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Scientific Reports Jun 2024This study introduces a novel approach for synthesizing a Cu(II)-based coordination polymer (CP), {[Cu(L)(4,4´-OBA)]·HO}n (1), using a mixed ligand method. The CP was...
This study introduces a novel approach for synthesizing a Cu(II)-based coordination polymer (CP), {[Cu(L)(4,4´-OBA)]·HO}n (1), using a mixed ligand method. The CP was successfully prepared by reacting Cu(NO)·3HO with the ligand 3,6-bis(benzimidazol-1-yl)pyridazine in the presence of 4,4´-HOBA, demonstrating an innovative synthesis strategy. Furthermore, a novel hydrogel composed of hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) with a porous structure was developed for drug delivery purposes. This hydrogel facilitates the encapsulation of CP1, and enables the loading of paclitaxel onto the composite to form HA/CMCS-CP1@paclitaxel. In vitro cell experiments demonstrated the promising modulation of thyroid cancer biomarker genes S100A6 and ARID1A by HA/CMCS-CP1@paclitaxel. Finally, reinforcement learning simulations were employed to optimize novel metal-organic frameworks, underscoring the innovative contributions of this study.
Topics: Paclitaxel; Copper; Hydrogels; Humans; Thyroid Neoplasms; Chitosan; Cell Line, Tumor; Hyaluronic Acid; Coordination Complexes; Drug Carriers; Metal-Organic Frameworks
PubMed: 38844812
DOI: 10.1038/s41598-024-63940-w -
Signal Transduction and Targeted Therapy Jun 2024Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety...
First-line penpulimab (an anti-PD1 antibody) and anlotinib (an angiogenesis inhibitor) with nab-paclitaxel/gemcitabine (PAAG) in metastatic pancreatic cancer: a prospective, multicentre, biomolecular exploratory, phase II trial.
Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4-62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3-99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1-11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy. In conclusion, PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC. The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.
Topics: Humans; Male; Pancreatic Neoplasms; Female; Paclitaxel; Middle Aged; Aged; Deoxycytidine; Gemcitabine; Indoles; Albumins; Quinolines; Antineoplastic Combined Chemotherapy Protocols; Prospective Studies; Adult; Neoplasm Metastasis; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Programmed Cell Death 1 Receptor
PubMed: 38844468
DOI: 10.1038/s41392-024-01857-6 -
Respiratory Medicine and Research Apr 2024Studies have shown improvement in overall survival with anti-PD1/PD-L1 molecules in combination with cisplatin/carboplatin and etoposide as a first-line treatment for...
Study design and rationale for IFCT- 2203 TAXIO: A study that aims to evaluate the effectiveness of a first-line chemotherapy regimen without etoposide, combined with durvalumab, for patients with extensive disease small cell lung cancer.
BACKGROUND
Studies have shown improvement in overall survival with anti-PD1/PD-L1 molecules in combination with cisplatin/carboplatin and etoposide as a first-line treatment for Small Cell Lung Cancer (SCLC). However, first-line efficacy remains limited and well below that observed in Non-Small Cell Lung Cancer (NSCLC). Etoposide may have a detrimental effect on lymphocyte activation, which could explain the limited benefit of immunotherapy in the first line and the lack of benefit in the second line for patients previously exposed to high levels of etoposide.
METHODS
We initiated a multicenter, single-arm, open-label phase II study of a chemotherapy regimen with durvalumab, combined with carboplatin and paclitaxel for extensive disease SCLC. Eligible patients will receive durvalumab plus carboplatin and paclitaxel every 3 weeks for up to 4 cycles, followed by durvalumab every 4 weeks until progression or unacceptable toxicity. A total of 67 patients will be enrolled in this study, with a 12-month enrollment period and 36-month follow-up. The primary endpoint is Overall Survival (OS) rate at 12 months. Secondary endpoints are best response rate, OS, OS at 24- and 36 months, progression free survival (PFS), duration of response, quality of life and safety.
RESULTS
This study aims to establish the efficacy of durvalumab combined with carboplatin and paclitaxel in patients with extensive disease Small Cell Lung Cancer.
CLINICAL TRIAL REGISTRATION
EU CT: 2023-504670-38-00.
PubMed: 38843598
DOI: 10.1016/j.resmer.2024.101113 -
Frontiers in Neurology 2024Symptomatic intracranial in-stent restenosis (sISR) poses a major challenge in the management of cerebrovascular diseases, often requiring effective and safe treatment...
BACKGROUND
Symptomatic intracranial in-stent restenosis (sISR) poses a major challenge in the management of cerebrovascular diseases, often requiring effective and safe treatment options.
OBJECTIVES
This study aims to evaluate the efficacy and safety of paclitaxel-coated balloon (PCB) angioplasty for treating sISR.
METHODS
We conducted a retrospective analysis of five patients aged 49-74 years, who were treated with PCB angioplasty between January 2017 and June 2022. Treatment procedures included pre-operative digital subtraction angiography, antiplatelet therapy, and the use of the SeQuent Please balloon. Patients received aspirin and clopidogrel prior to and after the procedure.
RESULTS
The procedure achieved a 100% success rate. The degree of ISR was significantly reduced from an average pre-operative rate of 72±18.9% to a post-operative rate of 34±8.22%. Long-term follow-up showed that the majority of patients did not experience restenosis, confirming the long-term effectiveness of the treatment.
CONCLUSIONS
PCB angioplasty demonstrates significant potential as an effective and safe treatment option for patients with sISR, especially those considered to be at high risk. This study supports further investigation into PCB angioplasty as a standard treatment for sISR.
PubMed: 38841701
DOI: 10.3389/fneur.2024.1360609 -
Scientific Reports Jun 2024Alternaria alternata fungus is a potent paclitaxel producer isolated from Corylus avellana. The major challenge is the lack of optimized media for endophytic fungi...
Alternaria alternata fungus is a potent paclitaxel producer isolated from Corylus avellana. The major challenge is the lack of optimized media for endophytic fungi productivity. In the effort to maximize the production of taxoids by A. alternata, several fermentation conditions, including pH (pH 4.0-7.0), different types and concentrations of carbon (fructose, glucose, sucrose, mannitol, sorbitol, and malt extract), and nitrogen (urea, ammonium nitrate, potassium nitrate, ammonium phosphate, and ammonium sulfate) were applied step by step. Based on the results, A. alternata in a medium containing sucrose 5% (w/v) and ammonium phosphate 2.5 mM at pH 6.0 showed a rapid and sustainable growth rate, the highest paclitaxel yield (94.8 µg gFW vs 2.8 µg gFW in controls), and the maximum content of amino acids. Additionally, the effect of pectin was evaluated on fungus, and mycelia harvested. Pectin significantly enhanced the growth and taxoid yield on day 21 (respectively 171% and 116% of their corresponding on day 7). The results were checked out by mathematical modeling as well. Accordingly, these findings suggest a low-cost, eco-friendly, and easy-to-produce approach with excellent biotechnological potential for the industrial manufacture of taxoids.
Topics: Alternaria; Fermentation; Pectins; Culture Media; Paclitaxel; Models, Theoretical; Hydrogen-Ion Concentration; Nitrogen
PubMed: 38839906
DOI: 10.1038/s41598-024-63681-w -
Supportive Care in Cancer : Official... Jun 2024Alopecia is a common side-effect of chemotherapy and can be extremely distressing to patients. Scalp cooling can be used to reduce hair loss, but the optimal duration of... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Alopecia is a common side-effect of chemotherapy and can be extremely distressing to patients. Scalp cooling can be used to reduce hair loss, but the optimal duration of cooling remains unclear. Our aim was to determine whether increasing the duration of scalp cooling improves hair preservation.
METHODS
Patients with HER2-negative, non-metastatic, breast cancer received scalp cooling during adjuvant chemotherapy: three cycles of epirubicin/cyclophosphamide (EC) followed by three cycles of paclitaxel. The patients were randomly assigned to two groups. Group A (n=18) wore a Paxman cooling cap during each infusion and for 30 min post-infusion while Group B (n=19) wore the cap from 30 min before to 2 h after each infusion. All patients were asked to complete a questionnaire recording hair loss/regrowth, adverse events, and quality of life. Success of treatment was defined as <50% hair loss.
RESULTS
The success rates after each of the three cycles did not differ significantly between the two groups (EC: Group A: 40%, Group B: 44%; paclitaxel: Group A: 50%, Group B: 36%; p>0.05). Hair regrowth was significantly higher in Group B at the 8-week follow-up, but not at the 6-month follow-up. Head discomfort affected more patients in Group B than in Group A during the first session (94% vs. 62%, respectively; p=0.039).
CONCLUSION
Long duration scalp cooling during chemotherapy might increase patients' discomfort and does not appear to improve hair preservation.
Topics: Humans; Alopecia; Female; Breast Neoplasms; Pilot Projects; Middle Aged; Chemotherapy, Adjuvant; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Paclitaxel; Adult; Scalp; Epirubicin; Quality of Life; Hypothermia, Induced; Time Factors; Aged; Surveys and Questionnaires
PubMed: 38839667
DOI: 10.1007/s00520-024-08579-z -
Cell Reports. Medicine Jun 2024Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in...
Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC. Eligibility criteria included a percentage of cells expressing nuclear AR by immunohistochemistry (iAR) of at least 10% and a reduction in sonographic volume of less than 70% after four cycles of doxorubicin and cyclophosphamide. Twenty-four patients were enrolled. Ten achieved a pathologic complete response or residual cancer burden-I. ZT was safe, with no unexpected side effects. An iAR of at least 70% had a positive predictive value of 0.92 and a negative predictive value of 0.97 in predicting LAR-enriched TNBC according to RNA-based assays. Our data support future trials of AR blockade in early-stage LAR-enriched TNBC.
Topics: Humans; Triple Negative Breast Neoplasms; Phenylthiohydantoin; Nitriles; Benzamides; Female; Receptors, Androgen; Middle Aged; Neoadjuvant Therapy; Paclitaxel; Aged; Adult; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38838676
DOI: 10.1016/j.xcrm.2024.101595 -
Surgical Case Reports Jun 2024Advances in chemotherapy have increased clinical experience with conversion surgery for inoperable advanced gastric cancer. This report describes three patients with...
BACKGROUND
Advances in chemotherapy have increased clinical experience with conversion surgery for inoperable advanced gastric cancer. This report describes three patients with unresectable gastric cancer accompanied by multiple liver metastases. In all three patients, nivolumab resolved the liver metastases and subsequent conversion surgery achieved a pathological complete response.
CASE PRESENTATION
In Case 1, a 68-year-old man with clinical Stage IVB gastric cancer and multiple liver metastases initiated first-line therapy with SOX plus nivolumab. The patient completed 13 cycles; however, only nivolumab was continued for 3 cycles because of adverse events. Distal gastrectomy and partial hepatic resection were performed because of a significant reduction in the size of the liver metastases as observed on magnetic resonance imaging (MRI). In Case 2, a 72-year-old man with clinical Stage IVB gastric cancer and multiple liver metastases initiated first-line therapy with SOX. Because of the subsequent emergence of new liver metastases, the patient transitioned to ramucirumab plus paclitaxel as second-line therapy. Third-line therapy with nivolumab was initiated because of side effects. MRI revealed necrosis within the liver metastasis, and the patient underwent proximal gastrectomy and partial hepatectomy. In Case 3, a 51-year-old woman with clinical Stage IVB gastric cancer accompanied by multiple metastases of the liver and para-aortic lymph nodes began first-line therapy with SOX plus nivolumab. The patient completed 10 cycles; however, only nivolumab was continued for 5 cycles because of adverse events. Computed tomography showed a significant decrease in the size of the para-aortic lymph nodes, while MRI indicated the presence of a singular liver metastasis. Distal gastrectomy and partial hepatic resection were subsequently performed. In all three cases, MRI revealed the presence of liver metastases; however, pathological examination showed no viable tumor cells.
CONCLUSIONS
We herein present three cases in which chemotherapy, including nivolumab, elicited a response in patients with multiple unresectable liver metastases, ultimately culminating in R0 resection through conversion surgery. Although MRI showed liver metastases, pathological analysis revealed no cancer, underscoring the beneficial impact of chemotherapy.
PubMed: 38837046
DOI: 10.1186/s40792-024-01929-3 -
Frontiers in Immunology 2024Dendritic cell (DC)-based vaccines have emerged as a promising strategy in cancer immunotherapy due to low toxicity. However, the therapeutic efficacy of DC as a...
Dendritic cell (DC)-based vaccines have emerged as a promising strategy in cancer immunotherapy due to low toxicity. However, the therapeutic efficacy of DC as a monotherapy is insufficient due to highly immunosuppressive tumor environment. To address these limitations of DC as immunotherapeutic agent, we have developed a polymeric nanocomplex incorporating (1) oncolytic adenovirus (oAd) co-expressing interleukin (IL)-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) and (2) arginine-grafted bioreducible polymer with PEGylated paclitaxel (APP) to restore antitumor immune surveillance function in tumor milieu and potentiate immunostimulatory attributes of DC vaccine. Nanohybrid complex (oAd/APP) in combination with DC (oAd/APP+DC) induced superior expression level of antitumor cytokines (IL-12, GM-CSF, and interferon gamma) than either oAd/APP or DC monotherapy in tumor tissues, thus resulting in superior intratumoral infiltration of both endogenous and exogenous DCs. Furthermore, oAd/APP+DC treatment led superior migration of DC to secondary lymphoid organs, such as draining lymph nodes and spleen, in comparison with either monotherapy. Superior migration profile of DCs in oAd/APP+DC treatment group resulted in more prolific activation of tumor-specific T cells in these lymphoid organs and greater intratumoral infiltration of T cells. Additionally, oAd/APP+DC treatment led to lower subset of tumor infiltrating lymphocytes and splenocytes being immunosuppressive regulatory T cells than any other treatment groups. Collectively, oAd/APP+DC led to superior induction of antitumor immune response and amelioration of immunosuppressive tumor microenvironment to elicit potent tumor growth inhibition than either monotherapy.
Topics: Dendritic Cells; Animals; Paclitaxel; Adenoviridae; Mice; Oncolytic Viruses; Oncolytic Virotherapy; Combined Modality Therapy; Cell Line, Tumor; Humans; Mice, Inbred C57BL; Cancer Vaccines; Immunotherapy; Granulocyte-Macrophage Colony-Stimulating Factor; Female; Tumor Microenvironment
PubMed: 38835775
DOI: 10.3389/fimmu.2024.1355566 -
NPJ Breast Cancer Jun 2024The KEYNOTE-522 (KN522) regimen for neoadjuvant treatment of triple negative breast cancer (TNBC) utilized q3week dosing for doxorubicin plus cyclophosphamide (AC);...
The KEYNOTE-522 (KN522) regimen for neoadjuvant treatment of triple negative breast cancer (TNBC) utilized q3week dosing for doxorubicin plus cyclophosphamide (AC); however, dose-dense AC (ddAC) has demonstrated superior overall survival (OS) compared to q3week AC in anthracycline and taxane-based regimens. We performed a retrospective analysis assessing the use of ddAC in KN522 and the impact of sequencing ddAC before or after carboplatin/paclitaxel (CbT) plus pembrolizumab on multiple outcomes. 128 patients with TNBC were included. Overall pathologic complete response (pCR) rate of 56%. Sequencing of ddAC vs CbT first showed no difference in pCR rate (ddAC 55% vs. CbT 58%, p = 0.77). However, ddAC first compared to CbT first correlated with a significant increase in the incidence of overall treatment delays (ddAC 70% vs. CbT 51%, p = 0.03), with cytopenias most frequent (ddAC 59% vs. CbT 31%, p = 0.001). ddAC in a modified KN522 regimen is safe, tolerable, and effective. Efficacy is comparable regardless of chemotherapy sequencing, but ddAC first is significantly associated with higher rates of treatment delays and cytopenias.
PubMed: 38834621
DOI: 10.1038/s41523-024-00643-5