle-stimulating hormone, and lactate dehydrogenase levels were 25.2 mIU/ml, 0.1 mIU/ml, and 406 U/l, respectively. According to the clinical and radiological findings, we decided to perform an exploratory laparotomy and found a tumor originating from the uterus, not the ovarium. We did not observe liver nodules and any enlargement of abdominal lymph nodes. Subsequently, we performed hysterectomy. The histopathological findings supported the diagnosis of choriocarcinoma. The patient was discharged uneventfully on postoperative day 5. Thereafter, the patient underwent nine cycles of chemotherapy, including carboplatin (600 mg/m2 IV), etoposide (120 mg/m2 IV), and bleomycin (15 mg/m2 IV). However, on the basis of the clinical findings of a palpable mass and partial intestinal obstruction, the tumor relapsed soon after the ninth cycle of chemotherapy. Currently, the patient is undergoing chemotherapy again. CONCLUSIONS: Although pure non-gestational uterine choriocarcinoma is rare, it should be considered as one of the differential diagnoses for intraabdominal tumors in a child, so as to better guide and counsel families regarding the surgical plan and prognosis, respectively. In the present case, the patient's response to chemotherapy was poor, implying that the treatment of non-gestational choriocarcinoma is still challenging, particularly in the pediatric population.


Subject(s)
Choriocarcinoma, Non-gestational , Hysterectomy , Uterine Neoplasms , Humans , Female , Uterine Neoplasms/diagnosis , Uterine Neoplasms/surgery , Uterine Neoplasms/pathology , Uterine Neoplasms/drug therapy , Uterine Neoplasms/therapy , Child, Preschool , Choriocarcinoma, Non-gestational/diagnosis , Choriocarcinoma, Non-gestational/pathology , Choriocarcinoma, Non-gestational/drug therapy , Choriocarcinoma, Non-gestational/therapy , Tomography, X-Ray Computed , Diagnosis, Differential , Laparotomy , Uterine Hemorrhage/etiology , Etoposide/therapeutic use , Etoposide/administration & dosage
6.
BMJ Case Rep ; 17(7)2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39002953

ABSTRACT

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition that can be either familial or acquired and, if untreated, frequently results in multiorgan failure and death. Treatment of HLH typically requires a combination of glucocorticoids and cytotoxic chemotherapy. We describe the case of a woman who presented with signs and symptoms concerning for HLH who was later found to have a primary central nervous system (CNS) diffuse large B-cell lymphoma. Her HLH symptoms were successfully treated with high doses of dexamethasone, and her primary CNS lymphoma was treated with high-dose methotrexate and rituximab. This is a rare case of HLH secondary to primary CNS lymphoma where HLH was controlled with steroids alone and did not require the use of an etoposide-based regimen or cyclophosphamide, doxorubicin, vincristine and prednisone.


Subject(s)
Central Nervous System Neoplasms , Etoposide , Lymphohistiocytosis, Hemophagocytic , Lymphoma, Large B-Cell, Diffuse , Humans , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/complications , Female , Etoposide/therapeutic use , Etoposide/administration & dosage , Central Nervous System Neoplasms/drug therapy , Central Nervous System Neoplasms/complications , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/complications , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dexamethasone/therapeutic use , Dexamethasone/administration & dosage , Rituximab/therapeutic use , Rituximab/administration & dosage , Methotrexate/therapeutic use , Methotrexate/administration & dosage , Middle Aged , Treatment Outcome
7.
Front Immunol ; 15: 1338162, 2024.
Article in English | MEDLINE | ID: mdl-38957470

ABSTRACT

Introduction: Chemoresistance constitutes a prevalent factor that significantly impacts thesurvival of patients undergoing treatment for smal-cell lung cancer (SCLC). Chemotherapy resistance in SCLC patients is generally classified as primary or acquired resistance, each governedby distinct mechanisms that remain inadequately researched. Methods: In this study, we performed transcriptome screening of peripheral blood plasma obtainedfrom 17 patients before and after receiving combined etoposide and platinum treatment. We firs testimated pseudo-single-cell analysis using xCell and ESTIMATE and identified differentially expressed genes (DEGs), then performed network analysis to discover key hub genes involved in chemotherapy resistance. Results: Our analysis showed a significant increase in class-switched memory B cell scores acrossboth chemotherapy resistance patterns, indicating their potential crucial role in mediatingresistance. Moreover, network analysis identifed PRICKLE3, TNFSFI0, ACSLl and EP300 as potential contributors to primary resistance, with SNWl, SENP2 and SMNDCl emerging assignificant factors in acquired resistance, providing valuable insights into chemotherapy resistancein SCLC. Discussion: These findings offer valuable insights for understanding chemotherapy resistance and related gene signatures in SCLC, which could help further biological validation studies.


Subject(s)
Biomarkers, Tumor , Drug Resistance, Neoplasm , Gene Expression Profiling , Lung Neoplasms , Small Cell Lung Carcinoma , Transcriptome , Humans , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/genetics , Small Cell Lung Carcinoma/blood , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/blood , Drug Resistance, Neoplasm/genetics , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Female , Male , Middle Aged , Gene Expression Regulation, Neoplastic , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Etoposide/therapeutic use , Etoposide/pharmacology
8.
Theranostics ; 14(9): 3439-3469, 2024.
Article in English | MEDLINE | ID: mdl-38948053

ABSTRACT

Rationale: Synergic reprogramming of metabolic dominates neuroblastoma (NB) progression. It is of great clinical implications to develop an individualized risk prognostication approach with stratification-guided therapeutic options for NB based on elucidating molecular mechanisms of metabolic reprogramming. Methods: With a machine learning-based multi-step program, the synergic mechanisms of metabolic reprogramming-driven malignant progression of NB were elucidated at single-cell and metabolite flux dimensions. Subsequently, a promising metabolic reprogramming-associated prognostic signature (MPS) and individualized therapeutic approaches based on MPS-stratification were developed and further validated independently using pre-clinical models. Results: MPS-identified MPS-I NB showed significantly higher activity of metabolic reprogramming than MPS-II counterparts. MPS demonstrated improved accuracy compared to current clinical characteristics [AUC: 0.915 vs. 0.657 (MYCN), 0.713 (INSS-stage), and 0.808 (INRG-stratification)] in predicting prognosis. AZD7762 and etoposide were identified as potent therapeutics against MPS-I and II NB, respectively. Subsequent biological tests revealed AZD7762 substantially inhibited growth, migration, and invasion of MPS-I NB cells, more effectively than that of MPS-II cells. Conversely, etoposide had better therapeutic effects on MPS-II NB cells. More encouragingly, AZD7762 and etoposide significantly inhibited in-vivo subcutaneous tumorigenesis, proliferation, and pulmonary metastasis in MPS-I and MPS-II samples, respectively; thereby prolonging survival of tumor-bearing mice. Mechanistically, AZD7762 and etoposide-induced apoptosis of the MPS-I and MPS-II cells, respectively, through mitochondria-dependent pathways; and MPS-I NB resisted etoposide-induced apoptosis by addiction of glutamate metabolism and acetyl coenzyme A. MPS-I NB progression was fueled by multiple metabolic reprogramming-driven factors including multidrug resistance, immunosuppressive and tumor-promoting inflammatory microenvironments. Immunologically, MPS-I NB suppressed immune cells via MIF and THBS signaling pathways. Metabolically, the malignant proliferation of MPS-I NB cells was remarkably supported by reprogrammed glutamate metabolism, tricarboxylic acid cycle, urea cycle, etc. Furthermore, MPS-I NB cells manifested a distinct tumor-promoting developmental lineage and self-communication patterns, as evidenced by enhanced oncogenic signaling pathways activated with development and self-communications. Conclusions: This study provides deep insights into the molecular mechanisms underlying metabolic reprogramming-mediated malignant progression of NB. It also sheds light on developing targeted medications guided by the novel precise risk prognostication approaches, which could contribute to a significantly improved therapeutic strategy for NB.


Subject(s)
Disease Progression , Etoposide , Neuroblastoma , Tumor Microenvironment , Neuroblastoma/drug therapy , Neuroblastoma/metabolism , Neuroblastoma/pathology , Tumor Microenvironment/drug effects , Humans , Animals , Mice , Cell Line, Tumor , Etoposide/pharmacology , Etoposide/therapeutic use , Prognosis , Cellular Reprogramming/drug effects , Cell Proliferation/drug effects , Xenograft Model Antitumor Assays , Molecular Targeted Therapy/methods , Machine Learning , Apoptosis/drug effects , Metabolic Reprogramming
9.
Zhonghua Xue Ye Xue Za Zhi ; 45(4): 351-356, 2024 Apr 14.
Article in Chinese | MEDLINE | ID: mdl-38951062

ABSTRACT

Objective: The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) . Methods: Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1∶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed. Results: ①Collection results: the ETO and CTX groups [2 (1-3) d vs 2 (1-5) d; P<0.001] and CD34(+) cells [7.62×10(6) (2.26×10(6)-37.20×10(6)) /kg vs 2.73×10(6) (0.53×10(6)-9.85×10(6)) /kg; P<0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) (P<0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; P<0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. ②Adverse reactions: granular deficiency with fever (21.5%[14/65] vs. 10.7%[6/56]; P=0.110), requiring platelet transfusion [10.7% (7/65) vs 1.8% (1/56) ; P=0.047]. ③Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34(+) cells infused in the two groups was 4.62×10(6) (2.14×10(6)-19.89×10(6)) /kg versus 2.62×10(6) (1.12×10(6)-5.31×10(6)) /kg (P<0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d (P=0.049), and platelet implantation time was 11 (0-19) d vs. 12 (0-34) d (P=0.035). One case in the CTX group experienced delayed platelet implantation. Conclusion: The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34(+) cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.


Subject(s)
Cyclophosphamide , Etoposide , Granulocyte Colony-Stimulating Factor , Hematopoietic Stem Cell Mobilization , Multiple Myeloma , Transplantation, Autologous , Humans , Multiple Myeloma/therapy , Etoposide/administration & dosage , Hematopoietic Stem Cell Mobilization/methods , Cyclophosphamide/administration & dosage , Granulocyte Colony-Stimulating Factor/administration & dosage , Retrospective Studies , Peripheral Blood Stem Cells , Peripheral Blood Stem Cell Transplantation/methods , Female , Male , Middle Aged
10.
J Immunother Cancer ; 12(7)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38955418

ABSTRACT

PURPOSE: Small-cell lung cancer (SCLC) is an aggressive disease with a dismal prognosis. The addition of immune checkpoints inhibitors to standard platinum-based chemotherapy in first-line setting achieves a durable benefit only in a patient subgroup. Thus, the identification of predictive biomarkers is an urgent unmet medical need. EXPERIMENTAL DESIGN: Tumor samples from naive extensive-stage (ES) SCLC patients receiving atezolizumab plus carboplatin-etoposide were analyzed by gene expression profiling and two 9-color multiplex immunofluorescence panels, to characterize the immune infiltrate and SCLC subtypes. Associations of tissue biomarkers with time-to-treatment failure (TTF), progression-free survival (PFS) and overall survival (OS), were assessed. RESULTS: 42 patients were included. Higher expression of exhausted CD8-related genes was independently associated with a longer TTF and PFS while increased density of B lymphocytes correlated with longer TTF and OS. Higher percentage of M2-like macrophages close to tumor cells and of CD8+T cells close to CD4+T lymphocytes correlated with increased risk of TF and longer survival, respectively. A lower risk of TF, disease progression and death was associated with a higher density of ASCL1+tumor cells while the expression of POU2F3 correlated with a shorter survival. A composite score combining the expression of exhausted CD8-related genes, B lymphocyte density, ASCL1 tumor expression and quantification of CD163+macrophages close to tumor cells, was able to stratify patients into high-risk and low-risk groups. CONCLUSIONS: In conclusion, we identified tissue biomarkers and a combined score that can predict a higher benefit from chemoimmunotherapy in ES-SCLC patients.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Carboplatin , Etoposide , Lung Neoplasms , Small Cell Lung Carcinoma , Tumor Microenvironment , Humans , Carboplatin/therapeutic use , Carboplatin/administration & dosage , Carboplatin/pharmacology , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Male , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Female , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/genetics , Small Cell Lung Carcinoma/immunology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Etoposide/therapeutic use , Etoposide/pharmacology , Etoposide/administration & dosage , Aged , Middle Aged , Gene Expression Profiling/methods , Adult , Neoplasm Staging
11.
Talanta ; 277: 126298, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38823330

ABSTRACT

Combination drug therapy represents an effective strategy for treating certain drug-resistant and intractable cancer cases. However, determining the optimal combination of drugs and dosages is challenging due to clonal diversity in patients' tumors and the lack of rapid drug sensitivity evaluation methods. Microfluidic technology offers promising solutions to this issue. In this study, we propose a versatile microfluidic chip platform capable of integrating all processes, including dilution, treatment, and detection, for in vitro drug sensitivity assays. This platform innovatively incorporates several modules, including automated discrete drug logarithmic concentration generation, on-chip cell perfusion culture, and parallel drug treatments of cancer cell models. Moreover, it is compatible with microplate readers or high-content imaging systems for swift detection and automated monitoring, simplifying on-chip drug evaluation. Proof of concept is demonstrated by assessing the in vitro potency of two drugs, cisplatin, and etoposide, against the lung adenocarcinoma A549 cell line, under both single-drug and combination treatment conditions. The findings reveal that, compared to conventional microplate approaches with static cultivation, this on-chip automated perfusion bioassays yield comparable IC50 values with lower variation and a 50 % reduction in drug preparation time. This versatile dilution-treatment-detection microfluidic platform offers a promising tool for rapid and precise drug assessments, facilitating in vitro drug sensitivity evaluation in personalized cancer chemotherapy.


Subject(s)
Cisplatin , Drug Screening Assays, Antitumor , Etoposide , Lab-On-A-Chip Devices , Lung Neoplasms , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Etoposide/pharmacology , Cisplatin/pharmacology , Drug Screening Assays, Antitumor/instrumentation , A549 Cells , Antineoplastic Agents/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Microfluidic Analytical Techniques/instrumentation
12.
BMB Rep ; 57(6): 299-304, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38835116

ABSTRACT

Upregulation of PRAME (preferentially expressed antigen of melanoma) has been implicated in the progression of a variety of cancers, including melanoma. The tumor suppressor p53 is a transcriptional regulator that mediates cell cycle arrest and apoptosis in response to stress signals. Here, we report that PRAME is a novel repressive target of p53. This was supported by analysis of melanoma cell lines carrying wild-type p53 and human melanoma databases. mRNA expression of PRAME was downregulated by p53 overexpression and activation using DNA-damaging agents, but upregulated by p53 depletion. We identified a p53-responsive element (p53RE) in the promoter region of PRAME. Luciferase and ChIP assays showed that p53 represses the transcriptional activity of the PRAME promoter and is recruited to the p53RE together with HDAC1 upon etoposide treatment. The functional significance of p53 activationmediated PRAME downregulation was demonstrated by measuring colony formation and p27 expression in melanoma cells. These data suggest that p53 activation, which leads to PRAME downregulation, could be a therapeutic strategy in melanoma cells. [BMB Reports 2024; 57(6): 299-304].


Subject(s)
Antigens, Neoplasm , Melanoma , Promoter Regions, Genetic , Tumor Suppressor Protein p53 , Humans , Tumor Suppressor Protein p53/metabolism , Melanoma/metabolism , Melanoma/genetics , Melanoma/pathology , Antigens, Neoplasm/metabolism , Antigens, Neoplasm/genetics , Cell Line, Tumor , Promoter Regions, Genetic/genetics , Gene Expression Regulation, Neoplastic , Etoposide/pharmacology , Histone Deacetylase 1/metabolism , Down-Regulation/drug effects
13.
Medicine (Baltimore) ; 103(23): e38487, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847733

ABSTRACT

Lung cancer is one of the most malignant tumors with fastest morbidity and mortality. Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer with early metastasis and poor prognosis. At present, there is a lack of effective indicators to predict prognosis of SCLC patients. Delta-like 3 protein (DLL3) is selectively expressed on the surface of SCLC and is involved in proliferation and invasion. Neuron-specific enolase (NSE) is an enolase isoenzyme that is generally regarded as a biomarker for SCLC and may correlate with stage of SCLC, prognosis and chemotherapy response. NSE can be influenced by different types of factors. To explore the associations between expression levels of DLL3 in tumor tissues with platinum/etoposide chemotherapy response, and assess the prognostic values of DLL3, NSE and other potential prognostic factors in advanced SCLC patients were herein studied. Ninety-seven patients diagnosed with SCLC in Zhongda Hospital from 2014 to 2020 were enrolled in the study. Serum NSE levels were tested using ELISA methods before any treatment. The expression of DLL3 in tumor tissue was detected by Immunohistochemistry (IHC). We investigated the relationship of DLL3 expression with chemotherapy and survival. Progression free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Multivariate Cox-proportional hazard regression was used to identify predictors of PFS and OS. DLL3 was detected in 84.5% (82/97) of all patients' tumor samples by IHC, mainly located on the surface of SCLC cells. Lower DLL3 expression was associated with longer PFS and better chemotherapy response. OS had no significant differences. Multivariate analysis by Cox Hazard model showed that, high DLL3 expression and maximum tumor size >5 cm were independent risk factors for PFS, where NSE < 35 ng/mL and age < 70 were independent prognostic factors for OS. Early stage was independent prognostic factors for PFS and OS (P < .05 log-rank). DLL3 was expressed in the most of SCLCs. DLL3 expression level in the tumor and NSE level in the serum may be useful biomarkers to predict the prognosis of SCLC. DLL3 may be a potential therapeutic target for SCLC in the future.


Subject(s)
Biomarkers, Tumor , Lung Neoplasms , Phosphopyruvate Hydratase , Small Cell Lung Carcinoma , Humans , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/blood , Small Cell Lung Carcinoma/mortality , Small Cell Lung Carcinoma/pathology , Male , Female , Phosphopyruvate Hydratase/blood , Lung Neoplasms/drug therapy , Lung Neoplasms/blood , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Middle Aged , Prognosis , Biomarkers, Tumor/blood , Biomarkers, Tumor/metabolism , Aged , Membrane Proteins/blood , Membrane Proteins/metabolism , Intracellular Signaling Peptides and Proteins/blood , Intracellular Signaling Peptides and Proteins/metabolism , Etoposide/therapeutic use , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Predictive Value of Tests , Kaplan-Meier Estimate
14.
Life Sci Alliance ; 7(8)2024 Aug.
Article in English | MEDLINE | ID: mdl-38843934

ABSTRACT

RNA-binding proteins are frequently deregulated in cancer and emerge as effectors of the DNA damage response (DDR). The non-POU domain-containing octamer-binding protein NONO/p54nrb is a multifunctional RNA-binding protein that not only modulates the production and processing of mRNA, but also promotes the repair of DNA double-strand breaks (DSBs). Here, we investigate the impact of Nono deletion in the murine KP (KRas G12D , Trp53 -/- ) cell-based lung cancer model. We show that the deletion of Nono impairs the response to DNA damage induced by the topoisomerase II inhibitor etoposide or the radiomimetic drug bleomycin. Nono-deficient KP (KPN) cells display hyperactivation of DSB signalling and high levels of DSBs. The defects in the DDR are accompanied by reduced RNA polymerase II promoter occupancy, impaired nascent RNA synthesis, and attenuated induction of the DDR factor growth arrest and DNA damage-inducible beta (Gadd45b). Our data characterise Gadd45b as a putative Nono-dependent effector of the DDR and suggest that Nono mediates a genome-protective crosstalk of the DDR with the RNA metabolism via induction of Gadd45b.


Subject(s)
DNA Damage , DNA Repair , RNA-Binding Proteins , Animals , Mice , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , DNA Breaks, Double-Stranded , Antigens, Differentiation/metabolism , Antigens, Differentiation/genetics , Bleomycin/pharmacology , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Etoposide/pharmacology , Signal Transduction , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Cell Line, Tumor , RNA Polymerase II/metabolism , Humans , GADD45 Proteins
15.
Int J Clin Oncol ; 29(8): 1081-1087, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38904887

ABSTRACT

BACKGROUND: Multidrug chemotherapy for Ewing sarcoma can lead to severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, "Does primary prophylaxis with G-CSF benefit chemotherapy for Ewing sarcoma?" and CQ #2, "Does G-CSF-based intensified chemotherapy improve Ewing sarcoma treatment outcomes?". METHODS: A comprehensive literature search was conducted in PubMed, Cochrane Library, and Ichushi web databases, including English and Japanese articles published from 1990 to 2019. Two reviewers assessed the extracted papers and analyzed overall survival (OS), febrile neutropenia (FN) incidence, infection-related mortality, quality of life (QOL), and pain. RESULTS: Twenty-five English and five Japanese articles were identified for CQ #1. After screening, a cohort study of vincristine, ifosfamide, doxorubicin, and etoposide chemotherapy with 851 patients was selected. Incidence of FN was 60.8% with G-CSF and 65.8% without; statistical tests were not conducted. Data on OS, infection-related mortality, QOL, or pain was unavailable. Consequently, CQ #1 was redefined as a future research question. As for CQ #2, we found two English and five Japanese papers, of which one high-quality randomized controlled trial on G-CSF use in intensified chemotherapy was included. This trial showed trends toward lower mortality and a significant increase in event-free survival for 2-week interval regimen with the G-CSF primary prophylactic use compared with 3-week interval. CONCLUSION: This review indicated that G-CSF's efficacy as primary prophylaxis in Ewing sarcoma, except in children, is uncertain despite its common use. This review tentatively endorses intensified chemotherapy with G-CSF primary prophylaxis for Ewing sarcoma.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Granulocyte Colony-Stimulating Factor , Sarcoma, Ewing , Humans , Sarcoma, Ewing/drug therapy , Granulocyte Colony-Stimulating Factor/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Japan , Bone Neoplasms/drug therapy , Practice Guidelines as Topic , Doxorubicin/therapeutic use , Doxorubicin/adverse effects , Doxorubicin/administration & dosage , Quality of Life , Etoposide/therapeutic use , Etoposide/administration & dosage , Ifosfamide/therapeutic use , Ifosfamide/adverse effects , Ifosfamide/administration & dosage , Medical Oncology/methods , Vincristine/therapeutic use , Vincristine/adverse effects
16.
J Med Case Rep ; 18(1): 298, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38944668

ABSTRACT

BACKGROUND: Choriocarcinoma is a highly malignant pregnancy-related trophoblastic neoplasm, characterized by early metastasis to the lungs. Therefore, patients may manifest nongynecological symptoms owing to distant metastases. The incidence of choriocarcinoma after a term pregnancy is really rare (1/160,000 pregnancies). CASE PRESENTATION: We report a case of a 20-year-old Iranian woman, gravida 2 para 1 live 1 abortion 1, who was referred to our gynecology department with sudden onset dyspnea and pain in the left hemithorax the day after her labor. The index pregnancy was without any complications. After the initial workup, the elevation of ß-human chorionic gonadotropin (HCG) levels (> 1,000,000) along with the identification of clinical (vaginal lesions) and radiological evidence of distant metastases (bilateral pulmonary nodes) directed us toward pulmonary metastatic choriocarcinoma diagnosis. After the oncology consult, the etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy regimen was started for the patient. She responded well to the treatment and is currently continuing her chemotherapy process. CONCLUSION: The prognosis of choriocarcinoma is very good if the treatment is started on time. We suggest that clinicians should consider gestational trophoblastic neoplasia in their differential diagnosis of the post-natal period complications, especially after a term and nonmolar pregnancy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Choriocarcinoma , Lung Neoplasms , Uterine Neoplasms , Humans , Female , Pregnancy , Lung Neoplasms/secondary , Lung Neoplasms/drug therapy , Choriocarcinoma/secondary , Choriocarcinoma/drug therapy , Choriocarcinoma/diagnosis , Choriocarcinoma/pathology , Uterine Neoplasms/drug therapy , Uterine Neoplasms/pathology , Young Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Methotrexate/therapeutic use , Vincristine/therapeutic use , Dactinomycin/therapeutic use , Etoposide/therapeutic use , Etoposide/administration & dosage , Chorionic Gonadotropin, beta Subunit, Human/blood , Cyclophosphamide/therapeutic use , Dyspnea/etiology , Pregnancy Complications, Neoplastic/drug therapy
17.
Front Immunol ; 15: 1371379, 2024.
Article in English | MEDLINE | ID: mdl-38881888

ABSTRACT

SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) is a devastating subtype of thoracic tumor with SMARCA4 inactivation and is characterized by rapid progression, poor prognosis, and high risk of postoperative recurrence. However, effective treatments for SMARCA4-dUT are lacking. Herein, we describe a patient with SMARCA4-dUT who exhibited an impressive response to the anti-programmed cell death protein-1 (PD-1) antibody (tislelizumab) in combination with conventional chemotherapy (etoposide and cisplatin). To the best of our knowledge, this is the first case of SMARCA4-dUT treated with chemotherapy, comprising etoposide and cisplatin, combined with anti-PD-1 inhibitors. Immunotherapy combined with etoposide and cisplatin may be a promising strategy to treat SMARCA4-dUT.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , DNA Helicases , Transcription Factors , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , DNA Helicases/genetics , DNA Helicases/deficiency , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Transcription Factors/genetics , Nuclear Proteins/genetics , Nuclear Proteins/deficiency , Etoposide/therapeutic use , Etoposide/administration & dosage , Male , Cisplatin/therapeutic use , Cisplatin/administration & dosage , Treatment Outcome , Female
18.
Langmuir ; 40(24): 12792-12801, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38848468

ABSTRACT

Herein, we constructed the branch-shaped SiO2/nano GO (nGO)/Fe3O4/selenium quantum dots (QDs) (SeQDs) nanoparticles (SGF/SeQDs) embodying magnetism, fluorescence, and microwave stimulus response properties to enhance the performance of releasing drugs. The SGF/SeQDs composite was characterized by technologies including powder X-ray diffraction, transmission electron microscopy, infrared spectroscopy, etc. In the nanoparticles, the branch-shaped SiO2 provides a large specific surface area, nGO as the dielectric loss-style material promotes microwave-absorbing performance, and the Fe3O4 serves as a magnetic targeting agent and microwave absorber. Integrating nGO and Fe3O4 could further strengthen the microwave absorption of the entire composite; selenium features both fluorescence and anticancer effects. The synthesized nanoparticles as carriers exhibited a branch-like mesoporous sphere of ∼260 nm, a specific surface area of 258.57 m2 g-1, a saturation magnetization of 24.59 emu g-1, and good microwave thermal conversion performance that the temperature was elevated from 25 to 70 °C under microwave irradiation. These physical characteristics, including large pore volume (5.30 nm), high specific surface area, and fibrous morphology, are in favor of loading drugs. Meanwhile, the cumulative etoposide (VP16) loading rate of the nanoparticles reached to 21 wt % after 360 min. The noncovalent interaction between the VP16 and SGF/SeQDs was mainly the hydrogen-bonding effect during the loading process. Furthermore, the drug release rates at 180 min were up to 81.46, 61.92, and 56.84 wt % at pH 4, 5, and 7, respectively. At 25, 37, and 50 °C, the rates of drug release reach 25.40, 56.84, and 65.32 wt %, respectively. After microwave stimulation at pH 7, the rate of releasing drug increased distinctly from 56.84 to 71.74 wt % compared to that of nonmicrowave irradiation. Cytotoxicity tests manifested that the carrier had good biocompatibility. Therefore, the nanoparticles are looking forward to paving one platform for further applications in biomedicine and drug delivery systems.


Subject(s)
Drug Carriers , Quantum Dots , Selenium , Silicon Dioxide , Silicon Dioxide/chemistry , Drug Carriers/chemistry , Drug Carriers/chemical synthesis , Humans , Quantum Dots/chemistry , Quantum Dots/toxicity , Selenium/chemistry , Microwaves , Drug Liberation , Nanoparticles/chemistry , Cell Survival/drug effects , Etoposide/chemistry , Etoposide/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Particle Size , Surface Properties , Ferrosoferric Oxide/chemistry
19.
Biol Pharm Bull ; 47(6): 1189-1195, 2024.
Article in English | MEDLINE | ID: mdl-38897969

ABSTRACT

Although carboplatin (CBDCA) is classified as a moderately emetogenic agent, the majority of guidelines recommend the use of a neurokinin-1 receptor antagonist in addition to a 5-hydroxytryptamine type 3 receptor antagonist with dexamethasone (DEX) for CBDCA-containing chemotherapy because of its higher emetogenic risk. However, the additional efficacy of aprepitant (APR) in CBDCA-containing treatment remains controversial, and data on multiple-day treatments are limited. Etoposide (ETP) was administered on days 1-3 in the CBDCA + ETP regimen, and it is important to evaluate suitable antiemetic therapy for the regimen. Therefore, we evaluated the efficacy of additional APR in CBDCA + ETP. Patients were divided into two groups and retrospectively evaluated. One was the control group, which was prophylactically administered palonosetron (PALO) and DEX, and the other was the APR group, which received APR orally with PALO and DEX. The primary endpoint was complete response (CR) between the groups. The overall CR rates were 75.0 and 76.4% in the control and APR groups, respectively, with no significant difference (p = 1.00). In the acute phase, it was 88.9 and 97.2%, respectively, and 86.1 and 79.2% in the delayed phase, respectively, without significant differences (p = 0.10 and 0.38, respectively). The incidence and severity of nausea, vomiting, and anorexia were not significantly different between the two groups in the acute and delayed phases. Our findings suggest that combining APR with PALO and DEX does not improve the CR rate in CBDCA + ETP therapy.


Subject(s)
Antiemetics , Aprepitant , Carboplatin , Dexamethasone , Etoposide , Nausea , Palonosetron , Vomiting , Aprepitant/therapeutic use , Aprepitant/administration & dosage , Carboplatin/administration & dosage , Carboplatin/therapeutic use , Carboplatin/adverse effects , Humans , Dexamethasone/administration & dosage , Dexamethasone/therapeutic use , Palonosetron/administration & dosage , Palonosetron/therapeutic use , Male , Etoposide/administration & dosage , Etoposide/therapeutic use , Antiemetics/administration & dosage , Antiemetics/therapeutic use , Female , Middle Aged , Vomiting/chemically induced , Vomiting/prevention & control , Aged , Nausea/chemically induced , Nausea/prevention & control , Retrospective Studies , Adult , Drug Therapy, Combination , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Quinuclidines/administration & dosage , Quinuclidines/therapeutic use , Morpholines/administration & dosage , Morpholines/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Isoquinolines/administration & dosage , Isoquinolines/therapeutic use , Treatment Outcome
20.
Medicine (Baltimore) ; 103(25): e38616, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38905364

ABSTRACT

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome for which early recognition and treatment are essential for improving outcomes. HLH is characterized by uncontrolled immune activation leading to fever, cytopenias, hepatosplenomegaly, coagulation abnormalities, and elevated typical markers. This condition can be genetic or secondary, with the latter often triggered by infections. Here, we present a unique case of HLH secondary to acute otitis media (AOM), a common ear infection. PATIENT CONCERNS: We describe a 4-year-old boy who initially presented with a high fever and otalgia, later diagnosed with bilateral AOM. Despite antibiotic treatment, his condition deteriorated. DIAGNOSIS: The patient fulfilled diagnostic criteria for HLH. INTERVENTIONS: Aggressive treatment by using combination therapy with immunoglobulins, intravenous steroids (dexamethasone), cyclosporine, and etoposide was performed. OUTCOMES: After 1 month of treatment, improvement in the otologic symptoms was observed, and hematological findings gradually improved and normalized. LESSIONS: The link between AOM and HLH may be associated with inflammatory responses and immunological mechanisms, highlighting the importance of considering HLH in severe infection cases. This case emphasizes the need for prompt diagnosis and management, especially in secondary HLH scenarios, to improve patient outcomes. It is imperative to be aware of the potential correlation between these 2 conditions, and healthcare professionals should consider the likelihood of HLH.


Subject(s)
Lymphohistiocytosis, Hemophagocytic , Otitis Media , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/drug therapy , Male , Child, Preschool , Otitis Media/complications , Otitis Media/drug therapy , Acute Disease , Dexamethasone/therapeutic use , Dexamethasone/administration & dosage , Cyclosporine/therapeutic use , Cyclosporine/administration & dosage , Etoposide/therapeutic use , Etoposide/administration & dosage , Immunoglobulins, Intravenous/therapeutic use
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