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Journal of Ovarian Research Jun 2024This study aimed to investigate the mitigating effect of N-acetylcysteine (NAC) on doxorubicin (DOX)-induced ovarian and uterine toxicity in rats using laboratory tests,...
BACKGROUND
This study aimed to investigate the mitigating effect of N-acetylcysteine (NAC) on doxorubicin (DOX)-induced ovarian and uterine toxicity in rats using laboratory tests, ultrasonographic (US) imaging, and histopathology analysis.
METHODS
Forty-eight rats were divided into six groups (n = 8) as follows: Group A (control) (0.5 mL saline administered intraperitoneally [IP]), Group B (a single 10 mg/kg dose of DOX administered IP on day 1), Group C (a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice), Group D (100 mg/kg of NAC administered IP for 21 days), Group E ( a single 10 mg/kg dose of DOX administered IP on day 1 and 100 mg/kg of NAC administered IP for 21 days), and Group F (100 mg/kg of NAC administered IP for 21 days and a single 10 mg/kg dose of DOX administered IP 24 h before sacrifice). The ovaries were examined using B-mode US on days 1, 14, and 21, and the histopathological examinations of the ovaries and the uterus were undertaken after sacrifice on day 22.
RESULTS
Histomorphological analyses showed that ovarian weight decreased after DOX administration in Group B but not in Group E. US revealed a transient increase in ovarian size in Group B and E, reverting to baseline levels over time, as well as a progressive increase in peritoneal fluid in Groups B and E. Group B exhibited a significant decrease in the thickness of the endometrium and myometrium and uterine cornual length, which was not observed in Group E. Histopathological examination showed that DOX caused a decline in follicular count, especially in primordial, secondary, and Graafian follicles, and resulted in follicular atresia, predominantly in Group B. Destructive degeneration/necrosis and vascular changes were most prominently seen in the corpus luteum of Groups C and B. In NAC-treated rats (Groups E and F), although germ cell damage was present, atretic follicles and vascular changes, such as hyperemia and congestion, were reduced. The anti-müllerian hormone (AMH) level was the highest in Group F.
CONCLUSIONS
NAC, an antioxidant, attenuated DOX-induced gonadotoxicity in rats.
Topics: Animals; Female; Doxorubicin; Acetylcysteine; Rats; Ovary; Ultrasonography; Uterus; Antibiotics, Antineoplastic
PubMed: 38943148
DOI: 10.1186/s13048-024-01459-4 -
Biomeditsinskaia Khimiia Jun 2024The cytokine profile of primary coronary artery endothelial cells cultivated in the presence of doxorubicin (2 μg/ml and 6 μg/ml) was evaluated using enzyme-linked...
The cytokine profile of primary coronary artery endothelial cells cultivated in the presence of doxorubicin (2 μg/ml and 6 μg/ml) was evaluated using enzyme-linked immunosorbent assay and qPCR. Cultivation of cells in the presence of these concentrations of doxorubicin for 24 h, upregulated expression of the following genes: IL6 (by 2.30 and 2.66 times, respectively), IL1B (by 1.25 and 3.44 times), and CXCL8 (by 6.47 times and 6.42 times), MIF (2.34 and 2.28 times), CCL2 (4.22 and 3.98 times). Under these conditions the following genes were downregulated: IL10, IL1R2, TNF. Cultivation of cells in the presence of doxorubicin (2 μg/ml and 6 μg/ml) for 24 h also increased the secretion of IL-6.
Topics: Humans; Doxorubicin; Coronary Vessels; Endothelial Cells; Interleukin-6; Cells, Cultured; Interleukin-1beta; Cytokines; Gene Expression Regulation; Interleukin-8; Chemokine CCL2; Tumor Necrosis Factor-alpha; Interleukin-10
PubMed: 38940204
DOI: 10.18097/PBMC20247003156 -
In Vivo (Athens, Greece) 2024Anthracycline-based chemotherapies including doxorubicin monotherapy are recommended in major guidelines for patients with advanced or metastatic retroperitoneal sarcoma...
BACKGROUND/AIM
Anthracycline-based chemotherapies including doxorubicin monotherapy are recommended in major guidelines for patients with advanced or metastatic retroperitoneal sarcoma (RPS); however, few studies have reported the outcomes of doxorubicin monotherapy for these patients. We herein investigated the oncological efficacy and safety of doxorubicin monotherapy for patients with advanced or metastatic RPS in real-world clinical practice.
PATIENTS AND METHODS
Sixteen patients diagnosed with advanced or metastatic retroperitoneal sarcoma, receiving doxorubicin monotherapy as first-line treatment between February 2017 and March 2023 at our Institution were analyzed. Response rate, progression-free survival (PFS) periods, overall survival (OS) period, and adverse event (AE) profiles were retrospectively investigated.
RESULTS
The median age of patients was 69.5 years. Best responses to doxorubicin were as follows: complete response, 0 patients (0.0%); partial response, 3 (18.8%); stable disease, 9 (56.3%); and progressive disease, 4 (25.0%). The objective response rate and disease control rate were 18.8 and 75.0%, respectively. During the observation period (median, 22 months, range=2-53 months), median PFS and OS periods were 8.0 and 24.0 months, respectively. The following AEs Grade ≥3 occurred: neutropenia in 14 patients (87.5%), febrile neutropenia in 5 (31.3%), leukopenia in 2 (12.5%), thrombocytopenia in 1 (6.3%), and heart failure in 1 (6.3%). Grade ≥3 nausea and vomiting did not occur and there was no treatment-related death.
CONCLUSION
The oncological outcomes of doxorubicin monotherapy for RPS in real-world clinical practice were not inferior to those of the EORTC trial. The incidence of hematological AEs was higher; however, severe gastrointestinal AEs were prevented by prophylactic antiemetics and there were no treatment-related deaths. Collectively, doxorubicin monotherapy with appropriate prophylactic agents is a valid option for patients with advanced or metastatic RPS.
Topics: Humans; Female; Male; Aged; Doxorubicin; Middle Aged; Sarcoma; Retroperitoneal Neoplasms; Treatment Outcome; Aged, 80 and over; Neoplasm Metastasis; Adult; Retrospective Studies; Neoplasm Staging
PubMed: 38936944
DOI: 10.21873/invivo.13640 -
Cytoprotective Role of Autophagy in CDIP1 Expression-Induced Apoptosis in MCF-7 Breast Cancer Cells.International Journal of Molecular... Jun 2024Cell death-inducing p53-target protein 1 (CDIP1) is a proapoptotic protein that is normally expressed at low levels and is upregulated by genotoxic and endoplasmic...
Cell death-inducing p53-target protein 1 (CDIP1) is a proapoptotic protein that is normally expressed at low levels and is upregulated by genotoxic and endoplasmic reticulum stresses. CDIP1 has been reported to be localized to endosomes and to interact with several proteins, including B-cell receptor-associated protein 31 (BAP31) and apoptosis-linked gene 2 (ALG-2). However, the cellular and molecular mechanisms underlying CDIP1 expression-induced apoptosis remain unclear. In this study, we first demonstrated that CDIP1 was upregulated after treatment with the anticancer drug adriamycin in human breast cancer MCF-7 cells but was degraded rapidly in the lysosomal pathway. We also demonstrated that treatment with the cyclin-dependent kinase 5 (CDK5) inhibitor roscovitine led to an increase in the electrophoretic mobility of CDIP1. In addition, a phosphomimetic mutation at Ser-32 in CDIP1 resulted in an increase in CDIP1 expression-induced apoptosis. We also found that CDIP1 expression led to the induction of autophagy prior to apoptosis. Treatment of cells expressing CDIP1 with SAR405, an inhibitor of the class III phosphatidylinositol 3-kinase VPS34, caused a reduction in autophagy and promoted apoptosis. Therefore, autophagy is thought to be a defense mechanism against CDIP1 expression-induced apoptosis.
Topics: Humans; Autophagy; Apoptosis; MCF-7 Cells; Breast Neoplasms; Female; Apoptosis Regulatory Proteins; Doxorubicin; Gene Expression Regulation, Neoplastic; Class III Phosphatidylinositol 3-Kinases; Cytoprotection
PubMed: 38928226
DOI: 10.3390/ijms25126520 -
International Journal of Molecular... Jun 2024Breast cancer stands as one of the foremost cause of cancer-related deaths globally, characterized by its varied molecular subtypes. Each subtype requires a distinct...
Breast cancer stands as one of the foremost cause of cancer-related deaths globally, characterized by its varied molecular subtypes. Each subtype requires a distinct therapeutic strategy. Although advancements in treatment have enhanced patient outcomes, significant hurdles remain, including treatment toxicity and restricted effectiveness. Here, we explore the anticancer potential of novel 1,4-naphthoquinone/4-quinolone hybrids on breast cancer cell lines. The synthesized compounds demonstrated selective cytotoxicity against Luminal and triple-negative breast cancer (TNBC) cells, which represent the two main molecular types of breast cancer that depend most on cytotoxic chemotherapy, with potency comparable to doxorubicin, a standard chemotherapeutic widely used in breast cancer treatment. Notably, these derivatives exhibited superior selectivity indices (SI) when compared to doxorubicin, indicating lower toxicity towards non-tumor MCF10A cells. Compounds 11a and 11b displayed an improvement in IC values when compared to their precursor, 1,4-naphthoquinone, for both MCF-7 and MDA-MB-231 and a comparable value to doxorubicin for MCF-7 cells. Also, their SI values were superior to those seen for the two reference compounds for both cell lines tested. Mechanistic studies revealed the ability of the compounds to induce apoptosis and inhibit clonogenic potential. Additionally, the irreversibility of their effects on cell viability underscores their promising therapeutic utility. In 3D-cell culture models, the compounds induced morphological changes indicative of reduced viability, supporting their efficacy in a more physiologically relevant model of study. The pharmacokinetics of the synthesized compounds were predicted using the SwissADME webserver, indicating that these compounds exhibit favorable drug-likeness properties and potential as antitumor agents. Overall, our findings underscore the promise of these hybrid compounds as potential candidates for breast cancer chemotherapy, emphasizing their selectivity and efficacy.
Topics: Humans; Naphthoquinones; Antineoplastic Agents; Female; Breast Neoplasms; Cell Line, Tumor; MCF-7 Cells; Quinolones; Apoptosis; Cell Culture Techniques, Three Dimensional; Doxorubicin; Cell Proliferation; Cell Survival
PubMed: 38928197
DOI: 10.3390/ijms25126490 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To compare the prognostic value of two predictive models based on C-reactive protein (CRP) and albumin (ALB), namely the CRP to ALB ratio (CAR) and the Glasgow... (Comparative Study)
Comparative Study
OBJECTIVE
To compare the prognostic value of two predictive models based on C-reactive protein (CRP) and albumin (ALB), namely the CRP to ALB ratio (CAR) and the Glasgow prognostic score (GPS), in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL).
METHODS
The data of newly diagnosed DLBCL patients admitted to our center from May 2014 to January 2022 were reviewed. A total of 111 patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with detailed clinical, laboratory data and follow-up information were included. The receiver operating characteristic (ROC) curve was performed to evaluate the predictive value of pre-treatment CAR on disease progression and survival. Furthermore, the association between CAR and baseline clinical, laboratory characteristics of patients was evaluated, and progression-free survival (PFS) and overall survival (OS) were compared between different CAR and GPS subgroups. Finally, the univariate and multivariate COX propor-tional hazard regression models were used to analyze the factors affecting disease outcomes.
RESULTS
ROC curve showed that the area under the curve (AUC) of CAR predicting PFS and OS in DLBCL patients was 0.687 ( =0.002) and 0.695 ( =0.005), respectively, with the optimal cut-off value of 0.11 for both predicting PFS and OS. Compared with the lower CAR (<0.11) group, the higher CAR (≥0.11) group had more clinical risk factors, including age >60 years ( =0.025), ECOG score ≥2 ( =0.004), Lugano stage III-IV ( < 0.001), non-germinal center B-cell-like (non-GCB) subtype ( =0.035), elevated lactate dehydrogenase (LDH) ( < 0.001), extranodal involved site >1 ( =0.004) and IPI score >2 ( < 0.001). The interim response evaluation of patients showed that the overall response rate (ORR) and complete response rate (CRR) in the lower CAR group were both significantly better than those in the higher CAR group (ORR: 96.9% 80.0%, =0.035; CRR: 63.6% 32.5%, =0.008). With a median follow-up of 24 months, patients with lower CAR had significantly longer median PFS and OS than those with higher CAR (median PFS: not reached 67 months, =0.0026; median OS: not reached 67 months, =0.002), while there was no statistical difference in PFS ( =0.11) and OS ( =0.11) in patients with GPS of 0, 1, and 2. Multivariate Cox regression analysis indicated that only sex (male) and IPI score >2 were independent risk factors for both PFS and OS.
CONCLUSION
CAR is significantly correlated with disease progression and survival in DLBCL patients; And compared with GPS, CAR has more advantages in predicting disease outcomes in DLBCL patients.
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Prognosis; C-Reactive Protein; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Serum Albumin; Male; Female; Vincristine; Prednisone; Rituximab; Cyclophosphamide; Doxorubicin; Middle Aged
PubMed: 38926961
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.013 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To investigate the clinical efficacy and prognosis of Rituximab combined with DHAX and CHOP regimen in the first-line treatment of elderly patients with newly diagnosed...
OBJECTIVE
To investigate the clinical efficacy and prognosis of Rituximab combined with DHAX and CHOP regimen in the first-line treatment of elderly patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).
METHODS
A total of 36 elderly patients with DLBCL who were admitted and treated with 3 of more courses of treatment from August 2011 to August 2021 were retrospectively analyzed, and they were divided into rituximab±DHAX (R±DHAX) regimen group (18 cases) and rituximab±CHOP (R-CHOP) regimen group (18 cases) according to the treatment plan, and clinical features, efficacy and survival of the patients were observed.
RESULTS
Compared with R-CHOP group, patients of the R±DHAX group were older, and had worse performance status and higher IPI score, the differences between two groups in age, ECOG score and IPI score were statistically significant ( =0.005 =0.018, =0.035), but there were no significant differences beween two groups in gender, whether there were B symptoms, whether LDH was elevated, whether there was extranodal involvement, cell origin, bone marrow infiltration, and whether rituximab was combined ( =0.738, =1, =0.315, =0.305, =0.413, =0.177, =0.711, =0.229). The efficacy could be evaluated in 36 cases, including CR 14 (38.9%), PR 17 (47.2%), PD 5 (13.9%), and ORR of 86.1% (31/36). There were no statistically significant differences in CR[(27.8%(5/18) 50.0%(9/18); >0.05] and PR [44.4%(8/18) 50.0%(9/18); >0.05] of R±DHAX group and R-CHOP group, there was statistically significant difference in ORR[72.2%(13/18) 100.0%(18/18); =0.045] between two groups. The 1-year OS of R±DHAX group and R-CHOP group was (38.9±11.5%)% and (94.4±7.4%)%, respectively, 2-year OS was (16.7±8.8)% and (72.2±10.6)%, respectively, and the differences between two groups were statistically significant ( =0.001, =0.002). The median survival time in the R±DHAX group was 11 months(95% :8.9-13.1), and the median survival time in the R-CHOP group was not reached, and there was a statistically significant difference between the groups ( < 0.001).
CONCLUSION
For elderly DLBCL patients, R±DHAX may not be superior to R-CHOP in OS, and ECOG score, IPI score and age may affect the survival of elderly DLBCL patients. However, R±DHAX regimen is safe, tolerable and has a certain efficacy, which can be used as one of the clinical treatment options for elderly DLBCL.
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Rituximab; Aged; Cyclophosphamide; Vincristine; Prednisone; Doxorubicin; Prognosis; Male; Female; Cytarabine; Treatment Outcome
PubMed: 38926958
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.010 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To investigate the effectiveness, safety, and related prognostic factors of the treatment of follicular lymphoma (FL) with a regimen containing Bendamustine.
[The Reduction of CD4 T Lymphocytes after the Treatment of Follicular Lymphoma with the Bendamustine Containing Regimen May Predict the Occurrence of Infection and Efficacy].
OBJECTIVE
To investigate the effectiveness, safety, and related prognostic factors of the treatment of follicular lymphoma (FL) with a regimen containing Bendamustine.
METHODS
The clinical data of 129 FL patients who were treated with Bendamustine containing regimen were collected from January 1,2020 to October 30,2022 in the Hematology Department of Lianyungang Second People's Hospital and Jiangsu Provincial People's Hospital. The patients were divided into three groups: Bendamustine plus Rituximab (BR), Bendamustine plus Obinutuzumab (GB), Rituximab + Cyclophosphamide + Epirubicin / Doxorubicin + Vindesine + Prednisone (R-CHOP). The efficacy, safety and related prognostic factors of the treatment of FL with a regimen based on Bendamustine were retrospectively analyzed.
RESULTS
The ORR was 98% for the BR group, 94% for the GB group, and 72.3% for the R-CHOP group, while the CR rate was 61.2%,70% and 40.4%, respectively. The ORR and CR rates of the R-CHOP group were statistically different from those of the BR group and GB group ( < 0.05). The 3-year PFS rate of the BR group, GB group, and R-CHOP group was 89.6%, 90.9%, 48.9%, respectively. There was a statistically significant difference in 3-year PFS between the R-CHOP group, BR group, and GB group ( < 0.05), while there was no statistically significant difference in 3-year OS( >0.05). Hematological adverse reactions were mainly bone marrow suppression. Lymphocytes and CD4T lymphocytes decreased to the lowest level about 6 months after treatment, and the incidence of lymphopenia in BR group and GB group was higher than that in R-CHOP group, with a statistical difference ( < 0.05). The higher incidence of non-Hematological adverse reactions were pulmonary infection, EB virus infection, hepatitis B virus reactivation, and gastrointestinal reactions without statistical difference in 3 groups ( >0.05), and were all controllable. The Receiver operating characteristic of CD4T lymphocyte count showed that AUC of BR group was 0.802, and the critical value was 258/uL; AUC of GB group was 0.754 with a critical value of 322/uL.
CONCLUSION
The treatment of FL with the Bendamustine containing regimen has good efficacy and controllable adverse reactions, but lymphocytopenia was significant after treatment, and the curative efficacy in combination with various CD20 monoclonal antibodies was different. The lowest CD4T lymphocyte count can be used as a predictive factor for the occurrence of infection and efficacy of the Bendamustine containing regimen for FL.
Topics: Humans; Bendamustine Hydrochloride; Lymphoma, Follicular; Male; Female; Antineoplastic Combined Chemotherapy Protocols; Retrospective Studies; CD4-Positive T-Lymphocytes; Middle Aged; Rituximab; Doxorubicin; Cyclophosphamide; Prednisone; Adult; Prognosis; Infections; Treatment Outcome; Vincristine
PubMed: 38926957
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.009 -
Anticancer Research Jul 2024Pulsed electromagnetic field (PEMF) stimulation enhances the efficacy of several anticancer drugs. Doxorubicin is an anticancer drug used to treat various types of...
BACKGROUND/AIM
Pulsed electromagnetic field (PEMF) stimulation enhances the efficacy of several anticancer drugs. Doxorubicin is an anticancer drug used to treat various types of cancer, including breast cancer. However, the effect of PEMF stimulation on the efficacy of doxorubicin and the underlying mechanisms remain unclear. Thus, this study aimed to investigate the effect of PEMF stimulation on the anticancer activity of doxorubicin in MDA-MB-231 human breast cancer cells.
MATERIALS AND METHODS
MDA-MB-231 cells were seeded and allowed to incubate for 48 h. The cells were treated with doxorubicin, cisplatin, 5-fluorouracil, or paclitaxel for 48 h. Subsequently, the cells were stimulated with a 60-min PEMF session thrice a day (with an interval of 4 h between each session) for 24 or 48 h. Cell viability was assessed by trypan blue dye exclusion assay and cell-cycle analysis was analyzed by flow cytometry. Molecular mechanisms involved in late G arrest were confirmed by a western blot assay and confocal microscopy.
RESULTS
MDA-MB-231 cells treated with a combination of doxorubicin and PEMF had remarkably lower viability than those treated with doxorubicin alone. PEMF stimulation increased doxorubicin-induced cell-cycle arrest in the late G phase by suppressing cyclin-dependent kinase 1 (CDK1) activity through the enhancement of myelin transcription factor 1 (MYT1) expression, cell division cycle 25C (CDC25C) phosphorylation, and stratifin (14-3-3σ) expression. PEMF also increased doxorubicin-induced DNA damage by inhibiting DNA topoisomerase II alpha (TOP2A).
CONCLUSION
These findings support the use of PEMF stimulation as an adjuvant to strengthen the antiproliferative effect of doxorubicin on breast cancer cells.
Topics: Humans; Doxorubicin; Breast Neoplasms; Female; Cell Line, Tumor; Cell Survival; G2 Phase Cell Cycle Checkpoints; Electromagnetic Fields; DNA Topoisomerases, Type II; Cell Proliferation; Paclitaxel; Fluorouracil; Poly-ADP-Ribose Binding Proteins; cdc25 Phosphatases; Cyclin-Dependent Kinase 2
PubMed: 38925852
DOI: 10.21873/anticanres.17096 -
Anticancer Research Jul 2024This study evaluated the feasibility and safety of whole-body hyperthermia pressurized intraperitoneal aerosol chemotherapy (WBH-PIPAC) in patients with peritoneal...
BACKGROUND/AIM
This study evaluated the feasibility and safety of whole-body hyperthermia pressurized intraperitoneal aerosol chemotherapy (WBH-PIPAC) in patients with peritoneal surface malignancies.
PATIENTS AND METHODS
This study retrospectively analyzed a database of 28 patients who had received one cycle of normothermic PIPAC prior to repetitive WBH-PIPACs. WBH (39-40°C) was induced using a Water-filtered infrared A device. Doxorubicin plus cisplatin or oxaliplatin was nebulized into a constant capnoperitoneum of 20 mmHg for 30 min at doses of 6.0 mg, 30.0 mg, or 120 mg per m body surface area, respectively. The primary outcome measures were feasibility and perioperative complications.
RESULTS
The median age was 62 years (range=45-78 years). Primary tumor sites included the upper gastrointestinal tract (n=9), colon/rectum (n=7), hepato-pancreato-biliary system (n=3), peritoneum (n=2), ovaries (n=2), and unknown primary (n=5). The induction of WBH failed in one patient (6 liters ascites). After a median warming period of 95 min (53-117 min), the median rectal temperature (T) was 39.5°C (39.2-39.9°C). No hyperthermia-related side effects were observed. Twenty-seven patients received 50 WBH-PIPACs. The median time of therapeutic capnoperitoneum and treatment time with T ≥39°C was 39 min (37-43 min) and 66 min (53-69 min), respectively. The overall rate of postoperative procedure-related complications was 9/50, including seven grade I and two grade II complications. There were no grade III-V complications.
CONCLUSION
In a highly selected group of patients, the feasibility and perioperative safety of WBH-PIPAC was comparable to normothermic PIPAC.
Topics: Humans; Middle Aged; Female; Aged; Male; Peritoneal Neoplasms; Feasibility Studies; Retrospective Studies; Aerosols; Hyperthermia, Induced; Cisplatin; Doxorubicin; Antineoplastic Combined Chemotherapy Protocols; Hyperthermic Intraperitoneal Chemotherapy; Oxaliplatin
PubMed: 38925817
DOI: 10.21873/anticanres.17117