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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 2024Everolimus-resistant Caki/EV and 786/EV cells have been established from human derived renal cell carcinoma cells, Caki-2 and 786-O, respectively. These cells exhibit...
BACKGROUND/AIM
Everolimus-resistant Caki/EV and 786/EV cells have been established from human derived renal cell carcinoma cells, Caki-2 and 786-O, respectively. These cells exhibit resistance to everolimus and to other mTOR inhibitors and erlotinib. However, the sensitivity of these resistant cells to classical and cytotoxic anticancer drugs remain unclear. The aim of the study was to examine sensitivity of Caki/EV and 786/EV cells to classical and cytotoxic anticancer drugs.
MATERIALS AND METHODS
Sensitivity to classical and cytotoxic anticancer drugs in Caki/EV and 786/EV cells was evaluated using the WST-1 (tetrazolium salts) colorimetric assay and was compared to those of the corresponding parental cells. The mRNA expression levels were measured using SYBR green based quantitative reverse transcription-polymerase chain reaction.
RESULTS
Sensitivity to vinblastine, vincristine, paclitaxel, doxorubicin, etoposide, SN-38 (active metabolite of irinotecan), 5-fluorouracil, cisplatin, and carboplatin varied in the resistant cells. Sensitivity to carboplatin and SN-38 was comparable between resistant cells and their parental cells, whereas sensitivity to vinca alkaloids, etoposide, 5-fluorouracil, and cisplatin decreased in the resistant cells. However, sensitivity to paclitaxel and doxorubicin was remarkably enhanced in both resistant cells compared to that of parental cells, this could be partially explained by down-regulation of ABCB1 mRNA expression.
CONCLUSION
The everolimus-resistant Caki/EV and 786/EV cells showed cross-resistance to classical and cytotoxic anticancer drugs. However, Caki/EV and 786/EV cells exhibited a remarkable increase in sensitivity to paclitaxel and doxorubicin, and ABCB1 mRNA was down-regulated in response to long-term exposure to everolimus.
Topics: Humans; Everolimus; ATP Binding Cassette Transporter, Subfamily B; Carcinoma, Renal Cell; Drug Resistance, Neoplasm; Down-Regulation; Kidney Neoplasms; Cell Line, Tumor; Antineoplastic Agents; Gene Expression Regulation, Neoplastic
PubMed: 38925842
DOI: 10.21873/anticanres.17099 -
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 -
Anticancer Research Jul 2024There is limited evidence regarding the systemic treatment of retroperitoneal soft-tissue sarcoma, and the current Japanese guidelines fail to make definitive...
BACKGROUND/AIM
There is limited evidence regarding the systemic treatment of retroperitoneal soft-tissue sarcoma, and the current Japanese guidelines fail to make definitive suggestions. Here, we report our experience with combination chemotherapy of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) in this population.
PATIENTS AND METHODS
We retrospectively reviewed the records of eight patients (three male and five female) who received MAID for pathologically diagnosed metastatic unresectable retroperitoneal sarcoma (either leiomyosarcoma or pleomorphic sarcoma) between October 2019 and January 2022. Treatment efficacy, tolerability (need for dose reduction), and safety profiles were evaluated and summarized.
RESULTS
At initiation, the median age was 56.0 years, and the body mass index was 20.0 kg/cm Six patients had Eastern Cooperative Oncology Group performance status scores of 0. The net clinical benefit was a partial response in three (37.5%) patients, stable disease in four (50.0%), and progressive disease in one (12.5%). During the median 90.8 weeks of follow-up, disease in five patients progressed, resulting in a median progression-free survival of 48.4 weeks, and five deaths occurred, resulting in an overall survival of 95.1 weeks. Commonly observed adverse events were neutropenia (eight patients), anemia (eight patients), and decreased platelet count (seven patients), which led to dose reduction (60-80%) in six patients.
CONCLUSION
MAID combination therapy may be an acceptable option for advanced retroperitoneal sarcoma; however, its benefits must be carefully assessed owing to its not insignificant toxicity.
Topics: Humans; Male; Female; Middle Aged; Ifosfamide; Doxorubicin; Antineoplastic Combined Chemotherapy Protocols; Retroperitoneal Neoplasms; Sarcoma; Mesna; Aged; Dacarbazine; Retrospective Studies; Adult
PubMed: 38925814
DOI: 10.21873/anticanres.17137 -
Anticancer Research Jul 2024The porous glass membrane pumping emulsification device enhances local therapeutic effects of transarterial chemoembolization for hepatocellular carcinoma (HCC);...
BACKGROUND/AIM
The porous glass membrane pumping emulsification device enhances local therapeutic effects of transarterial chemoembolization for hepatocellular carcinoma (HCC); however, limited clinical outcomes have been reported. This study aimed to investigate the efficacy and safety of transarterial chemoembolization using the glass membrane pumping emulsification device for HCC.
PATIENTS AND METHODS
Between 2019 and 2023, 58 patients (median age=73 years) with unresectable HCC underwent 73 transarterial chemoembolizations using the glass membrane pumping emulsification device at the Nagoya University Hospital. Treatment effects were assessed using contrast-enhanced computed tomography 1-3 months after therapy and every 2-3 months thereafter.
RESULTS
The median size of treated tumors was 25.5 mm (45 solitary nodules). The median dosage of ethiodized oil mixed with the epirubicin solution was 3 ml. Complete and partial response were observed in 73% and 11% of patients, respectively. Local control rates at 6 and 12 months were 82.8% and 59.8%, respectively. The median time to recurrence after treatment was 581 days. No major treatment-related complications occurred. The number of tumors and therapeutic effects of the initial transarterial chemoembolization were significantly associated with better local control.
CONCLUSION
The glass membrane pumping emulsification device facilitated the accumulation of more concentrated ethiodized oil within the tumor and effective local control.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Chemoembolization, Therapeutic; Male; Female; Aged; Middle Aged; Glass; Treatment Outcome; Aged, 80 and over; Porosity; Epirubicin; Emulsions; Ethiodized Oil; Adult
PubMed: 38925808
DOI: 10.21873/anticanres.17133 -
International Journal of Pharmaceutics Jun 2024pH-responsive polymeric micelles have been extensively studied for nanomedicine and take advantage of pH differentials in tissues for the delivery of large doses of...
Oligoelectrolyte-mediated, pH-triggered release of hydrophobic drugs from non-responsive micelles: Influence of oligo(2-vinyl pyridine)-loading on drug-loading, release and cytotoxicity.
pH-responsive polymeric micelles have been extensively studied for nanomedicine and take advantage of pH differentials in tissues for the delivery of large doses of cytotoxic drugs at specific target sites. Despite significant advances in this area, there is a lack of versatile and adaptable strategies to render micelles pH-responsive that could be widely applied to different payloads and applications. To address this deficiency, we introduce the concept of oligoelectrolyte-mediated, pH-triggered release of hydrophobic drugs from non-responsive polymeric micelles as a highly effective approach with broad scope. Herein, we investigate the influence of the oligoelectrolyte, oligo(2-vinyl pyridine) (OVP), loading and polymer molecular weight on the pH-sensitivity, drug loading/release and cytotoxicity of poly(ethylene glycol-b-ε-caprolactone) (PEG-b-PCL) micelles using copolymers with either short or long hydrophobic blocks (PEGPCL and PEGPCL, respectively). The micelles were characterized as a function of pH (7.4 to 3.5). Dynamic light scattering (DLS) revealed narrow particle size distributions (PSDs) for both the blank and OVP-loaded micelles at pH 7.4. While OVP encapsulation resulted in an increase in the hydrodynamic diameter (D) (cf. blank micelles), a decrease in the pH below 6.5 led to a decrease in the D consistent with the ionization and release of OVP and core collapse, which were further supported by proton nuclear magnetic resonance (H NMR) spectroscopy and UV-visible (UV-vis) spectrophotometry. The change in zeta potential (ζ) with pH for the OVP-loaded PEGPCL and PEGPCL micelles was different, suggesting that the location/distribution of OVP in the micelles is influenced by the polymer molecular weight. In general, co-encapsulation of drugs (doxorubicin (DOX), gossypol (GP), paclitaxel (PX) or 7-ethyl-10-hydroxycamptothecin (SN38)) and OVP in the micelles proceeded efficiently with high encapsulation efficiency percentages (EE%). In vitro release studies revealed the rapid, pH-triggered release of drugs from OVP-loaded PEGPCL micelles within hours, with higher OVP loadings providing faster and more complete release. In comparison, no triggered release was observed for the OVP-loaded PEGPCL micelles, implying a strong molecular weight dependency. In metabolic assays the drug- and OVP-loaded PEGPCL micelles were found to result in significant enhancement of the cytotoxicity compared to drug-loaded micelles (no OVP) or other controls. Importantly, micelles with low OVP loadings were found to be nearly as effective as those with high OVP loadings. These results provide key insights into the tunability of the oligoelectrolyte-mediated approach for the effective formulation of pH-responsive micelles and pH-triggered drug release.
PubMed: 38925236
DOI: 10.1016/j.ijpharm.2024.124368 -
Journal of Biomaterials Science.... Jun 2024This study aimed to synthesize and characterize chitosan-coated noisomal doxorubicin for the purpose of enhancing its medical application, particularly in the field of...
This study aimed to synthesize and characterize chitosan-coated noisomal doxorubicin for the purpose of enhancing its medical application, particularly in the field of cancer treatment. Doxorubicin, a potent chemotherapeutic agent, was encapsulated within noisomes, which are lipid-based nanocarriers known for their ability to efficiently deliver drugs to target sites. Chitosan, a biocompatible and biodegradable polysaccharide, was used to coat the surface of the noisomes to improve their stability and enhance drug release properties. The synthesized chitosan-coated noisomal doxorubicin was subjected to various characterization techniques to evaluate its physicochemical properties. Transmission electron microscopy (TEM) revealed a spherical structure with a diameter of 500-550 ± 5.45 nm and zeta potential of +11 ± 0.13 mV with no aggregation or agglomeration. Chitosan-coated noisomes can loaded doxorubicin with entrapping efficacy 75.19 ± 1.45%. While scanning electron microscopy (SEM) revealed well-defined pores within a fibrous surface. It is observed that chitosan-coated niosomes loading doxorubicin have optimum roughness (22.88 ± 0.71 nm). UV spectroscopy was employed to assess the drug encapsulation efficiency and release profile. Differential scanning calorimetry (DSC) helped determine the thermal behavior, which indicated a broad endotherm peak at 52.4 °C, while X-ray diffraction (XRD) analysis provided information about the crystallinity of the formulation with an intense peak at 23.79°. Fourier-transform infrared spectroscopy (FTIR) indicated the formation of new bonds between the drug and the polymer. The findings from this study will contribute to the knowledge of the physical and chemical properties of the synthesized formulation, which is crucial for ensuring its stability, drug release kinetics, and biological activity. The enhanced chitosan-coated noisomal doxorubicin has the potential to improve the effectiveness and safety of doxorubicin in cancer treatment, offering a promising strategy for enhanced medical applications.
PubMed: 38923918
DOI: 10.1080/09205063.2024.2370591 -
Chemistry, An Asian Journal Jun 2024The anticancer efficacy of doxorubicin, an anthracycline-based and FDA-approved chemotherapeutic drug, is significantly hindered by acquired chemoresistance and severe...
The anticancer efficacy of doxorubicin, an anthracycline-based and FDA-approved chemotherapeutic drug, is significantly hindered by acquired chemoresistance and severe side effects, despite its potent anticancer properties. To overcome these challenges, we developed an innovative therapeutic formulation that integrates targeted chemotherapy and phototherapy within a single platform using gold nanoparticles (AuNPs). This novel nanoconjugate, designated as Dox-Fe@FA-AuNPs, is co-functionalized with folic acid, doxorubicin, and an iron(III)-phenolate/carboxylate complex, enabling cancer-specific drug activation. Here, we report the synthesis, characterization, and comprehensive physico-chemical and biological evaluations of Dox-Fe@FA-AuNPs. The nanoconjugate exhibited excellent solubility, stability, and enhanced cellular uptake in folate receptor-positive cancer cells. The nanoconjugate was potently cytotoxic against HeLa and MDA-MB-231 cancer cells (HeLa: 105.5 ± 16.52 µg mL-1; MDA-MB-231: 112.0 ± 12.31 µg mL-1; MDA-MB-231 (3D): 156.31 ± 19.35 µg mL-1) while less cytotoxic to the folate(-) cancer cells (MCF-7, A549 and HepG2). The cytotoxicity was attributed to the pH-dependent release of doxorubicin, which preferentially occurs in the acidic tumor microenvironment. Additionally, under red light irradiation, the nanoconjugate generated ROS, inducing caspase-3/7-dependent apoptosis with a photo-index (PI) >50, and inhibited cancer cell migration. Our findings underscore the potential of Dox-Fe@FA-AuNPs as a highly effective and sustainable platform for targeted chemo-phototherapy.
PubMed: 38923831
DOI: 10.1002/asia.202400616